The Dinuclear Zn(II) Complex Catalyzed Cyclization of a Series of 2-Hydroxypropyl Aryl Phosphate RNA Models:  Progressive Change in Mechanism from Rate-Limiting P−O Bond Cleavage to Substrate Binding

2007 ◽  
Vol 129 (51) ◽  
pp. 16238-16248 ◽  
Author(s):  
Shannon E. Bunn ◽  
C. Tony Liu ◽  
Zhong-Lin Lu ◽  
Alexei A. Neverov ◽  
R. Stan Brown
Keyword(s):  
Bond Cleavage ◽  
Substrate Binding ◽  
Progressive Change ◽  
Rate Limiting

The molecular mechanism of the open–closed protein conformational cycle transitions and coupled substrate binding, activation and product release events in lysine 5,6-aminomutase

2016 ◽  
Vol 52 (38) ◽  
pp. 6399-6402 ◽  
Author(s):  
Hsin-Hsi Lo ◽  
Hsin-Hua Lin ◽  
Amarendra Nath Maity ◽  
Shyue-Chu Ke
Keyword(s):  
Molecular Mechanism ◽  
Bond Cleavage ◽  
Substrate Binding ◽  
Closed Cycle ◽  
Product Release

The contributions of Lys370α and Asp298α to the critical Co–C bond cleavage trigger and open–closed cycle transitions of lysine 5,6-aminomutase.

Ligand-Accelerated Non-Directed C–H Cyanation of Arenes

2018 ◽  
Author(s):  
Luoyan Liu ◽  
Kap-Sun Yeung ◽  
jin-quan yu
Keyword(s):  
Natural Products ◽  
Bond Cleavage ◽  
Drug Molecules ◽  
Kinetic Isotope ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Broad Scope ◽  
Synthetic Utility ◽  
Rate Limiting

<p>We herein report the first example of a 2-pyridone accelerated non-directed C−H cyanation with an arene as the limiting reagent. This protocol is compatible with a broad scope of arenes, including advanced intermediates, drug molecules, and natural products. A kinetic isotope experiment (k<sub>H</sub>/k<sub>D</sub> = 4.40) indicates that the C–H bond cleavage is the rate-limiting step. Also, the reaction is readily scalable, further showcasing the synthetic utility of this method.<i></i></p>

scholarly journals Design, Synthesis, andIn VitroKinetics Study of Atenolol Prodrugs for the Use in Aqueous Formulations

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Rafik Karaman ◽  
Alaa Qtait ◽  
Khulod Khayyat Dajani ◽  
Saleh Abu Lafi
Keyword(s):  
Density Functional ◽  
Bond Cleavage ◽  
Parent Drug ◽  
Acid Group ◽  
Amide Bond ◽  
Design Synthesis ◽  
Rate Limiting Step ◽  
Amide Bond Cleavage ◽  
Rate Limiting

Based on DFT, MP2, and the density functional from Truhlar group (hybrid GGA: MPW1k) calculations for an acid-catalyzed hydrolysis of nine Kirby’s N-alkylmaleamic acids and two atenolol prodrugs were designed. The calculations demonstrated that the amide bond cleavage is due to intramolecular nucleophilic catalysis by the adjacent carboxylic acid group and the rate-limiting step is determined based on the nature of the amine leaving group. In addition, a linear correlation of the calculated and experimental rate values has drawn credible basis for designing atenolol prodrugs that are bitterless, are stable in neutral aqueous solutions, and have the potential to release the parent drug in a sustained release manner. For example, based on the calculated B3LYP/6-31 G (d,p) rates, the predictedt1/2(a time needed for 50% of the prodrug to be converted into drug) values for atenolol prodrugs ProD 1-ProD 2 at pH 2 were 65.3 hours (6.3 hours as calculated by GGA: MPW1K) and 11.8 minutes, respectively.In vitrokinetic study of atenolol prodrug ProD 1 demonstrated that thet1/2was largely affected by the pH of the medium. The determinedt1/2values in 1N HCl, buffer pH 2, and buffer pH 5 were 2.53, 3.82, and 133 hours, respectively.

scholarly journals Enzyme catalysis by entropy without Circe effect

2016 ◽  
Vol 113 (9) ◽  
pp. 2406-2411 ◽  
Author(s):  
Masoud Kazemi ◽  
Fahmi Himo ◽  
Johan Åqvist
Keyword(s):  
Free Energy ◽  
Density Functional ◽  
Cytidine Deaminase ◽  
Binding Free Energy ◽  
Substrate Binding ◽  
Enzymatic Reaction ◽  
Valence Bond ◽  
Activation Entropy ◽  
Uncatalyzed Reaction ◽  
Rate Limiting

