A5042280018- Microbial Metabolic Engineering and Bioproduction
- Asymmetric Hydrogenation and Catalysis
- Enzyme Catalysis and Immobilization
- Cyclopropane Reaction Mechanisms
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Mitochondrial Function and Pathology
- Catalysis for Biomass Conversion
- Protein Structure and Dynamics
- Plant biochemistry and biosynthesis
- Catalytic Alkyne Reactions
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Microbial Natural Products and Biosynthesis
- Viral Infections and Immunology Research
- Synthesis and Properties of Aromatic Compounds
- SARS-CoV-2 and COVID-19 Research
- Steroid Chemistry and Biochemistry
- Spectroscopy and Quantum Chemical Studies
- Ionic liquids properties and applications
- Photosynthetic Processes and Mechanisms
- Axial and Atropisomeric Chirality Synthesis
- Carbon dioxide utilization in catalysis
- Molecular Junctions and Nanostructures
- Electron Spin Resonance Studies
- DNA and Nucleic Acid Chemistry
University of California, Los Angeles
2011-2024
AbbVie (United States)
2022
Medical College of Wisconsin
2018-2022
UCLA Health
2014
University of San Francisco
2008-2011
Fluorine helps: A fluorinated triazolium salt precatalyst has been developed that efficiently promotes the asymmetric intermolecular Stetter reaction of enolizable aldehydes and nitrostyrenes (see scheme). Trans fluorination catalyst architecture results in unparalleled reactivity enantioselectivity desired transformation. DFT study provides evidence an electrostatic interaction as source increased enantio-induction. Detailed facts importance to specialist readers are published "Supporting...
Significance Ketoreductases are the most commonly used enzymes in industrial pharmaceutical synthesis. We investigated nature of enantioselectivity closely related mutant ketoreductases that reduce almost-symmetrical 3-oxacyclopentanone and 3-thiacyclopentanone, which difficult to enantioselectively by other means. present efficiencies select variants their crystallographic structures. Our experimental theoretical studies reveal how mutations modulate stereoselectivity reduction. Molecular...
Nature uses four methods of carbon chain elongation for the production 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination quantum mechanical (QM) modeling, protein-substrate protein metabolic engineering, we have engineered enzymes involved in leucine biosynthesis use as synthetic "+1" recursive pathway to extend 2-ketoacids. This modified preferentially selects longer-chain substrates catalysis, compared non-recursive natural pathway, can recursively catalyze five...
This Account describes the use of molecular dynamics (MD) simulations to reveal how mutations alter structure and organization enzyme active sites. As proposed by Pauling about 70 years ago elaborated many others since then, biocatalysis is efficient when functional groups in site an are optimal positions for transition state stabilization. Changes mechanism covalent interactions often critical parts catalysis. We describe our explorations dynamical preorganization sites using MD, studying...
Quantum mechanical studies of the mechanism gold-catalyzed rearrangements acetylenic amine-N-oxides to piperidinones or azepanones have revealed a new involving concerted heteroretroene reaction, formally 1,5 hydrogen shift from N-alkyl groups vinyl position gold-coordinated methyleneisoxazolidinium methyleneoxazinanium. Density functional calculations (B3LYP, B3LYP-D3) on reproduce experimental regioselectivities and provide an explanation as why is transferred smaller amine substituent. In...
The asymmetric intermolecular Stetter reaction was investigated using the B3LYP and M06-2X functionals. Fluorination of a triazolium bicyclic catalyst had been found to significantly influence yields enantiomeric ratios. Computations indicate that improved reactivity fluorinated is due better electrostatic interactions between nitroalkene catalyst. Computational investigations preferred conformations ground state acyl anion equivalent, transition structures leading both enantiomers products,...
Several alkynylindoles undergo gold(I)-catalyzed cyclization reactions to form a single isomer in each case. Density functional theory shows why this reaction is favored over the many possible regio- and stereoisomeric pathways. This transformation involves two-step no-intermediate mechanism with surface bifurcations leading two or three products. Such could explain reactivity enyne reactions.
Fluor hilft: Ein fluoriertes Triazoliumsalz wurde entwickelt, das als Präkatalysator für die asymmetrische intermolekulare Stetter-Reaktion von enolisierbaren Aldehyden und Nitrostyrolen dient (siehe Schema). Die trans-Fluorierung der Katalysatorarchitektur führt zu einer unerreichten Reaktivität Enantioselektivität in gewünschten Reaktion. Eine DFT-Studie liefert Belege eine elektrostatische Wechselwirkung Quelle gesteigerten Enantioinduktion. Detailed facts of importance to specialist...
Abstract Extensive molecular dynamics (MD) simulations on designed and evolved enzymes for the Kemp Elimination were performed. Over thirty different systems including combinations of three protein scaffolds used in computational design (KE70, KE59 HG3), several directed evolution variants ligands (5‐nitrobenzo[ d ]isoxazole, 6‐nitro‐1 H ‐benzo[ ][1,2,3]triazole), screened computationally. The study was focused mostly which X‐ray structures are available. MD to monitor organization active...
Lipopolysaccharide (LPS) is an essential element of nearly all Gram-negative bacterial outer membranes and serves to protect the cell from adverse environmental stresses. Seven members lipopolysaccharide transport (Lpt) protein family function together LPS inner membrane (IM) leaflet bacteria such as Escherichia coli. Each these proteins has a solved crystal structure, including LptC, which largely periplasmic that associated with IM LptB2 FG complex anchored by N-terminal helix. LptC...
The selective androgen receptor modulator, (S)-(7-cyano-4-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic acid isopropyl ester, LY2452473, is a promising treatment of side effects prostate cancer therapies. An acid-catalyzed Fischer indolization central step in its synthesis. reaction leads to only one the two possible indole regioisomers, along with minor decomposition products. Computations show that formation observed most favored energetically, while potential...
In this experiment students are exposed to concepts in inorganic synthesis and various spectroscopies as applied a tri-tungsten cluster with applications biomedical imaging. The tungsten−acetate cluster, Na[W3(μ-O)2(CH3COO)9], 1, was synthesized characterized by 1H-NMR, UV-vis, FT-IR Raman spectroscopy. 1H-NMR shows three characteristic chemical shifts of the bridging (δ 2.30 ppm), terminal 2.15 free 2.07 ppm) acetate groups methanol-d4. UV-vis spectrum two distinct absorption peaks at 376...
Intramolecular conjugate displacement (ICD) reactions, developed by the Clive group, form carbocycles and polycyclic amines intramolecular nucleophilic attack on a Michael acceptor with an allylic leaving group. Quantum mechanical investigations density functional theory show that ICDs involve stepwise addition, forming intermediate stabilized carbanion, followed elimination. The electron-withdrawing nature of group facilitates addition negative hyperconjugation; twist-boat conformation is...
Experimentally, tri-trans-[12]annulene and tris(cyclohexeno)[12]annulene exhibit differing reactivities. Whereas the former, after isomerizing to its di-trans isomer, undergoes sequential electrocyclizations, latter follows a Diels-Alder pathway initial electrocyclization. B3PW91/6-31+G*//B3LYP/6-31G* calculations indicate that cyclohexenofusion simultaneously hinders second electrocyclization facilitates reaction, primarily by inducing greater puckering in intermediate eight-membered ring.