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

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 (<i>K</i> _<i>d</i> ) 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.