@article{20527, abstract = {Arising from C. Yang et al. Nature Chemistry https://doi.org/10.1038/s41557-023-01212-2 (2023) In this work Yang et al.1 claim that an enantioselective Michael addition reaction with a barrier of 16 kcal mol−1 occurs at the single-molecule level in frozen solvent by measuring fluctuations in current flowing across graphene-based molecular devices. The article, however, contains major scientific errors that undermine their conclusions. We highlight issues with the fabrication of the devices, a lack of characterization, discrepancies between theory and experiment, unreliable inelastic electron tunnelling spectra (IETS) and a perceived misinterpretation of noise as evidence of reaction.}, author = {Venkataraman, Latha and van Ruitenbeek, Jan}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {11}, pages = {1767--1769}, publisher = {Springer Nature}, title = {{Questioning claims of monitoring the Michael addition reaction at the single-molecule level}}, doi = {10.1038/s41557-024-01631-9}, volume = {16}, year = {2024}, } @article{21819, abstract = {The ability of molecular photoswitches to convert on/off responses into large macroscale property change is fundamental to light-responsive materials. However, moving beyond simple binary responses necessitates the introduction of new elements that control the chemistry of the photoswitching process at the molecular scale. To achieve this goal, we designed, synthesized and developed a single photochrome, based on a modified donor–acceptor Stenhouse adduct (DASA), capable of independently addressing multiple molecular states. The multi-stage photoswitch enables complex switching phenomena. To demonstrate this, we show spatial control of the transformation of a three-stage photoswitch by tuning the population of intermediates along the multi-step reaction pathway of the DASAs without interfering with either the first or final stage. This allows for a photonic three-stage logic gate where the secondary wavelength solely negates the input of the primary wavelength. These results provide a new strategy to move beyond traditional on/off binary photochromic systems and enable the design of future molecular logic systems.}, author = {Stricker, Friedrich J and Sanchez, David M. and Raucci, Umberto and Dolinski, Neil D. and Zayas, Manuel S. and Meisner, Jan and Hawker, Craig. J. and Martínez, Todd. J. and Read de Alaniz, Javier}, issn = {1755-4349}, journal = {Nature Chemistry}, pages = {942--948}, publisher = {Springer Nature}, title = {{A multi-stage single photochrome system for controlled photoswitching responses}}, doi = {10.1038/s41557-022-00947-8}, volume = {14}, year = {2022}, } @article{17871, abstract = {Single-molecule topological insulators are promising candidates as conducting wires over nanometre length scales. A key advantage is their ability to exhibit quasi-metallic transport, in contrast to conjugated molecular wires which typically exhibit a low conductance that decays as the wire length increases. Here, we study a family of oligophenylene-bridged bis(triarylamines) with tunable and stable mono- or di-radicaloid character. These wires can undergo one- and two-electron chemical oxidations to the corresponding mono-cation and di-cation, respectively. We show that the oxidized wires exhibit reversed conductance decay with increasing length, consistent with the expectation for Su–Schrieffer–Heeger-type one-dimensional topological insulators. The 2.6-nm-long di-cation reported here displays a conductance greater than 0.1G0, where G0 is the conductance quantum, a factor of 5,400 greater than the neutral form. The observed conductance–length relationship is similar between the mono-cation and di-cation series. Density functional theory calculations elucidate how the frontier orbitals and delocalization of radicals facilitate the observed non-classical quasi-metallic behaviour.}, author = {Li, Liang and Low, Jonathan Z. and Wilhelm, Jan and Liao, Guanming and Gunasekaran, Suman and Prindle, Claudia R. and Starr, Rachel L. and Golze, Dorothea and Nuckolls, Colin and Steigerwald, Michael L. and Evers, Ferdinand and Campos, Luis M. and Yin, Xiaodong and Venkataraman, Latha}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {9}, pages = {1061--1067}, publisher = {Springer Nature}, title = {{Highly conducting single-molecule topological insulators based on mono- and di-radical cations}}, doi = {10.1038/s41557-022-00978-1}, volume = {14}, year = {2022}, } @article{13357, abstract = {Coulombic interactions can be used to assemble charged nanoparticles into higher-order structures, but the process requires oppositely charged partners that are similarly sized. The ability to mediate the assembly of such charged nanoparticles using structurally simple small molecules would greatly facilitate the fabrication of nanostructured materials and harnessing their applications in catalysis, sensing and photonics. Here we show that small molecules with as few as three electric charges can effectively induce attractive interactions between oppositely charged nanoparticles in water. These interactions can guide the assembly of charged nanoparticles into colloidal crystals of a quality previously only thought to result from their co-crystallization with oppositely charged nanoparticles of a similar size. Transient nanoparticle assemblies can be generated using positively charged nanoparticles and multiply charged anions that are enzymatically hydrolysed into mono- and/or dianions. Our findings demonstrate an approach for the facile fabrication, manipulation and further investigation of static and dynamic nanostructured materials in aqueous environments.