B.S., M.S., University of Burdwan, India Ph.D., Indian Institute of Technology, Kanpur Postdoctoral work: Stanford University, Harvard University, Massachusetts Institute of Technology

Bioinorganic chemistry, design of antitumor drugs, modeling of active sites of metalloenzymes, design of catalysts for hydrocarbon oxidation, studies on intermediates in non-heme oxygenase chemistry, design of NO-donors for photodynamic therapy

Pradip Mascharak is interested in bioinorganic chemistry. His research activity includes modeling the active sites of enzymes that contain transition metal ions. This research involves syntheses of metal complexes/clusters with biologically relevant designed ligands that mimic various metalloenzymes in their structural, spectroscopic and catalytic behaviors. The ultimate goal is to elucidate the mechanism(s) of the complex biological transformations occurring at the metal-containing active sites. At this time, two enzymes are under study. The first one, nitrile hydratase (NHase), is involved in microbial assimilation of organic nitriles. The active site of this enzyme contains either a low-spin Fe(III) or non-corrin Co(III). The second enzyme is acetyl Co-A synthase/CO dehydrogenase (ACS/CODH), an enzyme involved in CO2-fixation by various anaerobic chemotrophs. The so-called A-cluster of ACS/CODH contains a Ni-Ni-Fe4S4 unit. Both these active sites have very unusual coordination structures. The metal centers are attached to the peptide backbone via carboxamido nitrogens and Cys-sulfurs. In addition, two of the three Cys-S centers of NHase are post-translationally modified to Cys-sulfenato (-SO-) and -sulfinato (-SO2-) groups. During the past few years, Mascharak's group has synthesized and structurally characterized series of designed metal complexes that resemble such active sites very closely and studied their reactivities to establish the mechanism of nitrile hydrolysis and acetyl group formation from CO and CH3 at the metal sites. Several of the model complexes have been used to perform analogous chemical transformations under very different conditions. Syntheses of novel bio-inspired catalysts on the basis of these studies are in progress. In recent years, metal nitrosyls like sodium nitroprusside have been used to control blood pressure and related hypertensive episodes. NO complexes that release NO upon illumination have been tried as agents in photodynamic therapy. During the past few years, Mascharak' group is involved in synthesizing designed metal nitrosyls that photorelease NO under very mild conditions (low intensity visible or UV light). Various chemical principles guide the design of such nitrosyls that deliver NO to biological targets under specific conditions. A variety of spectroscopic, magnetic and photochemical studies are performed to identify the factors responsible for the controlled release of NO from such nitrosyls upon illumination. Results of parallel theoretical studies are also utilized to elucidate the electronic origin of the NO photolability. At the present time, attempts are also being made to attach these NO-donors on beads of inert matrix that could be selectively placed at biological targets and then conveniently triggered to release burst of NO upon illumination. During the past three years, the group has turned their focus on Carbon monoxide (CO), another surprising addition to the list of small signaling molecule in biology. Low doses of CO is shown to provide cytoprotective action to oxidatively damaged tissues (such as during stroke and ischemia). Mascharak's group has initiated syntheses of designed metal-CO complexes (based on Smart Design principles and theoretical calculations) that could be employed to deliver CO at biological targets under the control of light. Another research project in Mascharak's group is related to the area of new "Green Chemistry". For some time, this group has been studying oxidation of various organic substrates (including alkanes and alkenes) by non-heme iron and cobalt complexes in conjunction with O2, H2O2 and ROOH. The goal of this project is to synthesize catalysts that operate under mild conditions (less energy requirements) and utilize safer reagents (like O2) for oxidations.

M. A. Gonzalez, H. Han, A. Moyes, A. Radinos, A. J. Hobbs, N. Coombs, S. R. J. Oliver and P. K. Mascharak, Light-Triggered Carbon Monoxide Delivery with Al-MCM-41-based Nanoparticles Bearing a Designed Manganese Carbonyl Complex. J. Mater. Chem. B. 2014, 2, 2107-2113.

S. J. Carrington, I. Chakraborty and P. K. Mascharak, Rapid CO Release from a Mn(I) Carbonyl Complex Derived from azopyridine upon Exposure to Visible Light and its Phototoxicity Toward Malignant Cells. Chem. Commun. 2013, 49, 11254-11256.

T. deBoer-Maggard, A. Resendez and P. K. Mascharak, Construction of a Biomimetic Peroxynitrite -Generating Platform: A Two-component System to Synthesize Peroxynitrite in Situ Under the Control of Light. ChemBioChem, 2013, 14, 2106-2109.

B. J. Heilman, J. St. John, S. R. J. Oliver and P. K. Mascharak, Light-triggered Eradication of Acinetobacter baumannii by means of NO Delivery from a Porous Material with an Entrapped Metal Nitrosyl. J. Am. Chem. Soc. 2012, 134, 11573-11582.

N. L. Fry and P. K. Mascharak, Photolability of NO in Designed Metal Nitrosyls with Carboxamido-N Donors: A Theoretical Attempt to Unravel the Mechanism. (Invited Perspective Article) Dalton Transactions, 2012, 41, 4726-4735.

M. A. Gonzalez, N. L. Fry, R. Burt, R. Davda, A. Hobbs and P. K. Mascharak, Designed Metal Carbonyls as Carbon Monoxide (CO) Releasing Molecules (CORMs): Rapid CO Release and Delivery to Myoglobin in Aqueous Buffer, and Vasorelaxation of Mouse Aorta. Inorg. Chem. 2011, 50, 3127-3134.

N. L. Fry and P. K. Mascharak, Photoactive Ruthenium Nitrosyls as NO Donors: How to Sensitize them Toward Visible Light Acc. Chem. Res. 2011, 44, 289-298.

G. M. Halpenny and P. K. Mascharak, Emerging Antimicrobial Applications of Nitric Oxide (NO) and NO-Releasing Materials. (Invited Review) Anti-Infect. Agents Med. Chem. 2010, 9, 187-197.

G. M. Halpenny and P. K. Mascharak, Eradication of Pathogenic Bacteria by Remote Delivery of NO via Light-triggering of Nitrosyl-Containing Materials. ACS Med. Chem. Lett. 2010, 1, 180- 183.

M. J. Rose, N. M. Betterley, A. G. Oliver and P. K. Mascharak, Binding of Nitric Oxide (NO) to a Synthetic Model of Iron-Containing Nitrile Hydratase and Its Photorelease: Relevance to Photoregulation of Fe-NHase by NO. Inorg. Chem. 2010, 49, 1854-1864.

N. L. Fry, M. J. Rose, D. L. Rogow, C. Nyitray, M. Kaur and P. K. Mascharak, Ruthenium Nitrosyls Derived from Tetradentate Ligands Containing Carboxamido-N and Phenolato-O Donors: Syntheses, Structures, Photolability and Time Dependent Density Functional Theory Studies. Inorg. Chem. 2010, 49, 1487-1495.

A. A. Eroy-Reveles and P. K. Mascharak, Nitric Oxide-donating Materials and Their Potential in Pharmacological Applications. Future Medicinal Chemistry 2009, 1(8), 1497-1507.