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. Author manuscript; available in PMC: 2019 Sep 26.
Published in final edited form as: Adv Funct Mater. 2018 Jan 19;28(11):1706046. doi: 10.1002/adfm.201706046

Table 1.

Bio-orthogonal chemistries to crosslink hydrogels.

Gelation Chemistry Reactive Group #1 Reactive Group #2 Reaction Product Notes References
Copper-catalyzed azide-alkyne cycloaddition (CuAAC) graphic file with name nihms-1513042-t0010.jpg graphic file with name nihms-1513042-t0011.jpg graphic file with name nihms-1513042-t0012.jpg Potential Cu2+ toxicity may necessitate use of chelating ligands [24]

graphic file with name nihms-1513042-t0013.jpg graphic file with name nihms-1513042-t0014.jpg graphic file with name nihms-1513042-t0015.jpg X: H (Slow reaction kinetics) X: F (Improved kinetics) [25, 2730, 123, 124]
Strain-promoted azide-alkyne cycloaddition (SPAAC) graphic file with name nihms-1513042-t0016.jpg graphic file with name nihms-1513042-t0017.jpg graphic file with name nihms-1513042-t0018.jpg [3133]
graphic file with name nihms-1513042-t0019.jpg graphic file with name nihms-1513042-t0020.jpg graphic file with name nihms-1513042-t0021.jpg [3437, 162]

Inverse electron demand Diels-Alder (IED-DA) graphic file with name nihms-1513042-t0022.jpg graphic file with name nihms-1513042-t0023.jpg graphic file with name nihms-1513042-t0024.jpg [5154, 132]
graphic file with name nihms-1513042-t0025.jpg graphic file with name nihms-1513042-t0026.jpg graphic file with name nihms-1513042-t0027.jpg Extremely rapid gelation kinetics [56]

Diels-Alder (DA) graphic file with name nihms-1513042-t0028.jpg graphic file with name nihms-1513042-t0029.jpg graphic file with name nihms-1513042-t0030.jpg Maleimides can cross-react with thiols [5868, 70, 71]
graphic file with name nihms-1513042-t0031.jpg graphic file with name nihms-1513042-t0032.jpg graphic file with name nihms-1513042-t0033.jpg Reversible under physiological conditions [74]
Staudinger ligation graphic file with name nihms-1513042-t0034.jpg graphic file with name nihms-1513042-t0035.jpg graphic file with name nihms-1513042-t0036.jpg Slow reaction kinetics [35, 75, 76]

Nitrile Oxide Cycloaddition graphic file with name nihms-1513042-t0037.jpg graphic file with name nihms-1513042-t0038.jpg graphic file with name nihms-1513042-t0039.jpg Highly reactive nitrile oxide must be generated in situ [78, 79]