Reactions of platinum(II) complexes with sulfur- and nitrogen- containing biomolecules: Selective intermolecular migration of the thioether-bound platinum(II) complex to the n7 nitrogen atom of guanosine-5'-monophosphate

Abstract

© 2018, University of Kragujevac, Faculty of Science. All rights reserved. The interactions of platinum(II) complexes with nitrogen- and sulfur-containing biomolecules are responsible for aider antitumor activity due to attack on DNA or a variety of toxic side eff ects. Therefore, the monofunctional Pt(II) complexes, [Pt(Gly-Gly-N,N,O)I]+ (Gly-Gly is the dipeptide glycyl-glycine coordinated through the oxygen and two nitrogen atoms) and [Pt(Gly-L-Met-S,N,N)Cl] (Gly-L-Met is the dipeptide glycyl-L-methionine coordinated through the sulfur and two nitrogen atoms) have been used to study their interactions with S-methylglutathione (GS-Me) and guanosine- 5'-monophosphate (5'-GMP). All reactions have been studied by 1H NMR spectroscopy and at room temperature in 50 mM phosphate buff er at pD 7.4. The investigation of the competitive binding of 5'-GMP and GS-Me to the Pt(II) complexes (1:1:1 molar ratio) has shown that in the initial stages of the reaction the corresponding Pt(II) complex only reacts with GS-Me, and second step of the reaction is very slow intermolecular displacement of the S-bound thioether ligand with N7 atom of the guanine base of 5'-GMP. The obtained results have been analyzed in relation to the antitumor activity and toxicity of Pt(II) complexes.