Mechanical Manipulation of Quantum Interference in Single-Molecule Junctions.

Mechanosensitive molecular junctions, where conductance is sensitive to an applied stress such as force or displacement, are a class of nanoelectromechanical systems unique for their ability to exploit quantum mechanical phenomena. Most studies so far relied on reconfiguration of the molecule-electrode interface to impart mechanosensitivity, but this approach is limited and, generally, poorly reproducible. Alternatively, devices that exploit conformational flexibility of molecular wires have been recently proposed. The mechanosensitive properties of molecular wires containing the 1,1'-dinaphthyl moiety are presented here. Rotation along the chemical bond between the two naphthyl units is possible, giving rise to two conformers (transoid and cisoid) that have distinctive transport properties. When assembled as single-molecule junctions, it is possible to mechanically trigger the transoid to cisoid transition, resulting in an exquisitely sensitive mechanical switch with high switching ratio (> 102). Theoretical modeling shows that charge reconfiguration upon transoid to cisoid transition is responsible for the observed behavior, with generation and subsequent lifting of quantum interference features. These findings expand the experimental toolbox of molecular electronics with a novel chemical structure with outstanding electromechanical properties, further demonstrating the importance of subtle changes in charge delocalization on the transport properties of single-molecule devices.

An Orthogonal Conductance Pathway in Spiropyrans for Well-Defined Electrosteric Switching Single-Molecule Junctions.

While a multitude of studies have appeared touting the use of molecules as electronic components, the design of molecular switches is crucial for the next steps in molecular electronics. In this work, single-molecule devices incorporating spiropyrans, made using break junction techniques, are described. Linear spiropyrans with electrode-contacting groups linked by alkynyl spacers to both the indoline and chromenone moieties have previously provided very low conductance values, and removing the alkynyl spacer has resulted in a total loss of conductance. An orthogonal T-shaped approach to single-molecule junctions incorporating spiropyran moieties in which the conducting pathway lies orthogonal to the molecule backbone is described and characterized. This approach has provided singlemolecule conductance features with good correlation to molecular length. Additional higher conducting states are accessible using switching induced by UV light or protonation. Theoretical modeling demonstrates that upon (photo)chemical isomerization to the merocyanine, two cooperating phenomena increase conductance: release of steric hindrance allows the conductance pathway to become more planar (raising the mid-bandgap transmission) and a bound state introduces sharp interference near the Fermi level of the electrodes similarly responding to the change in state. This design step paves the way for future use of spiropyrans in single-molecule devices and electrosteric switches.

A Systematic Study of Methyl Carbodithioate Esters as Effective Gold Contact Groups for Single-Molecule Electronics.

There are several binding groups used within molecular electronics for anchoring molecules to metal electrodes (e.g., R-SMe, R-NH2, R-CS2 -, R-S-). However, some anchoring groups that bind strongly to electrodes have poor/unknown stability, some have weak electrode coupling, while for some their binding motifs are not well defined. Further binding groups are required to aid molecular design and to achieve a suitable balance in performance across a range of properties. We present an in-depth investigation into the use of carbodithioate esters as contact groups for single-molecule conductance measurements, using scanning tunnelling microscopy break junction measurements (STM-BJ) and detailed surface spectroscopic analysis. We demonstrate that the methyl carbodithioate ester acts as an effective contact for gold electrodes in STM-BJ measurements. Surface enhanced Raman measurements demonstrate that the C=S functionality remains intact when adsorbed on to gold nanoparticles. A gold(I) complex was also synthesised showing a stable C=S→AuI interaction from the ester. Comparison with a benzyl thiomethyl ether demonstrates that the C=S moiety significantly contributes to charge transport in single-molecule junctions. The overall performance of the CS2Me group demonstrates it should be used more extensively and has strong potential for the fabrication of larger area devices with long-term stability.

The 24-h activity cycle and cardiovascular outcomes: establishing biological plausibility using arterial stiffness as an intermediate outcome.

