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A temperature dependence of saturated vapor pressure of isavuconazole (IVZ), an antimycotic drug, was found by using the method of inert gas-carrier transfer and the thermodynamic functions of sublimation were calculated at a temperature of 298.15 K. The value of the compound standard molar enthalpy of sublimation was found to be 138.1 ± 0.5 kJ·mol−1. The IVZ thermophysical properties—melting point and enthalpy—equaled 302.7 K and 29.9 kJ mol−1, respectively. The isothermal saturation method was used to determine the drug solubility in seven pharmaceutically relevant solvents within the temperature range from 293.15 to 313.15 K. The IVZ solubility in the studied solvents increased in the following order: buffer pH 7.4, buffer pH 2.0, buffer pH 1.2, hexane, 1-octanol, 1-propanol, ethanol. Depending on the solvent chemical nature, the compound solubility varied from 6.7 × 10−6 to 0.3 mol·L−1. The Hansen s approach was used for evaluating and analyzing the solubility data of drug. The results show that this model well-described intermolecular interactions in the solutions studied. It was established that in comparison with the van’t Hoff model, the modified Apelblat one ensured the best correlation with the experimental solubility data of the studied drug. The activity coefficients at infinite dilution and dissolution excess thermodynamic functions of IVZ were calculated in each of the solvents. Temperature dependences of the compound partition coefficients were obtained in a binary 1-octanol/buffer pH 7.4 system and the transfer thermodynamic functions were calculated. The drug distribution from the aqueous solution to the organic medium was found to be spontaneous and entropy-driven.

This paper presents new experimental data on some key physicochemical properties of original bioactive 6-(acetylamino)-N-(5-ethyl-1,3,4-thiadiazol-2-yl) hexanamide (AETH). Thermal analysis of the compound under study has been carried out using differential scanning calorimetry and thermogravimetric techniques. AETH solubility data in five pharmaceutically relevant solvents in the temperature range from 288.15 to 318.15 K have been obtained by the classic saturation shake-flask method. The bioactive compound has poor solubility in hexane and buffer solutions, while it is slightly soluble in selected alcohols. The experimental solubility results have been correlated by means of modified Apelblat and van’t Hoff equations. The selected thermodynamic models produced acceptable results. The Hansen solubility parameters and their components for AETH and solvents have been evaluated by using the van Krevelen–Hoftyzer atomic group contribution method. The ideal solubility and the solution activity coefficient at equilibrium in the selected solvents have been quantified based on experimental values of melting enthalpy and temperature. All the investigated solutions exhibit a positive deviation from ideality with the maximal solubility in alcohols. The equilibrium vapor pressure of the compound studied has been determined as a function of temperature in the range of 433.15–454.15 K by the transpiration method. The standard thermodynamic parameters of AETH sublimation have been calculated. It has been concluded that the high crystal lattice energy value equal to 131.5 kJ/mol is the dominant factor determining the poor solubility of the bioactive compound.

The saturated vapor pressure of Clonixin has been measured by the transpiration method in the temperature range of 419.15–443.15 К, and the thermodynamic functions of sublimation have been calculated. It has been found that the energy of the compound crystal lattice is equal to 108.4 kJ·mol−1. The drug solubility in solvents imitating biological media of the body (buffer pH 2.0 and 7.4, 1-octanol, hexane) and the distribution coefficients in the systems 1-octanol/buffer (pH 2.0 and 7.4) have been determined by the shake-flask method in the temperature range of 293.15–313.15 К. The compound solubility values in these solvents lie within the interval from 1.78·10−4 to 8.01·10−2 mol/l. The coefficients of the drug distribution from buffer pH 2.0 in 1-octanol are one order of magnitude higher than from buffer pH 7.4. Based on the experimental data, the thermodynamic functions of the drug dissolution, transfer and solvation have been calculated in the chosen solvents.

The main aim of this work has been to improve the solubility of bioactive 6-(acetylamino)-N-(5-ethyl-1,3,4-thiadiazol-2-yl)-hexanamide by forming an inclusion complex with 2-hydroxypropyl-β-cyclodextrin. UV–vis spectroscopy was applied to studying the host-guest interaction in the buffer solution pH 7.4. Phase solubility and Job's methods were used to confirm the formation of an inclusion complex with 1:1 stoichiometry and 103 kg·mol−1 stability constant. It has been established that in the presence of 0.069 mol·kg−1 of 2HP-β-CD, the compound solubility is equal to 11.60·10−3 mol·kg−1, which corresponds to a 7-time increase in this parameter compared to the solubility in pure buffer. The thermodynamic functions of complex formation have been determined and it has been found that the inclusion process is spontaneous and thermodynamically advantageous. Data from 1H NMR experiments also provided formation evidence of the inclusion complex between study compound and 2HP-β-CD. The inclusion complex in solid state has been obtained by grinding and characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray diffractometry. The kinetic characteristics of dissolution process for the supramolecular complex have been obtained.

The derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors have been synthesized. The different substituents were introduced into position 8 of the carboline fragment of the molecule: methyl-, methoxy-, fluorine- and chlorine-. Biological tests have shown that all the studied compounds can modulate glutamate-dependent uptake of calcium ions in rats’ cerebral cortex synaptosomes. The shake-flask method was used to measure the solubility of the compounds in the buffer solution (pH 7.4), hexane and 1-octanol within the temperature interval of 293.15–313.15 К. All the derivatives have been found to have low solubility (not exceeding 8 ∙ 10−4 mole fractions) in the mentioned solvents. The effect of thermophysical and protolytic properties of the compounds on the solubility have been studied and the thermodynamic functions of compounds dissolution in the solvents used have been calculated. Keywords: Novel bioactive compounds, Neurocorrection activity, Thermophysical properties, Dissolution

The apparent distribution coefficients of the potential bioactive compounds of the N-aryl-(3-sulfur-1-azabicyclo[3,3,1] non-2-ylidene) amine series in organic solvent/buffer pH 7.4 systems at five temperatures from 293.15 to 315.15 K have been determined by the shake-flask method. The logDO/B values of substances between 1-octanol and the aqueous phase range from 1.76 to 2.06 and at 298 K decrease depending on the chemical nature of the substituents of the phenyl fragment in the following order: cyan- > ethyl- > acetyl- > methyl-, chloro- > isopropyl-. The replacement of 1-octanol by hexane shifts the equilibrium of the substances from the organic phase to the buffer and the resulting values logDH/B

The thermophysical properties of the antiarrhythmic drug Dofetilide have been studied and it has been established that it represents a mixture of polymorphic modifications. The drug solubility in the following aqueous and organic solvents modeling physiological media has been determined: buffer pH 7.4, buffer pH 2.0, 1-octanol and hexane in the temperature range of 293.15–313.15 K by the shake-flask method. The drug solubility changes from 2.4 10−6 to 12.7 10−3 mol·L-1 depending on the solvent chemical nature and at the temperature 298.15 K decreases in the following order: buffer pH 2.0 > buffer pH 7.4 > 1-octanol > hexane. The distribution coefficients of Dofetilide in two-phase systems of 1-octanol/buffer (pH 7.4 and 2.0) and hexane/buffer (pH 7.4 and 2.0) have been determined within the temperature range of 293.15–313.15 K. In all the studied systems, an increase in the buffer solution acidity from pH 7.4 to pH 2.0 lowers the drug distribution coefficient. The experimental data and the calculated thermodynamic functions of Dofetilide transfer from aqueous phase to organic solvent have been discussed based on the compound protolytic properties.

The pharmaceutically relevant physico-chemical properties as solubility and lipophilicity of antimicrobial moxifloxacin (MFX) in modelling solvents and biphasic systems were determined using the shake flask method from 293.15 to 313.15 K. The equilibrium MFX solubility (x, mol. frac.) was changed in next order: ethanol (1.08 · 10−2) > 1-octanol (1.18 · 10−3) > buffer pH 2.0 (1.37 · 10−3) > buffer pH 7.4 (6.45 · 10−4) > hexane (1.13 · 10−5). The obtained result good correlated with relative polarity of selected solvents. MFX solubility in buffer solutions is higher in an acid medium, and tends to decrease at increasing pH values, that explained by protolytic properties of compound studied. The experimental solubility values of MFX in selected solvents were mathematically described by two classical models (modified Apelblat and van’t Hoff equations) with good fitting accuracy. A graphical representation of the Hansen solubility parameters for the studied solute/solvent systems is provided in the form of a Bagley diagram. MFX was described as slightly lipophilic drug. Thermodynamic functions of solubility and transfer processes were calculated on base temperature dependencies of solubility and apparent partition coefficients, respectively. The solubility process was characterized as endothermic in the all studied solvents.

New thiazolo[4,5-d]pyrimidine derivatives were synthesized as potential antifungal agents. The amorphous nature of the obtained compounds was verified by DSC and PXRD. The kinetic and equilibrium solubilities of the derivatives were studied by the shake-flask method in pharmaceutically relevant solvents: buffer pH 2.0, buffer pH 7.4 and 1-octanol. It has been found that within the temperature range of (293.15–313.15) K the solubility of the compounds does not exceed 5 10-4 mol·L-1 in aqueous solvents and 6 10-2 mol·L-1 in alcohol. The solubility values were correlated by van’t Hoff and modified Apelblat equations. Based on the partition coefficients in the system 1-octanol/ buffer pH 7.4 the lipophilicity of the compounds have been estimated. The thermodynamic functions of dissolution and partition for the compounds studied in the solvents selected were calculated. It has been established that the transfer process of compounds from the aqueous phase to the organic is endothermic and entropy-controlled. The efficiency of the some computer’s programs to predict partition coefficients has been tested using experimental data. It was shown that the in vitro antifungal activity of the studied compounds increases with growth solubility in aqueous solvents.

