design of light-activated metal nitrosyls, ..

In recent years, the unique chemistry of nitric oxide (NO) has drawn much attention due to its regulatory role in several biological processes.- Endogenous NO produced by nitric oxide synthase (NOS) has been shown to participate as a signaling molecule in vasodilation and neurotransmission (both in low nM concentrations), and in cell apoptosis (in high μM concentrations),. These findings have spurred the development of several synthetic exogenous NO donors that mimic and even enhance the utility of endogenous NO production. For example, organic nitrites (trinitroglycerol) and S-nitrosothiols (SNAP) have been used clinically as vasodilators., These compounds are systemic donors that release NO in response to stimuli such as heat, pH change, or enzymatic activity. As a consequence, they cannot be used in site-specific controlled delivery of NO and there is a clear need for compounds that can provide high doses of NO at selected targets under controlled conditions.

The is of academic interest as an intermediate for the synthesis of metal carbonyl complexes .
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Generally this metal based drugs exhibit fewer toxicity problems than drugs based on other metals [8–10] .In addition to the prospects of using ruthenium nitrosyls as biologically active compounds, the ability of these complexes to form light-induced long-lived metastable linkage isomers is of interest as well [11–13] .


The synthesis of metal carbonyls is subject of intense ..

Transition metal nitrosyls in organic synthesis and in pollution control
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Complexes 1 and 2 were glued to a thin glass fiber with epoxy resin and collected on a Bruker APEX II diffractometer equipped with a fine focus, 2.0 kW sealed tube X-ray source (Mo Kα radiation, λ = 0.7103 Å) operating at 50kV and 30 mA at 273 K. The crystallographic collection and refinement parameters for complexes 1 and 2 are listed in . The empirical absorption correction was based on equivalent reflections and other possible effects, such as absorption by the glass fiber, were simultaneously corrected. Each structure was solved by direct methods followed by successive difference Fourier methods. All non-hydrogen atoms were refined anisotropically. Computations were performed using SHELXTL and final full-matrix refinements were against F. The SMART software was used for collecting frames of data, indexing reflections, and determination of lattice constants; SAINT-PLUS for integration of intensity of reflections and scaling; SADABS for absorption correction; and SHELXTL for space groups and structure determinations, refinements, graphics, and structure reporting.


The nitrogen atom in bent metal nitrosyls ..

Chemical Research Society of India (CSRI) Medal
Outstanding Faculty Award, PBSci Division, UCSC
Gandhi Medal
Fellow of the American Association for the Advancement of Science
Alfred Sloan Fellow
Excellence through Diversity Award, UCSC
Innovations in Teaching Award, UCSC

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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 has been 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.