NMR STUDIES OF PLATINUM(II) COMPLEXES OF NUCLEOSIDES AND NUCLEOTIDES
Abstract
Proton and ('13)C NMR spectroscopy were used extensively in studying the interactions of various concentrations of enPt(II) and cis-(H(,3)N)(,2)Pt(II) with 25 mM purine and pyrimidine nucleoside and nucleotide solutions. These studies were made over wide pH and concentration ranges. The reactivity of the Pt(II) complexes is kinetically, not thermodynamically controlled. Both cytidine and uridine react with enPt(II) in aqueous solution. Cytidine reacts fairly rapidly, its reactions being complete after a few hours, while uridine requires many days for its reactions to reach completion. Both nucleosides are bound at N-3 by the metal ion. In each system both the mono and bis nucleoside complexes are formed. NMR evidence is given for a secondary binding site on cytidine but not for uridine. The effect of pH upon the ('1)H resonance of the en ligand is also discussed. The effects of platination on the chemical shift of the cytidine protons is small when compared to protonation at N-3. No reaction occurred at the C-5 position of either pyrimidine ring. A greater ring current diamagnetic anisotropy was observed in the enPt(II)/Urd system than in the corresponding enPt(II)/Cyd system. The reactions of 5'-GMP, 5'-AMP, 1-MeAMP, 5'-IMP and Ado with enPt(II), cis-(H(,3)N)(,2)Pt(II) and trans-(H(,3)N)(,2)Pt(II) were investigated. Binding at N-7 of the four purine nucleotides was verified using ('1)H NMR when r (LESSTHEQ) 0.5. The bis complex was formed exclusively for 5'-GMP, 5'-AMP and 5'-IMP at r (LESSTHEQ) 0.5. At r > 0.5 very broad resonances occurred in the NMR spectra which were indicative of a polycondensation reaction. A stacked arrangement of purine rings bound through the N-1 and N-7 positions by Pt(II) was proposed. No evidence was obtained for chelation through N-7 and O-6 at r > 0.5. The reactions with Ado were very complex and indicated that multiple binding sites, probably N-1 and N-7, were involved in binding at all metal ion concentrations studied. When 5'-AMP was reacted with the platinum complexes, only the trans-(H(,3)N)(,2)Pt(II)/5'-AMP system displayed complexity similar to that observed for the Ado system. Reactions of the Pt(II) complexes with 5'-IMP was very similar to those observed for 5'-GMP. Study of a model system containing a 2:2:3:3 ratio of 5'-GMP, 5'-CMP, 5'-AMP and 5'-UMP showed that enPt(II), cis-(H(,3)N)(,2)Pt(II) and trans-(H(,3)N)(,2)Pt(II) reacted only with the purine rings. The cis isomer and enPt(II) reacted with almost equal amounts of GMP and AMP at pH 7.0 while the trans isomer favored GMP. At the metal ion concentrations studied only the bis complexes, e.g., {enPt(GMP)(,2)}('2-), {enPt(AMP)(,2)}('2-) and {enPt(GMP)(AMP)}('2-), were formed.
Degree
Ph.D.
Subject Area
Chemistry
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