Electron Density Distribution Research Articles

3D fluid simulation of the propagation of a nanosecond discharge in air above a liquid surface: investigation of the pattern formation under various conditions and comparison with experiments

Abstract Plasma-liquid interaction remains one of the fundamental processes influencing the various applications. Understanding the influence of external parameters on discharge properties, particularly the discharge dynamic at the liquid surface, is therefore essential. In previous studies, we investigated the impact of voltage polarity, gap distance, and liquid dielectric permittivity and electrical conductivity on nanosecond discharges initiated in air at atmospheric pressure in a pin-to-liquid configuration. Herein, we present a 3D fluid model, improved with stochastic photoionization, to simulate the discharge dynamics under the previously mentioned conditions. The model outputs are compared with the discharge dynamics measured experimentally. For instance, filamentation and the homogeneous emission over solution’s surface measured in positive and negative discharges, respectively, are well reproduced by the simulation. Furthermore, the simulation allowed us to report other plasma properties not accessible experimentally such as the spatio-temporal distributions of electric field (E-field) and electron density. Notably, we observe that the E-field at the front of the negative surface ionization wave (SIW) is nearly four times lower than that of the positive SIW, which may explain the absence of filaments for negative discharges. Furthermore, we find that increasing solution conductivity or gap distance reduce the radial propagation velocity of the circular SIW front and stopping its expansion before a destabilization can occur. The simulation allowed investigating the influence of photoionization strength, and we find that increasing the number of ionizing photons leads to supress the filamentation while keeping the ionization front circular and propagating at high speed.

Tuning the electronic structure and SMSI by integrating trimetallic sites with defective ceria for the CO2 reduction reaction

Heterogeneous catalysts have emerged as a potential key for closing the carbon cycle by converting carbon dioxide (CO 2 ) into value-added chemicals. In this work, we report a highly active and stable ceria (CeO 2 )-based electronically tuned trimetallic catalyst for CO 2 to CO conversion. A unique distribution of electron density between the defective ceria support and the trimetallic nanoparticles (of Ni, Cu, Zn) was established by creating the strong metal support interaction (SMSI) between them. The catalyst showed CO productivity of 49,279 mmol g −1 h −1 at 650 °C. CO selectivity up to 99% and excellent stability (rate remained unchanged even after 100 h) stemmed from the synergistic interactions among Ni-Cu-Zn sites and their SMSI with the defective ceria support. High-energy-resolution fluorescence-detection X-ray absorption spectroscopy (HERFD-XAS) confirmed this SMSI, further corroborated by in situ electron energy loss spectroscopy (EELS) and density functional theory (DFT) simulations. The in situ studies (HERFD-XAS & EELS) indicated the key role of oxygen vacancies of defective CeO 2 during catalysis. The in situ transmission electron microscopy (TEM) imaging under catalytic conditions visualized the movement and growth of active trimetallic sites, which completely stopped once SMSI was established. In situ FTIR (supported by DFT) provided a molecular-level understanding of the formation of various reaction intermediates and their conversion into products, which followed a complex coupling of direct dissociation and redox pathway assisted by hydrogen, simultaneously on different active sites. Thus, sophisticated manipulation of electronic properties of trimetallic sites and defect dynamics significantly enhanced catalytic performance during CO 2 to CO conversion.

A comprehensive study of the influence of non-covalent interactions on electron density redistribution during the reaction between acetic acid and methylamine.

A chemical reaction can be described, from a physicochemical perspective, as a redistribution of electron density. Additionally, non-covalent interactions locally modify the electron density distribution. This study aims to characterize the modification of reactivity caused by the presence of non-covalent interactions such as hydrogen bonds, in a reaction involving the formation of two bonds and the breaking of two others: CH₃COOH + NH₂CH₃ → CH₃CONHCH₃. In this work, we will follow the how a reaction mechanism involving the formation of two chemical bonds and the breaking of two other chemical bonds is affected by non-covalent interaction. To this end, the reaction force will be used to define the region of the reagents, the region of the transition state, and the region of the products. We will analyze the redistributions of electron density and electron pairs in each of the regions of the reaction mechanisms, using QTAIM and ELF, topological analyses, respectively, for the reaction between methylamine and acetic acid, in the presence of 0 to 4 water molecules. DFT calculations were carried out at the LC-ωPBE/6-311 + + G(d,p) + GD3BJ level along the intrinsic reaction coordinate of the one-step reaction leading to the formation of methylacetamide.

