696 



14. EFFECTS OF pH OX ENZYME INHIBITION 



The effect of the vicinal group can be estimated by the procedure discussed 

 in Chapter 6. The interaction energy between two ionic groups is given by 

 Eq. 6-109 and the changes in p/{^, due to such interaction are plotted in 

 Fig. 14-14. The following points should be noted about these calculations: 

 (1) the repulsion correction factor, r = 0.92, for ion-ion interactions was 

 not used because the groups are not in contact at their equilibrium dis- 

 tance, (2) the dispersion energy was omitted since it does not change with 

 the protonation of the vicinal group, (3) the ion-dipole interaction at dis- 



pK. 



Fig. 14-13. Different types of effects of 

 an ionizing vicinal group on the inhi- 

 bitor constant. Curve A: charges on in- 

 hibitor and vicinal group are opposite. 

 Curve B: charges on inhibitor and vici- 

 nal group are the same. Curve C: charges 

 on inhibitor and vicinal group are oppo- 

 site and pX/ — pH curve has slope of — 1 . 



tances above 5 A can be neglected (Table 6-18), and (4) hydration of the 

 ionic grouj^s has been assumed. Of course such calculations are only ap- 

 proximate, due primarily to the ambient water molecules and the uncer- 

 tainty of the value of the dielectric constant, but some confidence in their 

 general validity is found in the experimental data on the effects of charged 

 groups on acidic dissociations. 



The problem of the effects of charged groups on ionization was first 

 treated theoretically by Bjerrum (1923) but this simple approach did 

 not correlate very well with the experimental results. The treatment 

 was refined by Kirkwood and Westheimer (1938) and Westheimer and 



