N'-(Pyridin-3-ylmethylene)benzenesulfonohydrazide: Crystal structure, DFT, Hirshfeld surface and in silico anticancer studies

Abstract

A new Schiff base, N'-(pyridin-3-ylmethylene)benzenesulfonohydrazide, was synthesized and characterized by elemental analysis, IR, Mass, 1H NMR and 13C NMR spectroscopy, and single-crystal X-ray determination. The asymmetric molecule crystallized in the monoclinic crystal system and P2(1)/c space group. Crystal data for C12H11N3O2S: a = 9.7547(4) Å, b = 9.8108(4) Å, c = 13.1130(5) Å, β = 109.038(2)°, V = 1186.29(8) Å3, Z = 4, μ(MoKα) = 0.270 mm-1, Dcalc = 1.463 g/cm3, 13338 reflections measured (5.296° ≤ 2Θ ≤ 55.484°), 2790 unique (Rint = 0.0494, Rsigma = 0.0400) which were used in all calculations. The final R1 was 0.0345 (I > 2σ(I)) and wR2 was 0.0914 (all data). In the crystal structure of the compound C12H11N3O2S, molecules are linked in a continuous chain by intermolecular of N∙∙∙HN=N hydrogen bonds. The pyridine moiety is planar, while the benzenesulfonohydrazide group adopts a gauche conformation about C-S-N angle (105.54°). The Hirshfeld surface analysis and fingerprint plots were used to establish the presence, nature, and percentage contribution of the different intermolecular interactions, including N-H∙∙∙N, C-H∙∙∙O, C-H∙∙∙C, and π∙∙∙π interactions, with the C-H contacts having the most significant contribution. The pairwise interaction energies were calculated at the B3LYP/6-31G(d,p) level of theory, and interaction energy profiles showed that the electrostatic forces had the most significant contribution to the total interaction energies of the different molecular pairs in the crystal. In-silico technique was used to examine the compound as a possible anticancer agent. The molecule demonstrated zero violation of the criteria of Lipinski’s rule of five with a polar surface area of 116.03 Å2. The molecule displayed favorable binding interactions with ten selected validated anticancer protein targets ranging from -9.58 to -11.95 kcal/mol and -2.73 to -5.73 kcal/mol on scoring and rescoring, respectively, with London dG and Affinity dG scoring functions. Two proteins; farnesyl transferase and signaling protein, preferred interactions with the Schiff-base over their co-crystallized inhibitors according to London dG scoring. Analysis of binding poses indicated that the Schiff-base made contact with amino acid residues of the two proteins through the N-H, sulphonyl oxygen, and phenyl groups, and this could be exploited in chemical and structural modification towards activity optimization.

Describing auxin solid state intermolecular interactions using contact descriptors, shape property and molecular fingerprint: comparison of pure auxin crystal and auxin-TIR1 co-crystal

“…Contact descriptors are used in crystallography, DFT, and drug discovery analyses to identify the more important contacts, interactions, and noncovalent interactions that are at the origin of structure stabilization [28]. In this line, short contact descriptors like di, de, and dnorm are combined to the shape descriptors and surface properties such as the Shape index and the electrostatic potential mapped on the Hirshfeld surface (HS) to describe the molecular environment of various structures [21,22]. HS analysis is therefore a very good way to visualize interactions in the solid-state.…”

“…Indeed, describing contact interactions using the Hirshfeld surface has emerged as a powerful way to depict close contacts like hydrogen bonds, π-π stabilization, acceptor, and donor group localization [21]. In addition, for a selected molecule, the contribution of all contacts atom pairswise can be combined to form two-dimensional molecular fingerprints that are highly sensitive to the chemical environment [22]. Analyzing the results provided by these techniques could give more information about the interaction features that could be helped to correlate contacts, stability, and activity.…”

Structure and Computational Studies of New Sulfonamide Compound: {(4-nitrophenyl)sulfonyl}tryptophan

“…This is probably due to a slight disorder in the heterocyclic indole ring in structure A. The sulfonamide S1-N1 bond length of 1.624(3) Å, is slightly shorter than the expected average N-S bond length (1.771(4) Å) [51,52], probably due to the influence of the electronegative oxygen atoms on the S1 atom resulting in a decrease in the N1-S1 bond length. The N3-C15 bond length of the p-nitro substituent of 1.473(4) Å is longer than the N2-C10 (1.356(7) Å) and N2-C9 (1.358(8) Å) bonds of the aromatic indole ring.…”

Evaluation of Anticancer Activity of Schiff bases Derived from Pyridine and their Metal Complexes- A Review

“…A new Schiff base synthesized from 3-pyridine carboxaldehyde with benzene sulfono hydrazide and in silico anticancer studies done which showed that the compound is similar to drug and it made favorable binding interaction with selected anticancer drug target 53 .…”