Effect of Leaving Ligands of Platinum(II) Diamine Complexes on DNA and Protein Residues

<p>Platinum compounds are widely used drugs in cancer treatments. Although DNA is the biological target, reaction of platinum compounds with proteins is also potentially significant. Our objective is to study the effects of leaving ligands on the relative reactivity between 5'-GMP (guanosine 5' phosphate), a key DNA target, and N-Acetyl - L-Methionine (N-AcMet), a key protein target. We have used NMR spectroscopy to monitor reactions with N-AcMet and 5'-GMP added to a platinum complex to see which products are formed preferentially. Previous research showed that both a non-bulky complex such as [Pt(en)(D₂O)₂]²⁺ [en=ethylenediamine], and a bulky complex such as [Pt(Me₄en)(D₂O)₂]²⁺ [Me₄en= N, N, N', N'-tetramethylethylenediamine] react more quickly with 5'-GMP than with N-AcMet. To improve the activity of platinum compounds in our current research, oxalates as leaving ligands are used. The results suggest that [Pt(en)(Ox)] [Ox= oxalate] reacts faster with N-AcMet than with 5'-GMP. Also, [Pt(Me₄en)(Ox)] reacts slowly with 5'-GMP without N-AcMet and the reaction favors N-AcMet when both ligands are added simultaneously. Interestingly, the formation of the sulfur-oxygen chelate is slow enough to be observable in the oxalate reaction; but the mono product is not independently observed in the dinitrate complex.</p>

Name thesis:degree_name

Master of Science

Discipline thesis:degree_discipline

Department of Chemistry

Year

2013

Author dc:creator

• Kolli, Ramya

Contributors dc:contributor

• Kevin M. Williams (Director), Rajalingam Dakshinamurthy, Stuart Burris

• Oxalates
• Cancer-Chemotherapy
• Chemistry- Analytic
• Platinum Compounds
• Cisplatin
• Analytical Chemistry
• Chemical Actions and Uses
• Chemicals and Drugs
• Chemistry
• Medicinal and Pharmaceutical Chemistry

Repository record dc:identifier

https://digitalcommons.wku.edu/theses/1268

OAI identifier oai:identifier

oai:digitalcommons.wku.edu:theses-2268