Structural landscape of multicomponent solids based on sulfa drugs

Abstract

Our attempts to cocrystallize three sulfa drugs (SDs), viz., sulfamerazine (smr), sulfamethazine (smz) and sulfamethoxazole (smx) with four coformers, viz., niflumic acid and flufenamic acid, 4-aminopyridine and piperazine led to eight new solids. Although the molecular structures of smr, smx and smz are comparable, their propensities to form multiple solid forms with the four selected coformers were found to be different. smr and smx reacted with 4-aminopyridine and piperazine yielding four salts while its reaction with niflumic and flufenamic acids resulted in the precipitation of only the reactants. In contrast, smz formed cocrystals with niflumic and flufenamic acids and salts with 4-aminopyridine and piperazine. To understand this discrepancy, we investigated the structural chemistry of these solids by analysing the interactions of key synthons present in the single component SDs as well as those reported in the literature. The study reveals that recognition of the nature of key synthons occurring in single component SDs and the ability to break and form new synthons with coformers can be a viable strategy to design multicomponent solids based on sulfa drugs.