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1. Advancing the Mechanosensitivity of Atropisomeric Diarylethene Mechanophores Through a Lever-Arm Effect

   https://doi.org/10.26434/chemrxiv-2024-smxcc-v2  

   Zhang, Cijun; Kouznetsova, Tatiana B; Zhu, Boyu; Sweeney, Liam; Lancer, Max; Gitsov, Ivan; Craig, Stephen L; Hu, Xiaoran (November 2024, Cambridge University Press)

   Understanding structure-mechanical activity relationships (SMARs) in polymer mechanochemistry is essential for the rational design of mechanophores with desired properties, yet SMARs in noncovalent mechanical transformations remain relatively underexplored. In this study, we designed a subset of diarylethene mechanophores based on a lever-arm hypothesis and systematically investigated their mechanical activity toward a noncovalent-yet-chemical conversion of atro-pisomer stereochemistry. Results from DFT calculations, single-molecule force spectroscopy (SMFS) measurements, and ultrasonication experiments collectively support the lever-arm hypothesis and confirm the exceptional sensitivity of chemo-mechanical coupling in these atropisomers. Notably, the transition force for the diarylethene M3 featuring extended 5-phenylbenzo[b]thiophene aryl groups is determined to be 131 pN ± 4 pN by SMFS. This value is lower than typically recorded for other mechanically induced chemical processes, highlighting its exceptional sensitivity to low-magnitude forces. This work contributes a fundamental understanding of chemo-mechanical coupling in atropisomeric configurational mechanophores and paves the way for designing highly sensitive mechanochemical processes that could facilitate the study of nanoscale mechanical behaviors across scientific disciplines. 

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2. The tension-activated carbon–carbon bond

   https://doi.org/10.1016/j.chempr.2024.05.012  

   Sun, Yunyan; Kevlishvili, Ilia; Kouznetsova, Tatiana B; Burke, Zach P; Craig, Stephen L; Kulik, Heather J; Moore, Jeffrey S (June 2024, Chem)

   Mechanical force drives distinct chemical reactions; yet, its vectoral nature results in complicated coupling with reaction trajectories. Here, we utilize a physical organic model inspired by the classical Morse potential and its differential forms to identify effective force constant (keff) and reaction energy (ΔE) as key molecular features that govern mechanochemical kinetics. Through a comprehensive experimental and computational investigation with four norborn-2-en-7-one (NEO) mechanophores, we establish the relationship between these features and the force-dependent energetic changes along the reaction pathways. We show that the complex kinetic behavior of the tensioned bonds is generally and quantitatively predicted by a simple multivariate linear regression based on the two easily computed features with a straightforward workflow. These results demonstrate a general mechanistic framework for mechanochemical reactions under tensile force and provide a highly accessible tool for the large-scale computational screening in the design of mechanophores. 

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3. Mechanical unfolding of ensemble biomolecular structures by shear force

   https://doi.org/10.1039/d1sc02257a  

   Hu, Changpeng; Jonchhe, Sagun; Pokhrel, Pravin; Karna, Deepak; Mao, Hanbin (August 2021, Chemical Science)

   Mechanical unfolding of biomolecular structures has been exclusively performed at the single-molecule level by single-molecule force spectroscopy (SMFS) techniques. Here we transformed sophisticated mechanical investigations on individual molecules into a simple platform suitable for molecular ensembles. By using shear flow inside a homogenizer tip, DNA secondary structures such as i-motifs are unfolded by shear force up to 50 pN at a 77 796 s −1 shear rate. We found that the larger the molecules, the higher the exerted shear forces. This shear force approach revealed affinity between ligands and i-motif structures. It also demonstrated a mechano-click reaction in which a Cu( i ) catalyzed azide–alkyne cycloaddition was modulated by shear force. We anticipate that this ensemble force spectroscopy method can investigate intra- and inter-molecular interactions with the throughput, accuracy, and robustness unparalleled to those of SMFS methods. 

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4. Generalized focused-ion-beam milling strategy to tune mechanical properties of AFM cantilevers for single-molecule force spectroscopy studies

   https://doi.org/10.1063/5.0257032  

   Hatchell, Christopher B; Jacobson, David R (June 2025, Review of Scientific Instruments)

   Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) enables the characterization of individual biological molecules through the application of mechanical force. The spatiotemporal resolution of such measurements depends greatly on the AFM cantilever that is used, specifically its stiffness, hydrodynamic drag, and material composition. Prior work has shown that focused ion beam (FIB) lithographic modification of small cantilevers can be used to lower the spring constant (and thus force noise) and drift while maintaining a relatively fast time response. Published methods for implementing such optimization rely on specific FIB instruments and cantilever types, limiting broad implementation of these methods to improve SMFS data quality. Here, we show that it is possible to achieve such optimized properties using generalized techniques applicable to a broader array of FIB instruments and starting from new types of cantilevers that are presently commercially available. Modified cantilevers exhibited a 90% reduction in spring constant, sub-pN force drift to tens of seconds, and a time response of ∼25 μs in the liquid environment relevant to biological measurements. 

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5. Molecular Machines from Topological Linkages

   https://doi.org/10.4230/LIPIcs.DNA.27.7  

   Breik, Keenan; Luchsinger, Austin; Soloveichik, David (July 2021, 27th International Conference on DNA Computing and Molecular Programming (DNA 27))

   Lakin, Matthew R.; Sulc, Petr (Ed.)

   Life is built upon amazingly sophisticated molecular machines whose behavior combines mechanical and chemical action. Engineering of similarly complex nanoscale devices from first principles remains an as yet unrealized goal of bioengineering. In this paper we formalize a simple model of mechanical motion (mechanical linkages) combined with chemical bonding. The model has a natural implementation using DNA with double-stranded rigid links, and single-stranded flexible joints and binding sites. Surprisingly, we show that much of the complex behavior is preserved in an idealized topological model which considers solely the graph connectivity of the linkages. We show a number of artifacts including Boolean logic, catalysts, a fueled motor, and chemo-mechanical coupling, all of which can be understood and reasoned about in the topological model. The variety of achieved behaviors supports the use of topological chemical linkages in understanding and engineering complex molecular behaviors. 

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