Salts of the anti-HIV drug lamivudine with phthalic and salicylic acids

Abstract

Salts of the anti-HIV drug lamivudine, with phthalic acid and salicylic acid as counterions, were investigated in this study. Neither the packing of the (lamivudine)+(phthalic acid)− ion pairs nor the conformation of the lamivudine moiety itself were similar to those found in other multicomponent molecular salts of the drug, such as hydrogen maleate and saccharinate ones, even though all three salts crystallize in the same P212121 orthorhombic space group with similar unit cell metrics. Lamivudine salicylate assumes a different crystal structure to those of the hydrogen maleate and saccharinate salts, crystallizing in the P21 monoclinic space group as a monohydrate whose (lamivudine)+(salicylic acid)− ion pair is assembled through two hydrogen bonds with cytosine as a dual donor to both oxygens of the carboxylate, such as in the pairing of lamivudine with a phthalic acid counterion. In lamivudine salicylate monohydrate, the drug conformation is related to the hydrogen maleate and saccharinate salts. However, such a conformational similarity is not related to the intermolecular interaction patterns. Lamivudine and water molecules alternate into helical chains in the salicylate salt monohydrate.