Fluorine induced conformational switching and modulation in photophysical properties of 7-fluorotryptophan: Spectroscopic, quantum chemical calculation and molecular dynamics simulation studies

Abstract

7-Fluorotryptophan (7F-Trp) is an important noncanonical derivative of tryptophan (Trp) amino acid which depicts high in vivo stability for the positron emission tomography imaging of Trp metabolism. Irrespective of biological importance of 7F-Trp, molecular level understanding about its fluorescence behavior and the photophysical properties in different solvents are still unknown. Hence, the photophysical properties of 7F-Trp in presence of biochemically important alcoholic solvents ethanol (ETH), 2,2,2 trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-propan-2-ol (HFIP) has been investigated using spectroscopic, quantum chemical calculation, molecular dynamic simulation and compared with Trp to understand the role of fluorine in its fluorescence behavior. The substitution of fluorine on Trp decreases its fluorescence intensity significantly. The presence of fluorine on tryptophan perturbs the interaction of its backbone containing COO− and NH3+ with the chromophoric indole group which probably decreases the barrier of the conical intersection leading to decreased fluorescence intensity of 7F-Trp compared to Trp. The fluorescence intensity of Trp and 7F-Trp decreases in presence of fluorinated alcohols compared to ETH. However, the decrease in fluorescence intensity of 7F-Trp is less than Trp and peak maxima are blue shifted. Moreover, the trend of excited state lifetime of 7F-Trp in fluorinated alcohols is opposite to Trp suggesting that the interaction of 7F-Trp with fluorinated solvents is different than Trp. The excited state lifetime of Trp in alcoholic solvents is controlled mainly by solvent polarity. In contrast, the weak interaction mediated by the fluorine of 7F-Trp with the fluorine and OH groups of fluorinated solvents plays an important role in modulation of its excited state lifetime. This study clearly depicts that noncanonical fluorine of 7F-Trp plays an important role in controlling its fluorescence properties in the biochemically important alcoholic solvents.