Investigation of Pharmaceutical Importance of 2H-Pyran-2-One Analogues via Computational Approaches

Highly functionalized spirocyclic ketals were synthesized through asymmetric oxidative spirocyclization via carbanion-induced ring transformation of 2H-pyran-2-ones with 1,4-cyclohexandione monoethyleneketal under alkaline conditions. Further acidic-hydrolysis of obtained spirocyclic ketals yields highly substituted 2-tetralone in good yield. Computational analysis based on the DFT calculations and MD simulations has been performed in order to predict and understand global and local reactivity properties of newly synthesized derivatives. DFT calculations covered fundamental reactivity descriptors such as molecular electrostatic potential and average local ionization energies. Nitrogen atom and benzene rings have been recognized as the most important molecular sites from these aspects. Additionally, to predict whether studied compounds are stable towards the autoxidation mechanism, we have also studied the bond dissociation energies for hydrogen abstraction and identified the derivative which might form potentially genotoxic impurities. Interactions with water, including both global and local aspects, have been covered thanks to the MD simulations and calculations of interaction energies with water, counting of formed hydrogen interactions, and radial distribution functions. MD simulations were also used to identify which excipient could be used together with these compounds, and it has been established that the polyvinylpyrrolidone polymer could be highly compatible with these compounds, from the aspect of calculated solubility parameters.

THERMODYNAMIC ANALYSIS OF TRICALCIUM SILICATE HYDRATION

Thermodynamic analysis of the hydration processes of tricalcium silicate 3CaO•SiO2 is difficult due to the unreliability of the initial data for hydration products. In addition, there are disagreements about the basicity of the hydration phases (3CaO•SiO2•3H2O or 2CaO•SiO2•2H2O). For the latter, there is no free energy of formation in the reference literature. There are also no data on the water solubility of these calcium hydrosilicates. The proposed values of ∆G0298 for these hydrosilicates, equal to 1064,3 and 639,7, as well as the enthalpies of formation (∆Н0298), equal to 1157,2 and 696,9 kcal/mol, re-spectively. Further thermodynamic calculations were performed using these values. To calculate the composition of the liquid phase, a simplified Born-Haber cycle is used. The values of the calculated heat release of tricalcium silicate with the formation of C3S2H3 and C2SH2, obtained using the pro-posed values of enthalpies, differ little from each other and are close to the experimental data. The calculated solubility of C3S2H3 is 0,7 g/l CaO, and C2SH2 is 0,92 g/l CaO. Since the solubility of C3S2H3 is much lower than of Ca(OH)2 (portlandite), which is formed during hydration of tricalcium silicate in large quantities, C3S2H3 is unstable under these conditions and its basicity increases. It is suggested that C3S2H3 is the main hydration product of CEM III and other cements with a high content of active mineral additives, and C2SH2 is CEM I and CEM II.

Określenie możliwości zastosowania symulacji komputerowej do przewidywania kierunku przebiegu reakcji podczas zatłaczania wód złożowych

Currently, practically the entire volume of water extracted in the process of hydrocarbon exploitation is utilized by injection into deposits. Changes in the physico-chemical parameters (pH, red-ox potential, temperature, etc.) of the water during extraction and the contact of the injected water with the native water and deposit rock may result in the precipitation of sediment particles and suspensions. It causes clogging of the near-wellbore zone and limits the amount of water that can be injected with the injection well. Due to the high complexity of the system: the injected water–reservoir rock, and a wide range of interactions between individual components, the analytical data does not always allow for the correct interpretation of the course of the processes and determination of their impact on the permeability of the near-well zone. Using the results of physico-chemical analyses of the composition of separator water samples with different properties – two samples with low mineralization S1K (575 mg/dm3) and S4K (551 mg/dm3), a sample with high S2K (306 428 mg/dm3) and medium mineralization S3K (79 858 mg/dm3) – calculations were performed using the PHREEQC program for the three databases: phreeqc.dat, wateq4f.dat and pitzer.dat. It was found that in the case of low mineralization waters, the results obtained in each of the databases are similar for the minerals present in all the databases. However, in the case of solutions with high mineralization, there are significant differences in the obtained results. The calculated solubility indices allowed to determine the direction of the precipitation/dissolution reaction of individual minerals in the deposit and to indicate the risks, mainly with the formation of iron compounds deposits, for the operation of the injection well. Laboratory tests of water mixing were also carried out. The formation of iron oxide deposits that could damage the near-well zone was observed, which confirmed the results obtained during computer simulations.

Thermodynamic Modeling of Boron Species in the Ternary System Na2O-B2O3-H2O at 298.15 K

The solubilities; concentration of four boron species B(OH)3, B(OH)4−, B3O3(OH)4−, and B4O5(OH)42−; and H+ (OH–) in the system Na2O–B2O3–H2O were calculated with the Pitzer model. The boron species B5O6(OH)4− was not considered in the model calculation. The calculated solubility and pH data are in accordance with the experimental results. The Pitzer model can be used to describe the experimental values. The distributions of the four boron species in the solution were obtained. The mole fractions of the four boron species are mainly affected by the ratio of B2O3 and Na2O in the solution. The dominant boron species in the solution saturated with different salts vary greatly. The results can supply a theoretical reference for sodium borate separation from brine.

