DNA hydrolysis promoted by di- and multi-nuclear metal complexes

DNA hydrolysis mediated by di- and multi-nuclear metal complexes is of increasing importance in biotechnology and medicine. Many systems for enzyme-mediated nucleic acid hydrolysis, including type 11 restriction endonucleases and phosphatases, contain di- and multi-nuclear metal active sites. Recent progress in the design of di- and multi-nuclear metal artificial nucleases has included Fe3+, Zn2+, Cu2+, Co3+ and Ln(3+/4+)-azamacrocyclic, aminocarboxylic and pyridyl- or benzimidazolyl-based organic ligands complexes and their conjugates to biomacromolecules. The focus in this article is on di- and multi-nuclear metal complexes that promote DNA cleavage via hydrolytic rather than oxidative pathway. Our purpose is to highlight the relationships between the structures of di- and multi-nuclear metal complexes and their functions, the cooperativities between metal and ligands and between metal sites in the course of DNA hydrolysis and the problems that are faced toward the development of di- and multi-nuclear metal-based artificial restriction enzymes by applying the principles of coordination chemistry and enzymatic chemistry. In order to be able to conveniently compare kinetic data that have been reported for many di- and multi-nuclear metal complexes, we propose two parameters alpha and beta that are associated with the kinetic studies on DNA hydrolysis. The former alpha is defined as the ratio of the hydrolytic rate constant mediated by a di- or multi-nuclear metal complex to that by the analogous mononuclear complex under identical or similar conditions, indicating the degree of cooperativity between metal sites. The latter beta is recognized as a rate enhancement over unhydrolyzed double-stranded DNA. (C) 2003 Published by Elsevier B.V.