scholarly journals Oxidations of Benzhydrazide and Phenylacetic Hydrazide by Hexachloroiridate(IV): Reaction Mechanism and Structure–Reactivity Relationship

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 308 ◽  
Author(s):  
Xiaolai Zhang
Keyword(s):  
Reaction Mechanism ◽  
Rational Design ◽  
Outer Sphere ◽  
Order Rate Constant ◽  
Second Order ◽  
Spectroscopic Techniques ◽  
Oxidation Reactions ◽  
Product Analysis ◽  
Pka Values ◽  
Rate Determining Steps

Benz(o)hydrazide (BH) is the basic aryl hydrazide; aryl hydrazides have been pursued in the course of drug discovery. Oxidations of BH and phenylacetic hydrazide (PAH) by hexachloroiridate(IV) ([IrCl6]2−) were investigated by use of stopped-flow spectral, rapid spectral scan, RP-HPLC and NMR spectroscopic techniques. The oxidation reactions followed well-defined second-order kinetics and the observed second-order rate constant k′ versus pH profiles were established over a wide pH range. Product analysis revealed that BH and PAH were cleanly oxidized to benzoic acid and phenylacetic acid, respectively. A reaction mechanism was proposed, resembling those suggested previously for the oxidations of isoniazid (INH) and nicotinic hydrazide (NH) by [IrCl6]2−. Rate constants of the rate-determining steps were evaluated, confirming a huge reactivity span of the protolysis species observed previously. The enolate species of BH is extremely reactive towards reduction of [IrCl6]2−. The determined middle-ranged negative values of activation entropies together with rapid scan spectra manifest that an outer-sphere electron transfer is probably taking place in the rate-determining steps. The reactivity of neutral species of hydrazides is clearly not correlated to the corresponding pKa values of the hydrazides. On the other hand, a linear correlation, logkenolate = (0.16 ± 0.07)pKenol + (6.1 ± 0.8), is found for the aryl hydrazides studied so far. The big intercept and the small slope of this correlation may pave a way for a rational design of new antioxidants based on aryl hydrazides. The present work also provides the pKa values for BH and PAH at 25.0 °C and 1.0 M ionic strength which were not reported before.

scholarly journals Kinetic Analysis of the Reduction Processes of a Cisplatin Pt(IV) Prodrug by Mesna, Thioglycolic Acid, and Thiolactic Acid

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yanqing Xia ◽  
Hongwu Tian ◽  
Yanlei Li ◽  
Xinru Yang ◽  
Jinming Liu ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Thioglycolic Acid ◽  
Thiol Group ◽  
Order Rate Constant ◽  
Second Order ◽  
Transient Species ◽  
Reduction Processes ◽  
Wide Ph Range ◽  
Reaction Stoichiometry ◽  
Rate Determining Steps

Although Mesna is an FDA-approved chemotherapeutic adjuvant and an antioxidant based largely on its antioxidative properties, kinetic and mechanistic studies of its redox reactions are limited. A kinetic analysis of the reduction processes of cis-diamminetetrachloroplatinum(IV) (cis-[Pt(NH3)2Cl4], a cisplatin Pt(IV) prodrug) by thiol-containing compounds Mesna, thioglycolic acid (TGA), and DL-thiolactic acid (TLA) was carried out in this work at 25.0°C and 1.0 M ionic strength. The reduction processes were followed under pseudo-first-order conditions and were found to strictly obey overall second-order kinetics; the observed second-order rate constant k′ versus pH profiles were established in a wide pH range. A general reaction stoichiometry of Δ[Pt(IV)] : Δ[Thiol]tot = 1 : 2 was revealed for all the thiols; the thiols were oxidized to their corresponding disulfides which were identified by mass spectrometry. Reaction mechanisms are proposed which involves all the prololytic species of the thiols attacking the Pt(IV) prodrug in parallel, designating as the rate-determining steps. Transient species chlorothiol and/or chlorothiolate are formed in these steps; for each particular thiol, these transient species can be trapped rapidly by another thiol molecule which is in excess in the reaction mixture, giving rise to a disulfide as the oxidation product. The rate constants of the rate-determining steps were elucidated, revealing reactivity enhancements of (1.4–8.9) × 105 times when the thiols become thiolates. The species versus pH and reactivity of species versus pH distribution diagrams were constructed, demonstrating that the species ‒SCH2CH2SO3‒ of Mesna largely governs the total reactivity when pH > 5; in contrast, the form of Mesna per se (mainly as HSCH2CH2SO3‒) makes a negligible contribution. In addition, a well-determined dissociation constant for the Mesna thiol group (pKa2 = 8.85 ± 0.05 at 25.0°C and μ = 1.0 M) is offered in this work, which was determined by both kinetic approach and spectrophotometic titration method.

