Experimental and quantum-chemical methods were used to determine the thermodynamic properties of one of the representatives of the 1,6-diazabicyclo[4.1.0]heptane molecular system which is of interest in design of new promising high-energy density materials. The combustion energy of this compound at 298.15 K was measured using isoperibolic macrocalorimeter with a static bomb. The enthalpy of sublimation was determined by Knudsen cell mass spectrometry method. The heat capacity in the range of 6-350 K was studied using vacuum adiabatic calorimetry. No phase transitions were found by analyzing the behavior of the heat capacity curve. It has been shown that purification of a substance by recrystallization can lead to encapsulation of the solvent inside the crystalline structure. Using high-level quantum chemical calculations, the enthalpy of formation and thermodynamic functions of this compound in the gas phase were obtained. When calculating thermodynamic functions, the conformational isomerism of the studied molecule was taken into account. As a result, a complete set of standard thermodynamic functions was obtained for the studied compound, including formation functions, both in the crystalline and gaseous phases over a wide temperature range.

The gas phase enthalpies of formation of parent molecules, porphin and calix[4]pyrrole, were determined using high-level G4 and DLPNO-CCSD(T1) methods and these values were used as reference values for predicting the enthalpies of formation of porphyrins and calix[4]pyrroles. Calculations for the remaining compounds were performed using the revDSD-PBEP86-D4 method which provides a good balance between accuracy and computational cost. The solid-phase enthalpies of formation were obtained using the enthalpies of sublimation evaluated from their correlation with the descriptors of the molecular electrostatic potential. The calculated results were employed to resolve contradictions in the available experimental data.

At vapor-liquid equilibrium, the thermodynamic properties of the liquid and vapor phases are intrinsically linked through the thermodynamics of vaporization. However, the standard enthalpies of formation and vaporization of α,ω-alkanediols reported in the literature to date are inconsistent with this fundamental thermodynamic relationship. The aim of this work is to evaluate the existing data and provide recommendations for standard enthalpies of formation and standard enthalpies of vaporization for technical applications. For this purpose, available data are critically analyzed using a "top-down/bottom-up" approach based on gas-phase properties and a bottom-up approach starting from the liquid phase. For those α,ω-alkanediols where discrepancies remain, the relevant thermodynamic properties were re-determined with a combination of combustion calorimetry, vapor pressure measurements and quantum chemical calculations. Based on the comprehensive evaluation, it was shown that the thermodynamic properties of α,ω-alkanediols deviate from the regular trends typically expected for homologous series. Due to the significant contribution of intramolecular hydrogen bond conformers in the gas-phase population, the properties of 1,2-ethanediol, 1,3-propanediol and 1,4-butanediol exhibit distinct particularities compared to long-chained α,ω-alkanediols. Starting from 1,5-pentanediol, the enthalpies of vaporization and the standard enthalpies of formation in the gas phase follow a regular linear trend, attributed to the predominance of conformers without intramolecular hydrogen bonding. The recommended accurate thermodynamic data provide the basis for the development of technical processes utilizing diols from renewable sources in future work.

Heat capacities of 2-furfurylamine were measured by low-temperature adiabatic calorimetry in the temperature range from 5.6 to 356.1 K. Two phase transitions, solid phase transition and melting, were revealed at temperatures of 180.4 K and 228.17 K. Thermodynamic characteristics determined from experimental data show that the mechanism of solid phase transition is intermediate between order-disorder and displacive type. This conclusion is in agreement with X-ray crystallography data (Seidel et al., 2019). The standard thermodynamic functions in the condensed state (molar heat capacity, enthalpy, entropy and Gibbs energy) were calculated in the temperature range 5 - 350 K. Using the determined value of entropy for liquid 2-furfurylamine and available value of fH degrees m(l), the properties of formation, fS degrees m(l) and fG degrees m(l), were obtained. The thermodynamic functions of gaseous 2-furfurylamine were calculated taking into account the internal rotation in this molecule. The required molecular constants were determined from quantum chemical calculations.

