Molecular mechanics and dynamics calculations were used to simulate reactions of oxaliplatin and Pt(Me2dach)(oxalate) with methionine and guanine, where Me2dach is N,N-dimethyl-1,2-diaminocyclohexane. The results were consistent with steric effects that resulted in chelation when Pt(Me2dach)(oxalate) reacted with N-acetylmethionine experimentally (Williams et al., 2013). The energy difference due to ligand bulk that was predicted using molecular mechanics was also consistent with experimental results: oxaliplatin’s ligand bulk did not prevent the formation of bis products with 9-ethylguanine and N-acetylmethionine, but the ligand bulk of Pt(Me2dach)(oxalate) did prevent bis product formation with N-acetylmethionine, resulting in chelation with the sulfur and oxygen atoms of the methionine residue (Williams et al., 2013).Pt(Me2dach)(oxalate) did not prevent bis products with 9-ethylguanine (Williams et al., 2013).
Advisor(s) or Committee Chair
Dr. Kevin Williams
Jackson, Daniel C., "Molecular Mechanics of Oxaliplatin and an Oxaliplatin Derivative with Their Relevant Biological Targets" (2013). Honors College Capstone Experience/Thesis Projects. Paper 417.