Acetonitrile Solvent Research Articles

In situ Derivatization of Lung Cancer Biomarker Aldehydes by Parallel-DPX-Cork and Quantification by HPLC-DAD

Lung cancer is one of the main causes of death for thousands of people yearly around the world. Biomarker aldehydes, such as hexanal and heptanal, are compounds related to the development of lung cancer, which can be detected in the early stages of this disease. A methodology was proposed to determine these aldehydes in urine, with a new configuration associated with the sample preparation step. A novel strategy with a parallel-disposable pipette extraction (DPX)-cork device was used, offering a fast and affordable extraction methodology with analysis performed by high performance liquid chromatography with diode array detector. In optimization steps, multivariate and univariate designs were applied, providing the following conditions: urine sample centrifuged at 3500 rpm for 15 min, 30 μL and 6 min of dinitrophenylhydrazine impregnation, 10× urine diluted in ultrapure water, pH adjusted to 4.8, 7 extraction cycles with 1.5 min each, 30 mg of cork, 2 desorption cycles and solvent acetonitrile with 300 μL. Limits of detection were 0.13 ng mL-1 for both analytes and limits of quantification were 0.40 and 0.41 ng mL-1 for hexanal and heptanal, respectively. Intraday and interday precisions ranged from 4 to 21%. Relative recoveries ranged from 86 to 107%, assessed at three concentrations. Urine samples were analyzed, but the presence of aldehydes was not detected.

The electrophilic aromatic bromination of benzenes: mechanistic and regioselective insights from density functional theory.

The HBr-assisted electrophilic aromatic bromination of benzene, anisole and nitrobenzene was investigated using static DFT calculations in gas phase and implicit apolar (CCl4) and polar (acetonitrile) solvent models at the ωB97X-D/cc-pVTZ level of theory. The reaction profiles corresponding to either a direct substitution reaction or an addition-elimination process were constructed and insight into the preferred regioselectivity was provided using a combination of conceptual DFT reactivity indices, aromaticity indices, Wiberg bond indices and the non-covalent interaction index. Our results show that under the considered reaction conditions the bromination reaction preferentially occurs through an addition-elimination mechanism and without formation of a stable charged Wheland intermediate. The ortho/para directing effect of the electron-donating methoxy-group in anisole was ascribed to a synergy between strong electron delocalisation and attractive interactions. In contrast, the preferred meta-addition on nitrobenzene could not be traced back to any of these effects, nor to the intrinsic reactivity property of the reactant. In this case, an electrostatic clash between the ipso-carbon of the ring and the nitrogen atom resulting from the later nature of the rate-determining step, with respect to anisole, appeared to play a crucial role.

Structural change dynamics of heteroleptic Cu(I) complexes observed by ultrafast emission spectroscopy.

[Cu(I)(dmp)(P)2]+ (dmp = 2,9-dimethyl-1,10-phenanthroline derivatives; P = phosphine ligand) is one of the most promising photosensitizers used in a photo-catalytic system for reducing CO2, for which the quantum yield is as high as 57%. In this work, time-resolved emission spectra of Cu(I) complexes in solutions were investigated using femtosecond fluorescence up-conversion and nanosecond time-resolved emission spectroscopic systems. The temporal profiles of emission intensities less than 10 ps in acetonitrile solution were reproduced using a tri-exponential function with three-time constants of 0.040 ps, 0.78 ps and 8.0 ps. We found that only the second time constant is dependent on the solvent (acetonitrile: 0.78 ps, butyronitrile: 1.4 ps), indicating that the 0.78 ps spectral change is attributed to the structural change of the Cu(I) complex. The oscillator strengths of transition species are derived from the intensities in the time-resolved emission spectra (species-associated spectra). Based on the oscillator strengths, we concluded that the 0.040 ps process is the Sn → S1 internal conversion and the 0.78 ps process is a structural change in the S1 state. The final time constant of 8.0 ps is assigned to the S1 → T1 intersystem crossing because the 3MLCT state (τT1 = 97 ns) is generated after the decay. The DFT calculation showed that the 0.78 ps spectral change (∼600 cm-1 redshift) is attributed to Jahn-Teller distortion around the metal center, and there is a large structural change in the ligand, which results in a large Stokes shift in the Sn state (7.3 × 103 cm-1).

