Aziridine Scaffolds for the Detection and Quantification of Hydrogen-Bonding Interactions through Transition-State Stabilization

2010 ◽  
Vol 50 (3) ◽  
pp. 741-744 ◽  
Author(s):  
Luciana Giordano ◽  
Cam T. Hoang ◽  
Michael Shipman ◽  
James H. R. Tucker ◽  
Tiffany R. Walsh
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Hydrogen Bonding Interactions ◽  
Transition State Stabilization ◽  
Detection And Quantification

Aziridine Scaffolds for the Detection and Quantification of Hydrogen-Bonding Interactions through Transition-State Stabilization

2010 ◽  
Vol 123 (3) ◽  
pp. 767-770
Author(s):  
Luciana Giordano ◽  
Cam T. Hoang ◽  
Michael Shipman ◽  
James H. R. Tucker ◽  
Tiffany R. Walsh
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Hydrogen Bonding Interactions ◽  
Transition State Stabilization ◽  
Detection And Quantification

scholarly journals Binding energy and specificity in the catalytic mechanism of yeast aldose reductases

1999 ◽  
Vol 344 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Bernd NIDETZKY ◽  
Peter MAYR ◽  
Philipp HADWIGER ◽  
Arnold E. STüTZ
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Catalytic Mechanism ◽  
Relative Proportion ◽  
Binding Constants ◽  
Stabilization Energy ◽  
Binary Complex ◽  
Hydrogen Bonding Interactions ◽  
Transition State Stabilization ◽  
Hydroxy Groups

Derivatives of D-xylose and D-glucose, in which the hydroxy groups at C-5, and C-5 and C-6 were replaced by fluorine, hydrogen and azide, were synthesized and used as substrates of the NAD(P)H-dependent aldehyde reduction catalysed by aldose reductases isolated from the yeasts Candida tenuis, C. intermedia and Cryptococcus flavus. Steady-state kinetic analysis showed that, in comparison with the parent aldoses, the derivatives were reduced with up to 3000-fold increased catalytic efficiencies (kcat/Km), reflecting apparent substrate binding constants (Km) decreased to as little as 1/250 and, for D-glucose derivatives, up to 5.5-fold increased maximum initial rates (kcat). The effects on Km mirror the relative proportion of free aldehyde that is available in aqueous solution for binding to the binary complex enzyme-NAD(P)H. The effects on kcat reflect non-productive binding of the pyranose ring of sugars; this occurs preferentially with the NADPH-dependent enzymes. No transition-state stabilization energy seems to be derived from hydrogen-bonding interactions between enzyme-NAD(P)H and positions C-5 and C-6 of the aldose. In contrast, unfavourable interactions with the C-6 group are used together with non-productive binding to bring about specificity (6-10 kJ/mol) in a series of D-aldoses and to prevent the reaction with poor substrates such as D-glucose. Azide introduced at C-5 or C-6 destabilizes the transition state of reduction of the corresponding hydrogen-substituted aldoses by approx. 4-9 kJ/mol. The total transition state stabilization energy derived from hydrogen bonds between hydroxy groups of the substrate and enzyme-NAD(P)H is similar for all yeast aldose reductases (yALRs), at approx. 12-17 kJ/mol. Three out of four yALRs manage on only hydrophobic enzyme-substrate interactions to achieve optimal kcat, whereas the NAD(P)H-dependent enzyme from C. intermedia requires additional, probably hydrogen-bonding, interactions with the substrate for efficient turnover.

scholarly journals A crystallographic study of the Toho-1 β-lactamase acylation mechanism

2014 ◽  
Vol 70 (a1) ◽  
pp. C1207-C1207
Author(s):  
Leighton Coates
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Substrate Binding ◽  
Ligand Complex ◽  
Transition State Analog ◽  
Hydrogen Bonding Interactions ◽  
Active Site Region ◽  
Neutron Crystallography

