PKa, values for

Table 2. Predicted intrinsic and apparent pKa values for the Cys403 residue in Yersinia phosphatase for different models of the structure the data refer to a temperature of 293 K and an ionic strength corresponding to 150 mM of monovalent salt. See the text for the detailed description of the conditions under which each pK estimation was made. The experimentally determined value is 4.67 [39]...

Jones and Civcir prepared a variety of alternating oligomeric furanipyridine compounds and studied their NMR chemical shifts as well as the pKa values for the corresponding conjugate acids. All of these compounds were synthesized by Paal-Knorr reactions of 1,4-diketones with hot polyphosphoric acid. A representative example is the conversion of 24 into 25 in 82% yield. ... 

The spectral changes which occur in increasingly acid solutions of polyaza-heterocycles may indicate a second ionization. This event, however, can readily be distinguished from dehydration by measuring the spectra in anhydrous dichloroacetic acid, provided that the pKa value for the anhydrous species is above 1. Anhydrous dichloroacetic acid has a Hammett acidity function (Hq) of — 0.9 (as determined using o-nitroaniline as the solute), and the ultraviolet spectrum of a base with a p > 1 would be that of the anhydrous cation in this 2 A. Albert and W. L. F. Armarego, J. Chem. Soc. 4237 (1963). 

Capacities at Various pH Values pKa Values for Phosphoric Acid Resin ... 

More specifically, the pi of any amino acid is the average of the two acid-dissociation constants that involve the neutral zwitterion. For the 13 amino acids with a neutral side chain, pi is the average of pKal and p/amino acids with either a strongly or weakly acidic side chain, pi is the average of the two lowest pKa values. For the three amino acids with a basic side chain, pi is the average of the two highest pKz values. 

The pKa values for 3-phenyl- and 6-methyl-3-phenyl-2//-thiopyran-S,S-dioxides have been discussed in connection with the aromatic stabilization energies of their corresponding anions (91JOC4218). 

Charton s at values for SOPh and S02Ph are based on the pKa values for phenylsulfinyl- and phenylsulfonyl-acetic acids137, which we have already discussed in connection with the transmission of electronic effects by SO and S02 (Section III.C). These groups have also been the subject of a detailed study by Hogeveen and Montanari172, who measured the pKa values of some 3-phenylthio-, 3-phenylsulfinyl- and... 

DMSO can be used as a dipolar non-hydroxylic solvent for the measurement of pKa values for various phenols bearing strongly electron-withdrawing substituents. These acidity scales in DMSO have been correlated with those in H20 or in the gas phase92. 

The work of Charton and Meislich (15) has already been referred to. Hogeveen (58) has reported a correlation of pKa values for tra s-3-substituted acrylic acids. Hogeveen (50) and Sandris (49) have studied the pKa values of 3-substituted cinnamic acids. Bowden (59) has also studied pKa values of frflns-3-substituted acrylic acids. 

The second problem involves the measurement of pKa values for carbonyl and thiocarbonyl derivatives. Grieg and Johnson (157) have pointed out that the measurement of pKa values for very weak bases (11) is an inaccurate and arbitrary process. Of particular difficulty for our purposes is the fact that different carbonyl derivatives may require different acidity functions. As a result of this situation, no attempt was made to make correlations of pKa data for carbonyl and thiocarbonyl derivatives with eq. (2). Because accurate pKa values can be measured for imines, these values were correlated with eq. (2), although the conformational problem remains. The imine sets were first studied by Charton and Charton (73), who correlated them with eq. (2). No correlations of data for carbonyl or thiocarbonyl derivatives with eq. (2) are extant in the literature. Bhaskar, Gosavi, and Rao (158) have reported that AG values for complex formation of substituted thioureas with iodine are a linear function of the Taft a values. Drago, Wenz, and Carlson (159) have reported similar results for complex formation between iodine and substituted amides. Oloffson (160) has reported a linear relationship between -AH for the complex of substituted N,N-dimethylamides with SbCls and the ffj constants. 

Dicarbonyl functions have been built into macrocyclic structures, and pKa values for the resulting macrocycles [60] have been determined (Alberts and Cram, 1979). When the open-chain model [62] is compared with the macrocycles [60], identical first pK values were found (pKa = 8.6). Thus for the diketones [60], no macrocyclic effect is noticeable. But for the dissociation of a second proton from the mono-aniorts of [60] much higher pKa values are found. To a certain extent. Coulomb repulsions (see Section 2) are probably the reason for this behaviour, but the large difference in the pKa values (ApKa = 2.9, see Table 26) argues for a special stabilization of the mono-anion. Again hydrogen bonds are not unreasonable. 