Liquid–liquid phase separation and crystallization of aspirin polymorphs from a water–acetonitrile mixed solvent medium through a swift cooling process

Screening of form-I and form-II polymorphs of the pharmaceutical solid aspirin in the vicinity of liquid–liquid phase separation in water–acetonitrile solvent mixtures through a novel swift cooling crystallization process is successfully attained.

Simple and Efficient Method for One Pot Multicomponent Synthesis of 3,4-Dihydropyrimidin-2-(1H)-One Derivatives Catalyzed by Organocatalyst: Benzoic Acid

The Biginelli reaction is one the useful multicomponent reactions and a very appropriate reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones derivatives. These 3,4-dihydropyrimidin-2(1H)-ones have biological and pharmacological properties which make them a very important class of medicinal chemistry. Although they are an important class of medicinal chemistry, the syntheses of these compounds have been catalyzed by large number of strong Bronsted acids and Lewis acids under thermal conditions. Small organic molecules, organocatalysts, have been used as catalysts for the Biginelli reaction in a small number as compared to Bronsted acids and Lewis acid. Benzoic acid, which is a small organic molecule, although an acid, has never been tested for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Benzoic acid is an inexpensive, non-toxic molecule, it has been successfully tested here as a catalyst for the one-pot three component synthesis of 3,4-dihydropyrimidin-2-(1H)-one derivatives via Biginelli reaction between β-keto ester, a variety of aromatic aldehydes and urea or thiourea under thermal conditions using 20 mol% benzoic acid in acetonitrile solvent refluxed for 12 h to give good to high yields. This synthetic method includes inexpensive, non-toxic, easily available benzoic acid as a catalyst and is carried out in a simple operational procedure.

Highly efficient conversion of CO2 into N-formamides catalyzed by a noble-metal-free aluminum-based MOF under mild conditions.

Formamides have critical application value in the chemical industry serving as solvents or reagents for the synthesis of pharmaceuticals, agrochemicals, and dyes. Herein, we selected a green-synthesis produced aluminum-based metal-organic framework (Al-MOF) material CAU-10pydc as a catalyst to study its performance in CO2 formylation reaction. At room temperature and in the green solvent acetonitrile, CAU-10pydc could highly effectively catalyze the reaction of CO2 and N-methylaniline to N-methyl-N-phenylformamide under mild conditions. CAU-10pydc could maintain its efficient catalytic performance after five catalytic cycles, and PXRD and SEM measurements demonstrated that CAU-10pydc is stable after cyclic catalysis. The universality of this catalyst was illustrated by nine substrates with high yields. The reaction mechanism was further analyzed by DFT calculations. To our knowledge, this work is the first example of a CO2 formylation reaction being catalyzed highly effectively by an Al-MOF under green conditions.

Solvent effect on the photolysis of 5‐fluorouracil: A kinetic study

AbstractA photodegradation study of 5‐fluorouracil (5‐FU) has been carried out in the water (pH 7.0) and organic solvents (chloroform, ethyl acetate, acetone, 1‐butanol, 1‐propanol, ethanol, methanol, and acetonitrile) using developed and validated high‐performance liquid chromatography (HPLC) method. The test method was found to be simple, accurate (% recovery, 100.25%–101.08%), precise (%RSD < 2.00), and sensitive. The apparent first‐order rate constants are in the range of 0.85 (chloroform) to 4.25 × 10−4 min−1 (water). The values obtained for kobs were found to be linear as a function of the dielectric constant indicating the involvement of the dipolar intermediate in the reaction. The increase in the rate of degradation of this intermediate is enhanced by the polarity of the medium. Rates of photolysis for 5‐FU show a linear relationship with the solvent acceptor number (AN) which indicates the degree of solute–solvent interaction. The values of kobs were found to be linear to the inverse of the viscosity of the medium due to the diffusion‐controlled process.

