Oil-gas-partition coefficient

A comparison of the minimum alveolar concentration (MAC) with the oil-gas partition coefficient of several inhalational anesthetic agents. 

The first chemical clue relating the structure of anesthetics to their potency was discovered in 1899 by a pharmacologist, Hans Horst Meyer, and an anesthetist, Charles Ernst Overton. Working independently, Meyer and Overton noted a strong correlation between the polarity of a compound and its potency as an anesthetic. They expressed polarity as the oil/gas partition coefficient, while anesthetic potency was expressed as the partial pressure in atmospheres. Figure 11.10 is a Meyer-Overton correlation for 18 anesthetics used on mice. Note that olive oil is used, and it has become the most commonly used reference solvent. 

The oil solubility of an anaesthetic is of interest, not only because it governs the passage of the anaesthetic into and out of the fat depots of the body, but also because there is a well-established correlation between anaesthetic potency and oil solubility. Figure 2.10 shows a linear inverse relationship between log narcotic concentration and log solubility in oleyl alcohol for a series of common anaesthetic gases. The ordinate of the graph represents the minimum alveolar concentration (MAC), which is that concentration of anaesthetic at which 50% of the patients cease to move in response to a stimulus. The abscissa shows the solubility expressed in terms of the oil/gas partition coefficient. Partition coefficients are widely used to express solubility and are the ratios of the concentration of the gas in the two phases in equilibrium at a given temperature. When, as in this case, one of the phases is the gas itself, the partition coefficient expressed as the liquid/gas (note the order of the phases) concentration ratio is equal to the... 

The correlation between anaesthetic potency and lipid solubility shown in Fig. 2.10 is valid for most inhaled anaesthetics and the product MAC X oil/gas partition coefficient (which should of course be a constant) varies by only a factor of 2 or 3 for potencies ranging over 100 000-fold. This constancy implies that inhaled anaesthetics act in the same manner at a specific hydrophobic site (the so-called unitary theory of anaesthesia). This has been challenged by more recent work that has identified compounds, including alkanes and poly-halogenated and perfluorinated compounds, which do not obey the Meyer- Overton hypothesis. It has been suggested that a contributory cause of deviation from this hypothesis may be the choice of lipid to represent the anaesthetic site of action of these compounds, implying that there may be multiple sites of action for inhaled anaesthetics. 

Figure 2.10 Narcotic concentrations of various anaesthetic agents plotted against solubility in oleyl alcohol (expressed as oil/gas partition coefficient).

These data are relevant clinically because of possible wide variation of body temperature in the surgical patient. Body temperature may be lowered as a result of preoperative sedation, by cutaneous vasodilation, by the infusion of cold fluids and by reduced metabolism under operating conditions. The increase in oil/gas partition coefficient with decreasing temperature means that the effective concentration at the hydrophobic site of action is increasing and hence the apparent potency of the anaesthetic increases. 

Sevo8urane. Sevofluranc. FC(H) -0-CH(CFj) . lu an oil/gas partition coefficient about one-half that uf isofltir-anc. and the blood/gas partition coefficient is about une-thini that of isofluranc. Pharmacokinetically. it reportedly has the advantages of rapid uptake and rapid elimination. It is metah-olizcd to about the same extent as enflurane. 

There exists a direct relationship between the anaesthetic activity of an agent and its lipid solubility. It offers a reasonably acceptable correlation between anaesthetic activity (pharmacologic) of a compound and its oil/water or oil/gas partition coefficient (physical). This hypothesis rightly advocates that the site of action of anaesthetics is usually hydrophobic in nature. It may be anticipated that the greater the lipid solubility of an anaesthetic agent the higher would be its potency. 

Figure 3. Linear relationship between oil/gas partition coefficient and minimum concentration in air required to produce anesthesia in mice on a log log scale. (Reproduced with permission from Ref. 64. Copyright 1987 Elsevier).

Abraham, M. H., P. L. Grellier, and R. A. McGill, Determination of olive oil-gas and hexadecane-gas partition coefficients, and calculation of the corresponding olive oil-water and hexadecane-water partition coefficients. J. Chem. Soc. Perkin Trans., 2, 797-803 (1987). 