Scheme 7.25 shows the role of quinone methide energy on the cation-quinone methide equilibrium. A high pKa value for this equilibrium is expected if the energy of the quinone methide approaches that of the carbocation. To construct this cycle, we used the Ka values that we determined for the protonated ketone (pKa — —0.9) and quinone methide (pKa = 6.6). This pKa difference requires that the keto form be more stable than the quinone methide by — 10.2kcal/mol. We obtained the calculated energy difference of lO.lkcal/mol from Hartree-Fock calculations using 6-31G and STO-3G basis sets, inset of Scheme 7.25. 

Boruah, R. C. Skibo, E. B. Determination of the pKa values for the mitomycin C redox couple by tritration, pH rate profile, and Nemst-Clark fits. Studies of methanol elimination, carbocation formation, and the carbocation/quinone methide equilibrium. J. Org. Chem. 1995, 60, 2232-2243. 

It was found that the log 5/pH curves were altered in the presence of as little as 0.5% v/v DMSO, in that the apparent pKa values, pA pp, derived from log S versus pH [481], were different from the true pKa values by about one log unit. The pA pp values were generally higher than the true pKa values for weak acids (positive shift), and lower than those for weak bases (negative shift). This has been called... 

Bacarella, A. L. Grunwald, E. Marshall, H. R Purlee, E. L., The potentiometric measurement of acid dissociation constants and pH in the system methanol-water. pKa values for carboxylic acids and anilinium ions, j. Org. Chem. 20, 747-762 (1955). 

His residues at configurations sampled using the popular link-host-atom exclusion scheme changes the free energy derivatives by 8-9 kcal/mol despite that the QM/MM frontiers are far from the zinc-bound water. With this effect taken into account, the calculated pKa value for the zinc-bound water in the WT CAII is in encouraging agreement with experiment the value is 7.1 (5.4) for the 20 (25) A-inner-region simulations, as compared to the experimental value of around 7 [86],... 

Table 10-1. Standard pKa values for titratable side chains in a protein [85, 97]...

Another interesting application area of PHMD simulations is to investigate electrostatic interactions in the unfolded states of proteins. A traditional view that unfolded proteins adopt random conformational states that are devoid of electrostatic and hydrophobic interactions, are recently challenged by experimental data [20, 69], REX-CPHMD folding simulations of the 35 residue C-terminal subdomain of the villin headpiece domain revealed a significant deviation from the standard pKa values for several titratable residues. Additional simulations, in which a charged group is neutralized confirmed the existence of specific electrostatic interactions in the unfolded states (JK and CLB, manuscript in preparation). 

We have already seen (p. 56) that the Ka, and hence pKa, value for an acid is not an intrinsic attribute of the species itself, because it varies from one solvent to another the value depending on the overall system of which the acid is a constituent. Values are normally quoted for aqueous solution, unless otherwise specified, because most data are available for that solvent. Most values are also quoted as at 25°, again because most data were obtained at this temperature. A constant temperature has to be specified as Ka, an equilibrium constant, varies with temperature. We have been concerned above with the relative... 

In considering relative acidity, classically it is only the thermodynamics of the situation that are of interest in that the pKa value for the acid (cf. p. 54) can be derived from the equilibrium above. The kinetics of the situation are normally of little significance, as proton transfer from atoms such as O, N, etc., is extremely rapid in solution. With carbon acids such as (1), however, the rate at which proton is transferred to the base may well be sufficiently slow as to constitute the limiting factor the acidity of (1) is then controlled kinetically rather than thermodynamically (cf. p. 280). 

A table of some pKa values for carbon acids is appended for convenience, before going on to discuss the factors that can contribute to the relative stabilisation of carbanions ... 

We selected liquid ammonia because of its pronounced solubilizing characteristics and powerful ionizing properties. At -33°C and atmospheric pressure, the pKa-value for auto-ionization of liquid ammonia [2NH3 = NH2 + NH4 ] is 34 and since the equivalent value for water is only 14, many substances (with pKa-values between 14 and 34) which are neutral in water should be capable of splitting off protons in liquid ammonia. Acidic... 

The pKa values for the two ionizations of fumarase can be determined experimentally to be approximately 5.9 and 7.5, thus these figures provide an appropriate way to define what, in the context of this problem, is meant by "medium" pH (Table 8.3). 

Thermochemistry. Chen et al.168 combined the Kohn-Sham formalism with finite difference calculations of the reaction field potential. The effect of mobile ions into on the reaction field potential Poisson-Boltzman equation. The authors used the DFT(B88/P86)/SCRF method to study solvation energies, dipole moments of solvated molecules, and absolute pKa values for a variety of small organic molecules. The list of molecules studied with this approach was subsequently extended182. A simplified version, where the reaction field was calculated only at the end of the SCF cycle, was applied to study redox potentials of several iron-sulphur clusters181. 

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