FULL PAPER Tri‐ and diorganotin(IV) derivatives of non‐steroidal anti‐ inflammatory drug sulindac: Characterization, electronic structures (DFT), DNA binding and plasmid cleavage studies Ranjana Kumari | Mala Nath Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, India Correspondence Mala Nath, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, India. Email: malanfcy@iitr.ernet.in Tri‐ and diorganotin(IV) derivatives of non‐steroidal anti‐inflammatory drug sulindac (Sul), coordinated with carboxylate oxygen, namely C 23 H 25 FO 3 SSn (1), C 38 H 31 FO 3 SSn (2), C 32 H 43 FO 3 SSn (3), C 52 H 42 F 2 O 6 S 2 Sn (4), C 44 H 44 S 2 Cl 2 O 6 F 2 Sn 2 (5), C 48 H 50 F 2 O 6 S 2 Sn (6) and C 56 H 66 F 2 O 6 S 2 Sn (7), have been synthesized and char- acterized using analytical and spectroscopic (IR, 1 H NMR, 13 C NMR, 119 Sn NMR and ESI‐MS) techniques. Optimized geometry and electronic structures of the com- plexes 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‐coordi- nated with distorted trigonal bipyramidal geometry. Probable mode of DNA binding with ligand (Sul) and complexes 1–7 has been revealed via various biophysical tech- niques (UV–visible spectroscopy, fluorometry and circular dichroism). Intrinsic binding constants (K b ) obtained from UV–visible spectroscopy for Sul and com- plexes 1–7 are 3.69 × 10 4 , and 7.3 × 10 3 , 1.14 × 10 4 , 1.47 × 10 4 , 1.55 × 10 4 , 1.49 × 10 4 , 2.02 × 10 4 , 1.17 × 10 4 M -1 , respectively. The quenching constants (K sv ) 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 com- plexes 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 circu- lar DNA by an increase in nicked form and also by the appearance of linear form with increasing concentration of drug or complexes. KEYWORDS circular dichroism, DNA binding, DNA cleavage, organotin derivatives, sulindac 1 | INTRODUCTION Successful applications of metal complexes in the treatment of numerous human diseases have led to a very important progress in medicinal organometallic chemistry in the past few years, allowing the rational design of novel, non‐ conventional platinum compounds, as well as innovative non‐platinum metal‐based antitumor agents. Organotin(IV) compounds in general and organotin(IV) carboxylates in particular have emerged as potentially biologically active compounds among non‐platinum chemotherapeutic metallopharmaceuticals. Organotin compounds are of interest in view of their considerable structural diversity. Among them the most ubiquitous are the organotin(IV) carboxylates. [1] Depending on the carboxylic acid used and the stoichiometry of the reactants, several products such as monomers, dimers, tetramers, oligomeric ladders and hexameric drums have been isolated. [2] Organotin(IV) carboxylates have received in- creasing attention in recent years, due to their significantly important biological properties and their varied applications. Received: 12 May 2016 Revised: 16 September 2016 Accepted: 21 September 2016 DOI 10.1002/aoc.3661 Appl Organometal Chem 2017; e3661; DOI: 10.1002/aoc.3661 Copyright © 2017 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/aoc 1 of 17