The temperature dependence of the saturated vapour pressure of the antifungal drugs – tioconazole (TCZ), miconazole (MCZ) and climbazole (CLZ) – was determined by the inert gas carrier transfer method. The standard molar enthalpies of sublimation at T = 298.15 K calculated from these data were 117.2 ± 0.5 kJ·mol-1 for TCZ ± 0.9, 106.2 ± 1.0 kJ·mol-1 for MCZ and 113.3 kJ·mol-1for CLZ. The vaporization and sublimation enthalpies of the compounds were found by the Langmuir and Clausius-Clapeyron equations without determining the vapour pressures of the drugs. Sublimation enthalpies derived by both these methods were in good agreement. It was shown that it was possible to estimate the thermodynamic sublimation functions by applying the space clusterization approach to the studied and structurally related compounds. In addition, the temperature and enthalpy of fusion of the compounds were measured by differential scanning calorimetry.

Three biologically active selenium bicyclic compounds – N-aryl-(3-seleno-azabicyclo[3.3.1]non-2-ylidene)amines were synthesized. The effect of the substances structure on their protolytic properties was investigated. The substance solubility in hexane and pharmaceutically relevant buffer solutions (pH 2.0 and pH 7.4) was measured in the temperature range of 293.15–313.15 K by the saturation shake-flask method. Temperature dependences of the distribution coefficients of the compounds in the two-phase systems “organic solvent (octanol, hexane)/buffer solution” were obtained. Thermodynamic parameters of distribution process were calculated.

The solubility of eight biologically active nonaromatic compounds with a common 3-thia-1-aza-bicyclo fragment in 1-octanol and hexane was determined in the temperature range of T = 293.15–315.15 K. The solubility of the substances in alcohol is approximately 2 orders of magnitude higher than in alkane and varies within 3.0 × 10–3 to 2.1 × 10–1 and 7.1 × 10–5to 13.5 × 10–3 mol. fractions, respectively. In accordance with the structure of the substituent at the para position of the phenyl ring, the studied compounds are arranged in the following order of decreasing solubility in both solvents: methyl- > fluoro- > ethyl- > trifluoromethyl- > cyano- > acetyl-. The ideal solubility of the substances in 1-octanol, calculated from thermophysical parameters was found to correlate with the reported experimental data. The activity coefficients of the substances in saturated solutions of organic solvents are determined by the method of distribution between two liquid phases. The thermodynamic aspects of the relation...

The saturated vapor pressures of 4 nonaromatic bicyclic 1,3-thiazine and 1,3-selenazine derivatives have been measured by the method of transpiration by inert gas-carrier in the temperature range of 308–392 K. Based on the experimental data the thermodynamic functions of sublimation have been calculated. The sublimation enthalpies of the compounds vary from 104 to 150 kJ mol −1 depending on the chemical nature of the substituent in the aryl moiety and the heteroatom in the bicyclic fragment. The crystal lattice energy of thiazines decreases with the introduction of substituents in the following order: cyano > acetyl > isopropyl. New approach has been suggested to evaluating sublimation enthalpy of the studied and structurally related compounds by using clusterization of the space of experimental points.

In this work we measured self-diffusion coefficients of 5 drugs (aspirin, caffeine, ethionamide, salicylic acid, and paracetamol) and 11 biologically active compounds of similar structure in deuterated water and 1-octanol by NMR. It has been found that an increase in the van der Waals volume of the molecules of the studied substances result in reduction of their diffusion mobility in both solvents. The analysis of the experimental data showed the influence of chemical nature and structural isomerization of the molecules on the diffusion mobility. Apparent permeability coefficients of the studied compounds were determined using an artificial phospholipid membrane made of egg lecithin as a model of in vivo absorption. Distribution coefficients in 1-octanol/buffer pH 7.4 system were measured. For the first time the model of the passive diffusion through the phospholipid membrane was validated based on the experimental data. To this end, the passive diffusion was considered as an additive process of molecule passage through the aqueous boundary layer before the membrane and 1-octanol barrier simulating the lipid layer of the membrane.

Vapor pressure of thioacetazone (TAZ) has been determined in the temperature range of 404.15–429.15 K by the transpiration method. The obtained data were used to calculate the standard molar enthalpy of sublimation that was found to be 164.1 kJ/mol at T = 298.15 K. The drug solubility was measured at seven temperatures from 288.15 to 318.15 K in modeling solvents: octanol, hexane and aqueous buffers pH 2.0 and 7.4 by the saturation shake-flask method by using spectrophotometric analysis. It has been found that TAZ has poor solubility in hexane and buffer solutions and limited solubility in octanol. The experimental data were well correlated by van’t Hoff and modified Apelblat equations. A temperature dependence of TAZ partition coefficient in the octanol/buffer pH 7.4 system has been derived. The partition coefficient value in this system (logP = 1.82) refers to the optimal interval for oral absorption drugs. The thermodynamic parameters of sublimation, solubility, solvation and transfer have been determined based on experimental data. The dominant effect of enthalpy and entropy contributions to the Gibbs energy of the investigated processes has been revealed.

The transpiration method was used to measure the vapor pressures as a function of temperature of the following antimicrobial drugs: ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin. Based on these results standard molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K were calculated and a correlation between the crystal lattice energy and the saturation vapor pressure in a number of fluoroquinolones was found. The thermophysical characteristics of the compounds studied were determined by DSC. The influence of different structural fragments of molecules substituents and the effects of hydrogen bonds in crystal lattices on the sublimation enthalpy was discussed.

