Comparison on biological inspection, optimization, cyclic voltammetry, and molecular docking evaluation of novel bivalent transition metal chelates of Schiff Base pincer ligand

Abstract

The presented work introduces a comprehensive study of the ligation behavior of the Schiff base ligand N-3-phenylallylidene nicotinohydrazide HNP toward transition metal cations, VO(II), Cu(II), and Cd(II), to synthesize novel solid chelates and examine their biological potencies. The ligand and its chelates were structurally elucidated using a diverse array of spectroscopic techniques, including FT-IR, UV–visible, 1H/13C NMR, ESR, PXRD, SEM, EDX, and LC/GCMS, besides thermal analysis TG/DTA, magnetic measurements, conductivity measurements, and elemental analysis. The comparison between the FT-IR spectra of both the ligand and its chelates revealed that HNP coordinated as a neutral bidentate with VO(II) and Cd(II) ions, while it coordinated as a mono-negative bidentate with the Cu(II) ion. The electronic absorption spectra depicted absorption bands at 19342 and 14925 cm−1 for the VO(II) and Cu(II) complexes, respectively, predicting square pyramidal and square planner arrangements. The cyclic voltammetry technique was used to study the electrochemical behavior of the Cu(II) ion in the absence/presence of HNP, whereas the chelation process in solution occurred spontaneously. Computational studies were applied using the Gaussian 09 program on the molecular structure of the isolated compounds based on the DFT/LAN2DZ/RB3LYP method to assess some chemical quantum parameters and perform correlation analyses between the theoretical and experimental FT-IR spectra. The values of R2 ranged from 0.99 to one, revealing a strong correlation between the theoretical and experimental data. Furthermore, molecular docking studies of the prepared compounds with the target proteins were performed using the MOE program. The docking results suggested that the VO(II) complex tended to be a biologically effective compound, wherein the VO(II) complex recorded inhibition grades of -6.16, -6.95, and -6.38 kcal/mol toward the target proteins and RMSD values of 0.92, 0.85, and 0.88 Å. Finally, the ligand and its complexes were screened for various biological assays, which highlighted the biological activity of the VO(II) complex. The VO(II) complex ranked as the highest antimicrobial with activity index values of 37.5, 59.1, and 26.9% against E. coli, Bacillus subtilis, and C. albicans, respectively. In addition, the VO(II) complex ranked as the highest antioxidant with an IC50 value of 63.09 μM and the highest capacity for DNA binding with an IC50 value of 43.8 μM. Furthermore, the VO(II) complex exhibited the highest cytotoxicity with IC50 values of 26.8, 21.8, and 32.4 μM against HePG-2, MCf-7, and Hela cell lines, respectively. Accordingly, this comprehensive study provides insight into the possible uses of these innovative chelates as potential therapeutics and enhances our comprehension of their molecular interactions and biological effectiveness.