Predicting CO2 solubility in aqueous and organic electrolyte solutions with ePC-SAFT advanced

Solvent influence and salt influence on CO2 solubility are essential factors toward the development of processes involving CO2 conversion. In this work, the equation of state (EOS) electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT advanced) was applied to model the CO2 solubility in single organic solvents (methanol, ethanol, N-methyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, γ-valerolactone, and acetonitrile). Further, CO2 solubility was predicted in aqueous solvent mixtures and in aqueous electrolyte solutions (NaCl, KCl, CsCl, MgCl2, CaCl2, NaNO3, KNO3, Mg(NO3)2, Ca(NO3)2, Na2SO4, K2SO4, MgSO4, NaHCO3, and K2CO3) with water as single solvent as well as in aqueous alcoholic solvent mixtures. CO2 solubility in systems with a lack of data (CsCl) was measured in this work with a high-pressure variable-volume view cell. Broad ranges of temperatures, pressures, and high concentrations of electrolytes were considered, and solvent effects, ion effects, and pH effects were studied. The nature of the considered systems required including dissociation reactions of carbonic acid in the modeling framework, most importantly for the systems containing carbonate salts. The results showed that i) CO2 solubility was the highest in non-polar solvents, ii) all salts caused salting-out effects on the CO2 solubility except carbonates (an apparent salting-in due to a pH shift), and that iii) the strength of salting-out effect was related to the charge density of the ions. The salt influence on CO2 solubility was predicted qualitatively correct with ePC-SAFT advanced; that is, fitting binary interaction parameters between ions and CO2 was not necessary, which is a result found for the first time. Finally, ePC-SAFT advanced allowed predicting the CO2 solubility in multi-component systems containing solvent mixtures, salt mixtures, or a solvent mixture with an additional salt over a broad range of conditions in good agreement with available literature data.

Interchangeability and Disorder in the Solid-State Structures of "Two Wall" Calix[4]pyrroles Equipped with Iodine and Ethynyl para-Substituents.

Herein, the synthesis and X-ray structures of three α,β "two wall" aryl-extended calix[4]pyrroles having either identical (symmetrically substituted) or different (non-symmetrically substituted) meso-aryl substituents (aryl=4-ethynylphenyl and 4-iodophenyl) are reported. The X-ray structure of the co-crystal formed by the two symmetrically substituted calix[4]pyrroles is also described. In the solid state, all studied α,β-calix[4]pyrroles exhibit a 1,3-alternate conformation with two co-crystallized acetonitrile solvent molecules H-bonded to adjacent cis-pyrrole rings. Remarkably, the 1,3-conformer of the non-symmetrically substituted iodophenyl/ethynylphenyl compound is intrinsically chiral. The two enantiomers are present in the average asymmetric unit in a 65 : 35 occupancy ratio displaying a head-to-tail directional disorder. This is due to the functional complementarity and the isosteric and isoelectronic properties of the para-substituents: iodo and ethynyl. That is, the negative belt of iodine is similar to the negative π-system of the C≡C triple bond and the σ-hole in the iodine atom is similar to the positive proton at the C≡C-H group.

