Communication: Energetics of reaction pathways for reactions of ethenol with the hydroxyl radical: The importance of internal hydrogen bonding at the transition state

2010 ◽  
Vol 133 (2) ◽  
pp. 021102 ◽  
Author(s):  
Oksana Tishchenko ◽  
Sonia Ilieva ◽  
Donald G. Truhlar
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Hydroxyl Radical ◽  
Reaction Pathways ◽  
Internal Hydrogen

Reactions of an Aluminium(I) Reagent with 1,2-, 1,3- and 1,5-Dienes: Dearomatisation, Reversibility, and a Pericyclic Mechanism

2019 ◽  
Author(s):  
Clare Bakewell ◽  
Martí Garçon ◽  
Richard Y Kong ◽  
Louisa O'Hare ◽  
Andrew J. P. White ◽  
...  
Keyword(s):  
Reaction Mechanism ◽  
Dft Calculations ◽  
Transition State ◽  
Reaction Pathways ◽  
Aromatic Rings ◽  
Aromatic Character ◽  
Pericyclic Reaction

The reactions of an aluminium(I) reagent with a series of 1,2-, 1,3- and 1,5-dienes are reported. In the case of 1,3-dienes the reaction occurs by a pericyclic reaction mechanism, specifically a cheletropic cycloaddition, to form aluminocyclopentene containing products. This mechanism has been interrogated by stereochemical experiments and DFT calculations. The stereochemical experiments show that the (4+1) cycloaddition follows a suprafacial topology, while calculations support a concerted albeit asynchronous pathway in which the transition state demonstrates aromatic character. Remarkably, the substrate scope of the (4+1) cycloaddition includes dienes that are either in part, or entirely, contained within aromatic rings. In these cases, reactions occur with dearomatisation of the substrate and can be reversible. In the case of 1,2- or 1,5-dienes complementary reactivity is observed; the orthogonal nature of the C=C π-bonds (1,2-diene) and the homoconjugated system (1,5-diene) both disfavour a (4+1) cycloaddition. Rather, reaction pathways are determined by an initial (2+1) cycloaddition to form an aluminocyclopropane intermediate which can in turn undergo insertion of a further C=C π-bond leading to complex organometallic products that incorporate fused hydrocarbon rings.

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].

scholarly journals More and Faster: Simultaneously Improving Reaction Coverage and Computational Cost in Automated Reaction Prediction Tasks

2020 ◽  
Author(s):  
Qiyuan Zhao ◽  
Brett Savoie
Keyword(s):  
Transition State ◽  
Domain Knowledge ◽  
Low Cost ◽  
Computational Cost ◽  
Chemical Degradation ◽  
Reaction Pathways ◽  
Reaction Networks ◽  
Complex Reaction ◽  
Success Rates ◽  
Reaction Prediction

<div> <div> <div> <p>Automated reaction prediction has the potential to elucidate complex reaction networks for applications ranging from combustion to materials degradation. Although substantial progress has been made in predicting specific reaction pathways and resolving mechanisms, the computational cost and inconsistent reaction coverage of automated prediction are still obstacles to exploring deep reaction networks without using heuristics. Here we show that cost can be reduced and reaction coverage can be increased simultaneously by relatively straight- forward modifications of the reaction enumeration, geometry initialization, and transition state convergence algorithms that are common to many emerging prediction methodologies. These changes are implemented in the context of Yet Another Reaction Program (YARP), our reaction prediction package, for which we report a head-to-head comparison with prevailing methods for two benchmark reaction prediction tasks. In all cases, we observe near perfect recapitulation of established reaction pathways and products by YARP, without the use of heuristics or other domain knowledge to guide reaction selection. In addition, YARP also discovers many new kinetically relevant pathways and products reported here for the first time. This is achieved while simultaneously reducing the cost of reaction characterization nearly 100-fold and increasing transition state success rates and intended rates over 2-fold and 10-fold, respectively, compared with recent benchmarks. This combination of ultra-low cost and high reaction-coverage creates opportunities to explore the reactivity of larger sys- tems and more complex reaction networks for applications like chemical degradation, where approaches based on domain heuristics fail. </p> </div> </div> </div>

