Single-molecule Scale Research Articles

Energy bandgap engineering of graphene nanoribbon by doping phosphorous impurities to create nano-heterostructures: A DFT study

Energy bandgap engineering is used to produce semiconductor heterostructure systems that perform processes such as the resonant tunneling in nanoelectronics and the solar energy conversion in solar cell applications. However, the performance of such systems degrades as their size is reduced. Graphene-based nanoelectronics has appeared as a candidate to enable high performance down to the single-molecule scale. Here, graphene nanoribbons (GNRs) can have bandgaps that are tunable by using chemical doping method. We have been predicted that bandgap engineering within a GNR may be achieved by varying the number and geometrical pattern of phosphorus (P) impurities in the GNS, so that we have carried out first-principles calculations of the energetic and electronic properties of P-doped GNR based on density functional theory (DFT) with Gaussian 09W packages. The geometric and electronic properties of the GNR with and without various dopants of phosphorus impurities were performed and discussed. Our results show that the electronic properties of GNR do not only depend on the phosphorus impurity concentrations, but also depend on the geometrical pattern of phosphorus impurities in the GNR. As a result, we can bandgap engineering of GNR by doping phosphorous impurities to create semiconductor heterostructure, which can be used in many important applications.

Optical Stark effect of a local defect on the TiO2(110) surface

Probing optical Stark effect at the single-molecule or atomic scale is crucial for understanding many photo-induced chemical and physical processes on surfaces. Here we report a study about optical Stark effect of single atomic defects on TiO2(110) surface with photo-assisted scanning tunneling spectroscopy. When a laser is coupled into the tunneling junction, the mid-gap state of OH-O2 defects changes remarkably in the differential conductance spectra. As laser power gradually increases, the energy of the mid-gap state shifts away from the Fermi level with increase in intensity and broadening of peak width. The observation can be explained as optical Stark effect with the Autler-Townes formula. This large optical Stark effect is due to the tip-enhancement and the strong dipole moment in the transient charged state during electron tunneling. Our study provides new aspects in exploring electron-photon interactions at the microscopic scale.

Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils

The formation and spreading of amyloid aggregates from the presynaptic protein α-synuclein in the brain play central roles in the pathogenesis of Parkinson's disease. Here, we use high-resolution atomic force microscopy to investigate the early oligomerization events of α-synuclein with single monomer angstrom resolution. We identify, visualize, and characterize directly the smallest elementary unit in the hierarchical assembly of amyloid fibrils, termed here single-strand protofilaments. We show that protofilaments form from the direct molecular assembly of unfolded monomeric α-synuclein polypeptide chains. To unravel protofilaments' internal structure and elastic properties, we manipulated nanomechanically these species by atomic force spectroscopy. The single-molecule scale identification and characterization of the fundamental unit of amyloid assemblies provide insights into early events underlying their formation and shed light on opportunities for therapeutic intervention at the early stages of aberrant protein self-assembly.

Towards Controlled Single-Molecule Manipulation Using "Real-Time" Molecular Dynamics Simulation: A GPU Implementation.

Molecular electronics saw its birth with the idea to build electronic circuitry with single molecules as individual components. Even though commercial applications are still modest, it has served an important part in the study of fundamental physics at the scale of single atoms and molecules. It is now a routine procedure in many research groups around the world to connect a single molecule between two metallic leads. What is unknown is the nature of this coupling between the molecule and the leads. We have demonstrated recently (Tewari, 2018, Ph.D. Thesis) our new setup based on a scanning tunneling microscope, which can be used to controllably manipulate single molecules and atomic chains. In this article, we will present the extension of our molecular dynamic simulator attached to this system for the manipulation of single molecules in real time using a graphics processing unit (GPU). This will not only aid in controlled lift-off of single molecules, but will also provide details about changes in the molecular conformations during the manipulation. This information could serve as important input for theoretical models and for bridging the gap between the theory and experiments.

Quantum-dot antibody conjugation visualized at the single-molecule scale with high-speed atomic force microscopy.

