Monomethoxy-4-aminoazobenzenes: a computational study Krishna L. Bhat a , Harold S. Freeman b , Janardhan Velga c , Les Sztandera a , Mendel Trachtman a , Charles W. Bock a, * a Chemistry Department, School of Science and Health, Philadelphia University, School House Lane and Henry Avenue, Philadelphia, PA 19144, USA b College of Textiles, North Carolina State University, Raleigh, NC 27695, USA c School of Textiles and Materials Technology, Philadelphia University, Philadelphia, PA 19144, USA Received 21 March 2000; accepted 18 May 2000 Abstract The structural and electronic properties of the positional isomers of monomethoxy-4-aminoazobenzene (n-OMe- AAB) have been investigated using density functional theory with a basis set that includes polarization functions on all the atoms. These azo dyes are of interest because their carcinogenic activities depend dramatically on the position (n) of the methoxy group, e.g. 3-OMe-AAB is a potent hepatocarcinogen in the rat, whereas 2-OMe-AAB is a non- carcinogen. While it is generally believed that the various isomers of OMe-AAB require metabolic activation via N- hydroxylation prior to reaction with cellular macromolecules, we have shown that there are structural and electronic features present in these isomers that correlate with their carcinogenic behavior. # 2000 Published by Elsevier Science Ltd. Keywords: Azo dyes; Carcinogen; Density functional theory 1. Introduction 3-Methoxy-4-aminoazobenzene (3-OMe-AAB) is a potent hepatocarcinogen in the rat [1]. This azo dye requires metabolic activation to N-hydroxy-3- methoxy-4-aminoazobenzene (N-OH-3-OMe-AAB) prior to reaction with cellular macromolecules [2]. This conclusion is in accord with the observation that 3-OMe-AAB is mutagenic on the Salmonella mammalian mutagenicity assay (Ames test) only after activation with S-9, the 9000 g supernatant fraction of liver homogenate, whereas N-OH-3- OMe-AAB is strongly mutagenic without S-9 activation [3,4]. Interestingly, changing the pos- ition of the methoxy group on the phenyl rings dramatically in¯uences the carcinogenic behavior of the resulting compound [5]. For example, 2- OMe-AAB is noncarcinogenic in rats whereas 4 0 - OMe-AAB is carcinogenic, but to a lesser degree than 3-OMe-AAB. This carcinogenic potency of 2- and 4 0 -OMe-AAB correlates well with their mutagenic activity in the Ames' Salmonella test, where neither 2-OMe-AAB nor its N-hydroxy derivative, N-OH-2-OMe-AAB, is mutagenic even after treatment with S-9; 4 0 -OMe-AAB is very slightly mutagenic in TA98 and N-OH-4 0 -OMe- 0143-7208/00/$ - see front matter # 2000 Published by Elsevier Science Ltd. PII: S0143-7208(00)00042-5 Dyes and Pigments 46 (2000) 109±119 * Corresponding author. Tel.: +1-215-951-2876; fax: +1- 215-951-6812. E-mail address: chuck@larry.texsci.edu (C.W. Bock).