Structural and solution study on binary peptide and ternary peptide–nucleobase complexes of palladium(II)

Abstract

The dipeptide complex [Pd(gly-L-hisN^α)Cl]·1.5H₂O 1(gly-L-hisN^α= monoanion of glycylhistidine, deprotonated at the amide N) has been prepared and structurally characterized. Co-ordination of Pd is through the terminal amino group of the glycyl entity. N(π) of the imidazole ring of the histidine, and the deprotonated amide nitrogen. Reactions of 1 with the model nucleobases 1-methyluracil (Hmura), 1-methylcytosine (mcyt), 9-methyladenine (made), 9-ethylguanine (Hegua) and 6-methoxy-9-methyl-guanine (momgua) have been studied in solution by ¹H NMR spectroscopy. The mcyt complex, [Pd(gly-L-hisN^α,O)(Mcyt)]·3.5H₂O (gly-L-hisN^α,O = dianion of glycylhistidine, deprotonated at the amide N and the carboxylic acid group) has been structurally characterized. Nucleobase co-ordination is via N³. Proton NMR spectra of complexes of 1 with all model bases are indicative of rotamer formation and, with the purine bases, of linkage isomerism (N⁷, N¹ and simultaneously with N⁷/N¹). In weakly acidic, neutral or slightly alkaline media or with an excess of 1, Hegua and, most likely, also made form complexes of Pd₃(nucleobase) stoichiometry with Pd binding through N¹ and N⁷ and the third Pd linked to one of these Pd(gly-L-his) entities. As a consequence, the resonances of some of the aromatic protons of the histidine imidazole ring are shifted upfield by as much as 1 ppm. Complex stability constants have been determined by means of ¹H NMR spectroscopy for a number of 1:1 complexes of 1 with model nucleobases. Competition experiments carried out at pD 7.1 indicate that 1 binds to the four model nucleobases in the following preference: Hegua-N⁷≈ mcyt-N³ made-N¹ > made-N⁷ > mura-N³.