Heavy Water Reduces the Electronic Conductance of Protein Wires via Deuteron Interactions with Aromatic Residues.

Proteins are versatile, self-assembling nanoelectronic components, but their hopping conductivity is expected to be influenced by solvent fluctuations. The role of the solvent was investigated by measuring the single molecule conductance of several proteins in both H2O and D2O. The conductance of a homologous series of protein wires decreases more rapidly with length in D2O, indicating a 6-fold decrease in carrier diffusion constant relative to the same protein in H2O. The effect was found to depend on the specific aromatic amino acid composition. A tryptophan zipper protein showed a decrease in conductance similar to that of the protein wires, whereas a phenylalanine zipper protein was insensitive to solvent changes. Tryptophan contains an indole amine, whereas the phenylalanine aromatic ring has no exchangeable protons, so the effect of heavy water on conductance is a consequence of specific D- or H-interactions with the aromatic residues.

Anisotropic Conductivity at the Single-Molecule Scale.

In most junctions built by wiring a single molecule between two electrodes, the electrons flow along only one axis: between the two anchoring groups. However, molecules can be anisotropic, and an orientation-dependent conductance is expected. Here, we fabricated single-molecule junctions by using the electrode potential to control the molecular orientation and access individual elements of the conductivity tensor. We measured the conductance in two directions, along the molecular plane as the benzene ring bridges two electrodes using anchoring groups (upright) and orthogonal to the molecular plane with the molecule lying flat on the substrate (planar). The perpendicular (planar) conductance is about 400 times higher than that along the molecular plane (upright). This offers a new method for designing a reversible room-temperature single-molecule electromechanical switch that controllably employs the electrode potential to orient the molecule in the junction in either "ON" or "OFF" conductance states.

Potential-Induced High-Conductance Transport Pathways through Single-Molecule Junctions.

Employing single molecules as electronic circuit building blocks is one promising approach to electronic device miniaturization. We report single-molecule junction formation where the orientation of molecules can be controlled externally by the working electrode potential. The scanning tunneling microscopy break junction (STM-BJ) method is used to bridge tetrafluoroterephthalic acid (TFTPA) and terephthalic acid (TPA) molecules between the Au(111) electrode and the STM tip to measure the single-molecule conductance through the junction. When the Au(111) electrode is at negative potentials (with respect to the zero-charge potential), a highly ordered and flat-oriented superstructure forms, allowing for direct contact between the π system of the benzene ring of the molecules and the Au(111) electrode, leading to junction formation with no anchoring group involvement. Our first-principles nonequilibrium Green's function (NEGF) computation shows a flat configuration yields a conductance that is 3 orders of magnitude larger than for a molecule vertically connected to the electrodes via anchoring groups. Conductances of 0.24 ± 0.04 and 0.22 ± 0.02 G0 are experimentally measured with the flat configurations of TFTPA and TPA, respectively. These values are at least 2 orders of magnitude higher than the experimental values previously reported for the conductance of TPA bridged through carboxylic acid anchoring groups (3.8 × 10-4-3.2 × 10-3 G0). In contrast, a positively charged surface triggers an order-disorder transition eliminating the high-conductance states, most likely because the formation of the flat-oriented junction is prevented. The dependence of TFTPA conductance on the electrode potential (electrode Fermi level) suggests a LUMO mediated transport mechanism. Calculation confirms the lack of an effect of the addition of an electron-withdrawing group are investigated.

Conformational Smear Characterization and Binning of Single-Molecule Conductance Measurements for Enhanced Molecular Recognition.

Electronic conduction or charge transport through single molecules depends primarily on molecular structure and anchoring groups and forms the basis for a wide range of studies from molecular electronics to DNA sequencing. Several high-throughput nanoelectronic methods such as mechanical break junctions, nanopores, conductive atomic force microscopy, scanning tunneling break junctions, and static nanoscale electrodes are often used for measuring single-molecule conductance. In these measurements, "smearing" due to conformational changes and other entropic factors leads to large variances in the observed molecular conductance, especially in individual measurements. Here, we show a method for characterizing smear in single-molecule conductance measurements and demonstrate how binning measurements according to smear can significantly enhance the use of individual conductance measurements for molecular recognition. Using quantum point contact measurements on single nucleotides within DNA macromolecules, we demonstrate that the distance over which molecular junctions are maintained is a measure of smear, and the resulting variance in unbiased single measurements depends on this smear parameter. Our ability to identify individual DNA nucleotides at 20× coverage increases from 81.3% accuracy without smear analysis to 93.9% with smear characterization and binning (SCRIB). Furthermore, merely 7 conductance measurements (7× coverage) are needed to achieve 97.8% accuracy for DNA nucleotide recognition when only low molecular smear measurements are used, which represents a significant improvement over contemporary sequencing methods. These results have important implications in a broad range of molecular electronics applications from designing robust molecular switches to nanoelectronic DNA sequencing.

Quantum Point Contact Single-Nucleotide Conductance for DNA and RNA Sequence Identification.