Towards a unified fold-cusp model for bond polarity scaling: electron rearrangements in the pyrolytic isomerization of cubane to cyclooctatetraene.

This study meticulously examines the criteria for assigning electron rearrangements along the intrinsic reaction coordinate (IRC) leading to bond formation and breaking processes during the pyrolytic isomerization of cubane (CUB) to 1,3,5,7-cyclooctatetraene (COT) from both thermochemical and bonding perspectives. Notably, no cusp-type function was detected in the initial thermal conversion step of CUB to bicyclo[4.2.0]octa-2,4,7-triene (BOT). Contrary to previous reports, all relevant fluxes of the pairing density must be described in terms of fold unfolding. The transannular ring opening in the second step highlights characteristics indicative of a cusp-type catastrophe, facilitating a direct comparison with fold features. This fact underscores the critical role of density symmetry persistence near topographical events in determining the type of bifurcation. A fold-cusp unified model for scaling the polarity of chemical bonds is proposed, integrating ubiquitous reaction classes such as isomerization, bimolecular nucleophilic substitution, and cycloaddition. The analysis reveals that bond polarity index (BPI) values within the [0, 10-5] au interval correlate with cusp unfolding, whereas fold spans over a broader [10-3, ∞) au spectrum. These insights emphasize that the cusp polynomial is suitable for describing chemical processes involving symmetric electron density distributions, particularly those involving homolytic bond cleavages; in contrast, fold characterizes most chemical events. Geometry optimization and frequency calculations were conducted using various DFT functionals. In line with recent findings concerning the rigorous application of BET, the characterization of bond formations and scissions via unfoldings was carried out by carefully monitoring the determinant of the Hessian matrix at all potentially degenerate CPs and their relative distance. The computed gas-phase activation enthalpies strongly align with experimental values, stressing the adequacy of the chosen levels of theory in describing the ELF topography along the IRC. The BPI was determined using the methodology proposed by Allen and collaborators.

Synthesis, crystal structure, hirshfeld study, DFT analysis, molecular docking study, antimicrobial activity of β-enaminonitrile bearing 1H-pyran

3-Amino-1-(3,4-dimethoxyphenyl)-8-methoxy-1H-benzo[f]chromene-2-carbonitrile (3-ABC, 4) was prepared and affirmed through the spectral data and single crystal X-rays diffraction. The molecule spatial attributes were revealed by the three-dimensional Hirshfeld surface, which is validated by comprehensive statistical evaluations. The key interactions that contribute to the crystal's stability and properties, such as π–π stacking and H⋯X contacts, were highlighted. The dominant forces in the crystal were explained by energy framework calculations and density functional theory analyses, which also show the geometric optimization aspects and molecular reactivity indicators. The focus is on the investigation of frontier molecular orbitals, aromaticity, and π–π stacking abilities. The research concluded by identifying electron density distributions, aromatic features, and possible reactivity sites, offering a complete picture of the compound's structural and electronic landscape. Compound 4 was screened for its antimicrobial capability against three Gram-positive, three Gram-negative bacteria, and three fungi, utilizing the reference antibiotic drug Ampicillin, Gentamycin, and Ketoconazole. Compound 4 exhibited favorable antimicrobial activities that were lower/resembled the reference antimicrobial agents with an IZ range of 15–31 mm. In addition, MIC, MBC, and MFC were assessed and screened for the target molecule 4, unveiling its revealing antimicrobial activities. Lastly, the molecular docking evaluation was implemented for the molecules interaction with the DHFR protein. The compounds exhibit significant interactions with the EGFR protein's active site.

Proton dose deposition in heterogeneous media: A TOPAS Monte Carlo simulation study.

This study investigated the influence of tissue electron density on proton beam dose distribution using TOPAS Monte Carlo simulation. Heterogeneous tissue models composed of 14 materials were constructed to simulate the dose deposition process of a 169.23MeV proton beam. The study analyzed the relationships between electron density and key parameters such as maximum dose, total dose, and dose distribution. Results showed that increasing electron density led to higher local maximum dose, lower total dose, and decreased Bragg peak depth, range, penumbra width, and full width at half maximum (FWHM). High-density tissues caused a sharp, concentrated Bragg peak at shallower depths, while low-density tissues caused a backward shift and widening of the Bragg peak. Differences in proton energy deposition in various tissues were the fundamental reasons for dose distribution variations. This study quantified the relationship between electron density and proton beam dose distribution, providing a reference for accurate dose calculation and optimization in proton therapy.

