Partition different solvent systems

Among the large number of existing lipophilicity parameters [31], the descriptor frequently estimated by in silica methods is the partition coefficient of a solute between 1-octanol and water, expressed as log Poet [32]. However, lipophilicity determination in different solvent systems, such as alkane/water system, proved its utility in (Q)SAR studies and therefore some predictive methods also emerged in this field. Many publically available databases include numerous experimental values collected through the literature the quality of the experimental data represents the cornerstone of most of the models developed to predict lipophilicity. 

The above equation is, however, invalid. In homologous series in which Eq. 2.2 holds, a is essentially the fraction value, fcm.%- But it is also well established that/( H/) is a variable quantity in different solvent systems. Log P values in octanol and cyclohexane have been determined by Taft and coworkers [21, 22] for a series of non-am-phitropic, monofunctional aliphatics. The partition coefficient obtained could be described and correlated by the following equations ... 

Partitioning of 121 solutes in five different solvent systems (octanol, heptane, chloroform, diethyl ether, and n-butylacetate) was carried out to determine the extent to which the hydrogen donor capacity of solutes affects the permeation of membranes,... 

The partitioning of a substance between two liquid phases (multistage partitioning, partition chromatography) and the extraction of solids require similar properties of a solvent [50-55]. When a substance has to be partitioned, a solvent system with limited miscibility of the components is required in order that the substance dissolves to a different extent in the two phases. The greater the chemical differences between any two solvents, the more limited their miscibility. Other requirements that the solvent system must fulfil are, inter alia, a favorable partition coefficient (the average partition coefficient of the component mixture should be between ca. 0.2 and 5), as high a separation... 

Partition coefficients from different solvent systems can also be compared and converted to the octanol/water scale, as was suggested by Collander (116). He stressed the importance of the following linear relationship log 2 = a logPj + b. This type of relationship works well when the two solvents are both alkanols. However, when two solvent systems have varying hydrogen bond donor and acceptor capabilities, the relationship tends to fray. A classical example involves the relationship between log P values in chloroform and octanol (117,118). 

El Tayar, N., Tsai, R.-S., Testa, B., Carrupt, P.-A. and Leo, A. (1991b). Partitioning of Solutes in Different Solvent Systems The Contribution of Hydrogen-Bonding Capacity and Polarity. J.Pharm.Sci., 80,596-598. 

Early in this century, Meyer (109) and Overton (110) showed that the relative potencies of drugs that affect the nervous system correlated with their oil/water partition coefficients. Fifty years later it was shown that partition coefficients in different solvent systems were correlated (111), thus establishing the basis for an extrathermodynamical treatment of partition coefficients. 

Further analysis of equation 39 reveals a reason for the validity of Collander s equation that correlates partition coefficients in different solvent systems (111). Thus, in equation 39 the terms (IW-IQ) and (Jy-JQ) both reflect a variable characteristic of the solvents. For small changes in this variable they should be proportional to each other... 

Thus, for the ir constants for the same molecular system RX depends linearly on the solvent systems in which they were determined. Since ir is an additive-constitutive property of the molecule we can obtain logP from the ir values of the constituting parts (23, 24). The linear relation between logP values for the same compound in different solvents should also hold. This is reflected in the linear relation between partition coefficients in different solvent systems as expressed by Collander (111)... 

El-Tayar N, Tsai RS, Test B, Carrupt PA, Leo A. Partitioning of solutes in different solvent systems contribution of hydrogen-bonding capacity and polarity. J Pharm Sci 1991 80 590-598. 

Log P values have been studied in approximately 100 organic liquid-water systems. Since it is virtually impossible to determine log P in a realistic biological medium, the octanol-water system has been widely adopted as a model of the lipid phase (Leo et al. 1971). Whilst there has been much debate about the suitability of this system (see, e.g., Dearden and Bres-nen 1988), it is the most widely used in pharmaceutical studies. Octanol and water are immiscible, but some water does dissolve in octanol in a hydrated state. This hydrated state contains 16 octanol aggregates, with the hydroxyl head groups surrounded by trapped aqueous solution. Lipophilic (unionized) species dissolve in the aliphatic regions of the octanol, whilst ionized species (see below) are drawn to the polar regions (Franks et al. 1993). The partitioning of solutes in different solvent systems has been reported by El-Tayar et al. (1991). 

The use of a single standard system for drug partitioning is justified by the Collander equation (eq. 20) [183], which relates partition coefficients from different solvent systems. 

Several hundreds of linear relationships between various kinds of (mostly nonspecific) biological data and n-octanol/water partition coefficients have been published e.g. [18, 182]). However, the choice of n-octanol/water as the standard system for drug partitioning must be reconsidered in the light of some recent results. Principal component analysis of partition coefficients from different solvent systems [188 —190] shows that lipophilicity depends on solute bulk, polar, and hydrogen-bonding effects [189] isotropic surface areas, i.e. areas where no water molecules bind and hydrated surface areas, were correlated with the first and the second principal components of such an analysis [190]. 

Paper partition chromatography (PPC) was the first used for separating thiamine phosphates in biological materials. A good PPC separation of thiamine phosphates was reported by using several different solvent systems. Photometry at 270 nm of eluted, individual spots allowed quantitation of each thiamine compound down to the lO-pg level. 

Chen and Shih [30] and Coulon and Ghoul [2] have summarized the requirement of different solvents systems for transesterification based on the partition coefficient of the solvent between octanol and water, log P. 

HSCCC is attracting attention based on its high separation scale, 100% recovery of sample, and mild operating conditions. It is a chromatographic separation process based on the partition coefficients of different analytes in two immiscible solvent systems (mobile phase and stationary phase) subjected to a centrifugal acceleration field. 

Gibbs transfer energy of an ion i from phase a to p AG g Gibbs energy for ion-solvent interaction in phase a A log P partition coefficient difference between two solvent systems A 0 Galvani potential difference between a and p phases Ag(pi/2 half-wave potential... 

Unfortunately, the dilute solution model is limited in its applicability to concentrated solutions. This causes problems for alloys such as Ni-based superalloys, high alloy steels, etc., and systems where elements partition strongly to the liquid and where solidification processes involve a high level of segregation. It is also not possible to combine dilute solution databases which have been assessed for different solvents. The solution to this problem is to use models which are applicable over the whole concentration range, some of which are described below. 

Different balance between intermolecular forces can be accessible via partition coefficients measured in solvents systems other than the traditional 1-octanol/water. Therefore there was a growing interest in the partition processes in several solvent/ water systems [64, 65] and in particular the critical quartet of solvents which was designed to merge the main information about a solute concerning its partition and transport. Only a few studies have been performed to characterize the lipophilicity profile of new chemical entities in different solvent/water systems and consequently the number of methods attempting to model such partitioning systems is limited. 

Ottaviani, G., Martel, S., Escalara, C., Nicolle, E. and Carrupt, P.A. (2008) The PAMPA technique as a HTS tool for partition coefficients determination in different solvent/water systems. European Journal of Pharmaceutical Sciences,... 

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