Membranes partitioning

A related alternahve is called ILC [104, 105]. Compounds with the same log P were shown to have very different degrees of membrane partitioning on ILC depending on the charge of the compound [105]. 

I mmobili zed-artifidal-membrane chromatography measurements of membrane partition coeffident and predicting drug membrane permeability. /. Chromatogr. A. 1996, 728,113-128. 

The pH-partition theory or nonionic permeability hypothesis was first described by Jacobs in 1940 [66]. According to this concept, only neutral, preferably nonpolar compounds are able to cross biological membranes. The transcellular permeability pH-profile is then essentially characterized by the membrane partition coefficient and the pKa of the compound. The simplest quantitative description of membrane permeation is given by ... 

Hollosy, F., Valko, K., Hersey, A., Nunhuck, S., Keri, G., Bevan, C. Estimation of volume of distribution in humans from high throughput HPLC-based measurements of human serum albumin binding and immobilized artificial membrane partitioning. J. Med. Chem. 2006, 49, 6958-6971. 

Wimley, W. C., White, S. H. Membrane partitioning distinguishing bilayer effects from the hydrophobic effect. Biochemistry 1993, 32, 6307-12. 

Figure 5.3 illustrates the key features of the Fujita study. In relation to the reference phenol in frame (a), frames (b), and (c) illustrate the effect of H-bonding, and frames (d) and (e) illustrate steric hindrance. Given that the H-bond donor strength of (b) is greater than that of (c), since pKa (b) steric hindrance in (d) produces negative 8, compared to (e). 

Figure 5.3 The effect of hydrogen bonding and steric hindrance on the difference between liposome-water and octanol-water partition coefficients 8 increased H-bond donor strength and decreased steric hindrance favor membrane partitioning in the substituted phenols [381]. [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Although the relationship in Fig. 5.6 is somewhat coarse, it is still useful in predictions. Since octanol-water log P prediction programs are omnipresent and adequately reliable, it can now be said that they can predict membrane-water partitioning, by using the equation in Fig. 5.6. Better yet, if one measures the value of loS Ka. one can estimate the membrane partition coefficient with the confidence of the variance expressed in Fig. 5.6. 

Using such dielectric-based predictions, when the methanol-apparent solubility, log Sq versus wt% methanol is extrapolated to 0% cosolvent, the aqueous solubility, log So, can be estimated when log S(0 is extrapolated to 100% cosolvent, the membrane solubility, log iS cm, can be estimated. The approximate membrane partition... 

Ong, S. Liu, H. Qiu, X. Bhat, G. Pidgeon, C., Membrane partition coefficients chromatographically measured using immobilized artificial membrane surfaces, Anal. Chem. 67, 755-762 (1995). 

An important extension of lipid-solute interaction components [20] to membrane partitioning is provided by solute molecular structure. Spacing between polar and nonpolar regions (Fig. 8) within a solute molecule may result in significant distortion of the KpDm product across the membrane polar headgroup/lipid core interface [21], Such interactions may be responsible for deviations from projected transport predictions based on simple partitioning theory translating to deviations from predicted absorption kinetics [1],... 

Given the low permeability of the antioxidant across MDCK cell monolayers and its large membrane partition coefficient, efflux kinetic studies using drug-loaded cell monolayers cultured on plastic dishes could yield useful information when coupled with the following biophysical model. The steady-state flux of drug from the cell monolayer is equal to the appearance rate in the receiver solution ... 

Raub TJ, CL Barsuhn, LR Williams, DE Decker, GA Sawada, NFH Ho. (1993). Use of a biophysical-kinetic model to understand the roles of protein binding and membrane partitioning on passive diffusion of highly lipophilic molecules across cellular barriers. J Drug Targeting 1 269-286. 

To be successful, SAR studies must be adapted to P-gp by implementing membrane partitioning of substrates, modifiers or inhibitors as suggested previously [36]. The aim of the present chapter is to evaluate the contribution of (i) membrane partitioning and (ii) receptor binding proper to the apparent binding of a compound to P-gp. 

Membrane Partitioning Determines Drug Concentration at Half-Maximum P-gp-ATPase Activation, Km... 

However, if substrate binding takes place in the lipid it is preceded by a membrane-partitioning step as shown in Eq. (3) ... 

Yang, Q., Liu, X. Y., Umetani, K., Kamo, N. and Miyake, J. (1999). Partitioning of triphenylalkylphosphonium homologues in gel bead-immobilized liposomes chromatographic measurement of their membrane partition coefficients, Biochim. Biophys. Acta-Biomem., 1417, 122-130. 

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