research communications
H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate
Hirshfeld surface analysis and DFT calculations of ethyl 2-[4-(methylsulfanyl)-1aLaboratory of Organic and Physical Chemistry, Applied Bioorganic Chemistry Team, Faculty of Sciences, Ibn Zohr University, Agadir, Morocco, bLaboratory of Organic Chemistry and Physical Chemistry, Research Team: Molecular, Modeling, Materials and Environment, Department of Chemistry, Faculty of, Sciences, University Ibn Zohr in Agadir, BP 8106 Agadir, Morocco, cLaboratory of Spectroscopy, Molecular Modeling, Materials, Nanomaterials, Water, and Environment, CERNE2D, Faculty of Sciences, Mohammed V University in Rabat, Av. Ibn Battouta, BP 1014, Rabat, Morocco, dDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA, eDepartment of Physics, Hacettepe University, 06800 Beytepe, Ankara, Türkiye, and fLaboratory of Heterocyclic Organic Chemistry, Medicines Science Research Center, Pharmacochemistry Competence Center, Mohammed V University in Rabat, Faculty of Sciences, Morocco
*Correspondence e-mail: n.sebbar@uiz.ac.ma
The 10H12N4O2S, contains two molecules differing slightly in the orientations of the methyl groups. In the crystal, a sandwich-type structure extending parallel to the ab plane is formed by weak C—H⋯O and C—H⋯N hydrogen bonds together with slipped π-stacking interactions. A Hirshfeld surface analysis of the indicates that the most important contributions to the crystal packing are from H⋯H (43.5%), H⋯O/O⋯H (17.9%) and H⋯N/N⋯H (17.4%) interactions. The molecular structure optimized by density functional theory (DFT) at the B3LYP/ 6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. Further calculations include the HOMO–LUMO energies and molecular electrostatic potential (MEP) surfaces.
of the title compound, CKeywords: crystal structure; hydrogen bond; π-stacking; pyrazolopyrimidine.
CCDC reference: 2221106
1. Chemical context
Pyrazolo[3,4-d]pyrimidine derivatives are an important class of nitrogen-containing compounds because of their pharmacological properties and their use as antitumor agents (Tintori et al., 2015). They are also applied as protein kinase inhibitors (Schenone et al., 2014; Rao & Chanda, 2020), and have anti-HSV (Moukha-Chafiq et al., 2007), antiviral (Moukha-Chafiq et al., 2006; Rashad et al., 2008), anti-avian influenza virus (H5N1) (Rashad et al., 2010), anti-inflammatory (Atatreh et al., 2019), anti-leishmanial (Jorda et al., 2011; Llanos-Cuentas et al., 1997), anticancer (Chauhan & Kumar, 2013), and antibacterial activity (Rostamizadeh et al., 2013).
As a continuation of our research on the development of N-substituted pyrazolo[3,4-d]pyrimidine derivatives and the evaluation of their potential pharmacological activities, the title compound, C10H12N4O2S, I, was synthesized by the reaction of ethyl 2-bromoacetate with 4-(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine and potassium carbonate in the presence of potassium chloride and tetra-n-butylammonium bromide as catalysts. We report herein the synthesis, molecular and crystal structures, Hirshfeld surface analysis, and density functional theory (DFT) computational calculations carried out at the B3LYP/6–311 G(d,p) level along with calculation of the molecular electrostatic potential (MEP) surfaces of I.
2. Structural commentary
The I contains two molecules (Fig. 1), differing slightly in the rotational orientations of the methyl groups (Fig. 2). For the molecule containing S1, the pyrazolopyrimidine moiety is planar to within 0.023 (2) Å (r.m.s. deviation = 0.0115) with N4 being the most distant atom from the mean plane. For the molecule containing S2, the bicyclic unit is planar to within 0.020 (3) Å (r.m.s. deviation = 0.0115) with C11 being the most distant atom from the mean plane. The dihedral angle between the mean planes of the bicyclic units is 2.16 (2)°.
of3. Supramolecular features
In the crystal, chains extending parallel to the a axis are formed by molecules containing S1 through weak C3—H3⋯N4 hydrogen bonds and parallel chains by molecules containing S2 through C13—H13⋯N8 hydrogen bonds (Table 1). The chains containing S1 are linked into sheets parallel to the ab plane by C5—H5⋯O2 hydrogen bonds while the chains containing S2 are interspersed between these layers and connect them by C19—H19A⋯O1 hydrogen bonds. In addition, the different molecules are associated through complementary π-stacking interactions between five- and six-membered rings [centroid–centroid distance = 3.422 (2) Å; slippage 1.034 Å] (Figs. 1 and 3).
4. Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of the title compound, a Hirshfeld surface (HS) analysis (Hirshfeld, 1977) was carried out by using Crystal Explorer 17.5 (Spackman et al., 2021). In the HS plotted over dnorm (Fig. 4a), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colors indicate distances shorter or longer than the van der Waals radii, respectively (Venkatesan et al., 2016). The shape-index of the HS is a tool to visualize the π–π stacking by the presence of adjacent red and blue triangles. If there are no adjacent red and/or blue triangles, then there are no π–π interactions. However, Fig. 4b clearly suggests that there are π–π interactions in I.
