Highly Sensitive Naphthalene-Based Twisted Intramolecular Charge Transfer Molecules for the Detection of In Vitro and In Cellulo Protein Aggregates

Abstract

Newly synthesized naphthalene-based twisted intramolecular charge transfer (TICT) molecules show 8.5- and 2.6-fold increases in fluorescence intensity upon binding with protein aggregates in comparison with the fluorescence enhancement for thioflavin T (ThT). The dissociation constant (Kd) values of these compounds with bovine serum albumin (BSA) aggregates are in the 145–176 nM range, which is 103 times lower than that of ThT. Along with the strong binding propensity, these molecules are also capable of measuring protein aggregate (BSA) concentration in the 500 to 5 pM level. Interestingly, one of the synthesized molecules was also able to bind with the intracellular protein aggregates.