1
24
FERNÁNDEZ-LIENCRES ET AL.
BIBLIOGRAPHY
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Figure 5 Isokinetic effect for nitrosation reaction of phe-
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CONCLUSION
The kinetics of the reactions between sodium ni-
trite and phenol or m-, o-, or p-cresol in potassium
hydrogen phthalate buffers of pH 2.5–5.7 shows: (i)
At pH Ͼ 3 the dominant reaction is C-nitrosation
through a mechanism that appears to consist of a dif-
fusion-controlled attack on the nitrosatable sub-
1
1
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ϩ
ϩ
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2
2
3
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ton transfer step. The latter step is supported by the
observation of basic catalysis by the buffer (which
did not form alternative nitrosating agents in the
form of nitrosyl compounds); (ii) The observed or-
der of substrate reactivities (o-cresol Ϸ m-cresol Ͼ
phenol ϾϾ p-cresol) is explained by the hypercon-
jugative effect of the methyl group in o- and m-cresol,
and by its blocking the para position in p-cresol; (iii)
1
4. L. Toth and K. Potthast, Chemical Aspects of the Smok-
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553, American Chemical Society, Washington, DC,
1994.
#
#
Analysis of the plot ⌬H /⌬S shows that the reaction
with p-cresol differs from those with o- and m-cresol
as regards the formation and decomposition of the
transition state; and (iv) The genotoxicity of nitrosat-
able phenols and their derivatives follows a different
order from that of these substances in their reactivi-
1
1
6. M. C. Archer, N-Nitroso Compounds: Occurrence, Bio-
logical Effects and Relevance to Human Cancer, I. K.
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ϩ
ϩ
ties with NO /NO H .
2
2
The authors thank the Commission of the European Com-
munities for supporting the research reported in this article
as part of a project on the nitrosatable molecules present in
foodstuffs (Contract No. 93CVVF1-610-0). Thanks are also
due to the Spanish Comisión Interministerial de Ciencia y
Tecnología (CICYT) for its support of research on precur-
sor mechanisms of carcinogenesis by N-nitroso compounds
18. D. L. H. Williams, Nitrosation, Cambridge University
Press, Cambridge, 1988.
(
Project No. ALI389/90), and to the Spanish Ministerio de
19. B. C. Challis and A. J. Lawson, J. Chem. Soc. (B), 770
(1971).
20. B. C. Challis and R. J. Higgins, J. Chem. Soc., Perkin
Trans. 2, 2365 (1972).
21. B. C. Challis and R. J. Higgins, J. Chem. Soc., Perkin
Trans. 2, 1597 (1973).
Educación y Ciencia and the Junta de Andalucía for finan-
cial assistance to S. González-Mancebo and M. P. Fernán-
dez-Liencres, respectively. M. P. Fernández-Liencres also
thank J. Casado for facilities afforded during her stay at the
University of Salamanca.