research communications
N-{N-[amino(dimethylamino)methyl]carbamimidoyl}-3-bromobenzenesulfonamide
and Hirshfeld surface analysis ofaDepartment of Chemistry, KU Leuven, Biomolecular Architecture, Celestijnenlaan 200F, Leuven (Heverlee), B-3001, Belgium, and bCollege of Materials Science and Engineering, Sichuan University, Chengdu, 610065, People's Republic of China
*Correspondence e-mail: luc.vanmeervelt@kuleuven.be
The title compound, C10H14BrN5O2S, is the bromobenzenesulfonamide derivative of the type 2 diabetes drug metformin. The contains two molecules with almost identical conformations but a different orientation of the bromophenyl moiety. Both molecules exhibit intramolecular N—H⋯N and N—H⋯O hydrogen bonds. The molecular packing features chain formation in the a-axis direction by alternating N—H⋯N and N—H⋯O interactions. In addition, ring motifs consisting of four molecules and π–π interactions between the phenyl rings contribute to the three-dimensional architecture. A Hirshfeld surface analysis shows that the largest contributions to surface contacts arise from contacts in which H atoms are involved.
Keywords: crystal structure; metformin; hydrogen-bond interactions; π–π interactions; Hirshfeld surface analysis.
CCDC reference: 2246792
1. Chemical context
Metformin is a widely known effective drug for type 2 diabetes, which does not cause weight gain and rarely causes hypoglycemia. Metformin works by decreasing gluconeogenesis in the liver, increasing insulin sensitivity and preventing insulin resistance (Giannarelli et al., 2003). In addition to antidiabetics, metformin shows confirmed benefits against aging (Barzilai et al., 2016) and various diseases such as polycystic ovary syndrome (Lord et al., 2003), cancers (Libby et al., 2009), obesity (Jing et al., 2018), liver disease (Lin et al., 2000) and cardiovascular disease (Rena & Lang, 2018). In recent decades, there has been great interest in metformin because of its multiple medical applications and low toxicity. However, metformin also has some disadvantages, such as low bioavailability, incomplete absorption, and gastrointestinal side effects. Gliclazide is an oral sulfonylurea antidiabetic agent that works by stimulating insulin synthesis (Sarkar et al., 2011). We think that the combination of the two with different mechanisms of action can synergize and result in a potent hypoglycemic effect. In addition, the combination can improve their physico-chemical properties and alleviate the side effects caused by high doses of a single drug.
Introducing sulfonyl into small medical molecules is an important strategy in modifying the molecular structure of drugs. Sulfonyl can provide two hydrogen-bond acceptors, and the introduction of the sulfonyl group can improve the bioactivity of the compound by increasing the hydrogen-bond interactions between drug and target. In addition, the sulfonyl group has a relatively stable structure, and the introduction of sulfonyl can block easily metabolizable sites and prolong its time of action, improving its bioavailability, and thereby improving the pharmacokinetic properties of small molecules. In summary, it makes sense to synthesize ion pairs of gliclazide and sulfonyl-modified metformin and investigate its pharmaceutical properties. Herein we report the 10H14BrN5O2S, obtained during our efforts to crystallize the with gliclazide.
and Hirshfeld surface analysis of the title compound, C2. Structural commentary
The title compound crystallizes in the triclinic P with two molecules (A containing S8 and B containing S27) in the (Fig. 1). Although both molecules have an almost identical conformation, the bromophenyl part shows two orientations related by a rotation of 180° (Fig. 2). The hydrogen atoms involved in the intramolecular hydrogen bonds N11⋯N15 (molecule A) and N30⋯N34 (molecule B) are shared by the two nitrogen atoms with an occupancy of 0.85 (4) at atoms N15 and N34, and 0.15 (4) at atoms N11 and N30. The dihedral angles between the phenyl ring (C1–C6 in A, C20–C25 in B) and the best plane through the N-containing moiety (N11–C19 in A and N30–C38 in B) are 87.12 (12) and 96.05 (12)° in A and B, respectively. Next to the intramolecular hydrogen bonds N15—H15B⋯N11 and N34—H34B⋯N30, a short interaction is present between atoms H16B and O9 in A, and H35B and O9 in B (Table 1).
3. Supramolecular features
The crystal packing of the title compound is characterized by N—H⋯N, N—H⋯O and π–π interactions. The two molecules A and B in the are linked by an N35—H35B⋯O9 interaction (Table 1). Molecule A interacts with a second molecule B by an N16—H16A⋯N32(−x, −y + 1, −z + 1) interaction, while molecule B forms an N34—H34A⋯O10(−x + 1, −y + 1, −z + 1) hydrogen-bond interaction (Table 1). These dimers [graph-set notation D11(2); Etter & MacDonald, 1990] are the building blocks for a three-dimensional network consisting of chains [graph-set notation C22(10)] and rings [graph-set notation R44(20)]. A chain running in the a-axis direction is formed by subsequent N16⋯N32 and N34⋯O10 interactions (Fig. 3). One ring motif consists of N16⋯N32 and N35 ⋯O9 interactions (Fig. 4), while N34⋯O10 and N35 ⋯O9 interactions result in the second ring motif (Fig. 5).