Several nanoscale electronic methods have been proposed for high-throughput single-molecule nucleic acid sequence identification. While many studies display a large ensemble of measurements as "electronic fingerprints" with some promise for distinguishing the DNA and RNA nucleobases (adenine, guanine, cytosine, thymine, and uracil), important metrics such as accuracy and confidence of base calling fall well below the current genomic methods. Issues such as unreliable metal-molecule junction formation, variation of nucleotide conformations, insufficient differences between the molecular orbitals responsible for single-nucleotide conduction, and lack of rigorous base calling algorithms lead to overlapping nanoelectronic measurements and poor nucleotide discrimination, especially at low coverage on single molecules. Here, we demonstrate a technique for reproducible conductance measurements on conformation-constrained single nucleotides and an advanced algorithmic approach for distinguishing the nucleobases. Our quantum point contact single-nucleotide conductance sequencing (QPICS) method uses combed and electrostatically bound single DNA and RNA nucleotides on a self-assembled monolayer of cysteamine molecules. We demonstrate that by varying the applied bias and pH conditions, molecular conductance can be switched ON and OFF, leading to reversible nucleotide perturbation for electronic recognition (NPER). We utilize NPER as a method to achieve >99.7% accuracy for DNA and RNA base calling at low molecular coverage (∼12×) using unbiased single measurements on DNA/RNA nucleotides, which represents a significant advance compared to existing sequencing methods. These results demonstrate the potential for utilizing simple surface modifications and existing biochemical moieties in individual nucleobases for a reliable, direct, single-molecule, nanoelectronic DNA and RNA nucleotide identification method for sequencing.

Single Nucleobase Identification Using Biophysical Signatures from Nanoelectronic Quantum Tunneling.

Nanoelectronic DNA sequencing can provide an important alternative to sequencing-by-synthesis by reducing sample preparation time, cost, and complexity as a high-throughput next-generation technique with accurate single-molecule identification. However, sample noise and signature overlap continue to prevent high-resolution and accurate sequencing results. Probing the molecular orbitals of chemically distinct DNA nucleobases offers a path for facile sequence identification, but molecular entropy (from nucleotide conformations) makes such identification difficult when relying only on the energies of lowest-unoccupied and highest-occupied molecular orbitals (LUMO and HOMO). Here, nine biophysical parameters are developed to better characterize molecular orbitals of individual nucleobases, intended for single-molecule DNA sequencing using quantum tunneling of charges. For this analysis, theoretical models for quantum tunneling are combined with transition voltage spectroscopy to obtain measurable parameters unique to the molecule within an electronic junction. Scanning tunneling spectroscopy is then used to measure these nine biophysical parameters for DNA nucleotides, and a modified machine learning algorithm identified nucleobases. The new parameters significantly improve base calling over merely using LUMO and HOMO frontier orbital energies. Furthermore, high accuracies for identifying DNA nucleobases were observed at different pH conditions. These results have significant implications for developing a robust and accurate high-throughput nanoelectronic DNA sequencing technique.

Amine-Directed Hydrogen-Bonded Two-Dimensional Supramolecular Structures.

Utilizing pure amine hydrogen bonding is a novel approach for constructing two-dimensional (2D) networks. Further, such systems are capable of undergoing structural modifications due to changes in pH. In this study, we designed a 2D network of triaminobenzene (TAB) molecules that by varying the pH from neutral to acidic, form either ordered or disordered structures on Au(111) surface as revealed in scanning tunneling microscopy images. In near-neutral solution (pH ≈5.5), protonation of TAB generates charged species capable of forming H-bonds between amine groups of neighboring molecules resulting in the formation of a 2D supramolecular structure on the electrified surface. At lower pH, due to the protonation of the amine groups, intermolecular hydrogen bonding is no longer possible and no ordered structure is observed on the surface. This opens the possibility to employ pH as a chemical trigger to induce a phase transition in the 2D molecular network of triaminobenzene molecules.

Orientation-controlled single-molecule junctions.

The conductivity of a single aromatic ring, perpendicular to its plane, is determined using a new strategy under ambient conditions and at room temperature by a combination of molecular assembly, scanning tunneling microscopy (STM) imaging, and STM break junction (STM-BJ) techniques. The construction of such molecular junctions exploits the formation of highly ordered structures of flat-oriented mesitylene molecules on Au(111) to enable direct tip/π contacts, a result that is not possible by conventional methods. The measured conductance of Au/π/Au junction is about 0.1 G(o) , two orders of magnitude higher than the conductance of phenyl rings connected to the electrodes by standard anchoring groups. Our experiments suggest that long-range ordered structures, which hold the aromatic ring in place and parallel to the surface, are essential to increase probability of the formation of orientation-controlled molecular junctions.

Single-molecule sensing of environmental pH--an STM break junction and NEGF-DFT approach.

Sensors play a significant role in the detection of toxic species and explosives, and in the remote control of chemical processes. In this work, we report a single-molecule-based pH switch/sensor that exploits the sensitivity of dye molecules to environmental pH to build metal-molecule-metal (m-M-m) devices using the scanning tunneling microscopy (STM) break junction technique. Dyes undergo pH-induced electronic modulation due to reversible structural transformation between a conjugated and a nonconjugated form, resulting in a change in the HOMO-LUMO gap. The dye-mediated m-M-m devices react to environmental pH with a high on/off ratio (≈100:1) of device conductivity. Density functional theory (DFT) calculations, carried out under the non-equilibrium Green's function (NEGF) framework, model charge transport through these molecules in the two possible forms and confirm that the HOMO-LUMO gap of dyes is nearly twice as large in the nonconjugated form as in the conjugated form.