The overall two-dimensional fingerprint plot, Fig. 5a, and those delineated into H⋯H, H⋯O/O⋯H, H⋯N/N⋯H, H⋯C/C⋯H, H⋯S/S⋯H, N⋯S/S⋯N, C⋯S/S⋯C, O⋯S/S⋯O and O⋯O contacts (McKinnon et al., 2007) are illustrated in Fig. 5b–j, respectively, together with their relative contributions to the Hirshfeld surface. The most important interaction is H⋯H, contributing 43.5% to the overall crystal packing, which is reflected in Fig. 5b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at de = di = 1.08 Å. The pair of the scattered points of spikes in the H⋯O/O⋯H fingerprint plot (17.9% contribution to the HS, Fig. 5c), has a symmetric distribution of points with the tips at de + di = 2.40 Å. The H⋯N/N⋯H contacts, Fig. 5d, contribute 17.4% to the HS, and the distribution of points also has the tips at de + di = 2.40 Å. The large number of H⋯H, H⋯O/O⋯H and H⋯N/N ⋯ H interactions suggest that van der Waals interactions play the major role in the crystal packing (Hathwar et al., 2015). In the absence of C—H⋯π interactions, the pair of characteristic wings resulting in the fingerprint plot delineated into H⋯C/C⋯H contacts, Fig. 5e, the 9.5% contribution to the HS is viewed with the tips at de + di = 2.67 Å. The H⋯S/S⋯H contacts, Fig. 5f, with a 8.9% contribution to the HS are viewed with the pair of the scattered points of spikes at de + di = 2.85 Å. The symmetric distribution of points of the N⋯S/S⋯N contacts, Fig. 5g, with a 1.7% contribution to the HS appear as a pair of spikes of scattered points with the tips at de + di = 3.33 Å. Finally, the contributions of the remaining C⋯S/S⋯C, O⋯S/S⋯O and O⋯O contacts (Fig. 5h–j) are smaller than 1.0% to the HS with low densities of points.
The Hirshfeld surface representations with the function dnorm plotted onto the surface are shown for the H⋯H, H⋯O/O⋯H, H⋯N/N⋯H and H⋯C/C⋯H interactions in Fig. 6a–d, respectively.
5. DFT calculations
The structure of I in the gas phase was optimized by means of density functional theory (DFT) using the hybrid B3LYP method and the 6–311 G(d,p) basis-set, which is based on Becke's model (Becke, 1993). It considers a mixture of the exact (Hartree–Fock) and density functional theory exchange utilizing the B3 functional, together with the LYP correlation functional (Lee et al., 1988). After obtaining the optimized molecular structure, the harmonic vibrational frequencies were calculated at the same theoretical level to confirm that the number of imaginary frequencies is zero for the stationary point. Both the structure optimization and harmonic vibrational frequency analysis of I were computed with the Gaussian 09 program (Frisch et al., 2009). Theoretical and experimental results related to bond lengths and angles are in good agreement and are summarized in Table 2. The DFT calculations provide some important information on the reactivity and site selectivity of the molecular framework. Numerical values for EHOMO and ELUMO (Fig. 7), (χ), hardness (η), potential (μ), (ω) and softness (σ) are compiled in Table 3. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 7. The HOMO and LUMO are localized in the plane extending from the entire ethyl 2-(4-(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)acetate system. The energy band gap [ΔE = ELUMO - EHOMO] of the molecule is 4.84 eV, and the frontier molecular orbital energies, EHOMO and ELUMO are −6.55 and −1.71 eV, respectively.
|
|
6. Molecular electrostatic (MEP)
Molecular electrostatic potential (MEP) surfaces can be used to predict reactive sites for electrophilic and nucleophilic attack. The calculation of MEP surfaces was carried out on the basis of B3LYP/6-31G-optimized structures using the program Gauss View. The total electron density onto which the electrostatic potential surface has been mapped is shown in Fig. 8. This figure provides a visual representation of the chemically active sites and comparative reactivity of atoms where the red regions denote the most negative electrostatic potential, blue represents regions with the most positive electrostatic potential, and green represents the region of zero potential. Fig. 8 confirms the existence of intermolecular C—H⋯O and C—H⋯N hydrogen-bonding interactions.
7. Database survey
A search of the Cambridge Structural Database (CSD: Groom et al., 2016; updated to March 2022) with the search fragment II (Fig. 9) gave 18 hits of which III (XOVRUX; El Fal et al., 2014) is the closest to I. All the others contain an additional methylsulfanyl substituent at the 6-position on the pyrimidine ring and a three-carbon chain attached to the nitrogen at the 1-position with various aromatic groups on the end of the chain including a second bis(methylsulfanyl)pyrazolopyrimidine moiety. These were designed to study possible intramolecular π-stacking interactions and are not considered close analogs of I. One other close analog is IV (El Hafi et al., 2017). In III, the molecule lies on a mirror plane and so is rigorously planar. There is only one molecule in the and the packing consists of head-to-tail π-stacking of the molecules along the c axis direction with a centroid-to-centroid distance of 3.6062 (8) Å. In IV, Z′ = 2 as in I but the two independent molecules do not have the pyrazolopyrimidine moieties approximately parallel to one another as in I. Instead of chains, a self-dimer is formed by each independent molecule, and each type of dimer is π-stacked in a head-to-tail fashion, forming stepped stacks inclined by ca ±51° to the bc plane.
8. Synthesis and crystallization
To a solution of 4-(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine (10 mmol), ethyl 2-bromoacetate (10 mmol) and potassium carbonate (6.51 mmol) in dimethylformamide (DMF; 40 ml) a catalytic amount of tetra-n-butylammonium bromide (0.33 mmol) was added. The mixture was stirred for 24 h. The solid material was removed by filtration and the solvent evaporated in vacuo. The resulting solid product was purified by recrystallization from ethanol to afford colorless crystals in 82% yield. 1H NMR (300 MHz, CDCl3): 1.23 (t, 3H, CH3); 2.69 (s, 3H, CH3); 4.20 (q, 2H, CH2); 5.20 (s, 2H, CH2); 8.08 (s,1H, H3); 8.70 (s, 1H, H6).
