Switchable phenolo-cyanine reporters containing reactive alkylcarboxylic groups for fluorescence-based targeted drug delivery monitoring

Three hydrophilic indocyanine dyes containing central 4-acetoxy-1,3-phenylene (O-acetyl-phenolic) moiety and 5-H, 5-sulfo and 5-methylencarboxylic substituents at both terminal indolenines were synthesized. Due to the π-conjugated system in these phenolo-cyanines being broken, these dyes absorb at shorter-wavelength region (∼400 nm) and have a negligible fluorescence. However, upon acetyl group cleavage (under hydrolytic physiological conditions) phenolo-cyanines transform into the π-conjugated quinono-cyanines that absorb at ∼600 nm and fluoresce at ∼715 nm with a Stokes shift (∼2700 cm⁻¹). These dyes can also decompose into the aldehydes. The electron donative 5-methylencarboxylic group was found to decrease the rates of both processes (acetyl group cleavage and decomposition) and increase the dynamic range of changing the fluorescence intensity, while the electron withdrawing 5-sulfo group has the opposite effect. The 5-methylencarboxylic derivative is suggested as a promising switchable reporter for fluorescence-based monitoring of targeted drug delivery.