research papers\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

Synthesis, crystal structures, anti­proliferative activities and reverse docking studies of eight novel Schiff bases derived from benzil

aSchool of Chemistry and Pharmaceutical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province 250353, People's Republic of China, bKey Laboratory of Pulp and Paper Science & Technology of Ministry of Education/Shandong Province, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province 250353, People's Republic of China, and cCollege of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Centre of Functionalized Probes for Chemical Imaging, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
*Correspondence e-mail: tanxuejie@163.com

Edited by F. A. Almeida Paz, University of Aveiro, Portugal (Received 5 June 2019; accepted 19 November 2019)

Eight novel Schiff bases derived from benzil dihydrazone (BDH) or benzil monohydrazone (BMH) and four fused-ring carbonyl com­pounds (3-formyl­indole, FI; 3-acetyl­indole, AI; 3-formyl-1-methyl­indole, MFI; 1-formyl­naph­thalene, FN) were synthesized and characterized by elemental analysis, ESI–QTOF–MS, 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. They are (1Z,2Z)-1,2-bis­{(E)-[(1H-indol-3-yl)methyl­idene]hy­dra­zinyl­idene}-1,2-di­phenyl­ethane (BDHFI), C32H24N6, (1Z,2Z)-1,2-bis­{(E)-[1-(1H-indol-3-yl)ethyl­idene]hydrazinyl­idene}-1,2-di­phenyl­ethane (BDHAI), C34H28N6, (1Z,2Z)-1,2-bis­{(E)-[(1-methyl-1H-indol-3-yl)methyl­idene]hy­dra­zin­yl­idene}-1,2-di­phenyl­ethane (BMHMFI) aceto­nitrile hemisolvate, C34H28N6·0.5CH3CN, (1Z,2Z)-1,2-bis­{(E)-[(naphthalen-1-yl)methyl­idene]hydrazinyl­idene}-1,2-di­phenyl­ethane (BDHFN), C36H26N4, (Z)-2-{(E)-[(1H-indol-3-yl)methyl­idene]hy­drazinyl­idene}-1,2-di­phenyl­ethanone (BMHFI), C23H17N3O, (Z)-2-{(E)-[1-(1H-indol-3-yl)ethyl­idene]hydrazinyl­idene}-1,2-di­phenyl­ethanone (BMHAI), C24H19N3O, (Z)-2-{(E)-[(1-methyl-1H-indol-3-yl)methyl­idene]hydrazinyl­idene}-1,2-di­phenyl­ethanone (BMHMFI), C24H19N3O, and (Z)-2-{(E)-[(naphthalen-1-yl)methyl­idene]hydrazinyl­idene}-1,2-di­phenyl­ethanone (BMHFN) C25H18N2O. Moreover, the in vitro cytotoxicity of the eight title com­pounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four (BDHMFI, BDHFN, BMHMFI and BMHFN) are inactive and the other four (BDHFI, BDHAI, BMHFI and BMHAI) show severe toxicities against human A549 and mouse 4T1 cells, similar to the standard cisplatin. All the com­pounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex-dock function in SYBYL-X 2.0 software. Three target proteins, i.e. human ether-á-go-go-related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine-protein kinase PIM1, were chosen as the targets. Finally, the ligand-based structure–activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.

1. Introduction

Schiff bases are important com­pounds in chemistry and biochemistry due to their flexibility (Mayans et al., 2018[Mayans, J., Font-Bardia, M., Di Bari, L., Arrico, L., Zinna, F., Pescitelli, G. & Escuer, A. (2018). Chem. Eur. J. 24, 7653-7663.]; Pramanik et al., 2018[Pramanik, K., Malpaharia, P., Colacio, E., Das, B. & Chandra, S. K. (2018). New J. Chem. 42, 6332-6342.]), easy preparation (Erxleben, 2018[Erxleben, A. (2018). Inorg. Chim. Acta, 472, 40-57.]; Ganguly et al., 2014[Ganguly, A., Chakraborty, P., Banerjee, K. & Choudhuri, S. K. (2014). Eur. J. Pharm. Sci. 51, 96-109.]), exceptional chelating ability (Malik et al., 2018[Malik, M. A., Dar, O. A., Gull, P., Wani, M. Y. & Hashmi, A. A. (2018). MedChemComm, 9, 409-436.]; Vardhan et al., 2015[Vardhan, H., Mehta, A., Nath, I. & Verpoort, F. (2015). RSC Adv. 5, 67011-67030.]) and to their broad spectrum of biological and pharmaceutical activities, such as anti­microbial (Anush et al., 2018[Anush, S. M., Vishalakshi, B., Kalluraya, B. & Manju, N. (2018). Int. J. Biol. Macromol. 119, 446-452.]; Unver & Bektas, 2018[Unver, Y. & Bektas, E. (2018). Lett. Drug. Des. & Discov. 15, 706-712.]; Bharathi et al., 2018[Bharathi Dileepan, A. G., Daniel Prakash, T., Ganesh Kumar, A., Shameela Rajam, P., Violet Dhayabaran, V. & Rajaram, R. (2018). J. Photochem. Photobiol. B, 183, 191-200.]; Carreño et al., 2018[Carreño, A., Zúñiga, C., Páez-Hernández, D., Gacitúa, M., Polanco, R., Otero, C., Arratia-Pérez, R. & Fuentes, J. A. (2018). New J. Chem. 42, 8851-8863.]), anti-inflammatory (Venkatesan et al., 2018[Venkatesan, V., Kumar, S. K. A., Bothra, S. & Sahoo, S. K. (2018). New J. Chem. 42, 6175-6182.]; Farag et al., 2017[Farag, A. K., Elkamhawy, A., Londhe, A. M., Lee, K.-T., Pae, A. N. & Roh, E. J. (2017). Eur. J. Med. Chem. 141, 657-675.]; Bano et al., 2017[Bano, B., Khan, K. M., Jabeen, A., Hameed, A., Faheem, A., Taha, M., Perveen, S. & Iqbal, S. (2017). ChemistrySelect, 2, 10050-10054.]; Khayyat et al., 2015[Khayyat, S., Amr, A. E. E., Salam, O. I. A. E., Al-Omar, M. A. & Abdalla, M. M. (2015). Int. J. Pharmacol. 11, 423-431.]) and anti­cancer properties (Unver & Bektas, 2018[Unver, Y. & Bektas, E. (2018). Lett. Drug. Des. & Discov. 15, 706-712.]; Santhosh Kumar et al., 2018[Santhosh Kumar, G., Poornachandra, Y., Kumar Gunda, S., Ratnakar Reddy, K., Mohmed, J., Shaik, K., Ganesh Kumar, C. & Narsaiah, B. (2018). Bioorg. Med. Chem. Lett. 28, 2328-2337.]; Kalaiarasi et al., 2018[Kalaiarasi, G., Rex Jeya Rajkumar, S., Aswini, G., Dharani, S., Fronczek, F. R. & Prabhakaran, R. (2018). Spectrochim. Acta A Mol. Biomol. Spectrosc. 200, 246-262.]; Ariyaeifar et al., 2018[Ariyaeifar, M., Amiri Rudbari, H., Sahihi, M., Kazemi, Z., Kajani, A. A., Zali-Boeini, H., Kordestani, N., Bruno, G. & Gharaghani, S. (2018). J. Mol. Struct. 1161, 497-511.]). Thus, the chemistry of Schiff bases has always been a promising field of research.

[Scheme 1]

As an organic helical mol­ecule with a long history (De et al., 2006[De, S., Chowdhury, S., Tocher, D. A. & Datta, D. (2006). CrystEngComm, 8, 670-673.]; Fisher & Stoufer, 1966[Fisher, H. M. & Stoufer, R. C. (1966). Inorg. Chem. 5, 1172-1177.]), benzil dihydrazone (BDH) is often used to construct polydentate diazine Schiff bases (Tan et al., 2015[Tan, X.-J., Hao, X.-Q., Zhao, Q.-Z., Cheng, S.-S., Xie, W.-L., Xing, D.-X., Liu, Y. & Song, L.-Z. (2015). J. Mol. Struct. 1099, 373-387.]), helical coordination com­plexes (Bai et al., 2012[Bai, Y., Gao, H., Qi, Z. Y. & Dang, D. B. (2012). Synth. React. Inorg. Met.-Org. Nano-Met. Chem. 42, 53-58.]; Drew et al., 2007[Drew, M. G. B., Parui, D., De, S., Chowdhury, S. & Datta, D. (2007). New J. Chem. 31, 1763-1768.]; Mukherjee et al., 2013[Mukherjee, A., Dutta, A., JANA, A. D. & Patra, G. K. (2013). Inorg. Chim. Acta, 404, 131-143.]) and, more importantly, a leading scaffold for the further design and synthesis of potential anti­cancer agents (Ke et al., 2013[Ke, S., Wei, Y., Shi, L., Yang, Q. & Yang, Z. (2013). Anticancer Agents Med. Chem. 13, 1291-1298.]). Here we aimed to use the BDH scaffold to construct some novel Schiff bases, especially those containing indole rings. Another set of novel Schiff bases based on benzil monohydrazone (BMH) were also constructed for com­parison.

As a privileged structure scaffold (de Sá Alves et al., 2009[Sá Alves, F. R. de, Barreiro, E. J. & Fraga, C. A. (2009). Mini Rev. Med. Chem. 9, 782-793.]; Evans et al., 1988[Evans, B. E., Rittle, K. E., Bock, M. G., DiPardo, R. M., Freidinger, R. M., Whitter, W. L., Lundell, G. F., Veber, D. F., Anderson, P. S., Chang, R. S., Lotti, V. J., Cerino, D. J., Chen, T. B., Kling, P. J., Kunkel, K. A., Springer, J. P. & Hirshfield, J. (1988). J. Med. Chem. 31, 2235-2246.]), indole derivatives play an important role in medicinal chemistry since they frequently exhibit broad and remarkable biological activities. Substituted indole rings have revealed anti­bacterial (El-Sawy et al., 2010[El-Sawy, E. R., Bassyouni, F. A., Abu-Bakr, S. H., Rady, H. M. & Abdlla, M. M. (2010). Acta Pharm. 60, 55-71.]; George et al., 2008[George, S., Parameswaran, M. K., Chakraborty, A. & Ravi, T. K. (2008). Acta Pharm. 58, 119-129.]), anti­tumour (Pedada et al., 2016[Pedada, R. S., Yarla, S. N., Tambade, J. P., Dhananjaya, L. B., Bishayee, A., Arunasree, M. K., Philip, H. G., Dharmapuri, G., Aliev, G., Putta, S. & Rangaiah, G. (2016). Eur. J. Med. Chem. 112, 289-297.]; Fortes et al., 2016[Fortes, M. P., da Silva, P. N. B., da Silva, T. G., Kaufman, T. S., Militão, G. C. G. & Silveira, C. C. (2016). Eur. J. Med. Chem. 118, 21-26.]; El-Sawy et al., 2012[El-Sawy, E. R., Mandour, A. H., Mahmoud, K., Islam, I. E. & Abo-Salem, H. M. (2012). Acta Pharm. 62, 157-179.], 2013[El-Sawy, E. R., Mandour, A. H., El-Hallouty, S. M., Shaker, K. H. & Abo-Salem, H. M. (2013). Arabian J. Chem. 6, 67-78.]; Wu et al., 2009[Wu, Y. S., Coumar, M. S., Chang, J. Y., Sun, H. Y., Kuo, F. M., Kuo, C. C., Chen, Y. J., Chang, C. Y., Hsiao, C. L., Liou, J. P., Chen, C. P., Yao, H. T., Chiang, Y. K., Tan, U. K., Chen, C. T., Chu, C. Y., Wu, S. Y., Yeh, T. K., Lin, C. Y. & Hsieh, H. P. (2009). J. Med. Chem. 52, 4941-4945.]; Pojarová et al., 2007[Pojarová, M., Kaufmann, D., Gastpar, R., Nishino, T., Reszka, P., Bednarski, P. J. & von Angerer, E. (2007). Bioorg. Med. Chem. 15, 7368-7379.]; Kamath et al., 2016[Kamath, P. R., Sunil, D., Ajees, A. A., Pai, K. S. R. & Biswas, S. (2016). Eur. J. Med. Chem. 120, 134-147.]), anti­fungal (Bai et al., 2018[Bai, J., Zhang, P., Bao, G., Gu, J.-G., Han, L., Zhang, L.-W. & Xu, Y. (2018). Appl. Microbiol. Biotechnol. 102, 8493-8500.]; Wang et al., 2018[Wang, Q., Qu, Y., Xia, Q., Song, H.-J., Song, H.-B., Liu, Y. & Wang, Q. (2018). Chem. Eur. J. 24, 11283-11287.]; Mishra et al., 2018[Mishra, S., Kaur, M., Chander, S., Murugesan, S., Nim, L., Arora, D. S. & Singh, P. (2018). Eur. J. Med. Chem. 155, 658-669.]; Yu et al., 2018[Yu, H.-F., Qin, X.-J., Ding, C.-F., Wei, X., Yang, J., Luo, J.-R., Liu, L., Khan, A., Zhang, L.-C., Xia, C.-F. & Luo, X.-D. (2018). Org. Lett. 20, 4116-4120.]), anti­viral (Cihan-Üstündağ et al., 2016[Cihan-Üstündağ, G., Gürsoy, E., Naesens, L., Ulusoy-Güzeldemirci, N. & Çapan, G. (2016). Bioorg. Med. Chem. 24, 240-246.]; Brigg et al., 2016[Brigg, S., Pribut, N., Basson, A. E., Avgenikos, M., Venter, R., Blackie, A., van Otterlo, W. A. L. & Pelly, S. C. (2016). Bioorg. Med. Chem. Lett. 26, 1580-1584.]; Zhao et al., 2006[Zhao, C., Zhao, Y., Chai, H. & Gong, P. (2006). Bioorg. Med. Chem. 14, 2552-2558.]; Sellitto et al., 2010[Sellitto, G., Faruolo, A., de Caprariis, P., Altamura, S., Paonessa, G. & Ciliberto, G. (2010). Bioorg. Med. Chem. 18, 6143-6148.]; Pu et al., 2017[Pu, C., Luo, R.-H., Zhang, M., Hou, X., Yan, G., Luo, J., Zheng, Y.-T. & Li, R. (2017). Bioorg. Med. Chem. Lett. 27, 4150-4155.]; Atienza et al., 2018[Atienza, B. J. P., Jensen, L. D., Noton, S. L., Ansalem, A. K. V., Hobman, T., Fearns, R., Marchant, D. J. & West, F. G. (2018). J. Org. Chem. 83, 6829-6842.]), anti-inflammatory (Mandour et al., 2010[Mandour, A. H., El-Sawy, E. R., Shaker, K. H. & Mustafa, M. A. (2010). Acta Pharm. 60, 73-88.]; Lamie et al., 2016[Lamie, P. F., Ali, W. A. M., Bazgier, V. & Rárová, L. (2016). Eur. J. Med. Chem. 123, 803-813.]), anti­oxidant (Estevão et al., 2010[Estevão, M. S., Carvalho, L. C., Ribeiro, D., Couto, D., Freitas, M., Gomes, A., Ferreira, L. M., Fernandes, E. & Marques, M. M. B. (2010). Eur. J. Med. Chem. 45, 4869-4878.]; Suzen & Buyukbingol, 2000[Suzen, S. & Buyukbingol, E. (2000). Farmaco, 55, 246-248.]; Mor et al., 2004[Mor, M., Silva, C., Vacondio, F., Plazzi, P. V., Bertoni, S., Spadoni, G., Diamantini, G., Bedini, A., Tarzia, G., Zusso, M., Franceschini, D. & Giusti, P. (2004). J. Pineal Res. 36, 95-102.]), anti­tuberculosis (Naidu et al., 2016[Naidu, K. M., Srinivasarao, S., Agnieszka, N., Ewa, A. K., Kumar, M. M. K. & Chandra Sekhar, K. V. G. (2016). Bioorg. Med. Chem. Lett. 26, 2245-2250.]; Zhao, 2018[Zhao, S.-Q., Xu, Y., Guan, J., Zhao, S., Zhang, G.-D. & Xu, Z. (2018). J. Heterocycl. Chem. 55, 2172-2177.]; Hong et al., 2017[Hong, W. D., Gibbons, P. D., Leung, S. C., Amewu, R., Stocks, P. A., Stachulski, A., Horta, P., Cristiano, M. L. S., Shone, A. E., Moss, D., Ardrey, A., Sharma, R., Warman, A. J., Bedingfield, P. T. P., Fisher, N. E., Aljayyoussi, G., Mead, S., Caws, M., Berry, N. G., Ward, S. A., Biagini, G. A., O'Neill, P. M. & Nixon, G. L. (2017). J. Med. Chem. 60, 3703-3726.]; Akula et al., 2016[Akula, M., Yogeeswari, P., Sriram, D., Jha, M. & Bhattacharya, A. (2016). RSC Adv. 6, 46073-46080.]), analgesic (Fanti­nati et al., 2017[Fantinati, A., Bianco, S., Guerrini, R., Salvadori, S., Pacifico, S., Cerlesi, M. C., Calo, G. & Trapella, C. (2017). Sci. Rep. UK, 7, 1-7.]; Bertamino et al., 2018[Bertamino, A., Iraci, N., Ostacolo, C., Ambrosino, P., Musella, S., Di Sarno, V., Ciaglia, T., Pepe, G., Sala, M., Soldovieri, M. V., Mosca, I., Gonzalez-Rodriguez, S., Fernandez-Carvajal, A., Ferrer-Montiel, A., Novellino, E., Taglialatela, M., Campiglia, P. & Gomez-Monterrey, I. (2018). J. Med. Chem. 61, 6140-6152.]; Ali Khan et al., 2018[Ali Khan, M. S., Misbah Ahmed, N., Arifuddin, M., Rehman, A. & Ling, M. P. (2018). Food Chem. Toxicol. 118, 953-962.]), anti­convulsant (Saini et al., 2016[Saini, T., Kumar, S. & Narasimhan, B. (2016). Cent. Nerv. Syst. Agents Med. Chem. 16, 19-28.]; Ndagijimana et al., 2013[Ndagijimana, A., Wang, X., Pan, G., Zhang, F., Feng, H. & Olaleye, O. (2013). Fitoterapia, 86, 35-47.]; Ma et al., 2016[Ma, J.-Y., Quan, Y.-C., Jin, H.-G., Zhen, X.-H., Zhang, X.-W. & Guan, L.-P. (2016). Chem. Biol. Drug Des. 87, 342-351.]; Ensch et al., 2018[Ensch, M., Maldonado, V. Y., Swain, G. M., Rechenberg, R., Becker, M. F., Schuelke, T. & Rusinek, C. A. (2018). Anal. Chem. 90, 1951-1958.]) and many other therapeutic and pharmacological properties. Numerous pharmaceutical mol­ecules with the indole group have been marketed. These include indomethacin, zafirlukast, sumatriptan, indole-3-acetic acid (IAA), serotonin, delavirdine, atevirdine etc. There are also large numbers of indole-containing drugs currently going through different clinical phases (Naim et al., 2016[Naim, M. J., Alam, O., Alam, Md. J., Bano, F., Alam, P. & Shrivastava, N. (2016). Int. J. Pharm. Sci. Res. 7, 51-62.]). Moreover, the indole nucleus is commonly found in several natural products and displays an indispensable role in therapeutic chemistry (Tzvetkov et al., 2014[Tzvetkov, N. T., Hinz, S., Küppers, P., Gastreich, M. & Müller, C. E. (2014). J. Med. Chem. 57, 6679-6703.]; Gurer-Orhan et al., 2016[Gurer-Orhan, H., Karaaslan, C., Ozcan, S., Firuzi, O., Tavakkoli, M., Saso, L. & Suzen, S. (2016). Bioorg. Med. Chem. 24, 1658-1664.]; Kumar et al., 2016[Kumar, D., Kumar, M. N., Akamatsu, K., Kusaka, E., Harada, H. & Ito, T. (2016). Bioorg. Med. Chem. Let. 20, 3916-3919.]; Johansson et al., 2013[Johansson, H., Jørgensen, B. T., Gloriam, E. D., Bräuner-Osborne, H. & Pedersen, S. D. (2013). RSC Adv. 3, 945-960.]; Blunt et al., 2011[Blunt, J. W., Copp, B. R., Munro, M. H., Northcote, P. T. & Prinsep, M. R. (2011). Nat. Prod. Rep. 28, 196-268.]; Gul & Hamann, 2005[Gul, W. & Hamann, M. T. (2005). Life Sci. 78, 442-453.]; Sugiyama et al., 2009[Sugiyama, Y., Ito, Y., Suzuki, M. & Hirota, A. (2009). J. Nat. Prod. 72, 2069-2071.]; Bao et al., 2007[Bao, B., Zhang, P., Lee, Y., Hong, J., Lee, C. O. & Jung, J. H. (2007). Mar. Drugs 5, 31-39.]; Shaaban et al., 2002[Shaaban, M., Maskey, R. P., Wagner-Döbler, I. & Laatsch, H. (2002). J. Nat. Prod. 65, 1660-1663.]; Shaaban & Abdel-Aziz, 2007[Shaaban, M. & Abdel-Aziz, M. S. (2007). Nat. Prod. Res. 21, 1205-1211.]; Ali Khan et al., 2018[Ali Khan, M. S., Misbah Ahmed, N., Arifuddin, M., Rehman, A. & Ling, M. P. (2018). Food Chem. Toxicol. 118, 953-962.]; Ndagijimana et al., 2013[Ndagijimana, A., Wang, X., Pan, G., Zhang, F., Feng, H. & Olaleye, O. (2013). Fitoterapia, 86, 35-47.]). Although indole derivatives have been the target of synthetic exploration for many years, more anti­cancer com­pounds incorporating the indole scaffold with improved anti­cancer properties are desired for the systematic study of structure–activity relationships (Hassam et al., 2012[Hassam, M., Basson, A. E., Liotta, D. C., Morris, L., van Otterlo, W. A. L. & Pelly, S. C. (2012). ACS Med. Chem. Lett. 3, 470-475.]; Dai et al., 2016[Dai, W., Jiang, X. L., Tao, J. Y. & Shi, F. (2016). J. Org. Chem. 81, 185-192.]; Singh et al., 2018[Singh, G., Kalra, P., Arora, A., Singh, A., Sharma, G., Sanchita, Maurya, I. K., Dutta, S., Munshi, P. & Verma, V. (2018). ChemistrySelect, 3, 2366-2375.]).

[Scheme 2]

In order to gain a deeper insight into the anti­tumour activity of various functionalized indoles, we have been conducting a systematic study on indole derivatives with different scaffolds, for example, novel Schiff bases derived from indole and biphenyl show lung A549 and breast 4T1 cancer cell inhibitory activities (IC50 = 20.5 and 18.5 µM, respectively) (Bu et al., 2017[Bu, F.-Z., Tan, X.-J., Xing, D.-X. & Wang, C. (2017). Acta Cryst. C73, 546-555.]; Tan et al., 2019[Tan, X.-J., Zhang, L.-Y., Sun, Y.-K. & Zhou, X.-M. (2019). Acta Cryst. C75, 97-106.]). We report here the synthesis, crystal structure and anti­proliferative activities of six Schiff bases derived from indole and BDH/BMH, as well as two com­parative com­pounds derived from naphthalene and BDH/BMH (see Scheme 1).

2. Experimental

2.1. Materials and measurements

The starting material benzil and related chemicals were purchased from Aladdin Reagent Chemicals and were used without further purification. Elemental (C, H and N) analyses were carried out with a PerkinElmer 2400 microanalyzer. Accurate mass measurements were acquired on an Agilent-6520 quadrupole time-of-flight tandem mass spectrometer. Melting points were determined on a WRS-2A electrothermal digital melting point apparatus (Shanghai Precision & Scientific Instrument Co. Ltd, China). 1H and 13C NMR spectra were recorded on a Bruker Avance 400 MHz instrument. The chemical shifts are reported in parts per million (ppm) relative to tetra­methyl­silane (SiMe4, δ = 0 ppm), referenced to the chemical shifts of the residual solvent peak [deuterated dimethyl sulfoxide (DMSO-d6)].