Ambident Heterocyclic Reactivity: Alkylation of 4-Substituted and 2,4-Disubstituted Benzimidazoles

1994 ◽  
Vol 47 (8) ◽  
pp. 1523 ◽  
Author(s):  
MR Haque ◽  
M Rasmussen
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Electrostatic Field ◽  
Transition States ◽  
Alkyl Halides ◽  
Methyl Group ◽  
Site Selectivity ◽  
Leaving Group ◽  
Standard Set ◽  
Specific Association

The N1/N3-alkylation patterns of 4-amino-, 4-methyl- and 4-nitro-benzimidazole anions, and their 2-methyl analogues, with a standard set of primary alkyl halides (in dimethylformamide, 30°) have been determined and compared. The observed regioselectivities are dominated by proximal effects-electrostatic field, non-bonded steric and in some cases specific association (hydrogen bonding)-the interplay of which is critically dependent on the (variable) geometries of the SN2 transition states involved, in particular on the N---C distance of the developing N-alkyl bonds. The presence of a symmetrically placed 2-methyl group produces an enhanced N1/N3 site selectivity, very sensitive to the loose-tight nature of the transition state. Halide leaving group effects on butylation regioselectivities of 2-unsubstituted, 2-ethoxy-, 2-methyl- and 2-chloro-4-methylbenzimidazole anions, whilst small, are consistent with a Bell-Evans-Polanyi analysis of SN2 transition state variations, with the earlier transition states of CH3(CH2)3I leading to reduced regioselectivities.

scholarly journals On the survival of peptide cations after electron capture: Role of internal hydrogen bonding and microsolvation

2006 ◽  
Vol 17 (12) ◽  
pp. 1675-1680 ◽  
Author(s):  
Tapas Chakraborty ◽  
Anne I. S. Holm ◽  
Preben Hvelplund ◽  
Steen Brøndsted Nielsen ◽  
Jean -Christophe Poully ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Electron Capture ◽  
Internal Hydrogen

Structure and Conformations of Gaba-Transaminase Inhibitors. I. Multisubstrate Analogs

1986 ◽  
Vol 39 (10) ◽  
pp. 1559
Author(s):  
PR Andrews ◽  
V Cody ◽  
MN Iskander ◽  
AI Jeffrey ◽  
MF Mackay ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Intramolecular Hydrogen Bonding ◽  
Side Chain ◽  
Gaba Transaminase ◽  
X Ray ◽  
Potential Energy Calculations ◽  
Phenolic Oxygen ◽  
Structural Differences ◽  
Intramolecular Hydrogen

Two multisubstrate analogues of the transition state in the reaction catalysed by the enzyme GABA- transaminase (E.C. 2.6.1.19), sulfonic acid pyridoxal dervative , C10H16N2O5S (1) and carboxylic acid pyridoxal derivative, C13H18N2O4 (2), have been characterized by X-ray analyses of crystals of (1). HCl , (1).H2O and (2). HCl . In each structure, the nitrogen on the side chain is the donor in intramolecular hydrogen bonding. However, it is only in (2). HCl that this interaction is with the phenolic oxygen as postulated in the proposed transition state of the reaction catalysed by GABA- transaminase . For both structures of (1), on the other hand, this interaction is with the oxygen of the ring hydroxymethyl substituent, and results in a seven- membered ring. Conformational analysis indicates that both modes of hydrogen bonding may be present in the pyridoxal derivatives, although no quantitative assessment is possible at the MINDO/3 or MNDO levels. Simple classical potential energy calculations indicate significant structural differences between the lowest energy conformations of these compounds and the calculated transition state. However, conformations which match the key features of the transition state are also relatively low in energy.

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