Salt Equilibria

Zwitterionic character is notable in several therapeutic area series, e.g. in angiotensin-converhng enzyme inhibitors, quinolone anhbacterials and thrombin inhibitors. The aqueous solubiUty measurement of zwitterions is very pH dependent as might be expected. The relationship of aqueous solubiUty to ionization state is extraordinarily complex if the zwitterion is of the type capable of an equi-Ubrium between true zwitterion and formally neutral forms (e.g. as in a quinolone antibacterial). For these types of complex equilibria, salt effects on solubility may be unexpectedly large, e.g. solubility unexpectedly may track with the chaotropic character of the salt... 

Figure 4.1b is a typical illustration of the Donnan equilibrium [1], A membrane impermeable to macroions (P" ) but permeable to small ions (M+, X ) and solvent molecules (S) divides a solution into two regions. The situation is a common one in colloid science, and the fact that the equilibrium salt concentration in region II (the simple electrolyte solution), [X ]n, is greater than that in region I (the region occupied by the macroions), [X ]I( has been used in countless dialysis experiments. It is also well known [2] that equilibrium involves the establishment of not only a pressure difference but also an electrical potential difference across the membrane and that, in the simple case where the mobile ions behave as ideal solutes, the equilibrium condition is expressed as... 

We arrive at the same conclusion if we assume that one of the two components is present in one phase only, as is often the case in practice, for example in the equilibrium, salt solution — water vapour. Here the concentration of the salt in the gaseous phase is practically zero. Thus the variable Cg disappears, but so also does equation (4), as the only process consistent with the nature of the system is the transfer of one component (water) from the one phase to the other. Here again there are 5 — 3 = 2 degrees of freedom. 

Zgf 2. In simple salts, it is the electron transfer from each donor to each acceptor molecule. In complex salts, it can be taken as the mean electron transfer per acceptor molecule. Suppose that is merely the bulk equilibrium value of a quantity z which can vary continuously throughout the allowed range of zq, 0 i. z t 2. However, as z varies, no change is allowed in the molecular structure of the crystal the structure is fixed to be that of the equilibrium salt, zq. z = 0 corresponds, therefore,to a system of neutral molecules in the structure of the charge transfer salt. 

At equilibrium, salt crystals are continuously dissolving, and Na and Cl" ions are continuously crystallizing. Both processes are occurring at the same rate. 

Where both ions of a given univalent electrolyte, AB, have appreciable solubility in phases a and j , an equilibrium salt distribution coefficient, Kj, can be defined as... 

The analysis by the BM method (Figure 15.3b) is simpler than by the SP method (Figure 15.3a). However, one problem is that the equilibrium salt adsorption is measured for a different (final)... 

The second equilibrium is the more important, giving rise to the nitronium ion, NOj, already mentioned as a product of the dis sociation of dinitrogen tetroxide. Several nitronium salts have been identified, for example nitronium chlorate(VII), (N02) (C104) . If pure nitric acid is dissolved in concentrated sulphuric acid, the freezing point of the latter is depressed to an extent suggesting the formation of four ions, thus ... 

These are similar to those of the alkali metals but are rather less soluble in water. However, calcium sulphide, for example, is not precipitated by addition of sulphide ions to a solution of a calcium salt, since in acid solution the equilibrium position... 

At this point the system has throe phases (CUSO4 CuS04,Hj0 HjO vapour) and the number of components is two (anhydrous salt water). Hence by the phase rule, F + F = C + 2, t.e., 3+F = 2 + 2, or F=l. The system is consequently univariant, in other words, only one variable, e.g., temperature, need be fixed to define the system completely the pressure of water vapour in equilibrium with CUSO4 and CuS04,Hj0 should be constant at constant temperature. 

Furthermore, it is the system. Hydrate I/Hydrate II (or Anhydrous Salt), that possesses a definite pressure at a particular temperature this is independent of the relative amounts, but is dependent upon the nature of the two components in equilibrium. It is incorrect, therefore, to speak of the vapour pressure of a salt hydrate. ... 

We may now understand the nature of the change which occurs when an anhydrous salt, say copper sulphate, is shaken with a wet organic solvent, such as benzene, at about 25°. The water will first combine to form the monohydrate in accordance with equation (i), and, provided suflScient anhydrous copper sulphate is employed, the effective concentration of water in the solvent is reduced to a value equivalent to about 1 mm. of ordinary water vapour. The complete removal of water is impossible indeed, the equilibrium vapour pressures of the least hydrated tem may be taken as a rough measure of the relative efficiencies of such drying agents. If the water present is more than sufficient to convert the anhydrous copper sulphate into the monohydrate, then reaction (i) will be followed by reaction (ii), i.e., the trihydrate will be formed the water vapour then remaining will be equivalent to about 6 mm. of ordinary water vapour. Thus the monohydrate is far less effective than the anhydrous compound for the removal of water. 

Because of the great solubility of sulphonic acids in water and the consequent difficulty in crystallisation, the free sulphonic adds are not usually isolated but are converted directly into the sodium salts. The simplest procedure is partly to neutralise the reaction mixture (say, with solid sodium bicarbonate) and then to pour it into water and add excess of sodium chloride. An equilibrium is set up, for example ... 

The equilibrium of the overall reaction Is shifted in the direction of the condensation product by the precipitation of the p diketone as its sodium salt. 

The Raman spectrum of nitric acid shows two weak bands at 1050 and 1400 cm. By comparison with the spectra of isolated nitronium salts ( 2.3.1), these bonds were attributed to the nitrate and nitronium ion respectively. Solutions of dinitrogen pentoxide in nitric acid show these bands , but not those characteristic of the covalent anhydride , indicating that the self-dehydration of nitric acid does not lead to molecular dinitrogen pentoxide. Later work on the Raman spectrum indicates that at —15 °C the concentrations of nitrate and nitronium ion are 0-37 mol 1 and 0 34 mol 1 , respectively. The infra-red spectrum of nitric acid shows absorption bands characteristic of the nitronium ion. The equivalence of the concentrations of nitronium and nitrate ions argues against the importance of the following equilibrium ... 

Small amounts of salt-like addition products (85) formed by reaction on the ring nitrogen may be present in the medium. (Scheme 60) but. as the equilibrium is shifted by further reaction on the exocyclic nitrogen, the only observed products are exocyclic acylation products (87) (130. 243. 244). Challis (245) reviewed the general features of acylation reactions these are intervention of tetrahedral intermediates, general base catalysis, nucleophilic catalysis. Each of these features should operate in aminothiazoles reactivity. 

A sufficient concentration of base B is necessary for the removal of a proton of the CH, group. In a first step, the equilibrium in Scheme 20 results, in which the monomeric anhydrobase Bi constitutes the conjugated base of the quaternary salt A,. As has been shown for other rings (24). the equilibrium depends upon the concentration of the different species and the relative strength of the bases B and Bj, and depends also upon the nature of X. 

Aldonic acids exist m equilibrium with their five or six membered lactones They can be isolated as carboxylate salts of their open chain forms on treatment with base... 

Equation 6.44 is written in terms of the concentrations of CH3COOH and CH3COO- at equilibrium. A more useful relationship relates the buffer s pH to the initial concentrations of weak acid and weak base. A general buffer equation can be derived by considering the following reactions for a weak acid, HA, and the salt of its conjugate weak base, NaA. 

---