This paper reports on the chemistry of platinum complexes containing bidentate pyridine-carboxylate (pyAc = pyridin-2-yl-acetate and picEt = pyridine-2-ethylcarboxylate, ethylpicolinate) (N,O) ligands. The pyridine-2-acetate and ethylpicolinate ligands form six- and five-membered chelates, respectively, upon formation of the Pt-carboxylate bond. In all reactions with picEt with various platinum complex starting materials, spontaneous de-esterification of the pendant carboxylate ester occurs to give directly the chelates K[PtCl2(pic-N,O)]-trans-[Pt(pic-N,O)(2)] and SP-4,2-[PtCl(pic-N,O)(NH3)] without any evidence of intermediates. The de-esterification is solvent dependent, and molecular modeling was used to explain this reaction. The reactions of the geometric isomers of [PtCl(pyAc-N,O)(NH3)) with 5'-guanosine monophosphate, 5'-GMP, and N-acetyl-L-methionine, AcMet, were investigated by NMR spectroscopy. The objective was to ascertain by model chemistry the feasibility of formation of ternary DNA-Pt-protein adducts in biology. Model nucleotide and peptide compounds were formed in situ by chloride displacement giving (PtL(pyAc-N,O)(NH3)](+) (L = 5'-GMP or AcMet). Competitive reactions were then examined by addition of the complementary ligand L. Sulfur displacement of coordinated 5'-GMP was slow. For SP-4,3-[Pt(AcMet)(NH3)-(PyAc-N,O)](+), a rapid displacement of the sulfur ligand by 5'-GMP was observed, giving SP-4,2-[Pt(5'-GMP-N7)-(pyAc-N,O)(NH3)](+).