Evaluation of safe mixed solvents in N-phenylbenzamide synthesis for alteration of hazardous dipolar aprotic solvents in amide drug syntheses

N-phenylbenzamide (N-PBA) was synthesized with the solvent-pair mixtures (1:1 v/v) containing hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) to investigate the replacement/limitation of hazardous dipolar aprotic solvents in amide drug synthesis. Pure solvents: dimethylformamide (DMF), dichloromethane (DCM), acetonitrile (ACN), acetone (Ace), tetrahydrofuran (THF), ethyl acetate (EtAc), dimethyl sulfoxide (DMSO), and mixed solvents: H2O-THF, H2O-DMSO, H2O-Ace, H2O-DMF, H2O–EtOH, H2O-IPA, EtOH-DMF, EtOH-DMSO were selected based on Kamlet-Taft (KT) parameters, GSK 2016 health-safety scores. Syntheses were carried out with an amide coupling system at 25 °C to evaluate the reaction yield observed with high-performance liquid chromatography (HPLC). The percent yield of 72.68 ± 0.35 (H2O-THF), 71.24 ± 1.93 (H2O-Ace), 80.27 ± 1.67 (EtOH-DMF), 67.27 ± 0.64 (EtOH-DMSO), 65.38 ± 1.55 (H2O-IPA) were found by adjusting the pH 10.8 in solvent mixtures for synthesis. A ninefold increase in the N-PBA yield was obtained by adjusting the pH 10.8 in mixed solvents. Besides, (77.12 ± 1.66, DMSO), and (92.44 ± 0.82, DMF) %yields in N-PBA were found using pure solvents. The aforementioned findings indicate that safe solvent mixtures can be utilized in amide drug synthesis to avoid/limit hazardous dipolar aprotic solvents.

Study of structure of nonaqueous reverse micelles with o-nitroaniline and methyl orange as molecular probes: comparison with an aqueous reverse micelles

Abstract Instead of water reversed micelles can also be formed with polar organic solvents possessed with high dielectric constant and very low solubility in oil phase. Nonaqueous reverse micelles or microemulsions represent an interesting microreactors for various reactions, especially for reactions, where reagents can react with water. Study of localization places of molecular probes in organic polar pockets of reverse micelles is topical. The solvatochromic behavior of optical probes ortho-nitroaniline (o-NA) and methyl orange (MO) was studied in nonaqueous reverse micelles on the basis of surfactants sodium bis (2-ethylhexyl) sulfosuccinate (AOT) and polyoxyethylene (4) lauryl ether (C12E4) and polar organic solvents (acetonitrile, dimethylformamide, glacial acetic acid, etc.) insoluble in oil phase hexane. The strength of binding of o-NA and MO to AOT and C12E4 reversed micelles was assesssed via binding constant (K b ) and association degree (α) respectively. Donor, acceptor, or dipole-dipole interactions ability of the solvent to the head groups of surfactant was taken into account in order to explain results obtained with UV–visible spectroscopic method. The binding constants of o-NA with reverse AOT micelles in the presence of various solvents in the pockets of reversed micelles increase in the following row water < glacial acetic acid < acetonitrile < dimethylformamide < dimethyl sulfoxide, but this sequence is reversed when o-NA binds to C12E4 reverse micelles. The high value of the proton donor or acidity parameter in the water molecule (x d = 0.37) determines the weak binding of o-NA to the head AOT groups (K b = 20.8) in case of aqueous reverse micelles. The high value of the dipole parameter in the dimethylformamide molecule (x n = 0.40) promotes its strong interaction with nonionic polyoxyethylene groups of C12E4, which results in low value of binding constant (K b = 26.5) in case of optical probe o-NA and low value of association degree (α = 0.60) using MO as absorption probe. The results of this article will contribute to the improvement of the concept of interfacial processes, viz.: (i) some issues of supramolecular chemistry, (ii) revealing the contribution of parameters of donor, acceptor or dipole-dipole interaction in a polar organic solvent at the surfactant/nonpolar organic solvent interface, and (iii) features of the dissolution of optical probes in non-aqueous reverse micelles.

