solvates
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This study investigates venetoclax solvates and their nonsolvated forms through desolvation. Seven solvates were prepared and their structures solved from single-crystal X-ray diffraction data. Among these, two are cavity solvates while the remaining five are channel solvates, with three being isomorphous. Desolvation experiments led to two solvent-free crystalline polymorphs of venetoclax, forms A and B. Notably, the acetone solvate remained stable and did not convert to a nonsolvated form. Form B has a higher melting point and a faster intrinsic dissolution rate than form A. Advanced computational tools, including Solvate Analyser and CSD-Particle, provided insights into crystal surface properties and desolvation behaviour. Properties such as lattice energy, molecular interaction energy, attachment energy, surface rugosity and solvent arrangement within the crystal and on the surface were linked to solvate stability and subsequent transformation upon desolvation. A combination of FTIR, and 13C and 15N solid-state NMR spectroscopies showed that both short- and long-range molecular interactions and arrangements of venetoclax molecules in the desolvated forms closely resembled those in the parent solvates.
- Publikační typ
- časopisecké články MeSH
In this work we investigate the performance of the DFT method, augmented with an empirical dispersion function (DFT-D), paired with the PCM implicit solvation model, for the computation of noncovalent interaction energies of biologically-relevant, solvated model complexes. It is found that this method describes intermolecular interactions within water and ether (protein-like) environments with roughly the same accuracy as in the gas phase. Another important finding is that, when environmental effects are taken into account, the empirical dispersion term associated with the DFT-D method need be modified very little (or not at all), in order to obtain the optimum, most well balanced, performance.
- MeSH
- algoritmy MeSH
- biologické modely MeSH
- chemické modely MeSH
- DNA chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- kvantová teorie MeSH
- makromolekulární látky chemie MeSH
- povrchové vlastnosti MeSH
- přenos energie MeSH
- proteiny chemie MeSH
- RNA chemie MeSH
- rozpustnost MeSH
- roztoky MeSH
- termodynamika MeSH
- vodíková vazba MeSH
Two novel metallacarborane-based stationary phases for high performance liquid chromatography were synthesized and characterized utilizing linear solvation energy relationships concept. Interactions taking place between selected probes (45 analytes) and the stationary phases and the mobile phases consisting of a mixture of acetonitrile with buffer were described by the linear solvation energy relationship model in a broad range of acetonitrile/buffer ratios. The interaction properties of the metallacarborane phases were compared with plain silica, the starting material for the preparation of the metallacarborane phases, and with a typical silica-based reversed-phase sorbent. It was clearly demonstrated that the metallacarborane sorbents provide qualitatively and quantitatively different interactions with respect to both the plain silica and reversed-phase stationary phase. It was shown that these novel phases might have also a separation potential in the area of hydrophilic interaction liquid chromatography.
- MeSH
- chromatografie s reverzní fází přístrojové vybavení metody MeSH
- hydrofobní a hydrofilní interakce MeSH
- oxid křemičitý chemie MeSH
- uhličitany analýza chemie MeSH
- vysokoúčinná kapalinová chromatografie přístrojové vybavení metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The unwinding Gibbs energy (or duplex dissociation energy) is an important measure of the thermodynamic stability of DNA oligomers. This value can be measured experimentally or predicted by empirical models parametrised on experimental data. Our previously developed model based on accurate DFT-D calculations of interaction energies between nucleic acid bases corrected for solvation contribution. This work was successfully extended to cover variable lengths of oligomers. This model was further applied to oligomers containing inosine, an unnatural base. The results, however, are not satisfactory and it is clear that the model does not take into account all variables contributing to DNA stability. Inclusion of the backbone deformation energy did not improve the model. We also compared models based on DFT-D and forcefield calculations. Forcefield performs well in this application, because the systematic error in interaction energies is cancelled in the fitting procedure.
Biphasic solvent systems composed of an ionic liquid (IL) and supercritical carbon dioxide (scCO(2)) have become frequented in synthesis, extractions and electrochemistry. In the design of related applications, information on interphase partitioning of the target organics is essential, and the infinite-dilution partition coefficients of the organic solutes in IL-scCO(2) systems can conveniently be obtained by supercritical fluid chromatography. The data base of experimental partition coefficients obtained previously in this laboratory has been employed to test a generalized predictive model for the solute partition coefficients. The model is an amended version of that described before by Hiraga et al. (J. Supercrit. Fluids, in press). Because of difficulty of the problem to be modeled, the model involves several different concepts - linear solvation energy relationships, density-dependent solvent power of scCO(2), regular solution theory, and the Flory-Huggins theory of athermal solutions. The model shows a moderate success in correlating the infinite-dilution solute partition coefficients (K-factors) in individual IL-scCO(2) systems at varying temperature and pressure. However, larger K-factor data sets involving multiple IL-scCO(2) systems appear to be beyond reach of the model, especially when the ILs involved pertain to different cation classes.
Metronidazole belongs to the class of nitroimidazole molecules and has been considered as a potential radiosensitizer for radiation therapy. During the irradiation of biological tissue, secondary electrons are released that may interact with molecules of the surrounding environment. Here, we present a study of electron attachment to metronidazole that aims to investigate possible reactions in the molecule upon anion formation. Another purpose is to elucidate the effect of microhydration on electron-induced reactions in metronidazole. We use two crossed electron/molecular beam devices with the mass-spectrometric analysis of formed anions. The experiments are supported by quantum chemical calculations on thermodynamic properties such as electron affinities and thresholds of anion formation. For the single molecule, as well as the microhydrated condition, we observe the parent radical anion as the most abundant product anion upon electron attachment. A variety of fragment anions are observed for the isolated molecule, with NO2- as the most abundant fragment species. NO2- and all other fragment anions except weakly abundant OH- are quenched upon microhydration. The relative abundances suggest the parent radical anion of metronidazole as a biologically relevant species after the physicochemical stage of radiation damage. We also conclude from the present results that metronidazole is highly susceptible to low-energy electrons.
- Publikační typ
- časopisecké články MeSH