2.2. Synthesis and crystallization

As indicated in Scheme 2, a two-step process was used to synthesize all eight title com­pounds. In the first step, a mixture of benzil (0.42 g or 2 mmol) and hydrazine hydrate (80%, 0.20 ml or 4 mmol) was added to dry ethanol (20 ml) and the resulting solution refluxed for 3 h. Most of the ethanol was removed by distillation and the resulting solution was cooled to room temperature. Crude benzil dihydrazone (abbreviated as BDH) was filtered off, recrystallized from ethanol and dried in a vacuum. Pure BDH was obtained as colourless needle-shaped crystals {yield 85%, 0.41 g; m.p. 151.4–152.0 °C [literature m.p. 151–152 (Bach et al., 1982[Bach, R. D., Woodard, R. A., Anderson, T. J. & Glick, M. D. (1982). J. Org. Chem. 47, 3707-3712.]), 150–151.5 (Kim & Yoon, 2004[Kim, S. & Yoon, J.-Y. (2004). Sci. Synth. 27, 671-722.]), 149 (Salavati-Niasari & Hassani-Kabutarkhani, 2005[Salavati-Niasari, M. & Hassani-Kabutarkhani, M. (2005). Synth. React. Inorg. Met.-Org. Nano-Met. Chem. 35, 469-475.]), 152 (Chandra et al., 2007[Chandra, S., Verma, S. & Gautam, A. (2007). J. Saudi Chem. Soc. 11, 483-488.]), 172 (Singh et al., 2008[Singh, R. V., Fahmi, N., Swami, M. & Chauhan, S. (2008). J Macromol. Sci. A, 45, 159-163.]) and 172 °C (Chauhan et al., 2008[Chauhan, S., Swami, M., Malik, S. & Singh, R. V. (2008). Main Group Met. Chem. 31, 263-272.])]}. Elemental analysis found (calculated) for C14H14N4 (%): C 70.64 (70.57), H 5.97 (5.92), N 23.63 (23.51). On the other hand, if the molar ratio of benzil and hydrazine hydrate was set at 1:1, benzil monohydrazone (BMH) will be obtained in a similar yield. Pure BMH was obtained as a colourless crystal (m.p. 138.4–139.2 °C).

In the second step, all eight Schiff bases were readily prepared by a similar method (see Scheme 2). BDH/BMH and the required carbonyl com­pounds (FI, AI, MFI and FN) were stirred under reflux for 5 h in dry ethanol in a 1:2 (BDH versus carbonyl com­pounds) or 1:1 (BMH versus carbonyl com­pounds) molar ratio. After the reaction, the solvent was reduced in volume by slow evaporation and crystalline products were usually obtained. Recrystallization can purify the products. Their physical and spectroscopic properties are listed in the following sections. All NMR spectra are available in Figs. S1–S16 of the supporting information.

2.2.1. BDHFI

M.p. 274.0–275.0 °C. Elemental analysis found (calculated) for C32H24N6 (%): C 78.15 (78.03), H 4.98 (4.91), N 17.12 (17.06). HRMS (ESI): m/z calculated for C32H24N6 + H+: 493.2141 [M + H+]; found: 493.2142. 1H NMR (DMSO-d6): 11.637 (s, 2H, –NH), 8.757 (s, 2H, –N=CH), 7.878–7.825 (m, 6H, J = 7.2 Hz, Ar-H), 7.587 (d, 2H, J = 8.0 Hz, Ar-H), 7.450 (d, 6H, J = 8.0 Hz, Ar-H), 7.330 (d, 2H, J = 8.0 Hz, Ar-H), 7.076 (t, 2H, J = 8.0 Hz, Ar-H), 6.851 (t, 2H, J = 7.2 Hz, Ar-H). 13C NMR (DMSO-d6): 163.575 (CH=N), 156.485 (CH=N), 136.992 (Ar-C), 135.007 (Ar-C), 132.951 (Ar-C), 130.035 (Ar-C), 128.589 (Ar-C), 126.989 (Ar-C), 124.433 (Ar-C), 122.596 (Ar-C), 122.267 (Ar-C), 120.478 (Ar-C), 112.165 (Ar-C), 111.629 (Ar-C).

2.2.2. BDHAI

M.p. 270.2–271.7 °C. Elemental analysis found (calculated) for C34H28N6 (%): C 78.49 (78.44), H 5.47 (5.42), N 16.21 (16.14). HRMS (ESI): m/z calculated for C34H28N6 + H+: 521.2454 [M + H+]; found: 521.2456. 1H NMR (DMSO-d6): 11.473 (s, 2H, –NH), 7.877–7.754 (m, 8H, J = 6.8 Hz, Ar-H), 7.452–7.271 (m, 8H, J = 6.8 Hz, Ar-H), 7.020 (s, 2H, Ar-H), 6.713 (s, 2H, Ar-H), 2.418 (s, 6H –CH3). 13C NMR (DMSO-d6): 161.007 (CH=N), 136.915 (CH=N), 135.117 (Ar-C), 129.884 (Ar-C), 129.587 (Ar-C), 128.598 (Ar-C), 128.292 (Ar-C), 127.405 (Ar-C), 126.942 (Ar-C), 124.815 (Ar-C), 124.730 (Ar-C), 123.487 (Ar-C), 122.003 (Ar-C), 119.916 (Ar-C), 115.206 (Ar-C), 111.184 (Ar-C), 14.792 (–CH3).

2.2.3. BDHMFI

M.p. 214.6–215.3 °C. Elemental analysis found (calculated) for C34H28N6 (%): C 78.51 (78.44), H 5.46 (5.42), N 16.19 (16.14). HRMS (ESI): m/z calculated for C34H28N6 + H+: 521.2454 [M + H+]; found: 521.2454. 1H NMR (DMSO-d6): 8.731 (s, 2H, –N=CH), 7.874 (d, 4H, J = 7.2 Hz, Ar-H), 7.789 (s, 2H, Ar-H), 7.602 (d, 2H, J = 7.2 Hz, Ar-H), 7.474–7.373 (m, 8H, Ar-H), 7.151 (t, 2H, J = 7.2 Hz, Ar-H), 6.908 (t, 2H, J = 7.2 Hz, Ar-H), 3.733 (s, 6H –N—CH3). 13C NMR (DMSO-d6): 163.813 (CH=N), 155.643 (CH=N), 137.807 (Ar-C), 137.575 (Ar-C), 136.220 (Ar-C), 136.059 (Ar-C), 129.753 (Ar-C), 128.178 (Ar-C), 127.936 (Ar-C), 127.608 (Ar-C), 124.885 (Ar-C), 122.636 (Ar-C), 122.121 (Ar-C), 120.644 (Ar-C), 111.325 (Ar-C), 110.007 (Ar-C), 32.770 (–N—CH3).

2.2.4. BDHFN

M.p. 203.0–205.0 °C. Elemental analysis found (calculated) for C36H26N4 (%): C 84.08 (84.02), H 5.13 (5.09), N 10.94 (10.89). HRMS (ESI): m/z calculated for C36H26N4 + H+: 515.2236 [M + H+]; found: 515.2236. 1H NMR (DMSO-d6): 8.770 (s, 2H, –N=CH), 8.277 (t, 4H, J = 7.6 Hz, Ar-H), 7.883–7.766 (m, 6H, Ar-H), 7.585 (d, 2H, J = 8.0 Hz, Ar-H), 7.482–7.326 (m, 8H, Ar-H), 7.082 (t, 2H, J = 7.6 Hz, Ar-H), 6.857 (t, 2H, J = 7.6 Hz, Ar-H). 13C NMR (DMSO-d6): 163.655 (CH=N), 156.624 (CH=N), 139.670 (Ar-C), 137.877 (Ar-C), 136.970 (Ar-C), 134.977 (Ar-C), 133.068 (Ar-C), 130.076 (Ar-C), 128.623 (Ar-C), 126.980 (Ar-C), 124.391 (Ar-C), 122.620 (Ar-C), 122.270 (Ar-C), 120.504 (Ar-C), 112.123 (Ar-C), 111.655 (Ar-C).

2.2.5. BMHFI

M.p. 197–197.5 °C. Elemental analysis found (calculated) for C23H17N3O (%): C 77.59 (78.61), H 5.13 (4.88), N 12.22 (11.96). HRMS (ESI): m/z calculated for C23H17N3O + H+: 352.1450 [M + H+]; found: 352.1450. 1H NMR (DMSO-d6): 11.800 (s, 1H, –NH), 8.800 (s, 1H, –N=CH), 7.961–7.928 (m, 3H, J = 7.2 Hz, Ar-H), 7.767–7.218 (m, 10H, Ar-H), 7.087 (t, 1H, J = 7.6 Hz, Ar-H), 6.789 (t, 1H, J = 7.6 Hz, Ar-H). 13C NMR (DMSO-d6): 197.921(C=O), 163.669 (CH=N), 158.076 (CH=N), 137.065 (Ar-C), 135.223 (Ar-C), 134.228 (Ar-C), 134.056 (Ar-C), 132.698 (Ar-C), 131.033 (Ar-C), 130.507 (Ar-C), 129.266 (Ar-C), 129.180 (Ar-C), 128.936 (Ar-C), 128.554 (Ar-C), 128.369 (Ar-C), 127.445 (Ar-C), 126.900 (Ar-C), 124.230 (Ar-C), 122.793 (Ar-C), 121.724 (Ar-C), 120.659 (Ar-C), 111.860 (Ar-C), 111.605 (Ar-C).

2.2.6. BMHAI

M.p. 223.1–224.4 °C. Elemental analysis found (calculated) for C24H19N3O (%): C 79.24 (78.88), H 6.11 (5.24), N 12.03 (11.50). HRMS (ESI): m/z calculated for C24H19N3O + H+: 366.1606 [M + H+]; found: 366.1606. 1H NMR (DMSO-d6): 11.644 (s, 1H, –NH), 8.028–7.503 (m, 11H, J = 6.8 Hz, Ar-H), 7.318–7.266 (q, 2H, J = 8.4 Hz, Ar-H), 7.034–6.998 (t, 1H, J = 7.2 Hz, Ar-H), 6.649–6.612 (t, 1H, J = 7.2 Hz, Ar-H), 2.584 (s, 3H –CH3). 13C NMR (DMSO-d6): 198.911 (C=O), 163.948 (CH=N), 161.192 (CH=N), 136.957 (Ar-C), 134.953 (Ar-C), 134.166 (Ar-C), 133.209 (Ar-C), 131.003 (Ar-C), 130.813 (Ar-C), 129.467 (Ar-C), 129.226 (Ar-C), 129.056 (Ar-C), 128.868 (Ar-C), 126.831 (Ar-C), 124.468 (Ar-C), 122.699 (Ar-C), 122.632 (Ar-C), 122.147 (Ar-C), 121.559 (Ar-C), 121.275 (Ar-C), 120.132 (Ar-C), 114.671 (Ar-C), 111.414 (Ar-C), 14.688 (–CH3).

2.2.7. BMHMFI

M.p. 220.1–221.3 °C. Elemental analysis found (calculated) for C24H19N3O (%): C 79.25 (78.88), H 5.65 (5.24), N 11.89 (11.50). HRMS (ESI): m/z calculated for C24H19N3O + H+: 366.1606 [M + H+]; found: 366.1606. 1H NMR (DMSO-d6): 8.764 (s, 1H, –N=CH), 7.927 (d, 3H, J = 8.4 Hz, Ar-H), 7.749 (d, 2H, J = 7.6 Hz, Ar-H), 7.665–7.421 (m, 8H, Ar-H), 7.239–7.138 (m, 1H, Ar-H), 6.834 (t, 1H, J = 7.2 Hz, Ar-H), 3.799 (s, 3H –N—CH3). 13C NMR (DMSO-d6): 197.918 (C=O), 163.667 (CH=N), 157.569 (CH=N), 137.675 (Ar-C), 137.549 (Ar-C), 135.209 (Ar-C), 134.066 (Ar-C), 132.680 (Ar-C), 131.044 (Ar-C), 130.126 (Ar-C), 129.975 (Ar-C), 129.298 (Ar-C), 129.261 (Ar-C), 129.179 (Ar-C), 129.055 (Ar-C), 128.564 (Ar-C), 126.840 (Ar-C), 124.658 (Ar-C), 122.873 (Ar-C), 121.838 (Ar-C), 120.960 (Ar-C), 110.576 (Ar-C), 110.261 (Ar-C), 32.950 (–N—CH3).

2.2.8. BMHFN

M.p. 135.2–136.7 °C. Elemental analysis found (calculated) for C25H18N2O (%): C 82.18 (82.85), H 5.11 (5.01), N 7.84 (7.73). HRMS (ESI): m/z calculated for C25H18N2O + H+: 363.1497 [M + H+]; found: 363.1497. 1H NMR (DMSO-d6): 8.770 (s, 1H, –N=CH), 8.275 (t, 1H, J = 7.6 Hz, Ar-H), 8.167 (t, 3H, J = 7.6 Hz, Ar-H), 7.852 (q, 4H, J = 7.6 Hz, Ar-H), 7.589–7.320 (m, 6H, Ar-H), 7.080 (t, 2H, J = 7.2 Hz, Ar-H), 6.850 (t, 1H, J =7.6 Hz, Ar-H). 13C NMR (DMSO-d6): 196.873 (C=O), 162.531 (CH=N), 156.980 (CH=N), 139.701 (Ar-C), 137.101 (Ar-C), 136.981 (Ar-C), 135.238 (Ar-C), 134.231 (Ar-C), 134.107 (Ar-C), 132.702 (Ar-C), 131.051 (Ar-C), 130.515 (Ar-C), 129.277 (Ar-C), 129.176 (Ar-C), 128.907 (Ar-C), 128.499 (Ar-C), 128.402 (Ar-C), 127.391 (Ar-C), 126.879 (Ar-C), 124.121 (Ar-C), 122.741 (Ar-C), 121.698 (Ar-C), 120.571 (Ar-C), 111.761 (Ar-C), 109.432 (Ar-C).

2.3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1[link]. All H atoms in the eight com­pounds (except for the H atoms on C35 in BDHMFI) were found in difference Fourier maps and then allowed to ride on their parent atoms. The location and isotropic displacement parameters of the H atoms on C35 in BDHMFI were refined freely.

Table 1
Experimental details

Experiments were carried out with Mo Kα radiation using a Bruker SMART CCD area detector. Absorption was corrected by multi-scan methods (SADABS; Bruker, 2000[Bruker (2000). SMART, SAINT, SADABS, XPREP and SHELXTL. Bruker AXS Inc., Madison, Wisconsin, USA.]). Only H atoms were constrained to ride on their bonding partners, but with freely refined Uiso values.

  BDHFI BDHAI BDHMFI BDHFN
Crystal data
Chemical formula C32H24N6 C34H28N6 2C34H28N6·C2H3N C36H26N4
Mr 492.57 520.62 1082.30 514.61
Crystal system, space group Monoclinic, P21/c Triclinic, P[\overline{1}] Triclinic, P[\overline{1}] Monoclinic, C2/c
Temperature (K) 293 293 293 298
a, b, c (Å) 13.023 (4), 7.340 (2), 27.762 (9) 10.2585 (4), 11.9610 (5), 12.8232 (6) 11.2710 (6), 11.6944 (7), 12.5164 (6) 26.195 (8), 9.809 (3), 11.806 (4)
α, β, γ (°) 90, 97.693 (5), 90 64.941 (4), 79.573 (3), 76.829 (4) 79.875 (4), 87.701 (4), 64.941 (6) 90, 115.230 (5), 90
V3) 2630.0 (14) 1381.45 (11) 1470.10 (15) 2744.2 (15)
Z 4 2 1 4
μ (mm−1) 0.08 0.08 0.08 0.07
Crystal size (mm) 0.30 × 0.18 × 0.15 0.35 × 0.15 × 0.12 0.35 × 0.20 × 0.15 0.30 × 0.16 × 0.10
 
Data collection
Tmin, Tmax 0.903, 0.939 0.903, 0.939 0.905, 0.943 0.986, 0.993
No. of measured, independent and observed [I > 2σ(I)] reflections 13632, 5145, 2852 15195, 5328, 4490 13418, 5640, 4445 6631, 2413, 1197
Rint 0.046 0.026 0.029 0.058
(sin θ/λ)max−1) 0.617 0.618 0.617 0.595
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.103, 0.88 0.044, 0.129, 1.05 0.049, 0.151, 1.04 0.062, 0.130, 0.95
No. of reflections 5145 5328 5640 2413
No. of parameters 367 392 424 194
No. of restraints 0 0 2 0
Δρmax, Δρmin (e Å−3) 0.15, −0.22 0.19, −0.19 0.22, −0.17 0.11, −0.10
  BMHFI BMHAI BMHMFI BMHFN
Crystal data
Chemical formula C23H17N3O C24H19N3O C24H19N3O C25H18N2O
Mr 351.39 365.42 365.42 362.41
Crystal system, space group Orthorhombic, P212121 Tetragonal, P43212 Monoclinic, P21/c Monoclinic, P21/c
Temperature (K) 293 293 293 293
a, b, c (Å) 6.8767 (1), 8.3698 (2), 32.6317 (6) 8.3580 (1), 8.3580 (1), 54.6705 (7) 18.6779 (6), 8.6694 (3), 12.7956 (4) 17.2081 (13), 9.4075 (8), 11.9703 (9)
α, β, γ (°) 90, 90, 90 90, 90, 90 90, 106.910 (4), 90 90, 94.814 (7), 90
V3) 1878.17 (6) 3819.07 (10) 1982.36 (12) 1931.0 (3)
Z 4 8 4 4
μ (mm−1) 0.08 0.08 0.08 0.08
Crystal size (mm) 0.35 × 0.1 × 0.09 0.3 × 0.1 × 0.1 0.33 × 0.28 × 0.25 0.40 × 0.40 × 0.16
 
Data collection
Tmin, Tmax 0.903, 0.939 0.983, 0.998 0.971, 0.987 0.970, 0.989
No. of measured, independent and observed [I > 2σ(I)] reflections 10418, 3641, 3444 21746, 3759, 3565 9410, 3837, 2964 10556, 3396, 1411
Rint 0.023 0.030 0.021 0.078
(sin θ/λ)max−1) 0.618 0.618 0.618 0.595
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.096, 1.02 0.041, 0.113, 1.06 0.045, 0.140, 1.03 0.052, 0.083, 0.87
No. of reflections 3641 3759 3837 3396
No. of parameters 262 274 274 272
No. of restraints 0 0 0 0
Δρmax, Δρmin (e Å−3) 0.15, −0.13 0.16, −0.12 0.16, −0.15 0.15, −0.15
Absolute structure Not determined because of low anomalous signal Not determined because of low anomalous signal
Absolute structure parameter −1.4 (6) −1.5 (6)
Computer programs: SMART (Bruker, 2000[Bruker (2000). SMART, SAINT, SADABS, XPREP and SHELXTL. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT (Bruker, 2000[Bruker (2000). SMART, SAINT, SADABS, XPREP and SHELXTL. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS2016 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXTL (Bruker, 2000[Bruker (2000). SMART, SAINT, SADABS, XPREP and SHELXTL. Bruker AXS Inc., Madison, Wisconsin, USA.]), PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]), DIAMOND (Brandenburg & Putz, 1999[Brandenburg, K. & Putz, H. (1999). DIAMOND. Crystal Impact GbR, Bonn, Germany.]), SHELXL2016 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]) and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

2.4. Cytotoxicity assays

Human lung carcinoma A549 cells, mouse breast cancer 4T1 cells, human MRC-5 lung normal cells and normal mouse NIH 3T3 fibroblasts were purchased from the Shanghai Cell Bank, Type Culture Collection Committee, Chinese Academy of Sciences. The cells were cultured in F12K medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 2 mM glutamine, 100 U ml−1 penicillin and 100 µg ml−1 streptomycin, and maintained at 310 K in a humidified atmosphere of 5% CO2.

The cells (8000 cells) were seeded on 96-well microtiter plates in F12K medium with 10% FBS and incubated overnight. The cell culture medium was replaced by different doses of the com­pound solution, i.e. 1, 5, 10, 30, 50, 100 and 150 µM, and then the cells were cultured for another 72 h. The MTT reagent was added to the cell supernatant for a final concentration of 0.5 mg ml−1 of MTT. After 3 h, the cell culture medium was removed. Formazan crystals in adherent cells were dissolved in dimethyl sulfoxide (DMSO, 200 µl) and the absorbance of the formazan solution was measured. Each com­pound was tested in triplicate and the experiments were repeated three times.

Generally, the operations from cell culture to MTT assay for cell proliferation are the same as we reported before (Cheng et al., 2016[Cheng, S.-S., Shi, Y., Ma, X.-N., Xing, D.-X., Liu, L.-D., Liu, Y., Zhao, Y.-X., Sui, Q.-C. & Tan, X.-J. (2016). J. Mol. Struct. 1115, 228-240.]; Bu et al., 2017[Bu, F.-Z., Tan, X.-J., Xing, D.-X. & Wang, C. (2017). Acta Cryst. C73, 546-555.]; Tan et al., 2019[Tan, X.-J., Zhang, L.-Y., Sun, Y.-K. & Zhou, X.-M. (2019). Acta Cryst. C75, 97-106.]).

2.5. Mol­ecular docking and quantum chemistry calculations

Mol­ecular docking studies of all eight Schiff bases with 18 potential target proteins were performed using the SYBYL/Surflex-dock (Tripos, 2012[Tripos (2012). SYBYL-X. Version 2.0. Tripos International, St Louis, MO, USA. http://www.tripos.com.]) in order to screen the potential targets and illustrate the binding modes between proteins and ligands. All solvent mol­ecules except those within 5 Å around the natural ligand were removed from the protein structure. The mol­ecular structures of the ligands were first extracted from the single-crystal X-ray structure and then optimized by em­ploying density functional theory (DFT) at the B3LYP/6-311+G(d,p) level (Becke, 1993[Becke, A. D. (1993). J. Chem. Phys. 98, 5648-5652.]; Lee et al., 1988[Lee, C., Yang, W. & Parr, R. G. (1988). Phys. Rev. B, 37, 785-789.]; McLean & Chandler, 1980[McLean, A. D. & Chandler, G. S. (1980). J. Chem. Phys. 72, 5639-5648.]; Krishnan et al., 1980[Krishnan, R., Binkley, J. S., Seeger, R. & Pople, J. A. (1980). J. Chem. Phys. 72, 650-654.]). The default parameters were used regarding charges, bonds order and geometrical flexibility with no other constraints.

Except for the aforementioned structural optimizations, quantum chemistry calculations were also used to explore inter­molecular inter­actions in the BMHFI crystal (see §3.1.5[link]). Two methods, i.e. MP2/6-31G(d,p) and DFT/B3LYP/6-311G+(d,p), were used (Møller & Plesset, 1934[Møller, C. & Plesset, M. S. (1934). Phys. Rev. 46, 618-622.]; Rassolov et al., 2001[Rassolov, V. A., Ratner, M. A., Pople, J. A., Redfern, P. C. & Curtiss, L. A. (2001). J. Comput. Chem. 22, 976-984.]; Frisch et al., 1984[Frisch, M. J., Pople, J. A. & Binkley, J. S. (1984). J. Chem. Phys. 80, 3265-3269.]). The standard counterpoise method was applied to correct inter­action energies for the basis set superposition error (BSSE) (Boys & Bernardi, 1970[Boys, S. B. & Bernardi, F. (1970). Mol. Phys. 19, 553-566.]). All geometries are extracted from the inter­acting pairs in the crystal of BMHFI without any structural relaxation.

All calculations were carried out using the GAUSSIAN03 program package (Frisch et al., 2004[Frisch, M. J., et al. (2004). GAUSSIAN03. Revision C.02. Gaussian Inc., Wallingford, CT, USA. http://www.gaussian.com.]) on a Sunway BlueLight MPP supercom­puter housed at the National Supercom­puter Center in Jinan, China.

3. Results and discussion

3.1. X-ray structures of the eight title com­pounds

The identities of the conformations of the eight title com­pounds have been established through X-ray structure determinations, which clearly show the similarities and differences.

3.1.1. BDHFI

The monomeric structure of BDHFI is shown in Fig. 1[link](a), which indicates that the mol­ecule contains a pair of linkage arms (the connection point is the C1—C8 bond axis). The pair of linkage arms crosses each other in an X-shape; each arm has a similar conformation, i.e. the two C=N double bonds adopt the same Z,E conformations in both arms. In fact, the other three di-Schiff bases (BDHAI, BDHMFI and BDHFN) reported in this article are X-shaped mol­ecules and the two X-shaped arms in BDHFN are exactly the same (see §3.1.4[link]).

[Figure 1]
Figure 1
(a) The mol­ecular structure of BDHFI, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K. (b) The Hirshfeld surface for BDHFI, mapped over dnorm (−0.10 to 1.40 Å, same throughout this article). Four red spots correspond to N5—H35⋯N1(−x + 2, y + [{1\over 2}], −z + [{1\over 2}]) (marked a) and N6—H36⋯π (marked b) inter­actions, respectively. (c) The shape-index surface of BDHFI, identifying ππ stacking inter­actions (marked c). Only red and blue triangles on the surface are shown for clarity. (d) Hydrogen bonds a (green dashed lines) and b (red dashed lines) link mol­ecules into infinite 1D chains parallel to the crystallographic b and a axes, respectively, viewed along the crystallographic [8, [\overline{1}], 17] direction. Eight mol­ecules are illustrated by the simplified structure (centre of gravity) for clarity and the two colours (red and green) represent two different orientations.

