Dipolar ions, dissociation constants

Tetracycline antibiotics are closely related derivatives of the polycyclic naphtha-cenecarboxamide. They are amphoteric compounds with characteristic dissociation constants corresponding to the acidic hydroxyl group at position 3 (pK about 3.3), die dimethylamino group at position 4 (pK, about 7.5), and the hydroxyl group at position 12 (pK about 9.4). In aqueous solutions of pH 4-7, tetracyclines exist as dipolar ions, but as the pH increases to 8-9 marked dissociation of the dimethylamine cation occurs. They are soluble in acids, bases, and alcohols but are quite insoluble in organic solvents such as chloroform. Their ultraviolet spectra show strong absorption at around 270 and 360 nm in neutral and acidic solutions. Tetracyclines are readily transformed into fluorescent products in the presence of metal ions or under alkaline conditions. 

The dissociation constants fC — Kn for a multi-protic acid HrA are defined as stepwise or macroscopic constants (also called molecular constants). For some compounds, e.g. alanine, the pfCa values are far apart (pfC and pK2 are 2.4 and 9.8, respectively). The macroscopic constants can be assigned specifically, fCj to the carboxyl group and K2 to the protonated amino group. At the isoelectric pH of 6.1 the alanine exists almost entirely as the dipolar ion. However, for compounds in which the macroscopic pfCa values are closer together, they cannot be assigned to specific groups. We will consider some specific examples in the next section. 

The two monoprotonated forms of pyridoxine are the tautomeric pair shown in Eq. 6-75 and whose concentrations are related by the tautomeric ratio, R = [neutral form]/[dipolar ion], a pH-independent equilibrium constant with a value of 0.204/0.796 = 0.26 at 25°C.75 Evaluation of microscopic constants for dissociation of protons from compounds containing non-identical groups depends upon measurement of the tautomeric ratio, or ratios if more than two binding sites are present. In the case of pyridoxine, a spectrophotometric method was used to estimate R. 

The apparent ionization constants and ultraviolet absorption spectra of the three isomeric pyridine monocarboxylic acids were determined at 25 in aqueous KCI. As expected, it was confirmed that these acids exist in aqueous isoelectric solutions mainly in the dipolar ion form. Similar data for monocarboxylic and monosulfonic acids and polyvalent acids were obtained more recently. The dissociation constants and electrophoretic mobilities of fifteen substituted alkyl-, nitro-, and chloropyiidine carboxylic acids were also determined. The ultraviolet absorption spectra of a series of dihydropyridine-3, S-dicarboxylic acids were correlated with electronic and steric factors. ... 

The observed solubility of the protein represents the sum total of the concentrations of a great number of microscopically different forms— cations, anions, and dipolar ions—which are all present in a mobile equilibrium in any solution. As pH and ionic strength are altered, the relative concentrations of these different forms must also be altered. If we suppose the ionic strength to be held constant, the concentration of any one of these forms can be described in terms of the concentration of the isoelectric protein, which is directly in equilibrium with the solid phase, and of the various dissociation constants which relate the pH to the relative concentrations of the protein anions and cations. The... 

At a quantitative level, near criticality the FL theory overestimates dissociation largely, and WS theory deviates even more. The same is true for all versions of the PMSA. In WS theory the high ionicity is a consequence of the increase of the dielectric constant induced by dipolar pairs. The direct DD contribution of the free energy favors pair formation [221]. One can expect that an account for neutral (2,2) quadruples, as predicted by the MC studies, will improve the performance of DH-based theories, because the coupled mass action equilibria reduce dissociation. Moreover, quadrupolar ionic clusters yield no direct contribution to the dielectric constant, so that the increase of and the diminution of the association constant becomes less pronounced than estimated from the WS approach. Such an effect is suggested from dielectric constant data for electrolyte solutions at low T [138, 139], but these arguments may be subject to debate [215]. We note that according to all evidence from theory and MC simulations, charged triple ions [260], often assumed to explain conductance minima, do not seem to play a major role in the ion distribution. 

In WS theory, this high ionicity is a consequence of the increase of the dielectric constant induced by dipolar pairs. One can expect that an account for neutral quadruple ions, as predicted by the MC studies, will improve the performance of DH-based theories, because, the coupled mass action equilibria reduce dissociation, and, furthermore, quadruples yield no contribution to the dielectric constant. Such an effect is suggested from dielectric measurements for electrolyte solutions at low T [43]. 

The interaction with the cation noticeably affects the reactivity of the anion in media of low dielectric constant. Thus, on switching from the large tetra u-butylammonium to the small lithium cation, the reactivity sequence of the corresponding halides in the nucleophilic substitution of n-butyl 4-bromobenzenesulfonate in the weakly dissociating acetone is completely reversed (Eq. 3). Whereas the order obtained with bulky quaternary onium salts (Cl >Br >I ) corresponds to that of free, nonassociated halides in dipolar non-HBD solvents (e.g.. acetone), the sequence of the lithium halides (Cl
protic solvents, is mainly due to the increasing deactivation of the anion in the ion pair on increasing the cation charge density ... 

Note the strong dependence on the charge number. As shown elsewhere, the equilibrium constant of a 1 1 weak electrolyte like acetic acid is increased by an electric field of 100 kV cm to about 14%, that for a 2 2 electrolyte like MgS04 to about 110%. ° Compared to simple dipolar equilibria of small molecules where electric-field-induced changes in K are very small, we see that the dissociation step of simple ion pairs is associated... 

Measurements of the spin-lattice relaxation rates of the P nucleus in manganese-(ii) + ATP solutions have been used to determine the dissociation rate constant of the Mn -ATP complex it is given as 1.5xl0 s at 25 °C. (Incidentally, a detailed consideration of the results in terms of the dipolar interaction between the electron and nuclear spins leads to the conclusion that the a-P atom is further from the manganese ion than the j8- or y-P atoms, which are equidistant. This contrasts with the situation in Mn -xp where the three P atoms are equidistant from the metal. The matter is considered in greater detail in Part III.)... 

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