Stochasticity in single-entity electrochemistry

Most electrochemical processes are stochastic and discrete in nature. Yet experimental observables, for example, i vs E, are typically smooth and deterministic, because of many events/processes, for example, electron transfers, being averaged together. However, when the number of entities measured approaches a few or even one, stochasticity frequently emerges. Yet all is not lost! Probabilistic and statistical interpretation can generate insights matching or superseding those from macroscale/ensemble measurements, revealing phenomena that were hitherto averaged over. Herein, we review recent literature examples of stochastic processes in single-entity electrochemistry, highlighting strategies for interpreting stochasticity, contrasting them with macroscale measurements and describing the insights generated.     

Single-entity electrochemistry at confined sensing interfaces

Measurements at the single-entity level provide more precise diagnosis and understanding of basic biological and chemical processes. Recent advances in the chemical measurement provide a means for ultra-sensitive analysis. Confining the single analyte and electrons near the sensing interface can greatly enhance the sensitivity and selectivity. In this review, we summarize the recent progress in single-entity electrochemistry of single molecules, single particles, single cells and even brain analysis.The benefits of confining these entities to a compatible size sensing interface are exemplified. Finally, the opportunities and challenges of single entity electrochemistry are addressed.     

The role of macromolecular crowding in single-entity electrochemistry: Friend or foe?

The recent development of nanoscale probes has enabled the study of single molecules and single cells with unprecedented resolution and the expansion of the field of single-entity electrochemistry. There is a growing evidence suggesting that highly crowded intracellular environment facilitate nanoelectrochemical measurements in cells by improving the signal-to-noise ratio. In this opinion piece, we discuss the concept of macromolecular crowding and its implications in single-entity electrochemistry.     

Optical microscopy to study single nanoparticles electrochemistry: From reaction to motion

Nanoparticles (NPs)-based electrochemical devices are generating a growing interest and optical microscopy has recently proven to be a powerful tool to apprehend their electrochemical behavior. Through several striking examples, this review demonstrates how label-free optical imaging coupled to an electrochemical actuation can be used to probe operando the physical and electrochemical properties of single NPs, with high resolution and sensitivity and without additional emitters. Such an approach can be particularly relevant to establish clear structure-motion/reactivity relationships required to optimize NPs exploited as electrode materials.     

单体动态电化学

由于个体的差异性和异质性作用,整体平均测量掩盖了个体的本征性质和电化学性能之间的关联.单体碰撞电化学作为一种强大而方便的电化学方法,已被用于研究超微电极上自由扩散的单个个体随机碰撞过程中的电化学行为.然而,个体的动态行为与其电化学反应过程息息相关.因此,对于单体动态电化学行为的研究可实时获取单体在电极界面上的动态电化学...     

Quinone-based molecular electrochemistry and their contributions to medicinal chemistry: A look at the present and future

Molecular electrochemistry is closely linked to life sciences. Electron transfers play important roles in the bioactivation of redox-active drugs, in their metabolism/catabolism, and in their targeted release at precise destinations and frequently promote their ligand–target interactions. Altogether, this rich chemistry and the complexity of cellular environments and biocompartmentation often impede full investigation in situ of the whole chain of processes that sustain their therapeutic applications. Conversely, electrochemical ex situ investigations of drug properties and interactions performed in aqueous/aprotic/micellar/membrane/cell-mimetic media, combined with in vitro and in vivo data, are expected to provide extremely useful information on these processes. Therein, considering the ubiquitous case of quinones, we exemplified how such strategies allow controlling their beneficial or negative impact on cellular environments.     

Recent progress on nanopore electrochemistry and advanced data processing

Nanopore-based technology offers nanoscale chemical environments with intriguing confinement effects, which isolates individual analytes from the bulk solution. This confined space combines mass transportation and electrochemical measurement, providing new insight into single entity sensing. In this mini-review, we highlight the exciting progress on nanopore electrochemistry. Starting with a concise summary of nanopore-based electrodes, we introduce the fabrication methods and characterizations of the various nanopore electrodes. Then, the special attention focuses on the application of nanopore electrochemistry in single nanoparticle analyzing and intracellular electrochemical sensing. The advanced data analysis tools and Machine Learning algorithms for rapid encoding single-molecule characteristic sets are also covered, which promotes the sensitivity of nanopore electrochemistry and opens a new possibility for revealing single-entity heterogeneity.     

