Partition coefficients theory

Thus one must rely on macroscopic theories and empirical adjustments for the determination of potentials of mean force. Such empirical adjustments use free energy data as solubilities, partition coefficients, virial coefficients, phase diagrams, etc., while the frictional terms are derived from diffusion coefficients and macroscopic theories for hydrodynamic interactions. In this whole field of enquiry progress is slow and much work (and thought ) will be needed in the future. 

General anaesthetics have been in use for the last 100 years, yet their mechanism of action are still not yet clearly defined. For many years it was thought that general anaesthetics exerted their effects by dissolving in cell membranes and perturbing the lipid environment in a non-specific manner. This theory derived from the observation that for a number of drugs which induced anaesthesia, their potency correlated with their oil-water partition coefficients. This Meyer-Oveiton correlation was accepted for a number of years, however in the last 15-20 years evidence has shown that a more likely theory is that of specific interactions of anaesthetics with proteins, particularly those within the CNS that mediate neurotransmission [1]. 

Rikvold and Stell [319,320,365] have developed an expression for the partition coefficient in a random two-phase medium made up of spherical particles. They found the partition coefficient to be essentially an exponential function of the solute radius, which is in qualitative agreement with the Ogston theory. 

Ruelle, P. Universal model based on the mobile order and disorder theory for predicting lipophilidty and partition coefficients in all mutually immiscible two-phase liquid systems. Chem. Inf. Comput. Sci. 2000, 40, 681-700. 

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 ... 

However, as stated above, the partition coefficients measured by the shake-flask method or by potenhometric titration can be influenced by the potenhal difference between the two phases, and are therefore apparent values which depend on the experimental condihons (phase volume ratio, nature and concentrahons of all ions in the solutions). In particular, it has been shown that the difference between the apparent and the standard log Pi depends on the phase volume raho and that this relationship itself depends on the lipophilicity of the ion [80]. In theory, the most relevant case for in vivo extrapolation is when V /V 1 as it corresponds to the phase ratio encountered by a drug as it distributes within the body. The measurement of apparent log Pi values does not allow to differentiate between ion-pairing effect and partihoning of the ions due to the Galvani potential difference, and it has been shown that the apparent lipophilicity of a number of quaternary ion drugs is not due to ion-pair partitioning as inihally thought [80]. 

Essentially, extraction of an analyte from one phase into a second phase is dependent upon two main factors solubility and equilibrium. The principle by which solvent extraction is successful is that like dissolves like . To identify which solvent performs best in which system, a number of chemical properties must be considered to determine the efficiency and success of an extraction [77]. Separation of a solute from solid, liquid or gaseous sample by using a suitable solvent is reliant upon the relationship described by Nemst s distribution or partition law. The traditional distribution or partition coefficient is defined as Kn = Cs/C, where Cs is the concentration of the solute in the solid and Ci is the species concentration in the liquid. A small Kd value stands for a more powerful solvent which is more likely to accumulate the target analyte. The shape of the partition isotherm can be used to deduce the behaviour of the solute in the extracting solvent. In theory, partitioning of the analyte between polymer and solvent prevents complete extraction. However, as the quantity of extracting solvent is much larger than that of the polymeric material, and the partition coefficients usually favour the solvent, in practice at equilibrium very low levels in the polymer will result. 

Principles and Characteristics In boiling under reflux procedures a small amount of ground polymer (typically 3g) is placed in a headspace jar (typically 100 mL) and solvent (typically 30 mL) is added. After sealing, the jar is placed in an oven at a temperature where the solvent slowly refluxes. The solvent is, therefore, at the highest temperature possible without applying an external pressure. Consequently, reflux extractions tend to be much faster than Soxhlet extractions. Examples are Soxtec , Soxtherm , FEXTRA and intermittent extraction. Whilst, in theory, partitioning of the analyte between the polymer and solvent prevents complete extraction, this hardly ever constitutes a problem in practice. As the quantity of solvent is much larger than that of the polymer, and the partition coefficients usually favour the solvent, very low additive levels in the polymer result at equilibrium. Any solvent or solvent mixture can be used. 

One of the original concepts governing oral absorption of organic molecules is the pH partition hypothesis . This hypothesis states that only the nonionized form of the drug is able to permeate the membranes of epithelial cells lining the GI tract [26], According to the classical pH-partition theory, permeability is expected to correlate not with the intrinsic partition coefficient but with the so-called distribution coefficient D of the solute [27], where D is defined as ... 

Yethiraj and Hall [94] studied the density profiles, surface forces, and partition coefficient of freely jointed tangent hard-sphere chains between hard walls. The theory was able to capture the depletion of chain sites at the surface at low densities and the enhancement of chain sites at the surface at high densities. This theory is in qualitative agreement with simulations for the density profiles and partitioning of 4 and 20 bead chains, although several quantitative deficiencies are present. At low densities the theory overestimates the value of the density profile near the surface. Furthermore, it predicts a quadratic variation of density with distance near the surface, whereas in reality the density profile should be linear in distance, for long chains. At high densities the theory underestimates the value of the density near the surface. The theory is quite accurate, however, for the partition coefficient for hard chains in slit-like pores. 

Schantz, M.M., Martire, D.E. (1987) Determination of hydrocarbon-water partition coefficients from chromatographic data and based on solution thermodynamics and theory. J. Chromatogr. 391, 35-51. 

Mclntire, W. L. (1963). Trace-element partition coefficients —a review of theory and applications to geology. Geochim. Cosmochim. Acta, 27, 1209-64. 

By using a PES with a different thickness, one can conveniently change the AV ratio. This approach permits some control over the time required to reach equilibrium concentrations. Bartkow et al. (2004) has reported an excellent example of the impact of ratio or thickness on the time to equilibrium. These investigators showed that a 200 pm thick PE sheet took twice as long to reach equilibrium in air as a 100 pm thick PE sheet. In theory, changing membrane thickness will not affect polymer diffusivity and equilibrium membrane-water partition coefficients (I mwS) or solubility coefficients ( p). However, in practice different values of (membrane-air partition coefficient) and membrane... 

There have been relatively few applications of the rate theory to GPC, presumably because of the apparent complexity of this approach. One of the most widely quoted interpretations of the rate theory to GPC is that of Ouano and Baker (4). These authors have attempted to take advantage of the undoubted potential of the rate theory approach in constructing a model. They identified the key parameters in their model as the flow rate of the eluant, gel particle size, diffusion coefficient in the stationary and mobile phases and the partition coefficient for solute between phases. Although there is little doubt that the important parameters have been correctly identified, it is not immediately apparent how they are inter-related and hence how their coupled effect can be interpreted. A critical account of the various attempts which have been made to model the GPC process will be given elsewhere. 

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