p-AMINOBENZOIC ACID 



507 



the cell of the organism which has a buffering capacity presumably in 

 the same pH range. The molecular and ionized forms of ^-substituted 

 sulfonamides are also indicated in Figure 8. From the standpoint of geo- 

 metrical considerations, the p-aminobenzenesulfonyl group and the 

 p-aminobenzoate ion are very similar, the bond distances differing only 

 slightly, as indicated in Figure 8. Sulfones likewise are similar to the 

 p-aminobenzoate ion. 



6.7 A. 



() 



c 



|<-2.3 A-»| 

 y-Aminobenzoate ion 

 Figure 8 



N 



/ \l 



t S 



/ \ 



o „ o 



I-*— 2.4 A-»| 



Sulfonamide 



Sulfonamide ion 



The Structures of the p-Aminobenzoate Ion and Molecular and 

 Ionic Forms of Sulfonamides. 



If the substituent group, R, of the ^-substituted sulfonamide func- 

 tions solely in affecting the combining power of the p-aminobenzenesul- 

 fonyl group with the enzyme and the substituent within itself does not 

 possess groups which aid in this combining power, the activity of the 

 sulfonamide will depend upon the effect of the substituent group on the 

 combining power of the reactive groups, presumably the basic amino 

 group and the S0 2 group. Since only slight variations occur in the ioniza- 

 tion constants for the basic amino group of the ^-substituted sulfon- 

 amides, differences in combining power of these sulfonamides with the 

 inhibited enzyme cannot be attributed to the reactivity of the basic 

 amino group, and no relationship between the bacteriostatic activity and 

 these constants has been noted for these analogues. However, this may 

 become an important consideration for other analogues. 



The acid dissociation constants of ^-substituted sulfonamides vary 

 over a wide range, indicating that the properties of the sulfonamide 

 group are influenced greatly by the N 1 substituent. 



Since the p-aminobenzoate ion possesses an electronic charge which 

 greatly increases the negative character of the C0 2 " group, Bell and 

 Roblin postulate that this negative character of the C0 2 " increases the 

 affinity with which the molecule combines with the enzyme, and that the 

 more negative the S0 2 group in the sulfonamides, the greater the ability 



