Orthogonal, metal-free surface modification by strain-promoted azide–alkyne and nitrile oxide–alkene/alkyne cycloadditions

Abstract

In this article we present a fast and efficient methodology for biochemical surface patterning under extremely mild conditions. Micropatterned azide/benzaldoxime-surfaces were prepared by microcontact printing of a heterobifunctional cyclooctyne oxime linker on azide-terminated self-assembled monolayers (SAMs). Strain-promoted azide–alkyne cycloaddition (SPAAC) in combination with microcontact printing allows fast and effective surface patterning. The resulting bifunctional azide/oxime substrates could successfully be used for metal-free, orthogonal immobilization of various biomolecules by 1,3-dipolar cycloadditions at room temperature. Azide-decorated areas were modified by reaction with a cyclooctyne-conjugate using SPAAC, while benzaldoxime-decorated areas were activated by in situ oxidation to the reactive nitrile oxides and subsequent nitrile oxide cycloaddition with alkene- and alkyne-functionalized bioconjugates. In addition, orthogonal double immobilization was achieved by consecutive and independent SPAAC and nitrile oxide cycloadditions

Reactive self-assembled monolayers: from surface functionalization to gradient formation

“…66 In this work they demonstrated the orthogonality of SPAAC with other interfacial click reactions (e.g. 66 In this work they demonstrated the orthogonality of SPAAC with other interfacial click reactions (e.g.…”

Potassium Acyltrifluoroborate (KAT) Ligations are Orthogonal to Thiol‐Michael and SPAAC Reactions: Covalent Dual Immobilization of Proteins onto Synthetic PEG Hydrogels

“…Different, additional covalent bond formations are needed for immobilization of multiple proteins or peptides. This mandates that several bioorthogonal reactions – each with their own set of specific functional groups – be complementary to each other, exhibit no instability or cross‐reactions, and be individually addressable at a specific time intervals …”

Oxidative cyclizations of oximes using hypervalent iodine reagents

“…[17][18][19] In particular, the reaction of various aldoximes with alkynes in the presence of organohypervalent iodine(III) reagents such as DIB, 48,51,[54][55][56][57] BTI, 46,58,59 Koser's reagent, 49,60 or PhIO, 27,61 leads to oxidative heterocyclization yielding the corresponding isoxazoles. This procedure is applicable to various internal or terminal alkynes under mild condition.…”

“…46,54,60 The reactions of strained cyclic alkynes such as cyclooctyne derivatives with nitrile oxides generated from aldoximes and iodine(III) reagents are especially important in bioorthogonal chemistry. [55][56][57][58] For example, the reaction of lactose oxime with dibenzocyclooctyne derivatives using DIB gives the corresponding isoxazoles in good yields. 56 The obtained compound can be modified with the biotin tag, and can then be useful for an immobilization reaction to the surface of Streptavidin.…”