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.

Triorganotin complexes in cancer chemotherapy: Mechanistic insights and future perspectives

“…Trimethyltin, triphenyltin, and tri-n-butyltin derivatives of sulindac (110-112) exhibited significant hypochromicity and moderate redshifts, indicating that the complexes bind to DNA via a partial intercalative mode; their binding constants were 7.3 × 10 3 , 1.14 × 10 4 , and 1.47 × 10 4 M −1 , respectively. [139] The triphenyltin complex, when reacted with guanosine and 1,10-phenanthroline in aqueous methanol (113), was reported to interact with DNA via a nonclassical electrostatic interaction with an intrinsic binding constant of 2.46 × 10 5 M −1 (UV spectroscopy). [140] Additionally, a Stern-Volmer quenching constant of 2.9 × 10 6 M −1 (fluorescence spectroscopy) suggested an intercalation mode of binding.…”

New diorganotin(IV) complexes of Schiff base derived from 4‐amino‐3‐hydrazino‐5‐mercapto‐4H‐1,2,4‐triazole: Synthesis, structural characterization, density functional theory studies, atoms‐in‐molecules analysis and antifungal activity

“…The functional B3LYP has been credibly reported previously for electronic structure calculations of several organotin(IV) complexes with hetero donor atoms. [34][35][36]59,63] The frequency analysis indicates that the optimized geometric configuration is the local minima on the potential energy surface of R 2 Sn(L)Cl complexes. The optimized geometrical parameters and bond lengths in the coordination sphere of the studied complexes are presented in Table S7.…”

“…The diagnostic fragment ions observed in the mass spectra of complexes 1 and 2 have been reported previously for several complexes containing the R 2 Sn(IV) 2+ moiety. [57][58][59]…”

Structure and applications of organotin complex based on trimethyltin cation and quinaldic acid

“…Organotin complexes have attracted much consideration attributable to their properties, structural chemistry and potential applications in numerous scientific areas . Among the many potential applications are in gas storage, as cytotoxic agents and in chemical catalysis, as well as their industrial and agricultural applications .…”