Partition coefficients analysis

Two approaches to quantify/fQ, i.e., to establish a quantitative relationship between the structural features of a compoimd and its properties, are described in this section quantitative structure-property relationships (QSPR) and linear free energy relationships (LFER) cf. Section 3.4.2.2). The LFER approach is important for historical reasons because it contributed the first attempt to predict the property of a compound from an analysis of its structure. LFERs can be established only for congeneric series of compounds, i.e., sets of compounds that share the same skeleton and only have variations in the substituents attached to this skeleton. As examples of a QSPR approach, currently available methods for the prediction of the octanol/water partition coefficient, log P, and of aqueous solubility, log S, of organic compoimds are described in Section 10.1.4 and Section 10.15, respectively. 

Table 5.2. Analysis using the pseudophase model partition coefficients for 5.2 over CTAB or SDS micelles and water and second-order rate constants for the Diels-Alder reaction of 5.If and 5.1g with 5.2 in CTAB and SDS micelles at 25 C.

In contrast to SDS, CTAB and C12E7, CufDSjz micelles catalyse the Diels-Alder reaction between 1 and 2 with enzyme-like efficiency, leading to rate enhancements up to 1.8-10 compared to the reaction in acetonitrile. This results primarily from the essentially complete complexation off to the copper ions at the micellar surface. Comparison of the partition coefficients of 2 over the water phase and the micellar pseudophase, as derived from kinetic analysis using the pseudophase model, reveals a higher affinity of 2 for Cu(DS)2 than for SDS and CTAB. The inhibitory effect resulting from spatial separation of la-g and 2 is likely to be at least less pronoimced for Cu(DS)2 than for the other surfactants. 

A sample contains a weak acid analyte, HA, and a weak acid interferent, HB. The acid dissociation constants and partition coefficients for the weak acids are as follows Ra.HA = 1.0 X 10 Ra HB = 1.0 X f0 , RpjHA D,HB 500. (a) Calculate the extraction efficiency for HA and HB when 50.0 mF of sampk buffered to a pH of 7.0, is extracted with 50.0 mF of the organic solvent, (b) Which phase is enriched in the analyte (c) What are the recoveries for the analyte and interferent in this phase (d) What is the separation factor (e) A quantitative analysis is conducted on the contents of the phase enriched in analyte. What is the expected relative erroi if the selectivity coefficient, Rha.hb> is 0.500 and the initial ratio ofHB/HA was lO.O ... 

Carbon Black Partition Coefficient from the Analysis of C"(t) Signals... 

An analysis of partition coefficient data and drug solubilities in PCL and silicone rubber has been used to show how the relative permeabilities in PCL vary with the lipophilicity of the drug (58,59). The permeabilities of copolymers of e-caprolactone and dl-lactic acid have also been measured and found to be relatively invariant for compositions up to 50% lactic acid (67). The permeability then decreases rapidly to that of the homopolymer of dl-lactic acid, which is 10 times smaller than the value of PCL. These results have been discussed in terms of the polymer morphologies. 

It is interesting to note that Johansson andLofroth [183] found i to equal 1.09 for the diffusion analysis, but the partition coefficient followed a streched exponential with varying i from 1 to 2, indicating that the ratio of diffusion coefficient is not equal to the accessible volume fraction for large molecules, as is assumed in the ORMC model for gel electrophoresis. 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

To further analyze the relationships within descriptor space we performed a principle component analysis of the whole data matrix. Descriptors have been normalized before the analysis to have a mean of 0 and standard deviation of 1. The first two principal components explain 78% of variance within the data. The resultant loadings, which characterize contributions of the original descriptors to these principal components, are shown on Fig. 5.8. On the plot we can see that PSA, Hhed and Uhba are indeed closely grouped together. Calculated octanol-water partition coefficient CLOGP is located in the opposite corner of the property space. This analysis also demonstrates that CLOGP and PSA are the two parameters with... 

Nys, G. G., Rekker, R. F. Statistical analysis of a series of partition coefficients with special reference to the predictability of folding of drug molecules. Introduction of hydrophobic fragmental constants (/-values). Chim. Therap. 1973, 8, 521-535. 

A general definition of log P and log D, in its simplest form, can be given as the logarithm of the ratio (P or D) of the concentration of species of interest (the drug in a pharmaceutical context) in each phase, assuming the phases are immiscible and well separated prior to analysis. P is defined as the partition coefficient, whereas D is the distribution coefficient. However, the simplest form does not reveal some of the intricacies of the determination and use of these parameters, and further explanation is necessary. 

Galland, A., Girault, H., Testa, B., Carrupt, P. A. Solvatochromic analysis of partition coefficients in the o-nitrophenyl octyl ether (o-NPOE)/water system. Helv. Chim. Acta 2003, 86, 3533-3547. 

A measurement table is different from a contingency table. The latter results from counting the number of objects that belong simultaneously to various categories of two measurements (e.g. molar refractivity and partition coefficient of chemical compounds). It is also called a two-way table or cross-tabulation, as the total number of objects is split up in two ways according to the two measurements that are crossed with one another. The analysis of contingency tables is dealt with specifically in Chapter 32. 

Thomas JB, Bodnar RJ, Shimizu N, Sinha AK (2002) Determination of zircon/melt trace element partition coefficients from SIMS analysis of melt inclusions in zircon. Geochim Cosmochim Acta 66 2887-2901 Thompson GM, Malpas J (2000) Mineral/melt partition coefficients of oceanic alkali basalts determined on natural samples using laser ablation-inductively eouple plasma-mass spectrometry (LAM-ICP-MS). Mineral Mag 64 85-94... 

Where is the initial analyte concentration in the liquid phase, C( the concentration of analyte in the gas phase, K the gas-liquid partition coefficient for the analyte at the analysis temperature, V, the volume of liquid phase, and V, the volume of gas phase (318-321,324,325). From equation (8.3) it can be seen that the concentration of the analyte in the headspace above a liquid in equilibrium with a vapor phase will depend on the volume ratio of the geis and liquid phases and the compound-specific partition coefficient which, in turn, is matrix dependent. The sensitivity 1 of the headspace sampling method can be increased in some instances adjusting the pH, salting out or raising the... 

Carroll J, Harms IH. 1999. Uncertainty analysis of partition coefficients in a radionuclide transport model. Water Res 33(11) 2617-2626. 

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