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A Laser Raman spectroscopic study of the pH induced structural changes in Guanosine-5’ monophosphate and its derivativesPambi, Daniel 01 December 1988 (has links)
The purpose of this study was to determine the protonation sites in guanosine-5'-monophosphate (5'-GMP), and to correlate the ease of protonation with the chemical nature and composition of substituent groups. The laser Raman spectra of 5'-GMP, 7-methyl-guanosine-5'-monophosphate (m7-GMP), and 8-bromoguanosine-5'-monophosphate (8-Br-GMP) at various pH and pD values were recorded with a Spex Ramalog-6 spectrometer. Based on the spectral changes observed in these studies, the preferred order of protonation sites for 5'-GMP and 8-Br-GMP is N7, 06 and N3. In the case of m7-GMP, the preferred sites are 06 and N3. The opening of the imidazole ring in m7-GMP is observed at pH value of about 9.4. It appears that the presence of the methyl group has a stabilizing effect on the protonated (keto) species. As expected, the vibrational modes of the phosphate group are unaffected by substituents on the guanine part of 5'-GMP. The complete spectra and vibrational assignments for 5'-GMP, m7- GMP and 8-Br-GMP are presented in this thesis.
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Leaving Ligand Effects on Reactivity and Solubility of Monofunctional Platinum(II) Anticancer ComplexesMillay, Heidi Linn Hruska 01 October 2019 (has links)
Monofunctional platinum(II) complexes, such as phenanthriplatin and pyriplatin, have notably different characteristics from the bifunctional anticancer complexes, such as cisplatin and oxaliplatin, which have detrimental toxicities and resistance associated with them. The unique properties of the monofunctional complexes may be exploited to target cancer cells without producing the toxic side effects associated with the current FDA-approved platinum-based anticancer drugs. To advance the understanding of these monofunctional platinum(II) complexes, this study replaced the chloride leaving ligand with an acetate group, which should increase solubility and alter the rate of reactivity with key amino acid and nucleotide targets. Phenanthriplatin and pyriplatin compounds were reacted with silver acetate to form insoluble silver chloride and the desired complex. Proton nuclear magnetic resonance (1H NMR) spectroscopy was used to characterize the new complexes and conduct kinetic assays with guanosine 5'-monophosphate (5’-GMP). A rate constant of 2.9 (± 0.7) x 10-2 M-1s-1 was determined for the reaction between pyriplatin and 5’-GMP, previously. A preliminary rate constant of 1.8 (± 0.1) x 10-2 M-1s-1 was determined for the newly synthesized cis-[Pt(NH3)2(py)OAc]+ complex with 5’-GMP. Ligand exchange kinetics directly influences the anticancer activity and toxicity of platinum drugs. Initial results indicate that the solubility is increased, and the rate of reaction is decreased by the acetate ligand.
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