Both arms in BDHFI are rather flat. One arm consists of atoms C1–C7/N1/N2/C24–C31/N6/C32 and all 19 non-H atoms are essentially coplanar, with an average r.m.s. deviation of only 0.0811 Å and the largest r.m.s. deviation of −0.1435 Å occurring for atom N6. In another arm, all 19 non-H atoms are slightly less coplanar, with an average r.m.s. deviation of 0.1742 Å (the largest r.m.s. deviation of 0.3027 Å occurs for atom N5). The dihedral angle between the planes of these two arms is about 89.3°.

In the packing structure of BDHFI, three kinds of dominant noncovalent inter­actions (NCIs), including hydrogen bond a (Fig. 1[link]b), C—H⋯π inter­action b (Fig. 1[link]b) and ππ packing c (Fig. 1[link]c), can be found with the help of PLATON (Tables S1–S3 in the supporting information). The CrystalExplorer17 program (Hirshfeld, 1977[Hirshfeld, F. L. (1977). Theor. Chim. Acta, 44, 129-138.]; Turner et al., 2017[Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17. University of Western Australia. http://crystalexplorer.scb.uwa.edu.au/.]) was used to verify the strength of these NCIs. It is worth noting that the geometries of all NCIs, including these very weak ones, calculated by PLATON are listed in the supporting information for all eight com­pounds reported in this article (Tables S1–S21 in the supporting information). But only those strong NCIs that can be verified by CrystalExplorer17 will be analysed. For the convenience of description, different kinds of strong NCIs are simplified into various notations (the first column in Tables S1–S21 in the supporting information). These weak inter­molecular NCIs and all intra­molecular NCIs are not coded because they make less contribution to the packing structure. For example, the C3—H3⋯N3(x, y − 1, z) hydrogen bond (Table S1 in the supporting information) is not coded because its role is not apparent in the Hirshfeld surface analysis (Fig. 1[link]b). In rare cases, some `strong' inter­actions verified by CrystalExplorer17 have not been suggested by PLATON, for example, N3—H25⋯N2(x + [{1\over 2}], −y + [{1\over 2}], −z + [{1\over 4}]) and C24—H24A⋯O1(x + 1, y, z) in Fig. 6(b) (see §3.1.6[link]), and C11—H11⋯N1(x, −y − [{1\over 2}], z − [{1\over 2}]) in Fig. 7(b) (see §3.1.7[link]). Their roles will not be analysed.

Hydrogen bonds a and b link BDHFI mol­ecules into one-dimensional (1D) chains parallel to the b and a axes, respectively (Fig. 1[link]d), while ππ inter­action c links two mol­ecules into a dimer. These chains and dimers serve as the main building blocks for the three-dimensional (3D) structures with the aid of other kinds of NCIs, such as van der Waals.

It should be mentioned that all the mol­ecules in BDHFI adopt two relative orientations, which are highlighted with red and green colours, respectively (Fig. 1[link]d). If these two relatively small arene rings in one mol­ecule are omitted, the X-shaped mol­ecule can be regarded as a V-shaped one. These V-shaped mol­ecules open towards entirely opposite directions: the red ones are directed toward the positive half of the c axis, while the green ones are directed toward the negative half (both roughly). Inter­estingly, the mol­ecules in the other three di-Schiff bases have two similar orientations, so there also exist red and green highlighted mol­ecules in Figs. 2[link], 3[link] and 4[link]. While mol­ecules in the four mono-Schiff bases (BMHFI, BMHAI, BMHMFI and BMHFN) have four or eight orientations, mostly because of the two apparently asymmetrical arms (see §3.1.5 to §3.1.8[link][link][link][link]).

[Figure 2]
Figure 2
(a) The mol­ecular structure of BDHAI, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K. (b) The Hirshfeld surface for BDHAI, mapped over dnorm. Four red spots correspond to N6—H36⋯N4(−x, −y + 1, −z + 1) (marked a) and N5—H35⋯π (marked b) inter­actions, respectively. (c) The shape-index surface of BDHAI, identifying ππ stacking inter­actions (marked c and d). Only red and blue triangles on the surface are shown for clarity. (d) Four kinds of NCIs, i.e. a, b, c and d (shown with red, green, purple and yellow dashed lines, respectively), link BDHAI mol­ecules into an infinite 1D chain extending roughly along the [11[\overline{1}]] direction, viewed along the [7, [\overline{3}], 7] direction.
[Figure 3]
Figure 3
(a) The mol­ecular structure of BDHMFI, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K [symmetry code: (A) −x + 2, −y, −z]. (b) The dimer structure formed by two BDHMFI mol­ecules and one disordered aceto­nitrile mol­ecule through hydrogen bonds a (two red spots on the dnorm Hirshfeld surface). (c) The shape-index surface of BDHMFI, identifying ππ stacking inter­action b. Only red and blue triangles on the surface are shown for clarity. (d) NCIs a and b (shown with red and green dashed lines, respectively) link BDHMFI mol­ecules into an infinite 1D chain extending roughly along the [10[\overline{3}]] direction, viewed along the [1, 9, [\overline{5}]] direction.
[Figure 4]
Figure 4
(a) The mol­ecular structure of BDHFN, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K [symmetry code: (A) −x, y, −z + [{1\over 2}]]. (b) The contribution of C⋯C contacts in the 2D fingerprints of BDHFN, indicating ππ inter­action a. (c) The shape-index surface of BDHFN, identifying ππ stacking inter­action a (not marked as there is only one type of interaction). (d) 1D chains formed by ππ stacking inter­action a (shown with red dashed lines), viewed along the [501] direction. The upper one is illustrated by the simplified structure (centre of gravity).
3.1.2. BDHAI

Similar to BDHFI, BDHAI is an X-shaped mol­ecule with both arms being somewhat flat. But the coplanarity is worse than in BDHFI. In one arm, consisting of atoms C1–C7/N1/N2/C24–C31/N6/C32/C34, the average r.m.s. deviation is 0.3698 Å and the largest r.m.s. deviation of 0.8308 Å occurs for atom C7. In another arm, all 20 non-H atoms have an average r.m.s. deviation of 0.2542 Å and the largest r.m.s. deviation of 0.4662 Å occurs for atom N5. The dihedral angle between the planes of the two arms is about 98.0° (Fig. 2[link]a).

In the packing structure of BDHAI, the most important four NCIs link mol­ecules into dimers independently (Tables S4–S6 in the supporting information). Hydrogen bonds a link two mol­ecules into a dimer (Figs. 2[link]b and 2d), while b, c and d link two mol­ecules into another dimer (Figs. 2[link]b, 2c and 2d), whether they are used separately or collectively. But a, b, c and d will crosslink mol­ecules into infinite 1D chains if working together (Fig. 2[link]d).

3.1.3. BDHMFI

The monomeric structure of BDHMFI is depicted in Fig. 3[link](a), which contains one com­plete BDHMFI mol­ecule and a half aceto­nitrile mol­ecule in the asymmetric unit. The half aceto­nitrile mol­ecule lies on an inversion centre (atom C35, which resides on a centre of inversion at the origin) and was refined disordered into two parts with the site-occupancy factors being fixed at 0.5. The inversion operator will create two BDHMFI mol­ecules and one com­plete aceto­nitrile mol­ecule, which are linked together by hydrogen bonds a (Fig. 3[link]b). By the way, a only occurs between BDHMFI and aceto­nitrile (Figs. 3[link]b and 3d).

These two arms of X-shaped BDHMFI have a similar coplanarity to that in BDHFI. In one arm, consisting of atoms C1–C7/N1/N2/C24–C31/N6/C32/C34, the average r.m.s. devi­ation is 0.1063 Å and the largest r.m.s. deviation of 0.1870 Å occurs for atom C6. In another arm, all 20 non-H atoms have an average r.m.s. deviation of 0.1964 Å and the largest r.m.s. deviation of 0.4540 Å occurs for atom C33. The dihedral angle between the planes of these two arms is about 90.6°.

Either hydrogen bond a or ππ inter­action b links two adjacent BDHMFI mol­ecules into dimers, but they are not the same dimer (Figs. 3[link]b and 3c). If a and b collaborate together, 1D chains extending along the crystallographic [24, 1, [\overline{63}]] direction will be formed (Fig. 3[link]d).

3.1.4. BDHFN

The mol­ecular structure of BDHFN is shown in Fig. 4[link](a), which is the result of a glide reflection along the crystallographic c axis. That is to say, the asymmetric unit contains only one half BDHMFI mol­ecule, which happened to be one arm of the X-shaped structure. The dihedral angle between the planes of the naphthalene and arene rings is 22.6 (3)° and the dihedral angle between the two symmetry-related arms is 85.1 (4)°.

The only kind of hydrogen bond is intra­molecular inter­actions in the packing structure of BDHFN (Table S10 in the supporting information). Besides van der Waals, only one kind of inter­molecular ππ inter­action a plays an important role (Table S11 in the supporting information), which accounts for merely 6.1% of the Hirshfeld surface (Fig. 4[link]b). That is to say, it is van der Waals interactions that play a critical role in the crystal mol­ecular assembly. As for ππ inter­actions a (Fig. 4[link]c), they help to link BDHFN mol­ecules into 1D lines parallel to the crystallographic c axis (Fig. 4[link]d).

3.1.5. BMHFI

The mol­ecular structure of BMHFI is shown in Fig. 5[link](a), which indicates that the mol­ecule still contains a pair of linkage arms, but one arm is shorter than the other because one C=O group has not been converted into a Schiff base. The longer arm has a similar conformation to that in its corresponding di-Schiff base BDHFI, i.e. these two C=N double bonds adopt the same Z,E conformations. In fact, all eight Schiff bases reported in this paper adopt similar Z,E conformations.

[Figure 5]
Figure 5
(a) The mol­ecular structure of BMHFI, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K. (b) The Hirshfeld surface for BMHFI, mapped over dnorm. Three red spots correspond to N3—H24⋯O1(x + [{1\over 2}], −y + [{1\over 2}], −z) (marked a) and C3—H3⋯O1(x + 1, y, z) (marked b) inter­actions. (c) 1D chains formed by NCIs a and b (shown with green and red dashed lines, respectively), viewed perpendicular to the extending direction, i.e. the a axis. The upper two lines are illustrated by the simplified structure (centre of gravity). (d) 1D chains formed by the aforementioned NCIs a and b, viewed along the extending direction, i.e. the a axis, aiming to show the packing mode of four different orientations (simplified structure with four different colours).

As a whole, both arms in BMHFI are flat. The long arm has an average r.m.s. deviation of 0.2242 Å and the largest r.m.s. devi­ation of −0.3858 Å occurs for N3. The short arm has much better coplanarity, with an average r.m.s. deviation of only 0.0160 Å (the largest r.m.s. deviation of −0.0647 Å occurs for O1). The dihedral angle between the two arms is about 93.8°.

In the packing structure of BMHFI, two kinds of inter­molecular hydrogen bonds (a and b) (Table S12 in the supporting information) link mol­ecules into 1D chains parallel to the crystallographic a axis, whether they are used separately or collectively. Unlike its corresponding di-Schiff base BDHFI, BMHFI adopts four relative orientations, which are highlighted in red, green, purple and blue (Figs. 5[link]c and 5d). It should be noted that the colour intensity of the vivid spot representing hydrogen bond a is very high, indicating a strong hydrogen bond. Thus, the inter­molecular inter­action energy with the BSSE correction has been calculated using the MP2/6-31G(d,p) and B3LYP/6-311G+(d,p) methods on the basis of dimer geometries extracted from the crystal structure. The calculated inter­action energies for a and b are −50.97 and −19.92 kJ mol−1 (MP2), and −19.71 and −4.25 kJ mol−1 (DFT), respectively, indicating a much stronger favourable binding energy for a than that for b, which agrees with the colour intensity in the dnorm map (Fig. 5[link]b).

3.1.6. BMHAI

The `long arm' in BMHAI assumes less coplanarity than that in BMHFI, and even less than that in BDHAI, which can be deduced from the dihedral angles between the indole and arene rings (Fig. 6[link]a). In BMHFI, the value is 20.4 (4)°, while in BDHAI, the dihedral angles are 23.6 (4) and 39.9 (5)°, but in BMHAI, this value is increased to 54.5 (3)°.

[Figure 6]
Figure 6
(a) The mol­ecular structure of BMHAI, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K [symmetry code: (A) −x, y, −z + [{1\over 2}]]. (b) The Hirshfeld surface for BMHAI, mapped over dnorm. Three kinds of inter­molecular hydrogen bonds and one kind of intra­molecular hydrogen bond can be visualized as red spots, but only hydrogen bond a was confirmed by the PLATON program (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]). (c) 1D chains along the a and b axes formed by the aforementioned hydrogen bonds a (shown with red dashed lines), viewed along the a axis, aiming to show the packing mode of the eight different orientations as a simplified structure with eight different colours, i.e. orange, red, green, blue, purple, violet, yellow and indigo.

There are eight kinds of mol­ecular orientations and one kind of inter­molecular hydrogen bond, i.e. a, in the crystal structure of BMHAI (Figs. 6[link]b and 6c) (Tables S15–S17 in the supporting information). Hydrogen bonds a link mol­ecules into two kinds of 1D chains, one is parallel to the crystallographic a axis (these mol­ecules are simplified into green, blue, yellow and indigo skeletons in Fig. 6[link]c) and the other is parallel to the b axis (these mol­ecules are simplified into orange, red, purple and violet skeletons in Fig. 6[link]c).

3.1.7. BMHMFI

Both the `long arm' and the `short arm' in BMHMFI have good coplanarity. The dihedral angle between the planes of the indole and arene rings in the `long arm' is only 14.0 (2)°. The long arm has an average r.m.s. deviation of 0.1492 Å and the largest r.m.s. deviation is 0.3816 Å for atom C24; the short arm has an average r.m.s. deviation of only 0.0324 Å and the largest r.m.s. deviation is 0.1135 Å for atom O1. These two arms are roughly perpendicular to each other, with a dihedral angle of 91.1 (3)° (Fig. 7[link]a).

[Figure 7]
Figure 7
(a) The mol­ecular structure of BMHMFI, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K. (b) The Hirshfeld surface for BMHMFI, mapped over dnorm. The inter­molecular hydrogen bonds a calculated using PLATON, but another kind of hydrogen bond [C11—H11⋯N1(x, −y − [{1\over 2}], z − [{1\over 2}]), which can be found as red spots] was not suggested by PLATON. (c) The shape-index surface of BMHMFI, identifying ππ stacking inter­actions b and c. (d) 1D chains formed by C—H⋯π inter­actions a (shown with red dashed lines) can be woven into a 2D layer structure by ππ inter­actions b and c (shown with green and blue dashed lines, respectively), viewed along the a axis.

The most intense red spots represent a C23—H23⋯ring(C17–C22)(−x + 1, y + [{1\over 2}], −z + [{1\over 2}]) inter­action, coded as a (Fig. 7[link]b) (Table S18 in the supporting information), which links mol­ecules into a 1D chain parallel to the b axis (Fig. 7[link]d). The second intense spot represents a C11—H11⋯N1(x, −y − [{1\over 2}], z − [{1\over 2}]) hydrogen bond (Fig. 7[link]b), which was not suggested by PLATON. Thus, its role in the packing structure will not be analysed in this article. Two kinds of inter­molecular ππ inter­actions (b and c) always co-exist (Fig. 7[link]c) (Table S19 in the supporting information), and they link two adjacent mol­ecules into a dimer (Fig. 7[link]d). The collaboration of a, b and c links mol­ecules into a 2D layer structure (Fig. 7[link]d).

3.1.8. BMHFN

The dihedral angle between the planes of the naphthalene and benzene rings in the `long arm' is 24.2 (5)°. The dihedral angle between the long and short arms is about 81.4 (5)° (Fig. 8[link]a).

[Figure 8]
Figure 8
(a) The mol­ecular structure of BMHFN, showing the atom-labelling scheme, with displacement ellipsoids for non-H atoms drawn at the 30% probability level at 293 K. (b) The Hirshfeld surface for BMHFN, mapped over dnorm. Two red spots correspond to C5—H5⋯O1(−x + 1, y − [{1\over 2}], −z + [{3\over 2}]) (marked a). (c) The shape-index surface of BMHFN, identifying ππ stacking inter­actions b, c and d. Only red and blue triangles on the surface are shown for clarity. (d) 2D layer structure formed by NCIs a b, c and d (shown with red, green, blue and yellow dashed lines, respectively), viewed along the a axis. Four discontinuous lines are shown, the left two (along the b axis) are formed by NCI a and the top two (along the c axis) are formed by NCIs b and d. Mol­ecules in the bottom right corner are illustrated by the simplified structure (centre of gravity), showing four kinds of orientations.

There are four kinds of mol­ecular orientations and four kinds of inter­molecular NCIs (a, b, c and d) in the crystal structure of BMHFN (Figs. 8[link]b, 8c and 8d) (Tables S20 and S21 in the supporting information). Hydrogen bond a links mol­ecules into 1D chains parallel to the crystallographic b axis (Figs. 8[link]b and 8d). Among these three types of ππ stacking inter­actions, b and d always co-exist and link mol­ecules into 1D chains parallel to the crystallographic c axis (Figs. 8[link]c and 8d), c joins two mol­ecules (red and green, and blue and yellow; Fig. 8[link]d) into dimers. The co-operation of all three types of ππ stacking inter­actions (b, c and d) links mol­ecules into a 2D layer structure extending along the crystallographic (100) plane (Fig. 8[link]d). In fact, all four kinds of inter­molecular NCIs crosslink mol­ecules into the same infinite 2D layer structure.

3.2. Cytotoxicity assays – inhibition of lung and breast cancer cell growth

To study the growth inhibitory effects of these eight Schiff bases on lung/breast cancer cells, we treated human A549 and mouse 4T1 cells with the com­pounds and examined the growth of cells with an MTT assay. Meanwhile, MRC-5 normal lung cells and NIH 3T3 fibroblasts were also tested using the same method in order to evaluate the selective cytotoxicity of these new com­pounds. All experiments were carried out with cisplatin (a com­pound used as a chemotherapy drug to treat many types of cancers) for com­parison. The cytotoxic activities as 50% inhibitory concentration (IC50) values are shown in Table 2[link].

Table 2
Inhibition of A549, 4T1, MRC-5 and NIH 3T3 cell growth by the title com­pounds com­pared with cisplatin (μM)

Compound A549 cells, IC50 4T1 cells, IC50 MRC-5 cells, IC50 NIH 3T3 fibroblasts, IC50
BDHFI 8.0±0.5 7.5±0.5 24.5±1.5 29.5±1.0
BDHAI 8.5±0.6 7.0±0.6 36.5±1.5 43.0±1.5
BDHMFI 125.0±1.0 122.0±1.0 >150.0 >150.0
BDHFN 130.0±1.0 125.0±1.0 >150.0 >150.0
BMHFI 46.5±0.5 32.5±0.5 88.0±1.5 85.0±1.5
BMHAI 43.0±0.5 30.0±0.5 83.0±1.5 76.0±1.5
BMHMFI 148.0±1.2 141.0±1.0 >150.0 >150.0
BMHFN 150.0±1.2 148.0±1.0 >150.0 >150.0
Cisplatin 6.5 ± 0.5 0.5 ± 0.1 22.5 ± 1.5 21.0 ± 1.0

As we can see, both BDHFI and BDHAI have similar cytotoxic activities to the standard cisplatin for both cancer cell lines. All mono-Schiff bases show slightly weaker inhibitory activity of A549 and 4T1 com­pared with their corresponding di-Schiff bases. Incorporating a CH3 group at the N—H position in the indole ring proved detrimental for anti­cancer activity (BDHMFI and BMHMFI), while substitution on the imine C atom has little effect (BDHAI and BMHAI). This might be due to the availability of enough space to accommodate a methyl group at this particular site of the inhibitor binding pocket, or the N—H group favours combination with the hydrogen-bonding pocket. In one word, for BDHFI, BDHAI, BMHFI and BMHAI, the normal indole rings should contribute greatly to their cytotoxicities. When indole rings are changed into 1-methylindole or naphthalene, the cytotoxicity is greatly decreased.

As for the selective cytotoxicity between normal and malignant cells, MTT assays reveal a similar pattern to what were seen in our previous work (Tan et al., 2019[Tan, X.-J., Zhang, L.-Y., Sun, Y.-K. & Zhou, X.-M. (2019). Acta Cryst. C75, 97-106.]). That is to say, all Schiff bases possess selective cytotoxicity on cancer cells over normal cells. But they have relevant inhibitory concentrations. The higher the IC50 value for selected malignant cells, the higher the value for responding normal cells. Among them, BDHFI, BDHAI, BMHFI and BMHAI displayed high potency and selectivity in all cell lines.

These experimental studies clearly predict cytotoxic activities of indole-containing Schiff bases. Such encouraging preliminary results confirm the feasibility and reliability of this excellent framework in the discovery of potent anti­tumour agents.

3.3. Reverse docking studies for target fishing

In order to find a few most possible mol­ecular targets for these Schiff bases, Swiss Target Prediction web server (http://www.swisstargetprediction.ch/) (Daina et al., 2019[Daina, A., Michielin, O. & Zoete, V. (2019). Nucleic Acids Res. 47, W357-W364.]; Gfeller et al., 2013[Gfeller, D., Michielin, O. & Zoete, V. (2013). Bioinformatics, 29, 3073-3079.]) was used for the initial selection of potential targets. For each of these eight Schiff bases, 100 most potential targets were selected for further evaluation. Then cross screenings were carried out among these eight sets of potential targets based on the following method. Firstly, eight sets of targets were divided into two groups according to the anti­proliferative activities of the Schiff bases. Four sets of potential targets related to BDHFI, BDHAI, BMHFI and BMHAI belong to group 1, and another four sets of potential targets related to BDHMFI, BDHFN, BMHMFI and BMHFN are group 2. Considering that all the Schiff bases in group 1 have a similar skeleton and have much higher activities than those in group 2, the targets in group 1 are probably the same, while the ligands in group 2 should not hit these targets. Technically, the most probable targets should be hit four times in group 1 and should not be hit in group 2. In our work, the targets that were hit four or three times in group 1 were selected (total of 32 targets) on account of random error in the prediction model. But if one target was also hit more than twice (including twice) in group 2, it should be removed (14 targets were removed). In the end, 18 targets remained for further screening through the reverse docking method.

As mentioned above, the initially assessed Rounds com­prised a total of 18 targets. Only two of these targets do not have detailed 3D structural information, i.e. Neurokinin 2 receptor and Serotonin 6 (5-HT6) receptor. Thus, homology models built using the SWISS-MODEL server (https://swissmodel.expasy.org/) (Waterhouse et al., 2018[Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F. T., de Beer, T. A. P., Rempfer, C., Bordoli, L., Lepore, R. & Schwede, T. (2018). Nucleic Acids Res. 46, W296-W303.]; Bienert et al., 2017[Bienert, S., Waterhouse, A., de Beer, T. A. P., Tauriello, G., Studer, G., Bordoli, L. & Schwede, T. (2017). Nucleic Acids Res. 45, D313-D319.]) and optimized by SYBYL-X (Tripos, 2012[Tripos (2012). SYBYL-X. Version 2.0. Tripos International, St Louis, MO, USA. http://www.tripos.com.]) were used. The structure of Neurokinin 2 receptor was modelled on the bovine rhodopsin crystal structure (PDB ID: 1f88) as a template (Chandrashekaran et al., 2009[Chandrashekaran, I. R., Rao, G. S. & Cowsik, S. M. (2009). J. Chem. Inf. Model. 49, 1734-1740.]), while the structure of the 5-HT6 receptor was modelled using the β2 adrenergic receptor template (PDB ID: 4lde) (Łażewska et al., 2017[Łażewska, D., Kurczab, R., Więcek, M., Kamińska, K., Satała, G., Jastrzębska-Więsek, M., Partyka, A., Bojarski, A. J., Wesołowska, A., Kieć-Kononowicz, K. & Handzlik, J. (2017). Eur. J. Med. Chem. 135, 117-124.]) (Figs. S17 and S18 in the supporting information). Though the obtained models exhibit only limited accuracy, it has been demonstrated that the modelled receptor pocket conformations can be validated or improved via docking of known ligands. For the Neurokinin 2 receptor, ligand 6-methyl­benzo[b]thio­phene-2-carb­oxy­lic acid (1-{(S)-1-benzyl-4-[4-(tetra­hydro­pyran-4-ylmeth­yl)piperazin-1-yl]butyl­carbamo­yl}cyclo­pent­yl)amide (abbreviated as 10i in the original article) was used as the well-known antagonist with high affinity (Fattori et al., 2010[Fattori, D., Porcelloni, M., D'Andrea, P., Catalioto, R.-M., Ettorre, A., Giuliani, S., Marastoni, E., Mauro, S., Meini, S., Rossi, C., Altamura, M. & Maggi, C. A. (2010). J. Med. Chem. 53, 4148-4165.]). As for the 5-HT6 receptor, AVN-492, a new promising ligand (now tested in phase I trials) was selected (Ivachtchenko et al., 2017[Ivachtchenko, A. V., Okun, I., Aladinskiy, V., Ivanenkov, Y., Koryakova, A., Karapetyan, R., Mitkin, O., Salimov, R. & Ivashchenko, A. (2017). J. Alzheimers Dis. 58, 1043-1063.]; Łażewska et al., 2019[Łażewska, D., Kurczab, R., Więcek, M., Satała, G., Kieć-Kononowicz, K. & Handzlik, J. (2019). Bioorg. Chem. 84, 319-325.]).