Investigation of the adsorption behavior of Cl and O2 on Al (111) surface based on density functional theory

This study systematically investigates the adsorption behavior of Cl and O2 on the Al surface using first-principle calculations based on density functional theory. The calculation results show that the surface energy of Al on (111) surface is 0.8539J / m2, which is the smallest, indicating that the lowest energy is required for crystal formation on the surface of Al (111). For Cl, the adsorption at the Top site is the most stable, and the adsorption energy is 4.71eV, while the adsorption of O2 at the FCC site is the most stable, and the adsorption energy is 9.92eV. The electronic structure and charge density distribution of Cl and O2 adsorbed on Al (111) surface are also studied. Compared with Cl, the adsorption energy of O2 on Al (111) surface is larger (1.84Å), the length of covalent bond formed is shorter, the number of electron transfer in the adsorption process is more (about 1.79 e), the width of hybrid orbital overlap is wider, and the combination with Al surface is closer. Therefore, the strong adsorption characteristics of O2 in the corrosion process lead to a greater impact on the Al alloy.

Numerical simulation of state parameter distributions and extreme ultraviolet radiation in laser-produced tin plasma

The laser-produced Sn plasma light source is a critical component in advanced extreme ultraviolet (EUV) lithography. The power and stability of EUV radiation within a 2% bandwidth centered at 13.5 nm are key indicators that determine success of the entire lithography process .The plasma state parameter distributions and the EUV radiation spectrum for a laser-produced Sn plasma light source are numerically simulated in this work. The radiative opacity of Sn plasma within the 12–16 nm range is calculated using a detailed-level-accounting model in the local thermodynamic equilibrium approximation. Next, the temperature distribution and the electron density distribution of plasma generated by nanosecond laser pulses interacting with both a Sn planar solid target and a liquid droplet target are simulated using the radiation hydrodynamics code for laser-produced plasma, RHDLPP. By combining the radiative opacity data with the plasma state data, the spectral simulation subroutine SpeIma3D is employed to model the spatially resolved EUV spectra for the planar target plasma and the angle-resolved EUV spectra for the droplet target plasma at a 60-degree observation angle. The variation of in-band radiation intensity at 13.5 nm within the 2% bandwidth as a function of observation angle is also analyzed for the droplet-target plasma. The simulated plasma state parameter distributions and EUV spectral results closely match existing experimental data, demonstrating the ability of RHDLPP code to model laser-produced Sn plasma EUV light sources. These findings provide valuable support for the development of EUV lithography and EUV light sources.

Spectroscopic, DFT, In Silico, and Estimation of Biological Activity of 2,4‐Dichloro‐6,7‐Dimethoxyquinazoline as a Potential Anti‐Alzheimer's Disease Therapeutic Agent

ABSTRACTAlzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive and behavioral decline. In this study, 2,4‐dichloro‐6,7‐dimethoxyquinazoline (DCDQ) was extensively analyzed using a combination of spectroscopic and computational approaches. Geometric parameters and vibrational modes were computed using DFT/B3LYP/6‐311++G(d,p), and experimental FT‐IR, FT‐Raman, and UV–vis spectrum confirmed the compound's structural properties. Time‐dependent DFT (TD‐DFT) calculations provided insights into the electronic structure, including HOMO‐LUMO energies and global reactivity descriptors. Molecular electrostatic potential (MEP) analysis and Mulliken population studies identified reactive sites and bonding characteristics, while NBO analysis revealed significant hyperconjugative interactions contributing to stability. Advanced topological analyses (ELF, LOL, NCI, and RDG) and QTAIM studies were performed using Multiwfn software to explore the compound's electron density distribution. Biological relevance was established through molecular docking studies, which highlighted a strong binding affinity of DCDQ with the 4EY7 protein (binding energy: −8.2 kcal/mol), suggesting its potential as a potent acetylcholinesterase (AChE) inhibitor. Molecular dynamics simulations further validated the stability of the protein‐ligand interaction. ADMET predictions also supported favorable pharmacokinetic and safety profiles of DCDQ. These findings collectively demonstrate the potential of DCDQ as a promising lead compound for the treatment of Alzheimer's disease, offering a solid foundation for future therapeutic development.

