Radiolabeled quaternary carbapenems and their interactions with human serum albumin

A simple method is described for labeling carbapenems with [14C]dimethyl sulfate. Reverse-phase high-performance liquid chromatography of the reaction was used to purify the product. Carbapenems with 2-substituents containing pyrid-3-yl and -4-yl moieties could be labeled by this method, but those containing a pyrid-2-yl group could not. Nonreversible binding of these labeled carbapenems to human serum albumin was investigated. Pyridinium-3-yl compounds displayed low binding rates (0.028 to 0.044%/h), whereas three of four pyridinium-4-yl compounds bound much faster (0.38 to 0.62%/h). It is postulated that these differences are related to the ability of the compound to stabilize a deprotonated form transiently.