β-lactam antibiotics have been used effectively over several decades against many types of highly virulent bacteria. The predominant cause of resistance to these antibiotics in Gram-negative bacterial pathogens is the production of serine β-lactamase enzymes. A key aspect of the class A serine β-lactamase mechanism that remains unresolved and controversial is the identity of the residue acting as the catalytic base during the acylation reaction. Multiple mechanisms have been proposed for the formation of the acyl-enzyme intermediate that are predicated on understanding the protonation states and hydrogen-bonding interactions among the important residues involved in substrate binding and catalysis of these enzymes. For resolving a controversy of this nature surrounding the catalytic mechanism, neutron crystallography is a powerful complement to X-ray crystallography that can explicitly determine the location of deuterium atoms in proteins, thereby directly revealing the hydrogen-bonding interactions of important amino acid residues. Neutron crystallography was used to unambiguously reveal the ground-state active site protonation states and the resulting hydrogen-bonding network in two ligand-free Toho-1 β-lactamase mutants which provided remarkably clear pictures of the active site region prior to substrate binding and subsequent acylation [1,2] and an acylation transition-state analog, benzothiophene-2-boronic acid (BZB), which was also isotopically enriched with 11B. The neutron structure revealed the locations of all deuterium atoms in the active site region and clearly indicated that Glu166 is protonated in the BZB transition-state analog complex. As a result, the complete hydrogen-bonding pathway throughout the active site region could then deduced for this protein-ligand complex that mimics the acylation tetrahedral intermediate [3].

THE INHIBITED AUTOXIDATION OF STYREN: PART IV. SOLVENT EFFECTS

1964 ◽  
Vol 42 (5) ◽  
pp. 1044-1056 ◽  
Author(s):  
J. A. Howard ◽  
K. U. Ingold
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Solvent Effects ◽  
Dielectric Constants ◽  
Hydroxyl Group ◽  
Phenolic Antioxidants ◽  
Oxidation Reactions ◽  
Effect Of Solvents ◽  
Hydrogen Bonding Interactions ◽  
Influence Of Solvents

The influence of solvents on the rate of the uninhibited oxidation of styrene can be roughly correlated with the dielectric constants of the solvents. It is suggested that the propagation reaction involves a dipolar transition state and that the magnitude of the solvent effects might be used to identify dipolar transition states in other oxidation reactions. The effect of solvents on the rate of oxidation of styrene inhibited by phenolic antioxidants is attributed to hydrogen bonding interactions between the phenolic hydroxyl group and the solvent. The magnitude of these interactions depends on the acidity of the phenol and on the degree of steric protection afforded the hydroxyl group by ortho-alkyl substituents.

Theoretical study of hydrogen bonding interactions in substituted nitroxide radicals

2021 ◽  
Author(s):  
Thufail M. Ismail ◽  
Neetha Mohan ◽  
P. K. Sajith
Keyword(s):  
Hydrogen Bonding ◽  
Interaction Energy ◽  
Electrostatic Potential ◽  
Molecular Electrostatic Potential ◽  
Theoretical Study ◽  
Nitroxide Radicals ◽  
Hydrogen Bonding Interactions ◽  
Bonded Complexes ◽  
Hydrogen Bonded

Interaction energy (Eint) of hydrogen bonded complexes of nitroxide radicals can be assessed in terms of the deepest minimum of molecular electrostatic potential (Vmin).

scholarly journals Circular linkage of intramolecular multi-hydrogen bonding frameworks through nucleophilic substitutions of β-dicarbonyls onto cyanuric chloride and subsequent tautomerisation

RSC Advances ◽  
2020 ◽  
Vol 10 (64) ◽  
pp. 39033-39036
Author(s):  
Ayano Awatani ◽  
Masaaki Suzuki
Keyword(s):  
Hydrogen Bonding ◽  
Cyanuric Chloride ◽  
Nucleophilic Substitutions ◽  
Hydrogen Bonding Interactions ◽  
Triazine Derivatives

Triply β-dicarbonyl-embedded 1,3,5-triazine derivatives result in formation of circular linkage of resonance-assisted hydrogen bonding interactions, which can be regarded as well-delocalized resonance hybrids.

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