Solubilization and stabilization of the cytotoxic agent coralyne.

Kinetic studies were carried out on the ring opening of the quaternary nitrogen cation, coralynium ion (I), to yield 6'-acetylpapaverine (III), on the cyclization of III to yield I, and on a photochemical reaction undergone by I in aqueous solutions exposed to visible light. From the results, it was concluded that: (a) I and III are in facile equilibrium in aqueous solution but appreciable amounts of III do not exist in dilute solutions with pH values below 10: (b) the photochemical reaction of I in water (presumably a photohydration) can be reversed by lyophilization, by heatiing, and by increasing the pH of solutions to values greater than 12; (c) the photochemical reaction of I can be inhibited by protecting the aqueous solutions from visible light, and the rate in the presence of light can be reduced by increasing the concentration of I in the solution; and (d) although the chloride and sulfoacetate salts of I react identically and have similar solubilities in water, it is possible to prepare more concentrated and, hence, more stable solutions of the sulfoacetate salt by including sodium hydroxide in the solvent. The solubility of coralyne chloride remains about the same in dilute sodium hydroxide as in water.