Knudsen cell mass spectrometry was used to study the evaporation of two ionic liquids, 1-ethyl-3-methylimidazolium methanesulfonate ([EtMIm][MS], MS = CH3SO3) and 1-butyl-3-methylimidazolium methanesulfonate ([BuMIm][MS]), accompanied by thermal decomposition (thermolysis). The independent occurrence of evaporation and thermolysis reactions made it possible to determine their thermodynamic and kinetic characteristics under identical experimental conditions. The saturated vapor pressures were measured and the standard enthalpies of vaporization of [EtMIm][MS](l) and [BuMIm][MS](l) were obtained. The standard thermodynamic functions of formation in the liquid and gaseous states at 298.15 K were estimated from the available experimental data and the results of quantum chemical calculations. The gaseous decomposition products of ionic liquids were identified and the pressures of the thermolysis products of [EtMIm][MS](l) were determined. According to the experimental data and quantum chemical calculations, the thermolysis of [EtMIm][MS](l) occurs through heterogeneous reactions far from the equilibrium state. The kinetics of the reactions is described in two ways. When the degree of sample conversion is used as a variable, the constant reaction rates at the initial stage of thermolysis correspond to a pseudo-zero order reaction with a monotonic increase in the degree of conversion. In the proposed alternative approach, the reaction rates are estimated from the fluxes of thermolysis products and are expressed in terms of ionic liquid concentration.

The evaporation and thermal decomposition (thermolysis) of 1-butyl-3-methylimidazolium chloride ionic liquid, [BuMIm][Cl](l), were studied in the temperature range of 373-463 K by thermogravimetry-mass spectrometry (TG-MS) and Knudsen cell mass spectrometry (KCMS) methods. The saturated vapor pressures and the enthalpy of vaporization of [BuMIm][Cl](l) were determined within 373-398 K, where the thermolysis of this ionic liquid occurs via the SN2 mechanism at a low rate. With increasing temperature, the thermolysis becomes more extensive, which is accompanied by the C2-methylation of [BuMIm][Cl](l). The resulting ion pairs [BuMMIm+] [Cl-] are thermally unstable and decomposed. A decrease in the vapor pressure of the ion pairs [BuMIm+][Cl-] at a constant temperature takes place due to side reactions, resulting in the suppression of the evaporation. Complex ionic compounds were found in the thermolysis/evaporation residues using atmospheric pressure chemical ionization (APCI) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) methods. The priority and possible pathways of reactions involving ion pairs and the thermolysis products were established by quantum chemical calculations.

The standard molar enthalpies of formation in the gas phase at T = 298.15 K for 43 furan derivatives were calculated using the DLPNO-CCSD(T-1)/CBS method in conjunction with isodesmic-type reactions to assess the accuracy of experimental data reported in the literature. The high accuracy of the experimental data was confirmed for almost half of the studied compounds (44%). For the remaining furans, the discrepancy between the experimental and theoretical values is larger than 5-70 kJmol(-1), and additional experimental measurements are obviously required to determine more accurate values of the enthalpy of combustion and/or enthalpy of phase change. The experimental enthalpies of formation of 12 furans are recommended as benchmark reference values for use in thermochemical calculations of furan-based compounds.

A comprehensive thermodynamic study of two ionic liquids EmimCl and BmimCl were carried out by experimental and calculation methods. Isobaric heat capacity of crystal and liquid EmimCl was determined by low temperature vacuum adiabatic calorimetry in the temperature range from 8 to 376 K. Experimental heat capacity curve of crystal EmimCl and literature data of BmimCl were fitted by linear combination of Einstein's functions and were integrated; as a result, the following thermodynamic functions for EmimCl and BmimCl were calculated: standard entropy S0m(T), heat content H0m(T)-H0m(0) and Gibbs energy G0m(T)-H0m(0). Melting parameters of these substances were measured by DSC and adiabatic calorimetry. Standard enthalpies of dissolution of crystal EmimCl and BmimCl in water at 298.15 K were measured by isothermal solution calorimetry. Based on these data, standard enthalpies, entropies and Gibbs energies of formation were calculated for crystal and liquid phases of EmimCl and BmimCl at 298.15 K. Standard enthalpies of EmimCl and BmimCl formation in the gaseous state at 298.15 K were defined via quantum chemistry methods. The analysis and comparison of the obtained thermodynamic characteristics with the literature data was carried out.

