Faculty

Our research interests lie in the broad field of inorganic chemistry as it interfaces with biological and medicinal chemistry. One project will be directed toward designing metal chelators as chemotherapeutics for Alzheimer's disease (AD). Two other areas will focus on utilizing metal peptide complexes as catalysts for selective oxidative transformations and as agents for detoxification of hydrogen peroxide. Students in our group will engage in synthetic chemistry (organic and inorganic syntheses), physical methods (NMR, EPR, IR, CD, and UV-vis spectroscopy, mass spectrometry, and X-ray crystallography), as well as biological techniques (mammalian cell culture and analysis).

Metal Chelator-Based Chemotherapeutic Agents for Alzheimer's Disease (AD). A distinct feature of AD is accumulation of toxic amyloid-beta (A beta) aggregates, which is accelerated by the presence of divalent ions such as Cu(II) and Zn(II) . In particular, Cu-A beta may catalytically generate reactive oxygen species (ROS) leading to increased oxidative stress and consequent deterioration of AD conditions. Metal-induced A beta aggregation and ROS formation can be alleviated by metal chelators. Therefore, we will develop a new generation of nontoxic, small molecule-based metal chelators for Cu(II) and Zn(II) as effective therapeutics for AD.

Metallopeptides as Efficient and Selective Oxidation Catalysts. Selective oxidation reactions of organic compounds are of great significance for the synthesis of fine chemicals and industrial production of useful compounds. To achieve efficiency and selectivity, transition metal complexes and metalloenzymes have been employed as catalysts. Their utility and general applicability are still limited, however. We will design metallopeptides as a new class of catalysts for selective oxidative functionalization under mild conditions. Metallopeptide-based catalysts would combine advantages of both metalloenzymes and small-molecule catalysts that are involved in oxidation chemistry.

Metal-Based Reagents Toward Detoxification of H2O2 in Biological Systems. Impaired detoxification of hydrogen peroxide (H2O2) and the resulting oxidative stress are implicated in human diseases including a number of forms of cancer. In cellular antioxidant defense systems, catalase acts as an enzmatic scavenger of H2O2, converting it to dioxygen adn water. Inspired by teh structure and function of this enzyme, we will construct an efficient detoxifier of H2O2 in biological systems.

Awards

ACS Division of Inorganic Chemistry Young Investigator Award, 2007

Representative Publications

1. Lim, M.H., Lau, I.H., Barton, J.K., "DNA Strand Cleavage Near a CC Mismatch Directed by a Metalloinsertor", Inorg. Chem., 2007, 46, 9528.

2. Lim, M.H., Lippard, S.J., "Metal-Based Turn-On Fluorescent Probes for Sensing Nitric Oxide", Acc. Chem. Res., 2007, 40, 41.

3. Lim, M.H., "Preparation of a Copper-Based Fluorescent Probe for Nitric Oxide and Its Use in Mammalian Cultured Cells", Nat. Protocols, 2007, 2, 408.

4. Lim, M.H., et al., "Direct Nitric Oxide Detection In Aqueous Solution by Copper(II) Flyorescein Complexes", J. Am. Chem. Soc., 2006, 128, 14364.

5. Lim, M.H., Xu, D., Lippard, S.J., "Visualization of Nitric Oxide in Living Cells by a Copper-Based Fluorescent Probe", Nat. Chem. Bio., 2006, 2, 375.

6. Lim, M.H., Lippard, S.J., "Copper Complexes for Fluorescence-Based NO Detection in Aqueous Solution", J. Am Chem. Soc., 2005, 127, 12170.

7. Lim, M.H., et al., "An Fe^IV=O Complex of a Tetradentate Tripodal Nonheme Ligand", Proc. Natl. Acad. Sci. USA, 2003, 100, 3665.