Synthesis of dendritic self-immolative molecules triggered by reactive electrophilic alkylating agents: Assessment for colorimetric disclosure of such agents

Abstract

The development of efficient chemoselective self-immolative molecules for use as sensors necessitates optimization of the degradation characteristics of the self-immolative unit to permit effective signal generation (e.g. colour changes) in relation to the triggering event. One approach is to utilise degradable dendritic structures to allow multiple copies of signalling molecules to be released in return for a single triggering event. To this end, degradable isomeric dendrons featuring aniline-core units for the detection of reactive electrophilic species have been prepared and their reactions studied. A route employing protected phosphorous-borane adducts was key to their synthesis. Following deprotection of these adducts, to activate the self-immolative dendron, alkylation by an electrophilic species and subsequent elimination events, under basic conditions as employed for related molecules incapable of generating an amplified response, were investigated. These studies revealed, in contrast to the findings with other structurally-related self-immolative dendritic molecules, that the degradation profiles of these dendrons do not afford amplified responses in relation to the number of triggering events. In the light of the expenditure of resources required to generate well-defined dendritic materials, this study provides a cautionary perspective against the assumption that such branched molecules will always afford an amplified signal.