Single-Molecule Electron Transfer in Electrochemical Environments Jingdong Zhang, † Alexander M. Kuznetsov, ‡ Igor G. Medvedev, ‡ Qijin Chi, † Tim Albrecht, § Palle S. Jensen, † and Jens Ulstrup* ,† Department of Chemistry, Building 207 and NanoDTU, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark, The A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskij Prospect 31, 119071 Moscow, Russia, and Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, U.K. Received November 27, 2007 Contents 1. Introduction 2738 2. Single-Molecule Electrochemical Science and Technology: A Brief Overview 2740 2.1. A Primer of Single-Molecule Science 2740 2.2. Single-Molecule Fluorescence and Chemical Dynamics 2740 2.3. The Scanning Probe Microscopies STM and AFM, and Nanoscale Electrochemical Imaging and Chemical Reactivity 2741 2.3.1. In Situ STM, and Electrochemical Nanogap Electrodes and Nanowires 2741 2.3.2. Some Notions from AFM 2742 2.4. Molecular Electronics 2743 2.4.1. Notions of Single-Molecule Electronic Conductivity of Nonredox Molecules 2743 2.4.2. Molecular Rectification and Amplification 2744 2.4.3. Electrochemical Switching, Molecular Wiring, and Electronic Circuits 2745 3. Theoretical Frames of Interfacial Electrochemical ET at Macroscopic and Molecular Scales 2746 3.1. Elements of the Formal Theory of Interfacial Electrochemical ET 2746 3.1.1. Nonadiabatic Electrochemical ET Reactions 2746 3.1.2. Adiabatic Electrochemical ET Reactions 2748 3.1.3. The Intermediate Region 2749 3.2. Electrochemically Controlled Single-Electron Transitions 2749 3.3. ET Concepts and Formalism at the Molecular Scale: Nonredox Molecules 2749 3.4. ET Concepts and Formalism at the Molecular Scale - Redox Molecules 2750 3.4.1. Totally Nonadiabatic Transitions 2751 3.4.2. Reaction Free Energy of the Transition and the Electrode Potentials 2752 3.4.3. The Strong-Coupling Limit and Coherent Transitions in Electrochemical in Situ STM 2755 3.5. Two-Center Molecular Redox Targets 2757 3.6. Low-Temperature Behavior of a Multilevel Molecular-Scale Bridge 2758 3.7. Redox Switching of the Bridge Molecule 2758 3.8. Noise in Bridge Molecular Tunneling Contacts 2759 3.8.1. Shot Noise 2759 3.8.2. Telegraphic Noise 2759 3.9. Double Tunneling Contact with a Redox Group (Redox Molecule/NP Hybrids) 2760 3.10. Some Concluding Observations on Redox Mediated Single-molecule Contacts 2760 4. A Primary Target Class: Small Nonredox Molecules 2761 4.1. Self-Assembled Molecular Monolayers: Nonredox Paradigms 2761 4.2. Electrochemistry and In Situ STM Imaging and Image Interpretation 2761 4.3. Electrochemistry and In Situ STM of Nonredox Alkanethiol-Based Molecules 2762 4.3.1. Packing Modes and Image Interpretation of Straight and Branched Alkanethiols 2762 4.3.2. Structural and Electronic In Situ STM Interpretation: Cysteine, Cystine, and Homocysteine 2763 4.3.3. The SAM-Formation Process in Real Time: Cysteamine and 1-Propanethiol 2764 4.3.4. Thermally Gated Single-molecule Conductivity of Nonredox Molecules 2766 5. Redox Molecules and New Electrochemical Molecular Tunneling Paradigms 2767 5.1. Single-Molecule Electrochemical Tunneling Spectroscopy of Redox Molecules 2767 5.2. Metalloporphyrins and Metallophthalocyanines 2767 5.3. Organic Redox Molecules in Electrochemical Break-junctions 2767 5.4. The Viologens 2768 5.5. Transition Metal Complexes 2769 6. Bioelectrochemistry at Molecular Levels of Structural and Functional Resolution 2771 6.1. Protein Film Voltammetry and Ordered Surface Structures of Linker Molecules 2771 6.2. Redox Metalloproteins at Bare and Modified Au(111) Electrodes 2772 6.2.1. Pyrococcus furiosus Ferredoxin 2772 6.2.2. The Heme Proteins: Horse Heart and Yeast Cytochrome c, De Novo Designed Synthetic 4-Alpha Helix Bundle Heme Protein and Two-Center Cytochrome c 4 2773 6.3. The Blue Copper Proteins 2776 6.3.1. The Blue Copper Protein Pseudomonas aeruginosa Azurin: A Nanoscale Bioelectrochemical Paradigm 2776 6.4. Redox Metalloenzymes in Electrocatalytic Action at the Single-Molecule Level: The Multicopper and Multiheme Nitrite Reductases 2778 * To whom correspondence should be addressed. † Technical University of Denmark. ‡ Russian Academy of Sciences. § Imperial College London. Chem. Rev. 2008, 108, 2737–2791 2737 10.1021/cr068073+ CCC: $71.00  2008 American Chemical Society Published on Web 07/11/2008