Metal ion binding affinities and activation of phosphate esters studied by threshold collision-induced dissociation and ab initio theory

ANYL 351

Mary T. Rodgers, mrodgers@chem.wayne.edu, Chunhai Ruan, ruanch@chem.wayne.edu, and Hai Huang. Department of Chemistry, Wayne State University, 5101 Cass Avenue, 33 Chemistry, Detroit, MI 48202
Metal ions bind to DNA and regulate gene expression, act as drugs, or are used as tools for molecular biology studies. Binding of metal ions to the phosphate backbone can lead to cleavage of the phosphodiester linkages. If preferential cleavage of the 3’- or 5’-phosphodiester linkages can be achieved, facile sequencing of the nucleic acid becomes possible. The collision-induced dissociation (CID) of metal cationized phosphate esters is studied to characterize the strength of the metal ion-phosphate ester interactions and their ability to produce selective cleavage of the phosphodiester bonds. Results for triethyl phosphate (TEP), chosen as a model for the 5’-phosphodiester linkage, are presented. Two types of reactions are observed: simple noncovalent metal ion-phosphate ester bond cleavage and activated dissociation of the phosphate ester resulting in the elimination of neutral ethene molecules. The measured cross section thresholds are analyzed to extract absolute binding energies and/or activation energies for these systems.