Intercalative binding of two new five-coordinated anticancer Pt(II) complexes to DNA: experimental and computational approaches

Binding interaction of two organoplatinum complexes, [Pt(C<^>N)Cl(dppa)], 1, and [Pt(C<^>N)Cl(dppm)], 2, (C<^>N = N(1), C(2 ')-chelated, deprotonated 2-phenylpyridine, dppa = bis(diphenylphosphino)amine, dppm = bis(diphenylphosphino)methane), as anti-tumor agents, with calf thymus DNA (CT-DNA) under pseudo-physiological conditions has been investigated using various biophysical techniques viz., UV-Vis and fluorescence spectroscopies, viscosity measurements, and thermal denaturation experiments. A hypochromic shift in UV-Vis absorption titration, fluorescence enhancement of Pt(II) complexes in the presence of CT-DNA, fluorescence quenching in competitive ethidium bromide displacement assay, and an uptrend in the viscosity (eta) and melting temperature (T-m) indicated the existence of a tight intercalative interaction of Pt(II) complexes with CT-DNA. The fluorescence quenching of CT-DNA was a combined quenching of static and dynamic with Stern-Volmer quenching constants of 7.520 x 10(3) M-1 for complex 1 and 5.183 x 10(3) M-1 for complex 2, at low concentrations of Pt(II) complexes. Besides the experimental studies, computational studies were done. Molecular modeling studies confirmed the intercalation of the studied complexes by the phenyl groups of dppa and dppm, leading to pi-pi interactions but with a certain steric hindrance because of the size and shape of the considered complexes. The combination of experimental and computational data showed that reported Pt(II) complexes are promising structures and could be developed for cancer therapeutic applications.