124 Alexander Hollaender and George E. Stapleton 



2. Different groups may be added to the sulphur, provided 

 that their form is such that they do not unbalance the molecule. 



3. The NHg group must be left free; otherwise, the toxicity 

 increases or the protective ability is drastically reduced. 



4. The compound (AET) is stable at pH 3 and can be 

 hydrolysed only at pH's in excess of 8 with amino alkyl 

 mercaptans and dicyandiamide as the breakdown products. 



5. Compounds found to be protective give a positive 

 -SH test at pH 7*5. Doherty's explanation for this is that 

 AET exists in multiple forms, and equilibria among these 

 forms can be changed by modifying the pH. Some of the 

 different stages that AET goes through are shown in Fig. 3. 



CHg CHj CHj CH^ CHp CHp 



I I 0H~ I I 0H~ I I 



^"2 /S ^^ HN^ ^S ^=^ HN^ SH 



O \ l> c 



CHo — CHp 

 I I 



d 



Fig, 3. Multiple equilibrium structures of AET. 



6. All compounds that are active in protecting mice appear 

 to be able to form a h type ring structure (Fig. 3) in solution 

 at a neutral pH similar to a thiazoline ring. 



7. A solution of AET appears to be a mixture of different 

 types of isomers, whose forms are very similar to coenzyme A 

 (Bashford and Huennekins, 1955) and glutathione (Calvin, 

 1954), which are known to exist in several isomeric forms. 



Unfortunately, AET is not one of the best compounds for 

 protecting 'Esch. coli but it is considerably more successful than 

 cysteamine in protecting mice. It almost doubles the LD50 

 and is now used routinely in our laboratory for protection 

 studies with mice. 



From experiments- on bacterial cells, we are just beginning 



