Bose, Rathindra N.
Ph.D. (Doctor of Philosophy)
Department of Chemistry and Biochemistry
A series of mononuclear platinum(II) pyrophosphato complexes was synthesized and characterized by x-ray crystallography and phosphorous-31 and platinum-195 NMR spectroscopy. Phosphorous-31 NMR chemical shifts for these compounds lay in the range of 1.78–2.12 ppm for the fully deprotonated species. These compounds are remarkably stable with respect to hydrolysis in both the presence and absence of pyrophosphatase, with no loss of ligand observed in a week’s time at neutral pH. At pH 4, these compounds undergo slow acid-catalyzed hydrolysis resulting in the formation of pyrophosphato bridged dinuclear species. Platinum(II) pyrophosphato complexes were oxidized to trans-dihydroxo platinum(IV) analogues by reaction with hydrogen peroxide. This reaction follows second-order kinetics, with second-order rate constants lying between 2.3 and 4.9 M⁻¹s⁻¹. These rate constants were observed to be independent of pH in the range of 7-9. All compounds were observed to behave as diprotic acids, with pKₐ₁ values lying in the range of 1.2 to 2.9 and pKₐ₂ values in the range of 4.3 to 4.7. Proton NMR studies have shown that these complexes do not bind mononucleotides (dGMP, dAMP) or di-nucleotides (dGpG) within 48 hours at 25°C. In contrast, platinum(II) pyrophosphato complexes react readily with cysteine in a two-step process which first involves opening of the pyrophosphate chelate to form a monodentate intermediate with second-order rate constants lying between 1.4E-3 and 4.3E-3 M⁻¹s⁻¹, followed by deligation of the pyrophosphate ion. Reaction of platinum(IV) complexes with cysteine and glutathione occurs via reduction to platinum(II). These reactions are much slower than the corresponding reactions with platinum(II), with second-order rate constants on the order of 10⁻⁴ M⁻¹s⁻¹ for reaction with cysteine.
Mishur, Robert John, "Synthesis, characterization, redox kinetics, and assessment of DNA and thiol binding of a new class of platinum(II) and -(IV) pyrophosphato complexes" (2008). Graduate Research Theses & Dissertations. 5193.
xiv, 177 pages
Northern Illinois University
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