Maleimide and its derivatives are prepared from maleic anhydride by treatment with amines followed by dehydration. A special feature of the reactivity of maleimides is their susceptibility to additions across the double bond either by Michael additions or via Diels-Alder reactions. Bismaleimides are a class of compounds with two maleimide groups connected by the nitrogen atoms via a linker, and are used as crosslinking reagents in thermosetpolymer chemistry. Compounds containing a maleimide group linked with another reactive group, such as an activated N-hydroxysuccinimide ester, are called maleimide heterobifunctional reagents.
Maleimide-mediated methodologies are among the most used in bioconjugation. Due to exceptionally fast reaction rates and significantly high selectivity towards cysteine residues in proteins, a large variety of maleimide heterobifunctional reagents are used for the preparation of targeted therapeutics, assemblies for studying proteins in their biological context, protein-based microarrays, or proteins immobilisation. For instance, emerging promising targeted drug therapies, antibody-drug conjugates, are constituted of three main components: a monoclonal antibody, a cytotoxic drug, and a linker molecule often containing a maleimide group, which binds the drug and the antibody. Maleimides linked to polyethylene glycol chains are often used as flexible linking molecules to attach proteins to surfaces. The double bond readily reacts with the thiol group found on cysteine to form a stable carbon-sulfur bond. Attaching the other end of the polyethylene chain to a bead or solid support allows for easy separation of protein from other molecules in solution, provided these molecules do not also possess thiol groups. Maleimide-functionalised polymers and liposomes exhibit enhanced ability to adhere to mucosal surfaces due to the reactions with thiol-containing mucins. This could be applicable in the design of dosage forms for transmucosal drug delivery.
Technological applications
Mono- and bismaleimide-based polymers are used for high temperature applications up to 250 °C. Maleimides linked to rubber chains are often used as flexible linking molecules to reinforce the rubber. The double bond readily reacts with all hydroxy, amine or thiol groups found on the matrix to form a stable carbon-oxygen, carbon-nitrogen, or carbon-sulfur bond, respectively. Lockheed Martin's F-35B is reportedly composed of bismaleimide materials, in addition to the use of advanced carbon fiberthermoset polymer matrix composites.