9. Refinement
Crystal, data collection and . Although intensity statistics indicated the centrosymmetric Pbca, structure solution by direct and revealed serious disorder. The use of dual space methods (SHELXT; Sheldrick, 2015a) gave an ordered solution in the non-centrosymmetric Pca21 as the only option. The model refined smoothly and gave a reasonable value for the H atoms attached to carbon were placed in calculated positions (C—H = 0.95–0.99 Å using isotropic displacement parameters 1.2–1.5 times those of the parent atoms).
details are given in Table 4Supporting information
CCDC reference: 2221106
https://doi.org/10.1107/S2056989022011112/wm5664sup1.cif
contains datablocks I, global. DOI:Supporting information file. DOI: https://doi.org/10.1107/S2056989022011112/wm5664Isup3.cdx
Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989022011112/wm5664Isup4.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989022011112/wm5664Isup4.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/1 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: publCIF (Westrip, 2010).C10H12N4O2S | Dx = 1.423 Mg m−3 |
Mr = 252.30 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pna21 | Cell parameters from 9868 reflections |
a = 15.207 (2) Å | θ = 2.8–29.2° |
b = 7.9249 (11) Å | µ = 0.27 mm−1 |
c = 19.540 (3) Å | T = 150 K |
V = 2354.9 (6) Å3 | Column, colourless |
Z = 8 | 0.40 × 0.17 × 0.17 mm |
F(000) = 1056 |
Bruker Smart APEX CCD diffractometer | 6339 independent reflections |
Radiation source: fine-focus sealed tube | 5436 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.034 |
Detector resolution: 8.3333 pixels mm-1 | θmax = 29.2°, θmin = 2.1° |
φ and ω scans | h = −20→20 |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | k = −10→10 |
Tmin = 0.86, Tmax = 0.96 | l = −26→26 |
43340 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.043 | H-atom parameters constrained |
wR(F2) = 0.122 | w = 1/[σ2(Fo2) + (0.0807P)2 + 0.1629P] where P = (Fo2 + 2Fc2)/3 |
S = 1.09 | (Δ/σ)max = 0.001 |
6339 reflections | Δρmax = 0.57 e Å−3 |
311 parameters | Δρmin = −0.47 e Å−3 |
1 restraint | Absolute structure: Flack x determined using 2355 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Primary atom site location: dual | Absolute structure parameter: 0.08 (4) |
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = –30.00 and 210.00°. The scan time was 20 sec/frame. |
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. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å). All were included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms. Although intensity statistics indicated a centric space group, solution in the centric space group by direct and Patterson methods indicated serious disorder while use of dual space methods (SHELXT, Sheldrick, 2015a) gave an ordered solution in the non-centric space group as the only option. Inspection of the resulting two independent molecules indicated slight differences in the rotational orientations of the methyl groups. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.74531 (5) | 1.26019 (8) | 0.57534 (6) | 0.0250 (2) | |
O1 | 0.59288 (18) | 0.5947 (3) | 0.71430 (14) | 0.0419 (6) | |
O2 | 0.54002 (17) | 0.3444 (3) | 0.67778 (13) | 0.0348 (5) | |
N1 | 0.81795 (14) | 0.9505 (3) | 0.57177 (13) | 0.0203 (4) | |