Opto‐electrochemical In Situ Monitoring of the Cathodic Formation of Single Cobalt Nanoparticles

Single‐particle electrochemistry at a nanoelectrode is explored by dark‐field optical microscopy. The analysis of the scattered light allows in situ dynamic monitoring of the electrodeposition of single cobalt nanoparticles down to a radius of 65 nm. Larger sub‐micrometer particles are directly sized optically by super‐localization of the edges and the scattered light contains complementary information concerning the particle redox chemistry. This opto‐electrochemical approach is used to derive mechanistic insights about electrocatalysis that are not accessible from single‐particle electrochemistry.     

Electrochemistry probed one molecule at a time

Probing electrochemical reactions at the single-reaction level is the ultimate goal for electroanalytical chemistry. The development of electrical approaches and optical methods has enabled addressing the electrochemistry of individual molecules in various systems such as scanning probe microscopy, fixed nanogaps, nanopores, single-molecule fluorescence microscopy, and single-molecule electrochemiluminescence microscopy, which can bring new views on fundamental electrochemistry, electroanalytical applications, and electrochemical cells. We conclude with potential directions for further improving the spatial and temporal resolution and developing new techniques towards meeting the requirements for achieving the outlined goals.     

Electrodeposition in aqueous nanoreactors

One frontier of measurement science is pushing the limit of what is measurable. Nanoelectrochemistry has transformed what is measurable at the nanoscale, elucidating reactivity of single atoms, molecules, and nanoparticles, one by one. The ability to interrogate physicochemical properties of single entities has elucidated new truths of nature that are otherwise averaged out during measurements over many entities (ensemble experiments). Single-entity experiments also give access to the ultimate sensitivity in measurement science: the specific detection of one single entity (not nanomolar quantities, not picomolar quantities—one single unit). One exciting subset of single-entity electrochemistry, and the topic of this review, is the study of reactions in nanoreactors of subfemtoliter (10^?15 L) volumes with a particular focus on nanoparticle synthesis.     

Molecular electronics at electrode–electrolyte interfaces

Four contemporary examples, all published in recent years, of studies of molecular electronics at electrode–electrolyte interfaces are reviewed in this opinion article. The first illustrative example involves the switching of the redox active molecular wire between redox states, with concomitant changes in molecular conductance. This example illustrates how molecular electronics at electrode–electrolyte interfaces can be used to analyse mechanisms of electron transfer, to distinguish electrolyte effects and to provide details not readily available from ensemble measurements. The second example shows that the fluctuations of molecular conductance of a redox active molecular wire can be followed as a function of electrode potential. This shows how the stochastic kinetics of individual reaction events at electrode–electrolyte interfaces can be followed. The third example demonstrates how electrochemistry can be used to control quantum interference in single molecular wires. The fourth example shows a single-molecule electrochemical transistor concept for well-defined metal cluster containing molecular wires.     

Electrochemical parameters and techniques in drug development, with an emphasis on quinones and related compounds

This review article summarizes recent applications of electrochemical techniques to redox-active drug development and mechanistic studies. It includes a general introduction to the use of electrochemistry in biology, with a focus on how electrochemistry can uniquely provide both kinetic and thermodynamic information. A number of studies are reported from the literature and the authors' laboratories, including the investigation of reactive oxygen species, biooxidative/bioreductive activation of pro-drugs, and DNA alkylation, with a particular emphasis on quinones and related compounds. Data from techniques ranging from traditional cyclic voltammetry to sophisticated single cell studies are presented. The examples herein presented illustrate how electrochemical, biochemical and medical knowledge can be integrated to develop strategies for the design and development of redox-selective therapeutics.     

Characterization of ultrafast processes at metal/solution interfaces: Towards femtoelectrochemistry

The essential part of electrochemistry is charge transfer. To understand this process in great detail, one needs to probe the relevant kinetics and dynamics on time scales spanning from femtoseconds to seconds or even longer. Although a conventional electrochemical detection scheme is sufficient for nanosecond or slower processes, it does not offer high enough time resolution for probing ultrafast processes, such as solvent reorganization, electron tunneling, and surface isomerization, that occur on faster, for example picosecond or femtosecond, timescales. These are indispensable parameters in the advanced charge transfer theories. In this review, some recent studies using ultrashort lasers to explore the ultrafast dynamics at the metal/solution interface are reviewed. The focus is on optical pump-probe and optical pump-push with electrochemical probe schemes. The connection of these studies with conventional electrochemistry and the limitations of these detection schemes are discussed.     

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.     

Stochastic collision electrochemistry of single silver nanoparticles

The electrochemical oxidation of single colloidal Ag nanoparticles (NPs) at an electrode surface has previously been studied as an in situ particle-sizing methodology. However, the discovery of multipeak amperometric behavior in 2017 sparked new interest toward understanding the precise physical mechanism of the manner in which a freely diffusing Ag NP interacts with the electrode surface. Random walk simulations, unique electrochemical experiments, and correlated optical/spectroscopic techniques have revealed exciting new results regarding the physical and chemical processes occurring on single NP collision.     

