246 



6. INTERACTIONS OF INHIBITORS WITH ENZYMES 



One of the most important and most difficult problems is the evaluation 

 of the dielectric constant applicable to a particular separation of charges. 

 A reliable estimation of intermolecular forces, particularly those involving 

 ionic groups, can be made only with an accurate assignment of the dielectric 

 constant. At the present time this is impossible but an approach to at 

 least reasonable values has been made. 



Variation of Dielectric Constant with Distance 



The dielectric constant of the medium near an ion may be estimated 

 theoretically by assuming certain models of water orientation in the elec- 

 trical field of the ion or evaluated indirectly from experimental dissocia- 

 tion constants of dicarboxylic acids (the electrostatic effect of one car- 

 boxylate ion on the pK^ of the other acidic group being dependent on the 

 dielectric constant). Calculations of the former type often involve the as- 

 sumption of one rigidly oriented layer of water molecules around the ion 

 and a homogeneous dielectric outside this. Since it is likely that there are 

 partially oriented water molecules beyond the first bound layer and since 

 the structure of the hydrated ion is not certain, it is felt that this proce- 

 dure is not satisfactory. Figure 6-11 presents the variation of the dielectric 



60- 



40 - 



20- 



12 A 



Fig. 6-11. Variation of the dielectric constant with the distance from a uni- 

 valent ion at 37.5° as calculated by different methods. Curve (1) from Conway 

 tt al. (1951), curve (2) from Schwarzenbach (1936), and curve (3) from Grahame 

 (1950) and Ritson and Hasted (1948). 



