Aminoalkoxyazobenzene dyes - Studies leading to the mechanism of mutagenesis

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Title: Aminoalkoxyazobenzene dyes - Studies leading to the mechanism of mutagenesis
Author: Jeong, Euigyung
Advisors: Harold Stanley Freeman, Committee Chair
David Hinks, Committee Member
Larry D Claxton, Committee Member
Carl L Bumgardner, Committee Member
Abstract: This study is an extension of previous work in our laboratories pertaining to the effects of substituents on the mutagenicity of aminoazobenzene-based dyes (cf. 52 - 66). A key outcome of the previous work was the recognition that bulky alkoxy substituents placed ortho to the primary amino (-NH2) group significantly reduced or removed mutagenicity. In this regard, the ortho-OCH2CH2OH group gave a significant reduction in mutagenicity, with the notable exception of the dye in which R1 = OCH2CH2OH and R2 = N(CH2CH2OH)2 (dye 66). Interestingly, this dye was not mutagenic following reductive cleavage of the azo group, suggesting that metabolism involving the N(CH2CH2OH)2 group was associated with mutagenic activity. It is not clear, however, how the combination R1 = OCH2CH2OH and R2 = N(CH2CH2OH)2 contributes to the anomalous behavior of dye 66. With the above-mentioned results in mind, the present thesis pertains to the synthesis of three analogs of dye 66 (cf. 67 - 69) and the determination of their mutagenicity. These novel structures permit an assessment of the importance of the R2 = N(CH2CH2OH)2 group in producing a mutagenic response when R1 = OCH2CH2OH, as this group is replaced by: 1) NHCH2CH2OH (dye 67), 2) N(CH2CH2OAc)2 (dye 68), and 3) N(CH2CH2OH)2 (dye 69). The target dyes were synthesized by diazotizing and coupling the appropriate alkoxylated anilines to the corresponding N-substituted anilines, and their structures were established by 1H NMR and high resolution FAB and ESI mass spectrometry. Surprisingly, all three dyes were obtained as viscous oils that could not be induced to crystallize. Mutagenicity was assessed in Salmonella strain TA98 with and without S9 enzyme activation, since mutagenicity was observed in dye 66 only in that strain. In this way, the effects of the structural changes would be most evident. The results of the mutagenicity assessment indicated that removing one of the N-hydroxyethylamino groups (cf. dye 67) causes an increase in mutagenicity, while either acetylating the N,N-bis(hydroxyethyl)amino group to give dye 68 or increasing the length of the hydroxyethyl groups to give dye 69 removed mutagenicity. These results suggest that the presence of a free N-hydroxyethyl group in the coupler moiety is responsible for the mutagenicity of parent dye 66. R1 R2 52 OCH3 H 53 OCH2CH3 H 54 OCH2CH2CH3 H 55 OCH2CH2CH2CH3 H 56 OCH2CH2OH H 57 OCH3 N(CH2CH3)2 58 OCH2CH3 N(CH2CH3)2 59 OCH2CH2CH3 N(CH2CH3)2 60 OCH2CH2CH2CH3 N(CH2CH3)2 61 OCH2CH2OH N(CH2CH3)2 62 OCH3 N(CH2CH2OH)2 63 OCH2CH3 N(CH2CH2OH)2 64 OCH2CH2CH3 N(CH2CH2OH)2 65 OCH2CH2CH2CH3 N(CH2CH2OH)2 66 OCH2CH2OH N(CH2CH2OH)2 67 OCH2CH2OH NH(CH2CH2OH) 68 OCH2CH2OH N(CH2CH2OAc)2 69 OCH2CH2OH N(CH2 CH2CH2OH)2
Date: 2004-12-09
Degree: MS
Discipline: Textile Chemistry

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