The influence of structure on the orientation of the veratrum alkaloids at the air/water interface

Abstract

The veratrum alkaloids—veracevine, veratridine, cevadine, and veratramine—have similar chemical structures yet are quite distinct in their pharmacological actions. Veracevine is inactive, veratridine and cevadine are “labilizers” or “unstabilizers”, and veratramine is an antagonist for cevadine and veratridine. The properties of these compounds at the air/water interface also reveal marked differences. Surface tension measurements in water show surface activity decreases in the order veratramine > veratridine > cevadine ⪢ veracevine. A Langmuir-type film balance was used to measure their F-A curves. Films of the alkaloids were unstable because of their slight solubility in the substrate, and a technique was devised which permits reproducible F-A measurements. Despite these precautions, veracevine did not form any films. The F-A curves for veratridine and cevadine show (a) an inflection which corresponds to their areas when oriented horizontally at the a/w interface, and (b) an area in which the molecules are tight-packed corresponding to molecular areas for the vertical orientation of the molecules. Veratramine shows no inflection in the F-A curve, but the tight-packed film occurs at an area in which this molecule is oriented almost horizontal to the a/w interface. Interpretation of these results is in terms of the distribution of hydrophobic and hydrophilic groups on the molecules; their implication for pharmacological action is discussed.