}, author = {Bian, Tong and Gardin, Andrea and Gemen, Julius and Houben, Lothar and Perego, Claudio and Lee, Byeongdu and Elad, Nadav and Chu, Zonglin and Pavan, Giovanni M. and Klajn, Rafal}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {General Chemical Engineering, General Chemistry}, number = {10}, pages = {940--949}, publisher = {Springer Nature}, title = {{Electrostatic co-assembly of nanoparticles with oppositely charged small molecules into static and dynamic superstructures}}, doi = {10.1038/s41557-021-00752-9}, volume = {13}, year = {2021}, } @article{9250, abstract = {Aprotic alkali metal–O2 batteries face two major obstacles to their chemistry occurring efficiently, the insulating nature of the formed alkali superoxides/peroxides and parasitic reactions that are caused by the highly reactive singlet oxygen (1O2). Redox mediators are recognized to be key for improving rechargeability. However, it is unclear how they affect 1O2 formation, which hinders strategies for their improvement. Here we clarify the mechanism of mediated peroxide and superoxide oxidation and thus explain how redox mediators either enhance or suppress 1O2 formation. We show that charging commences with peroxide oxidation to a superoxide intermediate and that redox potentials above ~3.5 V versus Li/Li+ drive 1O2 evolution from superoxide oxidation, while disproportionation always generates some 1O2. We find that 1O2 suppression requires oxidation to be faster than the generation of 1O2 from disproportionation. Oxidation rates decrease with growing driving force following Marcus inverted-region behaviour, establishing a region of maximum rate.}, author = {Petit, Yann K. and Mourad, Eléonore and Prehal, Christian and Leypold, Christian and Windischbacher, Andreas and Mijailovic, Daniel and Slugovc, Christian and Borisov, Sergey M. and Zojer, Egbert and Brutti, Sergio and Fontaine, Olivier and Freunberger, Stefan Alexander}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {General Chemistry, General Chemical Engineering}, number = {5}, pages = {465--471}, publisher = {Springer Nature}, title = {{Mechanism of mediated alkali peroxide oxidation and triplet versus singlet oxygen formation}}, doi = {10.1038/s41557-021-00643-z}, volume = {13}, year = {2021}, } @article{21084, abstract = {Self-assembly is a powerful method to obtain large discrete functional molecular architectures. When using a single building block, self-assembly generally yields symmetrical objects in which all the subunits relate similarly to their neighbours. Here we report the discovery of a family of self-constructing cyclic macromolecules with stable folded conformations of low symmetry, which include some with a prime number (13, 17 and 23) of units, despite being formed from a single component. The formation of these objects amounts to the production of polymers with a perfectly uniform length. Design rules for the spontaneous emergence of such macromolecules include endowing monomers with a strong potential for non-covalent interactions that remain frustrated in competing entropically favoured yet conformationally restrained smaller cycles. The process can also be templated by a guest molecule that itself has an asymmetrical structure, which paves the way to molecular imprinting techniques at the level of single polymer chains.}, author = {Pappas, Charalampos G. and Mandal, Pradeep K and Liu, Bin and Kauffmann, Brice and Miao, Xiaoming and Komáromy, Dávid and Hoffmann, Waldemar and Manz, Christian and Chang, Rayoon and Liu, Kai and Pagel, Kevin and Huc, Ivan and Otto, Sijbren}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {12}, pages = {1180--1186}, publisher = {Springer Nature}, title = {{Emergence of low-symmetry foldamers from single monomers}}, doi = {10.1038/s41557-020-00565-2}, volume = {12}, year = {2020}, } @article{10351, abstract = {Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.}, author = {Michaels, Thomas C. T. and Šarić, Anđela and Curk, Samo and Bernfur, Katja and Arosio, Paolo and Meisl, Georg and Dear, Alexander J. and Cohen, Samuel I. A. and Dobson, Christopher M. and Vendruscolo, Michele and Linse, Sara and Knowles, Tuomas P. J.