Kinetics and mechanism of oxidation of the anti-tubercular prodrug isoniazid and its analog by iridium(<scp>iv</scp>) as models for biological redox systems

Dong, Jingran; Ren, Yiwei; Sun, Shiqi; Jiao, Yang; Nan, Chunixa; Shi, Hongmei; Xu, Jin-Quan; Duan, Jie; Shi, Tiesheng; Elding, Lars Ivar

doi:10.1039/c7dt00885f

Cited by 22 publications

(23 citation statements)

References 53 publications

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“…For probing some useful information in the reaction course of BH with [IrCl 6 ] 2− , rapid scan spectra were recorded on the stopped-flow spectrometer under a set of reaction conditions. The obtained spectra are shown in Figure 1, which are similar to those acquired previously in the oxidations of INH and hydrazines with [IrCl 6 ] 2− [14,28]. This type of rapid scan spectra renders a few salient features [14,28]: (1) neither a substitution reaction on the Ir(IV) complex nor a strong association between the [IrCl 6 ] 2− and BH before the rate-determining step(s) underwent since the two disappearing bands around 428 and 488 nm which originate from [IrCl 6 ] 2− showed no shifts and no new absorption bands emerged.…”

Section: Spectral Analysis Of Reaction Coursesupporting

confidence: 80%

“…Mechanistically, the anti-tubercular action of INH involves its activation by enzymes generating hydrazyl free radical(s) in the activation course [11][12][13][14]. The involvement of free radicals may not be surprising since numerous oxidation reactions are taking place in biologically and/or biomedically relevant processes which involve a single electron transfer.…”

Section: Introductionmentioning

confidence: 99%

“…[IrCl 6 ] 2− is a well-known single electron oxidizing agent [15][16][17][18][19] and it has been utilized as a redox probe for acquiring chemical information of 2 of 15 oxidative stress [20]. In a recent kinetic study of oxidations of INH and its analog nicotinic hydrazide (NH) by [IrCl 6 ] 2− [14], it was found for the first time that the four protolysis species of INH and NH showed a huge reactivity difference (about 10 9 times) towards reduction of the Ir(IV) complex and the enolate forms of INH and NH were extremely reactive. Inspired by this study, we carried out a similar kinetic investigation of the oxidations of benz(o)hydrazide (BH) and phenylacetic hydrazide (PAH); the structures of INH, NH, BH, and PAH are illustrated in Figure S1 in Supplementary Materials (SM).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

2020

Molecules

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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.

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Section: Spectral Analysis Of Reaction Coursesupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

2020

Molecules

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“…A straightforward way of examining the reactivity of the Hcy species under the physiological pH (7.4) is to construct the reactivity versus pH distribution diagram . The Hcy species versus pH distribution diagram is displayed in Fig.…”

Section: Resultsmentioning

confidence: 99%

Reduction of Cisplatin and Carboplatin Pt(IV) Prodrugs by Homocysteine: Kinetic and Mechanistic Investigations

Tian

Dong

Chi

et al. 2017

Int. J. Chem. Kinet.

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Pt(IV) anticancer active complexes are commonly regarded as prodrugs, and the reduction of the prodrugs to their Pt(II) analogs is the activation process. The reduction of a cisplatin prodrug cis-[Pt(NH 3 ) 2 Cl 4 ] and a carboplatin prodrug cis,trans-[Pt(cbdca)(NH 3 ) 2 Cl 2 ] by DL-homocysteine (Hcy) has been investigated kinetically in a wide pH range in this work. The reduction process follows overall second-order kinetics: −d[Pt(IV)]/dt = k [Hcy] tot [Pt(IV)], where [Hcy] tot stands for the total concentration of Hcy and k pertains to the observed second-order rate constants. The k versus pH profiles have been established for both prodrugs. Spectrohotometric titrations reveal a stoichiometry of [Pt(IV)]: [Hcy] tot = 1:2; homocystine is identified as the major oxidation product of Hcy by high-resolution mass spectrometry. A reaction mechanism has been proposed, which involves all the four protolysis species of Hcy attacking the Pt(IV) prodrugs in parallel. Moreover, these parallel attacks are the rate-determining steps, resulting in a Cl + transfer from the Pt(IV) prodrugs to the attacking sulfur atom. Rate constants An Accumet Basic AB15 Plus pH meter, equipped with an Accumet AccutupH R combination pH electrode (Fisher Scientific, Pittsburgh, PA), was used to measure the pH values of buffer solutions. Each time, the electrode was calibrated using the standard buffers

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“…The reaction stoichiometry was investigated by spectrophotometric titrations as we have used recently . The measured absorption values for the series of reaction mixtures as a function of [HONH 2 ] tot are shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

New kinetic and mechanistic findings in the oxidation of hydroxylamine by Cerium(IV) in perchloric acid media

Tian

Yao

et al. 2018

Int J of Chemical Kinetics

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The oxidation of hydroxylamine (HONH 2 ) by Ce(IV) in perchloric acid media took place fast and was followed by a stopped-flow spectrometer. A rate law of −d[Ce(IV)] tot /dt = k ′ [HONH 2 ] tot [Ce(IV)] tot was proved, where k ′ stands for the observed second-order rate constant and [Ce(IV)] tot and [HONH 2 ] tot represent the total concentrations of Ce(IV) and HONH 2 , respectively. The dependencies of k ′ on [H + ] and on ionic strength were investigated. Rapid scan spectra recorded for a typical reaction course and a stoichiometric measurement unraveled several additional characters for the redox reaction. Based on experimental results, a reaction mechanism is proposed, which involves Ce 4+ , Ce(OH) 3+ , and Ce(OH) 2 2+ attacking on HONH 3 + in parallel. Moreover, these parallel attacking reactions are the ratedetermining steps, generating free radicals • ONH 2 , which are rapidly oxidized to nitrate by Ce(IV). Rate constants of these rate-determining steps have been evaluated; a reactivity trend of Ce 4+ > Ce(OH) 3+ > Ce(OH) 2 2+ is disclosed, but the reactivity differences among them are very small. The rate-determining steps are rationalized in terms of an outer-sphere electron transfer, and possible transition states are proposed in the cases of Ce(OH) 3+ and Ce(OH) 2 2+ to account for the small reactivity differences. The obtained kinetic and mechanistic results in the present work are compared with those acquired previously for the same reaction but in sulfuric acid and nitric media. It is concluded that the reaction media can play a dominant role in determining the reaction kinetics, mechanisms, and the product(s) in the oxidation of hydroxylamine by Ce(IV). K E Y W O R D SCe(IV), hydroxylamine, kinetic mechanism, oxidation 856

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Kinetics and mechanism of oxidation of the anti-tubercular prodrug isoniazid and its analog by iridium(iv) as models for biological redox systems

Cited by 22 publications

References 53 publications

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

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

Reduction of Cisplatin and Carboplatin Pt(IV) Prodrugs by Homocysteine: Kinetic and Mechanistic Investigations

New kinetic and mechanistic findings in the oxidation of hydroxylamine by Cerium(IV) in perchloric acid media

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