Optimised Protocol for Drying Aqueous Enzyme Solutions in Organic Solvents – Comparison of Free and Immobilised Candida antarctica Lipase B

AbstractHere, we propose an optimised protocol for controlling the initial water activity (aw) in organic reaction mixtures with soluble lipase to ensure reproducible and consistent enzyme activity measurements. Pre‐equilibration above saturated salt solutions was used to set aw of the reaction media, where aw was tracked with a hygrometer. Consistent stirring of the suspension and volume correction to compensate for solvent evaporation were found to be critical. The protocol was tested on Candida antarctica lipase B (CALB) in soluble and immobilised forms in three organic solvents (acetonitrile, methyl tert‐butyl ether, and hexane) at four different water activities ranging from 0.12 to 0.97. Soluble and immobilised CALB had similar aw‐profiles and showed the highest enzyme activity in hexane. The optimised protocol expands the possibility to study enzyme kinetics from immobilised enzymes to soluble enzymes.

Mechanistic Study of Diketopiperazine Formation during Solid-Phase Peptide Synthesis of Tirzepatide.

This study focused on investigating diketopiperazine (DKP) and the formation of associated double-amino-acid deletion impurities during linear solid-phase peptide synthesis (SPPS) of tirzepatide (TZP). We identified that the DKP formation primarily occurred during the Fmoc-deprotection reaction and post-coupling aging of the unstable Fmoc-Pro-Pro-Ser-resin active pharmaceutical ingredient (API) intermediate. Similar phenomena have also been observed for other TZP active pharmaceutical ingredient (API) intermediates that contain a penultimate proline amino acid, such as Fmoc-Ala-Pro-Pro-Pro-Ser-resin, Fmoc-Pro-Pro-Pro-Ser-resin, and Fmoc-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-resin, which are intermediates for both hybrid and linear synthesis approaches. During post-coupling aging, it is found that Fmoc deprotection can proceed in dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), and acetonitrile (ACN) solvents without any piperidine addition. Density functional theory (DFT) calculations showed that a peptide that has a penultimate proline stabilizes the transition state through the C-H···π interaction during Fmoc decomposition, which causes those peptides to be more prone to cascade-deprotection reactions. Pseudo-reaction pathways are then proposed, and a corresponding macrokinetics model is developed to allow accurate prediction of the TZP peptide intermediate self-deprotection and DKP formation rate. Based on those studies, control strategies for minimizing DKP formation were further investigated and an alternative to Fmoc protection was identified (Bsmoc-protected amino acids), which eliminated the formation of the DKP byproducts. In addition, the use of oxyma additives and lower storage temperature was demonstrated to markedly improve the peptide intermediate stability to DKP degradation pathways.

Controlling the Hydrophilicity of the Electrochemical Interface to Modulate the Oxygen-Atom Transfer in Electrocatalytic Epoxidation Reactions.

The electrocatalytic epoxidation of alkenes at heterogeneous catalysts using water as the sole oxygen source is a promising safe route toward the sustainable synthesis of epoxides, which are essential building blocks in organic chemistry. However, the physicochemical parameters governing the oxygen-atom transfer to the alkene and the impact of the electrolyte structure on the epoxidation reaction are yet to be understood. Here, we study the electrocatalytic epoxidation of cyclooctene at the surface of gold in hybrid organic/aqueous mixtures using acetonitrile (ACN) solvent. Gold was selected, as in ACN/water electrolytes gold oxide is formed by reactivity with water at potentials less anodic than the oxygen evolution reaction (OER). This unique property allows us to demonstrate that a sacrificial mechanism is responsible for cyclooctene epoxidation at metallic gold surfaces, proceeding through cyclooctene activation, while epoxidation at gold oxide shares similar reaction intermediates with the OER and proceeds via the activation of water. More importantly, we show that the hydrophilicity of the electrode/electrolyte interface can be tuned by changing the nature of the supporting salt cation, hence affecting the reaction selectivity. At low overpotential, hydrophilic interfaces formed using strong Lewis acid cations are found to favor gold passivation. Instead, hydrophobic interfaces created by the use of large organic cations favor the oxidation of cyclooctene and the formation of epoxide. Our study directly demonstrates how tuning the hydrophilicity of electrochemical interfaces can improve both the yield and selectivity of anodic reactions at the surface of heterogeneous catalysts.