Entropic effects have often been invoked to explain the extraordinary catalytic power of enzymes. In particular, the hypothesis that enzymes can use part of the substrate-binding free energy to reduce the entropic penalty associated with the subsequent chemical transformation has been very influential. The enzymatic reaction of cytidine deaminase appears to be a distinct example. Here, substrate binding is associated with a significant entropy loss that closely matches the activation entropy penalty for the uncatalyzed reaction in water, whereas the activation entropy for the rate-limiting catalytic step in the enzyme is close to zero. Herein, we report extensive computer simulations of the cytidine deaminase reaction and its temperature dependence. The energetics of the catalytic reaction is first evaluated by density functional theory calculations. These results are then used to parametrize an empirical valence bond description of the reaction, which allows efficient sampling by molecular dynamics simulations and computation of Arrhenius plots. The thermodynamic activation parameters calculated by this approach are in excellent agreement with experimental data and indeed show an activation entropy close to zero for the rate-limiting transition state. However, the origin of this effect is a change of reaction mechanism compared the uncatalyzed reaction. The enzyme operates by hydroxide ion attack, which is intrinsically associated with a favorable activation entropy. Hence, this has little to do with utilization of binding free energy to pay the entropic penalty but rather reflects how a preorganized active site can stabilize a reaction path that is not operational in solution.

Evidence for rate limiting C-H bond cleavage in the leuckart reaction

Tetrahedron ◽  
1990 ◽  
Vol 46 (6) ◽  
pp. 1899-1910 ◽  
Author(s):  
Peter I. Awachie ◽  
Vincent C. Agwada
Keyword(s):  
Bond Cleavage ◽  
Rate Limiting

scholarly journals Substrate Binding Is the Rate-limiting Step in Thromboxane Synthase Catalysis

2001 ◽  
Vol 276 (18) ◽  
pp. 14737-14743 ◽  
Author(s):  
Lee-Ho Wang ◽  
Ah-Lim Tsai ◽  
Pei-Yung Hsu
Keyword(s):  
Substrate Binding ◽  
Thromboxane Synthase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

scholarly journals OH-Initiated Atmospheric Degradation of Hydroxyalkyl Hydroperoxides: Mechanism, Kinetics, and Structure-Activity Relationship

2021 ◽  
Author(s):  
Long Chen ◽  
Yu Huang ◽  
Yonggang Xue ◽  
Zhihui Jia ◽  
Wenliang Wang
Keyword(s):  
Bond Cleavage ◽  
Radical Reaction ◽  
Peroxyl Radicals ◽  
Atmospheric Conditions ◽  
Transformation Mechanism ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
New Findings ◽  
Bond Scission ◽  
Rate Limiting

Abstract. Hydroxyalkyl hydroperoxides (HHPs), formed in the reactions of Criegee intermediates (CIs) with water vapour, play essential roles in the formation of secondary organic aerosol (SOA) under atmospheric conditions. However, the transformation mechanism for OH-initiated oxidation of HHPs is remain incompletely understood. Herein, the quantum chemical and kinetics modeling methods are applied to insight into the detailed mechanisms of OH-initiated oxidation of distinct HHPs formed form the reactions of CH2OO, anti-CH3CHOO and (CH3)2COO) with water vapor. The calculations show that H-abstraction by OH radical from the -OOH group of distinct HHPs is predominate as the main products peroxyl radicals (RO2), and the barrier of dominant pathway is increased as the number of methyl group is increased. In pristine environments, the self-reaction of RO2 radical initially produces tetroxide intermediate via a head-to-head interaction, then it decomposes into propagation and termination products through the asymmetric two-step O-O bond scission, in which the rate-limiting step is the first O-O bond cleavage. The barrier height of distinct RO2 radicals reactions with HO2 radical is independent on the number of methyl substitution. Compared to the rate coefficient of parent system, it is increased by a factor of 3–5 when one or two methyl groups introduce into the C1-position. The autoxidation of RO2 radicals are unlikely to proceed in the atmosphere due to their dramatically high barriers and strongly endergonic. In urban environments, the rate-limiting step is the hydrogen abstraction by O2 in the processes of HOCH2OO radical reaction with NO, while it becomes the O-O bond scission when one or two methyl substitutions occur at the C1-position of HOCH2OO radical. These new findings are expected to deepen our current understanding for the photochemistry oxidation of hydroperoxides under realistic atmospheric conditions.

scholarly journals C–H Bond Cleavage Is Rate-Limiting for Oxidative C–P Bond Cleavage by the Mixed Valence Diiron-Dependent Oxygenase PhnZ

Biochemistry ◽  
2019 ◽  
Vol 58 (52) ◽  
pp. 5271-5280 ◽  
Author(s):  
Simanga R. Gama ◽  
Becky Suet Yan Lo ◽  
Jacqueline Séguin ◽  
Katharina Pallitsch ◽  
Friedrich Hammerschmidt ◽  
...  
Keyword(s):  
Bond Cleavage ◽  
Mixed Valence ◽  
Rate Limiting
Sign in / Sign up

Export Citation Format

Share Document