N2 | 0.73831 (15) | 0.6863 (3) | 0.57468 (14) | 0.0204 (5) | |
N3 | 0.58118 (17) | 0.7265 (3) | 0.58391 (18) | 0.0197 (6) | |
N4 | 0.52384 (15) | 0.8591 (3) | 0.58972 (14) | 0.0231 (5) | |
C1 | 0.66249 (16) | 0.9581 (3) | 0.57980 (16) | 0.0184 (5) | |
C2 | 0.74420 (16) | 1.0407 (3) | 0.57571 (17) | 0.0188 (5) | |
C3 | 0.8103 (2) | 0.7801 (4) | 0.5709 (2) | 0.0212 (6) | |
H3 | 0.863935 | 0.719525 | 0.567069 | 0.025* | |
C4 | 0.66523 (19) | 0.7812 (4) | 0.57899 (19) | 0.0180 (5) | |
C5 | 0.57179 (18) | 0.9976 (4) | 0.58628 (16) | 0.0216 (6) | |
H5 | 0.548698 | 1.108876 | 0.587910 | 0.026* | |
C6 | 0.86041 (19) | 1.3043 (5) | 0.5889 (2) | 0.0373 (8) | |
H6A | 0.895983 | 1.226210 | 0.561563 | 0.056* | |
H6B | 0.874605 | 1.290078 | 0.637458 | 0.056* | |
H6C | 0.873159 | 1.420555 | 0.574958 | 0.056* | |
C7 | 0.55178 (19) | 0.5563 (4) | 0.59599 (17) | 0.0232 (6) | |
H7A | 0.584817 | 0.478246 | 0.565940 | 0.028* | |
H7B | 0.488659 | 0.547292 | 0.584154 | 0.028* | |
C8 | 0.56492 (19) | 0.5045 (4) | 0.67034 (17) | 0.0257 (6) | |
C9 | 0.5480 (4) | 0.2701 (5) | 0.7460 (3) | 0.0477 (12) | |
H9A | 0.542499 | 0.359900 | 0.780977 | 0.057* | |
H9B | 0.499792 | 0.188164 | 0.753279 | 0.057* | |
C10 | 0.6321 (4) | 0.1852 (10) | 0.7541 (3) | 0.090 (2) | |
H10A | 0.631397 | 0.078866 | 0.728508 | 0.135* | |
H10B | 0.642387 | 0.161832 | 0.802687 | 0.135* | |
H10C | 0.679172 | 0.257702 | 0.736533 | 0.135* | |
S2 | 0.50616 (5) | 1.26544 (10) | 0.41974 (6) | 0.0261 (3) | |
O3 | 0.64984 (17) | 0.5962 (3) | 0.28477 (13) | 0.0395 (6) | |
O4 | 0.71465 (15) | 0.3538 (3) | 0.31719 (13) | 0.0300 (5) | |
N5 | 0.43223 (15) | 0.9564 (3) | 0.42506 (13) | 0.0213 (5) | |
N6 | 0.51119 (14) | 0.6911 (3) | 0.42374 (14) | 0.0201 (5) | |
N7 | 0.66818 (17) | 0.7297 (3) | 0.4129 (2) | 0.0209 (6) | |
N8 | 0.72609 (15) | 0.8609 (3) | 0.40662 (15) | 0.0232 (5) | |
C11 | 0.58765 (16) | 0.9615 (3) | 0.41661 (15) | 0.0184 (5) | |
C12 | 0.50642 (16) | 1.0450 (3) | 0.42037 (17) | 0.0200 (5) | |
C13 | 0.4397 (2) | 0.7853 (4) | 0.4266 (2) | 0.0213 (6) | |
H13 | 0.385810 | 0.725187 | 0.430208 | 0.026* | |
C14 | 0.58423 (18) | 0.7855 (4) | 0.41793 (19) | 0.0174 (5) | |
C15 | 0.67840 (18) | 1.0008 (4) | 0.40924 (17) | 0.0220 (6) | |
H15 | 0.701635 | 1.111868 | 0.406561 | 0.026* | |
C16 | 0.3923 (2) | 1.3134 (4) | 0.4044 (2) | 0.0348 (8) | |
H16A | 0.384436 | 1.436092 | 0.402463 | 0.052* | |
H16B | 0.356391 | 1.267027 | 0.441574 | 0.052* | |
H16C | 0.373922 | 1.263363 | 0.360831 | 0.052* | |
C17 | 0.69686 (19) | 0.5584 (4) | 0.40147 (17) | 0.0207 (6) | |
H17A | 0.663159 | 0.481025 | 0.431350 | 0.025* | |
H17B | 0.759899 | 0.548007 | 0.413395 | 0.025* | |
C18 | 0.68337 (19) | 0.5091 (4) | 0.32713 (16) | 0.0248 (6) | |
C19 | 0.7050 (3) | 0.2858 (6) | 0.2481 (2) | 0.0409 (9) | |
H19A | 0.756035 | 0.213066 | 0.237211 | 0.049* | |
H19B | 0.703735 | 0.379662 | 0.214671 | 0.049* | |
C20 | 0.6230 (3) | 0.1864 (8) | 0.2426 (2) | 0.0609 (13) | |
H20A | 0.572189 | 0.262094 | 0.246137 | 0.091* | |
H20B | 0.620777 | 0.103087 | 0.279587 | 0.091* | |
H20C | 0.621549 | 0.128263 | 0.198327 | 0.091* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0147 (4) | 0.0169 (3) | 0.0433 (6) | −0.0013 (2) | 0.0009 (4) | 0.0005 (3) |
O1 | 0.0495 (14) | 0.0413 (14) | 0.0348 (13) | −0.0087 (12) | −0.0086 (11) | −0.0026 (11) |
O2 | 0.0448 (14) | 0.0269 (12) | 0.0328 (11) | −0.0026 (10) | 0.0048 (10) | 0.0066 (10) |