Eventually, all eight Schiff bases were docked into these 18 possible targets with the program SYBYL-X (Tripos, 2012[Tripos (2012). SYBYL-X. Version 2.0. Tripos International, St Louis, MO, USA. http://www.tripos.com.]) by calculating the Total Score of Surflex-dock (Table 3[link]) (Rarey et al., 1996[Rarey, M., Kramer, B., Lengauer, T. & Klebe, G. (1996). J. Mol. Biol. 261, 470-489.]). The docking results were then com­pared with MTT results to gain insight into the most possible mol­ecular targets. Spearman's rank correlation coefficient ρ (Fieller et al., 1957[Fieller, E. C., Hartley, H. O. & Pearson, E. S. (1957). Biometrika, 44, 470-481.]) was introduced to assess the strength of each target's monotonic relationship (Table 3[link]). The closer ρ is to 1, the stronger the monotonic relationship. As we can see, ρ values of three targets [i.e. human ether-á-go-go-related (hERG) potassium channel, inhibitor of apoptosis protein 3 and serine/threonine-protein kinase PIM1] are above 0.80, their correlations can be described as `very strong' (bold in Table 3[link]). Thus, they can be regarded as the most possible targets.

Table 3
Total scores and Spearman's rank correlation coefficients (ρ in the last two rows) of 18 possible targets (PDB IDs are in brackets; two targets in the last two columns were docked using homology modules for the absence of detailed 3D information)

[\rho _{\rm A549} = 1- {{6\Sigma \left( {{\rm Rank}_i} - {\rm Rank} _{\rm A549} \right)}^2 \over{n\left( n^2 - 1\right)}} \eqno(1)]

[\rho _{\rm 4T_1} = 1- {{6\Sigma \left( {{\rm Rank}_i} - {\rm Rank} _{\rm 4T_1} \right)}^2 \over{n\left( n^2 - 1\right)}} \eqno(2)]

  c-Jun N-terminal kinase 3(2r9s) CaM kinase II (2vz6) Delta opioid receptor (4n6h) Gonadotropin-releasing hormone receptor (6nbf) hERG (3o0u) Inhibitor of apoptosis protein 3 (5c3h) Kinesin-like protein 1 (3zcw) Mu opioid receptor (4dkl) Probable G-protein coupled receptor 88 (5xf1)
Ligandi 12.24 9.27 9.37 7.76 9.87 7.33 19.68 10.53 6.67
BDHFI 8.08 8.43 7.56 6.19 6.90 6.23 10.44 8.57 6.85
BDHAI 8.16 8.82 7.44 6.36 8.02 6.14 6.99 9.46 6.15
BDHMFI 5.96 6.92 6.53 6.77 4.54 5.07 8.61 8.23 5.28
BDHFN 5.94 7.59 7.05 5.00 6.25 5.33 9.04 7.45 5.84
BMHFI 6.64 7.32 7.44 5.29 5.97 5.83 9.44 7.31 4.39
BMHAI 5.60 6.80 6.32 5.88 6.41 4.77 8.27 6.15 4.52
BMHMFI 6.39 5.98 6.65 4.19 4.91 4.42 7.76 6.36 4.58
BMHFN 5.59 6.03 6.45 4.67 4.20 4.30 6.16 6.47 4.37
ρA549ii 0.67 0.74 0.57 0.71 0.86 0.83 0.48 0.52 0.62
ρ4T1iii 0.69 0.76 0.55 0.74 0.88 0.81 0.33 0.55 0.60
                   
  Protein kinase C alpha (4ra4) Serine/threonine-protein kinase AKT2 (3d0e) Serine/threonine-protein kinase PIM1 (1yxt) Serine/threonine-protein kinase PIM2 (4x7q) Serine/threonine-protein kinase PIM3 (5dwr) Sigma opioid receptor (6dk0) Tryptase beta-1 (4mpu) Neurokinin 2 receptor (by homology) 5-HT6 receptor (by homology)
Ligandi 7.34 16.79 32.82 15.18 10.64 10.81 23.41 10.04 9.00
BDHFI 6.35 8.22 9.73 6.70 8.00 8.34 7.39 9.28 7.95
BDHAI 6.79 6.40 9.60 8.19 9.92 7.17 8.12 8.80 4.56
BDHMFI 5.27 5.65 6.64 5.56 4.45 1.87 6.02 8.17 6.40
BDHFN 5.47 5.51 7.59 5.63 5.51 5.23 7.99 8.73 7.07
BMHFI 4.43 7.06 7.95 7.87 6.39 6.41 5.44 6.71 5.05
BMHAI 4.87 6.67 7.01 7.68 7.49 8.27 5.51 5.68 5.50
BMHMFI 5.06 6.77 5.52 5.92 6.42 7.00 5.05 6.00 4.43
BMHFN 4.30 7.46 5.80 5.92 6.06 6.23 5.22 6.44 6.18
ρA549ii 0.60 0.12 0.86 0.62 0.69 0.69 0.62 0.52 0.17
ρ4T1iii 0.62 0.00 0.83 0.69 0.71 0.64 0.67 0.50 0.02
Notes: (i) for all proteins with crystal structures, the `ligand' means the natural ligand included in the protein structure; for the last two proteins built by homology modelling, the `ligand' means the known ligand reported before, i.e. 10i and AVN-492 (see text). (ii) see equation (1)[link] above; (iii) see equation (2)[link] above, n = 8. Ranki is the rank value of each Schiff base in the virtual screening, which is determined according to its sequence listed in descending order of total score value (see Table S22 in the supporting information). RankA549/Rank4T1 is the rank value of each Schiff base in the A549/4T1 cell growth MTT assays, which is determined according to its sequence listed in ascending order of IC50 value (see Table 2[link] and Table S23 in the supporting information).

3.4. Comparison of binding modes between active and less active ligands

Among the three most possible targets, hERG (PDB ID 3o0u) has the highest Spearman's rank correlation coefficient values and is ranked as the best, so the com­parison of binding modes is performed based on the docking results of eight Schiff bases with hERG, in order to gain insight into the nature of the structure–activity relationships.

According to our docking simulation, shown in Fig. 9[link], the active and less active ligands have different binding modes. In both BDHFI and BDHAI, two hydrogen bonds were formed, one is between the indole N—H group and GLN19/GLU59, and the other is between an imine N atom and HOH267/GLY66. But in both BDHMFI and BDHFN, no hydrogen bond was formed and aromatic hydro­phobic inter­actions dominate the affinity between the protein and the ligand. This phenomenon can be confirmed by the Polar values, which are 2.60 and 2.18 for BDHFI and BDHAI, respectively, but zero for BDHMFI and BDHFN.

[Figure 9]
Figure 9
The calculated binding modes of BDHFI, BDHAI, BDHMFI and BDHFN with hERG (PDB ID: 3o0u). Hydrogen bonds are shown with orange dotted lines. If no hydrogen bond is formed, surfaces that contain the active sites are displayed (red surface). Total score values and seven additional contributing parts or scores are listed underneath for com­parison.

As for the BMH series of four mono-Schiff bases, all of them exhibit one to five hydrogen bonds within the active site (Fig. 10[link]). Indole N—H groups and imine N atoms form one or two hydrogen bonds in both BMHFI and BMHAI. A carboxyl O atom forms an extra hydrogen bond in BMHAI, which is the reason why it has a higher Total Score (also Polar value) than BMHFI. BMHMFI and BMHFN can form only one hydrogen bond with protein through a carboxyl O or imine N atom, so their docking Total Scores (also Polar values) are lower than those of BMHFI and BMHAI. Put simply, the more hydrogen bonds formed, the higher the Total Score values in the docking simulations, and the better the anti­proliferative activities of the ligands.

[Figure 10]
Figure 10
The calculated binding modes of BMHFI, BMHAI, BMHMFI and BMHFN with hERG (PDB ID: 3o0u). Hydrogen bonds are shown with orange dotted lines. Total score values and seven additional contributing parts or scores are listed underneath for com­parison.

There is one phenomenon that seems confusing, i.e. BDHFN has a higher Total Score than BMHFI (6.25 versus 5.97), but the former has a lower cytotoxic activity than the latter. Apparently, the deviation between docking predictions and experimental activities may partly explain this result. Here, we consider another class of scoring function based on a potential of mean force, so-called PMF-based scores, which is a knowledge-based scoring approach based on the work of Muegge and Martin (Muegge & Martin, 1999[Muegge, I. & Martin, Y. C. (1999). J. Med. Chem. 42, 791-804.]; Muegge, 2006[Muegge, I. (2006). J. Med. Chem. 49, 5895-5902.]). The PMF-based scoring functions are statistical, because it is calculated as the sum of the overall atom-pair inter­action Helmholtz free energies between the protein and ligand, neglecting other characteristics of the environment and mutual orientation of the atom (Lizunov et al., 2015[Lizunov, A. Y., Gonchar, A. L., Zaitseva, N. I. & Zosimov, V. V. (2015). J. Chem. Inf. Model. 55, 2121-2137.]). As we know, the higher the PMF value, the poorer the protein–ligand binding affinity (Sharma & Ghoshal, 2006[Sharma, P. & Ghoshal, N. (2006). J. Chem. Inf. Model. 46, 1763-1774.]). From the seventh columns in Figs. 9[link] and 10[link], we can see that BDHFN has the highest PMF score (68.14) and is ranked as the worst with respect to the means of the distance-dependent Helmholtz free energies. That is to say, a long distance between the protein and ligand has a detrimental contribution to the affinity, which has not been reflected apparently in the Total Score. On the other hand, this phenomenon confirms the conclusion that PMF has essential differences with all of the other scoring functions. Its unique knowledge-based algorithm parameterized using crystal com­plexes is distinctive (Liu et al., 2012[Liu, S., Fu, R., Zhou, L.-H. & Chen, S.-P. (2012). PLoS One, 7, e38086.]).

The above explanation is also suitable to BMHAI versus BDHFI/BDHAI. The former exhibit five hydrogen bonds within the active site, but it has a lower Total Score and weaker cytotoxic activity than the latter two. The PMF score of BMHAI is 6.08, revealing poorer binding affinities com­pared with the meager binding scores of BDHFI and BDHAI (−5.70 and −6.26, respectively).

In brief, all of the docking results were in good agreement with the experimental results, indicating the most probable target and reasonable structure–activity relationships.

4. Conclusion

Schiff bases have been used widely in the pharmaceutical industry because of their anti­microbial, anti-inflammatory and anti­cancer properties. We have described the synthesis and structural characterization of eight novel Schiff bases derived from BDH/BMH. These synthesized Schiff base com­pounds have similar mol­ecular structures despite having different terminal fused two-ring aromatics and different substituents. MTT assays proved that the BDH series of com­pounds show higher inhibitory activity com­pared with the BMH series. The biological screening results favour the activities of indole-containing Schiff bases instead of naphthalene-containing ones. The cytotoxic activity is also affected by the nature of the substituents at the indole N atom; the replacement of hydrogen by methyl will decrease the cytotoxic activities greatly, while the same replacement on the imine C—H group has little effect. Generally, our in vitro findings show that four of these com­pounds have high anti­proliferative activity against human lung cancer cell line A549 and mouse breast cancer cell line 4T1; two show obvious and com­parable activities with cisplatin. All com­pounds exhibited weaker cytotoxicity against normal cells than cancer cells.

Swiss Target Prediction online servers were used to screen com­pounds against large numbers of mol­ecular targets. After careful examination, 18 possible targets were generated for further screening through the reverse docking approach. Afterwards, the three most possible targets were chosen on account of their correlation with experimental data. Bearing the highest consistency, the docking results of hERG (PDB ID: 3o0u) with eight Schiff bases can easily explain the structure–activity relationships obtained experimentally.

In conclusion, the present work indicates that introduction of an indole ring on the terminal of this kind of X-shaped Schiff base leads to the generation of potent anti­cancer agents.

Supporting information


Computing details top

For all structures, data collection: SMART (Bruker, 2000); cell refinement: SMART (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS2016 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: SHELXTL (Bruker, 2000), PLATON (Spek, 2009) and DIAMOND (Brandenburg & Putz, 1999); software used to prepare material for publication: SHELXL2016 (Sheldrick, 2015b) and WinGX (Farrugia, 2012).