Synthesis and antifungal activity of hybrids of thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazoles are presented. The solubility and lipophilicity of compounds was assessed and it was discovered that compounds with piperazine linker exhibited significant antifungal activity against filamentous and yeast fungi.

Novel (5Z)-3-(3-(4-acetylpiperazin-1-yl)-2-hydroxypropyl)-5-(4-chlorobenzylidene)thiazolidine-2,4-dione was synthesized as a potent antimicrobial agent. Its melting enthalpy and melting point temperature were measured to be 44.4 kJ∙mol−1 and 433.9 K, respectively. The solubility of the compound studied was determined in pharmaceutically and industrially relevant organic solvents within the temperature range of 293.15–313.15 К. The solubility was found to increase in the systems with the following solvents: hexane, buffer рН 7.4, buffer рН 2.0, 1-octanol, 1-propanol, ethanol, and methanol. The compound solubility values were correlated by the modified Apelblat equation, two-suffix Margules and Wilson models with good agreement. The activity coefficients at infinite dilution and excess thermodynamic functions of the compound in eaсh solvent were calculated. The compound ability to disperse, polar and hydrogen interactions were described using Hansen solubility parameters. The temperature dependences of the distribution coefficients of the compound in 1-octanol/buffer (pH 2.0 and 7.4) two-phase systems were determined. The distribution process was characterized as thermodynamically favorable, endotermic and entropy-driven.

Four novel potential antifungal 1,2,4-triazole hybrids of thiazolopyrimidines with different - methyl-, methoxy-, chloro-, and fluoro- substituents in the molecule phenyl ring were synthesized and characterized by 1H NMR spectra. The PXRD and DSC techniques showed that the solid phases of the obtained compounds were amorphous. The kinetic solubility of the substances was studied in aqueous media of various acidity degrees. The equilibrium solubility of the derivatives was determined in buffers (pH 2.0 and 7.4) and 1-octanol at (293.15–313.15) K by the shake flask method. The compound solubility in the buffers did not exceed 9.0∙10−4 mol/L and decreased when the substituent was changed as follows: methoxy-, methyl-, chloro-, and fluoro-. The methoxy-derivative was found to have the more higher solubility in 1-octanol - 1.3∙10−2 mol∙L−1 at 298.15 K. The solubility behavior of the substances was studied based on Hansen solubility parameters. The solubility values were correlated by the modified van't Hoff and modified Apelblat equations. The best result was achieved with the modified Apelblat model. The partition coefficients of the compounds in the 1-octanol/buffer pH 7.4 system were determined at (293.15–313.15) K. The logPO/B values of the substances ranged from 0.80 to 1.27 at 298.15 K, depending on the chemical nature of the substituents that indicates to good balance between their solubility and permeability. The thermodynamic functions of dissolution and partition for the compounds studied in the solvents selected were calculated. A diagram approach was used to analyze the enthalpy and entropy contributions to the Gibbs energy of dissolution of the substances studied.

The sulfasalazine melting temperature and molar enthalpy have been determined by the DSC method. The shake flask method has been used to measure the drug solubility in buffer solutions (pH 2.0 and 7.4), hexane, and octanol and to determine the distribution coefficients in the octanol/buffer systems in the temperature range of 293.15–313.15 K. The calculated thermodynamic functions were then used to study the influence of the solvent type and sulfasalazine protolytic properties on the drug dissolution and distribution.

Inclusion complexation of 2-hydroxypropyl-β-cyclodextrin with biologically active compounds 2-hydroxybenzaldehyde isonicotinoylhydrazone and 2-hydroxy-3-methoxybenzaldehyde isonicotinoylhydrazone in buffer pH 7.4 solution and in solid state have been investigated. The solubility of compounds at different concentrations 2-hydroxypropyl-β-cyclodextrin was studied by phase solubility method. The profile displayed a typical AL-type, indicating the formation of 1:1 stoichiometric inclusion complex. Solution state complexation in buffer was validated by ultra violet absorption. Stoichiometry of complex was confirmed by Job’s method. The water solubility of compounds studied was significantly increased through complexation with 2-hydroxypropyl-β-cyclodextrin. Complexation stability constants and thermodynamic parameters have been calculated. It has been concluded that inclusion complexation is an exothermal and enthalpy-determined process. The solid state inclusion complex was prepared by the ball-milling method and characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffraction. The dissolution rate of the active pharmaceutical ingredient of the supramolecular complexes were obtained.

The solubility of antituberculosis drug ethionamide and structural analogues in buffer solutions, octanol and hexane within the temperature range from (293.15–313.15) K was measured using the shake-flack method. All the compounds studied appeared to have the solubility neither more than 10−3 mol fraction in aqueous solutions. At that the solubility in buffer pH 7.4 is lower than that in pH 2.0 which is determined by the ionization state. The solubility in octanol was estimated to be essentially higher than in hexane that is explained by the specific interactions of the compounds with the solvent. Thermodynamic solubility and solvation functions for the substances in the solvents studied were calculated. The partition coefficients of the compounds were measured in the octanol – buffer pH 7.4 system. The solubility values of the unionized molecular species of the investigated compounds using the partition coefficients and HYBOT descriptors for the biologically active substances were calculated. Comparison of the experimental and calculated solubility values showed the acceptability of the proposed approach for predicting the solubility of the compounds of aromatic thioamide series.