The Ostwald partition coefficient, L, is a widely used and physically intuitive measure of gas solubilities and oil-water partition coefficients. It is defined as the ratio of concentrations of a solute between two phases at equilibrium. These two phases can be the ideal gas and a liquid phase, in which case the Ostwald partition coefficient gives the gas solubility, or two immiscible liquids - e.g., oil and water - in which case L is an oil-water partition coefficient. For the gas solubility of component 2 in liquid 1,... 

Abraham, M.H., Grellier, RL. and McGill, R.A. (1987). Determination of Ohve Oil-Gas and Hexadecane-Gas Partition Coefficients, and Calculation of the Corresponding Olive Oil-Water and Hexadecane-Water Partition Coefficients. J.Chem.Soc.Perkin Trans.2,797-803. Abraham, M.H., Grellier, P.L., Hamerton, I., McGill, R.A., Prior, D.V. and Whiting, G.S. (1988). 

Temperature also influences anaesthetic solubility temperature increase leads to a decrease in solubility as expected from section 2.4.1. Table 2.4 shows the temperamre coefficients of the both water/gas, 2water/gas d oil/gas, Aoii/gas partition coefficients for a range of anaesthetic gases. 

O. Dugstad, T. Bjomstad, and I. Hundere. Measurements and appliea-tion of partition coefficients of compounds suitable for tracing gas injected into oil reservoirs. Rev Inst Franc Petrol, 47(2) 205-215, March-April 1992. 

Abraham, M.H. and Ibrahim, A. (2006) Gas to olive oil partition coefficients a linear free energy analysis. Journal of Chemical Information and Modeling, 46, 1735-1741. 

Agent Molecular formula Partition coefficient Oil/gas Blood/gas Boiling point, C Year introduced... 

During mastication, nonvolatile flavor molecules must move from within the food, through the saliva to the taste receptors on the tongue, and the inside of the mouth, whereas volatile flavor molecules must move from the food, through the saliva and into the gas phase, where they are carried to the aroma receptors in the nasal cavity. The two major factors that determine the rate at which these processes occur are the equilibrium partition coefficient (because this determines the initial flavor concentration gradients at the various boundaries) and the mass transfer coefficient (because this determines the speed at which the molecules move from one location to another). A variety of mathematical models have been developed to describe the release of flavor molecules from oil-in-water emulsions. 

Cabala, R., Svobodova, J., Feltl, L. and Tichy, M. (1992). Direct Determination of Partition Coefficients of Volatile Liquids Between Oil and Gas by Gas Chromatography and Its Use in QSAR Analysis. Chromatographia, 34,601-606. 

Shell (48) used a simple foam model (49) for their Bishop Fee pilot. The foam generation rate was matched by using an effective surfactant partition coefficient that took into account surfactant losses and foam generation inefficiencies. The value of this coefficient was selected so that the numerical surfactant propagation rate was equal to the actual growth rate. Foam was considered to exist in grid blocks where steam was present and the surfactant concentration was at least 0.1 wt%. The foam mobility was assumed to be the gas-phase relative permeability divided by the steam viscosity and the MRF. The MRF increased with increasing surfactant concentration. The predicted incremental oil production [5.5% of the... 

Offshore oil production requires many chemicals for well drilling, for the treatment of the produced oil, for the treatment of gas, and for the stimulation and workover of the wells [100,101]. Altogether,25 classes of chemicals are used in offshore oil production [102]. The chemicals are undergoing increasingly detailed testing. As in other Quantitative Structure-Activity Relationships (QSAR), the octanol/water partition coefficient (Kq, ) is a crucial factor determining the environmental behavior and toxicity of the chemicals [103]. Toxicity... 

Abraham et al. [14] have reported solubility correlations for a wide variety of systems that follow Henry s law. Gas/liquid partition coefficients for biofluids are modelled by a suitable combination of gas/water and gas/oil partition coefficients, thus allowing for the hydrophobicity of a given biological tissue or fluid. This method is furthermore able to provide a measure for the tissue/blood distribution of non-electrolytes (which may also be estimated using octanol-water partition coefficients [15]). 

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