Using static method to measure tolmetin solubility at different pressures and temperatures in supercritical carbon dioxide

Tolmetin is a non-steroidal anti-inflammatory drug being used to decrease the level of hormones which are the reasons for pain, swelling, tiredness, and stiffness for osteoarthritis and rheumatoid arthritis cases. We evaluated its solubility in supercritical carbon dioxide (SC-CO2) with the aim of drug nanonization, considering temperature and pressure variations between 120 and 400 bar and 308–338 K, in the experiments. In this way, a PVT solubility cell based on static solubility approach coupled with a simple gravimetric procedure was utilized to evaluate the solubility of tolmetin. The solubility values between 5.00 × 10−5 and 2.59 × 10−3 mol fraction were obtained for tolmetin depending on the pressure and temperature of the cell. The measured data demonstrated a direct correlation between pressure and solubility of tolmetin, while the effect of temperature was a dual effect depending on the crossover pressure (160 bar). The calculated solubility data were modeled using several semi-empirical correlations, and the fitting parameters were calculated using the experimental data via appropriate optimization method. The correlated solubility data revealed that the KJ model was the most accurate one with an average absolute relative deviation percent (AARD%) of 6.9. Moreover, the carried out self-consistency analysis utilizing these correlations illustrated great potential of these models to extrapolate the solubility of tolmetin beyond the measured conditions.

Solubility Enhancement of Betamethasone, Meloxicam and Piroxicam by Use of Choline-Based Deep Eutectic Solvents

Background: The low aqueous solubility of three important drugs (betamethasone (BETA), meloxicam (MEL) and piroxicam (PIR)) have been increased by use of deep eutectic solvents (DESs) based choline chloride/urea (ChCl/U), choline chloride/ethylene glycol (ChCl/EG) and choline chloride/glycerol (ChCl/G) as new class of solvents at T = (298.15 to 313.15) K. Methods: DESs were prepared by combination of the ChCl/EG, U and G with the molar ratios: 1:2. The solubility of drugs in the aqueous DESs solutions was measured at different temperatures with shake flask method. Results: The solubility of the investigated drugs increased with increasing the weight fraction of DESs. The solubility data were correlated by e-NRTL and Wilson models. Also, the thermodynamic functions, Gibbs energy, enthalpy, and entropy of dissolution were calculated. Conclusion: At the same composition of co-solvents and temperature, the BETA, PIR and MEL solubility was highest in (ChCl/U + water), (ChCl/U + water) and (ChCl/EG + water) respectively. The calculated solubility based on these models was in good agreement with the experimental values. In addition, the results show that, the main contribution for drugs solubility in the aqueous DES solutions is the enthalpy.

Investigation on the Interaction between Cellulosic Paper and Organic Acids Based on Molecular Dynamics

Organic acid is an important factor that accelerates the aging of cellulosic insulation materials. In this study, the interactions between cellulose and five acids, representative of what may be found in an aging transformer, were studied using molecular dynamics. The adsorption process of the five acids onto the surface of crystalline cellulose shows that the three low molecular acids are more readily adsorbed onto cellulose than the two high molecular acids. The deformation and adsorption energies of the acids all increase with an increase in molecular weight when they are stably interacting with cellulose. However, the differences between adsorption energies and deformation energies are positive for the three low molecular acids, whereas they are negative for the two high molecular acids. This indicates that the attachments onto cellulose of low molecular acids are considerably more stabilized than those of the high molecular acids. This is consistent with the experimental results. Furthermore, based on the calculated solubility parameters of acids, the experimental result that the three low molecular acids are to a large degree absorbed onto the cellulose, whereas the two high molecular acids remain in the oil, was theoretically elucidated using the theory of similarity and intermiscibility.

The Solubility of Hydrocarbon Gases in Glassy Polymers: Fractal Modeling

This work describes the fractal modeling of the solubility ofn-alkanes,n-alkenes, methylacetylene, allene, ethylacetylene, and butadiene hydrocarbon gases in glassy poly(vinyltrimethylsilane) (PVTMS). The proposed equation represents satisfactorily the solubility coefficients of the hydrocarbon gases in glassy PVTMS as a function of the fractal dimension of the polymer and the effective diameter of a gas penetrant molecule. It is found that the calculated solubility coefficients have a good correlation with the experimental data. The proposed model can predict the solubility of hydrocarbon gases in glassy polymers.

Measurement and Correlation of Solubilities and Surface Tension of Caffeine in Water

The solubility of caffeine in water between 323.15 and 353.15 K was measured using the balance method. The solubility trend was modeled by use of the modified Apelblat equation and Yaws equation. The calculated solubility values according to the two empirical equations compare favorably with the experimental data. Besides, the relationship between supersaturated ratio and induction time was studied with the method of laser, basing on which, the surface tension of caffeine at 283.15 K, 293.15 K and 298.15 K in water was calculated.