Conjugates of semiconductor quantum dots (QDs) and antibodies have emerged as a promising bioprobes due to their great combination of QD's efficient fluorescence and the high specificity of antigen-antibody reactions. For further developments in this field, it is essential to understand the molecular conformation of the QD-antibody conjugates at the single-molecule scale. Here, we report on the direct imaging of QD-antibody conjugates at the single-molecule scale by using high-speed atomic force microscopy (HS-AFM). Owing to the high spatiotemporal resolution of HS-AFM, we observed the dynamic splitting of individual antibodies during the conjugation process. QD-antibody conjugates were also clearly visualized at the single-molecule scale details. Several important features were even discovered through dynamic observation of the QD-antibody conjugates. We observed an intermediate state of conjugation, where the antibodies attached and detached to QDs repeatedly. We also revealed that the attached antibodies were not steady but drastically fluctuated in their recognition areas due to the Brownian motion. We also demonstrated that HS-AFM observation is useful for the quantitative analysis of fabricated conjugates.

Anomalous Current/Voltage Behaviors of Polyoxometalate/Porphyrin Derivative Complexes

Polyoxometalate (POM) derivatives have been reported to show various specific electronic properties. For example, (NH4)6V10O28 and H7SiW9V3O40 show negative differential resistance (NDR) when measured by scanning tunneling spectroscopic (STS) technique in air.1,2 We have reported that a composite of H3PMo12O40 with single-walled carbon nanotubes (SWNT) showed complex phenomena depending on the size of the POM nanoparticles. When the size of the POM was smaller than ~6 nm with a semiconducting SWNT, the composite showed rectification with positive bias suppression. By contrast, if the size of the POM was larger, the suppression was observed at negative bias. However, when the SWNT is metallic, the suppression occurred at the opposite bias.3 There are several POM/porphyrin derivatives or analogues reported, saddle-distorted Mo(V)-dodecaphenylporphyrin with Keggin-type H2SiW12O40,4 cyclo[8]pyrrole with H4SiW12O40,5 tetraphenylporphyrin (TPP) with SW10V2O40.6 The electronic properties of these complexes are interesting to measure in macro-scale and in single molecule-scale, because of the versatile electronic behaviors are expected from multi redox characters of POM cores tuned by the surrounding porphyrin derivatives. The single crystal structure of [H4TPP][SV2W10O40] was successfully determined, in which one POM anion is surrounded by four H4TPP cations. Although this complex is dissociated in solution, the casted sample retains crystalline structures partially as observed by the powder X-ray diffraction study. Devices were made by casting the solution of the complex on Au electrodes with 5 μm gap. The current-voltage curve at ambient conditions showed broad negative differential resistance (NDR) with large hysteresis. The impedance measurements between 10-1 to 106 Hz at 0.0 to 3.0 V DC bias indicated that in low frequency range (<10 Hz) the impedance is lower at high DC bias voltage. However, in high frequency range (> 10Hz) the impedance is almost independent on voltage. The impedance results indicate that non-linear NDR behavior observed in DC measurement is because of a slow process of the carrier movement, probably by ionic conductance. References (1) Ogawa, T.; Handayani, M. In Molecular Architectonics; Ogawa, T., Ed.; Springer Nature: Switzerland, 2017, p 419. (2) Watson, B. A.; Barteau, M. A.; Haggerty, L.; Lenhoff, A. M.; Weber, R. S. Langmuir 1992, 8, 1145. (3) Hong, L.; Tanaka, H.; Ogawa, T. J. Mat. Chem., C 2013, 1, 1137. (4) Yokoyama, A.; Kojima, T.; Ohkubo, K.; Fukuzumi, S. Chem. Commun. 2007, 3997. (5) Okujima, T.; Matsumoto, H.; Mori, S.; Nakae, T.; Takase, M.; Uno, H. Tetrahedron Lett. 2016, 57, 3160. (6) Shi, Z. H.; Zhou, Y. S.; Zhang, L. J.; Mu, C. C.; Ren, H. Z.; ul Hassan, D.; Yang, D.; Asif, H. M. RSC Adv. 2014, 4, 50277. Figure 1

Fluctuation in Interface and Electronic Structure of Single-Molecule Junctions Investigated by Current versus Bias Voltage Characteristics.

