Fluids: Their function and movement
Bernie Garrett in Fluids and Electrolytes, 2017
Most of the cytosol is water, and pH is maintained at between 7.3 and 7.5, depending on the cell type, whereas the pH of the ECF is maintained more precisely at close to 7.4.10 Although water is known to be vital for cellular activities, its functions in the cytosol are actually not that well understood.8,11,12 It is thought that whilst the majority of intracellular water has the same structure as pure water, approximately 5% of it is strongly bound with solutes or macromolecules as the water of solvation.13 This water of solvation (the process by which solvent molecules interact with ions or other molecules) is not active in osmosis and, as it acts as a single entity with the solutes, may also have different solvent properties to pure water.
Supercritical Fluid Extraction as a Sample Preparation Tool in Analytical Toxicology
Steven H. Y. Wong, Iraving Sunshine in Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Although solubilization of an analyte by SFs is certainly a necessary condition for extraction, it represents only one aspect of the SFE process. A growing body of research in the environmental SFE literature has demonstrated that the nature of the matrix and the manner in which analytes are incorporated in that matrix have a profound influence on both extraction kinetics and the conditions required for optimum extraction with SFs.25,26,33–36,48,49 SFE of trace analytes from adsorbing matrices proceeds through several distinct steps, which have been described by Pawliszyn50 for porous environmental solids as: 1) removal (desorption) of the analyte from the matrix binding site; 2) diffusion of the analyte through the matrix to the matrix-fluid interface; 3) solvation of the analyte by the SF; and 4) diffusion of the solubilized analyte through the porous matrix to the flowing bulk SF for its subsequent removal and collection from the extraction system. Which of these processes constitutes the rate-determining step will depend on the specific analyte, the matrix, and the type and strength of interactions that exist between the matrix and the analyte. The ability of the SF or SF-modifier mixture to overcome analyte-matrix bonding is in many cases of greater importance than high analyte solubility for obtaining efficient SFE recoveries.7,11 Consequently, knowledge of the physical and chemical nature of the matrix and the chemical nature of analyte-matrix interactions must be considered, along with analyte solubility for successful method development using SFE.
Useful Principles for the Crystallization of Proteins
Hartmut Michel in Crystallization of Membrane Proteins, 1991
The greater difficulties that arise in the crystallization of macromolecules in comparison with conventional small molecules stem from the greater complexity, lability, and dynamic properties of proteins and nucleic acids (for excellent texts on the properties of such macromolecules see Reference 18 and 86). The rather simple explanation offered above of labile and metastable regions of supersaturation are still applicable to macromolecules, but it must now be borne in mind that as conditions are adjusted to transport the solution away from equilibrium by alteration of its physical and chemical properties, the very nature of the solute molecules is changing as well. As temperature, pH, pressure, or solvation are changed, so are the conformation, charge state, or size of the solute macromolecules.
Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450
Published in Drug Metabolism Reviews, 2020
Chaitanya K. Jaladanki, Anuj Gahlawat, Gajanan Rathod, Hardeep Sandhu, Kousar Jahan, Prasad V. Bharatam
QC methods have a limitation in terms of the size of the system, which can be studied. The time required to solve the elecronic structure of a given system exponentially depends on the number of electrons present in it. The Cpd I model (Figure 4) used for a majority of studies is the iron (IV)-oxo -porphine with SH¯ as the axial ligand (Wallar and Lipscomb 1996; Himo and Siegbahn 2003; Shaik et al. 2005; Shaik et al. 2010; Taxak et al. 2011; Boulenc et al. 2012; Taxak et al. 2012; Hirao et al. 2013; Taxak, Kalra, et al. 2013; Taxak, Patel, et al. 2013; Taxak, Prasad, et al. 2013; Arfeen et al. 2014), as it has been proved to be sufficient in obtaining reliable results for the reactions catalyzed by CYP450 enzymes. Commonly, the hybrid B3LYP functional is being employed for geometry optimizations for Cpd I in these metabolic studies, where the Los Alamos effective core potential coupled with the double-ζ LACVP (or LanL2DZ) basis set is chosen for heme iron (Hay and Wadt 1985; Wallar and Lipscomb 1996) and 6-31 + G(d) basis set for the remaining atoms. Single point energy calculations are thereafter, carried out employing triple-ζ potential on iron and 6-311++G (d, p) basis set on other atoms. The solvation effects are also considered for the enzymatic reactions, which occur in aqueous solution. Several scientific groups have employed chlorobenzene (ε = 5.7) as the implicit solvent using Integral Equation Formalism variant of Polarizable Continuum Model (IEFPCM) to account for bulk polarity effects of the protein environment in the active site of CYP 450s.
Solubility enhancement of mefenamic acid by inclusion complex with β-cyclodextrin: in silico modelling, formulation, characterisation, and in vitro studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Dounia Sid, Milad Baitiche, Zineb Elbahri, Ferhat Djerboua, Mokhtar Boutahala, Zouhair Bouaziz, Marc Le Borgne
In this work, the phase solubility diagram and job’s plot experiment were used to determine the stoichiometry of the MA:β-CD complex. Then molecular modelling approach helped (i) to select the most stable inclusion complex (2:1), (ii) to determine intermolecular energy contributions, and (iii) to predict hydrophilic surfaces and drug solubility (e.g. solvation energy). Inclusion complexes of MA:β-CD in the 2:1 molar ratio were prepared using three methods, namely PM, KN, and CE. FTIR and NMR studies showed no evidence of chemical reactions between the drug and β-CD. DSC, XRPD, and SEM experiments confirmed partial amorphism of the MA after inclusion complexation indicating that MA was well dispersed in the β-CD cavities. These results suggest an enhanced dissolution profile compared to the crystalline form. All three formulations showed a significant improvement of the MA dissolution; however, the CE complex exhibited the highest KH value. The CE method is thus the most appropriate method to get improved MA dissolution properties. Actually, the (2:1) MA:β-CD binary complex obtained by CE method constitutes an interesting alternative to formulate MA. Protein denaturation and membrane stabilisation assays also confirmed the therapeutic benefits of MA when used as (2:1) MA:β-CD complex. Finally, this approach of preparing inclusion complexes in an optimised ratio could allow other poor-water soluble NSAIDs to be studied again.
Dissolution thermodynamics and preferential solvation of genistein in some (ethanol + water) mixtures at different temperatures
Published in Drug Development and Industrial Pharmacy, 2022
Guanjun Nan, Yanru Huang, Zhengzheng Liu, Yu Liu, Yunzhe Li, Guangde Yang
The modified Apelblat equation was commonly applied to correlate the solubility of solute in given solvent mixtures [40]. The constants A and B represent the variation in solution activity coefficient and are an indication of the influence of non-ideal solution on the solubility of genistein, whereas the parameter C reflects the effect of temperature on the fusion enthalpy [41]. Yalkowsky model belongs to the log-linear model. It is simple and only requires the aqueous solubility of the solute. The model constant σ is the solubilization power of the cosolvent [42]. λh model is another way to describe solvation behavior involving the activity, solubility and temperature. The value of λ reflects the non-ideality of the solution system, and h estimates the enthalpy of solution [43]. In the combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) equation, the mole fraction solubility of genistein as a function of mole fraction of ethanol can be calculated in various ethanol and water mixtures at a given temperature.
Related Knowledge Centers
- Chemical Kinetics
- Coordination Number
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- Equilibrium Constant
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- Coordination Complex
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- Chemical Polarity