Molecular mechanics and dynamics calculations have been used to study the 9-Ethylguanine and N-Ac-L-methionine complexes that could react with chloro[2-(4-methyl-1,4-diazepan-1-yl)ethanamine]platinum(II). The AMBER force field has been supplemented with previous modifications for platinum complexes. By utilizing the modifications made previously to the AMBER force field, we were able to model the Chloro[2-(4-Methyl-1,4-diazepan-1-yl)ethanamine]platinum(II) complex and possible reaction products with methionine and 9-Ethylguanine adducts. Experimental studies have revealed that the triamine ligand can be partially displaced by methionine or guanine, and MM studies suggested the reason for the partial dissociation could include significant interligand strain.  Thus, products modelled include those formed by displacement of one nitrogen atom, the chloride atom, or both.  All possible rotamers and chirality combinations were generated for possible reaction products. For the methionine adducts, we found that certain orientations of the methionine residue led to much lower energy structures, and the differences in minimum energy structures of rotamers could help explain the experimental observation that an initial methionine product can be replaced by a more stable product.  Complexes with two 9-ethylguanine residues coordinated to the platinum generally showed less strain than those with two methionine residues, consistent with the experimental observation of the former but not the latter.

Molecular mechanics analysis of a platinum triamine complex and its possible products with biologically relevant targets

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.