802 15. EFFECTS OF VARIOUS FACTORS ON INHIBITION 



expression such as D ^= 6d — 7 (Eq. 6-72) must be used. We may for con- 

 venience call the effective dielectric constants for short-range molecular 

 interactions the microscopic dielectric constants. A problem immediately 

 arises. If the bulk dielectric constant of pure water at 37.5° is 74.1 and of 

 a 30% dioxane solution is 48.6, is the microscopic dielectric constant re- 

 duced to the same degree in the dioxane mixture? One might imagine that 

 in the interaction of two ions or ionic groups the ions would be surrounded 

 preferentially by the more polar water molecules and that the presence 

 of the dioxane would not be as important as in the bulk phase. In other 

 words, the interaction energy of two ions up to separation distances around 

 10 A might be dependent more upon the dielectric properties of water than 

 would be predicted on the basis of the effect of dioxane on the bulk proper- 

 ties. If the ions are not solvated appreciably by the organic solvent that is 

 added, they must be pictured as primarily hydrated as in aqueous media 

 and the interactions between them must still be determined to a great ex- 

 tent by these hydration layers. Of course, when the concentration of the 

 organic solvent becomes high, it is likely that the total hydration of ions 

 is reduced but in mixtures compatible with enzyme work the ions must 

 certainly retain their jirimary hydration sheaths. Thus some uncertainty 

 is introduced into the nature of the variation of the microscopic dielectric 

 constant with the composition of the medium. However, ionic reaction 

 rates and equilibria have occasionally been shown to vary with the dielec- 

 tric constant in a predictable manner and the approach must be considered 

 as qualitatively valid. Many discrepancies have also been observed and a 

 nonlinear relationship between the microscopic and bulk dielectric con- 

 stants may be responsible for these, along with other factors which will 

 be discussed in succeeding sections. 



Various Theoretical Dielectric Effects on Enzyme Interactions 



Changing the composition of a medium by the addition of organic solvents 

 may have several possible effects on enzyme reactions and their inhibition. 

 A modification of the interaction energy between a substance and an en- 

 zyme due to a simple alteration of the dielectric constant is not the only 

 thing that must be considered in experiments of this type. The rate at which 

 an inhibitor binds to an enzyme and the degree of inhibition will usually 

 be directly affected by the change in dielectric properties, but in addition 

 the following factors must be borne in mind in any quantitative treatment. 



(a) The p^^'s of acidic or basic groups on the enzyme or the inhibitor 

 may be altered by the change in the dielectric constant. The attraction be- 

 tween a proton and an anionic group will be increased as the dielectric 

 constant is lowered and, hence, the association of the proton will be greater, 

 resulting in a decrease of the acidic dissociation constant. The ionization 



