776 



6. ARSENICALS 



the relative molar activity is observed (Fig. 6-10). The activity of nonacidic 

 derivatives (e. g., p-CONH2-9?-AsO) shows little or no dependency on the 

 pH over this range, indicating that it is the substituted acidic group which 

 is involved and not the arsenoxide radical. Furthermore, at any one pH, 

 the order of activity is approximately that of increasing Y)K^, as expected; 

 e. g., p-SOgH-T^-AsO, with a very low pZ^ of 2.0, is never to any extent 



4.9 p-lCHjIjCOOH 

 S.3S p-CONH 



4-(CHj),C00H 

 5.55 o-COOH 

 7 pHCH. 



5.0 5.5 



7.5 8.0 



Fig. 6-10. Effects of pH on the trypanocidal 

 activities of various arsenicals. The substi- 

 tuent groups on phenylarsenoxide and the 

 piiCa's are shown to the left of each curve. 

 (From Eagle, 1945.) 



un-ionized in the pH range studied, and is fairly inactive. Penetration was 

 believed to be the important factor, inasmuch as no differences in reactivity 

 of the arsenicals with thiols can be observed when the pH is altered. Eagle 

 made some ingenious calculations to support this concept. The total activity 

 at pH 8 was assumed to be due to the ionic species, and then the activity 

 to be expected at pH 6 was calculated on this basis and compared with the 

 observed activity at pH 6 (Table 6-17). If the assumptions made are valid, 

 one can estimate the contributions made by either the acid or ionic form 

 at pH 6 for each arsenical. The agreement is satisfactory, considering the 

 various complicating factors, such as preferential binding of the acid form 



