P/fa-Values

The protonation equilibria for nine hydroxamic acids in solutions have been studied pH-potentiometrically via a modified Irving and Rossotti technique. The dissociation constants (p/fa values) of hydroxamic acids and the thermodynamic functions (AG°, AH°, AS°, and 5) for the successive and overall protonation processes of hydroxamic acids have been derived at different temperatures in water and in three different mixtures of water and dioxane (the mole fractions of dioxane were 0.083, 0.174, and 0.33). Titrations were also carried out in water ionic strengths of (0.15, 0.20, and 0.25) mol dm NaNOg, and the resulting dissociation constants are reported. A detailed thermodynamic analysis of the effects of organic solvent (dioxane), temperature, and ionic strength on the protonation processes of hydroxamic acids is presented and discussed to determine the factors which control these processes. 

The results for dinuclear and polynuclear oxoacids are also consistent with this interpretation. Thus for phosphoric acid, H4P2O7, the successive p/fa values are 1.5, 2.4, 6.6 and 9.2 the 10-fold decrease between p/f and p/f2 (instead of a decrease of 10 ) is related to the fact that ionization occurs from two different PO4 units. The third stage ionization, however, is less than the first stage and the differ-... 

Predicting Acid-Base Reactions from p/fa Values... 

The conformation of a molecule can also affect its acidity. The following p fa values were determined for these compounds ... 

Table 18 p/fa values of macrocycle [36] containing two intra-annular carboxylic groups and an open-chain analogue [37] in DMSO/H2O (2 1 v/v). 

One final anomaly we have already commented on the enhanced value for the effect of para-substituents on the ionization of 2,6-di-fert-butylphenol in 1 1 v/v Et0H-H20 at 25 °C (Section III.D). In this solvent phenol itself has a p/fa value of 11.16, and the values for the 4-NO and 4-NO2 derivatives are 6.9 and 7.49, respectively134, i.e. NO has a greater acid-strengthening effect on phenol than NO2 does, as we have already seen above for solutions in water. However, the p/fa values of 2,6-di-fert-butylphenol and its 4-NO and 4-NO2 derivatives in 1 1 v/v Et0H-H20 are 14.22, 9.41 and 7.49, respectively134, i.e. the acid-strengthening effects of NO and NO2 are reversed. The apparent a value of p-NO is now about 0.9. Presumably there is a considerable amount of quinonoid form in this system. 

The solute benzene radical cation was formed on pulse radiolysis of an acidic aqueous solution of benzene. The transient optical absorption bands (A-max = 310, 350-500 nm) were assigned to the solute benzene radical cation which is formed on acid-catalysed dehydration of the OH adduct. The radical cation is able to undergo an electron-transfer reaction with Br and was found to be a strong electron oxidant. Pulse radiolysis has been used to study the complex reaction that follows electron addition to hydroxybenzophenones (HOBPs). The various radical species involved have been characterized spectrally and their p/fa values evaluated. The differences... 

The p fa value of 4-ethoxycarbonylbicyclo[2.2.2]octane-l-carboxylic acid in 50% w/w EtOH-H20 at 25 °C is 6.40, compared with 6.87 for the parent compound, i.e. ApKa = 0.47. These values are used by Charton80 to define a primary 07 value for C02Et through equation 11 ... 

Like pH and pA"Sp, any dissociation constant may be conveniently written as a p/fa value, where p/fa = —log10 A a. That is, the p/fa of Reaction 2.41 at 25 °C and 1 bar pressure is about 9.2 (Table 2.10). Furthermore, like pH, p/fa values are often sensitive to temperature. In hydrothermal waters, for example, the pA a value of Reaction 2.43 declines with increasing temperature so that the value approaches 7.11 at 300 °C (Zakaznova-Herzog, Seward and Suleimenov, 2006), 1936 Table 2.10. 

There are numerous other modifications of nucleobases possible, many of which are biologically relevant in that they lead to alternations in p/fa values, changes in tautomer structure as well as their base pairing patterns (55). Examples include ligands such as N6-methoxyadenine, which is a promutagen (66, 67) as well as 8-oxoadenine and 8-oxoguanine (68), which are known mutagens. 