The combustion energy and standard molar enthalpy of formation of liquid furfurylamine were determined using an isoperibol calorimeter with a static bomb. The theoretical calculations were used for the interpretation of experimental calorimetric result. The DLPNO-CCSD(T1)/CBS method in conjunction with isodesmic-type reactions was used to calculate the gas-phase enthalpy of formation of this compound. At the same level of theory, the interconversion of the gauche and anti conformers of furfurylamine and the N-H & BULL;& BULL;& BULL;N hydrogen bonding between them leading to the association into dimeric units were studied. The calculated values of equilibrium and rate constants for reaction gauche & RARR; anti and enthalpy of dimerization of two conformers suggest that the gaseous furfurylamine exists predominantly in the dimeric form. An additional support for the strong association of furfurylamine in the vapor phase was obtained from comparison of the enthalpies of formation in liquid and gaseous states: the consistency between these two values was achieved only when a correction for dimerization was applied.

The combustion energy and standard molar enthalpy of formation of crystalline 6-phenyl-1,5-diazabicyclo[3.1.0]hexane (PDABH) were determined using an isoperibolic calorimeter with a static bomb. PDABH is the first diaziridine for which the experimental value of the enthalpy of formation was obtained. This value was validated by the theoretical values of gas phase enthalpy of formation and enthalpy of sublimation. The gas phase enthalpy of formation was calculated using the DLPNO-CCSD(T1)/CBS method in conjunction with isodesmic-type reactions. This method was chosen in comparison to another high quality evaluative method (G4), which has been shown to provide unreliable results for cyclic nitrogen containing compounds. The descriptors of the molecular electrostatic potential (MEP) were used to estimate the enthalpy of sublimation of PDABH. The proposed MEP model is based on experimental enthalpies of sublimation for 75 compounds structurally similar to PDABH. The high-level ab initio calculations of gas phase enthalpies of formation combined with enthalpies of sublimations estimated using descriptors of MEP allow predicting the enthalpies of formation of diaziridines in the solid phase.

Comparative evaluation of the pharmacokinetics, safety profile and tolerability of Ranquilon® 1 mg tablets with a single administration under fasting and fed conditions among healthy male and female volunteers.

At the beginning of 2020, a novel coronavirus designated as SARS-CoV-2 emerged in China and caused an outbreak of coronavirus disease 2019 (COVID-19). Pandemic has threatened global mental health via disruptive societal changes and neuropsychiatric sequelae including depression, anxiety and sleep disorders after SARS-CoV-2 infection. Virus is able to access CNS through blood circulation or neural pathway. Brain damage can be also due to hypoxia, hypercoagulation and endothelial dysfunction. The effects of psychological stressors and drug therapy may be also relevant for development of neuropsychiatric disorders after COVID-19. Women and patients with a history of mental disorders are more susceptible to neuropsychiatric disorders and frequently present with more severe complications. Affective, anxiety or psychotic disorders can persist for 6 months after recovery from COVID-19. These data highlight the need in drug therapy to treat depression and anxiety, to normalize sleep and to prevent the development of serious neuropsychiatric sequelae of infection.

The use of ionic liquids (IL) at elevated temperatures has revealed interest in the study of evaporation and thermal decomposition (thermolysis) processes that determine the thermal stability of IL. In this work the evaporation of 1-ethyl-3-methyl-imidazolium chloride ([EtMIm][Cl]), which is accompanied by the significant thermal decomposition, was studied by the Knudsen cell mass spectrometry. The composition of gas phase over [EtMIm][Cl] and its change in time were established in the temperature range of 403- 449 K. The saturated vapor pressures, vaporization enthalpy and rate constants of thermolysis reactions were determined. The equilibrium and rate constants for gas-phase thermolysis reactions of [EtMIm][Cl] were calculated by the quantum chemical methods. Based on the results of experiments and calculations, the processes responsible for mass loss - thermolysis and evaporation - were quantitatively described. (c) 2023 Elsevier B.V. All rights reserved.

The liquid phase standard molar enthalpy of formation of 2-methyltetrahydrofuran was determined by isoperibolic calorimetry of combustion. The purity of the sample was determined by the g.l.c and the cryoscopic methods. Using available enthalpy of vaporization, the gas phase enthalpy of formation was obtained. This value agrees well with that calculated by DLPNO-CCSD(T1)/CBS method. (c) 2021 Elsevier Ltd.

