## Doctoral Dissertations

#### Title

Non-random double strand cleavage of DNA by a monofunctional metal complex: Binding, mechanistic, and molecular recognition studies of ((2S,8R)-5-amino-2,8-dibenzyl-5-methyl-3,7-diazanonanedioate)copper(II)

January 1998

#### Keywords

Biology, Molecular|Biology, Genetics|Chemistry, Biochemistry

Ph.D.

#### Abstract

Double strand breaks in duplex DNA are thought to be significant sources of cell lethality because they appear to be less readily repaired by DNA repair mechanisms. A study of the binding, mechanistic, and molecular recognition of ((2S,8R)-5-amino-2,8-dibenzyl-5-methyl-3,7-diazanonanedioato)copper(II) (1), which effects nonrandom double strand cleavage of duplex DNA is presented. Complex 1 creates double strand breaks via hydroxy radical $\rm (OH\cdot)$ produced through Haber-Weiss chemistry, which is directed to the DNA strand by hydrophobic and electrostatic binding recognition elements. The cleavage chemistry has also been studied kinetically, giving half-lives of 34.5, 20.8 and 100 min for single-strand breaks, double strand breaks, and base propenal release, respectively. Molecular recognition by the complex has been studied with relaxation and $\sp2$H NMR methods; these studies indicate that the scD, scL-phenylalanine-derived hydrophobic side chains interact with the DNA surface in an asymmetric fashion. ^

COinS