Anticancer activity and biomolecular interaction of Pt(II) complexes: Their synthesis, characterisation and DFT study

Abstract

AbstractCis‐[Pt (TEEDA)Cl2]; 1 (where TEEDA = N,N,N′‐triethylethylenediamine) was synthesised, and its SCXRD structure was determined. Complex 1 crystallises in the monoclinic space group I2/a; (z = 8) and unit cell parameters are a = 15.1919(4) Å; b = 9.6049(3) Å; c = 16.7825 Å; α = 90.00°; β = 94.784(3)° and γ = 90.00°. Complex 1 was hydrolysed to diaqua species cis‐[Pt (TEEDA)(H2O)2]2+; 2 L‐cysteine (L‐cys) and N‐acetyl‐L‐cysteine (N‐ac‐L‐cys) chelated complex cis‐[Pt (TEEDA)(L‐cys)]+ 3 and cis‐[Pt (TEEDA)(N‐ac‐L‐cys)] 4 were synthesised and characterised by spectroscopic methods. Kinetic study of substitution reactions of Complex 2 to Complexes 3 and 4 have been explored with the thiols L‐cys and N‐ac‐L‐cys, respectively. The theoretical study with density functional theory (DFT) has been considered to optimise the structures of Complexes 1–4 for HOMO–LUMO energy calculation, TD‐DFT simulation and natural bond orbital (NBO) analysis to support structural characterisation of the complexes. Various electronic properties, known as DFT‐based descriptors, have been calculated from frontier molecular orbital energies to correlate with the adduct formation aptitude of the complexes with DNA and BSA. The binding aptitude and binding mode of the complexes with DNA and BSA have been performed by UV‐Vis and spectrofluorometric titration methods. To observe the interaction of the complexes with CT‐DNA, gel electrophoresis experiment has been carried out. A molecular docking study of the complexes was performed with DNA and BSA. The anticancer activity and ROS generation of the complexes were investigated on different cancer cell lines and fibroblast cells with DCF‐DA using FITC filter.