Molybdenum Cofactor

Posted June 24th, 2010 at 3:59 pm.

Abstract: Jenny Chen
Mentor: Dr. Burgmayer
It has been evident that molybdenum cofactor (Moco) is crucial to the function of three enzymes: sulfite oxidase, aldehyde oxidase, and xanthine oxidase. Variations caused by mutations in different genes, molybdenum cofactor deficiency is a human disease that leads to sulphite intoxication, neurological damage, lens dislocation, abnormal physiognomy, and other abnormalities. Combined with the deficiencies of the molybdenum-containing enzymes mentioned, the rare genetic disease triggers health abnormalities and defects responsible for fatalities, especially in infants. And because most treatment methods have been unsuccessful, the understanding of Moco, its catalytic functions, and the important roles it plays on human health can help further research and the development of treatments for molybdenum cofactor deficiency in humans.

The molybdenum-containing enzymes share similar pterin at their catalytic sites, the molybdenum cofactor, and the transition metal molybdenum is only biologically active when complexed by the cofactor. The Burgmayer group has been investigating the structural and electronic nature of Moco and has created a model consisted of a molybdenum dithiolene complex, synthesized by reactions involving a molybdenum tetrasulfido compound and a pterinyl alkyne. Through the oxidation of the molybdenum from Mo0 to MoIV, the tetrasulfide ligand in the molybdenum tetrasulfido reagent is produced in a two-step pathway. As the most effect methodology, several pterinyl alkyne reagents have been synthesized in a six-step pathway, highlighting the Sonogashira cross coupling reaction as the last step. Some of the pterinyl alkynes used in the synthesis of the molybdenum dithiolene complex include DIFPEPP, PEPP, AEP, BOPP, BMOPP, BOQO, and BMOQO.

The objective of this research is to improve the efficacy of the molybdenum dithiolene complex synthesis. Using collective methodologies from previous research projects of the Burgmayer group members, including several procedures pioneered by Kelly Matz, this research focuses on a larger-scaled reproduction of the synthesis and the convergence of [Et4N]+[Tp*Mo+4(S)S4]-, the tetrasulfide, and BMOPP, a dimethylated, pterinyl alkyne, in hopes of products with better purity and higher yields. In addition, several experiments with other pterinyl alkyne reagents will be carried out with the objective of shielding and protecting the sulfurs in the molybdenum dithiolene complexes produced.

The first pathway has almost been successfully replicated with confirmations of compound identities using melting point, MS, IR, and 1H NMR. Members of this group have also continued to work on a replicable procedure to synthesis pure [Et4N]+[Tp*Mo+4(S)S4]-. There have been implementations of new techniques in order to monitor the synthesis of [Et4N]+[Tp*Mo+4(S)S4]-. During the past few years, this reaction was reduced from 7 days to 2-4 days due to the brown-to-green color change, the indication of completion. However, the MS data taken of our green product recently showed the presence of [Et4N]+[Tp*Mo(CO)3]-, which indicated that the reaction did not run to completion after 4 days. Finding a more effective way of synthesizing pure [Et4N]+[Tp*Mo+4(S)S4]- is important to the overall Moco model.

Filed under: 2010,Burgmayer, Dr. Sharon,Chen, Jenny Tags: by Lisa Klinman

Comments are closed.