Modeling interface roughness scattering with incorporation of potential energy and wave-function fluctuations: Enhancing mobility in AlN/GaN digital alloys

Interface roughness (IFR) scattering significantly impacts the mobility of two-dimensional electron gases (2DEGs) in heterostructures. While existing models for IFR scattering have advanced our understanding, they have notable limitations. The model developed by Jin et al. in 2007, while incorporating a realistic barrier height and roughness-induced changes in potential and subband wave-functions, employs a first-order roughness expansion. The formulation introduced by Lizzit et al. in 2014, although avoiding the first-order approximation for better higher-order effect modeling, omits IFR-induced change in electron density distribution. To address these limitations, we introduce a novel model that comprehensively accounts for all IFR-induced effects while avoiding any expansion approximations, by incorporating IFR-modified subband energies and wave-functions obtained from the numerical solution of the Schrödinger equation during the calculation of IFR scattering matrix elements. In addition, we have included models for other relevant scattering mechanisms, including charged dislocation lines, ionized impurities, acoustic phonons, and polar optical phonons. A comprehensive numerical analysis of carrier mobility has been performed for an AlN/GaN high electron mobility transistor, yielding results consistent with experimental data. Furthermore, to investigate the impact of device architecture on 2DEG mobility, we study the effects of layer thickness and modulation doping profiles in AlN/GaN digital alloys. Our findings reveal strategies for engineering high mobility at elevated 2DEG concentrations, potentially advancing the development of high-performance semiconductor devices.

Numerical studies of the voltage amplitude effect on plasma characteristics in atmospheric pressure driven by dual LF-RF frequency discharge

Abstract Dielectric barrier discharges (DBDs) are primarily utilized as efficient sources of large-volume diffuse plasmas. However, the synergistic interaction of certain key plasma factors limits their broader application. In the present study, we report on numerical investigations of the effects of voltage amplitude in dual-frequency excitation on atmospheric DBDs using a 50 kHz/5 MHz frequency combination. Our results indicate that varying the voltages for LF and RF significantly influences the electron dynamics during discharge, resulting in distinct spatiotemporal distributions of electron and metastable particle densities. These findings contribute to the regulation of discharges under atmospheric pressure conditions and facilitate the attainment of non-equilibrium and nonlinear plasma parameters.

EMC3-EIRENE simulations of edge plasma and impurity transport by toroidally localized argon seeding on CFETR X-divertor

Abstract Three-dimensional (3D) Edge Monte Carlo transport code EMC3-EIRENE has been employed to study edge plasma and impurity transport with toroidally localized argon seeding on Chinese fusion engineering testing reactor (CFETR) X-divertor configuration. The argon impurity seeded at different poloidal locations has been investigated to evaluate the varied profile of the main plasma in the scrape-off layer (SOL) and on the divertor targets, which shows a strong dependence on the poloidal position of argon gas puffing. The argon impurity seeded at the upstream SOL regions can result in a toroidally asymmetric distribution of electron density and temperature, while a toroidally symmetric distribution is obtained for argon seeded at the strike point regions. The deposition pattern of electron density and temperature shows the several lobe-like and island-like structures on the 3D divertor targets of CFETR with upstream argon injections, whereas the perturbed profile is achieved for argon seeding at the strike point regions. In order to verify the toroidal asymmetry of heat loads distribution, the argon impurity seeded at different poloidal locations has been investigated to estimate its influence on toroidal heat loads on divertor plates. The argon injected at the strike point regions gives rise to a toroidal asymmetry of heat loads distribution on divertor targets, while a toroidal symmetry of heat loads distribution is gained for argon injected at the upstream SOL locations.

B─C Bonding Configuration Manipulation Strategy Toward Synergistic Optimization of Polarization Loss and Conductive Loss for Highly Efficient Electromagnetic Wave Absorption

AbstractIn non‐metallic atom‐doped carbonaceous materials, the disparity in electronegativity between the doped constituents and carbon atoms predetermines the bonding topology of covalent bonds and the distribution of electron density. This, consequently, influences the polarization and electron transport behavior within the doped domain and the electromagnetic wave attenuation attributes of the carbonaceous material. However, the influence of covalent bonds formed by doping with weakly electronegative atoms on electron density distribution, polarization effects, and electromagnetic wave attenuation remains uncharted. To address this deficiency, this study fabricates a porous carbonaceous material (NCP) and incorporates boron‐doped atoms to form a material with tunable B─C bonding configurations (B‐NCP). By modulating the B─C bonding configuration and proportion, it is feasible to achieve the synergistic optimization of conductive loss and polarization loss of the B‐NCP specimen. The optimized prototype B‐NCP‐1200 sample displays exceptionally efficient electromagnetic wave absorption capabilities with a minimum reflection loss (RLmin) of −52.03 dB and an effective absorption bandwidth (EAB) of 5.36 GHz. This study presents a conscientious model for comprehending the electromagnetic attenuation mechanisms associated with weakly electronegative atom doping in carbon‐based electromagnetic wave‐absorbing materials.