Interplay between electrochemistry and optical imaging: The whole is greater than the sum of the parts

Optical techniques can afford a powerful characterisation of the solid–liquid interface that is composed of an electrode immersed in an electrolyte. While a typical electrochemical measurement such as current intensity is averaged over the entire electrode surface, the access to surface heterogeneity can provide an increased level of information enabling to rationalise and optimise the performance of chemical or biochemical sensors. In this opinion article, we will briefly review the different strategies developed to translate an electrochemical process into a luminescence signal. Also, several key examples will be selected and commented in order to highlight the key advantages of coupling electrochemistry with optical imaging, essentially fluorescence and electrochemiluminescence.     

Electro-oxidation of amino-functionalized multiwalled carbon nanotubes

We report the electrochemistry of amino-functionalized multiwalled carbon nanotubes (MWCNTs-NH₂) in the pH range from 0.3 to 6.4 using quantitative cyclic voltammetry (CV) and single entity electrochemistry measurements, making comparison with non-functionalized MWCNTs. CV showed the latter to both catalyze the solvent (water) decomposition and to undergo irreversible electro-oxidation forming oxygen containing surface functionality. The MWCNTs-NH₂ additionally undergo an irreversible oxidation to an extent which is dependent on the pH of the solution, reflecting the variable amount of deprotonated amino groups present as a function of pH. Nano-impact experiments conducted at the single particle level confirmed the oxidation of both types of MWCNTs, showing agreement with the CV. The pK_a of the amino groups in MWCNTs was determined via both electrochemical methods giving consistent values of ca. 2.5.

A new and generic approach to the study of the oxidation of different forms of CNTs is found by using quantitative single entity and ensemble electrochemistry measurements.     

Studying single molecule electrochemistry with scanning tunneling microscope break-junction technique

The fundamental principle of molecular electronics is to comprehend electrical properties of single molecules connected between two probe electrodes. In recent years, substantial advances in this field have been made to underpin experimental and theoretical understanding of single molecule electrochemistry. By using scanning tunneling microscope (STM) break-junction technique, the switching events of electrical current from single molecule bridge tuning by electrochemical gating are investigated to uncover the relationship between electrochemical electron transfer and charge transport processes in chemical and biological molecule junctions. In this short review, we outline the latest works of single molecule electrochemistry studied with STM break-junction technique from Nongjian Tao's group, and share the insights on the opportunities and challenges for future research.     

Scanning electrochemical cell microscopy: High-resolution structure−property studies of mono- and polycrystalline electrode materials

Scanning electrochemical cell microscopy (SECCM) is a nanopipette-based scanning electrochemical probe microscopy technique that utilises a mobile droplet cell to measure and visualise electrode activity with high spatiotemporal resolution. This article spotlights the use of SECCM for studying the electrochemistry of crystalline electrode materials, ranging from well-defined monocrystals (e.g., transition metal dichalcogenides: MoS₂, WS₂ and WSe₂) to structurally/compositionally heterogeneous polycrystals (e.g., polycrystalline Pt, Au, Pd, Cu, Zn, low carbon steel, boron-doped diamond) and covering the diverse areas of (photo)electrocatalysis, corrosion science, surface science and electroanalysis. In particular, it is emphasised how nanoscale-resolved information from SECCM is readily related to electrode structure and properties, collected at a commensurate scale with complementary, co-located microscopy/spectroscopy techniques, to allow structure–property relationships to be assigned directly and unambiguously.     

Structure and dynamics of nanoscale electrical double layer

Electrical double layer (EDL) at substrate–solution interface plays essential roles in basic electrochemistry, energy conversion, desalination and separation, stochastic single-entity sensing, and other applications. The EDL structure generally refers to the inhomogeneous distribution of solution ions at the interfacial region. Dynamic changes in the EDL structure due to the transport of charges at the nanometer scale are the physicochemical origin of recently resolved novel nanotransport phenomena. High surface area materials and devices are potentially advantageous for better applications by providing more accessible interfaces. It is of high importance to emphasize that interfacial structures are indications of capacity, while the efficiency is often related to dynamics. This review discusses emerging transport phenomena under steady-state conditions and the transient deviations in prototype channel-type nanopores as unit elements for porous electrodes/membranes. The fundamental governing mechanism and structure–function correlations will be discussed in the context of energy harvesting and storage, desalination and phase transition, and resistive pulse sensing at the nanometer scale toward single-event/entity resolutions.