(1Z,2Z)-1,2-Bis{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (1-BDHFI) top
Crystal data top
C32H24N6F(000) = 1032
Mr = 492.57Dx = 1.244 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 13.023 (4) ÅCell parameters from 380 reflections
b = 7.340 (2) Åθ = 2.5–26.0°
c = 27.762 (9) ŵ = 0.08 mm1
β = 97.693 (5)°T = 293 K
V = 2630.0 (14) Å3Block, yellow
Z = 40.30 × 0.18 × 0.15 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
5145 independent reflections
Radiation source: fine-focus sealed tube2852 reflections with I > 2σ(I)
Detector resolution: 10.13 pixels mm-1Rint = 0.046
phi and ω scansθmax = 26.0°, θmin = 1.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 1613
Tmin = 0.903, Tmax = 0.939k = 89
13632 measured reflectionsl = 3334
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049Only H-atom displacement parameters refined
wR(F2) = 0.103 w = 1/[σ2(Fo2) + (0.0408P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.88(Δ/σ)max < 0.001
5145 reflectionsΔρmax = 0.15 e Å3
367 parametersΔρmin = 0.22 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.83514 (13)0.3197 (2)0.09431 (6)0.0363 (4)
C20.92588 (13)0.2300 (2)0.07841 (6)0.0378 (5)
C30.94898 (15)0.0495 (3)0.08906 (7)0.0474 (5)
H30.9048430.0184270.1057490.060 (6)*
C41.03531 (16)0.0314 (3)0.07558 (8)0.0600 (6)
H41.0490330.1533320.0829800.069 (7)*
C51.10143 (19)0.0661 (3)0.05130 (8)0.0713 (7)
H51.1602560.0112040.0421830.084 (8)*
C61.08036 (19)0.2454 (4)0.04047 (9)0.0768 (7)
H61.1252080.3125450.0239800.089 (8)*
C70.99353 (16)0.3268 (3)0.05380 (7)0.0592 (6)
H70.9800680.4486150.0461760.051 (6)*
C80.82392 (13)0.5230 (2)0.08899 (6)0.0377 (4)
C90.74742 (14)0.5987 (3)0.05028 (7)0.0437 (5)
C100.70293 (18)0.4886 (4)0.01317 (8)0.0734 (7)
H100.7202980.3657460.0130030.079 (8)*
C110.6329 (2)0.5586 (5)0.02378 (10)0.1124 (11)
H110.6038630.4830890.0488810.153 (13)*
C120.6059 (2)0.7378 (5)0.02370 (11)0.1102 (11)
H120.5581790.7842820.0485810.119 (10)*
C130.64870 (18)0.8485 (4)0.01274 (10)0.0823 (8)
H130.6304520.9709990.0127090.077 (8)*
C140.71892 (15)0.7801 (3)0.04968 (8)0.0580 (6)
H140.7476070.8567900.0745670.066 (7)*
C150.99888 (13)0.6384 (3)0.18379 (7)0.0411 (5)
H150.9849270.7627140.1831580.046 (5)*
C161.07404 (13)0.5654 (2)0.22132 (6)0.0385 (5)
C171.12335 (12)0.3906 (3)0.22344 (6)0.0369 (4)
C181.12274 (14)0.2432 (3)0.19159 (7)0.0439 (5)
H181.0848850.2484670.1607390.042 (5)*
C191.17878 (15)0.0908 (3)0.20652 (8)0.0539 (6)
H191.1777560.0084830.1856390.058 (6)*
C201.23696 (15)0.0810 (3)0.25202 (8)0.0580 (6)
H201.2742980.0243870.2610140.061 (6)*
C211.24053 (15)0.2222 (3)0.28373 (8)0.0544 (6)
H211.2800950.2157100.3141600.055 (6)*
C221.18325 (13)0.3765 (3)0.26927 (7)0.0416 (5)
C231.10613 (14)0.6476 (3)0.26490 (7)0.0486 (5)
H231.0864670.7635530.2735940.043 (5)*
C240.62285 (14)0.2475 (3)0.14849 (7)0.0484 (5)
H240.6342320.1239680.1544520.048 (6)*
C250.53425 (14)0.3321 (3)0.16411 (7)0.0505 (5)
C260.49308 (14)0.5105 (3)0.15329 (7)0.0505 (5)
C270.52005 (16)0.6557 (3)0.12573 (8)0.0562 (6)
H270.5792670.6504870.1104110.052 (6)*
C280.45807 (19)0.8070 (3)0.12143 (10)0.0786 (7)
H280.4761530.9053000.1031740.076 (8)*
C290.3689 (2)0.8173 (4)0.14363 (12)0.1049 (10)
H290.3280370.9214660.1397020.122 (10)*
C300.3405 (2)0.6771 (4)0.17108 (12)0.1036 (10)
H300.2811590.6835430.1862790.101 (9)*
C310.40318 (18)0.5254 (4)0.17543 (10)0.0733 (7)
C320.46970 (18)0.2500 (4)0.19247 (9)0.0773 (7)
H320.4776610.1323460.2048730.071 (7)*
N10.76775 (11)0.2260 (2)0.11353 (5)0.0405 (4)
N20.68695 (11)0.3368 (2)0.12654 (5)0.0433 (4)
N30.88012 (11)0.6319 (2)0.11766 (5)0.0419 (4)
N40.95074 (11)0.5349 (2)0.15116 (5)0.0432 (4)
N51.17037 (12)0.5365 (2)0.29348 (6)0.0519 (5)
H351.1989340.5617880.3224480.065 (7)*
N60.39279 (16)0.3652 (3)0.19973 (9)0.0954 (8)
H360.3443380.3418550.2170390.103 (9)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0382 (11)0.0372 (11)0.0317 (10)0.0033 (9)0.0014 (9)0.0022 (9)
C20.0403 (11)0.0408 (12)0.0317 (10)0.0045 (9)0.0029 (9)0.0017 (9)
C30.0471 (12)0.0435 (13)0.0517 (12)0.0016 (10)0.0076 (10)0.0016 (11)
C40.0624 (15)0.0486 (15)0.0702 (16)0.0082 (12)0.0130 (12)0.0046 (12)
C50.0667 (17)0.0754 (18)0.0768 (17)0.0164 (15)0.0276 (14)0.0022 (15)
C60.0735 (17)0.0847 (19)0.0810 (18)0.0034 (15)0.0430 (15)0.0145 (16)
C70.0676 (15)0.0539 (15)0.0602 (14)0.0078 (12)0.0244 (12)0.0141 (12)
C80.0348 (10)0.0393 (12)0.0395 (11)0.0019 (9)0.0063 (9)0.0061 (9)
C90.0402 (11)0.0441 (12)0.0460 (12)0.0054 (10)0.0029 (9)0.0133 (10)
C100.0896 (19)0.0590 (17)0.0626 (15)0.0068 (14)0.0226 (14)0.0078 (13)
C110.139 (3)0.095 (2)0.084 (2)0.016 (2)0.059 (2)0.0148 (19)
C120.100 (2)0.109 (3)0.104 (2)0.008 (2)0.0505 (19)0.045 (2)
C130.0655 (16)0.0687 (19)0.107 (2)0.0087 (15)0.0107 (15)0.0384 (17)
C140.0476 (13)0.0526 (14)0.0711 (15)0.0012 (11)0.0019 (12)0.0162 (13)
C150.0357 (11)0.0341 (12)0.0541 (13)0.0003 (9)0.0086 (10)0.0037 (10)
C160.0303 (10)0.0425 (12)0.0421 (11)0.0002 (9)0.0028 (9)0.0082 (10)
C170.0279 (10)0.0447 (12)0.0384 (11)0.0037 (9)0.0052 (8)0.0024 (9)
C180.0381 (11)0.0480 (13)0.0445 (12)0.0010 (10)0.0016 (9)0.0051 (10)
C190.0461 (13)0.0457 (13)0.0700 (15)0.0040 (11)0.0084 (11)0.0045 (13)
C200.0451 (13)0.0558 (15)0.0730 (16)0.0089 (12)0.0069 (12)0.0171 (13)
C210.0378 (12)0.0779 (17)0.0457 (13)0.0011 (12)0.0010 (10)0.0176 (13)
C220.0323 (10)0.0540 (13)0.0388 (11)0.0034 (10)0.0059 (9)0.0001 (10)
C230.0365 (11)0.0500 (14)0.0592 (13)0.0020 (10)0.0054 (10)0.0159 (11)
C240.0394 (12)0.0478 (14)0.0568 (13)0.0046 (10)0.0017 (10)0.0080 (11)
C250.0363 (12)0.0561 (14)0.0599 (14)0.0085 (11)0.0097 (10)0.0034 (11)
C260.0360 (12)0.0565 (14)0.0593 (14)0.0070 (10)0.0076 (10)0.0086 (12)
C270.0464 (13)0.0570 (15)0.0650 (15)0.0012 (12)0.0071 (11)0.0049 (12)
C280.0728 (18)0.0533 (16)0.112 (2)0.0033 (14)0.0201 (16)0.0005 (16)
C290.078 (2)0.070 (2)0.173 (3)0.0164 (18)0.040 (2)0.009 (2)
C300.0711 (19)0.083 (2)0.169 (3)0.0079 (17)0.061 (2)0.018 (2)
C310.0542 (15)0.0665 (17)0.105 (2)0.0063 (14)0.0320 (14)0.0091 (16)
C320.0602 (16)0.0682 (18)0.109 (2)0.0021 (14)0.0310 (15)0.0156 (16)
N10.0377 (9)0.0403 (9)0.0432 (9)0.0002 (8)0.0047 (8)0.0053 (8)
N20.0371 (9)0.0443 (10)0.0486 (10)0.0012 (8)0.0064 (8)0.0054 (8)
N30.0391 (9)0.0377 (10)0.0472 (9)0.0001 (8)0.0012 (8)0.0063 (8)
N40.0424 (9)0.0375 (9)0.0471 (10)0.0013 (8)0.0034 (8)0.0011 (8)
N50.0405 (10)0.0736 (13)0.0397 (10)0.0041 (9)0.0013 (8)0.0112 (10)
N60.0672 (14)0.0917 (18)0.141 (2)0.0066 (13)0.0629 (15)0.0055 (16)
Geometric parameters (Å, º) top
C1—N11.286 (2)C18—C191.370 (2)
C1—C21.471 (2)C18—H180.9300
C1—C81.505 (2)C19—C201.385 (3)
C2—C71.382 (2)C19—H190.9300
C2—C31.382 (2)C20—C211.357 (3)
C3—C41.367 (3)C20—H200.9300
C3—H30.9300C21—C221.386 (3)
C4—C51.365 (3)C21—H210.9300
C4—H40.9300C22—N51.374 (2)
C5—C61.370 (3)C23—N51.348 (2)
C5—H50.9300C23—H230.9300
C6—C71.373 (3)C24—N21.278 (2)
C6—H60.9300C24—C251.428 (3)
C7—H70.9300C24—H240.9300
C8—N31.286 (2)C25—C321.367 (3)
C8—C91.473 (2)C25—C261.431 (3)
C9—C101.375 (3)C26—C271.384 (3)
C9—C141.382 (3)C26—C311.398 (3)
C10—C111.378 (3)C27—C281.369 (3)
C10—H100.9300C27—H270.9300
C11—C121.361 (4)C28—C291.387 (3)
C11—H110.9300C28—H280.9300
C12—C131.358 (3)C29—C301.361 (4)
C12—H120.9300C29—H290.9300
C13—C141.374 (3)C30—C311.376 (3)
C13—H130.9300C30—H300.9300
C14—H140.9300C31—N61.371 (3)
C15—N41.280 (2)C32—N61.347 (3)
C15—C161.435 (2)C32—H320.9300
C15—H150.9300N1—N21.4146 (19)
C16—C231.367 (2)N3—N41.4104 (18)
C16—C171.432 (2)N5—H350.8600
C17—C181.397 (2)N6—H360.8600
C17—C221.404 (2)
N1—C1—C2120.37 (17)C17—C18—H18120.5
N1—C1—C8120.56 (16)C18—C19—C20121.5 (2)
C2—C1—C8119.05 (16)C18—C19—H19119.2
C7—C2—C3117.65 (19)C20—C19—H19119.2
C7—C2—C1120.61 (18)C21—C20—C19121.3 (2)
C3—C2—C1121.69 (17)C21—C20—H20119.4
C4—C3—C2121.4 (2)C19—C20—H20119.4
C4—C3—H3119.3C20—C21—C22117.78 (19)
C2—C3—H3119.3C20—C21—H21121.1
C5—C4—C3120.2 (2)C22—C21—H21121.1
C5—C4—H4119.9N5—C22—C21130.74 (18)
C3—C4—H4119.9N5—C22—C17106.91 (17)
C4—C5—C6119.4 (2)C21—C22—C17122.34 (19)
C4—C5—H5120.3N5—C23—C16110.24 (18)
C6—C5—H5120.3N5—C23—H23124.9
C5—C6—C7120.5 (2)C16—C23—H23124.9
C5—C6—H6119.8N2—C24—C25121.8 (2)
C7—C6—H6119.8N2—C24—H24119.1
C6—C7—C2120.8 (2)C25—C24—H24119.1
C6—C7—H7119.6C32—C25—C24124.6 (2)
C2—C7—H7119.6C32—C25—C26106.42 (19)
N3—C8—C9119.37 (17)C24—C25—C26129.00 (19)
N3—C8—C1121.09 (16)C27—C26—C31118.2 (2)
C9—C8—C1119.54 (16)C27—C26—C25134.79 (19)
C10—C9—C14118.1 (2)C31—C26—C25107.0 (2)
C10—C9—C8120.07 (19)C28—C27—C26118.9 (2)
C14—C9—C8121.78 (19)C28—C27—H27120.6
C9—C10—C11120.6 (3)C26—C27—H27120.6
C9—C10—H10119.7C27—C28—C29121.6 (3)
C11—C10—H10119.7C27—C28—H28119.2
C12—C11—C10120.3 (3)C29—C28—H28119.2
C12—C11—H11119.9C30—C29—C28120.9 (3)
C10—C11—H11119.9C30—C29—H29119.5
C13—C12—C11119.9 (3)C28—C29—H29119.5
C13—C12—H12120.0C29—C30—C31117.3 (3)
C11—C12—H12120.0C29—C30—H30121.4
C12—C13—C14120.2 (3)C31—C30—H30121.4
C12—C13—H13119.9N6—C31—C30129.8 (2)
C14—C13—H13119.9N6—C31—C26107.0 (2)
C13—C14—C9120.8 (2)C30—C31—C26123.2 (3)
C13—C14—H14119.6N6—C32—C25109.6 (2)
C9—C14—H14119.6N6—C32—H32125.2
N4—C15—C16120.91 (17)C25—C32—H32125.2
N4—C15—H15119.5C1—N1—N2111.77 (15)
C16—C15—H15119.5C24—N2—N1112.49 (16)
C23—C16—C17106.07 (16)C8—N3—N4111.16 (15)
C23—C16—C15125.16 (17)C15—N4—N3112.39 (15)
C17—C16—C15128.56 (16)C23—N5—C22109.62 (16)
C18—C17—C22118.16 (17)C23—N5—H35125.2
C18—C17—C16134.69 (17)C22—N5—H35125.2
C22—C17—C16107.15 (16)C32—N6—C31109.9 (2)
C19—C18—C17118.92 (18)C32—N6—H36125.0
C19—C18—H18120.5C31—N6—H36125.0
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H35···N1i0.862.142.948 (2)156
C3—H3···N3ii0.932.613.320 (3)133
Symmetry codes: (i) x+2, y+1/2, z+1/2; (ii) x, y1, z.
(1Z,2Z)-1,2-Bis{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethane (2-BDHAI) top
Crystal data top
C34H28N6Z = 2
Mr = 520.62F(000) = 548
Triclinic, P1Dx = 1.252 Mg m3
a = 10.2585 (4) ÅMo Kα radiation, λ = 0.71073 Å
b = 11.9610 (5) ÅCell parameters from 380 reflections
c = 12.8232 (6) Åθ = 2.5–26.0°
α = 64.941 (4)°µ = 0.08 mm1
β = 79.573 (3)°T = 293 K
γ = 76.829 (4)°Bar, yellow
V = 1381.45 (11) Å30.35 × 0.15 × 0.12 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
5328 independent reflections
Radiation source: fine-focus sealed tube4490 reflections with I > 2σ(I)
Detector resolution: 10.13 pixels mm-1Rint = 0.026
phi and ω scansθmax = 26.0°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 1212
Tmin = 0.903, Tmax = 0.939k = 1414
15195 measured reflectionsl = 1315
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullOnly H-atom displacement parameters refined
R[F2 > 2σ(F2)] = 0.044 w = 1/[σ2(Fo2) + (0.0694P)2 + 0.1725P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.129(Δ/σ)max < 0.001
S = 1.05Δρmax = 0.19 e Å3
5328 reflectionsΔρmin = 0.18 e Å3
392 parametersExtinction correction: SHELXL2016 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.083 (4)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.21600 (13)0.84926 (13)0.45306 (11)0.0462 (3)
C20.24638 (13)0.97764 (13)0.38744 (12)0.0491 (3)
C30.15001 (16)1.07464 (15)0.32585 (16)0.0648 (4)
H20.0671481.0576470.3225190.081 (6)*
C40.17520 (19)1.19565 (16)0.26959 (17)0.0746 (5)
H30.1099331.2590750.2277990.097 (7)*
C50.2954 (2)1.22291 (17)0.27488 (16)0.0739 (5)
H40.3112261.3049890.2383800.085 (6)*
C60.3928 (2)1.12876 (18)0.33426 (16)0.0747 (5)
H50.4749941.1471610.3374530.092 (6)*
C70.36938 (16)1.00565 (16)0.38983 (14)0.0618 (4)
H60.4365240.9421100.4286460.072 (5)*
C80.32668 (13)0.74348 (13)0.50875 (12)0.0483 (3)
C90.34159 (15)0.70585 (14)0.63212 (12)0.0551 (4)
C100.26077 (17)0.77226 (18)0.69346 (14)0.0658 (4)
H70.1963100.8403860.6567700.065 (5)*
C110.2755 (2)0.7377 (2)0.80900 (17)0.0877 (6)
H100.2211870.7828670.8493120.088 (6)*
C120.3700 (3)0.6372 (3)0.86403 (18)0.1028 (8)
H120.3793380.6137220.9416720.113 (8)*
C130.4506 (3)0.5713 (2)0.80406 (19)0.0961 (7)
H130.5143230.5029500.8416650.118 (8)*
C140.4385 (2)0.60529 (17)0.68842 (16)0.0721 (5)
H110.4950740.5609450.6483370.099 (7)*
C150.49611 (13)0.72877 (13)0.26579 (13)0.0491 (3)
C160.48156 (13)0.78461 (14)0.14310 (13)0.0501 (3)
C170.36770 (13)0.86989 (13)0.08418 (12)0.0484 (3)
C180.24161 (14)0.92420 (14)0.11937 (14)0.0546 (4)
H180.2142280.9040630.1974910.058 (4)*
C190.15878 (17)1.00782 (16)0.03671 (16)0.0668 (4)
H190.0749121.0444210.0597330.071 (5)*
C200.19753 (19)1.03927 (18)0.08130 (17)0.0753 (5)
H200.1386811.0954260.1350920.091 (6)*
C210.32077 (19)0.98860 (17)0.11877 (16)0.0722 (5)
H210.3470181.0095150.1971400.085 (6)*
C220.40519 (15)0.90475 (15)0.03532 (14)0.0580 (4)
C230.57959 (16)0.77510 (17)0.05713 (15)0.0646 (4)
H230.6650060.7273710.0696830.077 (5)*
C240.03270 (14)0.68082 (14)0.52381 (12)0.0518 (3)
C250.07215 (13)0.56489 (14)0.61098 (13)0.0506 (3)
C260.03001 (13)0.49580 (13)0.72570 (12)0.0466 (3)
C270.05813 (13)0.51142 (13)0.78861 (13)0.0493 (3)
H270.1082270.5759500.7540670.056 (4)*
C280.06910 (15)0.42989 (14)0.90189 (14)0.0572 (4)
H280.1264900.4402830.9443310.063 (4)*
C290.00429 (17)0.33154 (16)0.95472 (15)0.0654 (4)
H290.0054420.2776661.0315820.076 (5)*
C300.09047 (17)0.31280 (15)0.89550 (14)0.0638 (4)
H300.1391750.2472750.9308080.067 (5)*
C310.10219 (14)0.39519 (14)0.78113 (13)0.0523 (3)
C320.16427 (15)0.50232 (15)0.60219 (14)0.0587 (4)
H320.2080060.5258610.5366780.069 (5)*
C330.63359 (15)0.6710 (2)0.30611 (17)0.0733 (5)
H33A0.6272560.5984180.3771220.100 (7)*
H33B0.6706030.7306770.3185640.135 (10)*
H33C0.6908780.6468810.2484270.141 (10)*
C340.1161 (2)0.7575 (2)0.42427 (18)0.0840 (6)
H34A0.2097160.7609590.4519640.145 (10)*
H34B0.0964090.7199570.3690150.187 (15)*
H34C0.0954640.8408490.3880880.162 (12)*
N10.09402 (11)0.83288 (11)0.46297 (10)0.0520 (3)
N20.07283 (11)0.71200 (11)0.53875 (10)0.0511 (3)
N30.41191 (12)0.68906 (12)0.45120 (11)0.0548 (3)
N40.38813 (11)0.73680 (11)0.33433 (10)0.0519 (3)
N50.53458 (14)0.84467 (15)0.04798 (13)0.0703 (4)
H350.5798860.8505150.1129120.078 (6)*
N60.18231 (13)0.40170 (13)0.70225 (12)0.0616 (3)
H360.2352380.3500760.7146960.067 (5)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0423 (7)0.0552 (8)0.0428 (7)0.0102 (6)0.0023 (5)0.0209 (6)
C20.0477 (7)0.0542 (8)0.0474 (7)0.0112 (6)0.0035 (6)0.0240 (6)
C30.0527 (9)0.0554 (9)0.0832 (12)0.0035 (7)0.0033 (8)0.0290 (8)
C40.0773 (12)0.0530 (9)0.0828 (12)0.0011 (8)0.0006 (9)0.0258 (9)
C50.0939 (13)0.0564 (10)0.0705 (11)0.0265 (9)0.0144 (10)0.0263 (9)
C60.0774 (12)0.0841 (12)0.0683 (11)0.0422 (10)0.0061 (9)0.0267 (10)
C70.0584 (9)0.0682 (10)0.0558 (9)0.0233 (8)0.0028 (7)0.0168 (8)
C80.0423 (7)0.0525 (7)0.0497 (7)0.0145 (6)0.0069 (5)0.0159 (6)
C90.0551 (8)0.0637 (9)0.0482 (8)0.0273 (7)0.0065 (6)0.0146 (7)
C100.0615 (9)0.0890 (12)0.0559 (9)0.0315 (9)0.0007 (7)0.0307 (9)
C110.0973 (15)0.1285 (18)0.0574 (11)0.0604 (14)0.0098 (10)0.0423 (12)
C120.135 (2)0.129 (2)0.0500 (11)0.0707 (17)0.0199 (12)0.0125 (12)
C130.1239 (19)0.0874 (14)0.0670 (13)0.0360 (13)0.0424 (13)0.0009 (11)
C140.0827 (12)0.0656 (10)0.0621 (10)0.0199 (9)0.0247 (9)0.0091 (8)
C150.0371 (7)0.0541 (8)0.0646 (9)0.0047 (5)0.0092 (6)0.0316 (7)
C160.0397 (7)0.0592 (8)0.0596 (8)0.0084 (6)0.0049 (6)0.0314 (7)
C170.0443 (7)0.0536 (8)0.0555 (8)0.0133 (6)0.0074 (6)0.0260 (6)
C180.0440 (7)0.0601 (9)0.0617 (9)0.0089 (6)0.0080 (6)0.0249 (7)
C190.0504 (8)0.0666 (10)0.0792 (11)0.0039 (7)0.0157 (8)0.0245 (9)
C200.0709 (11)0.0730 (11)0.0739 (12)0.0109 (9)0.0270 (9)0.0144 (9)
C210.0812 (12)0.0785 (12)0.0560 (10)0.0214 (9)0.0127 (8)0.0197 (9)
C220.0572 (9)0.0658 (9)0.0582 (9)0.0174 (7)0.0040 (7)0.0287 (8)
C230.0454 (8)0.0799 (11)0.0728 (11)0.0033 (7)0.0008 (7)0.0403 (9)
C240.0452 (7)0.0626 (8)0.0514 (8)0.0116 (6)0.0077 (6)0.0238 (7)
C250.0412 (7)0.0605 (8)0.0553 (8)0.0120 (6)0.0053 (6)0.0261 (7)
C260.0370 (6)0.0511 (7)0.0550 (8)0.0065 (5)0.0015 (5)0.0259 (6)
C270.0393 (7)0.0533 (8)0.0597 (8)0.0076 (6)0.0050 (6)0.0268 (7)
C280.0507 (8)0.0632 (9)0.0612 (9)0.0041 (7)0.0113 (7)0.0285 (8)
C290.0717 (10)0.0629 (9)0.0559 (9)0.0118 (8)0.0085 (7)0.0173 (8)
C300.0667 (10)0.0600 (9)0.0637 (10)0.0212 (8)0.0015 (7)0.0205 (8)
C310.0451 (7)0.0556 (8)0.0615 (9)0.0124 (6)0.0015 (6)0.0279 (7)
C320.0517 (8)0.0719 (10)0.0592 (9)0.0199 (7)0.0093 (7)0.0264 (8)
C330.0415 (8)0.1008 (14)0.0788 (12)0.0007 (8)0.0161 (8)0.0393 (12)
C340.0788 (13)0.0926 (14)0.0750 (12)0.0343 (10)0.0343 (10)0.0076 (11)
N10.0446 (6)0.0569 (7)0.0529 (7)0.0122 (5)0.0037 (5)0.0189 (6)
N20.0433 (6)0.0556 (7)0.0527 (7)0.0142 (5)0.0052 (5)0.0170 (5)
N30.0479 (6)0.0619 (7)0.0532 (7)0.0043 (5)0.0122 (5)0.0211 (6)
N40.0417 (6)0.0623 (7)0.0527 (7)0.0022 (5)0.0094 (5)0.0253 (6)
N50.0636 (8)0.0916 (10)0.0592 (8)0.0122 (7)0.0065 (7)0.0386 (8)
N60.0556 (7)0.0690 (8)0.0689 (8)0.0282 (6)0.0055 (6)0.0271 (7)
Geometric parameters (Å, º) top
C1—N11.2858 (17)C19—H190.9300
C1—C21.4805 (19)C20—C211.369 (3)
C1—C81.5078 (19)C20—H200.9300
C2—C71.386 (2)C21—C221.390 (2)
C2—C31.390 (2)C21—H210.9300
C3—C41.379 (2)C22—N51.375 (2)
C3—H20.9300C23—N51.350 (2)
C4—C51.365 (3)C23—H230.9300
C4—H30.9300C24—N21.2913 (17)
C5—C61.372 (3)C24—C251.454 (2)
C5—H40.9300C24—C341.499 (2)
C6—C71.394 (2)C25—C321.3777 (19)
C6—H50.9300C25—C261.439 (2)
C7—H60.9300C26—C271.4042 (19)
C8—N31.2832 (18)C26—C311.4116 (19)
C8—C91.4771 (19)C27—C281.372 (2)
C9—C101.389 (2)C27—H270.9300
C9—C141.391 (2)C28—C291.398 (2)
C10—C111.387 (2)C28—H280.9300
C10—H70.9300C29—C301.373 (2)
C11—C121.371 (3)C29—H290.9300
C11—H100.9300C30—C311.386 (2)
C12—C131.372 (4)C30—H300.9300
C12—H120.9300C31—N61.3819 (19)
C13—C141.383 (3)C32—N61.355 (2)
C13—H130.9300C32—H320.9300
C14—H110.9300C33—H33A0.9600
C15—N41.2959 (17)C33—H33B0.9600
C15—C161.447 (2)C33—H33C0.9600
C15—C331.5004 (19)C34—H34A0.9600
C16—C231.376 (2)C34—H34B0.9600
C16—C171.4489 (19)C34—H34C0.9600
C17—C181.397 (2)N1—N21.3995 (16)
C17—C221.410 (2)N3—N41.4055 (16)
C18—C191.374 (2)N5—H350.8600