Introduction The pilot clinical study of GB-115, a new peptide antagonist of central cholecystokinin-1 receptors, revealed that drug was clinically effective in patients with generalized anxiety disorder (GAD) at dose 6 mg daily. Here, we provide results of post-hoc analysis of changes of anxiety and fatigue symptoms to give characterization of its clinical effects in clinically relevant doses. Objectives To research the changes of anxiety- and fatigue-related symptoms during GB-115 treatment in patients with generalized anxiety disorder (GAD). Methods Patients with GAD without somatic diseases aged 18-55 years were eligible in the study. Patients were prescribed with GB-115 6 mg daily for 21 days. Anxiety and fatigue symptoms were assessed with Hamilton Anxiety Rating Scale (HARS) and Multidimensional Fatigue Inventory (MFI-20). Variables are described as medians and interquartile range (IQR). Pre-post comparisons were performed using the Friedman ANOVA at 2-side p-value <0.05. Results 25 patients diagnosed with GAD (8 males, 17 females; median [IQR] age: 34 [29.75, 43.0]) included in the analysis. Median [IQR] HARS total score decreased from 22 [20, 24.5] to 19 [16, 20], 13 [10.5, 15.5], 9 [5.5, 11] and 5 [3.5, 8] on the Day 3,7,14 and 21, respectively (χ2=95.07, df=4, p<0.001). Median [IQR] MFI-20 score decreased from 70 [46, 75.5] to 59 [41, 74.5], 52 [37.5, 64.5], 37 [26.5, 63] and 28 [24, 48.5] on the Day 3, 7, 14 and 21, respectively (χ2= 55.41, df=4, p<0.001). None of patients had stimulation-related side effects. Conclusions GB-115 action in the treatment of GAD patients is characterized with anxiolytic action with mild psychostimulant properties. Disclosure No significant relationships.

A method for the thermal cyclization of tetrazol-5-ylamino-1,2,4,5-tetrazine has been developed, leading to the formation of a new heterocyclic system based on 1,2,4-triazole and 1,2,4,5-tetrazine, a fused tricyclic compound, from which a number of other tricyclic derivatives containing nitramine, nitro, and keto groups have been obtained. Based on experimental studies and quantum-chemical calculations enthalpies of formation of the new fused energetic materials in the solid state have been found. The enthalpy of formation of the new fused tricyclic compound bis [1, 2,4] triazolo [1,5-b:5',1'-f] [1,2,4,5] tetrazine-2,7-diamine, DATC, (3505 kJ kg(-1)) exceeds the enthalpies of formation of diaminotetrazine (2652 kJ kg(-1)) and 5-aminotetrazole (2442 kJ kg(-1)), which makes the resulting framework one of the most energetic heterocyclic compounds. In addition, DATC and its derivatives turned out to be low-sensitive and thermally stable explosives, the stability of which is comparable to the known thermostable explosives TATB and TACOT, but with higher detonation characteristics. N,N'-(bis([1,2,4]triazolo) [1,5-b:5',1'-f] [1,2,4,5]tetrazine-2,7-diyl)dinitramide was used as a starting acid to obtain salts with organic bases. The hydroxylamine salt, H(2)DNATC, turned out to be the most powerful compound, comparable in detonation characteristics (D = 9020 m s(-1)) to HMX, but having a higher burning rate (54 mm s(-1) at 10 MPa), and therefore it may be of interest as a high-energy fast-burning filler for composite propellants and gunpowder. Thermocouple-aided studies in the H(2)DNATC combustion wave made it possible to estimate the enthalpy of dissociation of the salt into gaseous components and to establish the combustion mechanism. The demonstrated thermal cyclization method for the preparation of fused tricyclic tetrazines provides new insights into the design of HEDMs, which may be useful for practical applications.

