Trifluoromethyl Acetophenone Research Articles

Solvation and its influence on the electronic structure and pharmacological activity of 2-fluoro-6-trifluromethyl acetophenone

The molecular framework and vibrational spectra of 2′-Fluoro-6′-Trifluoromethyl Acetophenone (MA3) in diverse solvent environments are being studied using quantum chemistry methods like DFT. The structure was successfully optimized using gas phase and solvent phases such as ethanol, diethyl sulfoxide, chloroform, and diethyl ether. Using FT-Raman and FT-IR techniques, both theoretical and experimental scenarios were examined. The IEFPCM model was used to explore the electronic properties, including HOMO-LUMO gaps, UV–Vis spectra, NBO, Mulliken analysis, and MEP, in various solvents. The TD-DFT approach and IEFPCM model were utilized to replicate the UV spectra. The Fukui function helped locate reactive sites and understand chemical interactions. Comprehensive topological analysis using Multiwfn – 3.8 suite integrated RDG, ALIE, ELF, and LOL to identify key binding sites and weak interactions. The molecular docking studies highlighted the compound’s binding affinities with target proteins, showcasing its potential pharmacological applications. This research underscores the critical role of solvation in determining the electronic and structural properties of MA3, paving the way for its application in drug development and other fields.

Engineered the Active Site of ω-Transaminase for Enhanced Asymmetric Synthesis Towards (S)-1-[4-(Trifluoromethyl)phenyl]ethylamine.

ω-Transaminase (ω-TA) is a promising biocatalyst for the synthesis of chiral amines. In this study, a ω-TA derived from Vitreoscilla stercoraria DSM 513 (VsTA) was heterologous expressed in recombinant E. coli cells and applied to reduce 4'-(trifluoromethyl)acetophenone (TAP) to (S)-1-[4-(trifluoromethyl)phenyl]ethylamine ((S)-TPE), a pharmaceutical intermediate of chiral amine. Aimed to a more efficient synthesis of (S)-TPE, VsTA was further engineered via a semi-rational strategy. Compared to wild-type VsTA, the obtained R411A variant exhibited 2.39 times higher activity towards TAP and enhanced catalytic activities towards other prochiral aromatic ketones. Additionally, better thermal stability for R411A variant was observed with 25.4% and 16.3% increase in half-life at 30°C and 40°C, respectively. Structure-guided analysis revealed that the activity improvement of R411A variant was attributed to the introduction of residue A411, which is responsible for the increase in the hydrophobicity of substrate tunnel and the alleviation of steric hindrance, thereby facilitating the accessibility of hydrophobic substrate TAP to the active center of VsTA. This study provides an efficient strategy for the engineering of ω-TA based on semi-rational approach and has the potential for the molecular modification of other biocatalysts.

Molecular imprinting of polymerised catalytic complexes in asymmetric catalysis

The hydride transfer reduction of prochiral ketones using rhodium based catalysts has been studied. In homogenous catalysis, acetophenone was quantitatively converted to ( R) phenyl ethanol 3 in 7 days, (67% ee) using two equivalent of (1 S,2 S)- N, N′-dimethyl-1,2-diphenylethane diamine per Rh. We then prepared polyurea supported complex: rhodium containing catalyst were prepared by complexation of the metal to nitrogen ligands in the backbone. Using this catalyst, acetophenone was quantitatively converted to ( S) phenyl ethanol in 1 day, enantiomeric excess was 60%. We have then polymerised preformed [rhodium(I)-( N, N′-dimethyl-1,2-diphenylethane diamine) 2] with di- and triisocyanates. Using the ( S, S) isomer of the diamine leads to the reduction of propiophenone into ( R) in 6 days with 47% ee In order to use molecular imprinting effect, we have polymerised [rhodium(I)-( N, N′-dimethyl-1,2-diphenylethane diamine) 2] in the presence of a chiral template: pure ( R) or ( S) sodium phenylethanolate. Reduction of various substrates was carried out. We have shown that the imprinting effect is obvious for molecule related in structure to the template (propiophenone, 4′-trifluoromethyl acetophenone) and it is not efficient if the substrate has a structure too different from the template one. The studying of conversion vs. global conversion has shown that the mechanism occurs via two parallel reactions on the same site without any interconversion of the final products. Phenyl ethyl ketone was reduced quantitatively in 2 days to ( R) phenyl ethanol ee 70%.