Emerging Bio-relevant Applications of Polymer Mechanochemistry

Polymer mechanochemistry has rapidly evolved since the mid-20o0s.Recent advancements highlight the development of mechanophore platforms for the controlled release of bioactive payloads and the exploration of biocompatible activation strategies.These platforms,ranging from furan-maleimide Diels-Alder adducts to disulfide motifs withβ-carbonate linkages,demonstrate promising prospects in targeted drug delivery.Additionally,supramolecular assemblies and free radical-generating mechanophores present innovative avenues for potential therapeutic applications.Biocompatible activation methods,notably high-intensity and/or low-intensity focused ultrasound,hold potential for in vivo applications.However,challenges persist in comprehending the fundamental physics of ultrasound and its utilization for activation.

High-Intensity Focused Ultrasound-Induced Disulfide Mechanophore Activation in Polymeric Nanostructures for Molecule Release

Ultrasound(US)activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule release.However,the typical US frequency used for mechanochemistry is around 20 kHz,producing inertial cavitation that exceeds the tolerance threshold of biological systems.Here,high-intensity focused US(HIFU)as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperbranched star polymers(HBSPs)and microgels(MGLs).The mechanism of molecular release is attributed to the thiol-disulfide exchange reaction and subsequent intramolecular cyclization.We reveal that HBSPs and MGLs effectively transduce HIFU as mechanical input to chemical output,demonstrated by the quantification of the release of fluorescent umbelliferone(UMB).Moreover,an in vitro study of drug release is carried out using camptothecin as the model drug,which is covalently loaded in MGLs,demonstrating the potential of our system for controlled drug delivery to cancer cells.

Polymer Mechanochemistry on Reactive Species Generated from Mechanochemical Reactions

Comprehensive Summary Polymer mechanochemistry on reactive species has attracted more and more attentions over the past 20 years,as the mechanochemical generation of reactive species has a great potential in developing different polymeric materials for various purposes,such as stress detection,self-healing,self-strengthening,controllable degradation and release of small molecules.In this review,we first discuss the recent progress on polymer mechanochemistry of the reactive species that are generated from the mechanochemical reactions of mechanophores.Five types of reactive species,including radical,zwitterion,ionic,carbene and neutral intermediates,and their applications were reviewed in detail.Since mechanochemical reactions are sensitive to the mechanophore structure and polymer framework,we then discuss how mechanophore isomerism,polymer structure,polymer attachment point,and polymer architecture influence the mechanophore activation.At last,we provide our perspectives on the polymer mechanochemistry of reactivespecies.

A Versatile BenzimidazoleSubstituted Spirolactam Mechanophore:When Excited State Intramolecular Proton Transfer Couples with Rhodamine

Exploration of multicolor mechanochromic bulk polymers based on a single mechanophore is a big challenge to date.Herein,we report a versatile benzimidazole-substituted spirolactam mechanophore where excited state intramolecular proton transfer(ESIPT)coupled with rhodamine.The mechanophore was facilely synthesized and then covalently linked to polyurethane(PU)chains.The PU film containing the mechanophore(1@PU)showed cooperative photochromism upon irradiation involving simultaneous enhancement of normalized enol and rhodol emissions based on a cooperative ESIPT process and the ring-opening reaction of spirolactam.Moreover,the film exhibited dual-mode multicolor mechanochromism upon stretching and compression.The normalized intensity of enol emission increased and the fluorescence turned from light green to cyan after stretching,then red coloration appeared from colorless after compressing.Control experiments and density functional theory calculations confirmed that the stretch-induced increase of enol emission was attributed to torsion of the dihedral angle between xanthene and benzimidazole in the mechanophore via force-induced disaggregation and direct force action on the isolated mechanophore.Torsion of the dihedral angle and the ring-opening reaction of spirolactam in a single mechanophore occurred sequentially during compression,resulting in an observed red coloration.This study might provide a glimpse into the design of novel multicolor mechanochromic mechanophores.

