HYDRATION OF IONS 259 



Importance of Hydration in Enzyme Interactions 



It was pointed out earlier that ionic interactions involve displacement 

 of water. To varying extents this is true for all molecular interactions in 

 solution. The reaction of an inhibitor with an enzyme is usually written 

 as E + I ^ EI but from the standpoint of the over-all interaction energy 

 it should be: 



E -w^ + I -Wy -> E -I -iv^ + {x + y - z)w (6-80) 



where w represents a bound water molecule and x, y, and z the number of 

 water molecules associated with each species; the number of waters dis- 

 placed would then be x -\- y — z and these will interact with free water 

 molecules. The interaction of water with enzyme or inhibitor may be of 

 any type (ion-dipole, dipole-dipole, or dispersion) and thus complexes 

 such as E— Wj. do not represent necessarily stable hydration layers but 

 indicate all energetically significant interactions of the molecules with 

 water. Even nonpolar molecules or groups, such as hydrocarbon side- 

 chains, exhibit some dispersion interaction with surrounding water mole- 

 cules, and when two nonpolar groups interact this water is displaced. 

 In such a case where dispersion forces only are important, x = y because 

 the interaction surface between the groups is the same ^s that for interac- 

 tion with the water, and z = since all the water must be displaced for 

 significant interaction between the groups: 



E -iv^ + I -iv^ ^ E-l +2xw (6-81) 



Since each dispersion interaction involves the polar izabilities of the sub- 

 stances we may write (Pe = — xKa-^a^ for the potential energy of each 

 group with its surrounding water. The over-all interaction energy is the 

 difference between the final and initial states. 



Inital state: fe = — xKaeCCu, — a;A'a,a,„ (6-82) 



Final state: (Pe = ~ xKa,/ — xKa^ai (6-83) 



The over-all dispersion interaction energy is thus: 



<Pe = — xK{a u, — Ui) {a a, — a J (6-84) 



and not — xKa^a^ as often assumed. The disruption of the water structure 

 and the entropy factors involved will be discussed later. The role of such 

 water dispersion forces in protein reactions has been considered by Pauling 

 and Pressman (1945) in the interactions of haptenic groups with antibody. 