}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {general chemical engineering, general chemistry}, number = {5}, pages = {445--451}, publisher = {Springer Nature}, title = {{Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide}}, doi = {10.1038/s41557-020-0452-1}, volume = {12}, year = {2020}, } @article{17922, abstract = {Gold–thiol contacts are ubiquitous across the physical and biological sciences in connecting organic molecules to surfaces. When thiols bind to gold in self-assembled monolayers (SAMs) the fate of the hydrogen remains a subject of profound debate—with implications for our understanding of their physical properties, spectroscopic features and formation mechanism(s). Exploiting measurements of the transmission through a molecular junction, which is highly sensitive to the nature of the molecule–electrode contact, we demonstrate here that the nature of the gold–sulfur bond in SAMs can be probed via single-molecule conductance measurements. Critically, we find that SAM measurements of dithiol-terminated molecular junctions yield a significantly lower conductance than solution measurements of the same molecule. Through numerous control experiments, conductance noise analysis and transport calculations based on density functional theory, we show that the gold–sulfur bond in SAMs prepared from the solution deposition of dithiols does not have chemisorbed character, which strongly suggests that under these widely used preparation conditions the hydrogen is retained.}, author = {Inkpen, Michael S. and Liu, Zhen–Fei and Li, Haixing and Campos, Luis M. and Neaton, Jeffrey B. and Venkataraman, Latha}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {4}, pages = {351--358}, publisher = {Springer Nature}, title = {{Non-chemisorbed gold–sulfur binding prevails in self-assembled monolayers}}, doi = {10.1038/s41557-019-0216-y}, volume = {11}, year = {2019}, } @article{21097, abstract = {Translation, the mRNA-templated synthesis of peptides by the ribosome, can be manipulated to incorporate variants of the 20 cognate amino acids. Such approaches for expanding the range of chemical entities that can be produced by the ribosome may accelerate the discovery of molecules that can perform functions for which poorly folded, short peptidic sequences are ill suited. Here, we show that the ribosome tolerates some artificial helical aromatic oligomers, so-called foldamers. Using a flexible tRNA-acylation ribozyme—flexizyme—foldamers were attached to tRNA, and the resulting acylated tRNAs were delivered to the ribosome to initiate the synthesis of non-cyclic and cyclic foldamer–peptide hybrid molecules. Passing through the ribosome exit tunnel requires the foldamers to unfold. Yet foldamers encode sufficient folding information to influence the peptide structure once translation is completed. We also show that in cyclic hybrids, the foldamer portion can fold into a helix and force the peptide segment to adopt a constrained and stretched conformation.}, author = {Rogers, Joseph M. and Kwon, Sunbum and Dawson, Simon J. and Mandal, Pradeep K and Suga, Hiroaki and Huc, Ivan}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {4}, pages = {405--412}, publisher = {Springer Nature}, title = {{Ribosomal synthesis and folding of peptide-helical aromatic foldamer hybrids}}, doi = {10.1038/s41557-018-0007-x}, volume = {10}, year = {2018}, } @article{10360, abstract = {Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer’s disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.}, author = {Cohen, Samuel I. A. and Cukalevski, Risto and Michaels, Thomas C. T. and Šarić, Anđela and Törnquist, Mattias and Vendruscolo, Michele and Dobson, Christopher M. and Buell, Alexander K. and Knowles, Tuomas P. J. and Linse, Sara}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {general chemical engineering, general chemistry}, number = {5}, pages = {523--531}, publisher = {Springer Nature}, title = {{Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide}}, doi = {10.1038/s41557-018-0023-x}, volume = {10}, year = {2018}, } @article{13394, abstract = {The ability to guide the assembly of nanosized objects reversibly with external stimuli, in particular light, is of fundamental importance, and it contributes to the development of applications as diverse as nanofabrication and controlled drug delivery. However, all the systems described to date are based on nanoparticles (NPs) that are inherently photoresponsive, which makes their preparation cumbersome and can markedly hamper their performance. Here we describe a conceptually new methodology to assemble NPs reversibly using light that does not require the particles to be functionalized with light-responsive ligands. Our strategy is based on the use of a photoswitchable medium that responds to light in such a way that it modulates the interparticle interactions. NP assembly proceeds quantitatively and without apparent fatigue, both in solution and in gels. Exposing the gels to light in a spatially controlled manner allowed us to draw images that spontaneously disappeared after a specific period of time.