Studies on biologically active acylhydrazones. Part 1. Acid–base equilibria and acid hydrolysis of pyridoxal aroylhydrazones and related compounds

Lees-Gayed, Nicholas; Abou‐Taleb, M. A.; El‐Bitash, I. A.; Iskander, Magdi F.

doi:10.1039/p29920000213

Cited by 18 publications

(3 citation statements)

References 30 publications

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“…The assignment of pK a values of ionisable protons in the HPCIH analogues conforms to reports of similar aroylhydrazones. [30][31][32][33][34][35][36] The first protonation constant (pK 1 ) is associated with the hydrazone N-NH-C=O group, while the lower pK a value (pK 2 ) is assigned to protonation of the 2-pyridyl ring, which is supported by crystallographic evidence reported here (Fig. 4).…”

Section: Protonation Constantssupporting

confidence: 78%

Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity

et al. 2007

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Section: Protonation Constantssupporting

confidence: 78%

Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity

et al. 2007

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“…2 In addition, for compounds of the 100 series, the calculations of log P calc values are uncertain because in neutral water solution the compounds do not have the structure 1 but the zwitterionic structure ( Fig. 3) (Lees-Gayed et al 1992;Richardson et al 1990). The zwitterionic form would be expected to be more soluble in water, and to have log P lower by an uncertain amount.…”

Section: Pitfalls In Calculations Of Log P By Rekker's Additive Methodsmentioning

confidence: 99%

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. Relationship of the lipophilicity of the apochelator to its ability to mobilize iron from reticulocytes in vitro: reappraisal of reported partition coefficients

Edward¹,

Chubb²,

Sangster³

1997

Can. J. Physiol. Pharmacol.

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The partition coefficients P between n-octanol and water of pyridoxal isonicotinoyl hydrazone and 34 analogues have been determined experimentally; the values indicate that the partition coefficients calculated for these compounds, and previously reported (P. Ponka, D.R. Richardson, J.T. Edward, and F.L. Chubb. Can. J. Physiol. Pharmacol. 72: 659-666. 1994; D.R. Richardson, E.H. Tran, and P. Ponka. Blood, 86: 4294-4306. 1994), are too low by 2-3 orders of magnitude. The calculations, using Rekker's additive method, failed because the molecules have two or more hydrophilic sites close together. More recent additive schemes (CLOGP, KOWWIN, ACD/LogP) also failed. The only reliable method was the semi-empirical method of Hansch. This requires the experimental determination of the partition coefficient of at least one representative in each series of compounds of related structure. In the present paper, determination of log P of three representatives enabled us to calculate the partition coefficients of the other 32 compounds with acceptable accuracy. The new results show that apochelators have maximum activity in releasing 59Fe from reticulocytes when they have log P = 2.8 (P = 630), and not log P = 0 (P = 1), as reported by Ponka et al. (P. Ponka, D.R Richardson, J.T. Edward, and F.L Chubb. Can. J. Physiol. Pharmacol. 72: 659-666 1994).

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“…So far, only one study reported rapid disappearance of CDX in various waters ( t 1/2 = 0.8−3.4 min) dosed with 1.0 mg Cl 2 /L of free chlorine, in which neither the effect of pH on reaction kinetics nor product formation were assessed (). CDX and DCDX are comprised of functional groups including N -oxide, hydrazone, and carbazate moieties that can be found in a broad range of pharmaceuticals, agrochemicals, and industrial chemicals for N -oxides ( , ), in medical agents and agricultural pesticides for hydrazones ( , ), and in weed-killing and fungicidal pesticides for carbazates ( , ). A fundamental understanding of the reactivity of these functional groups toward aqueous chlorine can have widespread applications.…”

Section: Introductionmentioning

confidence: 99%

Reaction Kinetics and Transformation of Carbadox and Structurally Related Compounds with Aqueous Chlorine

Shah

Kim

Huang

2006

Environ. Sci. Technol.

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The potential release of carbadox (CDX), a commonly used antibacterial agent in swine husbandry, into water systems is of a concern due to its carcinogenic and genotoxic effects. Until this study, the reactivity of carbadox (possessing quinoxaline N,N'-dioxide and hydrazone moieties) toward aqueous chlorine has yetto be investigated in depth. Chemical reactivity, reaction kinetics, and transformation pathways of carbadox and structurally related compounds with free chlorine under typical water treatment conditions were determined. This study found that only CDX and desoxycarbadox (DCDX), a main metabolite of CDX with no ring N-oxide groups, react rapidly with free chlorine while other structurally related compounds including olaquindox, quindoxin, quinoxaline N-oxide, quinoxaline, and quinoline N-oxide do not. The reaction kinetics of CDX and DCDX with chlorine are highly pH dependent (e.g., the apparent second-order rate constant, kapp, for CDX ranges from 51.8 to 3.15 x 10(4) M(-1)s(-1) at pH 4-11). The high reactivity of CDX and DCDX to chlorine involves deprotonation of their hydrazone N-H moieties where initial chlorine attack results in a reactive intermediate that is further attacked by nucleophiles in the matrix to yield non-chlorinated, hydroxylated, and larger molecular weight byproducts. All of the CDX's byproducts retain their biologically active N-oxide groups, suggesting that they may remain as active antibacterial agents.

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Studies on biologically active acylhydrazones. Part 1. Acid–base equilibria and acid hydrolysis of pyridoxal aroylhydrazones and related compounds

Cited by 18 publications

References 30 publications

Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity

Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. Relationship of the lipophilicity of the apochelator to its ability to mobilize iron from reticulocytes in vitro: reappraisal of reported partition coefficients

Reaction Kinetics and Transformation of Carbadox and Structurally Related Compounds with Aqueous Chlorine

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