6-Amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline: Insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

Abstract

In this work we report detailed structural and computational studies of 6-amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline (1). The structure is stabilized by the intramolecular N–H···N hydrogen bonds, C–H···F interactions, π···π interactions and C–F···F–C interactions. The listed interactions are also reflected on the Hirshfeld surfaces as well as the corresponding 2D fingerprint plots, which revealed that the crystal packing of 1 is mainly dictated by highly favored H···H and H···F contacts followed by also favored H···N, C···C and F···F contacts. The DFT calculations were performed to verify the structure of 1 as well as its electronic and optical properties. Compound 1 was predicted to exhibit preferred results for drug candidates in five parameters, namely lipophilicity, size, polarity, insolubility and flexibility. Furthermore, it was predicted that 1 is likely a potential inhibitor of family A G protein-coupled receptor and kinase; electrochemical transporter and voltage-gated ion channel; oxidoreductase, hydrolase, protease, family C G protein-coupled receptor and primary active transporter with the probabilities of 20.0%, 13.3% and 6.7%, respectively. At the same time, 1 was found to be active against Aryl hydrocarbon Receptor (AhR) and Mitochondrial Membrane Potential (MMP), hepatotoxic and mutagenic. According to the BOILED-Egg method for 1 the human blood-brain barrier (BBB) penetration property is negative and gastrointestinal absorption property is positive with the positive PGP effect on the molecule.