For the development of signal-responsive prodrugs, we envisioned the connection of tertiary amine therapeutics through quaternary ammonium salts by using nucleophilic substitution on electron deficient MBH-bromides (Figure ). Our group recently demonstrated that MBHacetates together with tertiary nitrogen nucleophiles form metastable, positively charged quaternary nitrogen adducts in buffered aqueous solution and outlined their potential for biomedical applications. To realize quaternary ammonium salt prodrugs, we designed a threestep synthesis route. We synthesized the clickable allyl bromide scaffold 1 through an MBH reaction between methyl acrylate and 4-azidobenzaldehyde and subsequent bromination of the product using phosphorous tribromide (see experimental details in Supplementary Information). Tertiary amine drugs 2-6 spontaneously react with 1 under ambient conditions, followed by precipitation in THF to give prodrug conjugates 8-12 in moderate to good yields (Figure ). We demonstrate the generality of the concept using a broad range of different therapeutics, including an anti-cancer drug (6), but also an antibiotic (3), muscle relaxant (4), anti-depressant (5) and an anesthetic (2) (Figure ).