Structural and electronic detail at the metal-molecule interface has a significant impact on the charge transport across the molecular junctions, but its precise understanding and control still remain elusive. On the single-molecule scale, the metal-molecule interface structures and relevant charge transport properties are subject to fluctuation, which contain the fundamental science of single-molecule transport and implication for manipulability of the transport properties in electronic devices. Here, we present a comprehensive approach to investigate the fluctuation in the metal-molecule interface in single-molecule junctions, based on current-voltage ( I- V) measurements in combination with first-principles simulation. Contrary to conventional molecular conductance studies, this I- V approach provides a correlated statistical description of both the degree of electronic coupling across the metal-molecule interface and the molecular orbital energy level. This statistical approach was employed to study fluctuation in single-molecule junctions of 1,4-butanediamine (DAB), pyrazine (PY), 4,4'-bipyridine (BPY), and fullerene (C60). We demonstrate that molecular-dependent fluctuation of σ-, π-, and π-plane-type interfaces can be captured by analyzing the molecular orbital (MO) energy level under mechanical perturbation. While the MO level of DAB with the σ-type interface shows weak distance dependence and fluctuation, the MO level of PY, BPY, and C60 features unique distance dependence and molecular-dependent fluctuation against the mechanical perturbation. The MO level of PY and BPY with the σ+π-type interface increases with the increase in the stretch distance. In contrast, the MO level of C60 with the π-plane-type interface decreases with the increase in the stretching perturbation. This study provides an approach to resolve the structural and electronic fluctuation in the single-molecule junctions and insight into the molecular-dependent fluctuation in the junctions.

Investigation on Single-Molecule Junctions Based on Current⁻Voltage Characteristics.

The relationship between the current through an electronic device and the voltage across its terminals is a current–voltage characteristic (I–V) that determine basic device performance. Currently, I–V measurement on a single-molecule scale can be performed using break junction technique, where a single molecule junction can be prepared by trapping a single molecule into a nanogap between metal electrodes. The single-molecule I–Vs provide not only the device performance, but also reflect information on energy dispersion of the electronic state and the electron-molecular vibration coupling in the junction. This mini review focuses on recent representative studies on I–Vs of the single molecule junctions that cover investigation on the single-molecule diode property, the molecular vibration, and the electronic structure as a form of transmission probability, and electronic density of states, including the spin state of the single-molecule junctions. In addition, thermoelectronic measurements based on I–Vs and identification of the charged carriers (i.e., electrons or holes) are presented. The analysis in the single-molecule I–Vs provides fundamental and essential information for a better understanding of the single-molecule science, and puts the single molecule junction to more practical use in molecular devices.

Controlling stacking order and charge transport in π-stacks of aromatic molecules based on surface assembly.

Here, we report a facile procedure based on surface self-assembly for controlling the π-π stacking order and relevant rectified charge transport properties in stacks of aromatic molecules on a single-molecule scale. A high rectification ratio of 10 was achieved and the rectification direction was uniquely determined by the controlled stacking order of the aromatic molecules on the graphene layers of HOPG.

Surface-Enhanced Raman Scattering in Molecular Junctions.

Surface-enhanced Raman scattering (SERS) is a surface-sensitive vibrational spectroscopy that allows Raman spectroscopy on a single molecular scale. Here, we present a review of SERS from molecular junctions, in which a single molecule or molecules are made to have contact from the top to the bottom of metal surfaces. The molecular junctions are nice platforms for SERS as well as transport measurement. Electronic characterization based on the transport measurements of molecular junctions has been extensively studied for the development of miniaturized electronic devices. Simultaneous SERS and transport measurement of the molecular junctions allow both structural (geometrical) and electronic information on the single molecule scale. The improvement of SERS measurement on molecular junctions open the door toward new nanoscience and nanotechnology in molecular electronics.

Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique

Charge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting that the junction environment was perturbing the process significantly. This study opens the possibility of using nano-structured environments like molecular junctions to tailor product ratios in chemical reactions.

Supramolecular Systems and Chemical Reactions in Single-Molecule Break Junctions.

The major challenges of molecular electronics are the understanding and manipulation of the electron transport through the single-molecule junction. With the single-molecule break junction techniques, including scanning tunneling microscope break junction technique and mechanically controllable break junction technique, the charge transport through various single-molecule and supramolecular junctions has been studied during the dynamic fabrication and continuous characterization of molecular junctions. This review starts from the charge transport characterization of supramolecular junctions through a variety of noncovalent interactions, such as hydrogen bond, π-π interaction, and electrostatic force. We further review the recent progress in constructing highly conductive molecular junctions via chemical reactions, the response of molecular junctions to external stimuli, as well as the application of break junction techniques in controlling and monitoring chemical reactions in situ. We suggest that beyond the measurement of single molecular conductance, the single-molecule break junction techniques provide a promising access to study molecular assembly and chemical reactions at the single-molecule scale.

Unraveling Hydrophobic Interactions at the Molecular Scale Using Force Spectroscopy and Molecular Dynamics Simulations.

Interactions between hydrophobic moieties steer ubiquitous processes in aqueous media, including the self-organization of biologic matter. Recent decades have seen tremendous progress in understanding these for macroscopic hydrophobic interfaces. Yet, it is still a challenge to experimentally measure hydrophobic interactions (HIs) at the single-molecule scale and thus to compare with theory. Here, we present a combined experimental-simulation approach to directly measure and quantify the sequence dependence and additivity of HIs in peptide systems at the single-molecule scale. We combine dynamic single-molecule force spectroscopy on model peptides with fully atomistic, both equilibrium and nonequilibrium, molecular dynamics (MD) simulations of the same systems. Specifically, we mutate a flexible (GS)5 peptide scaffold with increasing numbers of hydrophobic leucine monomers and measure the peptides' desorption from hydrophobic self-assembled monolayer surfaces. Based on the analysis of nonequilibrium work-trajectories, we measure an interaction free energy that scales linearly with 3.0-3.4 kBT per leucine. In good agreement, simulations indicate a similar trend with 2.1 kBT per leucine, while also providing a detailed molecular view into HIs. This approach potentially provides a roadmap for directly extracting qualitative and quantitative single-molecule interactions at solid/liquid interfaces in a wide range of fields, including interactions at biointerfaces and adhesive interactions in industrial applications.

New three-dimensional model based on finite element method of bone nanostructure: single TC molecule scale level

At the macroscopic scale, the bone mechanical behavior (fracture, elastic) depends mainly on its components’ nature at the nanoscopic scale (collagen, mineral). Thus, an understanding of the mechanical behavior of the elementary components is demanded to understand the phenomena that can be observed at the macroscopic scale. In this article, a new numerical model based on finite element method is proposed in order to describe the mechanical behavior of a single Tropocollagen molecule. Furthermore, a parametric study with different geometric properties covering the molecular composition and the rate hydration influence is presented. The proposed model has been tested under tensile loading. While focusing on the entropic response, the geometric parameter variation effect on the mechanical behavior of Tropocollagen molecule has been revealed using the model. Using numerical and experimental testing, the obtained numerical simulation results seem to be acceptable, showing a good agreement with those found in literature.

Single-Molecule Force Spectroscopy Quantification of Adhesive Forces in Cucurbit[8]Uril Host–Guest Ternary Complexes

Cucurbit[8]uril (CB[8]) heteroternary complexes display certain characteristics making them well-suited for molecular level adhesives. In particular, careful choice of host-guest binding pairs enables specific, fully reversible adhesion. Understanding the effect of the environment is also critical when developing new molecular level adhesives. Here we explore the binding forces involved in the methyl viologen·CB[8]·naphthol heteroternary complex using single-molecule force spectroscopy (SMFS) under a variety of conditions. From SMFS, the interaction of a single ternary complex was found to be in the region of 140 pN. Additionally, a number of surface interactions could be readily differentiated using the SMFS technique allowing for a deeper understanding of the dynamic heteroternary CB[8] system on the single-molecule scale.

