This award will support collaborative research between Dr. Ronald M. Milburn of Boston University and Dr. Alan Sargeson of the Australian National University (ANU). The objective of the research is to better understand metal ion mediated synthesis of phosphate derivates. Previous collaborative work between Dr. Milburn and Dr. Sargeson demonstrated extraordinary hydrolytic reactivity for a phosphate ester in a cobalt(III)/ phosphate ester system. This work has been the basis for further advances made at ANU, at Boston University, and elsewhere, in the area of metal ion promoted reactions of phosphate derivates (especially in the hydrolysis of phosphate esters and polyphosphates). The emphasis of the prior collaboration was on degradation of phosphate derivatives; this project will focus on synthesis of phosphate derivatives mediated by metal centers, including reactions which can lead to the formation of new phorphorus bond frameworks. Systems to be studied will include phosphate ester complexes of cobalt(III), for both mononuclear and dinuclear complexes, in which reaction between the phosphate ester and a proximate coordinated phosphate may lead to diphosphate formation (and concomitant ester hydrolysis). While the research is exploratory, its potential is significant for results of considerable importance in further understanding of metal ion/phosphate interplay in biological systems. The project represents excellent U.S.-Australian collaboration. Previous collaboration in phosphate chemistry between Dr. Milburn and Dr. Sargeson led to a variety of new ways to activate phosphate derivatives, which have been used worldwide. This collaborative work with its emphasis on synthesis of phosphate derivatives has the potential for similar impact. Overall, this research will advance basic understanding of both synthesis and degradation of phosphate derivates through the use of metal ions. There is also additional opportunity for this project to have potential application to biotechnology related-problems, in particular, those centering around developing metal ion hydrolytic reagents for site-specific cleavage of DNA/RNA regions.