C18—H180.9300N6—H360.8600
C19—C201.399 (3)
N1—C1—C2118.19 (12)C19—C20—H20119.5
N1—C1—C8122.27 (12)C20—C21—C22117.52 (17)
C2—C1—C8119.51 (11)C20—C21—H21121.2
C7—C2—C3118.12 (14)C22—C21—H21121.2
C7—C2—C1121.02 (13)N5—C22—C21129.92 (16)
C3—C2—C1120.80 (13)N5—C22—C17107.44 (14)
C4—C3—C2121.09 (16)C21—C22—C17122.61 (15)
C4—C3—H2119.5N5—C23—C16110.58 (14)
C2—C3—H2119.5N5—C23—H23124.7
C5—C4—C3120.37 (17)C16—C23—H23124.7
C5—C4—H3119.8N2—C24—C25116.86 (13)
C3—C4—H3119.8N2—C24—C34123.95 (14)
C4—C5—C6119.76 (16)C25—C24—C34119.18 (13)
C4—C5—H4120.1C32—C25—C26105.77 (13)
C6—C5—H4120.1C32—C25—C24126.47 (14)
C5—C6—C7120.38 (16)C26—C25—C24127.68 (12)
C5—C6—H5119.8C27—C26—C31118.54 (13)
C7—C6—H5119.8C27—C26—C25134.21 (13)
C2—C7—C6120.25 (16)C31—C26—C25107.20 (12)
C2—C7—H6119.9C28—C27—C26118.90 (13)
C6—C7—H6119.9C28—C27—H27120.5
N3—C8—C9118.99 (13)C26—C27—H27120.5
N3—C8—C1122.12 (12)C27—C28—C29121.28 (15)
C9—C8—C1118.80 (12)C27—C28—H28119.4
C10—C9—C14118.74 (16)C29—C28—H28119.4
C10—C9—C8120.44 (14)C30—C29—C28121.37 (15)
C14—C9—C8120.81 (15)C30—C29—H29119.3
C11—C10—C9120.5 (2)C28—C29—H29119.3
C11—C10—H7119.8C29—C30—C31117.54 (15)
C9—C10—H7119.8C29—C30—H30121.2
C12—C11—C10120.2 (2)C31—C30—H30121.2
C12—C11—H10119.9N6—C31—C30130.41 (14)
C10—C11—H10119.9N6—C31—C26107.20 (13)
C11—C12—C13119.71 (19)C30—C31—C26122.35 (14)
C11—C12—H12120.1N6—C32—C25110.60 (13)
C13—C12—H12120.1N6—C32—H32124.7
C12—C13—C14120.9 (2)C25—C32—H32124.7
C12—C13—H13119.6C15—C33—H33A109.5
C14—C13—H13119.6C15—C33—H33B109.5
C13—C14—C9119.9 (2)H33A—C33—H33B109.5
C13—C14—H11120.0C15—C33—H33C109.5
C9—C14—H11120.0H33A—C33—H33C109.5
N4—C15—C16116.92 (12)H33B—C33—H33C109.5
N4—C15—C33123.90 (14)C24—C34—H34A109.5
C16—C15—C33119.11 (13)C24—C34—H34B109.5
C23—C16—C15126.10 (13)H34A—C34—H34B109.5
C23—C16—C17105.66 (13)C24—C34—H34C109.5
C15—C16—C17128.03 (12)H34A—C34—H34C109.5
C18—C17—C22118.36 (14)H34B—C34—H34C109.5
C18—C17—C16134.83 (13)C1—N1—N2113.49 (11)
C22—C17—C16106.73 (12)C24—N2—N1114.33 (12)
C19—C18—C17118.92 (15)C8—N3—N4112.87 (11)
C19—C18—H18120.5C15—N4—N3113.57 (11)
C17—C18—H18120.5C23—N5—C22109.58 (13)
C18—C19—C20121.59 (16)C23—N5—H35125.2
C18—C19—H19119.2C22—N5—H35125.2
C20—C19—H19119.2C32—N6—C31109.22 (12)
C21—C20—C19120.99 (16)C32—N6—H36125.4
C21—C20—H20119.5C31—N6—H36125.4
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N6—H36···N4i0.862.363.1675 (17)156
C14—H11···N30.932.522.815 (2)99
C18—H18···N40.932.613.1003 (19)114
C27—H27···N20.932.593.0859 (19)114
C34—H34C···N10.962.292.712 (2)106
Symmetry code: (i) x, y+1, z+1.
(1Z,2Z)-1,2-Bis{(E)-[(1-methyl-1H-indol-3-yl)\ methylidene]hydrazinylidene}-1,2-diphenylethane acetonitrile hemisolvate (3-BDHMFI) top
Crystal data top
2C34H28N6·C2H3NZ = 1
Mr = 1082.30F(000) = 570
Triclinic, P1Dx = 1.222 Mg m3
a = 11.2710 (6) ÅMo Kα radiation, λ = 0.71073 Å
b = 11.6944 (7) ÅCell parameters from 380 reflections
c = 12.5164 (6) Åθ = 2.5–26.0°
α = 79.875 (4)°µ = 0.08 mm1
β = 87.701 (4)°T = 293 K
γ = 64.941 (6)°Block, yellow
V = 1470.10 (15) Å30.35 × 0.20 × 0.15 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
5640 independent reflections
Radiation source: fine-focus sealed tube4445 reflections with I > 2σ(I)
Detector resolution: 10.13 pixels mm-1Rint = 0.029
phi and ω scansθmax = 26.0°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 1313
Tmin = 0.905, Tmax = 0.943k = 1414
13418 measured reflectionsl = 1510
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullOnly H-atom displacement parameters refined
R[F2 > 2σ(F2)] = 0.049 w = 1/[σ2(Fo2) + (0.0801P)2 + 0.1656P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.151(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.22 e Å3
5640 reflectionsΔρmin = 0.17 e Å3
424 parametersExtinction correction: SHELXL2016 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
2 restraintsExtinction coefficient: 0.017 (2)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C11.02888 (14)0.32026 (15)0.22614 (13)0.0468 (4)
C20.90615 (15)0.33587 (15)0.17364 (13)0.0501 (4)
C30.84410 (18)0.4332 (2)0.08691 (16)0.0645 (5)
H30.8805440.4897210.0589700.072 (6)*
C40.7277 (2)0.4466 (2)0.04165 (18)0.0781 (6)
H40.6876320.5112740.0174950.099 (8)*
C50.6708 (2)0.3663 (3)0.0825 (2)0.0849 (7)
H50.5921780.3768840.0518940.107 (9)*
C60.7306 (2)0.2703 (3)0.1687 (2)0.0930 (8)
H60.6927320.2151440.1968160.116 (10)*
C70.8474 (2)0.2552 (2)0.21409 (19)0.0738 (6)
H70.8871720.1896800.2727780.076 (6)*
C81.09142 (14)0.20654 (15)0.31530 (13)0.0461 (3)
C91.04864 (15)0.22239 (16)0.42683 (13)0.0511 (4)
C100.98055 (18)0.34437 (19)0.45203 (16)0.0630 (5)
H100.9660440.4161520.3992840.081 (7)*
C110.9343 (2)0.3596 (2)0.55484 (18)0.0753 (6)
H110.8897230.4416330.5709510.110 (9)*
C120.9535 (2)0.2554 (3)0.63306 (18)0.0829 (7)
H120.9210760.2663310.7018410.095 (8)*
C131.0203 (3)0.1356 (3)0.60969 (18)0.0939 (8)
H131.0342290.0645900.6631290.118 (10)*
C141.0679 (2)0.1181 (2)0.50706 (17)0.0777 (6)
H141.1130590.0356000.4922030.091 (7)*
C151.28895 (16)0.00541 (16)0.16524 (14)0.0531 (4)
H151.3285600.0730730.2224190.064 (5)*
C161.33243 (15)0.02026 (16)0.05718 (14)0.0518 (4)
C171.28980 (15)0.07087 (16)0.04259 (14)0.0515 (4)
C181.19676 (17)0.19828 (18)0.07107 (16)0.0614 (5)
H181.1434220.2413460.0191300.052 (5)*
C191.1861 (2)0.2582 (2)0.17750 (19)0.0774 (6)
H191.1253060.3430310.1969330.097 (8)*
C201.2642 (2)0.1949 (2)0.25722 (19)0.0811 (6)
H201.2540780.2381430.3284650.086 (7)*
C211.3557 (2)0.0698 (2)0.23207 (17)0.0701 (5)
H211.4073650.0272640.2849910.078 (6)*
C221.36791 (16)0.00935 (17)0.12438 (14)0.0542 (4)
C231.43327 (17)0.12886 (17)0.03118 (15)0.0577 (4)
H231.4801190.2029370.0808140.062 (5)*
C241.22609 (15)0.46706 (16)0.23777 (13)0.0498 (4)
H241.1772960.5405140.1882210.052 (5)*
C251.34296 (15)0.45677 (15)0.28885 (13)0.0493 (4)
C261.43056 (16)0.35601 (16)0.37025 (13)0.0516 (4)
C271.4353 (2)0.23960 (18)0.42710 (16)0.0646 (5)
H271.3698240.2138410.4160840.060 (5)*
C281.5388 (2)0.1642 (2)0.49961 (18)0.0786 (6)
H281.5431290.0864250.5372320.087 (7)*
C291.6376 (2)0.2015 (2)0.51809 (18)0.0779 (6)
H291.7060430.1481780.5677710.094 (7)*
C301.63570 (19)0.3150 (2)0.46446 (16)0.0698 (5)
H301.7012420.3401560.4768420.068 (6)*
C311.53133 (16)0.39131 (17)0.39055 (14)0.0555 (4)
C321.39468 (16)0.54558 (17)0.26514 (15)0.0552 (4)
H321.3576550.6212790.2149530.068 (6)*
C331.55867 (19)0.2047 (2)0.13077 (19)0.0711 (6)
H33A1.6326910.2540200.0812170.161 (14)*
H33B1.5843070.1595870.1921920.148 (12)*
H33C1.5275550.2610020.1549030.097 (8)*
C341.5904 (2)0.5748 (2)0.3191 (2)0.0755 (6)
H34A1.6083360.5832000.3909180.137 (12)*
H34B1.5470200.6584320.2754750.135 (12)*
H34C1.6713100.5271120.2869920.125 (10)*
C351.0000000.0000000.0000000.173 (3)
C361.0793 (6)0.1065 (6)0.0557 (5)0.0879 (13)0.5
N11.07253 (12)0.40608 (13)0.19845 (11)0.0508 (3)
N21.18768 (12)0.37708 (13)0.25908 (11)0.0518 (3)
N31.17284 (13)0.09578 (13)0.29627 (11)0.0507 (3)
N41.19636 (13)0.09946 (13)0.18477 (11)0.0526 (3)
N51.45459 (13)0.11286 (14)0.07613 (12)0.0575 (4)
N61.50671 (14)0.50781 (15)0.32476 (12)0.0584 (4)
N71.1399 (6)0.1952 (6)0.1118 (5)0.1225 (18)0.5
H35A0.948 (6)0.003 (8)0.059 (4)0.25 (3)*
H35B1.025 (14)0.055 (10)0.029 (13)0.26 (6)*0.5
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0396 (7)0.0456 (8)0.0531 (8)0.0121 (6)0.0104 (6)0.0208 (7)
C20.0426 (8)0.0491 (8)0.0564 (9)0.0143 (7)0.0062 (6)0.0179 (7)
C30.0576 (10)0.0676 (11)0.0639 (11)0.0239 (9)0.0023 (8)0.0074 (9)
C40.0607 (11)0.0894 (15)0.0692 (13)0.0193 (11)0.0102 (10)0.0063 (11)
C50.0580 (11)0.1048 (18)0.0918 (16)0.0351 (12)0.0151 (11)0.0115 (13)
C60.0724 (13)0.1002 (18)0.116 (2)0.0521 (14)0.0175 (13)0.0022 (15)
C70.0634 (11)0.0706 (12)0.0878 (14)0.0331 (10)0.0137 (10)0.0010 (11)
C80.0385 (7)0.0481 (8)0.0530 (9)0.0163 (6)0.0068 (6)0.0180 (7)
C90.0420 (7)0.0575 (9)0.0539 (9)0.0176 (7)0.0071 (6)0.0205 (7)
C100.0605 (10)0.0645 (11)0.0661 (11)0.0225 (9)0.0168 (8)0.0298 (9)
C110.0735 (12)0.0859 (15)0.0723 (13)0.0295 (11)0.0224 (10)0.0440 (12)
C120.0815 (14)0.1096 (18)0.0604 (12)0.0359 (13)0.0220 (10)0.0384 (13)
C130.118 (2)0.0915 (17)0.0575 (12)0.0331 (15)0.0197 (12)0.0110 (12)
C140.0913 (15)0.0663 (12)0.0632 (12)0.0206 (11)0.0185 (10)0.0182 (10)
C150.0486 (8)0.0464 (8)0.0613 (10)0.0142 (7)0.0069 (7)0.0183 (7)
C160.0443 (8)0.0489 (8)0.0631 (10)0.0157 (7)0.0107 (7)0.0247 (7)
C170.0429 (7)0.0534 (9)0.0631 (10)0.0205 (7)0.0080 (7)0.0240 (8)
C180.0509 (9)0.0574 (10)0.0722 (12)0.0157 (8)0.0050 (8)0.0218 (9)
C190.0696 (12)0.0657 (12)0.0843 (14)0.0173 (10)0.0061 (10)0.0092 (10)
C200.0868 (15)0.0903 (16)0.0654 (13)0.0385 (13)0.0005 (11)0.0080 (11)
C210.0690 (12)0.0851 (14)0.0655 (12)0.0374 (11)0.0152 (9)0.0272 (10)
C220.0470 (8)0.0598 (10)0.0638 (10)0.0251 (8)0.0112 (7)0.0263 (8)
C230.0520 (9)0.0495 (9)0.0693 (11)0.0154 (7)0.0108 (8)0.0226 (8)
C240.0450 (8)0.0483 (8)0.0551 (9)0.0155 (7)0.0138 (7)0.0199 (7)
C250.0476 (8)0.0492 (8)0.0536 (9)0.0198 (7)0.0135 (7)0.0201 (7)
C260.0507 (8)0.0545 (9)0.0518 (9)0.0207 (7)0.0151 (7)0.0220 (7)
C270.0730 (12)0.0600 (11)0.0632 (11)0.0294 (9)0.0133 (9)0.0160 (9)
C280.0930 (16)0.0637 (12)0.0678 (12)0.0256 (11)0.0102 (11)0.0049 (10)
C290.0685 (12)0.0789 (14)0.0649 (12)0.0123 (11)0.0008 (10)0.0080 (10)
C300.0538 (10)0.0875 (14)0.0651 (11)0.0245 (10)0.0061 (8)0.0206 (10)
C310.0505 (9)0.0621 (10)0.0537 (9)0.0208 (8)0.0134 (7)0.0206 (8)
C320.0526 (9)0.0530 (9)0.0608 (10)0.0214 (7)0.0107 (7)0.0166 (8)
C330.0602 (11)0.0689 (12)0.0935 (14)0.0259 (10)0.0314 (10)0.0473 (11)
C340.0682 (12)0.0879 (15)0.0898 (15)0.0486 (12)0.0146 (11)0.0260 (12)
C350.101 (4)0.159 (7)0.271 (12)0.075 (5)0.041 (6)0.008 (7)
C360.073 (3)0.098 (4)0.101 (4)0.045 (3)0.006 (3)0.015 (3)
N10.0423 (6)0.0490 (7)0.0604 (8)0.0161 (6)0.0079 (6)0.0178 (6)
N20.0425 (7)0.0513 (8)0.0625 (8)0.0180 (6)0.0083 (6)0.0185 (6)
N30.0487 (7)0.0484 (7)0.0506 (7)0.0139 (6)0.0088 (6)0.0168 (6)
N40.0497 (7)0.0493 (7)0.0533 (8)0.0124 (6)0.0103 (6)0.0195 (6)
N50.0499 (7)0.0563 (8)0.0704 (9)0.0196 (7)0.0190 (6)0.0329 (7)
N60.0529 (8)0.0640 (9)0.0666 (9)0.0302 (7)0.0104 (6)0.0195 (7)
N70.123 (4)0.127 (4)0.113 (4)0.058 (4)0.005 (3)0.003 (3)
Geometric parameters (Å, º) top
C1—N11.285 (2)C21—C221.390 (3)
C1—C21.482 (2)C21—H210.9300
C1—C81.503 (2)C22—N51.387 (2)
C2—C31.384 (3)C23—N51.349 (2)
C2—C71.385 (3)C23—H230.9300
C3—C41.386 (3)C24—N21.282 (2)
C3—H30.9300C24—C251.437 (2)
C4—C51.367 (3)C24—H240.9300
C4—H40.9300C25—C321.377 (2)
C5—C61.368 (3)C25—C261.440 (2)
C5—H50.9300C26—C271.401 (3)
C6—C71.383 (3)C26—C311.408 (2)
C6—H60.9300C27—C281.377 (3)
C7—H70.9300C27—H270.9300
C8—N31.289 (2)C28—C291.397 (3)
C8—C91.475 (2)C28—H280.9300
C9—C141.380 (3)C29—C301.371 (3)
C9—C101.391 (2)C29—H290.9300
C10—C111.381 (3)C30—C311.394 (3)
C10—H100.9300C30—H300.9300
C11—C121.365 (3)C31—N61.384 (2)
C11—H110.9300C32—N61.354 (2)
C12—C131.359 (3)C32—H320.9300
C12—H120.9300C33—N51.457 (2)
C13—C141.387 (3)C33—H33A0.9600
C13—H130.9300C33—H33B0.9600
C14—H140.9300C33—H33C0.9600
C15—N41.286 (2)C34—N61.453 (2)
C15—C161.434 (2)C34—H34A0.9600
C15—H150.9300C34—H34B0.9600
C16—C231.380 (2)C34—H34C0.9600
C16—C171.440 (3)C35—C36i1.280 (7)
C17—C181.402 (2)C35—C361.280 (7)
C17—C221.411 (2)C35—H35A0.92 (2)
C18—C191.376 (3)C35—H35B0.93 (2)
C18—H180.9300C35—H35Ai0.92 (2)
C19—C201.399 (3)C35—H35Bi0.93 (2)
C19—H190.9300C36—N71.104 (7)
C20—C211.374 (3)N1—N21.4110 (19)
C20—H200.9300N3—N41.4067 (19)
N1—C1—C2119.59 (15)N5—C23—H23124.6
N1—C1—C8123.36 (14)C16—C23—H23124.6
C2—C1—C8116.93 (14)N2—C24—C25121.38 (16)
C3—C2—C7118.14 (16)N2—C24—H24119.3
C3—C2—C1121.77 (16)C25—C24—H24119.3
C7—C2—C1120.03 (16)C32—C25—C24124.65 (16)
C2—C3—C4120.1 (2)C32—C25—C26106.03 (15)
C2—C3—H3120.0C24—C25—C26129.31 (15)
C4—C3—H3120.0C27—C26—C31118.55 (17)
C5—C4—C3121.1 (2)C27—C26—C25134.91 (17)
C5—C4—H4119.4C31—C26—C25106.54 (15)
C3—C4—H4119.4C28—C27—C26118.6 (2)
C4—C5—C6119.4 (2)C28—C27—H27120.7
C4—C5—H5120.3C26—C27—H27120.7
C6—C5—H5120.3C27—C28—C29121.7 (2)
C5—C6—C7120.1 (2)C27—C28—H28119.2
C5—C6—H6119.9C29—C28—H28119.2
C7—C6—H6119.9C30—C29—C28121.3 (2)
C6—C7—C2121.1 (2)C30—C29—H29119.3
C6—C7—H7119.4C28—C29—H29119.3
C2—C7—H7119.4C29—C30—C31117.2 (2)
N3—C8—C9119.91 (15)C29—C30—H30121.4
N3—C8—C1122.34 (14)C31—C30—H30121.4
C9—C8—C1117.58 (13)N6—C31—C30129.16 (18)
C14—C9—C10118.14 (17)N6—C31—C26108.11 (15)
C14—C9—C8121.49 (16)C30—C31—C26122.72 (18)
C10—C9—C8120.27 (17)N6—C32—C25110.85 (16)
C11—C10—C9120.5 (2)N6—C32—H32124.6
C11—C10—H10119.8C25—C32—H32124.6
C9—C10—H10119.8N5—C33—H33A109.5
C12—C11—C10120.6 (2)N5—C33—H33B109.5
C12—C11—H11119.7H33A—C33—H33B109.5
C10—C11—H11119.7N5—C33—H33C109.5
C13—C12—C11119.5 (2)H33A—C33—H33C109.5
C13—C12—H12120.2H33B—C33—H33C109.5
C11—C12—H12120.2N6—C34—H34A109.5
C12—C13—C14120.8 (2)N6—C34—H34B109.5
C12—C13—H13119.6H34A—C34—H34B109.5
C14—C13—H13119.6N6—C34—H34C109.5
C9—C14—C13120.5 (2)H34A—C34—H34C109.5
C9—C14—H14119.8H34B—C34—H34C109.5
C13—C14—H14119.8C36i—C35—C36180.0
N4—C15—C16121.41 (16)C36i—C35—H35A96 (4)
N4—C15—H15119.3C36—C35—H35A84 (4)
C16—C15—H15119.3C36i—C35—H35B81 (8)
C23—C16—C15124.28 (17)C36—C35—H35B99 (8)
C23—C16—C17106.21 (15)H35A—C35—H35B86 (8)
C15—C16—C17129.43 (14)C36i—C35—H35Ai84 (4)
C18—C17—C22118.62 (17)C36—C35—H35Ai96 (4)
C18—C17—C16134.93 (16)H35A—C35—H35Ai180.0
C22—C17—C16106.42 (14)H35B—C35—H35Ai94 (8)
C19—C18—C17118.58 (18)C36i—C35—H35Bi99 (8)
C19—C18—H18120.7C36—C35—H35Bi81 (8)
C17—C18—H18120.7H35A—C35—H35Bi94 (8)
C18—C19—C20121.7 (2)H35B—C35—H35Bi180 (6)
C18—C19—H19119.2H35Ai—C35—H35Bi86 (8)
C20—C19—H19119.2N7—C36—C35173.2 (7)
C21—C20—C19121.1 (2)C1—N1—N2111.60 (14)
C21—C20—H20119.4C24—N2—N1111.89 (14)
C19—C20—H20119.4C8—N3—N4111.13 (13)
C20—C21—C22117.36 (19)C15—N4—N3112.23 (14)
C20—C21—H21121.3C23—N5—C22108.75 (13)
C22—C21—H21121.3C23—N5—C33125.59 (17)
N5—C22—C21129.47 (16)C22—N5—C33125.48 (17)
N5—C22—C17107.90 (16)C32—N6—C31108.47 (15)
C21—C22—C17122.60 (17)C32—N6—C34126.40 (17)
N5—C23—C16110.71 (17)C31—N6—C34125.10 (17)
Symmetry code: (i) x+2, y, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C12—H12···N7ii0.932.513.372 (6)155
Symmetry code: (ii) x+2, y, z+1.
(1Z,2Z)-1,2-Bis{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (4-BDHFN) top
Crystal data top
C36H26N4F(000) = 1080
Mr = 514.61Dx = 1.246 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
a = 26.195 (8) ÅCell parameters from 380 reflections
b = 9.809 (3) Åθ = 2.5–26.0°
c = 11.806 (4) ŵ = 0.07 mm1
β = 115.230 (5)°T = 298 K
V = 2744.2 (15) Å3Block, yellow
Z = 40.30 × 0.16 × 0.10 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
2413 independent reflections
Radiation source: fine-focus sealed tube1197 reflections with I > 2σ(I)
Detector resolution: 10.22 pixels mm-1Rint = 0.058
phi and ω scansθmax = 25.0°, θmin = 1.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 3129
Tmin = 0.986, Tmax = 0.993k = 1111
6631 measured reflectionsl = 1412
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.062Only H-atom displacement parameters refined
wR(F2) = 0.130 w = 1/[σ2(Fo2) + (0.0447P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.95(Δ/σ)max < 0.001
2413 reflectionsΔρmax = 0.11 e Å3
194 parametersΔρmin = 0.10 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.47469 (10)0.0592 (3)0.1862 (2)0.0498 (7)
C20.42618 (10)0.0283 (3)0.1669 (2)0.0492 (7)
C30.38212 (11)0.0443 (3)0.0497 (3)0.0657 (8)
H30.3826340.0023880.0184280.065 (8)*
C40.33781 (13)0.1281 (3)0.0331 (3)0.0816 (10)
H40.3084090.1371740.0463580.075 (9)*
C50.33585 (14)0.1977 (3)0.1294 (3)0.0845 (10)
H50.3056680.2553940.1163040.074 (9)*
C60.37835 (14)0.1830 (3)0.2459 (4)0.0864 (10)
H60.3772010.2299860.3132210.097 (11)*
C70.42297 (12)0.0986 (3)0.2640 (3)0.0715 (9)
H70.4517500.0889000.3441350.052 (7)*
C80.52380 (14)0.2815 (3)0.0423 (3)0.0670 (8)
H80.4898680.2857910.0292190.085 (11)*
C90.56973 (13)0.3652 (3)0.0431 (3)0.0660 (8)
C100.55680 (17)0.4528 (3)0.0558 (3)0.0855 (10)
H100.5200130.4540050.1180070.117 (14)*
C110.59585 (18)0.5391 (4)0.0671 (4)0.1027 (12)
H110.5854780.5984320.1347580.100 (11)*
C120.65000 (19)0.5357 (4)0.0229 (4)0.1035 (12)
H120.6765270.5938740.0157640.123 (13)*
C130.66715 (15)0.4466 (3)0.1267 (3)0.0799 (9)
C140.62661 (13)0.3581 (3)0.1381 (3)0.0635 (8)
C150.64564 (14)0.2666 (3)0.2393 (3)0.0694 (8)
H150.6199420.2075600.2488260.077 (9)*
C160.70059 (14)0.2621 (4)0.3236 (3)0.0824 (10)
H160.7121010.2002210.3894910.097 (12)*
C170.73971 (18)0.3498 (4)0.3116 (4)0.1014 (12)
H170.7772850.3462770.3697190.112 (13)*
C180.72364 (17)0.4395 (4)0.2167 (4)0.1034 (12)
H180.7502680.4978940.2103830.086 (10)*
N10.47400 (9)0.1318 (2)0.0954 (2)0.0609 (6)
N20.52522 (9)0.2036 (2)0.1286 (2)0.0634 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0526 (17)0.0542 (16)0.0440 (15)0.0071 (13)0.0219 (13)0.0013 (13)
C20.0451 (16)0.0574 (17)0.0440 (16)0.0016 (13)0.0179 (15)0.0031 (14)
C30.0600 (19)0.084 (2)0.0522 (19)0.0039 (17)0.0225 (18)0.0002 (17)
C40.054 (2)0.111 (3)0.070 (2)0.0156 (19)0.017 (2)0.017 (2)
C50.065 (2)0.100 (3)0.095 (3)0.030 (2)0.040 (2)0.019 (2)
C60.085 (3)0.096 (3)0.082 (3)0.025 (2)0.039 (2)0.006 (2)
C70.062 (2)0.087 (2)0.056 (2)0.0173 (17)0.0163 (19)0.0009 (17)
C80.072 (2)0.064 (2)0.065 (2)0.0010 (16)0.029 (2)0.0022 (16)
C90.074 (2)0.0621 (19)0.068 (2)0.0001 (17)0.036 (2)0.0008 (17)
C100.100 (3)0.081 (3)0.087 (3)0.000 (2)0.051 (3)0.022 (2)
C110.123 (3)0.091 (3)0.108 (3)0.014 (3)0.063 (3)0.036 (3)
C120.128 (3)0.084 (3)0.131 (4)0.009 (3)0.086 (3)0.019 (3)
C130.087 (3)0.074 (2)0.094 (3)0.012 (2)0.053 (2)0.005 (2)
C140.078 (2)0.0603 (19)0.064 (2)0.0020 (17)0.0415 (19)0.0036 (16)
C150.065 (2)0.080 (2)0.067 (2)0.0083 (19)0.031 (2)0.0062 (17)
C160.071 (2)0.096 (3)0.078 (2)0.005 (2)0.029 (2)0.004 (2)
C170.076 (3)0.120 (4)0.110 (3)0.017 (2)0.040 (3)0.002 (3)
C180.091 (3)0.103 (3)0.128 (4)0.028 (3)0.057 (3)0.004 (3)
N10.0583 (15)0.0688 (16)0.0549 (15)0.0016 (13)0.0235 (13)0.0049 (12)