Further dimer formation is obtained through π–π stacking between the phenyl rings (Fig. 6). For molecule A, the Cg1⋯Cg1(−x, −y + 1, −z) distance is 3.686 (3) Å and the slippage is 0.650 Å, while for molecule B the Cg2⋯Cg2(−x + 1, −y, −z) distance is 4.1086 (3) Å and the slippage is 1.936 Å (Cg1 and Cg2 are the centroids of rings C1–C6 and C20–C25, respectively).
A Hirshfeld surface analysis was performed, and two-dimensional fingerprint plots were created with Crystal Explorer21.3 (Spackman et al., 2021). The Hirshfeld surfaces of molecules A and B mapped over dnorm are given in Figs. 7 and 8, respectively. The bright-red spots in Fig. 7 near atoms O9 and O10 are indicative of the N34—H34A⋯O10 and N35—H35B⋯O9 hydrogen bonds, while the additional faint-red spots illustrate weaker C14⋯H23 (2.66 Å), H16A⋯N32 [2.54 (5) Å] and Br⋯Br [3.4165 (10) Å] interactions present in the crystal packing. The bright-red spots in Fig. 8 near atoms N32, H34A and H35B refer to the N16—H16A⋯N32, N34—H34A⋯O10 and N35—H35B⋯O9 hydrogen bonds, while the additional faint-red spots illustrate weaker H15A⋯N30 [2.70 (5) Å] and C14⋯H23 (2.66 Å) interactions present in the crystal packing. The relative distributions from the different interatomic contacts to the Hirshfeld surfaces are presented in Table 2. The most significant contributions to the Hirshfeld surface are H⋯H (35.0%, 34.0%), O⋯H/H⋯O (19.2%, 17.7%), H⋯Br/Br⋯H (14.1%, 14.6%), H⋯C/C⋯H (13.1%, 15.0%), and H⋯N/N⋯H (11.5%, 10.5%) contacts (values for molecule A and B, respectively).
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4. Database survey
A search of the Cambridge Structural Database (CSD, Version 5.43, update of November 2022; Groom et al., 2016) for the N-containing part of the title compound, as shown in Fig. 9a resulted in 17 hits [DEXBUF and DEXBUF01 (Nanubolu et al., 2013), DELKAK (Diniz et al., 2022), EQUTIV (Olar et al., 2010a), EWISAH (Polito-Lucas et al., 2021), JUMXOH (Bian et al., 2020), MAXJAA (Sun et al., 2022), NAKWAB (Manjunatha et al., 2020), NICCEJ (Satyanarayana Reddy et al., 2013), NUPXED (Dong et al., 2015), OJOSUC (Olar et al., 2010b), OJOSUC01 (Wei et al., 2014), QILBOF (Sánchez-Lara et al., 2018), ROLFUW (Jia et al., 2019), UKODUW01 (Feng et al., 2021), WIBSIJ (Lemoine et al., 1994), YEJVOC (Jiang et al., 2022); for more details, see the supporting information]. In contrast to the title compound, all 17 compounds bear a positve charge. The histogram of the torsion angle TOR1 illustrates that the majority of these fragments are non-planar (Fig. 9b). For the title compound, this torsion angle is −177.5 (4) and −171.8 (4)° in A and B, respectively.
5. Synthesis and crystallization
The reaction scheme to synthesize the title compound is given in Fig. 10.
Metformin hydrochloride (662.5 mg, 4.0 mmol) was dissolved in 1M sodium hydroxide solution (320 ml, 8.0 mmol). The mixture was stirred for 30 min at room temperature. After the reaction was complete, water was removed under reduced pressure and the residue was dissolved in cold anhydrous methanol. The sodium chloride was filtered off and the filtrate was evaporated under reduced pressure to obtain basic metformin.
The basic metformin (258.2 mg, 2.0 mmol) and 3-bromobenzenesulfonyl chloride (144 µL, 1.0 mmol) were dissolved in 6 mL of anhydrous dichloromethane and stirred under a nitrogen atmosphere for 3 h at room temperature. The solvent was removed on a rotary evaporator and the residue was purified by 2Cl2 = 1:10) to obtain the title compound as a colourless solid.
(eluent: MeOH: CHTo obtain its hydrochloride salt, the title compound was dissolved in ethanol and stirred at room temperature. An ethanol solution of hydrochloric acid was added dropwise until pH = 2 and the reaction was followed by TLC. After completion of the reaction, the solvent was removed under reduced pressure to obtain the hydrochloride salt.
The hydrochloride salt (76.7 mg, 0.2 mmol) and sodium gliclazide (69.3 mg, 0.2 mmol) were dissolved in 5 mL of acetone and stirred overnight at room temperature. The solvent was removed under reduced pressure and a light-yellow solid was obtained, which was expected to be the sulfonylurea salt of the title compound.
Cuboid-shaped colourless crystals were grown in an NMR tube by slow evaporation over two weeks using deuterated chloroform as solvent. However, the grown crystals consist of the title compound and not of its sulfonylurea salt.
