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Synthesis and performance of an alkylating agent sensor

University of British Columbia

4-(4-nitrobenzyl)pyridine (NBP) is a colorimetric indicator compound for many types of carcinogenic alkylating agents. It is used in the toxicological screening of pharmaceutical compounds, detection of chemical warfare agents, environmental hygiene technology, and other chemical analyses. We report a synthesis of NBP-derivatives that allow for the covalent incorporation of NBP into a solid state sensor. These derivatives have been tested in solution and found to be superior in the colorimetric assay of the alkylating agent cyclophosphamide. The derivatives have also been integrated into a polymeric silica material which changes color upon the exposure to dangerous alkylating agents like iodomethane. This material modernizes the NBP assay from a time consuming laboratory analysis to a real-time solid state sensor, which requires neither solvent nor additional reagents, and can detect gas and solution-phase alkylating agents. The NBP assay is used extensively in preliminary tests for determining toxicology profiles and mutagenicity of medicinal compounds because of its similar reactivity to guanine in DNA. The use of NBP as a DNA model suffers from the compound’s low solubility in water, its lack of reactive oxygen sites and dissimilar steric encumbrance compared to DNA. The compounds synthesized in this report attempt to address several of these problems associated with the use of NBP as a DNA model: (1) A water soluble derivative of NBP has been synthesized, and thus an aqueous assay may more closely reflect in vivo conditions, which is an important property in toxicology testing; (2) NBP-derivatives synthesized herein have reactive oxygen sites, which also improves the similarity of these compounds to DNA, since many hard carbocations react at oxygen in DNA; and (3) the polymeric nature of the solid sensors synthesized may more well reflect the sterics of DNA, which is a polymer.

Text

2016-03-31

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/50918

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/