Structural Chemistry and Biological Screening of Organotin(IV) Derivatives of Amide-based Carboxylates

Abstract

In the present study, twenty seven novel triorganotin(IV) amide-based carboxylates of general formula R3SnL were synthesized by reacting triorganotin(IV) chloride with carboxylates ligands (1:1 ratio) in dry methanol. The ligands used were (Z)-4-(4- methoxyphenylamino)-4-oxobut-2-enoic acid (IL1 ), (Z)-4-(3,5- bis(trifluoromethyl)phenylamino)-4-oxobut-2-enoic acid (IL2 ), (Z)-4-(p-toluidino)-4- oxobut-2-enoic acid (IL3 ), (Z)-4-(4-fluorophenylamino)-4-oxobut-2-enoic acid (IL4 ), 4-(1,3-dioxoisoindolin-2-yl)butanoic acid (IL5 ), 4-(4-methoxyphenylamino)-4- oxobutanoic acid (IL6 ), 4-(3,5-bis(trifluoromethyl)phenylamino)-4-oxobutanoic acid (IL7 ), 4-(p-toluidino)-4-oxobutanoic acid (IL8 ), 4-(4-fluorophenylamino)-4- oxobutanoic acid (IL9 ). The synthesized compounds were characterized by FT-IR, elemental analysis, NMR (1H, 13C, 119Sn &19F) and single crystal X-ray crystallography. The ligands coordinate to tin atom through oxygen (carboxylate and amide) showing distorted trigonal bipyramidal geometry with polymeric bridging behavior in solid state. However, the geometry is switched over from trigonal bipyramidal to tetrahedral upon dissolution as confirmed by multinuclear (1H, 13C, 19F and 119Sn) NMR. These synthesized organotin(IV) amide-based carboxylate complexes were selected for in vitro cytotoxic studies against various cell lines such as breast cancer cell lines (MCF-7) and human endometrial stromal cells (hESCs) by the MTT [Tetrazolium [3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The trimethyltin(IV) carboxylate was less active whereas tributyltin(IV) carboxylate and triphenyltin(IV) carboxylate complexes composed of carboxylate ligand having fluoro group were found to be most active against breast cancer cell lines as compared to iv standard drug (cisplatin). Some of the complexes showed less cytotoxicity against normal cell lines as compared to cancer cell line which need to be further evaluated. The prepared ligands and complexes were screened for antimicrobial activities against various strains of bacteria and fungi, and were found active. The tributyltin(IV) carboxylates unveiled the most active antimicrobial agents followed by triphenyltin (IV) carboxylates while trimethyltin(IV) carboxylates are the least active antimicrobial agents. The antileishmanial activities were evaluated which showed that tributytin(IV) carboxylates and triphenyltin carboxylates are the most active compound followed by trimethytin(IV) carboxylates. The synthesized ligands and their complexes were subjected to in vitro total antioxidant capacity, total reducing power and free radical scavenging activities. Some of the compounds were efficient and demonstrated their antioxidant strength equal to standard one (Ascorbic acid). Certain complexes were even much better antioxidant and near to the standard. However, a mix behavior was found among the three types of complexes. Additionally, hemolytic and shrimp assays were accomplished for the triorganotin(IV) carboxylates complexes so as to assess the cytotoxicity of the compounds. The successful synthesis of these complexes also open the question of thermal stability and to find it’s the electronic properties. Using DFT (Density-Functional Theory) we investigate the structural thermal stability and electronic structures of the complexes 1 & 4. The structural optimization and low formation energies predict that these compounds 1 and 4 are thermodynamically stable. The electronic calculations show that these complexes are non-magnetic and direct band gap semiconductors. However, we found the band gaps of 1.87 eV for complex 1 and 2.73 eV for complex 4. These values of the band-gaps are smaller by ~1 eV from experimentally observed values of v 2.92 eV and 3.8 eV for Complex 1 and complex 4 respectively which were expected. The charge-density predicts that H-O2 bonding in both 1 and 4 complexes have van der Walls nature of bonding. Finally, we also calculated the HOMO (highest-occupied molecular orbital), LUMO (lowest-unoccupied molecular orbital), Fermi level energy, and work function for 1 and 4 complexes to find its possible applications in electronic devices. Similarly we have also reported the DFT results on electronic structures and other properties of complexes 6, 7, 8, 9, 10, 11 and 12 which is comparable with the experimental data. DFT studies also confirmed an excellent correlation with the structural parameters obtained from XRD crystallographic data for different complexes.