Bio-Regulatory Activity and Nitrogen Function in Organic Compounds.

1. General considerations on oxygen toxicity suggest an important role for antioxidants as protectants for the more labile cellular components, including proteins and DNA. 2. Low effective levels of protectants against experimental oxygen poisoning suggest radical chain-breaking (model: NO) or self-regenerating (model: Co²⁺-Co³⁺) properties for these compounds. 3. Consideration of the elements of common biological occurrence suggests N (and possibly S) compounds as potentially important antioxidants. It is suggested that the unshared electron pair of N(III) is of importance in the activity of organic N-compounds against oxidants or oxidizing radicals. 4. Several chemical oxidations and a variety of conditions have been used in demonstrating the antioxidant activity of IAA and a variety of indoles, hydrazines and other N-compounds. Test systems include pyrogallol - O₂, S⁼ - H₂O₂ and I^- - H₂O₂, especially the last. Reaction media range from acidic to alkaline and include both aqueous and ethanolic systems. 5. Among the indoles, antioxidant activity can be related to structure. Their ability to decrease the initial rate of I^- oxidation is reduced by: (a) substitution at the 3-position; (b) introduction of an electron-withdrawing group at the 2- or 3-position and (c) replacement of N with another atom or heteroatom. This kind of activity may be increased however by: (a) introduction of OH into the benzene ring and (b) by introduction of an electron-releasing agent at the 2-position. Activity is not affected by (a) substitution on N, or (b) 3-substitution with an ethylamine group. 6. Activity among other chemical groups has not yet been related to structure, but several biologically active compounds including thyroxin and isoniazid are powerful antioxidants. Even simple aliphatic amines, including a tertiary amine, exhibit weak inhibiting properties. 7. A number of the active compounds are known to have some kind of biological activity at comparatively low concentrations, including serotonin, 5-hydroxy-IAA, indole and EDTA. 8. Experiments carried out on germination and early seedling growth with turnip, rice and lettuce show isoniazid, hydrazine, indole-3-ethylamine, and skatole, all powerful antioxidants, to be growth promoters as well. 9. It is concluded that although definite "cause-effect" relationships between antioxidative and biological activities have not yet been proven, the wide-spread occurrence of antioxidants together with our current information on oxygen toxicity calls for serious consideration when mechanism of hormone and regulator actions are under consideration. [ABSTRACT FROM AUTHOR]