Pyridine-carboxylate complexes of platinum. Effect of N,O-chelate formation on model bifunctional DNA-DNA and DNA-protein interactions.
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[PtCl(2)(pic-N,O)]-trans-[Pt(pic-N,O)(2)] and SP-4,2-[PtCl(pic-N,O)(NH(3))] 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)(NH(3))] 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)(NH(3))](+) (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)(NH(3))(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)(NH(3))](+).
Quintal
Susana M O
SM
Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
Qu
Yun
Y
Quiroga
Adorácion G
AG
Moniodis
Joseph
J
Nogueira
Helena I S
HI
Farrell
Nicholas
N
D002264:Carboxylic Acids / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D005240:Feasibility Studies; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry
D002264:Carboxylic Acids; D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D011506:Proteins; D011725:Pyridines; D010984:Platinum; D004247:DNA