N1 | 0.0137 (10) | 0.0205 (11) | 0.0267 (11) | −0.0007 (9) | 0.0008 (8) | −0.0002 (10) |
N2 | 0.0162 (11) | 0.0167 (11) | 0.0283 (12) | 0.0011 (8) | −0.0018 (8) | 0.0012 (12) |
N3 | 0.0109 (11) | 0.0192 (10) | 0.0290 (16) | 0.0011 (9) | −0.0001 (11) | −0.0014 (11) |
N4 | 0.0156 (10) | 0.0194 (12) | 0.0342 (14) | 0.0013 (9) | −0.0003 (9) | −0.0021 (10) |
C1 | 0.0118 (11) | 0.0186 (12) | 0.0249 (12) | 0.0001 (10) | 0.0005 (9) | −0.0009 (11) |
C2 | 0.0133 (11) | 0.0192 (11) | 0.0239 (12) | −0.0006 (10) | −0.0011 (9) | −0.0011 (12) |
C3 | 0.0143 (13) | 0.0228 (12) | 0.0264 (15) | 0.0022 (12) | −0.0011 (12) | 0.0004 (15) |
C4 | 0.0135 (12) | 0.0188 (11) | 0.0216 (14) | 0.0000 (11) | −0.0012 (11) | 0.0014 (14) |
C5 | 0.0133 (13) | 0.0198 (14) | 0.0316 (16) | 0.0005 (10) | 0.0006 (11) | 0.0001 (12) |
C6 | 0.0180 (14) | 0.0295 (18) | 0.064 (2) | −0.0067 (13) | −0.0016 (14) | −0.0057 (16) |
C7 | 0.0158 (13) | 0.0197 (14) | 0.0340 (17) | −0.0043 (11) | −0.0011 (11) | 0.0016 (12) |
C8 | 0.0196 (14) | 0.0269 (15) | 0.0305 (14) | 0.0007 (11) | 0.0017 (11) | −0.0002 (11) |
C9 | 0.070 (3) | 0.036 (2) | 0.036 (2) | 0.009 (2) | 0.015 (2) | 0.0150 (17) |
C10 | 0.086 (4) | 0.136 (5) | 0.048 (3) | 0.075 (4) | 0.008 (3) | 0.024 (3) |
S2 | 0.0150 (4) | 0.0169 (4) | 0.0464 (7) | 0.0009 (2) | 0.0005 (4) | −0.0014 (4) |
O3 | 0.0493 (14) | 0.0362 (13) | 0.0329 (12) | 0.0118 (12) | −0.0063 (11) | 0.0024 (10) |
O4 | 0.0330 (11) | 0.0229 (11) | 0.0341 (11) | 0.0074 (9) | 0.0022 (9) | −0.0045 (9) |
N5 | 0.0146 (10) | 0.0183 (11) | 0.0310 (12) | 0.0003 (9) | −0.0015 (9) | −0.0011 (10) |
N6 | 0.0145 (10) | 0.0201 (12) | 0.0258 (12) | −0.0028 (9) | 0.0001 (8) | 0.0012 (11) |
N7 | 0.0135 (12) | 0.0165 (11) | 0.0326 (17) | 0.0007 (9) | −0.0013 (12) | −0.0025 (11) |
N8 | 0.0138 (10) | 0.0239 (13) | 0.0318 (13) | −0.0030 (9) | 0.0014 (9) | 0.0005 (11) |
C11 | 0.0128 (11) | 0.0185 (12) | 0.0240 (12) | −0.0008 (10) | −0.0015 (9) | −0.0010 (11) |
C12 | 0.0165 (12) | 0.0182 (12) | 0.0252 (12) | 0.0001 (10) | 0.0000 (9) | −0.0019 (13) |
C13 | 0.0149 (13) | 0.0196 (12) | 0.0293 (16) | −0.0023 (12) | 0.0011 (12) | −0.0007 (15) |
C14 | 0.0127 (12) | 0.0184 (11) | 0.0211 (14) | −0.0002 (11) | 0.0005 (10) | 0.0004 (14) |
C15 | 0.0137 (12) | 0.0195 (14) | 0.0328 (17) | −0.0035 (10) | −0.0020 (11) | 0.0012 (12) |
C16 | 0.0188 (14) | 0.0225 (17) | 0.063 (2) | 0.0052 (12) | −0.0030 (14) | 0.0021 (15) |
C17 | 0.0160 (13) | 0.0160 (13) | 0.0299 (15) | 0.0021 (11) | 0.0005 (11) | 0.0006 (12) |
C18 | 0.0189 (13) | 0.0234 (15) | 0.0321 (15) | 0.0017 (11) | 0.0022 (11) | −0.0006 (12) |
C19 | 0.043 (2) | 0.047 (2) | 0.033 (2) | 0.0027 (19) | 0.0083 (18) | −0.0131 (19) |
C20 | 0.073 (3) | 0.082 (3) | 0.028 (2) | −0.012 (3) | −0.003 (2) | −0.007 (2) |
S1—C2 | 1.740 (3) | S2—C12 | 1.747 (3) |
S1—C6 | 1.804 (3) | S2—C16 | 1.798 (3) |
O1—C8 | 1.196 (4) | O3—C18 | 1.192 (4) |
O2—C8 | 1.332 (4) | O4—C18 | 1.334 (3) |
O2—C9 | 1.463 (5) | O4—C19 | 1.461 (5) |
N1—C2 | 1.332 (3) | N5—C12 | 1.332 (3) |
N1—C3 | 1.356 (4) | N5—C13 | 1.361 (4) |
N2—C3 | 1.325 (4) | N6—C13 | 1.320 (4) |
N2—C4 | 1.344 (4) | N6—C14 | 1.344 (4) |
N3—C4 | 1.353 (4) | N7—C14 | 1.355 (4) |
N3—N4 | 1.370 (3) | N7—N8 | 1.368 (3) |
N3—C7 | 1.440 (4) | N7—C17 | 1.443 (4) |
N4—C5 | 1.319 (4) | N8—C15 | 1.326 (4) |