This review proposes a biologically plausible working model for the relationship between the 24-h activity cycle (24-HAC) and cardiovascular disease. The 24-HAC encompasses moderate-to-vigorous physical activity (MVPA), light physical activity, sedentary behavior (SB), and sleep. MVPA confers the greatest relative cardioprotective effect, when considering MVPA represents just 2% of the day if physical activity guidelines (30 min/day) are met. While we have well-established guidelines for MVPA, those for the remaining activity behaviors are vague. The vague guidelines are attributable to our limited mechanistic understanding of the independent and additive effects of these behaviors on the cardiovascular system. Our proposed biological model places arterial stiffness, a measure of vascular aging, as the key intermediate outcome. Starting with prolonged exposure to SB or static standing, we propose that the reported transient increases in arterial stiffness are driven by a cascade of negative hemodynamic effects following venous pooling. The subsequent autonomic, metabolic, and hormonal changes further impair vascular function. Vascular dysfunction can be offset by using mechanistic-informed interruption strategies and by engaging in protective behaviors throughout the day. Physical activity, especially MVPA, can confer protection by chronically improving endothelial function and associated protective mechanisms. Conversely, poor sleep, especially in duration and quality, negatively affects hormonal, metabolic, autonomic, and hemodynamic variables that can confound the physiological responses to next-day activity behaviors. Our hope is that the proposed biologically plausible working model will assist in furthering our understanding of the effects of these complex, interrelated activity behaviors on the cardiovascular system.

Acute sedentary behavior and cardiovascular disease research: standardizing the methodological posture.

Sedentary behavior has been identified as an independent predictor of future cardiovascular disease risk and all-cause mortality. To explain this association, a growing body of literature has sought to investigate the physiological underpinnings of this association with the goal of developing a biologically plausible model. In time, this biologically plausible model can be tested, and effective, translatable public health guidelines can be developed. However, to ensure that evidence across studies can be effectively synthesized, it is necessary to ensure their congruency and comparability. Although there are several key factors that should be considered and controlled across prolonged sitting studies, one pertinent issue is that of participant posture. There is currently a discourse within the literature regarding the posture that cardiovascular assessments are performed in and rest periods between posture transitions and subsequent measures. This perspectives piece makes the case for standardizing approaches across the research area and offers practical recommendations for future work.

Single-Molecule Conductance Behavior of Molecular Bundles.

Controlling the orientation of complex molecules in molecular junctions is crucial to their development into functional devices. To date, this has been achieved through the use of multipodal compounds (i.e., containing more than two anchoring groups), resulting in the formation of tri/tetrapodal compounds. While such compounds have greatly improved orientation control, this comes at the cost of lower surface coverage. In this study, we examine an alternative approach for generating multimodal compounds by binding multiple independent molecular wires together through metal coordination to form a molecular bundle. This was achieved by coordinating iron(II) and cobalt(II) to 5,5'-bis(methylthio)-2,2'-bipyridine (L1) and (methylenebis(4,1-phenylene))bis(1-(5-(methylthio)pyridin-2-yl)methanimine) (L2) to give two monometallic complexes, Fe-1 and Co-1, and two bimetallic helicates, Fe-2 and Co-2. Using XPS, all of the complexes were shown to bind to a gold surface in a fac fashion through three thiomethyl groups. Using single-molecule conductance and DFT calculations, each of the ligands was shown to conduct as an independent wire with no impact from the rest of the complex. These results suggest that this is a useful approach for controlling the geometry of junction formation without altering the conductance behavior of the individual molecular wires.

Not So Innocent After All: Interfacial Chemistry Determines Charge-Transport Efficiency in Single-Molecule Junctions.

Most studies in molecular electronics focus on altering the molecular wire backbone to tune the electrical properties of the whole junction. However, it is often overlooked that the chemical structure of the groups anchoring the molecule to the metallic electrodes influences the electronic structure of the whole system and, therefore, its conductance. We synthesised electron-accepting dithienophosphole oxide derivatives and fabricated their single-molecule junctions. We found that the anchor group has a dramatic effect on charge-transport efficiency: in our case, electron-deficient 4-pyridyl contacts suppress conductance, while electron-rich 4-thioanisole termini promote efficient transport. Our calculations show that this is due to minute changes in charge distribution, probed at the electrode interface. Our findings provide a framework for efficient molecular junction design, especially valuable for compounds with strong electron withdrawing/donating backbones.

2,7- and 4,9-Dialkynyldihydropyrene Molecular Switches: Syntheses, Properties, and Charge Transport in Single-Molecule Junctions.