NMR spectra of the title compound were recorded on a 400 MHz NMR spectrometer: 1H NMR (400 MHz, CDCl3) δ 8.03 (t, J = 1.7 Hz, 1H, phenyl), 7.90–7.76 (m, 1H, phenyl), 7.64–7.57 (m, 1H, phenyl), 7.56–7.22 (m, 3H, phenyl and NH2), 7.06 (s, 1H, NH2), 5.19 (s, 1H, NH2), 2.99 (s, 6H, CH3). 13C NMR (101 MHz, CDCl3) δ 160.29 (s), 158.59 (s), 145.65 (s), 134.41 (s), 130.20 (s), 129.13 (s), 124.70 (s), 122.54 (s), 37.00 (s).
6. Refinement
Crystal data, data collection and structure . All hydrogen atoms bound to carbon were placed at idealized positions and refined using a riding model, with Uiso(H) values assigned as 1.2Ueq or 1.5Ueq (methyl only) of the parent atoms, with C—H distances of 0.93 (aromatic) and 0.96 Å (methyl). The hydrogen atoms bound to nitrogen were located in a difference-Fourier map and refined freely with Uiso(H) values assigned as 1.2Ueq of the parent atoms. The occupancy factors of hydrogen atoms H11 and H15B (molecule A), and H30 and H34B (molecule B) involved in intramolecular hydrogen bonds converged during to 0.85 (4) for H15B and H34B, and 0.15 (4) for H11 and H30.
details are summarized in Table 3
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Supporting information
CCDC reference: 2246792
https://doi.org/10.1107/S2056989023002165/pk2683sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989023002165/pk2683Isup2.hkl
CSD survey results. DOI: https://doi.org/10.1107/S2056989023002165/pk2683sup3.pdf
Supporting information file. DOI: https://doi.org/10.1107/S2056989023002165/pk2683Isup4.cml
Data collection: CrysAlis PRO 1.171.42.73a (Rigaku OD, 2022); cell
CrysAlis PRO 1.171.42.73a (Rigaku OD, 2022); data reduction: CrysAlis PRO 1.171.42.73a (Rigaku OD, 2022); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016/4 (Sheldrick, 2015b); molecular graphics: Olex2 1.3 (Dolomanov et al., 2009); software used to prepare material for publication: Olex2 1.3 (Dolomanov et al., 2009).C10H14BrN5O2S | Z = 4 |
Mr = 348.23 | F(000) = 704 |
Triclinic, P1 | Dx = 1.671 Mg m−3 |
a = 10.3839 (5) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 11.3296 (6) Å | Cell parameters from 4121 reflections |
c = 12.3477 (7) Å | θ = 2.8–25.9° |
α = 103.393 (5)° | µ = 3.13 mm−1 |
β = 96.380 (4)° | T = 294 K |
γ = 97.934 (4)° | Block, colourless |
V = 1384.10 (13) Å3 | 0.6 × 0.3 × 0.3 mm |
SuperNova, Single source at offset/far, Eos diffractometer | 5658 independent reflections |
Radiation source: micro-focus sealed X-ray tube, SuperNova (Mo) X-ray Source | 3549 reflections with I > 2σ(I) |
Mirror monochromator | Rint = 0.051 |
Detector resolution: 15.9631 pixels mm-1 | θmax = 26.4°, θmin = 2.5° |
ω scans | h = −12→12 |
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2022) | k = −14→14 |
Tmin = 0.417, Tmax = 1.000 | l = −15→15 |
16803 measured reflections |
