Synthesis and Performance of a Biomimetic Indicator for Alkylating Agents

4-(4-Nitrobenzyl)­pyridine (NBP) is
a colorimetric indicator compound
for many types of carcinogenic alkylating agents. Because of the similar
reactivity of NBP and guanine in DNA, NBP serves as a DNA model. NBP
assays are used in the toxicological screening of pharmaceutical compounds,
detection of chemical warfare agents, environmental hygiene technology,
preliminary toxicology tests, mutagenicity of medicinal compounds,
and other chemical analyses. Nevertheless, the use of NBP as a DNA
model suffers from the compound’s low water solubility, its
lack of reactive oxygen sites, and dissimilar steric encumbrance compared
to DNA. We report herein the design and synthesis of NBP derivatives
that address some of these issues. These derivatives have been tested
in solution and found to be superior in the colorimetric assay of
the alkylating anticancer drug cyclophosphamide. The derivatives have
also been integrated into a polymeric silica material which changes
color upon the exposure to dangerous alkylating agents, such as iodomethane
vapor, without the need for an exogenous base. 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 both gas- and solution-phase alkylating agents.