Fluorogenic heptamethine cyanines are highly desirable for biomedical imaging, yet there are limited strategies to develop them. Here, we report a polymethine reactivity-based approach in which a meso-carboxylate undergoes intramolecular nucleophilic attack at the γ-position, forming a cyclized structure that disrupts π-conjugation. These cyclizing Cy7 (c-Cy7) dyes have a solvent-dependent equilibrium between open (fluorescent) and closed (nonfluorescent) forms in polar and nonpolar solvents, respectively. Indolenine substitution can modulate cyclization equilibrium.
Kumarasiri et al. (Wed,) studied this question.