HYDRATION OF IONS 257 



teresting approach to this problem has been made by Samoilov (1957) 

 who considered the rate of exchange of water molecules between the bulk 

 phase and the hydration layers; if this rate is low, hydration must be strong. 

 The activation energies for this exchange were calculated for the common 

 ions, based on certain assumptions whose validity may be questioned, and 

 the following values in kcal/mole were obtained: Mg"^"^, 2.61; Li"^, 0.73; 

 Ca++, 0.45; Na+, 0.25; K+, - 0.25; CF, - 0.27; Br~, - 0.29, and I", 

 — 0.32. The negative values would indicate that certain water molecules 

 near the hydrated ions have greater freedom than in pure water. This 

 was termed " negative hydration " but is probably merely an expression 

 of the structure-breaking activity of these ions and should not be construed 

 as indicating a lack of hydration. 



A nonpolar molecule introduced into water will affect the structure 

 in at least two ways. In the first place, a hole must be made in the water 

 and this requires appreciable energy, which may be estimated roughly 

 from the latent heat of water (about 10 kcal/mole). In the second place, 

 a pure nonpolar molecule will interact so little with the surrounding water 

 molecules that icelike clusters tend to form at its surface, and thus these 

 nonpolar solutes are structure formers to some extent. This is experimen- 

 tally shown by the longer dielectric relaxation times observed in solutions 

 of nonpolar substances (Frank and Wen, 1957). If the solute possesses 

 groups that may participate in hydrogen bonding, these may act as nu- 

 clei for icelike clusters and further increase the structural component. 



Most molecules of interest in enzyme inhibition contain both polar and 

 nonpolar parts and it is of importance to consider the disposition of water 

 around such molecules. Fatty acids, for example, exist either as R — COOH 

 or R— C00~. In the former the water will be affected by the hydrocarbon 

 chain as described in the preceding paragraph; in addition there will be 

 some hydrogen bonding with the carboxyl group. When ionization occurs, 

 the anionic carboxylate group will become hydrated and there will probably 

 be a structure-breaking effect. Everett (1957) has presented evidence that 

 an anionic group in such molecules can exert an effect on the surround- 

 ing water structure to a distance of at least 5A. Thus in short-chain fatty 

 acids (such as formic or acetic acids), the noncarboxylate part of the 

 molecule will be of no or little importance since the water surrounding it 

 will be under the influence of the ionic group, whereas in long-chain fatty 

 acids (probably past butyric acid) only a fraction of the w^ater lying along 

 the hydrocarbon chain will be influenced by the ionic group. Situations 

 of this nature are very important in considerations of the interactions of 

 small molecules with enzymes, because the effective configuration of the 

 hydrated molecules and the changes that occur in the water structure upon 

 binding are factors of fundamental significance. 



One final word should be said concerning the orientation of water mole- 