The Sodium Channel Auxiliary Subunit β1 is Structurally Critical for Cardiac Conduction: Evidence from the Single Molecule Scale to the Whole Organ

Electrical impulse propagation in the heart's ventricles is thought to occur by means of direct flow of electric current from cell to cell via gap junctions (GJs) composed of connexin43 (Cx43). We recently demonstrated that cardiac sodium channels (Nav1.5) localized within the perinexus, an intercalated disk (ID) nanodomain adjacent to Cx43 GJ, may enable ephaptic coupling between cardiac myocytes. We hypothesized that the cell adhesion function of β1 may contribute to close intermembrane apposition within these nanodomains and thereby facilitate ephaptic coupling. Super-resolution STochastic Optical Reconstruction Microscopy-based Relative Localization Analysis (STORM-RLA) identified two populations of NaV1.5 within the ID in guinea pig ventricles: One, localized to the perinexus, within 200nm of Cx43 GJs, accounted for 47% of ID-localized NaV1.5 and the other, which co-distributed with N-Cadherin to plicate ID regions, accounted for 29% of ID-localized NaV1.5. These findings were confirmed by immuno-electron microscopy. Confocal microscopy revealed β1 enrichment at the ID, and suggested preferential localization to GJ-enriched interplicate ID regions. STORM-RLA confirmed the preferential localization of β1 to interplicate ID regions: Perinexal nanodomains accounted for 48% of ID-localized β1, whereas N-Cadherin-rich plicate regions accounted for only 8%. In order to test the role of β1 adhesion in the heart, we developed a novel peptide inhibitor of β1 adhesion - βadp1. In electric cell-substrate impedance spectroscopy studies, it inhibited the barrier function in β1-overexpressing 1610 cells but not in native 1610 cells. In guinea pig ventricles, βadp1 (100 µM) compromised the diffusion-resistance of the ID as assessed by perfusion of fixable fluorescent dyes: A 0.5kD molecule preferentially accumulated within IDs in control hearts but not in βadp1-treated hearts. Perinexal intermembrane spacing measured by transmission electron microscopy was increased in βadp1-treated hearts (48 ± 4 µm) compared to untreated hearts (17± 1µm) and those treated with a scrambled control peptide, βadp1-scr (22 ± 1 µm). Notably, neither peptide affected membrane spacing at other ID locations. In optical mapping studies, βadp1 but not βadp1-scr preferentially decreased transverse conduction velocity, increased anisotropy and precipitated spontaneous tachyarrhythmias in a dose-dependent manner. In conclusion, these results suggest a critical role of β1-mediated adhesion in generating close apposition between NaV1.5-rich perinexal membranes and thereby, facilitating ephaptic conduction in the heart. Further, these data highlight β1-mediated adhesion as a target for novel, mechanistically-driven antiarrhythmic therapy.

Membrane Recruitment can Increase the Number of Protein Assemblies by Many Folds: Insights from Theory and Reaction-Diffusion Simulation

A significant number of the cellular protein interaction networks, such as receptor-mediated signaling and vesicle trafficking pathways, includes reactions that involve membranes as a molecular assembly platform. Membranes both reduce the search space and induce a cooperative binding effect for stabilizing complexes with multiple membrane recruiter molecule binding sites. Mathematical models and computer simulations provide insight into the dynamics of complex formation and help identify general principles that govern successful recruitment and assembly on membranes. However, sufficiently long and physically accurate simulations of protein assemblies are quite challenging. In this work, using equilibrium theory and a very efficient in-lab developed single-molecule scale stochastic simulation software, we provide simple formulas for quantifying how the ratio of membrane-to-solution, both in vitro and in vivo, can change the observed protein-protein interaction strengths of peripheral membrane proteins by orders of magnitude. We show that the magnitude of complex formation enhancement has a simple functional form that applies whenever membrane recruiter concentrations are sufficiently high, and surprisingly, is independent of the protein binding strength. We propose that membrane localization works as a mechanism that ensures assembly only at specific times (after recruitment to surfaces) but does not precisely regulate the proteins involved since they benefit equally from surface restriction. This robust strategy is employed by adaptor proteins involved in clathrin-mediated endocytosis in both yeast and mammalian cells, where their relatively weak binding interactions with one another prevents protein coat assembly in solution, but transitions to a rapid assembly on the plasma membrane.

