Trajectory analysis. 1. Theoretical model for nucleophilic attack at .pi.-systems. The stabilizing and destabilizing orbital terms

Liotta, Charles L.; Burgess, Edward M.; Eberhardt, W.

doi:10.1021/ja00329a035

Cited by 41 publications

(18 citation statements)

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“…Finally, a fourth factor favoring catalysis is that the nicotinamide C4 hydride and Cys63-SG are on opposite sides of the flavin plane and roughly in line with the N5-C4a bond (Figure 8), in position for good HOMO-LUMO overlap20,54–55 and also consistent with optimal geometry for 1,2-addition of the hydride and the sulfur across a double bond47,56–57. This optimal geometry for a 1,2-addition raises the interesting possibility that the reduction of GR is not a distinct two-step process with hydride transfer to the flavin occurring first, followed by disulfide reduction, but instead is concerted, with hydride transfer linked to and enhanced by disulfide reduction.…”

Section: Resultsmentioning

confidence: 88%

Catalytic Cycle of Human Glutathione Reductase Near 1 Å Resolution

Berkholz

Faber

Savvides

et al. 2008

Journal of Molecular Biology

107

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SummaryEfficient enzyme catalysis depends on exquisite details of structure beyond those resolvable in typical medium-and high-resolution crystallographic analyses. Here we report synchrotron-based cryocrystallographic studies of natural substrate complexes of the flavoenzyme human glutathione reductase (GR) at nominal resolutions between 1.1 and 0.95 Å that reveal new aspects of its mechanism. Compression in the active site causes overlapping van der Waals radii and distortion in the nicotinamide ring of the NADPH substrate, which enhances catalysis via stereoelectronic effects. The bound NADPH and redox-active disulfide are positioned optimally on opposite sides of the flavin for a 1,2-addition across a flavin double bond. The new structures extend earlier observations to reveal that the redox-active disulfide loop in GR is an extreme case of sequential peptide bonds systematically deviating from planarity, a net deviation of 53° across 5 residues. But this apparent strain is not a factor in catalysis as it is present in both oxidized and reduced structures. Intriguingly, the flavin bond lengths in oxidized GR are intermediate between those expected for oxidized and reduced flavin, but we present evidence that this may not be due to the protein environment but instead to partial synchrotron reduction of the flavin by the synchrotron beam. Finally, of more general relevance, we present evidence that the structures of synchrotron-reduced disulfide bonds cannot generally be used as reliable models for naturally reduced disulfide bonds.

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Section: Resultsmentioning

confidence: 88%

Catalytic Cycle of Human Glutathione Reductase Near 1 Å Resolution

Berkholz

Faber

Savvides

et al. 2008

Journal of Molecular Biology

107

View full text Add to dashboard Cite

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“…The basic assumption on which a suitable model system is built is that the optical properties of CDs originate from an sp 2 carbon network with “>CC<” and αβ-unsaturated ketone (>CC–CO) as obtained from the infrared (IR) spectrum; Figure S3b shows that the peak at 1730 cm –1 that is related to (>CO) is abolished in the case of Ru:CNDEDAs and a new peak at 1580 cm –1 evolves due to formation of (>CN). Thus, the EDA can react with the αβ-unsaturated ketone by Michael addition, , which reduces the multiple types of conjugations to a single one (Figure h), improvising small organic molecule-like behavior. It is a well-known fact that with a decreasing level of sp 2 -hybridized C in a system, the fluorescence decreases.…”

Section: Resultsmentioning

confidence: 99%

Metamorphosis of Ruthenium-Doped Carbon Dots: In Search of the Origin of Photoluminescence and Beyond

Bera

Mondal

et al. 2016

Chem. Mater.

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Carbon dots (CDs) are known to have a wide range of applications, yet our understanding of their structures and chemistry remains uncertain because of their highly complex nanostructured framework. Here we attempt to elucidate the molecular structure and intrinsic mechanisms governing photoluminescence (PL) of CDs by trapping seven visibly distinct colored intermediates that evolved during pyrolytic metamorphosis of citric acid with dopant Ru(III). The "excitation-dependent" PL of doped CDs, Ru:CDs, can be tuned by ethylenediamine (EDA), yielding "excitation-independent" highly fluorescent nanodots, Ru:CNDEDAs. To mimic the optical and chemical properties of CDs, we devise a unique model cocktail comprising multiple fluorogenic molecules that truly supports the existence of chemically switchable conjugated moieties in CDs. We propose a plausible molecular level framework of CDs on the basis of spectroscopic findings and existing literature regarding thermal decomposition of CA. The PL of chemically engineered Ru:CNDEDAs is quenched efficiently by photoinduced electron transfer (PET) phenomenon. By exploiting the PET process, we also develop an important sensing platform for quantifying toxic and carcinogenic quinone derivatives in live HeLa cells that can be used for drug screening. Moreover, the distribution pattern of these photoluminiscent nanodots in HeLa cells is studied to demonstrate their utilities as endosomal markers.

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“…2b ). 30 Indeed, according to the calculated transition state for OH – addition to trans-N -methylacetamide or for HS – addition to trans-N -methylacetamide ·HCl, the preferred φ FL is not 0° but 52° or 61°, respectively. The Bürgi–Dunitz angle must then be modified as the complement of the Nu–C–P Nu angle ( Fig.…”

Section: Methodsmentioning

confidence: 99%