scholarly journals Antioxidative Reactivity of L-Ascorbic Acid and D-Isoascorbic Acid Species towards Reduction of Hexachloroiridate (IV)

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Han Zhang ◽  
Yanqing Xia ◽  
Peng Zhang ◽  
Liqian Hou ◽  
Ying Sun ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Rate Constants ◽  
Dehydroascorbic Acid ◽  
Outer Sphere ◽  
Spectrophotometric Titration ◽  
Second Order ◽  
Oxidation Products ◽  
Isoascorbic Acid ◽  
Parallel Reactions ◽  
Rate Determining Steps

The pair [IrCl6]2–/[IrCl6]3– has been demonstrated to be a good redox probe in biological systems while L-ascorbic acid (AA) is one of the most important antioxidants. D-isoascorbic acid (IAA) is an epimer of AA and is widely used as an antioxidant in various foods, beverages, meat, and fisher products. Reductions of [IrCl6]2– by AA and IAA have been analyzed kinetically and mechanistically in this work. The reductions strictly follow overall second-order kinetics and the observed second-order rate constants were collected in the pH region of 0 ≤ pH ≤ 2.33 at 25.0°C. Spectrophotometric titration experiments revealed a well-defined 1 : 2 stoichiometry, namely Δ[AA] : Δ[Ir(IV)] or Δ[IAA] : Δ[Ir(IV)] = 1 : 2, indicating that L-dehydroascorbic acid (DHA) and D-dehydroisoascorbic acid (DHIA) were the oxidation products of AA and IAA, respectively. A reaction mechanism is suggested involving parallel reactions of [IrCl6]2– with three protolysis species of AA/IAA (fully protonated, monoanionic, and dianionic forms) as the rate-determining steps and formation of ascorbic/isoascorbic and ascorbate/isoascorbate radicals; in each of the steps, [IrCl6]2– acquires an electron via an outer-sphere electron transfer mode. Rate constants of the rate-determining steps have been derived or estimated. The fully protonated forms of AA and IAA display virtually identical reactivity whereas ascorbate and isoascorbate monoanions have a significant reactivity difference. The ascorbate and isoascorbate dianions are extremely reactive and their reactions with [IrCl6]2– proceed with the diffusion-controlled rate. The species versus pH and the species reactivity versus pH distribution diagrams were constructed endowing that the ascorbate/isoascorbate monoanionic form dominated the total reactivity at physiological pH. In addition, the value of pKa1 = 3.74 ± 0.05 for IAA at 25.0°C and 1.0 M ionic strength was determined in this work.

scholarly journals Full Kinetics and a Mechanistic Investigation of the Green Protocol for Synthesis of β-Aminoketone in the Presence of Saccharose as a Catalyst by a One-Pot Three-Component Reaction

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sayyed Mostafa Habibi-Khorassani ◽  
Malek Taher Maghsoodlou ◽  
Mehdi Shahraki ◽  
Sadegh Talaie Far ◽  
Mir Rasul Mousavi
Keyword(s):  
Reaction Mechanism ◽  
Rate Constant ◽  
Order Rate Constant ◽  
Second Order ◽  
One Pot ◽  
Green Protocol ◽  
Order Rate ◽  
Rate Determining Step ◽  
Mechanistic Investigation ◽  
Three Component Reaction