Refinement on F2 | Primary atom site location: dual |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.053 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.117 | w = 1/[σ2(Fo2) + (0.035P)2 + 1.4413P] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
5658 reflections | Δρmax = 1.05 e Å−3 |
372 parameters | Δρmin = −0.88 e Å−3 |
0 restraints |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
C1 | −0.0600 (5) | 0.7080 (4) | 0.0460 (3) | 0.0392 (11) | |
C2 | 0.0355 (4) | 0.6995 (4) | 0.1296 (3) | 0.0357 (11) | |
H2 | 0.111511 | 0.758247 | 0.153617 | 0.043* | |
C3 | 0.0135 (4) | 0.5996 (4) | 0.1764 (3) | 0.0318 (10) | |
C4 | −0.0994 (5) | 0.5123 (4) | 0.1403 (4) | 0.0442 (12) | |
H4 | −0.112981 | 0.445965 | 0.172576 | 0.053* | |
C5 | −0.1915 (5) | 0.5246 (5) | 0.0562 (4) | 0.0530 (13) | |
H5 | −0.267409 | 0.465854 | 0.031437 | 0.064* | |
C6 | −0.1727 (5) | 0.6219 (5) | 0.0087 (4) | 0.0469 (13) | |
H6 | −0.235200 | 0.629864 | −0.048086 | 0.056* | |
Br7 | −0.03344 (6) | 0.84386 (6) | −0.02036 (5) | 0.0661 (2) | |
S8 | 0.13699 (11) | 0.58384 (11) | 0.28223 (9) | 0.0367 (3) | |
O9 | 0.0932 (3) | 0.4667 (3) | 0.3068 (3) | 0.0508 (9) | |
O10 | 0.2597 (3) | 0.5961 (3) | 0.2382 (3) | 0.0503 (9) | |
N11 | 0.1473 (3) | 0.6992 (3) | 0.3852 (3) | 0.0347 (9) | |
H11 | 0.214239 | 0.756936 | 0.396878 | 0.042* | 0.15 (4) |
C12 | 0.0568 (4) | 0.7124 (4) | 0.4561 (3) | 0.0337 (10) | |
N13 | 0.0563 (3) | 0.8161 (3) | 0.5341 (3) | 0.0324 (8) | |
C14 | 0.1437 (4) | 0.9194 (4) | 0.5488 (3) | 0.0308 (10) | |
N15 | 0.2461 (4) | 0.9308 (4) | 0.4932 (4) | 0.0435 (11) | |
H15A | 0.301 (5) | 0.992 (5) | 0.506 (4) | 0.052* | |
H15B | 0.253 (5) | 0.871 (5) | 0.438 (5) | 0.052* | 0.85 (4) |
N16 | −0.0418 (5) | 0.6209 (4) | 0.4518 (4) | 0.0513 (12) | |
H16A | −0.088 (5) | 0.634 (5) | 0.500 (4) | 0.062* | |
H16B | −0.035 (5) | 0.549 (5) | 0.422 (4) | 0.062* | |
N17 | 0.1270 (3) | 1.0179 (3) | 0.6273 (3) | 0.0364 (9) | |
C18 | 0.0186 (5) | 1.0110 (5) | 0.6928 (4) | 0.0543 (14) | |
H18A | −0.035482 | 0.931202 | 0.666556 | 0.081* | |
H18B | −0.033126 | 1.073065 | 0.684068 | 0.081* | |
H18C | 0.053284 | 1.024212 | 0.770841 | 0.081* | |
C19 | 0.2135 (5) | 1.1361 (4) | 0.6488 (4) | 0.0494 (13) | |
H19A | 0.303190 | 1.125183 | 0.663859 | 0.074* | |
H19B | 0.192002 | 1.192125 | 0.712777 | 0.074* | |
H19C | 0.202254 | 1.169086 | 0.584087 | 0.074* | |
C20 | 0.5361 (5) | 0.1808 (4) | 0.0442 (4) | 0.0398 (12) | |
C21 | 0.4466 (4) | 0.1344 (4) | 0.1054 (3) | 0.0359 (11) | |
H21 | 0.356697 | 0.128306 | 0.084312 | 0.043* | |
C22 | 0.4950 (4) | 0.0973 (4) | 0.1993 (3) | 0.0311 (10) | |
C23 | 0.6286 (5) | 0.1067 (4) | 0.2308 (4) | 0.0484 (13) | |
H23 | 0.660272 | 0.083478 | 0.294840 | 0.058* | |
C24 | 0.7145 (5) | 0.1507 (5) | 0.1663 (5) | 0.0645 (16) | |
H24 | 0.804515 | 0.155822 | 0.186400 | 0.077* | |
C25 | 0.6690 (5) | 0.1871 (5) | 0.0730 (5) | 0.0527 (14) | |
H25 | 0.727602 | 0.215887 | 0.029400 | 0.063* | |
Br26 | 0.47490 (7) | 0.23897 (6) | −0.08045 (5) | 0.0725 (2) | |
S27 | 0.38479 (12) | 0.04014 (10) | 0.28332 (9) | 0.0356 (3) | |
