Organic Synthesis, Peptide/Amino acid Catalysis, Supramolecular Chemistry, Material Chemistry, Biochemistry
Our research centrally involves application-directed molecule design and synthesis. We are also interested in discovery/development of catalysts for important organic and biology relevant reactions. Currently, there are three research directions in our laboratory.
Peptide-based asymmetric catalysis
Peptide-based asymmetric catalysts offer intriguing analogies to enzymatic systems. Peptide catalysts are based on the ability of peptides to form conformationally stabilized chiral environment for the catalytic moiety and well-defined secondary structures for the interaction between the substrate and catalyst to stabilize the preferred transition states.
In our laboratory, we are interested in simplifying catalytic peptide system using the following strategies:
- Utilize metals to attain rigid conformation for the catalytic center with the coordination sphere of the metal serving as the “secondary structure”.
- Implement a conformationally rigid scaffold to lock the conformation of the catalytic center.
- Employ bulky group(s) at a remote position to tune the catalytic activity and enantio-selectivity.
We aim to:
- Expand the scope of peptide-catalyzed reaction such that the new catalysts are not limited to substrates that can form hydrogen bond with them, they can also be applied to unfunctionalized substrates.
- Explore new reactions that can be catalyzed by peptide/amino acids.
- Study structure-activity relationships in peptide-catalyzed reactions and provide insights into catalytic mechanisms.
Porphyrin-based supramolecules as molecular·devices for solar energy conversion
In molecular-based photovoltaic devices, one of the most established examples is dye-sensitized solar cells (DSSC). In these systems, a monolayer of the light absorbers (dye molecules) self-assembles on high surface area electrodes based on nanocrystalline, mesoporous metal oxide such as TiO2 and the energy is transferred from the dye to the metallic system. Two of the major concerns in developing dye-sensitizer molecular systems are: broad spectral overlap with solar irradiation and efficient electron-transfer within the system.
One of the strategies employed to improve the function of supramolecular dye system is the addition of secondary donor/acceptor species. A transition metal center linked to an organic chromophore such as porphyrin will also largely add to the number of electron or energy transfer reactions within the assembly.
We aim to design and syntheses novel classes of supramolecules incorporating both porphyrin and Ru (II)-trisbipyridine species as dye sensitizer for photonic devices.
Identification and development of small molecule inhibitors targeting NS2-3 protease of Hepatitis C virus as potential therapeutic agents
Chronic infection with hepatitis C virus (HCV) has emerged as a major health problem as it can lead to un-curable cirrhosis and liver cancer. An estimated 170 million people worldwide have been infected with HCV. HCV is the leading cause of liver transplantation and results in up to 10,000 deaths annually in the U.S. Current treatments (interferon a alone or with ribavirin) have met with limited success and often with undesired side effects. Despite intense efforts dedicated to it in the past decade, many aspects of the disease as well as the biological life of the virus remains unclear.
This has made the drug discovery extremely challenging. Antiviral agents that directly block essential viral enzymes have demonstrated a straightforward approach to developing new therapies for Hepatitis C. The viral RNA genome encodes a polyprotein including two proteases essential for virus replication: the NS2-3 protease and the NS3-4A protease. In our laboratory, we aim to identify and develop potent small molecule inhibitors targeting Hepatitis C Virus NS2-3 Protease, for which there are no reported inhibitors, as potential therapeutic agents. The design of these molecules is based on the newly resolved crystal structure of the catalytic domain of HCV NS2-3 protease. The concepts of “multivalency” and “multifunction” are implemented into the design.
H. J. H. Wang, L. Jaquinod, M. Olmstead, M. Graca. H. Vicente, K. M. Smith and K. M. Kadish, “Synthesis and structure of b, b'-fused metallocenoporphyrins and their derivatives”, Inorganic Chemistry 2007, 46, 2898.
James P. Collman, Li Zeng, Hong J. H. Wang, Aiwen Lei, and John I. Brauman, “ Kinetics of (porphyrin)manganese(III)-catalyzed olefin epoxidation with a soluble iodosylbenzene derivative”, European Journal of Organic Chemistry 2006, 2707-2714.
James P. Collman, Hong J. H. Wang, Richard A. Decreau, Todd A. Eberspacher, Christopher J. Sunderland, “Synthesis and characterization of RhIII corroles: unusual reactivity patterns observed during metallation reactions”. Chemical Communications. 2005, 2497-2499.
H. J. H. Wang, L. Jaquinod, D.J. Nurco, M.G.H. Vicente and K.M. Smith, “B, B'-fusedmetallocenoporphyrins” Chemical Communications 2001, 2646-2647.