Unsymmetric Protonation Driven Highly Efficient H2O2 Photosynthesis in Supramolecular Photocatalysts via One-Step Two-Electron Oxygen Reduction.

Photocatalytic hydrogen peroxide (H2O2) production has emerged as an attractive alternative to the traditional anthraquinone process. However, its performance is often hindered by low selectivity and sluggish kinetics of oxygen reduction reaction (ORR). Herein, we report an anthrazoline-based supramolecular photocatalyst, SA-SADF-H+, featuring an unsymmetric protonation structure for H2O2 photosynthesis from water and air. The introduction of unsymmetric protonation disrupts the initial mirror symmetry of SADF, significantly enhancing the molecular dipole and facilitating efficient charge separation and electron transfer. Additionally, this modification increases the hydrophilicity of SA-SADF-H+, enabling the interaction of water and dissolved oxygen with the catalytic sites. The altered electron density distribution creates numerous dual active sites for Yeager-type O2 adsorption, facilitating an efficient ORR towards H2O2 via a direct one-step two-electron pathway. Notably, SA-SADF-H+ achieves an outstanding photocatalytic H2O2 production at a rate of 4666.7 μmol L-1 h-1, with a remarkable solar-to-chemical conversion (SCC) of 1.35 %, surpassing most organic photocatalytic systems. Furthermore, SA-SADF-H+ demonstrates remarkable photocatalytic antibacterial activity, achieving 100 % antibacterial efficiency against Staphylococcus aureus within 60 min.

Unsymmetric Protonation Driven Highly Efficient H2O2 Photosynthesis in Supramolecular Photocatalysts via One‐Step Two‐Electron Oxygen Reduction

AbstractPhotocatalytic hydrogen peroxide (H2O2) production has emerged as an attractive alternative to the traditional anthraquinone process. However, its performance is often hindered by low selectivity and sluggish kinetics of oxygen reduction reaction (ORR). Herein, we report an anthrazoline‐based supramolecular photocatalyst, SA‐SADF‐H+, featuring an unsymmetric protonation structure for H2O2 photosynthesis from water and air. The introduction of unsymmetric protonation disrupts the initial mirror symmetry of SADF, significantly enhancing the molecular dipole and facilitating efficient charge separation and electron transfer. Additionally, this modification increases the hydrophilicity of SA‐SADF‐H+, enabling the interaction of water and dissolved oxygen with the catalytic sites. The altered electron density distribution creates numerous dual active sites for Yeager‐type O2 adsorption, facilitating an efficient ORR towards H2O2 via a direct one‐step two‐electron pathway. Notably, SA‐SADF‐H+ achieves an outstanding photocatalytic H2O2 production at a rate of 4666.7 μmol L−1 h−1, with a remarkable solar‐to‐chemical conversion (SCC) of 1.35 %, surpassing most organic photocatalytic systems. Furthermore, SA‐SADF‐H+ demonstrates remarkable photocatalytic antibacterial activity, achieving 100 % antibacterial efficiency against Staphylococcus aureus within 60 min.

The effect of the external magnetic field on the power of the laser passing through the magnetized plasma and the calculation of the radius of convergence and the investigation of the condition of the beam's filamentation in the Medium

In this article, the power of a laser passing through a magnetized plasma medium which is affected by an external magnetic field is calculated.The change in the intensity of the magnetic field and its rotation around the axis of laser beam propagation in the plasma, on the power of the passing beam is investigated.This work is done based on the indirect effect of the magnetic field on the density distribution of electrons in the plasma, which we can consider the density changes as changes in the refractive index of the medium, so the laser power in this case is different from the case where there is no magnetic field. Also, the condition of beam filamentation has been researched as one of the third-order nonlinear phenomena, and the convergence radius has been calculated under these conditions.