This paper describes the syntheses of several functionalized dihydropyrene (DHP) molecular switches with different substitution patterns. Regioselective nucleophilic alkylation of a 5-substituted dimethyl isophthalate allowed the development of a workable synthetic protocol for the preparation of 2,7-alkyne-functionalized DHPs. Synthesis of DHPs with surface-anchoring groups in the 2,7- and 4,9-positions is described. The molecular structures of several intermediates and DHPs were elucidated by X-ray single-crystal diffraction. Molecular properties and switching capabilities of both types of DHPs were assessed by light irradiation experiments, spectroelectrochemistry, and cyclic voltammetry. Spectroelectrochemistry, in combination with density functional theory (DFT) calculations, shows reversible electrochemical switching from the DHP forms to the cyclophanediene (CPD) forms. Charge-transport behavior was assessed in single-molecule scanning tunneling microscope (STM) break junctions, combined with density functional theory-based quantum transport calculations. All DHPs with surface-contacting groups form stable molecular junctions. Experiments show that the molecular conductance depends on the substitution pattern of the DHP motif. The conductance was found to decrease with increasing applied bias.

Electrochemical gating for single-molecule electronics with hybrid Au|graphene contacts.

The single-molecular conductance of a redox active viologen molecular bridge between Au|graphene electrodes has been studied in an electrochemical gating configuration in an ionic liquid medium. A clear "off-on-off" conductance switching behaviour has been achieved through gating of the redox state when the electrochemical potential is swept. The Au|viologen|graphene junctions show single-molecule conductance maxima centred close to the equilibrium redox potentials for both reduction steps. The peak conductance of Au|viologen|graphene junctions during the first reduction is significantly higher than that of previously measured Au|viologen|Au junctions. This shows that even though the central viologen moiety is not directly linked to the enclosing electrodes, substituting one gold contact for a graphene one nevertheless has a significant impact on junction conductance values. The experimental data was compared against two theoretical models, namely a phase coherent tunnelling and an incoherent "hopping" model. The former is a simple gating monoelectronic model within density functional theory (DFT) which discloses the charge state evolution of the molecule with electrode potential. The latter model is the collective Kuznetsov Ulstrup model for 2-step sequential charge transport through the redox centre in the adiabatic limit. The comparison of both models to the experimental data is discussed for the first time. This work opens perspectives for graphene-based molecular transistors with more effective gating and fundamental understanding of electrochemical electron transfer at the single molecular level.

Redox-Addressable Single-Molecule Junctions Incorporating a Persistent Organic Radical.

Integrating radical (open-shell) species into non-cryogenic nanodevices is key to unlocking the potential of molecular electronics. While many efforts have been devoted to this issue, in the absence of a chemical/electrochemical potential the open-shell character is generally lost in contact with the metallic electrodes. Herein, single-molecule devices incorporating a 6-oxo-verdazyl persistent radical have been fabricated using break-junction techniques. The open-shell character is retained at room temperature, and electrochemical gating permits in situ reduction to a closed-shell anionic state in a single-molecule transistor configuration. Furthermore, electronically driven rectification arises from bias-dependent alignment of the open-shell resonances. The integration of radical character, transistor-like switching, and rectification in a single molecular component paves the way to further studies of the electronic, magnetic, and thermoelectric properties of open-shell species.

A Peierls Transition in Long Polymethine Molecular Wires: Evolution of Molecular Geometry and Single-Molecule Conductance.

Molecules capable of mediating charge transport over several nanometers with minimal decay in conductance have fundamental and technological implications. Polymethine cyanine dyes are fascinating molecular wires because up to a critical length, they have no bond-length alternation (BLA) and their electronic structure resembles a one-dimensional free-electron gas. Beyond this threshold, they undergo a symmetry-breaking Peierls transition, which increases the HOMO-LUMO gap. We have investigated cationic cyanines with central polymethine chains of 5-13 carbon atoms (Cy3+-Cy11+). The absorption spectra and crystal structures show that symmetry breaking is sensitive to the polarity of the medium and the size of the counterion. X-ray crystallography reveals that Cy9·PF6 and Cy11·B(C6F5)4 are Peierls distorted, with high BLA at one end of the π-system, away from the partially delocalized positive charge. This pattern of BLA distribution resembles that of solitons in polyacetylene. The single-molecule conductance is essentially independent of molecular length for the polymethine salts of Cy3+-Cy11+ with the large B(C6F5)4- counterion, but with the PF6- counterion, the conductance decreases for the longer molecules, Cy7+-Cy11+, because this smaller anion polarizes the π-system, inducing a symmetry-breaking transition. At higher bias (0.9 V), the conductance of the shorter chains, Cy3+-Cy7+, increases with length (negative attenuation factor, ß = -1.6 nm-1), but the conductance still drops in Cy9+ and Cy11+ with the small polarizing PF6- counteranion.

Molecular Structure-(Thermo)electric Property Relationships in Single-Molecule Junctions and Comparisons with Single- and Multiple-Parameter Models.

