PMC:6194691 / 211265-213636
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6194691","sourcedb":"PMC","sourceid":"6194691","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6194691","text":"The predictions of the simple theory presented in Sect. 4.1 for passive, non-specific transport of neutral solutes across the blood–brain barrier describes important features of this transport, but leaves quite large discrepancies between the theoretical predictions and the experimental results (see Fig. 25). A more elaborate approach, based on the use of linear free energy relations has been described by Abraham and colleagues [165, 171, 536, 537]. In this approach each compound is represented by a set of quantitative descriptors that are properties of the substance considered in isolation. (Thus for instance Kn-octanol/water is not permitted). These have been chosen as far as possible to represent sufficient independent properties of the substances to allow characterization of their interactions with water, solvents, and sites of action (see below). To predict a property, e.g. the PS product, each descriptor is multiplied by a coefficient which depends on the property, but not on the substance. The sum of the products of coefficients and descriptors is the prediction of the logarithm of the property for that substance. Whenever the property concerned is an equilibrium constant, the logarithm of that property is, up to a constant, a free energy. Hence the name “linear free energy relation” as the prediction can be regarded as a linear sum of contributions to a free energy.\nFig. 25 Comparison of the predictions of the solubility-diffusion theory and of the linear free energy relation (LFER) for the PS product of the series of 18 compounds considered by Gratton et al. [166]. The solubility-diffusion theory, described in Sect. 4.1, predicts that log[PS] is proportional to Koctanol/water MW−1/2. MW is in turn approximately proportional to the McGowan characteristic volume used by Gratton et al. The straight, grey line with slope 1 indicates the predicted proportionality. It has one adjustable parameter that determines the vertical position of the line. The LFER prediction, described in this Appendix and shown as the line with multiple segments, has four adjustable parameters, three coefficients of descriptors of the compounds and the constant determining the vertical position of the whole curve. The improvement in fit is statistically significant (extra sum of squares test [640], F = 8.85 for 17 and 14 degrees of freedom, p \u003c 0.001)","divisions":[{"label":"label","span":{"begin":1397,"end":1404}}],"tracks":[]}