Neutral species coefficients

Katritzky et a/.511 have measured rate coefficients for deuteration of 3,5-dimethylphenol and heterocyclic analogues. As in all of the deuteration work of this group, rates of exchange were measured by the nmr method, which is useful for following exchanges at more than one position in the molecule but is, of course, much less accurate than detritiation techniques. In this study, the chemical shift for the ortho and para protons for the parent compound was too small to allow separate integration, but it was apparent that rates of exchange at these two positions did not differ by a factor > 4. From the rate-acidity profile (Table 149) reaction clearly occurs on the neutral species at pD < 3.5 (the log kl versus pD slope was 0.96) and upon the anion at pD > 3.5 (slope zero), and the reactivity of the anion to the neutral molecule was estimated as 107-8, close to the value of 107 noted above. 

Charge is conserved. In this equation, all participants are neutral species, so charge is conserved regardless of the stoichiometric coefficients. 

As the solute descriptors (E, S, A, B and V) represent the solute influence on various solute-solvent phase interachons, the regression coefficients e, s, a, h and V correspond to the complementary effect of the solvent phases on these interactions. As an example, consider the product aA in Eq. (4). Since A is the H-bond acidity of the solute, a is the H-bond basicity of the system. In other words, the intermolecular forces discussed in Sections 12.1.1.2 and 12.1.1.3 are present in all Abraham s log P factorization equations, with the exception of those interactions involving ions. This is the reason why Abraham s equahons are valid for neutral species only. 

A comparahve analysis of coefficients and descriptors clarifies the relationship between lipophilicity and hydrophobicity (Y in Eq. 4 is the molar volume which assesses the solute s capacity to elicit nonpolar interactions (i.e. hydrophobic forces) which, as also clearly stated in the International Union of Pure and Applied Chemistry definitions [3] are not synonyms but, when only neutral species are concerned, may be considered as interchangeable. In the majority of partitioning systems, the lipophilicity is chiefly due to the hydrophobicity, as is clearly indicated by the finding that the product of numerical values of the descriptors V and of the coefficient v is larger in absolute value than the corresponding product of other couples of descriptors/coefficients [9]. This explains the very common linear rela-... 

Fig. 16.3 ionization scheme of niflumic acid (CAS-RN 4394-00-7). The macro- (pfCJ and microprotonation (p(t ) schemes of the compound are shown. The logP value is determined by partition of neutral species (dubbed as NO) only. The microconstants and partition coefficients of each microspecies as well as the nature and the concentration of... 

There are three possibilities of letting the neutral species appear in the ionic partition diagram. Indeed, as the partition coefficient of the neutral species is neither potential- nor pH-dependent, the variable can be either the neutral species in the aqueous phase or that in the organic phase. However, to account for the experimental reality, it is more convenient to introduce the total mole number of neutral species [297], defined as ... 

The partition coefficient of the neutral species can then be deduced from the pH-shift between pK and pK eff, but no reliable value can be obtained with poorly lipophilic compounds because pK ff corresponds to pK in this case (see Fig. 10 for the case of methyl orange). 

It should finally be noted that the amount of the neutral and zweitterionic forms of a compound in solution is determined by its tatuomeric equilibrium constant, defined as Kz = cz/cn. Therefore, the neutral species and the zwitterion coexist around the isoelectric pH, and membrane permeation is conditioned by Kx and by the partition coefficient values of both tautomers. 

To distinguish partition coefficients of neutral species from ionized species, the notation log PN and log/j/ may be used, respectively, or the symbol C or A may be used as a substitute for superscript /, denoting a cation or anion, respectively. [362],... 

The un-ionized form is assumed to be sufficiently lipophilic to traverse membranes in the pH-partition hypothesis. If it were not, no transfer could be predicted, irrespective of pH. The lipophilicity of compounds is experimentally determined as the partition coefficient (log P) or distribution coefficient (log D) [16]. The partition coefficient is the ratio of concentrations of the neutral species between aqueous and nonpolar phases, while the distribution coefficient is the ratio of all species between aqueous and nonpolar phases [17,18],... 

CLOGP Logarithm of the calculated octanol/water partition coefficient (for neutral species)... 

A log P Difference between log P in octanol/water and alkane/water log D Logarithm of the distribution coefficient in octanol/water at pH 7.4 log P Logarithm of the partition coefficient in octanol/water (for neutral species)... 

Then there are a number of pesticides, e.g. the phenolic herbicide dinoseb and the fungicide pentachlorophenol, whose speciation varies strongly in the environmental pH-range. For this reason, one has to consider the pwhen estimating their environmental fate. Structures of the compounds discussed in this section are depicted in Table 1, together with a listing of their pand octanol-water partition coefficients, Kow, of the neutral species (unless otherwise indicated). Typical basic pollutants include the industrial chemicals aniline and jV.jV-dimethylaniline. 

Figure 8,12 Salting-out phenomenon for aqueous CO2. Activity coefficient of neutral species increases with increasing salinity, determining decreased solubility of aqueous CO2 in water, T and P conditions being equal. Reprinted from Garrels and Christ (1965), with kind permission from Jones and Bartlett Publishers Inc., copyright 1990.

Polarity term, mainly related to hydrogen bonding capability of a solute Logarithm of the partition coefficient (P) of neutral species Logarithm of the distribution coefficient (D) at a selected pH, usually assumed to be measured in octanol/water... 

In this equation, log P is the partition coefficient for the neutral species, log Fnon the fraction of non-ionized compound. So the intrinsic solubility, Vl th lumenal vol-... 

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