Orthogonal click reactions enable the synthesis of ECM-mimetic PEG hydrogels without multi-arm precursors

Expanding the thiol–X toolbox: photoinitiation and materials application of the acid-catalyzed thiol–ene (ACT) reaction

“…27 The thiol-ene reaction follows a radical-mediated mechanism between a thiol and an electron-rich alkene, such as a vinyl, allyl, or norbornenyl functional group, whereas the thiol-Michael reaction follows an anion-mediated mechanism between a thiol and an electron deficient alkene, such as an acrylate, vinyl sulfone, or maleimide functional group (Scheme 1A and B, respectively). The self-limited, 1-to-1 reactivity combined with distinct mechanisms enables a sequential thiol-ene and thiol-Michael reaction scheme, which has been applied in the design of iterative peptide conjugations 28 and sequence-defined polymers. 29 A unique mechanistic pathway distinct from the thiol-ene and thiol-Michael reactions is the cation-mediated reaction between a thiol and a vinyl to produce S,X-acetals in the presence of dilute acid, 30,31 referred to here as the acid-catalyzed thiol-ene (ACT) reaction.…”

3D Patterning within Hydrogels for the Recreation of Functional Biological Environments

“…[ 186 ] Then, using a second photo‐aided click reaction, an alkene moiety presented in the polypeptide backbone was micropatterned with a thiol‐functionalised RGD sequence, signaling spreading of encapsulated fibroblasts. [ 92 ] Similarly, other bio‐molecules such as vascular endothelial growth factor [ 187 ] and ovalbumin [ 188 ] have been patterned in PEG hydrogels into overlapped squares, [ 186 ] stripes, [ 189 ] or more complex shapes [ 92 ] with the use of a photomask (Figure 6B). The technique facilitates control of pattern depth by modulating the focal point of a pulsed laser light with a multiphoton technique (e.g., confocal microscope).…”

Orthogonal synthesis and modification of polymer materials

“…Certain hydrogels, that is, crosslinked hydrophilic polymers, are well‐known to closely resemble natural tissue synthetically 49,50 . One of the most elaborate examples of this was reported by Jivan et al who prepared extracellular‐matrix mimetic hydrogels utilizing two orthogonal click reactions, namely the thiol–maleimide Michael addition and thiol–norborene click reactions 51 . First, the copolymer, misreferred to as a block copolymer in the report, was prepared via the thiol–maleimide Michael addition reaction and step growth polymerization between PEG‐bismaleimide and various di‐cysteine containing peptides (Figure 3).…”