Background:

• Jane Coffin Childs Postdoctoral Fellow, Stanford University, 1993-96
• Indiana University Teaching Excellence Recognition Award, 1998, 2000 and 2004

Our research group has four broad research themes:

1. Harnessing the power of naturally occurring chemical functionalities for applications as metal-mediated biomedical reagents. These systems are primarily based on radical or diradical intermediates whose reactivity is difficult to control and systematically modulate. Diradical reagents of this type may be effective for H-atom abstraction reactivity from biological substrates, or insertion into chemical bonds, thus possessing utility as photoaffinity labels.
2. The development of novel nano-scale architectures as hybrid materials for optics, photo-magnetic switching, and nanomedicine applications. Constructing these materials involves development of new synthetic strategies or novel ligand coatings with specific properties to enable optical or magnetic excitation.
3. Applications of spectroscopy to electronic structure of inorganic and bioinorganic metal sites involved in thermal or photoinduced processes such as electron transfer, energy transfer, or biochemical gene expression.
4. Synthesis of unique porphyrinoid architectures that have unusual optical properties, or periphery modifications for energy-related photoelectronic or synthetic applications requiring extended chromophores.

Research being conducted in my group is fundamental to these general themes. Our primary focus is the use of various steady state and time-resolved spectroscopic methods including optical absorption, Raman, and circular dichroism to investigate the structure and kinetics of biologically relevant intermediates involved in enzyme and drug-related reaction mechanisms. This information is important for determining the pathways by which multistep biochemical reactions occur.

In addition, we are interested in designing strategies to promote novel biochemical reactivity using excited-state photochemistry. The absorption of photons by molecules can be used to trigger release of ligands or redistribute charge within a complex. This leads to the formation of transient molecular and electronic structures that are highly reactive with biological substrates. Our goal is to study the structure and kinetics of these excited-state transients in order to prepare complexes with novel chemical reactivity.

One specific area of research is the design of photoactivatable DNA cleaving agents. DNA cleaving agents are particularly important because they play a prominent role in anticancer therapy and molecular biology. Many systems currently being studied rely on thermodynamically favorable chemical reactions involving reducing agents, hydrogen peroxide, or molecular oxygen. The efficiency, selectivity, and toxicity of these DNA cleavers are governed by several molecular properties that are difficult to control in concert. Photodynamic therapy has attempted to eliminate some of these parameters by driving antitumor reactions photochemically through generation of singlet oxygen. Although this approach has proven fruitful, the bimolecular nature of the reaction diminishes the effectiveness and specificity. Therefore, we are interested in the design of unimolecular DNA cleavers that can be triggered via low energy optical excitation. The strategy we are currently investigating involves the formation of excited state biradical species by either direct excitation or electron transfer. These reactive intermediates are potentially capable of performing hydrogen atom abstraction from DNA and hence double stranded cleavage.

	Copper and Palladium Metalloenediynes

Selected Publications:

Metal- Ligand Charge-Transfer-Promoted Photo-Electronic Bergman Cyclization of Copper Metalloenediynes : Photochemical DNA Cleavage via C-4' H-Atom Abstraction, Pedro. J. Benites, Rebecca C. Holmberg, Diwan S. Rawat, H. Holden Thorp, and Jeffrey M. Zaleski, J. Am. Chem. Soc.. ( 2003 ), 125, 6434-6446.

Signal Transduction by the Mediated Global Regulator RegB is by a Redox -active Cysteine, Lee R. Swem, Brian J. Kraft, Danielle L. Swem, Aaron T. Setterdahl, Shinji Masuda, David B. Knaff, Jeffrey M. Zaleski, and Carl E. Bauer, EMBO J. ( 2003), 22, 4699-4708.

Ambient Temperature Activation of Haloporphyrinic-Enediynes : Electronic Contributions to Bergman Cyclization, Mahendra Nath, John C. Huffman, and Jeffrey M. Zaleski, J. Am. Chem. Soc., ( 2003 ), 125, 11484-11485.

Geometric and Electronic Control of Thermal Bergman Cyclization, Diwan S. Rawat and Jeffrey M. Zaleski, Invited Review for Synlett, edited by P. Vollhardt ., ( Thieme Medical Publishers, Inc., New York), ( 2004 ), 3, 393-421.

A unique approach to metal-induced Bergman cyclization : Long-range enediyne activation by ligand -to-metal charge transfer, Sibaprasad Bhattacharyya, Maren Pink, Mu-Hyun Baik, and Jeffrey M. Zaleski, Angew . Chem. Int. Ed. Eng., ( 2005 ), 44 (4), 592-595.

Photochemical Preparation of Pyrrole Ring-contracted Chlorins by the Wolff Rearrangement, Jeffrey M. Zaleski, Tillmann Köpke, and Maren Pink, Org. Biomol . Chem., ( 2006 ), 4, 4059-4062.

Elucidation of the Extraordinary 4-membered Pyrrole Ring-contracted Azeteoporphyrinoid as an intermediate in Chlorin Oxidation, Tillmann Köpke, Maren Pink, and Jeffrey M. Zaleski, Chem. Commun ., ( 2006 ), 4940-4942.

Convenient, Rapid Synthesis of Ag Nanowires, Linfeng Gou, Mircea Chipara, Jeffrey M. Zaleski, Chem.Mat ., ( 2007 ), 19 (7), 1755-1760.

Diazo -containing Molecular Constructs as Potential Anticancer Agents: From Diazo [b]fluorine Natural Products to Photoactivatable Diazo-oxochlorins, Tillmann Köpke and Jeffrey M. Zaleski, Anti-cancer Agents in Medicinal Chemistry, ( 2008 ), 8(3), 292 -304.

Expansion by Contraction: Diversifying the Photochemical Reactivity Scope of Diazo-oxochlorins Toward Development of In Situ Alkylating Agents, Tillmann Köpke, Maren Pink, and Jeffrey M. Zaleski, J. Amer. Chem. Soc., ( 2008 ), in press.

Efficient Silver-Mediated Acetalation of ß,ß' -Functionalized Chlorins, Tillmann Köpke, Maren Pink, and Jeffrey M. Zaleski, Synlett, ( 2008 ), in press.