For the first time, in a green protocol, an investigation of the kinetics and mechanism of the reaction between benzaldehyde 1, 4-chloroanilinne 2, and acetophenone 3 compounds in the presence of saccharose as a catalyst was performed for generating β-aminoketone. For determining the kinetic parameters, the reaction was monitored by using the UV/Vis spectrophotometry technique. The second order rate constant (k1) was automatically calculated by the standard equations contained within the program. In the studied temperature range, the second order rate constant (ln k1, ln k1/T) depended on reciprocal temperature that was in good consistent with Arrhenius and Eyring equations, respectively. These data provided the suitable plots for calculating the activation energy and parameters (Ea, ΔG‡, ΔS‡, and ΔH‡) of the reaction. Furthermore, useful information was obtained from studying the effects of solvent, concentration, and catalyst on the reaction mechanism. The results showed that the first step of the reaction mechanism is a rate determining step (RDS). The obtained experimental data and also the steady state assumption confirmed the proposed mechanism.

scholarly journals The pH-dependence of second-order rate constants of enzyme modification may provide free-reactant pKa values

1977 ◽  
Vol 167 (3) ◽  
pp. 859-862 ◽  
Author(s):  
K Brocklehurst ◽  
H B F Dixon
Keyword(s):  
Rate Constant ◽  
Rate Constants ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
Second Order ◽  
Quasi Equilibrium ◽  
Pka Values ◽  
First Order ◽  
Order Rate ◽  
Parallel Reactions

1. Reactions of enzymes with site-specific reagents may involve intermediate adsorptive complexes formed by parallel reactions in several protonic states. Accordingly, a profile of the apparent second-order rate constant for the modification reaction (Kobs., the observed rate constant under conditions where the reagent concentration is low enough for the reaction to be first-order in reagent) against pH can, in general, reflect free-reactant-state molecular pKa values only if a quasi-equilibrium condition exists around the reactive protonic state (EHR) of the adsorptive complex. 2. Usually the condition for quasi-equilibrium is expressed in terms of the rate constants around EHR: (formula: see text) i.e. k mod. less than k-2. This often cannot be assessed directly, particularly if it is not possible to determine kmod. 3. It is shown that kmod. must be much less than k-2, however, if kobs. (the pH-independent value of kobs.) less than k+2. 4. Since probable values of k+2 greater than 10(6)M-1.S-1 and since values of kobs. for many modification reactions less than 10(6)M-1.S-1, the equilibrium assumption should be valid, and kinetic study of such reactions should provide reactant-state pKa values. 5. This may not apply to catalyses, because for them the value of kcat./Km may exceed 5 X 10(5)M-1.S-1. 6. The conditions under which the formation of an intermediate complex by parallel pathways may come to quasi-equilibrium are discussed in the Appendix.

The Synthesis and Catalytic Application of a New Class of Imprinted Silica

2003 ◽  
Vol 787 ◽  
Author(s):  
John D. Bass ◽  
Sandra L. Anderson ◽  
Alexander Katz
Keyword(s):  
Rational Design ◽  
Chemical Reactivity ◽  
Phenylboronic Acid ◽  
Coupling Reaction ◽  
Suzuki Coupling ◽  
Outer Sphere ◽  
Suzuki Coupling Reaction ◽  
New Class ◽  
Catalytic Application ◽  
Rate Acceleration

