Tri‐ and diorganotin(IV) derivatives of non‐steroidal anti‐inflammatory drug sulindac: Characterization, electronic structures (DFT), DNA binding and plasmid cleavage studies

Abstract

Tri‐ and diorganotin(IV) derivatives of non‐steroidal anti‐inflammatory drug sulindac (Sul), coordinated with carboxylate oxygen, namely C23H25FO3SSn (1), C38H31FO3SSn (2), C32H43FO3SSn (3), C52H42F2O6S2Sn (4), C44H44S2Cl2O6F2Sn2 (5), C48H50F2O6S2Sn (6) and C56H66F2O6S2Sn (7), have been synthesized and characterized using analytical and spectroscopic (IR, 1H NMR, 13C NMR, 119Sn NMR and ESI‐MS) techniques. Optimized geometry and electronic structures of the complexes obtained from density functional theory calculations indicate that complexes 1, 2, 3 and 7 are tetra‐coordinated with monodentate carboxylates, 4 and 6 are hexa‐coordinated with highly distorted octahedral geometry, whereas 5 is penta‐coordinated with distorted trigonal bipyramidal geometry. Probable mode of DNA binding with ligand (Sul) and complexes 1–7 has been revealed via various biophysical techniques (UV–visible spectroscopy, fluorometry and circular dichroism). Intrinsic binding constants (Kb) obtained from UV–visible spectroscopy for Sul and complexes 1–7 are 3.69 × 104, and 7.3 × 103, 1.14 × 104, 1.47 × 104, 1.55 × 104, 1.49 × 104, 2.02 × 104, 1.17 × 104 M−1, respectively. The quenching constants (Ksv) using fluorometric titrations, calculated from competitive binding of ethidium bromide versus Sul/complexes with calf thymus DNA, also correspond to the above results. Circular dichroism spectral patterns of calf thymus DNA with Sul and complexes 1–7 have also been investigated. All the results reveal that the complexes bind with DNA through partial intercalative mode. pBr322 plasmid fragmentation has also been studied using gel electrophoresis, which shows the fragmentation of circular DNA by an increase in nicked form and also by the appearance of linear form with increasing concentration of drug or complexes.