O28 | 0.4452 (3) | −0.0477 (3) | 0.3299 (3) | 0.0496 (9) | |
O29 | 0.2591 (3) | −0.0032 (3) | 0.2118 (3) | 0.0467 (8) | |
N30 | 0.3838 (3) | 0.1539 (3) | 0.3879 (3) | 0.0343 (9) | |
H30 | 0.428755 | 0.156416 | 0.451519 | 0.041* | 0.15 (4) |
C31 | 0.3160 (4) | 0.2461 (4) | 0.3813 (3) | 0.0319 (10) | |
N32 | 0.3220 (3) | 0.3472 (3) | 0.4660 (3) | 0.0330 (8) | |
C33 | 0.4065 (4) | 0.3742 (4) | 0.5619 (3) | 0.0307 (10) | |
N34 | 0.4890 (4) | 0.3022 (4) | 0.5916 (3) | 0.0414 (10) | |
H34A | 0.550 (5) | 0.327 (4) | 0.648 (4) | 0.050* | |
H34B | 0.486 (5) | 0.234 (5) | 0.543 (5) | 0.050* | 0.85 (4) |
N35 | 0.2361 (4) | 0.2468 (4) | 0.2884 (3) | 0.0434 (11) | |
H35A | 0.213 (5) | 0.182 (4) | 0.239 (4) | 0.052* | |
H35B | 0.196 (5) | 0.301 (4) | 0.295 (4) | 0.052* | |
N36 | 0.4036 (4) | 0.4825 (3) | 0.6346 (3) | 0.0418 (10) | |
C37 | 0.3317 (5) | 0.5744 (4) | 0.6032 (4) | 0.0510 (13) | |
H37A | 0.290176 | 0.544562 | 0.526308 | 0.076* | |
H37B | 0.391734 | 0.649473 | 0.611375 | 0.076* | |
H37C | 0.266048 | 0.589615 | 0.651189 | 0.076* | |
C38 | 0.4763 (5) | 0.5172 (5) | 0.7476 (4) | 0.0593 (15) | |
H38A | 0.473851 | 0.445938 | 0.777398 | 0.089* | |
H38B | 0.437222 | 0.578041 | 0.794622 | 0.089* | |
H38C | 0.565894 | 0.550465 | 0.745539 | 0.089* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.048 (3) | 0.042 (3) | 0.027 (2) | 0.016 (3) | 0.005 (2) | 0.003 (2) |
C2 | 0.035 (3) | 0.036 (3) | 0.033 (2) | 0.005 (2) | 0.002 (2) | 0.002 (2) |
C3 | 0.028 (3) | 0.033 (3) | 0.030 (2) | 0.008 (2) | 0.0028 (19) | −0.0012 (19) |
C4 | 0.040 (3) | 0.039 (3) | 0.049 (3) | 0.003 (2) | −0.001 (2) | 0.009 (2) |
C5 | 0.039 (3) | 0.047 (3) | 0.061 (3) | −0.003 (3) | −0.010 (3) | 0.005 (3) |
C6 | 0.037 (3) | 0.057 (3) | 0.040 (3) | 0.014 (3) | −0.008 (2) | 0.001 (3) |
Br7 | 0.0806 (4) | 0.0701 (4) | 0.0497 (3) | 0.0082 (3) | −0.0065 (3) | 0.0297 (3) |
S8 | 0.0382 (7) | 0.0386 (7) | 0.0329 (6) | 0.0165 (6) | 0.0017 (5) | 0.0036 (5) |
O9 | 0.070 (2) | 0.0349 (19) | 0.051 (2) | 0.0233 (18) | 0.0047 (18) | 0.0108 (16) |
O10 | 0.0370 (19) | 0.070 (2) | 0.0405 (18) | 0.0223 (18) | 0.0074 (15) | −0.0008 (17) |
N11 | 0.033 (2) | 0.038 (2) | 0.0307 (19) | 0.0037 (18) | 0.0064 (17) | 0.0028 (17) |
C12 | 0.036 (3) | 0.034 (3) | 0.033 (2) | 0.008 (2) | 0.003 (2) | 0.012 (2) |
N13 | 0.035 (2) | 0.030 (2) | 0.0323 (19) | 0.0048 (18) | 0.0110 (17) | 0.0060 (17) |
C14 | 0.034 (3) | 0.035 (3) | 0.024 (2) | 0.008 (2) | 0.0017 (19) | 0.0094 (19) |
N15 | 0.040 (3) | 0.041 (3) | 0.042 (2) | −0.012 (2) | 0.013 (2) | 0.003 (2) |
N16 | 0.060 (3) | 0.031 (2) | 0.061 (3) | −0.001 (2) | 0.028 (2) | 0.002 (2) |
N17 | 0.036 (2) | 0.035 (2) | 0.035 (2) | 0.0012 (19) | 0.0055 (18) | 0.0046 (17) |
C18 | 0.057 (4) | 0.048 (3) | 0.058 (3) | 0.012 (3) | 0.028 (3) | 0.003 (3) |
C19 | 0.052 (3) | 0.034 (3) | 0.056 (3) | 0.000 (3) | 0.002 (3) | 0.005 (2) |
C20 | 0.058 (3) | 0.030 (3) | 0.033 (2) | 0.011 (2) | 0.013 (2) | 0.006 (2) |
