A5088712681- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Pharmacogenetics and Drug Metabolism
- Metal-Catalyzed Oxygenation Mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- Enzyme Catalysis and Immobilization
- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- Computational Drug Discovery Methods
- Crystallography and molecular interactions
- Asymmetric Hydrogenation and Catalysis
- Metal complexes synthesis and properties
- Chemical Reactions and Isotopes
- Radical Photochemical Reactions
- Synthesis and Biological Evaluation
- Synthesis and Characterization of Heterocyclic Compounds
- Click Chemistry and Applications
- Supramolecular Chemistry and Complexes
- Metal-Organic Frameworks: Synthesis and Applications
- Metabolomics and Mass Spectrometry Studies
- Spectroscopy and Quantum Chemical Studies
- Chemical Synthesis and Analysis
- Crystal structures of chemical compounds
- Enzyme function and inhibition
- Microbial metabolism and enzyme function
San Jose State University
2013-2023
University of Louisville
2002-2011
California Institute of Technology
2008-2010
Division of Chemistry
2010
Montana State University
2008
University of Cincinnati
2006
P450s are heme thiolate enzymes that catalyze the regio- and stereoselective functionalization of unactivated C-H bonds using molecular dioxygen two electrons delivered by reductase. We have developed hybrid P450 BM3 domains containing a covalently attached Ru(II) photosensitizer in order to circumvent dependency on reductase perform reactions upon visible light irradiation. A highly active enzyme with improved stability modified is able light-driven hydroxylation lauric acid total turnover...
Proton wires: One-dimensional water chains play an important role in proton permeation through transmembrane proteins. The X-ray crystal structures as well solid-state 2H and 17O NMR calorimetry studies of two imidazole hydrates that stabilize infinite one-dimensional are reported (see picture; N blue, O red, H white). spectroscopic suggest molecules both compounds undergo different reorientational dynamics.
High-valent iron-oxo species are thought to be intermediates in the catalytic cycles of oxygenases and peroxidases. An attractive route these involves laser flash-quench oxidation ferric hemes, as demonstrated by our work on ferryl (compound II) porphyrin radical cation I) horseradish peroxidase. Extension this include cytochrome P450-BM3 (CYP102A1) has required covalent attachment a Ru II photosensitizer nonnative cysteine near heme ( ), order promote electron transfer from Fe III...
We have developed hybrid P450 BM3 enzymes consisting of a Ru(II)-diimine photosensitizer covalently attached to non-native single cysteine residues heme domain mutants. These are capable, upon light activation, selectively hydroxylating lauric acid with 40 times higher total turnover numbers compared the peroxide shunt.
The merging of photoredox trifluoromethylation with hybrid P450 BM3 variants has enabled the selective light-driven functionalization several arenes. This approach capitalizes on unique photochemical properties Ru(II)-diimine photosensitizer to initiate single electron transfer events. Under conditions, a CF3 radical promoted by d6 metal complex can add In enzymes, covalently attached provides necessary electrons perform, upon visible light activation, oxyfunctionalizations...
A new polyimidazole tripod N,N-bis((1-methyl-4-pivalamidoimidazol-2-yl)methyl)-N'-((1-methylimidazol-2-yl)methyl)amine (L2) has been synthesized and shown to form intramolecular hydrogen bonds with different axial ligands bonded Cu(II) in the solid state. The same hydrogen-bonding property of L2 appears responsible for stabilization a Cu(II)-OOH species solution. crystal structures three its complexes are reported. [Cu(L2)X]ClO4 complexes, 4-6 (X- = Cl-, OH-, or N3-) have distorted trigonal...
Ru(II)-diimine complexes covalently attached near the heme active site of P450 BM3 enzymes have been used to rapidly inject electrons and drive selective C-H functionalization upon visible light irradiation. Herein, we generated a series hybrid containing photosensitizer general formula [Ru(4,4'-X2bpy)2(PhenA)]2+ where X = Cl, H, tBu, Me OPhe, OMe, or NMe2, bpy 2,2'-bipyridine, PhenA 5-acetamido-1,10-phenanthroline. We then probed effect electron-withdrawing -donating groups at para position...
The self assembly of (bis(1-methyl-imidazol-2-yl)methyl)(1-methyl-4-nitroimidazol-2-yl)methyl)amine and boric acid results in a supramolecular structure containing bundled antiparallel imidazole-boric helices filled one-dimensional channels.
Protonenleiter: Ketten aus Wassermolekülen spielen eine wichtige Rolle bei der Permeation von Protonen durch Transmembranproteine. Berichtet wird über die Kristallstrukturen, 2H- und 17O-Festkörper-NMR-Spektren kalorimetrische Untersuchungen zweier Imidazolhydrate, endlose eindimensionale stabilisieren (siehe Bild; N blau, O rot, H weiß). Die 2H-NMR-Spektren weisen auf unterschiedliche Umorientierungsdynamik Wassermoleküle in beiden Verbindungen hin. Supporting information for this article...
The copper amine oxidase from Arthrobacter globiformis (AGAO) is reversibly inhibited by molecular wires comprising a Ru(II) complex head group and an aromatic tail joined alkane linker. crystal structures of series Ru(II)-wire-AGAO complexes differing with respect to the length linker have been determined. All lie in AGAO active-site channel, their contact trihydroxyphenylalanine quinone (TPQ) cofactor enzyme. TPQ consistently its active ("off-Cu") conformation, side chain so-called "gate"...
Ruthenium diimine complexes have previously been used to facilitate light-activated electron transfer in the study of redox metalloproteins. Excitation at 488 nm leads a photoexcited state, which complex can either accept or donate an electron, respectively, presence soluble sacrificial reductant oxidant. Here, we describe novel application these mediating light-induced changes cellular electrical activity. We demonstrate that RubpyC17 ([Ru(bpy)2(bpy-C17)]2+, where bpy is 2,2′-bipyridine and...
Underestimation of AO-mediated clearance by current <i>in vitro</i> assays leads to uncertainty in human dose projections, thereby reducing the likelihood success drug development. In present study we first evaluated development practices for AO substrates. Next, overall predictive performance vitro-in vivo</i> extrapolation (IVIVE) unbound hepatic intrinsic (CL<sub>int,u</sub>) and (CL<sub>int,u,AO</sub>) was assessed using a comprehensive literature database (human cytosol/ S9/...
Two unique metabolites (M18 and M19) were detected in feces of human volunteers dosed orally with [
A novel amide functionalized polyimidazole tripod ligand has been synthesized and used to prepare a mononuclear Fe(III) complex that characterized by X-ray crystallography other physical methods.