N20.0633 (16)0.0688 (16)0.0597 (16)0.0061 (13)0.0278 (14)0.0139 (13)
Geometric parameters (Å, º) top
C1—N11.280 (3)C9—C141.434 (3)
C1—C21.469 (3)C10—C111.378 (4)
C1—C1i1.525 (4)C10—H100.9300
C2—C71.371 (3)C11—C121.363 (4)
C2—C31.382 (3)C11—H110.9300
C3—C41.367 (4)C12—C131.414 (4)
C3—H30.9300C12—H120.9300
C4—C51.346 (4)C13—C181.409 (4)
C4—H40.9300C13—C141.422 (4)
C5—C61.359 (4)C14—C151.406 (4)
C5—H50.9300C15—C161.357 (4)
C6—C71.373 (4)C15—H150.9300
C6—H60.9300C16—C171.390 (4)
C7—H70.9300C16—H160.9300
C8—N21.261 (3)C17—C181.343 (4)
C8—C91.453 (4)C17—H170.9300
C8—H80.9300C18—H180.9300
C9—C101.371 (4)N1—N21.415 (3)
N1—C1—C2119.5 (2)C9—C10—H10118.5
N1—C1—C1i121.5 (2)C11—C10—H10118.5
C2—C1—C1i118.9 (2)C12—C11—C10118.6 (4)
C7—C2—C3117.3 (3)C12—C11—H11120.7
C7—C2—C1121.5 (2)C10—C11—H11120.7
C3—C2—C1121.3 (3)C11—C12—C13122.1 (4)
C4—C3—C2120.5 (3)C11—C12—H12118.9
C4—C3—H3119.8C13—C12—H12118.9
C2—C3—H3119.8C18—C13—C12121.9 (4)
C5—C4—C3121.3 (3)C18—C13—C14119.0 (3)
C5—C4—H4119.3C12—C13—C14119.0 (3)
C3—C4—H4119.3C15—C14—C13117.5 (3)
C4—C5—C6119.4 (3)C15—C14—C9124.7 (3)
C4—C5—H5120.3C13—C14—C9117.7 (3)
C6—C5—H5120.3C16—C15—C14121.6 (3)
C5—C6—C7119.8 (3)C16—C15—H15119.2
C5—C6—H6120.1C14—C15—H15119.2
C7—C6—H6120.1C15—C16—C17120.2 (4)
C2—C7—C6121.7 (3)C15—C16—H16119.9
C2—C7—H7119.2C17—C16—H16119.9
C6—C7—H7119.2C18—C17—C16120.5 (4)
N2—C8—C9126.7 (3)C18—C17—H17119.8
N2—C8—H8116.7C16—C17—H17119.8
C9—C8—H8116.7C17—C18—C13121.1 (4)
C10—C9—C14119.5 (3)C17—C18—H18119.4
C10—C9—C8116.4 (3)C13—C18—H18119.4
C14—C9—C8124.0 (3)C1—N1—N2111.8 (2)
C9—C10—C11123.0 (4)C8—N2—N1112.3 (2)
Symmetry code: (i) x+1, y, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C15—H15···N20.932.272.920 (4)126
(Z)-2-{(E)-[(1H-Indol-3-yl)methylidene]hydrazinylidene}-\ 1,2-diphenylethanone (5-BMHFI) top
Crystal data top
C23H17N3ODx = 1.243 Mg m3
Mr = 351.39Melting point: 470.4 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
a = 6.8767 (1) ÅCell parameters from 380 reflections
b = 8.3698 (2) Åθ = 2.5–26.0°
c = 32.6317 (6) ŵ = 0.08 mm1
V = 1878.17 (6) Å3T = 293 K
Z = 4Needle, yellow
F(000) = 7360.35 × 0.1 × 0.09 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
3641 independent reflections
Radiation source: fine-focus sealed tube3444 reflections with I > 2σ(I)
Detector resolution: 10.11 pixels mm-1Rint = 0.023
phi and ω scansθmax = 26.1°, θmin = 2.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 78
Tmin = 0.903, Tmax = 0.939k = 1010
10418 measured reflectionsl = 3940
Refinement top
Refinement on F2Only H-atom displacement parameters refined
Least-squares matrix: full w = 1/[σ2(Fo2) + (0.0555P)2 + 0.1425P]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.035(Δ/σ)max = 0.001
wR(F2) = 0.096Δρmax = 0.15 e Å3
S = 1.02Δρmin = 0.13 e Å3
3641 reflectionsExtinction correction: SHELXL2016 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
262 parametersExtinction coefficient: 0.014 (2)
0 restraintsAbsolute structure: Flack x determined using 1312 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
The diffraction data did not permit a clear determination of the absolute structure.
Hydrogen site location: inferred from neighbouring sitesAbsolute structure parameter: 1.4 (6)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.7517 (3)0.2656 (2)0.85621 (6)0.0427 (4)
C20.8141 (3)0.1859 (2)0.81814 (6)0.0470 (4)
C31.0008 (4)0.1258 (3)0.81425 (7)0.0669 (6)
H31.0892690.1380700.8355700.076 (8)*
C41.0561 (5)0.0477 (4)0.77895 (9)0.0874 (9)
H41.1817040.0074820.7766710.106 (11)*
C50.9281 (5)0.0289 (4)0.74721 (9)0.0923 (10)
H50.9663110.0246780.7235780.102 (10)*
C60.7443 (5)0.0890 (4)0.75035 (8)0.0843 (9)
H60.6574860.0768350.7287220.100 (10)*
C70.6864 (4)0.1677 (3)0.78550 (7)0.0636 (6)
H70.5610820.2088360.7873160.062 (7)*
C80.5398 (3)0.3144 (2)0.86038 (5)0.0423 (4)
C90.4897 (3)0.4854 (3)0.85595 (6)0.0494 (5)
C100.2996 (4)0.5330 (4)0.86342 (7)0.0711 (7)
H100.2053860.4583360.8705920.079 (9)*
C110.2525 (7)0.6924 (5)0.86005 (11)0.1074 (13)
H110.1257810.7255820.8651800.136 (15)*
C120.3901 (8)0.8024 (4)0.84926 (12)0.1188 (16)
H120.3561490.9096010.8471760.119 (12)*
C130.5766 (7)0.7565 (4)0.84152 (11)0.1043 (12)
H130.6695430.8317790.8340330.160 (18)*
C140.6268 (4)0.5965 (3)0.84490 (8)0.0704 (7)
H140.7538050.5643170.8396540.079 (9)*
C150.8754 (3)0.3567 (2)0.95253 (6)0.0472 (4)
H151.0033660.3211560.9512080.050 (6)*
C160.7994 (3)0.4113 (2)0.99091 (6)0.0457 (4)
C170.6165 (3)0.4884 (2)1.00009 (6)0.0438 (4)
C180.4611 (3)0.5458 (2)0.97686 (7)0.0521 (5)
H180.4623040.5369610.9484490.058 (6)*
C190.3066 (4)0.6156 (3)0.99655 (8)0.0646 (6)
H190.2030490.6547390.9812070.073 (7)*
C200.3018 (4)0.6290 (3)1.03919 (8)0.0685 (6)
H200.1952630.6769361.0517040.074 (8)*
C210.4506 (4)0.5730 (3)1.06286 (7)0.0614 (6)
H210.4465230.5804721.0912840.068 (7)*
C220.6087 (3)0.5045 (2)1.04290 (6)0.0490 (5)
C230.8892 (3)0.3850 (3)1.02803 (6)0.0558 (5)
H231.0097200.3362911.0313940.063 (7)*
N10.8691 (2)0.2859 (2)0.88638 (5)0.0493 (4)
N20.7709 (2)0.3555 (2)0.91982 (5)0.0481 (4)
N30.7772 (3)0.4399 (2)1.05867 (5)0.0580 (5)
H240.8062920.4355081.0842780.087 (9)*
O10.4184 (2)0.21208 (19)0.86624 (5)0.0593 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0455 (9)0.0417 (9)0.0410 (9)0.0001 (8)0.0002 (8)0.0052 (7)
C20.0552 (11)0.0454 (10)0.0403 (9)0.0018 (9)0.0022 (8)0.0040 (8)
C30.0636 (13)0.0814 (16)0.0558 (12)0.0192 (13)0.0002 (11)0.0060 (12)
C40.0847 (19)0.106 (2)0.0712 (16)0.0347 (18)0.0091 (14)0.0160 (15)
C50.115 (2)0.105 (2)0.0569 (14)0.026 (2)0.0091 (16)0.0225 (14)
C60.095 (2)0.111 (2)0.0468 (12)0.0072 (19)0.0077 (13)0.0148 (13)
C70.0627 (14)0.0796 (16)0.0486 (11)0.0074 (12)0.0031 (10)0.0037 (11)
C80.0438 (9)0.0491 (10)0.0342 (8)0.0034 (8)0.0009 (7)0.0032 (7)
C90.0552 (10)0.0531 (11)0.0400 (9)0.0087 (9)0.0072 (8)0.0021 (8)
C100.0679 (14)0.0868 (18)0.0585 (13)0.0256 (15)0.0039 (11)0.0098 (12)
C110.117 (3)0.108 (3)0.097 (2)0.069 (2)0.023 (2)0.030 (2)
C120.181 (4)0.0616 (18)0.114 (3)0.048 (3)0.063 (3)0.0235 (19)
C130.150 (3)0.0520 (15)0.111 (3)0.002 (2)0.043 (3)0.0109 (15)
C140.0793 (17)0.0521 (12)0.0798 (16)0.0026 (12)0.0157 (14)0.0109 (11)
C150.0434 (9)0.0473 (10)0.0509 (10)0.0047 (9)0.0062 (8)0.0019 (8)
C160.0475 (10)0.0425 (9)0.0469 (9)0.0014 (8)0.0118 (8)0.0030 (8)
C170.0496 (10)0.0350 (8)0.0467 (9)0.0023 (8)0.0065 (8)0.0021 (7)
C180.0551 (11)0.0477 (10)0.0535 (11)0.0026 (9)0.0131 (9)0.0002 (9)
C190.0568 (13)0.0599 (13)0.0770 (15)0.0121 (11)0.0091 (12)0.0001 (11)
C200.0628 (14)0.0628 (14)0.0798 (16)0.0096 (12)0.0087 (13)0.0073 (12)
C210.0763 (15)0.0548 (12)0.0531 (12)0.0016 (12)0.0053 (11)0.0072 (10)
C220.0602 (12)0.0402 (10)0.0466 (10)0.0005 (9)0.0058 (9)0.0012 (8)
C230.0575 (12)0.0551 (11)0.0548 (11)0.0090 (10)0.0158 (10)0.0058 (9)
N10.0456 (9)0.0585 (10)0.0437 (8)0.0059 (8)0.0012 (7)0.0030 (7)
N20.0450 (8)0.0569 (9)0.0424 (8)0.0056 (8)0.0019 (7)0.0038 (7)
N30.0738 (12)0.0595 (10)0.0407 (9)0.0084 (10)0.0158 (8)0.0051 (7)
O10.0542 (8)0.0652 (9)0.0586 (9)0.0152 (8)0.0019 (7)0.0079 (7)
Geometric parameters (Å, º) top
C1—N11.284 (3)C13—C141.387 (4)
C1—C21.474 (3)C13—H130.9300
C1—C81.520 (3)C14—H140.9300
C2—C31.385 (3)C15—N21.287 (2)
C2—C71.389 (3)C15—C161.432 (3)
C3—C41.378 (4)C15—H150.9300
C3—H30.9300C16—C231.377 (3)
C4—C51.368 (4)C16—C171.445 (3)
C4—H40.9300C17—C181.395 (3)
C5—C61.364 (4)C17—C221.404 (3)
C5—H50.9300C18—C191.372 (3)
C6—C71.381 (3)C18—H180.9300
C6—H60.9300C19—C201.396 (4)
C7—H70.9300C19—H190.9300
C8—O11.211 (2)C20—C211.365 (3)
C8—C91.479 (3)C20—H200.9300
C9—C141.372 (3)C21—C221.391 (3)
C9—C101.388 (3)C21—H210.9300
C10—C111.378 (5)C22—N31.378 (3)
C10—H100.9300C23—N31.343 (3)
C11—C121.366 (6)C23—H230.9300
C11—H110.9300N1—N21.410 (2)
C12—C131.362 (6)N3—H240.8600
C12—H120.9300
N1—C1—C2121.53 (18)C12—C13—H13120.3
N1—C1—C8119.90 (17)C14—C13—H13120.3
C2—C1—C8118.45 (16)C9—C14—C13120.3 (3)
C3—C2—C7118.4 (2)C9—C14—H14119.9
C3—C2—C1120.79 (19)C13—C14—H14119.9
C7—C2—C1120.79 (19)N2—C15—C16121.61 (18)
C4—C3—C2120.3 (2)N2—C15—H15119.2
C4—C3—H3119.8C16—C15—H15119.2
C2—C3—H3119.8C23—C16—C15123.68 (18)
C5—C4—C3120.7 (3)C23—C16—C17106.22 (17)
C5—C4—H4119.7C15—C16—C17129.90 (17)
C3—C4—H4119.7C18—C17—C22118.56 (18)
C6—C5—C4119.8 (3)C18—C17—C16135.04 (18)
C6—C5—H5120.1C22—C17—C16106.40 (17)
C4—C5—H5120.1C19—C18—C17119.0 (2)
C5—C6—C7120.3 (3)C19—C18—H18120.5
C5—C6—H6119.8C17—C18—H18120.5
C7—C6—H6119.8C18—C19—C20121.3 (2)
C6—C7—C2120.5 (2)C18—C19—H19119.4
C6—C7—H7119.8C20—C19—H19119.4
C2—C7—H7119.8C21—C20—C19121.3 (2)
O1—C8—C9122.64 (19)C21—C20—H20119.4
O1—C8—C1119.01 (18)C19—C20—H20119.4
C9—C8—C1118.33 (17)C20—C21—C22117.5 (2)
C14—C9—C10119.9 (2)C20—C21—H21121.2
C14—C9—C8121.4 (2)C22—C21—H21121.2
C10—C9—C8118.7 (2)N3—C22—C21130.1 (2)
C11—C10—C9119.0 (3)N3—C22—C17107.56 (18)
C11—C10—H10120.5C21—C22—C17122.37 (19)
C9—C10—H10120.5N3—C23—C16110.04 (18)
C12—C11—C10120.7 (4)N3—C23—H23125.0
C12—C11—H11119.7C16—C23—H23125.0
C10—C11—H11119.7C1—N1—N2110.30 (16)
C13—C12—C11120.7 (3)C15—N2—N1112.19 (16)
C13—C12—H12119.7C23—N3—C22109.78 (17)
C11—C12—H12119.7C23—N3—H24125.1
C12—C13—C14119.4 (4)C22—N3—H24125.1
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3···O1i0.932.553.413 (3)154
N3—H24···O1ii0.862.172.927 (2)146
Symmetry codes: (i) x+1, y, z; (ii) x+1/2, y+1/2, z+2.
(Z)-2-{(E)-[1-(1H-Indol-3-yl)ethylidene]hydrazinylidene}-\ 1,2-diphenylethanone (6-BMHAI) top
Crystal data top
C24H19N3ODx = 1.271 Mg m3
Mr = 365.42Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P43212Cell parameters from 380 reflections
a = 8.3580 (1) Åθ = 2.5–26.0°
c = 54.6705 (7) ŵ = 0.08 mm1
V = 3819.07 (10) Å3T = 293 K
Z = 8Needle, yellow
F(000) = 15360.3 × 0.1 × 0.1 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
3759 independent reflections
Radiation source: fine-focus sealed tube3565 reflections with I > 2σ(I)
Detector resolution: 10.32 pixels mm-1Rint = 0.030
phi and ω scansθmax = 26.0°, θmin = 1.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 610
Tmin = 0.983, Tmax = 0.998k = 99
21746 measured reflectionsl = 6666
Refinement top
Refinement on F2Only H-atom displacement parameters refined
Least-squares matrix: full w = 1/[σ2(Fo2) + (0.0638P)2 + 0.5669P]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.041(Δ/σ)max < 0.001
wR(F2) = 0.113Δρmax = 0.16 e Å3
S = 1.06Δρmin = 0.12 e Å3
3759 reflectionsExtinction correction: SHELXL2016 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
274 parametersExtinction coefficient: 0.0060 (10)
0 restraintsAbsolute structure: Flack x determined using 1258 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
The diffraction data did not permit a clear determination of the absolute structure.
Hydrogen site location: inferred from neighbouring sitesAbsolute structure parameter: 1.5 (6)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C11.1474 (3)0.3991 (2)0.03774 (4)0.0375 (4)
C21.0797 (3)0.4604 (2)0.01468 (4)0.0399 (5)
C31.1757 (3)0.5262 (3)0.00339 (4)0.0536 (6)
H31.2858320.5309780.0011070.093 (11)*
C41.1095 (4)0.5845 (4)0.02472 (4)0.0638 (7)
H41.1752430.6293700.0366110.085 (10)*
C50.9483 (4)0.5770 (4)0.02850 (5)0.0702 (8)
H50.9040200.6180150.0427920.112 (13)*
C60.8528 (4)0.5092 (5)0.01127 (6)0.0887 (12)
H60.7432890.5017150.0140350.134 (16)*
C70.9165 (3)0.4509 (4)0.01037 (5)0.0688 (8)
H70.8495690.4053480.0220410.080 (10)*
C81.0347 (3)0.3189 (2)0.05573 (3)0.0357 (4)
C91.0165 (3)0.1422 (3)0.05565 (4)0.0385 (5)
C100.9186 (3)0.0725 (3)0.07313 (4)0.0485 (6)
H100.8659940.1358540.0845670.064 (9)*
C110.8998 (4)0.0923 (3)0.07344 (5)0.0639 (7)
H110.8347220.1399260.0851660.107 (13)*
C120.9768 (4)0.1849 (3)0.05651 (6)0.0740 (9)
H120.9633750.2953300.0567590.110 (13)*
C131.0735 (4)0.1166 (3)0.03917 (7)0.0765 (9)
H131.1258330.1808290.0278090.097 (12)*
C141.0937 (3)0.0485 (3)0.03852 (5)0.0565 (6)
H141.1584690.0952950.0266860.061 (8)*
C151.4732 (2)0.3899 (3)0.07414 (4)0.0394 (5)
C161.5313 (2)0.2955 (3)0.09468 (4)0.0396 (5)
C171.4917 (2)0.1302 (3)0.09979 (4)0.0383 (5)
C181.3983 (3)0.0148 (3)0.08826 (4)0.0462 (5)
H181.3421700.0393090.0740570.064 (8)*
C191.3903 (4)0.1359 (3)0.09820 (5)0.0614 (7)
H191.3277600.2134860.0906330.071 (9)*
C201.4748 (5)0.1750 (4)0.11958 (5)0.0710 (9)
H201.4677850.2783560.1258070.094 (11)*
C211.5667 (4)0.0651 (4)0.13138 (5)0.0661 (8)
H211.6222140.0911230.1455720.097 (12)*
C221.5744 (3)0.0886 (3)0.12134 (4)0.0487 (6)
C231.6341 (3)0.3418 (3)0.11298 (5)0.0534 (6)
H231.6799500.4428410.1142890.073 (9)*
C241.5707 (3)0.5277 (3)0.06510 (5)0.0569 (7)
H24A1.6671580.5357190.0745490.156 (19)*
H24B1.5102080.6247740.0667280.18 (2)*
H24C1.5973080.5111500.0482030.121 (15)*
N11.2956 (2)0.4223 (2)0.04307 (3)0.0462 (5)
N21.3383 (2)0.3443 (2)0.06501 (3)0.0455 (5)
N31.6592 (3)0.2208 (3)0.12874 (4)0.0609 (6)
H251.7191090.2255410.1415060.074 (10)*
O10.9581 (2)0.4039 (2)0.06942 (3)0.0527 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0424 (11)0.0314 (10)0.0386 (10)0.0004 (8)0.0045 (9)0.0036 (8)
C20.0495 (12)0.0335 (10)0.0367 (10)0.0004 (9)0.0053 (9)0.0043 (8)
C30.0571 (15)0.0570 (15)0.0468 (12)0.0025 (11)0.0007 (11)0.0080 (11)
C40.085 (2)0.0643 (17)0.0427 (12)0.0019 (15)0.0041 (13)0.0151 (12)
C50.085 (2)0.079 (2)0.0462 (13)0.0060 (17)0.0175 (14)0.0186 (13)
C60.0621 (19)0.136 (4)0.0682 (18)0.003 (2)0.0228 (16)0.035 (2)
C70.0510 (15)0.101 (2)0.0540 (14)0.0045 (15)0.0100 (12)0.0274 (15)
C80.0386 (10)0.0359 (10)0.0326 (8)0.0017 (8)0.0067 (8)0.0027 (8)
C90.0420 (11)0.0354 (10)0.0380 (9)0.0012 (8)0.0074 (9)0.0031 (8)
C100.0533 (13)0.0490 (13)0.0433 (11)0.0057 (10)0.0038 (10)0.0080 (10)
C110.0720 (18)0.0547 (15)0.0649 (15)0.0184 (14)0.0094 (14)0.0209 (13)
C120.087 (2)0.0362 (14)0.098 (2)0.0104 (14)0.0130 (19)0.0024 (15)
C130.090 (2)0.0446 (15)0.095 (2)0.0013 (15)0.0128 (19)0.0203 (15)
C140.0642 (16)0.0440 (13)0.0614 (14)0.0059 (12)0.0087 (13)0.0086 (11)
C150.0322 (10)0.0393 (11)0.0467 (10)0.0002 (8)0.0004 (9)0.0020 (9)
C160.0311 (10)0.0456 (12)0.0420 (10)0.0012 (9)0.0029 (9)0.0015 (9)
C170.0336 (10)0.0460 (12)0.0354 (9)0.0072 (8)0.0017 (8)0.0040 (8)
C180.0480 (12)0.0470 (12)0.0437 (11)0.0002 (10)0.0013 (9)0.0032 (9)
C190.0777 (19)0.0472 (14)0.0593 (14)0.0006 (13)0.0133 (14)0.0079 (12)
C200.104 (3)0.0494 (15)0.0602 (15)0.0214 (16)0.0204 (17)0.0186 (13)
C210.083 (2)0.0711 (19)0.0446 (13)0.0318 (16)0.0022 (13)0.0160 (13)
C220.0447 (13)0.0619 (15)0.0395 (11)0.0159 (11)0.0005 (9)0.0034 (10)
C230.0412 (13)0.0594 (15)0.0597 (13)0.0011 (11)0.0118 (11)0.0079 (12)
C240.0482 (14)0.0501 (14)0.0723 (17)0.0120 (12)0.0006 (13)0.0104 (13)
N10.0433 (10)0.0463 (11)0.0489 (10)0.0053 (8)0.0090 (8)0.0139 (9)
N20.0409 (10)0.0468 (11)0.0489 (10)0.0065 (8)0.0108 (8)0.0144 (8)
N30.0518 (12)0.0784 (16)0.0525 (11)0.0118 (11)0.0218 (10)0.0041 (11)
O10.0628 (11)0.0440 (9)0.0512 (9)0.0070 (8)0.0083 (8)0.0033 (7)
Geometric parameters (Å, º) top
C1—N11.287 (3)C13—H130.9300
C1—C21.474 (3)C14—H140.9300
C1—C81.518 (3)C15—N21.290 (3)
C2—C31.386 (3)C15—C161.456 (3)
C2—C71.386 (4)C15—C241.495 (3)
C3—C41.380 (3)C16—C231.375 (3)
C3—H30.9300C16—C171.448 (3)
C4—C51.365 (4)C17—C181.392 (3)
C4—H40.9300C17—C221.409 (3)
C5—C61.358 (4)C18—C191.373 (3)
C5—H50.9300C18—H180.9300
C6—C71.386 (4)C19—C201.404 (4)
C6—H60.9300C19—H190.9300
C7—H70.9300C20—C211.360 (5)
C8—O11.214 (3)C20—H200.9300
C8—C91.485 (3)C21—C221.399 (4)
C9—C141.381 (3)C21—H210.9300
C9—C101.386 (3)C22—N31.373 (4)
C10—C111.387 (4)C23—N31.345 (4)
C10—H100.9300C23—H230.9300
C11—C121.367 (5)C24—H24A0.9600
C11—H110.9300C24—H24B0.9600
C12—C131.370 (5)C24—H24C0.9600
C12—H120.9300N1—N21.411 (2)
C13—C141.391 (4)N3—H250.8600
N1—C1—C2120.7 (2)C9—C14—H14120.4
N1—C1—C8121.11 (18)C13—C14—H14120.4
C2—C1—C8118.00 (18)N2—C15—C16115.46 (19)
C3—C2—C7118.1 (2)N2—C15—C24125.1 (2)
C3—C2—C1121.7 (2)C16—C15—C24119.4 (2)
C7—C2—C1120.2 (2)C23—C16—C17105.7 (2)
C4—C3—C2120.7 (3)C23—C16—C15128.1 (2)
C4—C3—H3119.7C17—C16—C15126.14 (19)
C2—C3—H3119.7C18—C17—C22118.9 (2)
C5—C4—C3120.5 (3)C18—C17—C16134.59 (19)
C5—C4—H4119.8C22—C17—C16106.5 (2)
C3—C4—H4119.8C19—C18—C17118.9 (2)
C6—C5—C4119.6 (2)C19—C18—H18120.5
C6—C5—H5120.2C17—C18—H18120.5
C4—C5—H5120.2C18—C19—C20121.2 (3)
C5—C6—C7120.9 (3)C18—C19—H19119.4
C5—C6—H6119.6C20—C19—H19119.4
C7—C6—H6119.6C21—C20—C19121.4 (3)
C6—C7—C2120.2 (3)C21—C20—H20119.3
C6—C7—H7119.9C19—C20—H20119.3
C2—C7—H7119.9C20—C21—C22117.4 (2)
O1—C8—C9122.0 (2)C20—C21—H21121.3
O1—C8—C1117.96 (19)C22—C21—H21121.3
C9—C8—C1120.03 (18)N3—C22—C21130.3 (2)
C14—C9—C10120.3 (2)N3—C22—C17107.5 (2)
C14—C9—C8121.2 (2)C21—C22—C17122.1 (3)
C10—C9—C8118.4 (2)N3—C23—C16110.6 (2)
C9—C10—C11119.5 (3)N3—C23—H23124.7
C9—C10—H10120.2C16—C23—H23124.7
C11—C10—H10120.2C15—C24—H24A109.5
C12—C11—C10120.0 (3)C15—C24—H24B109.5
C12—C11—H11120.0H24A—C24—H24B109.5
C10—C11—H11120.0C15—C24—H24C109.5
C11—C12—C13120.7 (2)H24A—C24—H24C109.5
C11—C12—H12119.7H24B—C24—H24C109.5
C13—C12—H12119.7C1—N1—N2111.51 (18)
C12—C13—C14120.1 (3)C15—N2—N1114.44 (18)
C12—C13—H13119.9C23—N3—C22109.6 (2)
C14—C13—H13119.9C23—N3—H25125.2
C9—C14—C13119.3 (3)C22—N3—H25125.2
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C18—H18···N20.932.603.074 (3)112
\ (Z)-2-{(E)-[(1-Methyl-1H-indol-3-yl)\ methylidene]hydrazinylidene}-1,2-diphenylethanone (7-BMHMFI) top
Crystal data top
C24H19N3OF(000) = 768
Mr = 365.42Dx = 1.224 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 18.6779 (6) ÅCell parameters from 380 reflections
b = 8.6694 (3) Åθ = 2.5–26.0°
c = 12.7956 (4) ŵ = 0.08 mm1
β = 106.910 (4)°T = 293 K
V = 1982.36 (12) Å3Block, yellow
Z = 40.33 × 0.28 × 0.25 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
3837 independent reflections
Radiation source: fine-focus sealed tube2964 reflections with I > 2σ(I)
Detector resolution: 10.11 pixels mm-1Rint = 0.021
