The method of measuring k35/k31 for the alkoxide-promoted deprotiochlorination and dedeuteriochlorination reactions has been applied to C6H5C,H(CH3)CH2C1 (I-Cl), C6H5C'HC1CH2C1 (V), and C6H5C'HC1CF2C1 (III). For reactions occurring with ethanolic sodium ethoxide the following values for k3S/k31 have been measured: I-Cl-A, 1.005 90 + 0.000 13, and I-Cl-d, 1.
In some cases it has been found that trans elimination from a vinylic halide proceeds by a concerted mechanism whereas the analogous cis elimination is carbanionic (and slower) (See S.
The valence-bond configuration mixing model (VBCM) is applied to the nucleophilic substitution reactions of a-carbonyl derivatives. The model appears to resolve satisfactorily a number of features of these reactions that current mechanisms have not dealt with. These include: (i) the dependence of the rate-enhancing effect of the carbonyl upon the nucleophilic strength of the entering group, (ii) the unusually large Hammett p value for the reaction of PhCOCHzBr with substituted pyridines, and (iii) the mechanism by which the rate-enhancing effect of the carbonyl group is transmitted to the reaction centre.
The cytotoxicity of many nitroaromatic compounds is mediated by bioreduction. There is a correlation between the one-electron-reduction potentials and cytotoxic potencies of simple nitroheterocycles such as nitroimidazoles, but no such correlation is observed with DNA-binding nitroacridines related to the drug nitracrine. A study of the reduction of 1-nitroacridines by the enzyme xanthine oxidase and by reduced flavin mononucleotide, FMNH, (as a model of the enzyme's active site) has been undertaken to explore the redox dependence in this series. The values of V,,,,,/K,,, for reduction by xanthine oxidase, XOD, and the second-order rate constants of reduction by F M N H, , analysed using Marcus electron-transfer theory, indicate a correlation between reduction potential and the rate of reduction, but suggest that the potential-energy barrier for electron transfer is small relative to that imposed by requirements for association, orientation and desolvation of the reactants. The close similarity in Marcus parameters for reduction by FMNH, and by XOD suggests that reduction occurs by a similar mechanism in each case. The free-energy change for electron transfer, AG:, is only 1-2 kJ mot-'. It appears that the rate of reduction is unlikely to be the only determinant of hypoxic cytotoxicity for the nitroacridines, although the applicability of findings with XOD t o other nitroreductases is uncertain.
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