Constant ionization

As examples of applications, we present the overall accuracy of predicted ionization constants for about 50 groups in 4 proteins, changes in the average charge of bovine pancreatic trypsin inhibitor at pH 7 along a molecular dynamics trajectory, and finally, we discuss some preliminary results obtained for protein kinases and protein phosphatases. 

In order to summarize the procedures used for computing ionization constants of titratable residues in proteins, the steps used in our algorithm will be enumerated below ... 

Use of a Monte Carlo or a cluster (Hybrid) algorithm to calculate ionization constants of the titratable groups, net average charges, and electrostatic free energies as functions of pH. 

It can be seen from Table 2 that the intrinsic values of the pK s are close to the model compound value that we use for Cys(8.3), and that interactions with surrounding titratable residues are responsible for the final apparent values of the ionization constants. It can also be seen that the best agreement with the experimental value is obtained for the YPT structure suplemented with the 27 N-terminal amino acids, although both the original YPT structure and the one with the crystal water molecule give values close to the experimentally determined one. Minimization, however, makes the agreement worse, probably because it w s done without the presence of any solvent molecules, which are important for the residues on the surface of the protein. For the YTS structure, which refers to the protein crystallized with an SO4 ion, the results with and without the ion included in the calculations, arc far from the experimental value. This may indicate that con-... 

Alkyl groups have little effect The ionization constants of all acids that have the general formula C H2 +iC02H are very similar to one another and equal approximately 10 (p/ifa = 5) Table 19 2 gives a few examples... 

Table 19 3 lists the ionization constants of some substituted benzoic acids The largest effects are observed when strongly electron withdrawing substituents are ortho to the carboxyl group An o nitro substituent for example increases the acidity of benzoic acid 100 fold Substituent effects are small at positions meta and para to the carboxyl group In those cases the values are clustered m the range 3 5-4 5... 

Separate ionization constants designated Ki and K2 respectively characterize the two successive ionization steps of a dicarboxylic acid... 

As with other dicarboxyhc acids the second ionization constant of carbonic acid IS far smaller than the first... 

As Table 24 2 shows most phenols have ionization constants similar to that of phenol Itself Substituent effects m general are small... 

At equilibrium, when the ionization and recombination rates are balanced, the ionization constant AT (in atm) is given by... 

The ionization constant can be calculated from the Saha equation. ... 

Polynitroparaffkis are stronger acids than the corresponding mononitroparaffins. Thus 1,1-dinitroethane has an ionization constant of 5.6 x 10 in water at 20°C trinitromethane is a typical strong acid with an ionization constant ki the range of 10 to 10 . Neutralization of these substances occurs rapidly, and they may be titrated readily. 

Peroxophosphoric Acids and Their Salts. In its usual impure form (H PO is the main contaminant), peroxomonophosphoric acid [13598-52-2] (5), is a viscous, coloress Hquid. The three ionization constants for peroxomonophosphoric acid are pifj = 1.1, P-A2 = 5.5, and pK (peroxide proton) = 12.8 (44). Oxidations comparable to those of peroxomonosulfuric acid, H2SO, occur in acid solutions of ca pH 2, but at higher pH values, H PO becomes less reactive as an oxidant and more unstable with respect to decomposition (44). The stmcture of H PO is probably similar to that of... 

A double end point, acid—base titration can be used to determine both sodium hydrosulfide and sodium sulfide content. Standardized hydrochloric acid is the titrant thymolphthalein and bromophenol blue are the indicators. Other bases having ionization constants in the ranges of the indicators used interfere with the analysis. Sodium thiosulfate and sodium thiocarbonate interfere quantitatively with the accuracy of the results. Detailed procedures to analyze sodium sulfide, sodium hydro sulfide, and sodium tetrasulfide are available (1). 

The concentration of tme carbonic acid (H2CO2) is negligible in comparison to dissolved carbon dioxide, eg, only 0.3% of the latter is hydrated to carbonic acid at 25°C. The ionization constant is a composite constant representing both the CO2 hydration reaction, iC, and ionization of tme H2CO2, ifj = ifjj QQ /(I + K). Temperature-dependent equations for and are (29)... 

Carbon dioxide, the final oxidation product of carbon, is not very reactive at ordinary temperatures. However, in water solution it forms carbonic acid [463-79-6] H2CO2, which forms salts and esters through the typical reactions of a weak acid. The first ionization constant is 3.5 x 10 at 291 K the second is 4.4 x 10 at 298 K. The pH of saturated carbon dioxide solutions varies from 3.7 at 101 kPa (1 atm) to 3.2 at 2,370 kPa (23.4 atm). A soHd hydrate [27592-78-5] 8H20, separates from aqueous solutions of carbon dioxide that are chilled at elevated pressures. 

Chemical Properties. Hydrogen cyanide is a weak acid its ionization constant is of the same magnitude as that of the natural amino acids (qv). Its stmcture is that of a linear, triply bonded molecule, HC=N. 

Pyridazine-3(2//)-thiones exist in the thione form (14), as is evident from an X-ray structure analysis of pyridazine-3(2//)-thione. 6-Mercaptopyridazine-3(2//)-thione is predominantly in the monothiolmonothione form (15) in aqueous solution and in the solid state, 6-hydroxypyridazine-3(2//)-thiones are in the hydroxythione form (16) and 6-aminopyridazine-3(2//)-thiones exist in the aminothione form (17) for further details see (73HC(28)755). Cinnoline-4(l//)-thiones and phthalazine-l(2//)-thione have been shown on the basis of UV data and ionization constants to exist in the thione forms. 

The use of UV spectroscopy as an identification method is continuously decreasing in relative importance compared to the use of NMR or mass spectrometry. However, due to the general validity of Beer s law, it continues to be an appropriate method for quantitative studies such as the measurement of ionization constants (Section 4.04.2.1.3(iv) and (v)) and the determination of tautomeric equilibrium constants (Section 4.04.4.1.5). 

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