phi and ω scansθmax = 26.1°, θmin = 2.3°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 1422
Tmin = 0.971, Tmax = 0.987k = 1010
9410 measured reflectionsl = 1515
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullOnly H-atom displacement parameters refined
R[F2 > 2σ(F2)] = 0.045 w = 1/[σ2(Fo2) + (0.0721P)2 + 0.203P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.140(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.16 e Å3
3837 reflectionsΔρmin = 0.15 e Å3
274 parametersExtinction correction: SHELXL2016 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.0045 (13)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.80896 (9)0.5549 (2)0.27473 (14)0.0584 (4)
C20.88286 (10)0.6191 (2)0.33323 (15)0.0659 (4)
C30.89301 (12)0.7045 (3)0.42794 (18)0.0837 (6)
H30.8529450.7206930.4559940.075 (6)*
C40.96264 (15)0.7658 (4)0.4811 (2)0.1081 (9)
H40.9690700.8233020.5445260.120 (10)*
C51.02223 (14)0.7419 (4)0.4403 (3)0.1200 (11)
H51.0687740.7840140.4756430.125 (10)*
C61.01287 (14)0.6567 (5)0.3485 (3)0.1234 (11)
H61.0533540.6398080.3214990.134 (11)*
C70.94374 (11)0.5945 (3)0.2945 (2)0.0953 (7)
H70.9382210.5359000.2318180.099 (8)*
C80.79924 (9)0.4658 (2)0.16966 (14)0.0603 (4)
C90.79785 (8)0.2948 (2)0.17403 (13)0.0576 (4)
C100.77856 (11)0.2110 (3)0.07773 (17)0.0757 (5)
H100.7667900.2615020.0107610.083 (6)*
C110.77691 (13)0.0510 (3)0.0818 (2)0.0955 (7)
H110.7630050.0053550.0172210.120 (9)*
C120.79548 (14)0.0243 (3)0.1796 (3)0.1008 (8)
H120.7950840.1314930.1814330.128 (10)*
C130.81477 (13)0.0581 (3)0.2755 (2)0.0891 (6)
H130.8272940.0067910.3422030.111 (9)*
C140.81552 (10)0.2171 (2)0.27258 (16)0.0679 (5)
H140.8280400.2726490.3375830.073 (6)*
C150.62962 (9)0.54270 (18)0.27528 (13)0.0556 (4)
H150.6359900.6053920.3362930.060 (5)*
C160.55620 (8)0.48955 (17)0.21907 (12)0.0496 (3)
C170.53199 (9)0.38820 (16)0.12688 (12)0.0487 (3)
C180.56873 (10)0.29923 (18)0.06710 (14)0.0592 (4)
H180.6206380.3003480.0839820.067 (5)*
C190.52650 (13)0.2104 (2)0.01693 (15)0.0733 (5)
H190.5503540.1495150.0565250.095 (7)*
C200.44874 (13)0.2091 (2)0.04436 (15)0.0771 (6)
H200.4218680.1482190.1023600.085 (6)*
C210.41058 (11)0.2957 (2)0.01205 (13)0.0644 (4)
H210.3585990.2953020.0066580.068 (5)*
C220.45351 (9)0.38363 (17)0.09833 (12)0.0522 (4)
C230.49247 (9)0.53965 (19)0.24184 (13)0.0556 (4)
H230.4918060.6064540.2984230.071 (5)*
C240.35385 (10)0.5102 (3)0.16663 (19)0.0815 (6)
H24A0.3317550.4192490.1868910.139 (11)*
H24B0.3261820.5404190.0939160.117 (9)*
H24C0.3526810.5921530.2165770.136 (11)*
N10.75252 (8)0.57812 (18)0.31109 (12)0.0640 (4)
N20.68730 (7)0.50715 (17)0.24473 (12)0.0591 (3)
N30.43088 (7)0.47817 (16)0.17043 (11)0.0557 (3)
O10.79386 (9)0.53693 (19)0.08597 (11)0.0846 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0518 (8)0.0596 (9)0.0633 (9)0.0000 (7)0.0160 (7)0.0068 (7)
C20.0539 (9)0.0692 (10)0.0702 (10)0.0027 (8)0.0113 (8)0.0106 (9)
C30.0734 (12)0.0917 (15)0.0820 (13)0.0150 (11)0.0162 (10)0.0051 (11)
C40.0916 (17)0.123 (2)0.0935 (17)0.0272 (16)0.0017 (13)0.0131 (16)
C50.0637 (14)0.161 (3)0.119 (2)0.0317 (16)0.0000 (14)0.005 (2)
C60.0605 (13)0.184 (3)0.125 (2)0.0248 (17)0.0246 (14)0.014 (2)
C70.0583 (11)0.132 (2)0.0959 (16)0.0114 (12)0.0230 (11)0.0120 (15)
C80.0471 (8)0.0759 (11)0.0583 (9)0.0023 (7)0.0157 (7)0.0095 (8)
C90.0421 (7)0.0717 (10)0.0614 (9)0.0081 (7)0.0188 (7)0.0002 (8)
C100.0638 (10)0.0927 (14)0.0693 (11)0.0210 (10)0.0173 (9)0.0073 (10)
C110.0848 (15)0.0903 (16)0.1062 (18)0.0155 (12)0.0196 (13)0.0320 (15)
C120.0933 (16)0.0695 (14)0.139 (2)0.0118 (12)0.0321 (16)0.0062 (15)
C130.0887 (15)0.0769 (13)0.1043 (17)0.0142 (11)0.0320 (13)0.0206 (13)
C140.0649 (10)0.0727 (11)0.0673 (10)0.0060 (8)0.0213 (8)0.0072 (9)
C150.0585 (9)0.0524 (8)0.0588 (9)0.0006 (7)0.0219 (7)0.0042 (7)
C160.0537 (8)0.0460 (7)0.0532 (8)0.0023 (6)0.0223 (6)0.0026 (6)
C170.0581 (8)0.0425 (7)0.0503 (7)0.0016 (6)0.0236 (6)0.0085 (6)
C180.0748 (11)0.0516 (8)0.0613 (9)0.0005 (7)0.0357 (8)0.0007 (7)
C190.1042 (15)0.0615 (10)0.0650 (10)0.0013 (10)0.0414 (11)0.0083 (8)
C200.1085 (16)0.0655 (11)0.0537 (9)0.0138 (10)0.0180 (10)0.0076 (8)
C210.0688 (10)0.0644 (10)0.0560 (9)0.0103 (8)0.0117 (8)0.0086 (8)
C220.0611 (9)0.0486 (8)0.0486 (8)0.0003 (6)0.0187 (7)0.0111 (6)
C230.0600 (9)0.0555 (8)0.0557 (8)0.0047 (7)0.0236 (7)0.0024 (7)
C240.0540 (10)0.0998 (16)0.0919 (14)0.0166 (10)0.0231 (10)0.0061 (13)
N10.0530 (7)0.0666 (9)0.0714 (9)0.0037 (6)0.0165 (6)0.0065 (7)
N20.0498 (7)0.0627 (8)0.0663 (8)0.0020 (6)0.0191 (6)0.0072 (7)
N30.0515 (7)0.0610 (8)0.0575 (7)0.0046 (6)0.0206 (6)0.0057 (6)
O10.0949 (10)0.0924 (10)0.0669 (8)0.0030 (8)0.0239 (7)0.0199 (7)
Geometric parameters (Å, º) top
C1—N11.286 (2)C13—H130.9300
C1—C21.474 (2)C14—H140.9300
C1—C81.515 (2)C15—N21.286 (2)
C2—C71.383 (3)C15—C161.427 (2)
C2—C31.385 (3)C15—H150.9300
C3—C41.386 (3)C16—C231.376 (2)
C3—H30.9300C16—C171.434 (2)
C4—C51.375 (4)C17—C181.399 (2)
C4—H40.9300C17—C221.404 (2)
C5—C61.355 (4)C18—C191.371 (3)
C5—H50.9300C18—H180.9300
C6—C71.384 (3)C19—C201.392 (3)
C6—H60.9300C19—H190.9300
C7—H70.9300C20—C211.375 (3)
C8—O11.214 (2)C20—H200.9300
C8—C91.483 (3)C21—C221.389 (2)
C9—C141.382 (2)C21—H210.9300
C9—C101.385 (3)C22—N31.389 (2)
C10—C111.388 (3)C23—N31.353 (2)
C10—H100.9300C23—H230.9300
C11—C121.364 (4)C24—N31.452 (2)
C11—H110.9300C24—H24A0.9600
C12—C131.374 (4)C24—H24B0.9600
C12—H120.9300C24—H24C0.9600
C13—C141.379 (3)N1—N21.4077 (19)
N1—C1—C2120.14 (17)C13—C14—H14119.7
N1—C1—C8120.11 (15)C9—C14—H14119.7
C2—C1—C8119.72 (15)N2—C15—C16122.45 (15)
C7—C2—C3118.56 (19)N2—C15—H15118.8
C7—C2—C1120.41 (19)C16—C15—H15118.8
C3—C2—C1121.03 (18)C23—C16—C15123.72 (15)
C2—C3—C4120.3 (2)C23—C16—C17106.40 (14)
C2—C3—H3119.9C15—C16—C17129.73 (14)
C4—C3—H3119.9C18—C17—C22118.90 (15)
C5—C4—C3120.2 (3)C18—C17—C16134.43 (15)
C5—C4—H4119.9C22—C17—C16106.66 (13)
C3—C4—H4119.9C19—C18—C17118.49 (17)
C6—C5—C4119.8 (2)C19—C18—H18120.8
C6—C5—H5120.1C17—C18—H18120.8
C4—C5—H5120.1C18—C19—C20121.50 (17)
C5—C6—C7120.7 (3)C18—C19—H19119.2
C5—C6—H6119.6C20—C19—H19119.2
C7—C6—H6119.6C21—C20—C19121.71 (18)
C2—C7—C6120.4 (3)C21—C20—H20119.1
C2—C7—H7119.8C19—C20—H20119.1
C6—C7—H7119.8C20—C21—C22116.71 (18)
O1—C8—C9122.88 (17)C20—C21—H21121.6
O1—C8—C1118.77 (18)C22—C21—H21121.6
C9—C8—C1118.35 (14)C21—C22—N3129.45 (16)
C14—C9—C10119.15 (19)C21—C22—C17122.67 (15)
C14—C9—C8121.27 (16)N3—C22—C17107.87 (13)
C10—C9—C8119.58 (17)N3—C23—C16110.52 (14)
C9—C10—C11119.6 (2)N3—C23—H23124.7
C9—C10—H10120.2C16—C23—H23124.7
C11—C10—H10120.2N3—C24—H24A109.5
C12—C11—C10120.7 (2)N3—C24—H24B109.5
C12—C11—H11119.7H24A—C24—H24B109.5
C10—C11—H11119.7N3—C24—H24C109.5
C11—C12—C13120.1 (2)H24A—C24—H24C109.5
C11—C12—H12120.0H24B—C24—H24C109.5
C13—C12—H12120.0C1—N1—N2111.71 (15)
C12—C13—C14119.8 (2)C15—N2—N1111.49 (14)
C12—C13—H13120.1C23—N3—C22108.54 (13)
C14—C13—H13120.1C23—N3—C24125.92 (16)
C13—C14—C9120.7 (2)C22—N3—C24125.50 (16)
(Z)-2-{(E)-[(Naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (8-BDHFN) top
Crystal data top
C25H18N2OF(000) = 760
Mr = 362.41Dx = 1.247 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 17.2081 (13) ÅCell parameters from 380 reflections
b = 9.4075 (8) Åθ = 2.5–26.0°
c = 11.9703 (9) ŵ = 0.08 mm1
β = 94.814 (7)°T = 293 K
V = 1931.0 (3) Å3Block, yellow
Z = 40.40 × 0.40 × 0.16 mm
Data collection top
Bruker SMART CCD area detector
diffractometer
3396 independent reflections
Radiation source: fine-focus sealed tube1411 reflections with I > 2σ(I)
Detector resolution: 10.12 pixels mm-1Rint = 0.078
phi and ω scansθmax = 25.0°, θmin = 3.0°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)
h = 2020
Tmin = 0.970, Tmax = 0.989k = 1110
10556 measured reflectionsl = 1414
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullOnly H-atom displacement parameters refined
R[F2 > 2σ(F2)] = 0.052 w = 1/[σ2(Fo2) + (0.0024P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.083(Δ/σ)max < 0.001
S = 0.87Δρmax = 0.14 e Å3
3396 reflectionsΔρmin = 0.14 e Å3
272 parametersExtinction correction: SHELXL2016 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.00135 (15)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.38170 (16)0.3245 (3)0.5324 (2)0.0479 (7)
C20.45003 (16)0.2405 (3)0.5767 (2)0.0492 (8)
C30.51422 (17)0.2274 (3)0.5158 (3)0.0695 (10)
H30.5152420.2744930.4475850.063 (9)*
C40.57683 (19)0.1451 (4)0.5553 (3)0.0787 (11)
H40.6195040.1359790.5130090.096 (12)*
C50.57676 (19)0.0761 (4)0.6569 (3)0.0700 (10)
H50.6191470.0208900.6836580.072 (10)*
C60.51344 (19)0.0901 (3)0.7175 (3)0.0696 (10)
H60.5128140.0443900.7863710.077 (10)*
C70.45071 (18)0.1709 (3)0.6779 (2)0.0628 (9)
H70.4079400.1787940.7200780.051 (8)*
C80.30593 (16)0.3112 (3)0.5892 (2)0.0506 (8)
C90.24449 (15)0.2118 (3)0.5424 (2)0.0471 (7)
C100.25215 (19)0.1364 (3)0.4446 (2)0.0645 (9)
H100.2966740.1471670.4064390.068 (10)*
C110.1942 (2)0.0460 (4)0.4042 (3)0.0811 (11)
H110.1996670.0048090.3387380.075 (11)*
C120.1284 (2)0.0298 (4)0.4592 (4)0.0904 (12)
H120.0892880.0320340.4311490.105 (14)*
C130.1199 (2)0.1044 (4)0.5554 (3)0.0878 (12)
H130.0748290.0939340.5923730.111 (13)*
C140.17771 (18)0.1948 (4)0.5978 (3)0.0675 (10)
H140.1719800.2445590.6637530.075 (11)*
C150.31775 (17)0.5533 (3)0.3302 (2)0.0556 (8)
H150.3669780.5678070.3056390.066 (9)*
C160.25293 (16)0.6289 (3)0.2709 (2)0.0491 (8)
C170.27243 (19)0.7208 (3)0.1884 (2)0.0634 (9)
H170.3245440.7310610.1747710.042 (7)*
C180.2158 (2)0.7989 (3)0.1247 (3)0.0724 (10)
H180.2305880.8600290.0692490.075 (10)*
C190.1399 (2)0.7866 (4)0.1429 (3)0.0739 (10)
H190.1028060.8397260.1000820.099 (12)*
C200.11607 (19)0.6942 (3)0.2262 (2)0.0578 (8)
C210.17273 (17)0.6118 (3)0.2911 (2)0.0489 (8)
C220.14497 (17)0.5146 (3)0.3686 (2)0.0534 (8)
H220.1803860.4577310.4111640.053 (9)*
C230.06746 (18)0.5025 (3)0.3824 (2)0.0632 (9)
H230.0508720.4376040.4339240.039 (8)*
C240.0127 (2)0.5861 (4)0.3203 (3)0.0771 (10)
H240.0399460.5781240.3314230.100 (12)*
C250.0365 (2)0.6792 (4)0.2435 (3)0.0790 (11)
H250.0003330.7339900.2016540.074 (10)*
N10.38670 (13)0.4055 (3)0.44718 (19)0.0589 (7)
N20.31309 (13)0.4685 (3)0.41351 (19)0.0569 (7)
O10.29977 (11)0.3808 (2)0.67417 (16)0.0753 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0473 (18)0.049 (2)0.0467 (17)0.0024 (16)0.0003 (14)0.0007 (15)
C20.0482 (18)0.055 (2)0.0429 (18)0.0022 (16)0.0030 (15)0.0009 (15)
C30.061 (2)0.090 (3)0.059 (2)0.013 (2)0.0103 (18)0.021 (2)
C40.051 (2)0.104 (3)0.081 (3)0.019 (2)0.012 (2)0.013 (2)
C50.056 (2)0.081 (3)0.071 (2)0.024 (2)0.0086 (18)0.002 (2)
C60.073 (2)0.081 (3)0.053 (2)0.022 (2)0.0043 (18)0.010 (2)
C70.062 (2)0.074 (3)0.0531 (19)0.0133 (19)0.0109 (18)0.0073 (18)
C80.0479 (19)0.056 (2)0.0477 (17)0.0112 (17)0.0042 (15)0.0088 (16)
C90.0436 (17)0.046 (2)0.0520 (18)0.0033 (16)0.0070 (14)0.0075 (15)
C100.063 (2)0.071 (3)0.060 (2)0.009 (2)0.0118 (19)0.0078 (18)
C110.084 (3)0.078 (3)0.079 (3)0.015 (2)0.003 (2)0.016 (2)
C120.074 (3)0.093 (3)0.101 (3)0.028 (3)0.010 (3)0.020 (3)
C130.060 (3)0.113 (4)0.092 (3)0.011 (2)0.013 (2)0.020 (3)
C140.059 (2)0.086 (3)0.059 (2)0.006 (2)0.0130 (18)0.007 (2)
C150.046 (2)0.061 (2)0.060 (2)0.0003 (17)0.0028 (16)0.0022 (17)
C160.054 (2)0.048 (2)0.0447 (17)0.0007 (17)0.0011 (15)0.0002 (15)
C170.060 (2)0.069 (3)0.061 (2)0.0101 (19)0.0059 (18)0.0118 (18)
C180.094 (3)0.059 (2)0.062 (2)0.002 (2)0.008 (2)0.0230 (19)
C190.077 (3)0.068 (3)0.074 (2)0.007 (2)0.009 (2)0.012 (2)
C200.066 (2)0.049 (2)0.057 (2)0.0008 (19)0.0016 (17)0.0001 (17)
C210.059 (2)0.045 (2)0.0420 (17)0.0005 (17)0.0022 (15)0.0001 (15)
C220.054 (2)0.057 (2)0.0481 (18)0.0011 (18)0.0054 (16)0.0010 (17)
C230.062 (2)0.064 (2)0.064 (2)0.001 (2)0.0039 (18)0.0066 (19)
C240.055 (2)0.082 (3)0.094 (3)0.006 (2)0.003 (2)0.006 (2)
C250.070 (3)0.074 (3)0.089 (3)0.019 (2)0.011 (2)0.020 (2)
N10.0497 (16)0.0657 (19)0.0605 (16)0.0099 (14)0.0009 (13)0.0128 (14)
N20.0538 (17)0.0599 (19)0.0564 (16)0.0068 (14)0.0019 (13)0.0143 (13)
O10.0744 (16)0.0946 (19)0.0576 (13)0.0072 (13)0.0088 (11)0.0200 (13)
Geometric parameters (Å, º) top
C1—N11.282 (3)C13—H130.9300
C1—C21.478 (3)C14—H140.9300
C1—C81.525 (3)C15—N21.284 (3)
C2—C71.376 (3)C15—C161.457 (3)
C2—C31.379 (3)C15—H150.9300
C3—C41.378 (4)C16—C171.374 (3)
C3—H30.9300C16—C211.430 (3)
C4—C51.379 (4)C17—C181.395 (4)
C4—H40.9300C17—H170.9300
C5—C61.366 (4)C18—C191.347 (4)
C5—H50.9300C18—H180.9300
C6—C71.372 (3)C19—C201.409 (4)
C6—H60.9300C19—H190.9300
C7—H70.9300C20—C251.409 (4)
C8—O11.221 (3)C20—C211.424 (3)
C8—C91.486 (4)C21—C221.414 (3)
C9—C101.384 (3)C22—C231.362 (3)
C9—C141.384 (3)C22—H220.9300
C10—C111.367 (4)C23—C241.393 (4)
C10—H100.9300C23—H230.9300
C11—C121.365 (4)C24—C251.357 (4)
C11—H110.9300C24—H240.9300
C12—C131.368 (4)C25—H250.9300
C12—H120.9300N1—N21.426 (3)
C13—C141.372 (4)
N1—C1—C2119.9 (3)C13—C14—C9120.0 (3)
N1—C1—C8121.4 (3)C13—C14—H14120.0
C2—C1—C8118.7 (2)C9—C14—H14120.0
C7—C2—C3118.4 (3)N2—C15—C16125.9 (3)
C7—C2—C1121.2 (3)N2—C15—H15117.0
C3—C2—C1120.4 (3)C16—C15—H15117.0
C4—C3—C2120.4 (3)C17—C16—C21119.3 (3)
C4—C3—H3119.8C17—C16—C15115.7 (3)
C2—C3—H3119.8C21—C16—C15124.9 (3)
C3—C4—C5120.6 (3)C16—C17—C18121.5 (3)
C3—C4—H4119.7C16—C17—H17119.3
C5—C4—H4119.7C18—C17—H17119.3
C6—C5—C4118.9 (3)C19—C18—C17120.6 (3)
C6—C5—H5120.5C19—C18—H18119.7
C4—C5—H5120.5C17—C18—H18119.7
C5—C6—C7120.6 (3)C18—C19—C20120.7 (3)
C5—C6—H6119.7C18—C19—H19119.6
C7—C6—H6119.7C20—C19—H19119.6
C6—C7—C2121.1 (3)C25—C20—C19120.6 (3)
C6—C7—H7119.4C25—C20—C21119.6 (3)
C2—C7—H7119.4C19—C20—C21119.7 (3)
O1—C8—C9122.9 (3)C22—C21—C20117.2 (3)
O1—C8—C1117.6 (3)C22—C21—C16124.6 (3)
C9—C8—C1119.4 (3)C20—C21—C16118.2 (3)
C10—C9—C14119.2 (3)C23—C22—C21121.4 (3)
C10—C9—C8121.8 (3)C23—C22—H22119.3
C14—C9—C8119.0 (3)C21—C22—H22119.3
C11—C10—C9119.9 (3)C22—C23—C24120.9 (3)
C11—C10—H10120.0C22—C23—H23119.5
C9—C10—H10120.0C24—C23—H23119.5
C12—C11—C10120.6 (4)C25—C24—C23119.8 (3)
C12—C11—H11119.7C25—C24—H24120.1
C10—C11—H11119.7C23—C24—H24120.1
C11—C12—C13120.0 (4)C24—C25—C20121.1 (3)
C11—C12—H12120.0C24—C25—H25119.5
C13—C12—H12120.0C20—C25—H25119.5
C12—C13—C14120.3 (4)C1—N1—N2110.8 (2)
C12—C13—H13119.8C15—N2—N1111.5 (2)
C14—C13—H13119.8
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H5···O1i0.932.493.355 (4)156
C3—H3···N10.932.532.827 (4)99
C14—H14···O10.932.542.826 (4)98
C22—H22···N20.932.282.930 (4)126
Symmetry code: (i) x+1, y1/2, z+3/2.
Inhibition of A549, 4T1 and MRC-5, NIH 3T3 cell growth by the title compounds, compared with cisplatin (µM) top
CompoundA549 cells, IC504T1 cells, IC50MRC-5 cells, IC50NIH 3T3 fibroblasts, IC50
BDHFI8.0±0.57.5±0.524.5±1.529.5±1.0
BDHAI8.5±0.67.0±0.636.5±1.543.0±1.5
BDHMFI125.0±1.0122.0±1.0> 150.0> 150.0
BDHFN130.0±1.0125.0±1.0> 150.0> 150.0
BMHFI46.5±0.532.5±0.588.0±1.585.0±1.5
BMHAI43.0±0.530.0±0.583.0±1.576.0±1.5
BMHMFI148.0±1.2141.0±1.0> 150.0> 150.0
BMHFN150.0±1.2148.0±1.0> 150.0> 150.0
Cisplatin6.5 ± 0.50.5 ± 0.122.5 ± 1.521.0 ± 1.0
Total scores and Spearman's rank correlation coefficients (ρ in the last two rows) of 18 possible targets (PDB IDs are in brackets; two targets in the last two columns were docked using homology modules for the absence of detailed 3D information) top
c-Jun N-terminal kinase 3(2R9S)CaM kinase II (2VZ6)Delta opioid receptor (4N6H)Gonadotropin-releasing hormone receptor (6NBF)hERG (3O0U)Inhibitor of apoptosis protein 3 (5C3H)Kinesin-like protein 1 (3ZCW)Mu opioid receptor (4DKL)Probable G-protein coupled receptor 88 (5XF1)
Ligandi12.249.279.377.769.877.3319.6810.536.67
BDHFI8.088.437.566.196.906.2310.448.576.85
BDHAI8.168.827.446.368.026.146.999.466.15
BDHMFI5.966.926.536.774.545.078.618.235.28
BDHFN5.947.597.055.006.255.339.047.455.84
BMHFI6.647.327.445.295.975.839.447.314.39
BMHAI5.606.806.325.886.414.778.276.154.52
BMHMFI6.395.986.654.194.914.427.766.364.58
BMHFN5.596.036.454.674.204.306.166.474.37
ρA549ii0.670.740.570.710.860.830.480.520.62
ρ4T1iii0.690.760.550.740.880.810.330.550.60
Protein kinase C alpha (4RA4)Serine/threonine-protein kinase AKT2 (3D0E)Serine/threonine-protein kinase PIM1 (1YXT)Serine/threonine-protein kinase PIM2 (4X7Q)Serine/threonine-protein kinase PIM3 (5DWR)Sigma opioid receptor (6DK0)Tryptase beta-1 (4MPU)Neurokinin 2 receptor(by homology)5-HT6 receptor(by homology)
Ligandi7.3416.7932.8215.1810.6410.8123.4110.049.00
BDHFI6.358.229.736.708.008.347.399.287.95
BDHAI6.796.409.608.199.927.178.128.804.56
BDHMFI5.275.656.645.564.451.876.028.176.40
BDHFN5.475.517.595.635.515.237.998.737.07
BMHFI4.437.067.957.876.396.415.446.715.05
BMHAI4.876.677.017.687.498.275.515.685.50
BMHMFI5.066.775.525.926.427.005.056.004.43
BMHFN4.307.465.805.926.066.235.226.446.18
ρA549ii0.600.120.860.620.690.690.620.520.17
ρ4T1iii0.620.000.830.690.710.640.670.500.02
Notes: (i) for all proteins with crystal structure, the `ligand' means the natural ligand included in the protein structure; for the last two proteins built by homology modelling, the `ligand' means the known ligand reported before, i.e. 10i and AVN-492 (see text). (ii) equation 1; (iii) equation 2, n = 8. Ranki is the rank value of each Schiff base in the virtual screening, which is determined according to its sequence listed in descending order of total score values (see Table S22 in the supporting information). RankA549/Rank4T1 is the rank value of each Schiff base in the A549/4T1 cell growth MTT assays, which is determined according to its sequence listed in ascending order of IC50 values (see Table 2 and Table S23 in the supporting information).
 

Funding information

Funding for this research was provided by: Key Laboratory of Pulp and Paper Science and Technology of Ministry of Education/Shandong Province of China (award Nos. KF201712 and KF201821); State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (grant No. ZZ20190115).

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