KENNETH V. THIMANN 27 



sorption to some reactive surface, a property essential for activity but 

 of course not sufficient by itself. Such a view agrees with the concept of 

 a coenzyme or similar function discussed above. It should, however, be 

 pointed out that A--cyclohexeneacetic acid (XIX) Is inactive, (compare 

 the activity of XVI) from which it seems that the double bond must 

 be adjacent to the side chain (3,17), as indeed it is in all the other active 

 substances. This would suggest that the adsorption to a surface may not 

 be as unspecific as it sounds and may require very definite configuration. 



The Side chain. — The acid group must be separated from the ring. 

 In the Avena test (with the indole ring) the one methylene group is 

 sharply optimal, but for primary activity the butyric acid with 3 

 methylene groups has about the same activity. The propionic and valeric 

 derivatives have definitely less activity in all tests, and this holds both 

 for indole and for naphthalene compounds. 



There are one or two cases of carboxyl groups attached directly to the 

 ring which must be considered. It was claimed that 2-bromo-3-nitro- 

 benzoic acid was active, but its action appears to rest on synergistic 

 effects rather than true primary activity. Veldstra and van de Westering 

 (.14) have kindly made available their studies on the naphthoic acids; 



.COOH 



COOH r"C 



COOH ^/^ /CH 



,CH, 



Hj 



XX XXI XXE 



the a-acid (XX) apparently has real but sUght activity, while the /3-acid 



(XXI) is inactive. However, hydrogenation of the substituted ring 



(XXII) increases the activity 5-10 times. It may be pointed out that in 

 these compounds the COOH is attached to one ring but may be con- 

 sidered separated from the other, that is, the compounds may be thought 

 of as derivatives of phenylacetic acid. This is particularly true when the 

 ring is hydrogenated. It is significant that the 5,6,7,8-tetrahydro- 

 derivative has very Httle if any activity, and this compound is of course 

 analogous to cyclohexane-i -acetic acid. The activity of naphthoic acid 



will be referred to again below. 



YYTTT 



