Solubility of palbociclib in supercritical carbon dioxide from experimental measurement and Peng-Robinson equation of state.

Palbociclib is a poorly water-soluble medicine which acts against metastatic breast cancer cells. Among various techniques to improve the solubility of this medicine, applying supercritical technologies to produce micro- and nano-sized particles is a possible option. For this purpose, extraction of solubility data is required. In this research, the solubility of palbociclib in supercritical carbon dioxide (ScCO2) at different equilibrium conditions was measured at temperatures between 308 and 338 K and pressures within 12-27 MPa, for the first time. The minimum and maximum solubility data were found to be 8.1 × 10-7 (at 338 K and 12 MPa) and 2.03 × 10-5 (at 338 K and 27 MPa), respectively. Thereafter, two sets of models, including ten semi-empirical equations and three Peng-Robinson (PR) based integrated models were used to correlate the experimental solubility data. Bian's model and PR equation of state using van der Waals mixing rules (PR + vdW) showed better accuracy among the examined semi-empirical and integrated models, respectively. Furthermore, the self-consistency of the obtained data was confirmed using two distinct semi-empirical models. At last, the total and vaporization enthalpies of palbociclib solubility in ScCO2 were calculated from correlation results of semi-empirical equations and estimated to be 40.41 and 52.67 kJ/mol, respectively.

First principles calculations on lithium diffusion near the surface and in the bulk of Fe-doped LiCoPO4.

The olivine phosphate LiCoPO4 is a prospective cathode material in high-voltage lithium-ion batteries. During lithium diffusion, the ions must overcome the diffusion energy barrier near the surface and in the bulk. Experimental studies have shown that Fe doping can enhance the electrochemical performance of LiCoPO4 with a doping concentration of x = 0.2 (LiFe0.2Co0.8PO4). DFT calculations can provide detailed understanding of the lithium diffusion mechanism, structural stability, and electronic properties for Fe-doped LiCoPO4 and elucidate the origins for this improvement from a microscopic viewpoint. In this study, the electronic structure of Fe-doped LiCoPO4 was calculated via first principles and compared with that of pristine LiCoPO4. To investigate the surface properties of LiCoPO4, surface energies with low indices were calculated. The results showed that the (010) surface has the lowest surface energy. Minimum energy diffusion pathways and energy barriers were calculated using the NEB method. Our calculations showed that the energy barrier for lithium-ion diffusion can be reduced by Fe doping modification. Furthermore, we investigated the diffusion processes of polarons and lithium ions migrating simultaneously. This study has implications for further application of LiCoPO4 as a cathode material.

A Benchmark Open-Source Implementation of COSMO-SAC.

The COSMO-SAC modeling approach has found wide application in science as well as in a range of industries due to its good predictive capabilities. While other models for liquid phases, as for example UNIFAC, are in general more accurate than COSMO-SAC, these models typically contain many adjustable parameters and can be limited in their applicability. In contrast, the COSMO-SAC model only contains a few universal parameters and subdivides the molecular surface area into charged segments that interact with each other. In recent years, additional improvements to the construction of the sigma profiles and evaluation of activity coefficients have been made. In this work, we present a comprehensive description of how to postprocess the results of a COSMO calculation through to the evaluation of thermodynamic properties. We also assembled a large database of COSMO files, consisting of 2261 compounds, freely available to academic and noncommercial users. We especially focus on the documentation of the implementation and provide the optimized source code in C++, wrappers in Python, and sample sigma profiles calculated from each approach, as well as tests and validation results. The misunderstandings in the literature relating to COSMO-SAC are described and corrected. The computational efficiency of the implementation is demonstrated.

Understanding the Differing Fluid Phase Behavior of Cyclohexane + Benzene and Their Hydroxylated or Aminated Forms.

The three binary mixtures cyclohexane + benzene, cyclohexanol + phenol, and cyclohexylamine + aniline exhibit qualitatively different vapor-liquid phase behavior, that is, azeotropic with a pressure maximum, azeotropic with a pressure minimum, and zeotropic, respectively. Employing molecular modeling and simulation, the COSMO-SAC model, and a cubic equation of state, the root of these effects is studied on the basis of phase equilibria, excess properties for volume, enthalpy, and Gibbs energy as well as microscopic structure. It is found that cyclohexane + benzene is characterized by more pronounced repulsive interactions, leading to pressure maximum azeotropy and a positive excess Gibbs energy. Functionalizing the aliphatic and aromatic rings with one amine group each introduces attractive hydrogen bonding interactions of moderate strength that counterbalance such that the mixture becomes zeotropic. The hydroxyl groups introduce strong hydrogen bonding interactions, leading to pressure minimum azeotropy and a negative excess Gibbs energy.

Rapid determination of entropy and free energy of mixtures from molecular dynamics simulations with the two-phase thermodynamic model.

The two-phase thermodynamic (2PT) model is generalized to determine the thermodynamic properties of mixtures. In this method, the vibrational density of states (DoS), obtained from the Fourier transform of the velocity autocorrelation function, and quantum statistics are combined to determine the entropy and free energy from the trajectory of a molecular dynamics simulation. In particular, the calculated DoS is decomposed into a solid-like and a gas-like component through the fluidicity parameter, allowing for treatments for the anharmonic effects in fluids. The 2PT method has been shown to provide reliable thermodynamic properties of pure substances over the whole phase diagram with only about a 20 ps MD trajectory. Here we show how the 2PT method can be used for mixtures with the same degree of accuracy and efficiency. We have examined the 2PT determined excess Gibbs free energies of Lennard-Jones (LJ) mixtures over a wide range of conditions (1 ≤ T* ≤ 3, 0.5 ≤ P* ≤ 2.5, 1 ≤ σ(BB)/σ(AA) ≤ 2, and 1 ≤ ε(BB)/ε(AA) ≤ 2), including the change of the off-diagonal LJ interactions. The 2PT determined values are in good agreement with those from Widom insertion or thermodynamic integration (TI). Our results suggest that the 2PT method can be a powerful method for understanding thermodynamic properties in more complicated multicomponent systems.

Efficient and accurate solvation energy calculation from polarizable continuum models.

A new approach is proposed to enhance the efficiency and accuracy for calculation of the long-range electrostatic interaction from implicit solvation models, i.e., the polarizable continuum model (PCM) and its variants, conductorlike PCM/conductorlike screening model and integral equation formalism PCM. In these methods the solvent electrostatics effects are represented by a set of discrete apparent charges distributed on tesserae of the molecular cavity surface embedding the solute. In principle, the accuracy of these methods is improved if the cavity surface is tessellated to finer tesserae; however, the computational time is increased rapidly. We show that such undesired dependency between accuracy and efficiency is a result of the inaccurate treatment of the apparent charge self-contribution to the potential and/or electric field. By taking into account the full effects due to the size and curvature of the segment occupied by each apparent charge, the error in calculated electrostatic solvation free energy is essentially zero for ions (point charge at the center of a sphere) regardless of the degree of tessellation used. For molecules where gradient of apparent charge density is nonzero at the cavity surface, we propose a multiple-sampling technique which significantly lowers the calculated error compared to the original PCM methods, especially when very few numbers of tesserae are used.