With the class of shock-absorbing proteins, nature created some of the most robust materials combining both mechanical strength and elasticity. Their excellent ability to dissipate energy to prevent surrounding cells from damage is an interesting property that regularly is exploited for applications in biomimetic materials. Similar to biomaterials, where mechanical stimuli are transmitted into a (bio)chemical response, mechanophoric catalysts transform mechanical energy into a chemical reaction. Force transmission is realized commonly by polymeric handles directing the applied force to the mechanophoric bond, which in turn leads to stress-induced activation of the catalyst. Therefore, shock-absorbing proteins able to take up and store mechanical energy elastically for subsequent force transduction to the labile bond seem to be perfect candidates to fulfill this task. Here, we report on the synthesis of two different latent mechanophoric copper(I) bis(N-heterocyclic carbene) complexes bearing either two carboxyl groups or two amino groups which allow conjugation reactions with either the N- or the C-terminus of amino acids or peptides. The chosen catalysts can be activated, for instance, by applying external mechanical force via ultrasound, removing one N-heterocyclic carbene (NHC) ligand. Post-modification of the mechanophoric catalysts via peptide coupling (Gly, Val) and first reactions showed that the mechanoresponsive behavior was still present after the coupling. Subsequent polycondensation of both catalysts lead to a polyamide including the Cu(I) moiety. Mechanochemical activation by ultrasound showed conversions in the copper(I)-catalyzed alkyne-azide “click” reaction (CuAAC) up to 9.9% proving the potential application for the time and spatial controlled CuAAC.

Abstract:The formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer's, Parkinson's or Huntington's disease. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process in vitro, where a sigmoidal growth phase follows an induction period. Here, we studied the fibrillation of amyloid β 1-40 (Aβ 40 ) in the presence of thermoresponsive polymers, expected to alter the Aβ 40 fibrillation kinetics due to their lower critical solution behavior. To probe the influence of molecular weight and the end groups of the polymer on its lower critical solution temperature (LCST), also considering its concentration dependence in the presence of buffer-salts needed for the aggregation studies of the amyloids, poly(oxazolines) (POx) with LCSTs ranging from 14.2-49.8˝C and poly(methoxy di(ethylene glycol)acrylates) with LCSTs ranging from 34.4-52.7˝C were synthesized. The two different polymers allowed the comparison of the influence of different molecular structures onto the fibrillation process. Mixtures of Aβ 40 with these polymers in varying concentrations were studied via time-dependent measurements of the thioflavin T (ThT) fluorescence. The studies revealed that amyloid fibrillation was accelerated in, accompanied by an extension of the lag phase of Aβ 40 fibrillation from 18.3 h in the absence to 19.3 h in the presence of the poly(methoxy di(ethylene glycol)acrylate) (3600 g/mol).

Elastin-like polypeptides (ELPs) are well known for their elastic and thermoresponsive behaviors. Their elasticity originates from the formation of a β-spiral which is the consequence of stacking type-II β-turns, formed from individual VPGVG pentapeptide units. Here, the synthesis of ELPs of varying chain lengths [VPGVG, (VPGVG) 2 , and (VPGVG) 4 ] and their coupling to a mechanoresponsive catalyst are reported. The attached ELP chains can act as "molecular springs," allowing for an efficient uptake and transmission of an applied force to the mechanophoric bond. This leads to stress-induced activation of the mechanophoric catalyst, in turn transforming mechanical energy into a "click" reaction. Secondary structure analysis via IR and CD spectroscopy revealed that the β-spiral formation of the ELP is not affected by the coupling process and the β-spiral is still intact in the mechanocatalyst after the coupling. Mechanochemical activation of the synthesized catalysts by an external applied force, studied via ultrasonication, showed conversions of the copper(I)-catalyzed alkyne-azide "click" reaction (CuAAC) up to 5.6% with an increasing chain length of the peptide, proving the potential to incorporate this chemistry into biomaterial engineering.

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