Paul H. Bell

CHEMICAL STUDIES ON POLYMYXIN: COMPARISON WITH “AEROSPORIN”*

This paper is a preliminary report on the chemistry of polymyxint and its degradation products. “Aero~porin”~ has been compared with particular samples of polymyxinz* a t a number of points of this study and the results of this comparison are included. The first of these is the study of the homogeneity of these samples of polymyxin. The second is the examination of the chemistry of polymyxin and the determination of its constituent parts. I n studying the purity of this chemotherapeutic agent, three problems arise immediately. 1s there more than one biologically active component? If so, can the mixture be separated? Having a material pure by bioassay, can chemically pure material be prepared? Affirmative answers can be returned to the first two questions, while the third must be left unanswered for lack of information. polymyxin is in the form of a hydrochloride. It is a nearly colorless powder which assays, in Stamford units? about 1500 units per milligram and melts with decomposition a t 228-230°C. (varying with rate of heating and degree of hydration). It is very soluble (more than 40 per cent) in water and methanol, and the solubility decreases in higher alcohols. It is levorotatory (a:’ = -40” (C = 1.05 in water)). It is insoluble in ethers, esters, ketones, hydrocarbons, and the chlorinated solvents. The birefringent base may be precipitated from concentrated aqueous solutions of the hydrochloride by saturation with ammonia. This form is slightly soluble in water and almost insoluble in alcohol, and decomposes at a higher temperature and over a range. The material forms water-insoluble salts with a number of precipitants such as picnc acid, helianthic acid, Reinecke salt, and the like. None of these was of a nature to permit their purification by conventional fractionation procedures such as crystallization or precipitation and, except for certain analytical purposes, they were without value for a study of the purity of the material. It was found that the material was distributed between water and those The work is divided into two main phases.

New Drug Leads from Enzyme Studies

with new knowledge in biochemistry. Research workers in the university laboratories are making important discoveries, but, more often than not, it falls to the biochemists in the pharmaceutical laboratory to develop these facts in such a manner that useful drugs result. Many times in the past it has been the highly motivated scientists in an industrial research group who, in their search for drugs, have forged ahead to determine the structure of a