Ab-initio investigations of icosahedral boron compounds with Al, Mg, C, O, Si atoms

The geometry and cohesive energy of isolated clusters — fragments of icosahedral boron compounds — with Al, Mg, C, O, Si substitution atoms have been calculated within the framework of DFT electron density theory using the Gamess software package. Electron density distribution between atoms has been investigated. The bulk modulus of the B12 cluster has been calculated on the basis of quantum chemical calculations and a thermodynamic series of cluster hardness has been constructed: HB22O2 > HB22C2 > HB24 > HB22Si2 > HB22Al2 > HB22Mg2. The calculated bulk modulus and hardness values based on the results of the first-principles study of the clusters are in good agreement with the experimental data for compounds with similar chemical compositions. The technique is applicable to the prediction of the choice of substitutional atoms in icosahedral boron groupings. Keywords: boron, boride, isolated cluster model, bulk modulus, hardness.

A “pre-constrained bimetallic” strategy for the preparation of efficient synergistic electrocatalytic hydrogen evolution catalysts

A micro-sized bimetallic nanoparticles (NPs) catalyst that anchors a mixture of Co and Pd atoms onto a porous nitrogen-doped carbon (NC) framework for electrocatalysis of hydrogen evolution reaction (HER). Programmable metal-porphyrin ligands serve as building blocks for attaching bimetallic sites (consisting of Co and Pd) in metal-organic frameworks for decentralized anchoring before pyrolysis. Experimental studies have shown the interaction between Pd and Co in Co20/Pd20-NC results in electron depletion near Co and electron accumulation near Pd, respectively. Therefore, there is an asymmetric local electron density distribution on the bimetallic site of Co20/Pd20-NC, which improves the activity of the catalyst. To achieve a current density of 10 mA·cm−2 in both acidic and alkaline conditions, the Co20/Pd20-NC exhibits noteworthy HER characteristics with overpotentials of 23 and 52 mV, respectively. The Co20/Pd20-NC prepares in this study which shows good characteristics in the process of electrocatalytic hydrogen evolution, and has a good application prospect.

Study of the structure of atomics by the method of electron scattering in the distorted-wave approximation: Atomic energy

Using distorted-wave approximation obtained the differential cross-section (DCS) of elastic scattering at energy of 80 eV of electrons on 49In, 31Ga, 34Se and 70Yb atoms, and calculated accordingly on the proposed mathematical method. The electron density distribution in the atom is chosen as a function calculated in the Dirac-Hartree-Fock-Slater approximation, which is a superposition of the spherically symmetric Yukawa potential. In addition, the DCSs were calculated for the electron density in the 49 In and 20 Ca atoms expressed as a three-parameter Fermi function at incident electron energy of 100 eV. The obtained theoretical calculations of the cross sections were compared with the experimental data. Besides, the proposed mathematical method simplifies the calculation of integral expressions and makes it possible to obtain a convenient and simple expression for the atomic form factor. Data on the scattering cross sections of electrons on atoms are of considerable interest both in the field of fundamental science for in-depth study of interaction processes and in practical applications, and are necessary in many areas of research, such as modeling low-temperature plasma, astrophysics phenomena, laser physics, and atmospheric effects etc. In addition to natural phenomena, the processes of collision of electrons with matter play an essential role in plasma technologies, such as, for example, microelectronics and biomedicine. Atomic physics, plasma physics and optics - fields directly related to electron-atom make a significant contribution to the fundamental understanding of the world. Despite the long study of the effects of electron scattering on atoms, and the results obtained in the physics of atomic collisions, this area still requires theoretical and experimental research, there is a significant lack of data on collision cross sections for their subsequent use in modeling and calculations. In particular, there are no systematized data on the cross sections for elastic scattering of high energy electrons by atomic.

Physicochemical properties and cytochromes P-450 kinetics of the trifluoroacetamido derivative of phenacetin

Substituting hydrogen atoms with fluorine alters physicochemical properties often resulting in improved drug action relative to the parent molecule. The high electronegativity of fluorine changes the electron density distribution of the molecule; however, the substitution does not significantly change the size of the molecule because hydrogen and fluorine have similar atomic radii. A trifluoroacetamido derivative (TFA-phenacetin) of phenacetin, an analgesic antipyretic drug, was synthesized to compare its lipophilicity to the parent molecule by determining octanol–water partition coefficients. TFA-phenacetin is over seven times more lipophilic than phenacetin, which suggests that TFA-phenacetin would have better bioavailability relative to phenacetin. The kinetics of cytochromes P-450 (CYP) catalyzed oxidation of phenacetin and TFA-phenacetin were compared using Sprague Dawley (SD) rat liver microsomes. Phenacetin and TFA-phenacetin have the same apparent binding affinity for the SD rat liver microsome CYP proteome and undergo CYP catalyzed oxidation at the same rate in the presence of SD rat liver microsomes.