The solubility of the antifungal drug fluconazole in buffer solutions of different acidity (pH 1.2, 2.0 and 7.4), 1-octanol and hexane in the temperature range (293.15–313.15) K is determined by the isothermal saturation method. The solubility of the compound in selected solvents increases as follows: hexane, buffer pH 7.4, buffer pH 2.0, 1- octanol, buffer pH 1.2, and does not exceed 0.2 mol·l−1. The temperature dependence of fluconazole saturated vapor pressure is obtained by the transpiration method. The sublimation enthalpy of the compound equals 131.4 ± 0.9 kJ·mol−1. Based on the HYBOT descriptors, it is shown that it is possible to estimate the sublimation enthalpy of compounds structurally similar to fluconazole.

The saturated vapor pressure of 5 biologically active compounds of the series of hydrogenated pyrido[4,3-b]indoles were measured using the transpiration method in the temperature range of (427.15–461.15) K. Based on the experimental data the thermodynamic functions of sublimation were calculated. The sublimation enthalpies of the compounds vary from 143.1 to 167.3 kJ·mol−1. It has been shown that the thermodynamic functions of sublimation can be estimated by the space clusterization approach for the studied and structurally related compounds The diagram approach has been used to study the effect of the chemical nature of substituents on sublimation, dissolution and solvation of the compounds in solvents modelling different biological media: buffer pH 7.4, 1-octanol and n-hexane. It has been established that structural modification of the molecules through the introduction of a fluorine atom into the indole fragment reduces the sublimation and solvation terms of the Gibbs energy of dissolution in buffer pH 7.4 and hexane, improving the solubility.

Temperature dependences of saturated vapor pressure for crystalline phases of 2-ethyl-4-pyridinecarbothioamide (ethionamide) and two parent compounds 2- and 4-pyridinecarbothioamide isomers were measured by the transpiration method. The results were used to determine the standard molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K. HYBOT descriptors application has shown an increase in the donor–acceptor ability of the molecules of the studied compounds to form hydrogen bonds to result in their crystal lattice energy growth. The obtained standard molar sublimation enthalpies have been compared with the literature results for 2- and 4-substituted pyridine isomers.

The solubility values of pyrazinamide, isoniazid, and p-aminobenzoic acid in buffers (рН 2.0 and 7.4) and octanol were measured in the temperature range of 293.15 to 313.15 K. The dissolution Gibbs energy, enthalpy, and entropy were calculated. The dissolving process was endothermic and enthalpy-determined. The activity coefficients of the compounds at infinite dilution were determined based on the solubility data and thermophysical parameters. A positive deviation from the ideality was observed in all the solutions. A common tendency of the solubility increase with a decrease in the activity coefficients at T = 298.15 K was revealed for the investigated solute-solvent systems. The excess thermodynamic solubility functions were calculated from the temperature dependences of the activity coefficients. The solvation processes were found to have a considerable influence on the solubility of the substances in solutions studied.

The solubility of the biologically active substances, salinazid and vanillin isoniazid, was measured in the buffer solutions (pH 2.0 and 7.4) and in octanol within the temperature range from (293.15 to 313.15) K. The solubility of the compounds in all the investigated solvents was revealed to be less than 10–3 mole fraction and increases with the solvents in the order: buffer at pH 7.4 < buffer at pH 2.0 < octanol. The enthalpies of dissolution and solvation were calculated. The temperature dependences of the distribution coefficients in the system buffer at pH 7.4/octanol system were obtained and the transfer thermodynamic functions were derived. The distribution coefficients were used to predict the solubility of the studied compounds in aqueous medium.

The inert gas transpiration technique was used for measuring the vapor pressures of the following biologically active compounds: 4-aminobenzoic acid, nicotinic acid, 4-aminobenzamide, 4-pyridinecarboxamide, N-(2-chloro-3-pyridinyl)-benzenesulfonamide, 4-nitro-N-2-thiazolyl-benzenesulfonamide, and 4-amino-N-(5-methyl-3-isoxazolyl)-benzenesulfon-amide in the appropriate temperature ranges. Differential scanning calorimetric analysis was applied to obtain the temperature and molar enthalpy of melting of the compounds studied. Standard molar enthalpies, entropies, and Gibbs energies of sublimation were derived at T = 298.15 K from the temperature dependences of the vapor pressure of the compounds. The obtained results allowed the estimation of the relationship between the sublimation thermodynamic parameters and the thermophysical properties of the substances. Correlation equations were used for calculating the saturated vapor pressures on the basis of the melting temperatures, sublimation enthalpies, and physicochemical HYBOT descriptors.