AbstractThe effect of chemical environment surrounding a synthetic heterogeneous catalyst active site is investigated using the hydrophilic imprinting of silica. Two model reaction systems have been used for this study: (i) Knoevenagel condensation of 3-nitrobenzaldehyde and malononitrile and (ii) Suzuki coupling of bromobenzene and phenylboronic acid. Using a catalyst in which isolated imprinted amines are surrounded by an acidic silanol-rich environment led to rate accelerations of over 120-fold relative to catalysts in which the amines are surrounded by a hydrophobic environment consisting of trimethylsilyl functional groups for system (i). This result parallels our previous study on the effect of the outer sphere composition on rate acceleration of Knoevenagel reactions using isophthalaldehyde as the aldehyde reactant. We also extended our method for the hydrophilic imprinting of bulk silica to organometallic systems, by successfully synthesizing a tethered palladium complex within the imprinted pocket. This material was used as an active catalyst for (ii). Our results show that a hydrophobic framework environment results in higher initial turnover frequencies than an acidic silanol-rich framework for the Suzuki coupling reaction of bromobenzene and phenylboronic acid, albeit with a lower overall effect than observed in the Knoevenagel system (i). Altogether, these results demonstrate the control of chemical reactivity via the rational design of the outer sphere using an imprinting approach.

Analytical resolution of a parallel second-order reaction mechanism

2003 ◽  
Vol 35 (6) ◽  
pp. 246-251
Author(s):  
A. E. Croce ◽  
L. V. Mogni ◽  
C. Vicente Irrazábal
Keyword(s):  
Reaction Mechanism ◽  
Order Reaction ◽  
Second Order ◽  
Second Order Reaction ◽  
Analytical Resolution

scholarly journals The reactivities and ionization properties of the active-site dithiol groups of mammalian protein disulphide-isomerase

1991 ◽  
Vol 275 (2) ◽  
pp. 335-339 ◽  
Author(s):  
H C Hawkins ◽  
R B Freedman
Keyword(s):  
Rate Constant ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
Second Order ◽  
Native Enzyme ◽  
Liver Protein ◽  
Thiol Groups ◽  
Protein Disulphide Isomerase ◽  
Order Rate ◽  
Reactive Groups

1. The number of reactive thiol groups in mammalian liver protein disulphide-isomerase (PDI) in various conditions was investigated by alkylation with iodo[14C]acetate. 2. Both the native enzyme, as isolated, and the urea-denatured enzyme contained negligible reactive thiol groups; the enzyme reduced with dithiothreitol contained two groups reactive towards iodoacetic acid at pH 7.5, and up to five reactive groups were detectable in the reduced denatured enzyme. 3. Modification of the two reactive groups in the reduced native enzyme led to complete inactivation, and the relationship between the loss of activity and the extent of modification was approximately linear. 4. Inactivation of PDI by alkylation of the reduced enzyme followed pseudo-first-order kinetics; a plot of the pH-dependence of the second-order rate constant for inactivation indicated that the essential reactive groups had a pK of 6.7 and a limiting second-order rate constant at high pH of 11 M-1.s-1. 5. Since sequence data on PDI show the presence within the polypeptide of two regions closely similar to thioredoxin, the data strongly indicate that these regions are chemically and functionally equivalent to thioredoxin. 6. The activity of PDI in thiol/disulphide interchange derives from the presence of vicinal dithiol groups in which one thiol group of each pair has an unusually low pK and high nucleophilic reactivity at physiological pH.

scholarly journals Rational design of a functional NOR in Mb to understand reaction mechanism (581.1)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Julian Reed ◽  
Saumen Chakraborty ◽  
Matthew Ross ◽  
Mark Nilges ◽  
Charles Schulz ◽  
...  
Keyword(s):  
Reaction Mechanism ◽  
Rational Design

Electrocatalytic Oxidative Upgrading of Biomass Platform Chemicals: From the Aspect of Reaction Mechanism

2021 ◽  
Author(s):  
Hua Zhou ◽  
Zhenhua Li ◽  
Lina Ma ◽  
Haohong Duan
Keyword(s):  
Reaction Mechanism ◽  
Oxygen Evolution ◽  
Oxygen Evolution Reaction ◽  
Oxidation Reactions ◽  
Platform Chemicals ◽  
Wide Range

Oxidation reactions provide a wide range of important chemicals in industry; however, most of them are produced from fossil feedstocks. As a candidate of oxygen evolution reaction (OER), the electrooxidation...

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