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Cis-[Pt (TEEDA)Cl 2 ]; 1 (where TEEDA = N,N,N 0 -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)(H 2 O) 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. K E Y W O R D S anticancer activity, DNA and BSA binding, kinetics and mechanism, MTT assay and DFT study, Pt(II) complex Saikat Mandal and Venkata P. Reddy B. contributed equally to this research work.

The potent bidentate carrier ligand 2-picolylamine (pic) has been used to synthesize Pt(II) complexes to know their bioactivity and anticancer property as reflected by PASS prediction software. The dichloro Pt(II) complex [Pt(pic)Cl 2 ], Pt-1, and its hydrolyzed diaqua complex [Pt(pic)(OH 2 ) 2 ] 2+ , Pt-2, were synthesized. The thiol-containing Pt(II) complexes [Pt(pic)(Lcys)] + , Pt-3, and [Pt(pic)(L-ac-L-cy)] + , Pt-4, were synthesized from Pt-2, which was obtained from hydrolysis of Pt-1. Their biomolecular interactions with BSA and DNA were executed by spectroscopic methods, and their cytototoxic property was tested by the MTT assay. In vitro biomolecular interactions of Pt(II) complexes with BSA and DNA were investigated by different spectroscopic and viscosity measurement methods for their pharmacokinetic and pharmacodynamic importance. The conformational change of BSA in the presence of a drug candidate was studied by Forster resonance energy transfer calculation and synchronous and three-dimensional fluorescence spectroscopic studies. A theoretical approach on optimization structures, highest occupied molecular orbital−lowest unoccupied molecular orbital energy, global reactivity parameters, time-dependent density functional theory, and molecular docking with BSA and DNA was executed to strengthen and support the experimental observations. In vitro cytotoxic profiles of the complexes like the anticancer activity and their level of reactive oxygen species production were brought under consideration on A549 cancer cells and the normal human embryonic kidney cell line HEK-293. The cytotoxic property was compared with that of the recognized anticancer drug cisplatin.

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