2-Amino-1,3-selenazine template derivatives in the form of hydrobromides were synthesized. Phenyl, para-isopropylphenyl, and para-fluorophenyl were used as substituents. The distribution coefficients of the compounds in two-component systems modeling biological membranes, pH 2.0 and 7.4 buffer solution–organic solvent, were determined by a shake-flask method within the temperature range of 293 K to 313 K. Influences of the molecular structure, pKa, and pH of the buffer solutions, temperature, and solvent chemical nature on the distribution processes were investigated. Distribution thermodynamic functions were calculated for the selenazines under 298 K. It was established that the selenazines studied are substances with high membrane permeability.

The temperature dependencies of the saturated vapor pressure for antituberculous drug compounds: pyrazinecarboxamide and three isonicotinic acid hydrazides were obtained using the method of inert gas-carrier transfer. The standard sublimation molar enthalpies, entropies and Gibbs energies were derived at T = 298.15 K. The temperature and fusion molar enthalpy of the compounds were measured using the differential scanning calorimetry technique. The influence of the structure of the studied compounds on the crystal lattice energy and volatility was analyzed. It was estimated that the saturated vapor pressure of the studied substances decreases when the molecule polarizability and donor–acceptor ability increase.

Complexation processes in the systems of 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) – pharmacologically active substances within the temperature range of 293–315 K were studied by the UV-spectroscopy method. 2HP-β-CD was shown to improve the solubility of the studied drugs in aqueous systems. It was proved that complexation leads to the formation of supramolecular inclusion compounds with a 1:1 component ratio. The obtained complex 2HP-β-CD–methylium, tris(1-pentyl-1H-indol-3-yl)-, chloride was found to be unstable in buffer pH 7.4. Stability constants of the complexes and thermodynamic parameters of the formation of the inclusion compound 2HP-β-CD-1H-indole-3-methanol and 1-pentyl-α,α-bis(1-pentyl-1H-indol-3-yl) were calculated. The negative values of the changes in the Gibbs energy and the enthalpy indicate that the inclusion process is spontaneous and exothermic. The excess of the enthalpy term over the entropic one indicates that the inclusion process is enthalpy-determined.

Novel bicyclic derivatives have been synthesized. The solubility of drug-like substances in phosphate buffer рН 7.4 has been measured within the range of (9.02 · 10−5 to 1.05 · 10−4) mol/l. The relationship between the chemical nature and the structure of the aryl substituents and the solubility parameter was investigated. The fusion temperatures, enthalpies and entropies have been determined experimentally. The influence of thermophysical characteristics and lipophilicity on the solubility was studied using regression analysis. The calculations by the solubility/lipophilicity equation showed an overall improvement of the predictions equal to 0.5 log units. It was concluded that the solvation has a considerable influence on the solubility of the compounds under consideration. It was also determined that the alkyl- and halogen-derivatives solubility values correlate with HYBOT descriptors characterizing the (donor + acceptor) properties of the substances. The thermodynamic parameters of the solubility process were calculated using the temperature dependences. The study also revealed that the solubility of the bicyclic compounds is characterized by high endothermicity of the processes and negative entropies.

Drug-like N-substituted 1-selena-3-azaspiro[5,5]undec-2-en-2-amine hydrobromides (1:1) have been synthesized. Phenyl, isopropylphenyl, and fluorophenyl substituents were used. The solubility of the obtained compounds in pharmaceutically relevant solvents within the temperature range from (298.15 to 318.15) K has been measured using the isothermal saturation technique. All of the compounds studied appear to have poor solubility of ∼10–6 mole fraction in phosphate buffer pH 7.4 and hexane. The solubility values enlarge substantially to ∼10–2 and 10–4 mole fraction, respectively, in octanol and muriatic buffer solution pH 2.0. The solubility of the selenazines in aqueous media was shown to increase as the number of protonated forms grew. The high solubility of the compounds in octanol was found to depend on the formation of intermolecular solvent–solute hydrogen bonds. Thermodynamic solubility functions for the substances in the solvents studied have been calculated. The solubility in all of the systems with...

New spiro-derivatives of 1,3-thiazine – potential neuroprotectors have been synthesized. It has been determined that the obtained compounds are biologically active and capable of blocking the glutamate-induced calcium ion uptake into synaptosomes of rat brain cortex. The inhibitory activity of the test substances was shown to depend on the chemical nature and structure of the substituents bound with an exocyclic nitrogen atom. Non-polar alkyl and polar radicals with halogen, oxygen and nitrogen atoms were used as substituents. It is typical of the active spiro-thiazines to have alkyl substituents in ortho- and para-position of the benzene ring. Among the investigated spiro-thiazines it is the derivatives with ethyl- and isopropyl-groups in the aril part of the molecules that are the lead-compounds with a high inhibitory ability. We measured the distribution coefficients of the substances in octanol/buffer and hexane/buffer systems and made conclusions about the ability of the investigated drug-like compounds to penetrate the biological membranes. By using the parabolic model we derived a quadratic equation that allowed us to evaluate quantitatively the inhibitory activity of spiro-thiazines with hydrophobic substituents based on lipophilicity data. We also studied the permeability through the phospholipidic membrane and introduced a correlation equation describing the dependence of the investigated spiro-thiazines activity on the descriptors characterizing the donor–acceptor properties.