}, author = {Kundu, Pintu K. and Samanta, Dipak and Leizrowice, Ron and Margulis, Baruch and Zhao, Hui and Börner, Martin and Udayabhaskararao, T. and Manna, Debasish and Klajn, Rafal}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {General Chemical Engineering, General Chemistry}, pages = {646--652}, publisher = {Springer Nature}, title = {{Light-controlled self-assembly of non-photoresponsive nanoparticles}}, doi = {10.1038/nchem.2303}, volume = {7}, year = {2015}, } @article{17975, abstract = {A new intersection between reaction chemistry and electronic circuitry is emerging from the ultraminiaturization of electronic devices. Over decades chemists have developed a nuanced understanding of stereoelectronics to establish how the electronic properties of molecules relate to their conformation; the recent advent of single-molecule break-junction techniques provides the means to alter this conformation with a level of control previously unimagined. Here we unite these ideas by demonstrating the first single-molecule switch that operates through a stereoelectronic effect. We demonstrate this behaviour in permethyloligosilanes with methylthiomethyl electrode linkers. The strong σ conjugation in the oligosilane backbone couples the stereoelectronic properties of the sulfur–methylene σ bonds that terminate the molecule. Theoretical calculations support the existence of three distinct dihedral conformations that differ drastically in their electronic character. We can shift between these three species by simply lengthening or compressing the molecular junction, and, in doing so, we can switch conductance digitally between two states.}, author = {Su, Timothy A. and Li, Haixing and Steigerwald, Michael L. and Venkataraman, Latha and Nuckolls, Colin}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {3}, pages = {215--220}, publisher = {Springer Nature}, title = {{Stereoelectronic switching in single-molecule junctions}}, doi = {10.1038/nchem.2180}, volume = {7}, year = {2015}, } @article{17976, abstract = {To develop advanced materials for electronic devices, it is of utmost importance to design organic building blocks with tunable functionality and to study their properties at the molecular level. For organic electronic and photovoltaic applications, the ability to vary the nature of charge carriers and so create either electron donors or acceptors is critical. Here we demonstrate that charge carriers in single-molecule junctions can be tuned within a family of molecules that contain electron-deficient thiophene-1,1-dioxide (TDO) building blocks. Oligomers of TDO were designed to increase electron affinity and maintain delocalized frontier orbitals while significantly decreasing the transport gap. Through thermopower measurements we show that the dominant charge carriers change from holes to electrons as the number of TDO units is increased. This results in a unique system in which the charge carrier depends on the backbone length, and provides a new means to tune p- and n-type transport in organic materials.}, author = {Dell, Emma J. and Capozzi, Brian and Xia, Jianlong and Venkataraman, Latha and Campos, Luis M.}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {3}, pages = {209--214}, publisher = {Springer Nature}, title = {{Molecular length dictates the nature of charge carriers in single-molecule junctions of oxidized oligothiophenes}}, doi = {10.1038/nchem.2160}, volume = {7}, year = {2015}, } @article{13415, abstract = {Systems in which nanoscale components of different types can be captured and/or released from organic scaffolds provide a fertile basis for the construction of dynamic, exchangeable functional materials. In such heterogeneous systems, the components interact with one another by means of programmable, noncovalent bonding interactions. Herein, we describe polymers that capture and release functionalized nanoparticles selectively during redox-controlled aggregation and disaggregation, respectively. The interactions between the polymer and the NPs are mediated by the reversible formation of polypseudorotaxanes, and give rise to architectures ranging from short chains composed of few nanoparticles to extended networks of nanoparticles crosslinked by the polymer. In the latter case, the polymer/nanoparticle aggregates precipitate from solution such that the polymer acts as a selective ‘sponge’ for the capture/release of the nanoparticles of different types.}, author = {Klajn, Rafal and Olson, Mark A. and Wesson, Paul J. and Fang, Lei and Coskun, Ali and Trabolsi, Ali and Soh, Siowling and Stoddart, J. Fraser and Grzybowski, Bartosz A.}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {General Chemical Engineering, General Chemistry}, pages = {733--738}, publisher = {Springer Nature}, title = {{Dynamic hook-and-eye nanoparticle sponges}}, doi = {10.1038/nchem.432}, volume = {1}, year = {2009}, }