Thiol–Maleimide Michael Addition Click Reaction: A New Route to Surface Modification of Porous Polymeric Monolith

A new and efficient approach based on the thiol–maleimide Michael addition click reaction is presented for the post‐polymerization modification of porous monoliths. To establish the method, a generic matrix containing N‐hydroxysuccinimide esters (NHS) as surface reactive units is synthesized inside a capillary column through photoinduced polymerization of N‐acryloxysuccininimide and ethylene glycol dimethylacrylate. The as‐obtained reactive monolith is further surface‐functionalized through nucleophilic substitution of the NHS units with 2‐aminoethanethiol. Following such an approach, free thiols are available for reacting with functional maleimides through Michael addition. Success of the successive molecular level surface functionalization steps is ascertained by Raman spectroscopy measurements. Of utmost importance, it is undoubtedly demonstrated that the chemical nature, i.e., hydrophilic versus hydrophobic, of the surface‐grafted maleimide governs the surface properties of the corresponding monoliths. More precisely, the electrochromatographic separation mode is found to be intimately correlated to the chemical nature—C8‐like versus COOH‐like—of the maleimide‐functionalized monolith allowing separation upon either reversed‐phase or hydrophilic interaction modes, respectively. Furthermore, the strategy is extended to enhancement of surface NHS reactivity enabling the efficient grafting of model biomacromolecule via a spacer arm‐driven effect.