Evidence of Splitting 1,2,3‐Triazole into an Alkyne and Azide by Low Mechanical Force in the Presence of Other Covalent Bonds

Abstract

The cycloaddition reaction of an alkyne and azide to form a 1,2,3-triazole is widely used in many areas. However, the stability of the triazole moiety under mechanical stress is unclear. To see if a triazole could be selectively split into an alkyne and azide in the presence of other typical covalent bonds, a mica surface functionalized with a molecule containing a triazole moiety in the middle and an activated ester at the end was prepared. An atomic force microscope (AFM) tip with amino groups on its surface was ramped over the mica surface at predefined locations, which could temporarily link the tip to the surface through amide bond formation. During retraction, the triazole or another bond in the linkage broke, and a force was recorded. The forces varied widely at different ramps from close to 0 pN to 860 pN due to nonspecific adhesions and to the inherent inconsistency of single bond rupture. If some of the forces were from triazole cycloreversion, there would be alkynes at the predefined ramping locations. The surface was reacted with an azide carboxylic acid followed by labeling with amino Au nanoparticles (AuNPs). AFM imaging revealed AuNPs at the predicted locations, which provided evidence that under certain conditions triazole could be split selectively in the presence of other bonds at forces below 860 pN.

Validation of the CoGEF Method as a Predictive Tool for Polymer Mechanochemistry

“…75 In another AFM study, the mechanochemical cycloreversion reaction of the strain-promoted azide−alkyne cycloaddition product 37 was probed, which suggested that cycloreversion of the triazole was achieved at the single molecule level as deduced through a series of subsequent labeling experiments. 62 Nevertheless, the methods employed in the study did not permit conclusive chemical analysis of the reaction products. The CoGEF calculation for compound 37 predicts C−O bond scission in the tether and not the cycloreversion reaction, similar to the results of previous computational studies on this scaffold.…”

“…Experimentally, the cycloreversion reaction of a 1,5-disubstituted 1,2,3-triazole was investigated using atomic force microscopy (AFM) methods leading to inconclusive results . In another AFM study, the mechanochemical cycloreversion reaction of the strain-promoted azide–alkyne cycloaddition product 37 was probed, which suggested that cycloreversion of the triazole was achieved at the single molecule level as deduced through a series of subsequent labeling experiments . Nevertheless, the methods employed in the study did not permit conclusive chemical analysis of the reaction products.…”

Polymer mechanochemistry-enabled pericyclic reactions

“…Using these cyclooctyne-azide cycloadducts in single molecule force experiments using AFM, Fang, Shahbazian-Yassar and co-workers designed an on-surface reaction cascade that ligated cyclooctyne generated by the mechanochemically induced cycloelimination with gold nanoparticles (AuNPs) to confirm the local character of their experiments. 107 The force-induced cycloelimination of 1,4-disubstituted triazoles on unstrained alkynes appears to be an unlikely reaction. In simulations and experiments, the required forces to cleave the triazole ring in a shear mechanism were too high and led to undesired rupture events in the adjacent polymer chains.…”

Force-induced retro-click reaction of triazoles competes with adjacent single-bond rupture

“… 29 Experimentally, cycloreversion was observed for forces below 860 pN in an Atomic Force Microscope (AFM). 30 On the other hand, in another AFM study, it was not possible to determine reliably whether cycloreversion did indeed take place, but it was pointed out that forces in the nN regime would be needed. 31 As can be seen from such contradictory experimental and theoretical findings, the feasibility of mechanical cycloreversion of 1,2,3-triazoles is widely debated.…”