Nitrosation Kinetics of Phenolic Components of Foods and Beverages

The kinetics of the reactions between sodium nitrite and phenol or m-, o-, or p-cresol in potassium hydrogen phthalate buffers of pH 2.5–5.7 were determined by integration of the monitored absorbance of the C-nitroso reaction products. At pH . 3, the dominant reaction was C-nitrosation through a mechanism that appears to consist of a diffusion-controlled attack on the nitrosatable substrate by NO/NO2H2 1 ions followed by a slow proton transfer step; the latter step is supported by the observation of basic catalysis by the buffer which does not form alternative nitrosating agents as nitrosyl compounds. The catalytic coefficients of both anionic forms of the buffer have been determined. The observed order of substrate reactivities (o-cresol < m-cresol . phenol .. p-cresol) is explained by the hyperconjugative effect of the methyl group in oand m-cresol, and by its blocking the para position in p-cresol. Analysis of a plot of DH against DS shows that the reaction with p-cresol differs from those with oand m-cresol as regards the formation and decomposition of the transition state. The genotoxicity of nitrosatable phenols is compared with their reactivity with NO/NO2H2 1. © 1997 John Wiley & Sons, Inc. Received May 8, 1995; accepted March 5, 1996 * On leave from Departamento de Química física y Analítica, Facultad de Ciencias Experimentales, Universidad, E-23071, Jaén, Spain. † Author to whom correspondence should be addressed. International Journal of Chemical Kinetics, Vol. 29, 119–125 (1997) © 1997 John Wiley & Sons, Inc. CCC 0538-8066/97/020119-07 120 FERNÁNDEZ-LIENCRES ET AL. cursors of genotoxic substances, it is of some concern that phenol, catechol, vanillin, and other phenolics have been detected in smoked fish and meats [14]. It has also been reported that the presence of phenolic compounds can block the N-nitrosation reactions of other substrates [15,16], and although this has been questioned on the grounds that N-nitrosation is catalyzed by monohydroxy phenols [17] (but not by all polyhydroxyphenols [15]), it should be borne in mind that catalytic activity is only observed when the concentration of nitrosating agent significantly exceeds the concentration of phenol, which rarely occurs in vivo or in environmentally significant situations. In spite of the biomedical significance of the nitrosation of phenolics, little research has been done on the mechanisms of these reactions [18]. However, according to Challis and co-workers [1,19–21] the Cnitrosation of simple phenols in perchloric media generally involves the formation of a dienone intermediate that loses a proton from its nitrosated carbon to yield the nitrosophenol in equilibrium with its oxime form. p-Alkylphenols yield the corresponding 2-nitrosocompounds, whereas p-bromophenol is transformed by a fast substitution reaction into p-nitrosophenol, although in both cases the nitrosocompound is rapidly oxidized to the corresponding nitrocompound. In the case of the nitrosation in perchloric media the 2-nitrosocompounds are considered to be rapidly oxidized to the corresponding nitrocompound. However, the course of the reaction between nitrite and p-methoxyphenol appears to depend on the concentration of perchloric acid in the medium: 4-methoxy2-nitrophenol is only formed if the perchloric acid concentration is low (pH 2–3), and even then it is not the major product; if perchloric acid concentration is high, benzoquinone is formed in quantitative yield [20]. Similar results for phenol and 4-phenoxyphenol as well as 4-methoxyphenol were obtained by Moodie and co-workers [22–24] in studies that, like others on the nitrosation of certain phenolic drugs [13,25–28], also showed that the course of these reactions can depend on the concentration of dissolved oxygen in the medium and on whether the concentration of nitrite is greater or less than that of the substrate. While different studies have been carried out in buffered media by buffers such as acetic-acetate or monochloroacetic-monochloroacetate ([29]; Challis et al., loc. cit.), practically no work has been done with buffers which do not form alternative nitrosating agents in the form of nitrosyl compounds. In this work we investigated the nitrosation of phenol and of m-, o-, and p-cresol by sodium nitrite in potassium hydrogen phthalate buffers that did not form any potential nitrosating agent.