Copper‐Free Clickable Coatings

Abstract

The copper‐catalyzed azide–alkyne 1,3‐dipolar cycloaddition (CuAAC) is extensively used for the functionalization of well‐defined polymeric materials. However, the necessity for copper, which is inherently toxic, limits the potential applications of these materials in the area of biology and biomedicine. Therefore, the first entirely copper‐free procedure for the synthesis of clickable coatings for the immobilization of functional molecules is reported. In the first step, azide‐functional coatings are prepared by thermal crosslinking of side‐chain azide‐functional polymers and dialkyne linkers. In a second step, three copper‐free click reactions (i.e., the Staudinger ligation, the dibenzocyclooctyne‐based strain‐promoted azide–alkyne [3+2] cycloaddition, and the methyl‐oxanorbornadiene‐based tandem cycloaddition−retro‐Diels−Alder (crDA) reaction) are used to functionalize the azide‐containing surfaces with fluorescent probes, allowing qualitative comparison with the traditional CuAAC.

A multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus

“…The divalent alkyne 7 [26] was prepared from ditosylate 6 by reaction with an excess of propargyl alcohol in the presence of potassium carbonate (Scheme 1). Compounds 9, [27] 11, [27] and 13 were prepared in one step from commercially available starting materials.…”

Efficient Synthesis of DNA Conjugates by Strain‐Promoted Azide–Cyclooctyne Cycloaddition in the Solid Phase

“…[17][18][19][20][21][22][23][24][25] Although azides have been the dipole of choice in most cases, more attractive kinetics have been observed with nitrile oxides. [26] Applications of strain-promoted conjugation are numerous and span diverse areas including bioimaging, [17,27,28] quantum dot formation, [29] peptide conjugation, [30] drug discovery, [18] drug delivery, [31] synthetic chemistry [23] and surface and materials science.…”

“…[26] Applications of strain-promoted conjugation are numerous and span diverse areas including bioimaging, [17,27,28] quantum dot formation, [29] peptide conjugation, [30] drug discovery, [18] drug delivery, [31] synthetic chemistry [23] and surface and materials science. [22,24] We have previously reported the postsynthetic modification of oligonucleotides by strain-promoted nitrile oxide cycloaddition chemistry (SPNOC), [8] and Filippov [32] and Manoharan [33] independently demonstrated conjugate formation by cycloaddition of azides to oligonucleotide cyclic alkynes. In their elegant studies, Filippov and Manoharan have concentrated on solution rather than solid phase conjugation.…”

Fast RNA conjugations on solid phase by strain-promoted cycloadditions

“…The reactivity of the first generation of monocyclic octynes have subsequently been ameliorated by incorporating a ring heteroatom, 24 electron withdrawing substituents, 20 or introducing further strain by fusing two aromatic rings to the (aza)cyclooctyne core, 25,26 SPAAC reactions have since found applications in bioimaging, 24,27 peptide conjugation, 28 drug delivery 29 and surface and materials science. 30,31 We have previously reported post-synthetic modification of DNA by strain-promoted cycloaddition of both azide and nitrile oxide dipoles to solid-supported DNA-cyclooctyne substrates. 32,33 Filippov et al, 34 and Manoharan et al, 35 have demonstrated azide-mediated oligonucleotide-dibenzocyclooctyne conjugation in solution phase, using the same methodology as that described for DNA-templated "click"-ligation demonstrated by Brown and El-Sagheer.…”