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Global and local chemical reactivities of mutagen X and simple derivatives

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Abstract

Registered by the World Health Organization (WHO), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is one of the strongest bacterial mutagens ever tested, as highlighted by the Ames Salmonella typhimurium TA100 assay. We provide new insights concerning this mutagenic activity on the basis of global and local theoretically defined electrophilicity indices. Our results further support the idea that mutagenicity of MX and its analogues is related more closely to one-electron transfer processes from the electron-rich biological environment than to adduct formation processes. We also stress that, although the Z-open tautomers are intrinsically more electrophilic than furanone ring analogues, the observed mutagenic activity is significantly correlated only to the electrophilicity response of the ring forms. In that context, we also emphasize that it is electrophilicity at the C α in the α–β unsaturated carbonyl moiety that exhibits a strong correlation with the observed mutagenic activity.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its analogues 

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Acknowledgments

This work has been supported by Fondo de Desarrollo de la Ciencia y la Tecnologia, FONDECYT, Chile through Projects 11100412 (ER) and 1100277 (EC). The authors are also indebted to Universidad Austral de Chile and Universidad Andres Bello by the continuous support provided through the S-2010-25, UNAB-DI 57-11R and the Centro Interdisciplinario de Modelamiento Fisiquimico CIMFQ-UNAB, grant DI-219-12N.

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Authors and Affiliations

  1. Instituto de Ciencias Quimicas, Facultad de Ciencias, Universidad Austral de Chile, Las encinas 220, Valdivia, Chile

    Elizabeth Rincon & Francisco Zuloaga

  2. Departamento de Ciencias Quimicas, Facultad de Ciencias, Universidad Andres Bello, Av. Republica 275, 8370146, Santiago, Chile

    Eduardo Chamorro

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  1. Elizabeth Rincon
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  2. Francisco Zuloaga
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Correspondence to Elizabeth Rincon.

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Rincon, E., Zuloaga, F. & Chamorro, E. Global and local chemical reactivities of mutagen X and simple derivatives. J Mol Model 19, 2573–2582 (2013). https://doi.org/10.1007/s00894-013-1799-7

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