Interaction of heterocyclic thiols/thiones eliminated from cephalosporins with iodine and its biological implications

Abstract

Hydrolysis of β-lactam antibiotics by β-lactamases (e.g., metallo-β-lactamase, mβl) is one of the major bacterial defense systems. These enzymes can catalyze the hydrolysis of a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. It is shown in this paper that the thiol/thione moieties eliminated from certain cephalosporins by mβl-mediated hydrolysis readily react with molecular iodine to produce ionic compounds having S-I bonds. While the reaction of MTT with iodine produced the corresponding disulfide, MDT and DMETT produced the charge-transfer complexes MDT-I₂ and DMETT-I₂, respectively. Addition of two equivalents of I₂ to MDT produced a novel cationic complex having an almost linear S-I⁺-S moiety and I^-₅ counter anion. However, this reaction appears to be highly solvent dependent. When the reaction of MDT with I₂ was carried out in water, the reaction produced a monocation having I^-₅, indicating the reactivity of MDT toward I₂ is very similar to that of the most commonly used antithyroid drug methimazole (MMI). In contrast to MMI, MDT and DMETT, the triazine-based compound MTDT acts as a weak donor toward iodine.