The vapor pressures of five novel bicyclic heterocycle derivatives were measured over the temperature 341.15 to 396.15 K using the transpiration method by means of an inert gas carrier. From these results the standard enthalpies and Gibbs free energies of sublimation at the temperature 298.15 K were calculated. The effects of alkyl- and chloro-substitutions on changes in the thermodynamic functions have been investigated. Quantitative structure–property relationship on the basis HYBOT physico-chemical descriptors for biologically active compounds have been developed to predict the sublimation enthalpies and Gibbs free energies of the compounds studied.

Equilibrium solubility of clotrimazole, an important antimycotic drug, was measured between (293.15–313.15) K in four pharmaceutically relevant solvents including buffer pH 2.0, buffer pH 7.4, hexane and 1-octanol. The experimental solubility results were correlated by modified Apelblat and van’t Hoff equations. The compound melting temperature and enthalpy were determined. The activity coefficients at infinite dilution of clotrimazole in each solvent were calculated from experimental data on solubility and thermophysical properties. Substitution aqueous solvents for organic ones leads to lower activity coefficients and higher solubility of the drug. The limiting partial molar excess enthalpies, entropies and Gibbs energies of clotrimazole were evaluated.

A new choline hydrate salt of Diclofenac (DCF) was obtained using crystallization from a solution of DCF sodium and choline chloride in ethanol. The structure of the compound was determined by single-crystal X-ray diffraction. The DCF anions, choline cations and water molecules were arranged as a two-dimensional bridge structure connected through hydrogen bonds. The “choline-skeleton” in the crystal is systematically disordered, showing two propeller-like cage structures. The formation of a new compound was confirmed by the powder X-ray diffraction method. The thermal behavior of the salt was characterized by the DSC, DTA and HSM techniques. The compound solubility was measured by the shake-flask method at a temperature of 25 °C in water and buffer solutions with different pH that simulated physiological media. It has been established that the solubility of the synthesized salt is higher than that of DCF sodium in all the aqueous solutions used.

Temperature dependencies of saturated vapor pressure of novel bicyclo-derivatives of 1,3-thiazine with methoxy- and carbonyl-substituents have been obtained by method of transference by means of an inert gas carrier. Thermodynamic functions of sublimation have been calculated. Correlations between thermodynamic functions of sublimation and thermophysical properties of the substances and molecular descriptors have been established. The enthalpies of solvation of compounds were calculated using the measured values of enthalpies of sublimation and of standard enthalpies of solution in hexane and buffer.

Novel drug-like spiro-derivatives of 1,3-thiazine were synthesized. Thermodynamic aspects of sublimation processes of the studied compounds were determined using temperature dependencies of the vapor pressures. Thermophysical characteristics of the molecular crystals were obtained and compared with the sublimation and structural parameters. Solubilities of spiro-derivatives in buffer and hexane were measured in the temperature interval 298.15–315.15 K by an isothermal saturation method. Temperature dependencies of partition coefficients for the studied substances in the systems buffer/organic phase were obtained. Thermodynamic functions describing the solubility, solvation and distribution processes were calculated. The diagram enabling analysis of the mechanism of transfer process was applied.

Temperature dependences of partition coefficient for 11 drug-like spiro-derivatives of 1,3-thiazine in the system aqueous phosphate buffer/organic phase (hexane, octanol) have been determined over the temperature range (293.15 to 315.15) K by the isothermal saturation method. The effects of aliphatic chain substituent structure and introduction of oxygen, chlorine, bromine and fluorine atoms on the partitioning processes of the substances studied were examined. It has been established that among the substances investigated halogen derivatives possess the lowest partition coefficients in buffer/hexane system and the highest ones in buffer/octanol system. Regularities between the partition coefficients and the descriptors reflecting the capability of the solutes to undergo specific and nonspecific interactions with solvent molecules were revealed. The thermodynamic functions describing the partitioning process were calculated. It was found that differences in the partition coefficients depend on the enthalpies of transfer.

Aqueous solubility and distribution of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin antimicrobials drugs in octanol/buffer system has been measured by the isothermal saturation method using buffer solutions pH2.0 and 7.4 in the temperature range of 293.15-313.15K. Thermophysical characteristics for the compounds have been determined by the DSC method. It has been established that the solubility of levofloxacin in these buffers is higher than that of the other fluoroquinolones. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor-acceptor capacity of the molecules on drugs solubility has been studied. According to the lipophilicity parameter fluoroquinolones are ranged in the following order: enrofloxacin>levofloxacin>ciprofloxacin>norfloxacin. The thermodynamic solubility and distribution functions of the studied compounds have been obtained. The permeability coefficients of the substances through an artificial phospholipid membrane were determined. The drugs with a lower aqueous solubility were estimated to have higher distribution coefficients and membrane permeability.

Temperature dependences of saturated vapor pressure for eight new molecular crystals of spiro-derivatives of 1,3-thiazine have been determined by transport method by means of an inert gas carrier. Thermodynamic functions of sublimation have been calculated. The processes of substances fusion have been examined by differential scanning calorimetry. The effect of alkyl substituents structure and introduction of halogen atoms on sublimation properties of spiro-compounds has been assessed. The correlation between thermodynamic parameters of sublimation processes and thermo-physical properties of the substances and molecular descriptors is established.