C21 | 0.039 (3) | 0.035 (3) | 0.032 (2) | 0.010 (2) | 0.008 (2) | 0.003 (2) |
C22 | 0.034 (3) | 0.027 (2) | 0.029 (2) | 0.005 (2) | 0.007 (2) | 0.0001 (18) |
C23 | 0.043 (3) | 0.054 (3) | 0.054 (3) | 0.010 (3) | 0.007 (3) | 0.025 (3) |
C24 | 0.036 (3) | 0.079 (4) | 0.089 (4) | 0.013 (3) | 0.015 (3) | 0.037 (4) |
C25 | 0.051 (4) | 0.047 (3) | 0.068 (4) | 0.009 (3) | 0.026 (3) | 0.021 (3) |
Br26 | 0.1075 (5) | 0.0769 (5) | 0.0443 (3) | 0.0238 (4) | 0.0172 (3) | 0.0299 (3) |
S27 | 0.0461 (7) | 0.0289 (6) | 0.0326 (6) | 0.0081 (6) | 0.0128 (5) | 0.0053 (5) |
O28 | 0.075 (2) | 0.0375 (19) | 0.0488 (19) | 0.0247 (18) | 0.0270 (18) | 0.0193 (16) |
O29 | 0.043 (2) | 0.045 (2) | 0.0437 (19) | −0.0034 (16) | 0.0109 (16) | −0.0031 (16) |
N30 | 0.044 (2) | 0.032 (2) | 0.0283 (18) | 0.0132 (18) | 0.0067 (17) | 0.0045 (16) |
C31 | 0.032 (3) | 0.033 (3) | 0.031 (2) | 0.005 (2) | 0.010 (2) | 0.008 (2) |
N32 | 0.032 (2) | 0.031 (2) | 0.035 (2) | 0.0084 (17) | 0.0030 (17) | 0.0033 (16) |
C33 | 0.024 (2) | 0.030 (2) | 0.035 (2) | 0.000 (2) | 0.008 (2) | 0.006 (2) |
N34 | 0.039 (3) | 0.040 (3) | 0.037 (2) | 0.008 (2) | −0.0092 (19) | 0.001 (2) |
N35 | 0.049 (3) | 0.043 (3) | 0.037 (2) | 0.019 (2) | −0.002 (2) | 0.0046 (19) |
N36 | 0.049 (2) | 0.034 (2) | 0.036 (2) | 0.007 (2) | 0.0013 (19) | −0.0022 (18) |
C37 | 0.056 (3) | 0.032 (3) | 0.060 (3) | 0.006 (3) | 0.008 (3) | 0.002 (2) |
C38 | 0.063 (4) | 0.054 (3) | 0.046 (3) | 0.013 (3) | −0.005 (3) | −0.014 (3) |
C1—C2 | 1.381 (6) | C20—C21 | 1.385 (6) |
C1—C6 | 1.374 (6) | C20—C25 | 1.374 (7) |
C1—Br7 | 1.906 (5) | C20—Br26 | 1.890 (4) |
C2—H2 | 0.9300 | C21—H21 | 0.9300 |
C2—C3 | 1.389 (6) | C21—C22 | 1.388 (6) |
C3—C4 | 1.382 (6) | C22—C23 | 1.381 (6) |
C3—S8 | 1.784 (4) | C22—S27 | 1.782 (4) |
C4—H4 | 0.9300 | C23—H23 | 0.9300 |
C4—C5 | 1.377 (6) | C23—C24 | 1.378 (7) |
C5—H5 | 0.9300 | C24—H24 | 0.9300 |
C5—C6 | 1.366 (7) | C24—C25 | 1.369 (7) |
C6—H6 | 0.9300 | C25—H25 | 0.9300 |
S8—O9 | 1.453 (3) | S27—O28 | 1.439 (3) |
S8—O10 | 1.441 (3) | S27—O29 | 1.446 (3) |
S8—N11 | 1.581 (4) | S27—N30 | 1.602 (3) |
N11—H11 | 0.8600 | N30—H30 | 0.8600 |
N11—C12 | 1.354 (5) | N30—C31 | 1.350 (5) |
C12—N13 | 1.336 (5) | C31—N32 | 1.349 (5) |
C12—N16 | 1.340 (6) | C31—N35 | 1.342 (6) |
N13—C14 | 1.341 (5) | N32—C33 | 1.340 (5) |
C14—N15 | 1.336 (5) | C33—N34 | 1.339 (5) |
C14—N17 | 1.343 (5) | C33—N36 | 1.349 (5) |
N15—H15A | 0.80 (5) | N34—H34A | 0.85 (5) |
N15—H15B | 0.86 (6) | N34—H34B | 0.85 (6) |
N16—H16A | 0.80 (5) | N35—H35A | 0.83 (5) |
N16—H16B | 0.83 (5) | N35—H35B | 0.78 (5) |
N17—C18 | 1.461 (5) | N36—C37 | 1.459 (6) |
N17—C19 | 1.457 (6) | N36—C38 | 1.449 (6) |
C18—H18A | 0.9600 | C37—H37A | 0.9600 |
C18—H18B | 0.9600 | C37—H37B | 0.9600 |
C18—H18C | 0.9600 | C37—H37C | 0.9600 |
C19—H19A | 0.9600 | C38—H38A | 0.9600 |
C19—H19B | 0.9600 | C38—H38B | 0.9600 |
C19—H19C | 0.9600 | C38—H38C | 0.9600 |
C2—C1—Br7 | 118.5 (4) | C21—C20—Br26 | 119.5 (4) |
C6—C1—C2 | 122.4 (4) | C25—C20—C21 | 121.3 (4) |