Computational smart polymer design based on elastin protein mutability.

Soluble elastin-like peptides (ELPs) can be engineered into a range of physical forms, from hydrogels and scaffolds to fibers and artificial tissues, finding numerous applications in medicine and engineering as "smart polymers". Elastin-like peptides are attractive candidates as a platform for novel biomaterial design because they exhibit a highly tunable response spectrum, with reversible phase transition capabilities. Here, we report the design of the first virtual library of elastin-like protein models using methods for enhanced sampling to study the effect of peptide chemistry, chain length, and salt concentration on the structural transitions of ELPs, exposing associated molecular mechanisms. We describe the behavior of the local molecular structure under increasing temperatures and the effect of peptide interactions with nearest hydration shell water molecules on peptide mobility and propensity to exhibit structural transitions. Shifts in the magnitude of structural transitions at the single-molecule scale are explained from the perspective of peptide-ion-water interactions in a library of four unique elastin-like peptide systems. Predictions of structural transitions are subsequently validated in experiment. This library is a valuable resource for recombinant protein design and synthesis as it elucidates mechanisms at the single-molecule level, paving a feedback path between simulation and experiment for smart material designs, with applications in biomedicine and diagnostic devices.

Controlling the formation process and atomic structures of single pyrazine molecular junction by tuning the strength of the metal-molecule interaction.

The formation process and atomic structures were investigated for single pyrazine molecular junctions sandwiched by three different Au, Ag, and Cu electrodes using a mechanically controllable break junction technique in ultrahigh vacuum conditions at 300 K. We demonstrated that the formation process of the single-molecule junction crucially depended on the choice of the metal electrodes. While single-molecule junction showing two distinct conductance states were found for the Au electrodes, only the single conductance state was evident for the Ag electrodes, and there was no junction formation for the Cu electrodes. These results suggested that metal-molecule interaction dominates the formation process and probability of the single-molecule junction. In addition to the metal-molecule interaction, temperature affected the formation process of the single-molecule junction. The single pyrazine molecular junction formed between Au electrodes exhibited significant temperature dependence where the junction-formation probability was about 8% at 300 K, while there was no junction-formation at 100 K. Instead of the junction formation, an Au atomic wire was formed at the low temperature. This study provides insight into the tuning of the junction-forming process for single-molecule junctions, which is needed to construct device structures on a single molecule scale.

Charge carrier transition in an ambipolar single-molecule junction: Its mechanical-modulation and reversibility

AbstractPrecise control from the bottom-up for realizing tunable functionality is of utmost importance to facilitate the development of molecular electronic devices. Until now, however, manipulating charge carriers over single-molecule scale remains intractable. The origin of the problem is that the nature of charge carriers is often hindered by the complexity of the investigated molecular systems. Here, via ab initio simulations, we show a force-modulated and switched ambipolar single-molecule junction with Au/cyclopropane-1,2-dithiol/Au structure. The cyclopropane ring in the molecule can be opened and closed reversibly and repeatedly by the mechanical force. This structural transition from its closed state to open state enables the ambipolarity in charge carriers—from p-type to n-type. Analysis of electronic structure reveals unambiguously the force-dependent correlation between C–S bond order and the nature of charge carriers. Based on this, we design a binary interconnected junction exhibiting resistance, rectification and negative differential resistance functionalities under mechanical modulation, i.e., loading/unloading or pull/push. This interesting phenomenon provides both illuminating insight and feasible controllability into charge carriers in molecules, and a very general idea and useful approach for single-molecule junctions in practical single-molecule devices.