TABLE 7.9 Comparison of p/fa Values of Several Acids in Different Solvents... 

Caswell and Schmir (1979) that PLNM/ALPH effects will be observed only in conformationally restricted systems. These authors studied products of hydrolysis of -imidate [92] and an equimolar mixture of this and the Z-imidate [93] as a function of pH. The percentage of ester in both cases was quantitatively described by the same titration curve, the yield of 101% ester at low pH falling to 65% at high pH, with the change governed by an apparent p/fa-value of 10.2. Rotation about the C—O or C—N bonds of the tetrahedral intermediate [94] is thus fast compared with its decomposition across the whole pH range. 

Analysis of the pH-dependence of the kinetic parameters and competitive inhibitor K values indicates that the p/fa values of the Bi and B2 groups are 7.6 and 6.0, respectively.791 These groups have not been identified, but the observed low degree of deuterium transfer ( 8%)80 82) suggests that the basic group Bi is polyprotic and, therefore, may be the -amino group of a lysine residue. 

The reader is reminded that other methods for measurement of p/fa values of weak acids exist, notably Streitwieser s method using cesium (lithium) cyclohexylamide in cyclohexylamine, which has been used to measure both kinetic and thermodynamic acidities (Streitwieser and Hammons, 1965 Szwarc et al., 1974). 

There is now convincing evidence that an acyl chymotrypsin intermediate is formed from both specific and non-specific substrates (Bender and Kezdy, 1964 Bender et al., 1964). This intermediate is undoubtedly an acylserine. Acyl- and phosphorylserine derivatives have been isolated and identified. In view of evidence such as a D2 O solvent isotope effect (Ah2oAd2o) °f 2-3 for both acylation and deacylation (Bender and Hamilton, 1962), alcohol and amine nucleophiles showing little dependence on the p/(fa -value of the nucleophile in reaction with furoyl enzyme (Inward and Jencks, 1965), and the influence of increasing steric bulk in the acyl group (Fife and Milstien, 1967 Milstien and Fife, 1968,. 1969), consistent... 

It is perhaps worth mentioning that substitution of other groups for the C-methyl group in amidinium ions has an effect on their p/fa -values, which is best correlated with Hammett s am -constants (p = —1T98), and the same is true of C-substituted N-phenylami-dinium ions (p = —12-08) (Charton, 1965). This is in line with the suggestion made on page 286, that am -constants are a measure of the inductive and mesomeric interactions of groups with a carbon in the sp2 state of hybridization. 

There is also a relationship between p fa-values of ethanol, phenol and acetic acid on the one hand, and ethylamine, aniline and acetamide on the other (Liler, 1971c, p. 108), which may be presented as a linear free energy relationship (Figure 6) by regarding Et, Ph and CH3 CO as substituents (R). This excellent relationship leaves no doubt that the acidic group in the R—NH3 series remains unchanged, i.e., that acetylammonium ion is formed in the protonation of acetamide in aqueous acid (half-protonation in ca. 19% sulphuric acid). 

Infrared evidence on alkyluracyl salts supports oxygen protonation (Cook, 1966). The p fa-value of the mono-cation is —3 38, according to Katritzky and Waring (1962), and —2 07, according to Antonovskii et al. (1972). 

When two amide groups in a six-membered aromatic ring are in opposition to each other, as in maleic hydrazide, the oxo structure [143] is not so highly stabilized and tautomerism is observed in which the 6-hydroxy-3-pyridazone form [144] predominates (Katritzky and Lagowski, 1963). The p/(fa-value of this compound is... 

These p/fa-values show that the inductive effect of the C=C bond accounts for about one half of the reduction in the basicity of the enamine nitrogen atom, the other half being due to the mesomeric effect (Stamhuis et al., 1965). The localization energy of the lone pair on the nitrogen, calculated from the second ApKa, is only about 1 6—1 7 kcal mole-1 (6-7-7-1 kj mol-1). There are indications from the substituent effects on the stretching frequency of the C=CH2 bond that this group is an electron sink of the same kind... 

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