The solubility of 11 new drug-like spiro-compounds in buffer solution (pH 7.4) and hexane was measured by the isothermal saturation technique in the temperature range of (293 to 315) K. The influence of substituent chemical nature, branching of aliphatic chain, and inclusion of oxygen and halogen atoms in molecule structure were investigated. The correlation dependences of the solubility on molecular descriptors and thermophysical properties were estimated. Standard thermodynamic solubility functions for the test compounds were calculated. The conclusion reveals the dominant contribution of dispersion forces in the solution process.

The thermodynamic characteristics of ultimately dilute solutions of n-alkanes and n-alkanols in columnar and isotropic poly(propyleneimine) dendrimer phases of three generations (G1-G3) were studied by reversed-phase gas chromatography. The influence of the structure of dendrimers and the chemical nature and the size of nonmesogen molecules on their ability to be dissolved in liquid crystalline phases is discussed. It was found that the compatibility of low-molecular-weight compounds with anisotropic phases increased as the number of dendrimer generation grew.

The effect of the generation number on sorption behavior of the liquid crystalline (LC) poly(propyleneimine)dendrimers G1–G4 terminated with n-hexadecyl groups has been studied by inverse gas chromatography. To examine the accessibility of the terminal-group shell by small molecules, methyl-substituted derivatives of benzene, pyridine, aniline, and naphthalene have been chosen as probe solutes. The retention volumes and activity coefficients of the solutes are not linearly related to the generation number. The highest thermodynamic solute–solvent compatibility is observed for the dendrimer G2. On the other hand, the highest structural selectivity is observed for the dendrimer G3. The said sorption features are rationalized in terms of local ordering and a higher degree of tightness of the terminal-group shell in the macromolecules of high generations.

The chelate cadmium dichloride complex with semicarbazide was synthesized. The use of this complex in the cytostatic combination therapy together with cyclophosphamide results in 67% survival of mice and a threefold increase in the average life span of survivors with P-388 leukemia.

The efficacy of the combination treatment of P388 leukemia with cisplatin (cPt) and the platinum(IV) nitroxyl complex BC118 [e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bis(acetato)-b,c-dichloroplatinum(iv)] applied in low doses was found to be synergistically increased. Thus, the use of 1/10 of their LD50 cured 100% of animals. The monotherapy with these drugs used in the same doses and at the same schedules showed moderate efficacy, and no animals survived. A synergistic increase in the toxicity was not observed. The rate of the development of resistance decreases in the series cPt+BC118, cPt, and BC118. Strains resistant to cPt+BC118 and BC118 are highly sensitive to doxorubicin, etoposide, and cyclophosphane.

This work reports on copper tetra(3-nitro-5-tert-butyl)phthalocyanine (CuPc*) exhibiting complex but well-controlled phase behavior. A key structural feature of this dye is the thermodynamically stable χ-type phase whose optical absorbance is red-shifted with respect to the CuPc* molecule. Small-angle X-ray scattering and optical spectroscopy have been used to watch the phase formation of CuPc* in the one-component system and binary composite with polystyrene (PS). The polymer exerts a powerful stabilizing effect on the lower phases of CuPc*, hence a manageable suite of the phase transformations β→α→χ is realized in the CuPc*–PS system. Regardless the phase type, the composite is highly transmissive in the blue-green region of the spectrum. Thus, it is applicable to reveal quantitative relationships between nonlinear optical properties and the supramolecular structure of phthalocyanines.

The thermodynamic characteristics and selectivity of sorption of disubstituted benzene, pyridine, and naphthalene by the p-n-nonyloxybenzoyloxy-p′-cyanoazobenzene, p-n-hexyloxycinnamoyloxy-p′-cyanoazobenzene liquid crystalline phases and their mixture was studied by gas chromatography. The reentrant nematic phase of a mixture of mesogens was found to possess high selectivity to structural isomers. The results of manifestation of liquid crystalline phase selectivity are discussed on the basis of the enthalpy and entropy characteristics of solution of sorbates.

The paper reports on binary composites prepared from fullerene C60 and π-rich cobalt tetrakis(4-amino-5-phenoxy)phthalocyanine (CoPc) being a mixture of four geometrical isomers. Co-aggregation has been conducted under aqueous and non-aqueous conditions by the Langmuir–Blodgett (LB) technique and drop-casting from o-xylene, respectively. The prepared LB composites are badly disordered whereas the cast ones are predominantly structured: depending on the C60/CoPc ratio, the wire-, worm-, or bead-like particles are observed. Optical spectroscopy is used to reveal the aggregation state of fullerene in the composites. The nano-scale heterogeneities resulting from homomolecular aggregation of fullerene are revealed only in the former case. Smooth co-aggregation under non-aqueous conditions is attributed to intermediate formation of the ternary C60–CoPc–xylene solvates. Formation of the well-shaped composite particles seems to be an optional post-aggregation process being favored by the molecular symmetry of the CoPc isomers.