Pairing of Aqueous and Nonaqueous Electrosynthetic Reactions Enabled by a Redox Reservoir Electrode.

Paired electrolysis methods are appealing for chemical synthesis because they generate valuable products at both electrodes; however, development of such reactions is complicated by the need for both half-reactions to proceed under mutually compatible conditions. Here, a modular electrochemical synthesis (ModES) strategy bypasses these constraints using a "redox reservoir" (RR) to pair electrochemical half-reactions across aqueous and nonaqueous solvents. Electrochemical oxidation reactions in organic solvents, the conversion of 4-t-butyltoluene to benzylic dimethyl acetal and aldehyde in methanol or the oxidative C-H amination of naphthalene in acetonitrile, and the reduction of oxygen to hydrogen peroxide in water were paired using nickel hexacyanoferrate as an RR that can selectively store and release protons (and electrons) while serving as the counter electrode for these reactions. Selective proton transport through the RR is optimized and confirmed to enable the ion balance, and thus the successful pairing, between redox half-reactions that proceed with different rates, on different scales, and in different solvents (methanol, acetonitrile, and water).

Highly selective epoxidation of styrene at ambient temperature under photo-assisted condition over bimetallic Eu and Ti-doped amino-functionalized mesoporous molecular sieve

Mesoporous molecular sieves silica materials had been functionalized employing 3-aminopropyltriethoxysilane as the surface decoration agent by a post-synthesis method and Eu and Ti with different loading ratio were synchronously anchored on amino-functionalized silica framework by incipient wetness impregnation method, respectively. The structures of the synthesized samples were evaluated by means of X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet-visible spectra, scanning electron microscope, transmission electron microscope, X-ray photoelectron spectroscopy and solid-state 29Si magic angle spinning nuclear magnetic resonance spectra. The results revealed that the highly ordered mesoporous two dimensional hexagonal structure and the mesoporous channel structure were well preserved and isolated tetrahedral surface Eu3+ and isolated [TiO4] or [HOTiO3] species were found to be grafted and highly dispersed in the amino-functionalized mesoporous framework. A significant enhancement in selectivity and conversion for the photocatalytic epoxidation of styrene has been achieved by synergistic effect based on surface ligand effect and electron density effect between Eu3+ and Ti4+ species on amino-functionalized mesoporous silica framework. The factors associated with the conversion of styrene and selectivity to styrene oxide such as the solvent, metal loading, the amount of NaOH, H2O2/Styrene, the amount of catalyst and reaction time were also investigated in details. The desired selectivity (84%) to styrene oxide and excellent conversion (32%) of styrene for the photocatalytic epoxidation of styrene with turnover frequency of 3.1 × 10−4s−1 were obtained using aqueous H2O2 as an oxidant in the presence of acetonitrile solvent under ambient temperature.

Singlet fission initiating triplet generations of BODIPY derivatives through pi -stacking: a theoretical study

The role of singlet fission (SF) in the triplet-state generation mechanism of 1,3,5,7-tetramethyl-boron-dipyrromethene derivatives is revealed by exploring the cause for the solvent dependence of the generation rate. Comparing the adsorption energy calculations of solvent molecules, i.e., cyclohexane, chloroform and acetonitrile molecules, to the derivatives with the pi -stacking energies of these derivatives surprisingly show that the hierarchy of the solvation energies and pi -stacking energies strongly correlates with the experimentally-suggested solvent dependence of the triplet-state generation of these derivatives for five and more adsorbing solvent molecules. Following this finding, the excitation spectra of these derivatives in acetonitrile solvent are explored using the proprietary spin-flip long-range corrected time-dependent density functional theory. It is, consequently, confirmed that the pi -stacking activates the second lowest singlet excitation to trigger the spin-allowed transition to the singlet doubly-excited tetraradical (TT)_1 state, which generates the long-lived quintet (TT)_1 state causing the SF. However, it is also found that the pi -stacking also get a slow intersystem crossing active around the intersections of the lowest singlet excitations with the lowest triplet T_1 excitations in parallel with the SF due to the charge transfer characters of the lowest singlet excitations. These results suggest that SF initiates the triplet-state generations through near-degenerate low-lying singlet and (TT) excitations with a considerable singlet-triplet energy gap after the pi -stacking of chromophores stronger than but not far from the solvation. Since these derivatives are organic photosensitizers, this study proposes that SF should be taken into consideration in developing novel heavy atom-free organic photosensitizers, which will contribute to a variety of research fields such as medical care, photobiology, energy science, and synthetic chemistry.

