Membrane models solvent-water systems

Equation 7 shows that as AP — oo, P — 1. The principal advantage of the solution—diffusion (SD) model is that only two parameters are needed to characterize the membrane system. As a result, this model has been widely appHed to both inorganic salt and organic solute systems. However, it has been indicated (26) that the SD model is limited to membranes having low water content. Also, for many RO membranes and solutes, particularly organics, the SD model does not adequately describe water or solute flux (27). Possible causes for these deviations include imperfections in the membrane barrier layer, pore flow (convection effects), and solute—solvent—membrane interactions. 

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

The partition coefficient or its logarithm serves as a quantitative measure of a compound s lipophilicity. For pharmaceuticals, water and 1-octanol are the two solvents used most frequently to measure lipophilicity. The two-phase octanol/water system closely models the cell membrane/interstitial fluid interface. While Lipinski s rules do not specify a minimum lipophilicity, a log P value of 5 or less prevents a drug from effectively hiding within membranes. 

Numerous examples available from the application of the octanol-water system allow translation between different solvents or the modeling of a lipid membrane, provided the Collander relation [19] is valid. 

The HPLC was realized with a Waters solvent delivery system. Separations of oligomers were obtained with a Nucleosil 5 pm C-18 reverse phase column from S.F.C.C. (France) (8). The eluent was distilled water filtered through a 0.45 lm Millipore membrane. The starch was dissolved in DMSO and the eluent was DMSO/MeOH (85/15 v/v) in 0.5 M ammonium acetate. The colxamn set was diol silica gel from Merck 2 x Si 1000 Diol, 1 x Si 500 Diol, 1 X Si 100 Diol thermostated at 60 C. The detector was either a differential refractometer from Waters (R 401) or an IOTA (Jobin Yvon). The second on line detector was a light scattering detector (Chromatix CMX 100) or a spectropolarimeter (Perkin Elmer model 241 working at 365 nm with a flow cell of path length 10 cm and a 30 ll volume). The value of [a]D are expressed from [Ct]355 data using a corrective factor. The partition coefficient Kd is expressed as ... 

Although continuum solvation models do appear to reproduce the structural and spectroscopic properties of many molecules in solution, parameterization remains an issue in studies involving solvents other than water. In addition, the extension of these approaches to study proteins embedded in anisotropic environments, such as cell membranes, is clearly a difficult undertaking96. As a result, several theoretical studies have been undertaken to develop semi-empirical methods that can calculate the electronic properties of very large systems, such as proteins28,97 98. The principal problem in describing systems comprised of many basis functions is the method for solving the semi-empirical SCF equations ... 

The inner hydrophobic core of a membrane can be modelled by the use of an organic solvent. Similarly a water or aqueous buffer can be used to mimic the aqueous filled compartment. If the organic solvent is not miscible with water then a two-phase system can be used to study the relative preference of a compound for the aqueous (hydrophiHc) or organic (hydrophobic, lipophilic) phase. 

Figure 17.2 illustrates our model for splitting water by solar energy. I" is important that all the redox reactions involved in thf system be reversible. The quinone compound in the organic solvent combines the two photocatalytic reactions, and its function can be compared to the electron relaying molecules in thylakoid membranes of chloroplasts. Electron transfer reactions via quinone compouncs in artificia systems have been studied as a model of photosynthesis22-23 and in an electrochemical system for acid concentration.24 ... 

In this section, we review our first examinations of tryptophan probing sensitivity and water dynamics in a series of important model systems from simple to complex, which range from a tripeptide [70], to a prototype membrane protein melittin [70], to a common drug transporter human serum albumin [71], and to lipid interface of a nanochannel [86]. At the end, we also give a special case that using indole moiety of tryptophan probes supramolecule crown ether solvation, and we observed solvent-induced supramolecule folding [87]. The obtained solvation dynamics in these systems are linked to properties or functions of these biological-relevant macromolecules. 

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