C6—C1—Br7 | 119.1 (3) | C25—C20—Br26 | 119.1 (4) |
C1—C2—H2 | 121.4 | C20—C21—H21 | 120.9 |
C1—C2—C3 | 117.2 (4) | C20—C21—C22 | 118.1 (4) |
C3—C2—H2 | 121.4 | C22—C21—H21 | 120.9 |
C2—C3—S8 | 118.3 (3) | C21—C22—S27 | 120.2 (3) |
C4—C3—C2 | 121.2 (4) | C23—C22—C21 | 120.9 (4) |
C4—C3—S8 | 120.4 (3) | C23—C22—S27 | 118.9 (3) |
C3—C4—H4 | 120.3 | C22—C23—H23 | 120.3 |
C5—C4—C3 | 119.3 (5) | C24—C23—C22 | 119.3 (5) |
C5—C4—H4 | 120.3 | C24—C23—H23 | 120.3 |
C4—C5—H5 | 119.6 | C23—C24—H24 | 119.6 |
C6—C5—C4 | 120.8 (5) | C25—C24—C23 | 120.8 (5) |
C6—C5—H5 | 119.6 | C25—C24—H24 | 119.6 |
C1—C6—H6 | 120.5 | C20—C25—H25 | 120.3 |
C5—C6—C1 | 119.0 (4) | C24—C25—C20 | 119.5 (5) |
C5—C6—H6 | 120.5 | C24—C25—H25 | 120.3 |
O9—S8—C3 | 105.9 (2) | O28—S27—C22 | 106.94 (19) |
O9—S8—N11 | 114.05 (19) | O28—S27—O29 | 117.7 (2) |
O10—S8—C3 | 106.56 (19) | O28—S27—N30 | 105.69 (19) |
O10—S8—O9 | 116.50 (19) | O29—S27—C22 | 106.34 (19) |
O10—S8—N11 | 106.7 (2) | O29—S27—N30 | 113.73 (18) |
N11—S8—C3 | 106.42 (19) | N30—S27—C22 | 105.63 (19) |
S8—N11—H11 | 118.1 | S27—N30—H30 | 118.3 |
C12—N11—S8 | 123.7 (3) | C31—N30—S27 | 123.3 (3) |
C12—N11—H11 | 118.1 | C31—N30—H30 | 118.3 |
N13—C12—N11 | 123.7 (4) | N32—C31—N30 | 124.1 (4) |
N13—C12—N16 | 114.6 (4) | N35—C31—N30 | 123.0 (4) |
N16—C12—N11 | 121.7 (4) | N35—C31—N32 | 112.9 (4) |
C12—N13—C14 | 123.6 (4) | C33—N32—C31 | 123.7 (4) |
N13—C14—N17 | 116.7 (4) | N32—C33—N36 | 115.6 (4) |
N15—C14—N13 | 125.2 (4) | N34—C33—N32 | 125.8 (4) |
N15—C14—N17 | 118.1 (4) | N34—C33—N36 | 118.6 (4) |
C14—N15—H15A | 124 (4) | C33—N34—H34A | 123 (3) |
C14—N15—H15B | 119 (4) | C33—N34—H34B | 115 (4) |
H15A—N15—H15B | 117 (5) | H34A—N34—H34B | 121 (5) |
C12—N16—H16A | 116 (4) | C31—N35—H35A | 119 (3) |
C12—N16—H16B | 119 (4) | C31—N35—H35B | 115 (4) |
H16A—N16—H16B | 120 (5) | H35A—N35—H35B | 123 (5) |
C14—N17—C18 | 120.9 (4) | C33—N36—C37 | 122.3 (4) |
C14—N17—C19 | 121.8 (4) | C33—N36—C38 | 122.0 (4) |
C19—N17—C18 | 117.3 (4) | C38—N36—C37 | 115.7 (4) |
N17—C18—H18A | 109.5 | N36—C37—H37A | 109.5 |
N17—C18—H18B | 109.5 | N36—C37—H37B | 109.5 |
N17—C18—H18C | 109.5 | N36—C37—H37C | 109.5 |
H18A—C18—H18B | 109.5 | H37A—C37—H37B | 109.5 |
H18A—C18—H18C | 109.5 | H37A—C37—H37C | 109.5 |
H18B—C18—H18C | 109.5 | H37B—C37—H37C | 109.5 |
N17—C19—H19A | 109.5 | N36—C38—H38A | 109.5 |
N17—C19—H19B | 109.5 | N36—C38—H38B | 109.5 |
N17—C19—H19C | 109.5 | N36—C38—H38C | 109.5 |
H19A—C19—H19B | 109.5 | H38A—C38—H38B | 109.5 |
H19A—C19—H19C | 109.5 | H38A—C38—H38C | 109.5 |
H19B—C19—H19C | 109.5 | H38B—C38—H38C | 109.5 |
C1—C2—C3—C4 | 0.1 (6) | C20—C21—C22—C23 | 0.1 (6) |
C1—C2—C3—S8 | 178.5 (3) | C20—C21—C22—S27 | 178.6 (3) |
C2—C1—C6—C5 | 0.3 (7) | C21—C20—C25—C24 | −2.2 (8) |
C2—C3—C4—C5 | 0.2 (6) | C21—C22—C23—C24 | −1.6 (7) |
C2—C3—S8—O9 | −174.6 (3) | C21—C22—S27—O28 | 149.4 (3) |
C2—C3—S8—O10 | −49.9 (4) | C21—C22—S27—O29 | 22.8 (4) |
