INDUCED REACTIVATION OF INHIBITED ENZYMES 



631 



The most commonly used reactivators have been hydroxamates and aldox- 

 imes of iV-methylpyridine, such as iV-methyhiicotinohydroxamate and 

 iV-raethylpicolinohydroxamate, and especially pyridine-2-aldoxime methio- 

 dide (2-PAM), which has been found to reactivate inhibited cholinesterase 



/V 



CO-NHO- 



^N 



CH, 



/\ 



CH=NOH 



iV-Methylp5Tidine- 

 2-aldoxime 



CH3 



iV-Methylnicotino- 

 hydroxamate 



^N 



r 



X'O-NHO" 



CH, 



iV-Methylpicolino- 

 hydroxamate 



in the tissues of poisoned animals. However, the oximes and dioximes of 

 certain bis (pyridinium) compounds have been found to be much more po- 

 tent reactivators than 2-PAM (Hobbiger et al., 1958). The relationships be- 



X 



CH=NOH 



^N^ ^CH=NOH 



I 

 (CH,)„CH3 



iV-Alkylpyridine- 

 2-aldoximes 



iV-Alkylpyiidine- 

 4-aldoximes 



?" 



=NOH 



^N 



/ 



(CH,)„CH2Br 



iV-Bromoalkylpyridine- 

 4-aldoximes 



CH=NOH 



CH = NOH 



CH=NOH 



Bis (pjTidinium) oximes 



I (CH2)„ I 



Bis (pyridinium) dioximes 



tween structure and reactivating potency are very interesting. In the first 

 place, the presence of a positively charged group adjacent to the nucleo- 

 philic group enhances the activity. Comparison of the various reactivators 

 in their unsubstituted and iV-methyl forms shows that the latter are al- 

 ways more potent. The reactivation rate constant for pyridine-2-aldoxime 

 is 0.0045 min-i and for iV-methylpyridine-2-aldoxime it is 0.14 min"^ 

 (Wilson et al, 1958). In addition, the 2-PAM is bound more tightly to the 



