Extended Structures Built on the Triphenoxymethane Platform: Modeling Metalloenzyme Active Sites

University Of Florida, Gainesville FL

Investigators

Abstract

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Michael Scott at the University of Florida to develop nitrogen donor ligands with the ability to hold metal ions in proximity to foster cooperativity during catalysis and to mimic metalloenzyme active sites. Amino acid groups will be incorporated onto the triphenoxymethane platform and these constructs will be used for both reactivity and binding studies. In analogy to the trinuclear metal catalysts found in multi-copper oxidases and metallophosphatases, several different examples of trinuclear Zn(II), Cu(II), and Cu(I) compounds will be synthesized. Using the triphenoxymethanes, an effort is also underway to build small ligands with three peptide arms. When amino acid groups are attached to triphenoxymethanes, the platform engenders a high degree of solubility and favorable intra-arm hydrogen-bonding contacts and the pre-organization of the groups to facilitate the binding of metals to the three arms and impart the important properties of chiral amino acids onto the metal centers. These same ligands will also be used to prepare trimetallic catalysts for the hydrolysis of phosphate esters such as RNA, since sequence selective catalysts for RNA hydrolysis have many important potential applications in in vitro and in vivo gene technology. Functional models will be developed for multi-copper oxidases, which are an extremely important family of oxygen-utilizing enzymes that are primarily found in higher order eukaryotic cells, especially plants, fungi, and vertebrates, and all are used for single electron oxidations of substrates. Students will develop a strong background in both organic and inorganic synthesis and characterization methods and will also become skilled at the collection and refinement of crystallographic data. A collaboration to increase the participation of female students and students from historically black colleges in the undergraduate and graduate research programs at the University of Florida allows faculty and students from Lincoln University to participate in this research during the summer. The students in the normal REU programs administered by the PI, both French and American, also will be involved in this research during their three-month summer stay.