C2—C3—S8—N11 | 63.6 (4) | C21—C22—S27—N30 | −98.3 (4) |
C3—C4—C5—C6 | −0.3 (7) | C22—C23—C24—C25 | 1.1 (8) |
C3—S8—N11—C12 | 74.5 (4) | C22—S27—N30—C31 | 78.0 (4) |
C4—C3—S8—O9 | 3.7 (4) | C23—C22—S27—O28 | −32.1 (4) |
C4—C3—S8—O10 | 128.4 (3) | C23—C22—S27—O29 | −158.7 (4) |
C4—C3—S8—N11 | −118.0 (3) | C23—C22—S27—N30 | 80.1 (4) |
C4—C5—C6—C1 | 0.0 (7) | C23—C24—C25—C20 | 0.7 (8) |
C6—C1—C2—C3 | −0.4 (6) | C25—C20—C21—C22 | 1.8 (7) |
Br7—C1—C2—C3 | 180.0 (3) | Br26—C20—C21—C22 | −177.3 (3) |
Br7—C1—C6—C5 | 179.9 (4) | Br26—C20—C25—C24 | 176.9 (4) |
S8—C3—C4—C5 | −178.1 (4) | S27—C22—C23—C24 | 180.0 (4) |
S8—N11—C12—N13 | −171.1 (3) | S27—N30—C31—N32 | −174.7 (3) |
S8—N11—C12—N16 | 7.9 (6) | S27—N30—C31—N35 | 4.6 (6) |
O9—S8—N11—C12 | −41.9 (4) | O28—S27—N30—C31 | −168.8 (3) |
O10—S8—N11—C12 | −172.0 (3) | O29—S27—N30—C31 | −38.2 (4) |
N11—C12—N13—C14 | 1.6 (6) | N30—C31—N32—C33 | 7.6 (7) |
C12—N13—C14—N15 | −4.1 (7) | C31—N32—C33—N34 | −5.4 (7) |
C12—N13—C14—N17 | 177.1 (4) | C31—N32—C33—N36 | 176.4 (4) |
N13—C14—N17—C18 | 0.1 (6) | N32—C33—N36—C37 | −10.9 (6) |
N13—C14—N17—C19 | −178.3 (4) | N32—C33—N36—C38 | 171.7 (4) |
N15—C14—N17—C18 | −178.7 (4) | N34—C33—N36—C37 | 170.8 (4) |
N15—C14—N17—C19 | 2.8 (6) | N34—C33—N36—C38 | −6.6 (6) |
N16—C12—N13—C14 | −177.5 (4) | N35—C31—N32—C33 | −171.8 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N15—H15B···N11 | 0.86 (6) | 2.02 (6) | 2.655 (6) | 130 (5) |
N16—H16B···O9 | 0.83 (6) | 2.19 (5) | 2.830 (6) | 134 (5) |
N34—H34B···N30 | 0.86 (6) | 2.02 (6) | 2.696 (5) | 135 (5) |
N35—H35A···O29 | 0.83 (5) | 2.18 (5) | 2.823 (6) | 136 (4) |
N35—H35B···O9 | 0.78 (5) | 2.27 (5) | 3.049 (6) | 175 (5) |
N16—H16A···N32i | 0.81 (5) | 2.54 (5) | 3.225 (6) | 144 (4) |
N34—H34A···O10ii | 0.85 (5) | 2.23 (5) | 3.063 (5) | 165 (4) |
Symmetry codes: (i) −x, −y+1, −z+1; (ii) −x+1, −y+1, −z+1. |
Contact | Molecule A | Molecule B |
C···C | 3.2 | 2.4 |
C···H/H···C | 13.1 | 15.0 |
H···H | 35.0 | 34.0 |
Br···C/C···Br | 0.2 | 2.1 |
Br···H/H···Br | 14.1 | 14.6 |
Br···Br | 1.7 | 0.0 |
S···C/C···S | 0.0 | 0.0 |
S···H/H···S | 0.1 | 0.1 |
S···Br/Br···S | 0.0 | 0.0 |
S···S | 0.0 | 0.0 |
O···C/C···O | 0.4 | 0.0 |
O···H/H···O | 19.2 | 17.7 |
O···Br/Br···O | 0.8 | 2.9 |
O···S/S···O | 0.0 | 0.0 |
O···O | 0.1 | 0.1 |
N···C/C···N | 0.3 | 0.2 |
N···H/H···N | 11.5 | 10.5 |
N···Br/Br···N | 0.0 | 0.0 |
N···S/S···N | 0.0 | 0.0 |
N···O/O···N | 0.0 | 0.0 |
N···N | 0.2 | 0.4 |
Acknowledgements
The authors thank Bingyu Li and Professor Wim De Borggraeve for assistance with the synthesis.
Funding information
KS thanks the Chinese Scholarship Council for a CSC Fellowship and LVM the Hercules Foundation for supporting the purchase of the diffractometer through project AKUL/09/0035. JL acknowledges the Sichuan Science and Technology Program (project No. 2022ZYD0016 and 2023JDRC0013), and the National Natural Science Foundation of China (project No. 21776120).
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