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

1,2-Borotropic shifts and B–N bond cleavage reactions in molybdenum hydrotris(3-isopropylpyrazolyl)borate chemistry: Mixed-valence MoVIMo2V and pyrazole-rich oxo-MoIV complexes

2009 ◽  
Vol 362 (12) ◽  
pp. 4570-4577 ◽  
Author(s):  
Jonathan M. White ◽  
Victor W.L. Ng ◽  
Damian C. Clarke ◽  
Paul D. Smith ◽  
Michelle K. Taylor ◽  
...  
Keyword(s):  
Bond Cleavage ◽  
Mixed Valence ◽  
Cleavage Reactions

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.

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 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 Reductive half-reaction of the H172Q mutant of trimethylamine dehydrogenase: evidence against a carbanion mechanism and assignment of kinetically influential ionizations in the enzyme–substrate complex

1999 ◽  
Vol 341 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Jaswir BASRAN ◽  
Michael J. SUTCLIFFE ◽  
Russ HILLE ◽  
Nigel S. SCRUTTON
Keyword(s):  
Active Site ◽  
Bond Cleavage ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Trimethylamine Dehydrogenase ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
Ph Range ◽  
Rate Limiting ◽  
Macroscopic Pka

The reactions of wild-type trimethylamine dehydrogenase (TMADH) and of a His-172 Gln (H172Q) mutant were studied by rapid-mixing stopped-flow spectroscopy over the pH range 6.0-10.5, to address the potential role of His-172 in abstracting a proton from the substrate in a ‘carbanion’ mechanism for C-H bond cleavage. The pH-dependence of the limiting rate for flavin reduction (klim) was studied as a function of pH for the wild-type enzyme with perdeuterated trimethylamine as substrate. The use of perdeuterated trimethylamine facilitated the unequivocal identification of two kinetically influential ionizations in the enzyme-substrate complex, with macroscopic pKa values of 6.5±0.2 and 8.4±0.1. A plot of klim/Kd revealed a bell-shaped curve and two kinetically influential ionizations with macroscopic pKa values of 9.4±0.1 and 10.5±0.1. Mutagenesis of His-172, a potential active-site base and a component of a novel Tyr-His-Asp triad in the active site of TMADH, revealed that the pKa of 8.4±0.1 for the wild-type enzyme-substrate complex represents ionization of the imidazolium side-chain of His-172. H172Q TMADH retains catalytic competence throughout the pH range investigated. At pH 10.5, and in contrast with the wild-type enzyme, flavin reduction in H172Q TMADH is biphasic. The fast phase is dependent on the trimethylamine concentration and exhibits a kinetic isotope effect of about 3; C-H bond cleavage is thus partially rate-limiting. In contrast, the slow phase does not show hyperbolic dependence on substrate concentration, and the observed rate shows no dependence on isotope, revealing that C-H bond cleavage is not rate-limiting. The analysis of H172Q TMADH, together with data recently acquired for the Y169F mutant of TMADH, reveals that C-H bond breakage is not initiated via abstraction of a proton from the substrate by an active-site base. The transfer of reducing equivalents to flavin via a carbanion mechanism is therefore unlikely.

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