Surface Functionalization by Strain‐Promoted Alkyne–Azide Click Reactions

Abstract

alkynes · azides · click chemistry · surface chemistry · surface functionalizationFunctionalization of surfaces becomes increasingly important given the ever-decreasing size of active devices and the concomitant increase in surface-to-volume ratios. As a result, efficient routes for such functionalizations through the attachment of functional monolayers or multilayers have become the focus of much research in the last decade, both for hard (typically inorganic) and soft (polymeric, dendritic) surfaces. Specific features of desirable surface modification techniques include the combination of high efficiency with mild, noncorrosive reaction conditions. This approach avoids workup to remove (surface-bound) by-products or excess reactants, which typically is not trivial or is practically impossible. Therefore click reactions, such as the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) with surfacebound alkynes or azides, [1] have been used to functionalize a wide range of surfaces.However, the presence of Cu I can be problematic: Cu ions are cytotoxic, disrupt double-stranded DNA, alter the structure of "protein-repelling" ethylene oxide moieties, and can change the intrinsic functional properties of the surfaces, such as the through-monolayer conductivity on semiconductor surfaces and the fluorescence of quantum dots. As a result, alternative approaches have been developed over the last five years, including metal-free ligation chemistry that either requires no further activation (e.g., N-hydroxysuccinimidebased amide formations) [2] or employs activated but traceless chemistry (e.g., photoinduced thiol-ene addition reactions). [3] Recently, several examples have been published that aim to combine traceless reactions with room-temperature conditions through the application of strain-promoted alkyneazide cycloadditions (SPAAC or Huisgen-Bertozzi-type cycloadditions) [4] to surfaces. This Highlight focuses on four such reactions and discusses the current state of affairs and goals for the years to come.Boons and co-workers modified the surface of organomicelles that were constructed from tailor-made block copolymers.[5] When amphiphilic copolymers of poly(ethylene oxide) and poly(e-caprolactone) were appended with amino groups, the resulting species could be treated with a dibenzocyclooctyne derivative that was functionalized with an activated ester (Figure 1 a). This approach led to the formation of micelles with a cyclooctyne-containing surface (Figure 1 b), which could be readily reacted with a range of azides, including fluorescent dyes, peptides, and azide-linked mannosides. The latter products bound specifically to surfaces onto which concanavalin A had been deposited. Similarly functionalized micelles could potentially also be used for drug delivery, and initial steps were made to demonstrate this potential.Quantum dots (QDs) are an attractive tool in fluorescence imaging techniques. Functionalization of QD surfaces has been carried out using a metal-free click reaction reported by Texier et al.[6] C...

“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.…”

Highly accelerated inverse electron-demand cycloaddition of electron-deficient azides with aliphatic cyclooctynes

“…The high mutual reactivity of reaction components, yet (relative) inertness for a large repertoire of other molecular functionalities, explains the fast-growing popularity of strainpromoted cycloadditions for application in material sciences 2 , surface functionalization 3 , bioconjugation 4 , chemical biology and even in vivo use (known as bioorthogonal chemistry) 5,6 .…”

Click Chemistry Plays a Dual Role in Biodegradable Polymer Design

“…As one of the most effective, site-specific reactions that are tolerant to water, oxygen, and a wide range of functionalities, azide-alkyne cycloaddition (AAC, click chemistry), [14, 16–25] especially copper-free click chemistry, has been a promising method for functionalizing bio-related systems. [14, 22, 23] It was also reported that the triazole rings resulting from click chemistry could imitate amide bonds serving as mechanical strength improving moieties. [20, 26] Herein, click chemistry was introduced into CABEs to serve a dual role and create a novel material chemistry design strategy to simultaneously improve the bulk material mechanical strength and enable easy surface site-specific biofunctionalization, which can also be broadly applied to other functional biodegradable polymer design…”