TY - JOUR

T1 - 6-Amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline: Insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

AU - Babashkina, Maria G.

AU - Safin, Damir A.

PY - 2023

Y1 - 2023

N2 - 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 center dot center dot center dot N hydrogen bonds, C-H center dot center dot center dot F interactions, pi center dot center dot center dot pi interactions and C-F center dot center dot center dot 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 center dot center dot center dot H and H center dot center dot center dot F contacts followed by also favored H center dot center dot center dot N, C center dot center dot center dot C and F center dot center dot center dot 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.

AB - 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 center dot center dot center dot N hydrogen bonds, C-H center dot center dot center dot F interactions, pi center dot center dot center dot pi interactions and C-F center dot center dot center dot 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 center dot center dot center dot H and H center dot center dot center dot F contacts followed by also favored H center dot center dot center dot N, C center dot center dot center dot C and F center dot center dot center dot 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.

UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=000799417900001

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85130618217

U2 - 10.1080/10406638.2022.2068622

DO - 10.1080/10406638.2022.2068622

M3 - Article

VL - 43

SP - 3324

EP - 3341

JO - Polycyclic Aromatic Compounds

JF - Polycyclic Aromatic Compounds

SN - 1040-6638

IS - 4

ER -