Physicochemical properties of the ternary complexes of Pt(ii) with uracil and small peptide moieties: an experimental and computational study

Abstract

A combined experimental and theoretical approach has been adopted to study the formation of mixed ligand peptide–nucleobase complexes of platinum(II), considering uracil as the primary ligand and dipeptides such as glycyl-L-valine, glycyl-L-leucine and L-alanyl-L-glutamine as secondary ligands. The ternary complexes prepared in both solid and aqueous phases, by following two synthetic procedures i.e. solvent-free mechanochemical and co-precipitation methods, respectively, exhibit similar physicochemical and spectral properties providing evidence of metal-coordination through the N₃ and O₄ atoms of uracil as well as the NH₂ and CO₂⁻ functions of the dipeptide molecules. Using the biologically relevant right-handed α-helical conformers of the dipeptides, gas and aqueous phase quantum mechanical modeling studies are undertaken employing the B3LYP and B3PW91 methods in conjunction with the 6-31++G(d,p) and LANL2DZ basis sets to elucidate the roles of metal-coordination and solvation in influencing the structural, electronic and vibrational properties of the complexes. The Pt(II) ion is found to exist in its low-spin state in the complexes. Effects of the explicit aqueous environment on the structural aspects of the complexes are also investigated. The B3LYP functional emerges to be more efficient in describing the vibrational spectra of the studied systems as compared to the B3PW91 method. Absorption titration experiments followed by in silico docking and molecular mechanical studies reveal that the synthesized complexes are able to bind to DNA minor-groove, primarily through H-bonding interactions.