Theoretically unveiling the effect of solvent polarities on ESDPT mechanisms and photophysical properties of hydroxyanthraquinones.

In this work, we were devoted to explore the effect of solvent polarities on the excited-state intramolecular proton transfer (ESIPT) process of 1-acetamido-4-hydroxyanthraquinone (AcHAQ) in three different polarity solvents (acetonitrile, chloroform, and cyclohexane) based on the density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, and thereby regulating the distribution ratio between the dual excited-state isomers (enol and keto). The calculated geometrical parameters and infrared (IR) vibrational spectra have confirmed the excited-state intramolecular hydrogen bond (IHB) strengthening mechanism. Natural bond orbital (NBO) population analysis indicates that the intramolecular charge transfer (ICT) around IHBs has enhanced IHB, thereby triggering the ESIPT reaction. In addition, results obtained from the scanned potential energy curve (PEC) manifest that ESIPT process prefers to occur along the O3-H2…O1 IHB and energy barriers corresponding to the proton transfer in ACN are the lowest among all the studied solvents.

A high-performance liquid chromatography-tandem mass spectrometry method for quantification of perampanel in human plasma: Effect of concomitant anti-seizure medications on perampanel concentration in patients with epilepsy

Perampanel is a first-in-class α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist and a novel anti-seizure medication. It is currently used as adjunctive treatment for partial seizures in patients over 12 years of age. With the increasing clinical application of perampanel, monitoring its concentration under certain clinical conditions is important. This study developed a rapid and sensitive high-performance liquid chromatography–tandem mass spectrometry method to quantify perampanel in human plasma. Protein precipitation with acetonitrile was performed for sample preparation. Perampanel and perampanel-d5 (internal standard) were analyzed under gradient conditions using a C18 column. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.4 mL/min. Mass detection was performed using multiple reaction monitoring in the positive ionization mode. The proposed method was validated over a range of 0.5–500 ng/mL for perampanel. The linearity (r2 value) was higher than 0.999, and the linear equation was y = 0.00116x + 0.0116. The accuracy of the low-, middle-, and high-quality control samples was between 103% and 113%, and the intra- and inter-day precisions were below 6.81%. The quality of the proposed method was evaluated in accordance with the US Food and Drug Administration Bioanalytical Method Validation Guidance for Industry. The plasma concentrations of perampanel in 25 patients were successfully determined to be 38.7–577.7 ng/mL using the validated method.

Highly Reactive Palladium-Catalyzed and Acetonitrile-Mediated Three-Component Reactions for Arylsulfone Synthesis.

Arylsulfone groups play an important role in the synthesis of functionalized molecules. The acetonitrile-mediated three-component reactions for arylsulfone synthesis were developed in the presence of a 0.00025 mol % palladium catalyst. Arylboronic acids reacted with potassium metabisulfite (K2S2O5) and benzyl bromide in the presence of LiF and a very low concentration of PdCl2 in acetonitrile solvents to produce the corresponding benzyl arylsulfones in moderate to good yields. Various arylboronic acids reacted with K2S2O5 and carbon electrophiles to produce the desired arylsulfones under the optimized conditions. It was proposed that acetonitrile accelerated the generation of aryl anion species from the reaction of arylboronic acids and LiF.