Byline: Sadaf Afzal, Zareen Akhter, Asghari Gul, Muhammad Arif Nadeem, Muhammad Nawaz Tahir and Fouzia Perveen
Abstract: Molecular structure of a diol-terminated Schiff base, 4-((4-(4-(3-ethoxy-4-hydroxybenzylideneamino)phenoxy)phenylimino)mriethyl)-2-ethoxyphenol (SB) was studied by single-crystal X-ray diffraction and calculated by using the density functional theory (DFT) method with 6-31G (d) basis set. SB crystallizes in a Tetragonal system in the I41/a space group. The crystal structure is mediated by the ethanol as solvent molecules. The thermal analysis data shows that the SB is stable upto ca. 372 C. The calculated molecular geometries and the vibration frequencies in the ground state have been compared with the experimental data.
The results show that the optimized geometries can reproduce well the crystal structural parameters, and the theoretical vibration frequencies show good agreement with the experimental data, although the experimental data is slightly different from the theoretical ones due to the intermolecular forces. Besides, the molecular electrostatic potential (MEP) and the frontier molecular orbital (FMO) analysis of the compounds were investigated by theoretical calculations. Molecular docking along with the quantitative structure activity relationship (QSAR) investigations showed groove binding as a preferred mode between SB-double stranded DNA(PDB ID-1BNA). Binding strength indicated worthy correlation with various physicochemical parameters like hydrophobic surface area (Vsurf), EHOMO, ELUMO, log P and molar refractivity (MR). Formation constant (Kf) showed good binding strength for SB-DNA complex, thus, could be studied further as anticancer drugs.
Keywords: X-ray structure determination; IR spectroscopy; DFT calculations; Electronic structure properties, Docking studies.
Schiff bases are condensation products of primary amines with carbonyl compounds, first reported by Schiff  in 1864. The common structural feature of these compounds is the azomethine group with a general formula RHC=N- R1, where R and R1 are alkyl, aryl, cyclo alkyl or heterocyclic groups which may be variously substituted. These are also known as imines or azomethines. Several studies [2-6] showed that the presence of a lone pair of electrons in sp2 hybridized orbital of nitrogen atom of the azomethine group is of considerable chemical and biological importance. Because of the relative easiness of preparation, synthetic flexibility, and the special property of C=N group, Schiff bases are generally excellent chelating agents, [6-10] especially when a functional group like -OH or -SH is present close to the azomethine group so as to form a five or six membered ring with the metal ion.
Versatility of Schiff base ligands and biological, analytical and industrial applications of their complexes make further investigations in this area highly desirable. Although there have been many studies on the synthesis and biological activities, there are only a few articles concerning the complete structural analysis. Since SB are biologically active, information about their 3-dimensional crystal structures, may be of great interest for rational drug design. On the other hand, we also aimed to obtain and analyze the electronic structures of SB. B3lyp theory with 6-31G* basis set was used since it is known to be quite a reliable method .
In this study, we present results of a detailed investigation of the structural...