Metal‐Free Click Chemistry Reactions on Surfaces

Abstract

In the last decade, interest in the functionalization of surfaces and materials has increased dramatically. In this regard, click chemistry deserves a central focus because of its mild reaction conditions, high efficiency, and easy post‐treatment. Among such novel click reactions, those that do not require any metal catalyst are of special interest, as metals may have undesirable effects in many fields. In this Review, the backgrounds and application of such metal‐free click reactions for the modification of surfaces are highlighted.

“Shine & Click” Photo‐Induced Interfacial Unmasking of Strained Alkynes on Small Water‐Soluble Gold Nanoparticles

“…[3] Since its discovery,t he SPAAC reaction has been used for the synthesis and/or modification of many materials, including dendrons and dendrimers, [4] topological polymers, [5] organo-micellesa nd liposomes, [6,7] micro-and nanoparticles, [8][9][10][11][12] as well as other materials urfaces. [13][14][15][16] More recently,T sukruk and co-workers prepared branched polyhedral oligomeric silsesquioxane nanoparticles by the interfacial SPAAC reaction. [17] Yi and co-workers reportedc hitosan-poly(ethylene glycol) microparticles featuring azadibenzocyclooctynes (ADIBO) and their potential to undergo bioconjugation in the SPAAC reactionw ith azide-modified proteins and antibodies to afford biosensing platforms.…”

Site‐Specific Immobilization of the Peptidoglycan Synthase PBP1B on a Surface Plasmon Resonance Chip Surface

“…To address this, we have designed a new immobilization method, based on site‐specific labeling, that can be generally applied to any (membrane) protein. Many different bioorthogonal chemical reactions have been described to site‐specifically label proteins for surface immobilization . We chose to anchor PBP1B to a chip surface by site‐specific incorporation of an azide‐containing unnatural amino acid in the N‐terminal sequence of the protein (Figure ), followed by covalent attachment to immobilized dibenzylcyclooctyne by copper‐free click chemistry, as this reaction occurs spontaneously under physiological conditions and does not need metal catalysts, which can have undesirable effects on protein activity .…”

“…Many different bioorthogonal chemical reactions have been described to site‐specifically label proteins for surface immobilization . We chose to anchor PBP1B to a chip surface by site‐specific incorporation of an azide‐containing unnatural amino acid in the N‐terminal sequence of the protein (Figure ), followed by covalent attachment to immobilized dibenzylcyclooctyne by copper‐free click chemistry, as this reaction occurs spontaneously under physiological conditions and does not need metal catalysts, which can have undesirable effects on protein activity . Immobilization by this method yields the correct topological orientation of the protein with an accessible and unaltered TPase domain, thereby allowing characterization of interactions with this domain.…”

Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On‐Demand Release

“…Herein, we have employed isocyanate‐bearing ligands to synthesize a bifunctional ION platform with both maleimide and alkyne moieties (Figure ) that can undergo orthogonal reactions with thiols (thiol–ene and thiol–yne reactions), conjugated dienes (Diels–Alder cycloaddition), and azide functional groups (1,3‐dipolar azide–alkyne cycloaddition) . Due to limitations in the characterization and purification of IONs, click reactions constitute an ideal scenario for functionalization towards biomedical applications . We demonstrate the applicability of this platform by loading a fluorophore as a drug model through the Diels–Alder reaction, and reacting the alkyne moieties by azide–alkyne cycloaddition with a polyethylene glycol (PEG)‐bearing biotin ligand for targeting.…”