Sodium Colistimethate I: Dissociations of Aminomethanesulfonates in Aqueous Solution

Abstract

Neutral solutions of aminomethanesulfonates are largely dissociated into hydroxymethylamino compounds and sulfite (and bisulfite) ions. Identical solutions are formed either by dissolving pure crystalline aminomethanesulfonic acids or by combining the amine, formaldehyde, and sulfite at appropriate pH. Solutions of aminomethanesulfonates can react with an additional molecule of formaldehyde bisulfite to give a disubstituted amine, which in turn dissociates to give more sulfite ion. Neutral solutions of sodium colistimethate comprise complex equilibria in which individual molecules are substituted by varying numbers of meth-anesulfonate or hydroxymethyl groups, possibly as many as 10, but with three or four of these species more highly favored than the rest (possibly for steric as well as statistical reasons). When more than three molecules each of formaldehyde and sulfite are available for reaction with colistin, no evidence for the existence of free colistin is found. Furthermore, the likelihood for the simultaneous existence of five unreacted amino groups in one molecule is very small.