The most probable single-molecule conductance of each member of a series of 12 conjugated molecular wires, 6 of which contain either a ruthenium or platinum center centrally placed within the backbone, has been determined. The measurement of a small, positive Seebeck coefficient has established that transmission through these molecules takes place by tunneling through the tail of the HOMO resonance near the middle of the HOMO-LUMO gap in each case. Despite the general similarities in the molecular lengths and frontier-orbital compositions, experimental and computationally determined trends in molecular conductance values across this series cannot be satisfactorily explained in terms of commonly discussed "single-parameter" models of junction conductance. Rather, the trends in molecular conductance are better rationalized from consideration of the complete molecular junction, with conductance values well described by transport calculations carried out at the DFT level of theory, on the basis of the Landauer-Büttiker model.

Folding a Single-Molecule Junction.

Stimuli-responsive molecular junctions, where the conductance can be altered by an external perturbation, are an important class of nanoelectronic devices. These have recently attracted interest as large effects can be introduced through exploitation of quantum phenomena. We show here that significant changes in conductance can be attained as a molecule is repeatedly compressed and relaxed, resulting in molecular folding along a flexible fragment and cycling between an anti and a syn conformation. Power spectral density analysis and DFT transport calculations show that through-space tunneling between two phenyl fragments is responsible for the conductance increase as the molecule is mechanically folded to the syn conformation. This phenomenon represents a novel class of mechanoresistive molecular devices, where the functional moiety is embedded in the conductive backbone and exploits intramolecular nonbonding interactions, in contrast to most studies where mechanoresistivity arises from changes in the molecule-electrode interface.

Celiac Disease and Bone Health in Children and Adolescents: A Systematic Review and Meta-Analysis.

CONTEXT: Celiac disease is characterized by deficits in bone mineral accrual and longitudinal growth. OBJECTIVE: The purpose of this study was to determine the differences in bone health and stature among children and adolescents with celiac disease versus healthy controls. DATA SOURCES: Articles published before February 27, 2018 were located using searches of the Physical Education Index (n = 186), PubMed (n = 180), Scopus (n = 3), SPORTDiscus (n = 3), and Web of Science (n = 4). STUDY SELECTION: Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed via dual-energy X-ray absorptiometry, and height was measured using a stadiometer. DATA EXTRACTION: Effect sizes (ES) were calculated as follows: the mean difference of the celiac disease group and healthy control group, divided by the pooled standard deviation. The inverse variance weight was used to calculate the overall mean ES. Random-effects models were used to aggregate a mean ES, 95% confidence intervals (CIs) and to identify potential moderators. RESULTS: The results of 30 effects gathered from 12 studies published between 1996 and 2017 indicated BMC (ES = -0.54, 95% CI: -0.69 to -0.40; p < 0.0001) and aBMD (ES = 0.72, 95% CI: -0.96 to -0.47; p < 0.0001) were lower in youth with celiac disease. LIMITATIONS: These results were limited to only cross-sectional and baseline data from longitudinal studies reporting BMC and BMD, however did not assess changes in bone health over time. CONCLUSION: Children and adolescents with celiac disease have suboptimal bone health and shorter stature.

A Chemically Soldered Polyoxometalate Single-Molecule Transistor.

Polyoxometalates have been proposed in the literature as nanoelectronic components, where they could offer key advantages with their structural versatility and rich electrochemistry. Apart from a few studies on their ensemble behaviour (as monolayers or thin films), this potential remains largely unexplored. We synthesised a pyridyl-capped Anderson-Evans polyoxometalate and used it to fabricate single-molecule junctions, using the organic termini to chemically "solder" a single cluster to two nanoelectrodes. Operating the device in an electrochemical environment allowed us to probe charge transport through different oxidation states of the polyoxometalate, and we report here an efficient three-state transistor behaviour. Conductance data fits a quantum tunnelling mechanism with different charge-transport probabilities through different charge states. Our results show the promise of polyoxometalates in nanoelectronics and give an insight on their single-entity electrochemical behaviour.

Dual Control of Molecular Conductance through pH and Potential in Single-Molecule Devices.

One of the principal aims of single-molecule electronics is to create practical devices out of individual molecules. Such devices are expected to play a particularly important role as novel sensors thanks to their response to wide ranging external stimuli. Here we show that the conductance of a molecular junction can depend on two independent stimuli simultaneously. Using a scanning tunnelling microscope break-junction technique (STM-BJ), we found that the conductance of 4,4'-vinylenedipyridine (44VDP) molecular junctions with Ni contacts depends on both the electrochemically applied gate voltage and the pH of the environment. Hence, not only can the Ni|44VDP|Ni junction function as a pH-sensitive switch, but the value of the pH at which switching takes place can be tuned electrically. Furthermore, through the simultaneous control of pH and potential the STM-BJ technique delivers unique insight into the acid-base reaction, including the observation of discrete proton transfers to and from a single molecule.