C1—C4 | 1.403 (4) | C11—C14 | 1.396 (4) |
C1—C2 | 1.406 (3) | C11—C12 | 1.403 (3) |
C1—C5 | 1.420 (4) | C11—C15 | 1.422 (4) |
C3—H3 | 0.9500 | C13—H13 | 0.9500 |
C5—H5 | 0.9500 | C15—H15 | 0.9500 |
C6—H6A | 0.9800 | C16—H16A | 0.9800 |
C6—H6B | 0.9800 | C16—H16B | 0.9800 |
C6—H6C | 0.9800 | C16—H16C | 0.9800 |
C7—C8 | 1.523 (4) | C17—C18 | 1.518 (4) |
C7—H7A | 0.9900 | C17—H17A | 0.9900 |
C7—H7B | 0.9900 | C17—H17B | 0.9900 |
C9—C10 | 1.453 (6) | C19—C20 | 1.480 (6) |
C9—H9A | 0.9900 | C19—H19A | 0.9900 |
C9—H9B | 0.9900 | C19—H19B | 0.9900 |
C10—H10A | 0.9800 | C20—H20A | 0.9800 |
C10—H10B | 0.9800 | C20—H20B | 0.9800 |
C10—H10C | 0.9800 | C20—H20C | 0.9800 |
C2—S1—C6 | 101.68 (14) | C12—S2—C16 | 102.41 (14) |
C8—O2—C9 | 117.3 (3) | C18—O4—C19 | 116.0 (3) |
C2—N1—C3 | 117.5 (2) | C12—N5—C13 | 117.1 (2) |
C3—N2—C4 | 111.9 (3) | C13—N6—C14 | 111.7 (3) |
C4—N3—N4 | 111.2 (2) | C14—N7—N8 | 111.4 (2) |
C4—N3—C7 | 127.2 (3) | C14—N7—C17 | 127.1 (3) |
N4—N3—C7 | 120.5 (2) | N8—N7—C17 | 120.4 (2) |
C5—N4—N3 | 106.4 (2) | C15—N8—N7 | 106.3 (2) |
C4—C1—C2 | 116.0 (2) | C14—C11—C12 | 115.9 (2) |
C4—C1—C5 | 104.5 (2) | C14—C11—C15 | 104.9 (2) |
C2—C1—C5 | 139.6 (2) | C12—C11—C15 | 139.2 (2) |
N1—C2—C1 | 119.9 (2) | N5—C12—C11 | 120.1 (2) |
N1—C2—S1 | 121.86 (19) | N5—C12—S2 | 121.70 (19) |
C1—C2—S1 | 118.28 (19) | C11—C12—S2 | 118.22 (19) |
N2—C3—N1 | 129.0 (3) | N6—C13—N5 | 129.1 (3) |
N2—C3—H3 | 115.5 | N6—C13—H13 | 115.5 |
N1—C3—H3 | 115.5 | N5—C13—H13 | 115.5 |
N2—C4—N3 | 127.3 (3) | N6—C14—N7 | 127.1 (3) |
N2—C4—C1 | 125.7 (3) | N6—C14—C11 | 126.0 (3) |
N3—C4—C1 | 106.9 (2) | N7—C14—C11 | 106.8 (2) |
N4—C5—C1 | 111.0 (2) | N8—C15—C11 | 110.6 (2) |
N4—C5—H5 | 124.5 | N8—C15—H15 | 124.7 |
C1—C5—H5 | 124.5 | C11—C15—H15 | 124.7 |
S1—C6—H6A | 109.5 | S2—C16—H16A | 109.5 |
S1—C6—H6B | 109.5 | S2—C16—H16B | 109.5 |
H6A—C6—H6B | 109.5 | H16A—C16—H16B | 109.5 |
S1—C6—H6C | 109.5 | S2—C16—H16C | 109.5 |
H6A—C6—H6C | 109.5 | H16A—C16—H16C | 109.5 |
H6B—C6—H6C | 109.5 | H16B—C16—H16C | 109.5 |
N3—C7—C8 | 111.6 (3) | N7—C17—C18 | 110.5 (3) |
N3—C7—H7A | 109.3 | N7—C17—H17A | 109.6 |
C8—C7—H7A | 109.3 | C18—C17—H17A | 109.6 |
N3—C7—H7B | 109.3 | N7—C17—H17B | 109.6 |
C8—C7—H7B | 109.3 | C18—C17—H17B | 109.6 |
H7A—C7—H7B | 108.0 | H17A—C17—H17B | 108.1 |
O1—C8—O2 | 126.3 (3) | O3—C18—O4 | 125.8 (3) |
O1—C8—C7 | 124.8 (3) | O3—C18—C17 | 125.0 (3) |
O2—C8—C7 | 108.9 (3) | O4—C18—C17 | 109.2 (3) |
C10—C9—O2 | 111.0 (4) | O4—C19—C20 | 110.4 (3) |
C10—C9—H9A | 109.4 | O4—C19—H19A | 109.6 |
O2—C9—H9A | 109.4 | C20—C19—H19A | 109.6 |
C10—C9—H9B | 109.4 | O4—C19—H19B | 109.6 |
O2—C9—H9B | 109.4 | C20—C19—H19B | 109.6 |
H9A—C9—H9B | 108.0 | H19A—C19—H19B | 108.1 |
C9—C10—H10A | 109.5 | C19—C20—H20A | 109.5 |
C9—C10—H10B | 109.5 | C19—C20—H20B | 109.5 |
H10A—C10—H10B | 109.5 | H20A—C20—H20B | 109.5 |
C9—C10—H10C | 109.5 | C19—C20—H20C | 109.5 |
H10A—C10—H10C | 109.5 | H20A—C20—H20C | 109.5 |
H10B—C10—H10C | 109.5 | H20B—C20—H20C | 109.5 |
C4—N3—N4—C5 | 1.9 (4) | C14—N7—N8—C15 | 1.4 (5) |
C7—N3—N4—C5 | 170.6 (3) | C17—N7—N8—C15 | 170.3 (3) |
C3—N1—C2—C1 | 0.9 (5) | C13—N5—C12—C11 | 0.6 (5) |
C3—N1—C2—S1 | −178.6 (3) | C13—N5—C12—S2 | −178.6 (3) |
C4—C1—C2—N1 | −0.4 (4) | C14—C11—C12—N5 | 0.2 (5) |
C5—C1—C2—N1 | 177.9 (3) | C15—C11—C12—N5 | 177.4 (3) |
C4—C1—C2—S1 | 179.2 (3) | C14—C11—C12—S2 | 179.4 (3) |
