Boronic Acids and Derivatives鈥擯robing the Structure鈥揂ctivity Relationships for Mutagenicity

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• 作者：Marvin M. Hansen ; Robert A. Jolly ; Ryan J. Linder
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：November 20, 2015
• 年：2015
• 卷：19
• 期：11
• 页码：1507-1516
• 全文大小：678K
• ISSN：1520-586X

文摘

Despite a recent publication describing boronic acids as a 鈥渘ovel class of bacterial mutagen,鈥?process and analytical chemists may not be aware of the potential worker exposure hazards, or of the need to assess boron compounds as potential genotoxic impurities (GTIs) per ICH M7. This publication provides new Ames data for 44 commercially available boronic acids, boronic acid derivatives, and boron-containing reagents. Trends in the Ames data are discussed from a structure鈥揳ctivity perspective. Common reagents such as bis(pinacolato)diboron and bis-boronic acid were shown to be mutagenic in the Ames assay. Currently available in silico computational models were found to provide little value in predicting the outcome of the Ames assay for boronic acids and derivatives. We propose oxygen-mediated oxidation of boron compounds to generate organic radicals as a potential mechanism for mutagenicity. It is hoped that this paper will result in increased awareness of this class of GTIs and prompt publication of additional Ames data for boronic acids and their derivatives that will lead to improved (Q)SAR models and an understanding of the mechanism of mutagenicity.