Introduction Personalized approach in drug therapy is an essential line of modern psychiatry. Experimental and clinical studies of anxiolytics have shown differences in drug effects in dependence on genetically determined reactions to stress and personal features. Objectives To evaluate of the therapeutic effects and effectiveness of bromodihydrochlorophenylbenzodiazepine and fabomotizole in dependence on individually-typological features of patients with anxiety disorders. Methods 45 patients (mean age 33,3±9,7 years) with generalized anxiety disorder (n=22) and panic disorders with agoraphobia (n=23) participated in this open-label study. 13 patients treated with typical anxiolytics bromodihydrochlorophenylbenzodiazepine at dose 2 mg daily and 32 patients treated with atypical fabomotizole at dose 30 mg daily. The duration of treatment was 14 days. Minnesota Multiphasic Personality Inventory, Psychiatric Symptoms Severity Evaluation Questionnaire and CGI-E were administered. Results Asthenic features (high pessimism, anxiety, individualism) were revealed in 26 patients and stenic features (high impulsivity, rigidity and optimism) were revealed in 19 patients. Patients with asthenic features had tranquilo-activating effect of bromodihydrochlorophenylbenzodiazepine, whereas patients with stenic features had tranquilo-sedative effect. The tranquilo-activating effect of fabomotizole was revealed in patients with stenic features. High efficacy of bromodihydrochlorophenylbenzodiazepine was observed in patients with asthenic personality traits (χ 2 = 7,8), whereas in fabomotizole-in patients with stenic individual typological features (χ 2 = 9,1). Conclusions Patients with stenic and asthenic features had differences in therapeutic effects and the effectiveness of anxiolytics. Personality features determine the sensitivity of patients with anxiety disorders to psychotropic drugs. Disclosure No significant relationships.

The DLPNO-CCSD(T1)/CBS method in conjunction with isodesmic-type reactions was used to calculate the enthalpies of formation of 30 polycyclic aromatic hydrocarbons (PAHs). The small reference species with well-determined experimental enthalpies of formation were used in these reactions. From comparison with available experimental data and other recently published high-level quantum chemical calculations, the reference values of the standard enthalpy of formation are recommended for 13 PAHs. The difference between the calculated and experimental values for these compounds does not exceed 2 kJ/mol and their experimental data can be considered as benchmark values for use in calculation of enthalpies of formation of various large PAHs and testing the accuracy of theoretical methods. The use of isodesmic-type reactions involving reference PAHs conserves the structural features of these compounds on both sides of the reaction which leads to a better error compensation. As a result, as shown in the example of coronene, a less-expensive DLPNO-CCSD(T)/CBS method can be used in this case for accurate prediction of enthalpies of formation of large PAHs.

The heat capacity and phase transitions of 2-methyltetrahydrofuran in the temperature range from 7 to 350 K were measured using adiabatic calorimetry. The smoothed molar thermodynamic functions in the condensed state were determined on the basis of these measurements. The thermodynamic functions of the formation were also calculated. The gas-phase entropy at 298.15 K was obtained using the entropy of crystal 2-methyltetrahydrofuran, entropy of fusion and entropy of vaporization. This entropy value was used to clarify some aspects of the discrepancies between the interpretations of pseudorotation in 2-methyltetrahydrofuran. An extended quantum chemical study of pseudorotation in 2-methyltetrahydrofuran was undertaken to provide additional insight into the conformational features of a molecule. The contribution of pseudorotation to the entropy was calculated for different pseudorotational potentials constructed using various theoretical models. The experimental entropy value is in best agreement with intramolecular conversion between two low energy conformers connected by the transition state with an energy of about 4 kJ mol(-1). The standard thermodynamic properties of 2-methyltetrahydrofuran in the gaseous state (T = 100 K to 1500 K) were calculated using experimental and theoretical molecular parameters.

The DLPNO-CCSD(T1)/CBS and G4 methods combined with isogyric, isodesmic, and homodesmotic working reactions were applied to calculate gas-phase enthalpies of formation for thirty-three C–H–N–O compounds with well-established experimental values. Unlike the G4 method, the DLPNO calculations, even together with isogyric reactions with small reference species, reproduce the experimental enthalpies of formation within chemical accuracy (≈ 4 kJ/mol). For more than half of the compounds, a better accuracy, within 2 kJ/mol, was achieved. These results make the DLPNO-CCSD(T1)/CBS method a promising tool for accurate prediction of enthalpy of formation of medium-sized organic compounds. Being convinced of its reliability, the DLPNO-CCSD(T1)/CBS method was also used to estimate the enthalpies of formation for some challenging compounds with conflicting values reported in the literature (glycerol, nitromethane, nitrobenzene, 1-aminoadamantane, piperazine, and others).