C5—C1—C2—S1 | −2.6 (6) | C15—C11—C12—S2 | −3.4 (6) |
C6—S1—C2—N1 | −12.7 (3) | C16—S2—C12—N5 | −14.1 (3) |
C6—S1—C2—C1 | 167.8 (3) | C16—S2—C12—C11 | 166.6 (3) |
C4—N2—C3—N1 | 0.9 (6) | C14—N6—C13—N5 | −0.7 (6) |
C2—N1—C3—N2 | −1.3 (6) | C12—N5—C13—N6 | −0.3 (5) |
C3—N2—C4—N3 | −179.6 (4) | C13—N6—C14—N7 | −179.2 (4) |
C3—N2—C4—C1 | −0.2 (5) | C13—N6—C14—C11 | 1.6 (5) |
N4—N3—C4—N2 | 177.9 (3) | N8—N7—C14—N6 | 179.0 (3) |
C7—N3—C4—N2 | 10.2 (7) | C17—N7—C14—N6 | 11.1 (7) |
N4—N3—C4—C1 | −1.6 (5) | N8—N7—C14—C11 | −1.6 (5) |
C7—N3—C4—C1 | −169.3 (3) | C17—N7—C14—C11 | −169.5 (3) |
C2—C1—C4—N2 | 0.0 (5) | C12—C11—C14—N6 | −1.4 (5) |
C5—C1—C4—N2 | −178.8 (3) | C15—C11—C14—N6 | −179.5 (3) |
C2—C1—C4—N3 | 179.5 (3) | C12—C11—C14—N7 | 179.2 (3) |
C5—C1—C4—N3 | 0.7 (4) | C15—C11—C14—N7 | 1.1 (4) |
N3—N4—C5—C1 | −1.5 (4) | N7—N8—C15—C11 | −0.7 (4) |
C4—C1—C5—N4 | 0.5 (4) | C14—C11—C15—N8 | −0.3 (4) |
C2—C1—C5—N4 | −177.9 (4) | C12—C11—C15—N8 | −177.7 (4) |
C4—N3—C7—C8 | 74.9 (5) | C14—N7—C17—C18 | 75.6 (5) |
N4—N3—C7—C8 | −91.8 (4) | N8—N7—C17—C18 | −91.4 (4) |
C9—O2—C8—O1 | −0.5 (5) | C19—O4—C18—O3 | −1.0 (5) |
C9—O2—C8—C7 | 179.7 (3) | C19—O4—C18—C17 | 178.8 (3) |
N3—C7—C8—O1 | 2.7 (4) | N7—C17—C18—O3 | −3.4 (4) |
N3—C7—C8—O2 | −177.5 (2) | N7—C17—C18—O4 | 176.7 (2) |
C8—O2—C9—C10 | −92.6 (5) | C18—O4—C19—C20 | −93.3 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
C3—H3···N4i | 0.95 | 2.55 | 3.450 (4) | 158 |
C5—H5···O2ii | 0.95 | 2.57 | 3.314 (4) | 136 |
C13—H13···N8iii | 0.95 | 2.56 | 3.470 (4) | 159 |
C19—H19A···O1iv | 0.99 | 2.52 | 3.490 (5) | 166 |
Symmetry codes: (i) x+1/2, −y+3/2, z; (ii) x, y+1, z; (iii) x−1/2, −y+3/2, z; (iv) −x+3/2, y−1/2, z−1/2. |
Bonds/angles | X-ray | B3LYP/6-311G(d,p) |
S1—C2 | 1.740 (3) | 1.765 |
S1—C6 | 1.804 (3) | 1.824 |
O1—C8 | 1.196 (4) | 1.204 |
O2—C8 | 1.332 (4) | 1.337 |
O2—C9 | 1.463 (5) | 1.453 |
N1—C2 | 1.332 (3) | 1.329 |
N1—C3 | 1.356 (4) | 1.350 |
N2—C3 | 1.325 (4) | 1.325 |
N2—C4 | 1.344 (4) | 1.339 |
N3—C4 | 1.353 (4) | 1.359 |
N3—N4 | 1.370 (3) | 1.363 |
N3—C7 | 1.440 (4) | 1.443 |
N4—C5 | 1.319 (4) | 1.318 |
C2—S1—C6 | 101.68 (14) | 101.324 |
C8—O2—C9 | 117.3 (3) | 117.442 |
C2—N1—C3 | 117.5 (2) | 117.378 |
C3—N2—C4 | 111.9 (3) | 112.041 |
C4—N3—N4 | 111.2 (2) | 111.358 |
C4—N3—C7 | 127.2 (3) | 127.628 |
N4—N3—C7 | 120.5 (2) | 120.828 |
C5—N4—N3 | 106.4 (2) | 106.802 |
C4—C1—C2 | 116.0 (2) | 115.050 |
C4—C1—C5 | 104.5 (2) | 104.373 |
C2—C1—C5 | 139.6 (2) | 140.577 |
N1—C2—C1 | 119.9 (2) | 120.011 |
N1—C2—S1 | 121.86 (19) | 119.923 |
C4—N3—N4—C5 | 1.9 (4) | 1.710 |
C7—N3—N4—C5 | 170.6 (3) | 171.115 |
C3—N1—C2—C1 | 0.9 (5) | 0.715 |
C3—N1—C2—S1 | -178.6 (3) | -179.843 |
C4—N2—C3—N1 | 0.9 (6) | 0.563 |
C2—N1—C3—N2 | -1.3 (6) | -1.149 |
Molecular Energy (a.u.) (eV) | Compound I |
Total Energy TE (eV) | -31458.99 |
EHOMO (eV) | -6.55 |
ELUMO (eV) | -1.71 |
Gap ΔE (eV) | 4.84 |
Dipole moment, µ (Debye) | 2.79 |
Ionisation potential, I (eV) | 6.55 |
Electron affinity, A | 1.71 |
Electronegativity, χ | 3.13 |
Hardness, η | 2.42 |
Electrophilicity index, ω | 3.53 |
Softness, σ | 0.41 |
Fraction of electron transferred, ΔN | 0.59 |
Funding information
JTM thanks Tulane University for support of the Tulane Crystallography Laboratory. TH is grateful to Hacettepe University Scientific Research Project Unit (grant No. 013 D04 602 004).
