Novel aminoquinoline-based solvatochromic fluorescence probe: Interaction with albumin, lysozyme and characterization of amyloid fibrils

Abstract

A novel aminoquinoline derivative (AQ) was synthesized and applied as a solvatochromic fluorescent probe to study proteins and their alterations. AQ is not fluorescent in aqueous solution but has its fluorescence quantum yield significantly increased upon binding to albumin. The generation of an induced circular dichroism signal in AQ confirmed the complexation. The Job's plot method revealed an 1:1 stoichiometry for the host-guest complex. The binding constant was determined by AQ fluorescence increase (2.7 × 105 mol−1 L) and by protein intrinsic fluorescence quenching (5.1 × 105 mol−1 L). The displacement of AQ from albumin by warfarin and ibuprofen showed that Sudlow's drug site-I is the preferential binding site. By applying the Bilot-Kawski solvatochromic model to the spectral shifts of fifteen solvents, the microenvironment dielectric constant at albumin site-I was estimated (ε = 14.8). In agreement, the average fluorescence lifetime of AQ complexed with albumin (6.11 ns) was close to dichloromethane (6.53 ns) and acetone (6.34 ns), which have dielectric constants of 8.9 and 21.0, respectively. Albumin was thermically treated to formation of amyloid fibril aggregates. AQ was able to differentiate the altered and native protein. Sodium dodecyl sulfate-induced aggregation of lysozyme to amyloid fibril was also efficiently detected by the AQ fluorescence increase. AQ was as efficient as the chromogenic bromocresol purple in the quantitative analysis of albumin. In conclusion, AQ can be considered a new solvatochromic fluorescent probe with several potential applications.