Molecular requirements for auxin action—I.

Abstract In order to obtain evidence for or against the concept that the biological activity of the indole auxins depends upon the fractional positive charge of the —NH group and its distance from the carboxyl group, two new indole compounds and their methyl and ethyl esters have been prepared. In these the intensity of the charge on the —NH would be predicted to be increased, while the auxin activity according to other theories should be decreased. Of these compounds, 2-chloro-indole-3-acetic acid has about 350 per cent of the activity of indoleacetic acid; the 2-bromo acid has 160 per cent activity, and the activities of the esters are even higher. Thus the activities of the 2-halogenated derivatives contrast strongly with that of the 2-methyl derivative, which has only 12 per cent of the activity ofindoleacetic acid. In a larger series of indole compounds with substituents on the benzene ring, the frequency of the i.r. solvent-bonded —NH stretching band in acetonitrile has been found to vary linearly with the Hammett sigma value for the substituent. The 2-halogenated derivatives agree perfectly with this behavior. Since σ measures the change in the tendency of an anion or proton to associate reversibly when a substituent is introduced, it is deduced that the —NH stretch frequency is a measure of the relative positive charge on the —NH group (other factors being equal). In standard auxin tests with the same compounds, using curvature of slit pea stems, it is shown that the log of the growth activity is also a roughly linear function of the solvent-bonded —NH stretch frequency and hence of σ, providing that gross steric effects and lipophilic properties of the compounds are not too different. The data are therefore all consistent with the theory stated above, and it is suggested that analogous considerations may hold for the biological activity of the indolealkylamines of the tryptamine and serotonin series.