References
Atatreh, N., Youssef, A. M., Ghattas, M. A., Al Sorkhy, M., Alrawashdeh, S., Al-Harbi, K. B., El-Ashmawy, I. M., Almundarij, T. I., Abdelghani, A. A. & Abd-El-Aziz, A. S. (2019). Bioorg. Chem. 86, 393–400. CrossRef CAS PubMed Google Scholar
Becke, A. D. (1993). J. Chem. Phys. 98, 5648–5652. CrossRef CAS Web of Science Google Scholar
Brandenburg, K. & Putz, H. (2012). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2016). APEX3 and SAINT. Bruker AXS, Inc., Madison, Wisconsin, USA. Google Scholar
Chauhan, M. & Kumar, R. (2013). Bioorg. Med. Chem. 21, 5657–5668. Web of Science CrossRef CAS PubMed Google Scholar
El Fal, M., Ramli, Y., Essassi, E. M., Saadi, M. & El Ammari, L. (2014). Acta Cryst. E70, o1281. CrossRef IUCr Journals Google Scholar
El Hafi, M., Boulhaoua, M., Ramli, Y., Benchidmi, M., Essassi, E. M. & Mague, J. T. (2017). IUCrData, 2, x171526. Google Scholar
Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J. A. Jr, Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, J. M., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, O., Foresman, J. B., Ortiz, J. V., Cioslowski, J. & Fox, D. J. (2009). GAUSSIAN09. Gaussian Inc., Wallingford, CT, US Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Hathwar, V. R., Sist, M., Jørgensen, M. R. V., Mamakhel, A. H., Wang, X., Hoffmann, C. M., Sugimoto, K., Overgaard, J. & Iversen, B. B. (2015). IUCrJ, 2, 563–574. Web of Science CSD CrossRef CAS PubMed IUCr Journals Google Scholar
Hirshfeld, H. L. (1977). Theor. Chim. Acta, 44, 129–138. CrossRef CAS Web of Science Google Scholar
Jorda, R., Sacerdoti-Sierra, N., Voller, J., Havlíček, L., Kráčalíková, K., Nowicki, M. W., Nasereddin, A., Kryštof, V., Strnad, M., Walkinshaw, M. D. & Jaffe, C. L. (2011). Bioorg. Med. Chem. Lett. 21, 4233–4237. CrossRef CAS PubMed Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Lee, C., Yang, W. & Parr, R. G. (1988). Phys. Rev. B, 37, 785–789. CrossRef CAS Web of Science Google Scholar
Llanos-Cuentas, A., Echevarria, J., Cruz, M., La Rosa, A., Campos, P., Campos, M., Franke, E., Berman, J., Modabber, F. & Marr, J. (1997). Clin. Infect. Dis. 25, 677–684. CAS PubMed Google Scholar
McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. pp. 3814–3816. Web of Science CrossRef Google Scholar
Moukha-Chafiq, O., Taha, M. L., Lazrek, H. B., Vasseur, J. J. & Clercq, E. D. (2006). Nucleosides Nucleotides Nucleic Acids, 25, 849–860. PubMed CAS Google Scholar
Moukha-chafiq, O., Taha, M. L. & Mouna, A. (2007). Nucleosides Nucleotides Nucleic Acids, 26, 1107–1110. PubMed CAS Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Rao, R. N. & Chanda, K. (2020). Bioorg. Chem. 99, 103801. Web of Science CrossRef PubMed Google Scholar
Rashad, A. E., Hegab, M. I., Abdel-Megeid, R. E., Micky, J. A. & Abdel-Megeid, F. M. (2008). Bioorg. Med. Chem. 16, 7102–7106. Web of Science CrossRef PubMed CAS Google Scholar
Rashad, A. E., Shamroukh, A. H., Abdel-Megeid, R. E., Mostafa, A., Ali, M. A. & Banert, K. (2010). Nucleosides Nucleotides Nucleic Acids, 29, 809–820. CrossRef CAS PubMed Google Scholar
Rostamizadeh, S., Nojavan, M., Aryan, R., Sadeghian, H. & Davoodnejad, M. (2013). Chin. Chem. Lett. 24, 629–632. Web of Science CrossRef CAS Google Scholar
Schenone, S., Radi, M., Musumeci, F., Brullo, C. & Botta, M. (2014). Chem. Rev. 114, 7189–7238. CrossRef CAS PubMed Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D. & Spackman, M. A. (2021). J. Appl. Cryst. 54, 1006–1011. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tintori, C., Fallacara, A. L., Radi, M., Zamperini, C., Dreassi, E., Crespan, E., Maga, G., Schenone, S., Musumeci, F., Brullo, C., Richters, A., Gasparrini, F., Angelucci, A., Festuccia, C., Delle Monache, S., Rauh, D. & Botta, M. (2015). J. Med. Chem. 58, 347–361. Web of Science CrossRef CAS PubMed Google Scholar
Venkatesan, P., Thamotharan, S., Ilangovan, A., Liang, H. & Sundius, T. (2016). Spectrochim. Acta A Mol. Biomol. Spectrosc. 153, 625–636. Web of Science CSD CrossRef CAS PubMed Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.