Hemilabile Ligands as Mechanosensitive Electrode Contacts for Molecular Electronics.

Single-molecule junctions that are sensitive to compression or elongation are an emerging class of nanoelectromechanical systems (NEMS). Although the molecule-electrode interface can be engineered to impart such functionality, most studies to date rely on poorly defined interactions. We focused on this issue by synthesizing molecular wires designed to have chemically defined hemilabile contacts based on (methylthio)thiophene moieties. We measured their conductance as a function of junction size and observed conductance changes of up to two orders of magnitude as junctions were compressed and stretched. Localised interactions between weakly coordinating thienyl sulfurs and the electrodes are responsible for the observed effect and allow reversible monodentate⇄bidentate contact transitions as the junction is modulated in size. We observed an up to ≈100-fold sensitivity boost of the (methylthio)thiophene-terminated molecular wire compared with its non-hemilabile (methylthio)benzene counterpart and demonstrate a previously unexplored application of hemilabile ligands to molecular electronics.

Unusual Length Dependence of the Conductance in Cumulene Molecular Wires.

Cumulenes are sometimes described as "metallic" because an infinitely long cumulene would have the band structure of a metal. Herein, we report the single-molecule conductance of a series of cumulenes and cumulene analogues, where the number of consecutive C=C bonds in the core is n=1, 2, 3, and 5. The [n]cumulenes with n=3 and 5 have almost the same conductance, and they are both more conductive than the alkene (n=1). This is remarkable because molecular conductance normally falls exponentially with length. The conductance of the allene (n=2) is much lower, because of its twisted geometry. Computational simulations predict a similar trend to the experimental results and indicate that the low conductance of the allene is a general feature of [n]cumulenes where n is even. The lack of length dependence in the conductance of [3] and [5]cumulenes is attributed to the strong decrease in the HOMO-LUMO gap with increasing length.

Bias-Driven Conductance Increase with Length in Porphyrin Tapes.

A key goal in molecular electronics has been to find molecules that facilitate efficient charge transport over long distances. Normally, molecular wires become less conductive with increasing length. Here, we report a series of fused porphyrin oligomers for which the conductance increases substantially with length by >10-fold at a bias of 0.7 V. This exceptional behavior can be attributed to the rapid decrease of the HOMO-LUMO gap with the length of fused porphyrins. In contrast, for butadiyne-linked porphyrin oligomers with moderate inter-ring coupling, a normal conductance decrease with length is found for all bias voltages explored (±1 V), although the attenuation factor (ß) decreases from ca. 2 nm-1 at low bias to <1 nm-1 at 0.9 V, highlighting that ß is not an intrinsic molecular property. Further theoretical analysis using density functional theory underlines the role of intersite coupling and indicates that this large increase in conductance with length at increasing voltages can be generalized to other molecular oligomers.

Detecting Mechanochemical Atropisomerization within an STM Break Junction.

We have employed the scanning tunneling microscope break-junction technique to investigate the single-molecule conductance of a family of 5,15-diaryl porphyrins bearing thioacetyl (SAc) or methylsulfide (SMe) binding groups at the ortho position of the phenyl rings (S2 compounds). These ortho substituents lead to two atropisomers, cis and trans, for each compound, which do not interconvert in solution under ambient conditions; even at high temperatures, isomerization takes several hours (half-life 15 h at 140 °C for SAc in C2Cl4D2). All the S2 compounds exhibit two conductance groups, and comparison with a monothiolated (S1) compound shows the higher group arises from a direct Au-porphyrin interaction. The lower conductance group is associated with the S-to-S pathway. When the binding group is SMe, the difference in junction length distribution reflects the difference in S-S distance (0.3 nm) between the two isomers. In the case of SAc, there are no significant differences between the plateau length distributions of the two isomers, and both show maximal stretching distances well exceeding their calculated junction lengths. Contact deformation accounts for part of the extra length, but the results indicate that cis-to-trans conversion takes place in the junction for the cis isomer. The barrier to atropisomerization is lower than the strength of the thiolate Au-S and Au-Au bonds, but higher than that of the Au-SMe bond, which explains why the strain in the junction only induces isomerization in the SAc compound.