Force-Triggered Guest Release from Mechanophore Incorporated Rotaxanes

We have developed a rotaxane-based mechanophore system that is capable of breaking a mechanical bond and releasing small molecules via force-triggered rotaxane disassembly.In this design,a cyclobutane mechanophore was fused to the ring component of a rotaxane,constructed through a template-mediated synthesis in high yields.Upon opening the ring component,the rotaxane disassembled to release the axle molecule.We successfully demonstrated and quantified the force-triggered release of the axlemolecule in both solution and solid-state samples.

Single-molecule observation of mechanical isomerization of spirothiopyran and subsequent Click addition

Spirothiopyran(STP)is particularly attractive when used as a mechanophore to endow polymers with both damage-signaling and.self-reinforcing capacity.It is,however,not clear the actual force required to induce the cycloreversion of STP into ring-opened thiomerocyanine(TMC),which reacts spontaneously with activated C=C bonds.Here,we used atomic force microscopy(AFM)-based single molecule force spectroscopy(SMFS)to study the mechanochemistry of STP mechanophore.It is found that the ring-opening of STP at room temperature requires forces of-200-400 pN,depending on the pulling speed.In addition,the reversibility of STP to TMC isomerization is demonstrated.Finally,mechanochemically induced intermolecular Click addition is achieved in single'molecule level by pulling STP in the presence of maleimide.

Rhodamine Mechanophore Functionalized Mechanochromic Double Network Hydrogels with High Sensitivity to Stress

Mechanochromic hydrogels, a new class of stimuli-responsive soft materials, have potential applications in a number of fields such as damage reporting and stress/strain sensing. We prepared a novel mechanochromic hydrogel using a strategy that has been developed to prepare dual-network(DN) hydrogels. A hydrophobic rhodamine derivative(Rh mechanophore) was covalently incorporated into a first network as a cross-linker. This first network embedded with Rh mechanophore within the DN hydrogel was pre-stretched. This guaranteed that the stress could be transferred extensively to the Rh-crosslinked first network once the hydrogel was under an applied force. Interestingly, we found that the threshold stress required to activate the mechanochromism of the hydrogel was less than 200 kPa, and much less than those in previous reports. Moreover, because of the excellent sensitivity of the hydrogel to stress, the DN hydrogel exhibited reversible freezing-induced mechanochromism. Benefiting from the sensitivity of Rh mechanophore to both p H and force, the DN hydrogel showed p H-regulated mechanochromic behavior. Our experimental results indicate that the preparation strategy we used introduces sensitive mechanochromism into the hydrogel and preserves the advantageous mechanical properties of the DN hydrogel. These results will be beneficial to the design and preparation of mechanochromic hydrogels with high stress sensitivity, and foster their practical applications in a number of fields such as damage reporting and stress/strain sensing.

Mechanophore activation enhanced by hydrogen bonding of diarylurea motifs:An efficient supramolecular force-transducing system

Macromolecules are efficient as mechanical transducers for mechanically induced chemical bond cleavage reactions.Although various classes of polymers have been studied as effective mechanical-force transducers for mechanophores,alternatives to polymer chains,that is,small molecules,have rarely been studied.In this paper,the role of hydrogen bonding as small-molecule mechanical-force transducers for the activation of mechano-responsive molecular units(mechanophores)in the bulk is investigated.The introduction of diarylurea linkage motifs,which are known as strong hydrogen bonding groups,enhances the mechanochemical activation of the fluorescent mechanophore tetraarylsuccinonitrile(TASN)as effectively as the attachment of a typical macromolecular transducer.Electron paramagnetic resonance measurements of mechanically activated TASN with diphenyl urea motifs demonstrate its higher carbon–carbon bond dissociation ratio compared to that of TASN without diphenyl urea motifs.This efficient supramolecular-forcetransducing system represents a new concept in the field of mechanochemistry,namely,the enhancement of mechanochemical bond scission by simply changing the substituents of a mechanophore,even in small molecules.

A mechanochemical two for one:Mechanical activation of norborn-2-en-7-one releases carbon monoxide and switches on aggregation-induced emission

Mechanical forces are typically considered to be destructive in polymeric materials,leading to degradation via nonspecific chain scission.However,the emergence of the mechanophore hypothesis has enabled the design of polymers that are able to harness these typically destructive forces and convert them into productive chemical transformations.