For many years, an oriented external electric field (OEEF) has been theoretically projected as an active and smart reagent for chemical reaction selectivity, isomerization, and catalysis ^[1][36]. Directing EEF along the coordinate of the reaction pathway has the potential to lower energy barriers and manipulate resonance stability, further driving chemical reactions ^[2][37]. Recently, this theoretical promise has witnessed a profound experimental breakthrough at the single-molecule scale, thanks to the promising SMJ technique. In the presence of an electric field, reacting species can undergo several known phenomena: (a) the Stark effect—which explains the shifting and/or splitting of the spectra lines of discrete molecules or atoms when exposed to an OEEF ^[3][4][5][38,39,40]. (b) Zwitterionic state stabilization—OEEF directly impacts the stability of charge-separated zwitterionic states by lowering the energy of the transition states; this stabilization effect helps to monitor the transient ionic species as the reaction progress ^[6][41]. (c) Bond cleavage—orienting an electric field in the reaction axis has the potential to polarize the bonds in the reaction coordinate which eventually causes heterolytic bond cleavage ^[7][42]. (d) Selectivity—OEEF has also been established to selectively catalyze chemical reactions by favoring the formation of specific product against another ^[1][8][36,43].

Synthetic chemists are often challenged with answering key questions about (i) how do chemical reactions occur? (ii) At what time scale do reactant species undergo chemical changes? (iii) What are the intermediate states of the reactant species undergoing a chemical reaction? Emerging intermediate chemistry also seeks the possibility of trapping intermediate species as an active precursor for secondary reactions. Thorough understanding of a chemical process requires in-depth investigation of both the dynamics and kinetics of a chemical reaction. While reaction dynamics focus on the mechanism of chemical changes while accounting for the drive causing the change, kinetics study concerns the rate at which the chemical transformation occurs (i.e., standard measure of the frequency at which reactant species undergo chemical changes) ^[9][10][2,6]. Careless observation of bulk reaction processes may potentially create ambiguity or misinterpretation, and consequently leads to misinformation of key reaction processes. One unique advantage of single-molecule investigation is that it enables direct tracking of the time trajectory of reaction pathways, which helps to unveil the molecular geometry of intermediates/transient states that are often inaccessible in ensemble measurements ^[11][12][46,47].

Recently, Yang et al. took advantage of the high stability and temporal resolution of the GMG junction to unveil an unprecedented time trajectory of the Diels–Alder reaction under a high electric field ^[13][50]. They used electric current signals to distinguish five different zwitterionic intermediate states and their time scales. The Diels–Alder reaction is considered “concerted” (all bond formations and breaking are mechanistic but in a single step); therefore, the time scale of the intermediate states is faster than the response of many conventional spectroscopy techniques. They also reacted maleimide with furan while changing the orientation of the external electric field and observed that orienting the electric field along the line connecting the partial charge delayed the transition structure. Jia et al. designed a reversible photo-switch by covalently trapping a single molecule of light-sensitive diarylethene in the nano-space of two graphene electrodes ^[14][51]. The original form of the molecule is insulating and denoted as being open form. In the GMG junction, they varied the wavelength of light to excite electrons in the molecule, which induced reversible switching of the current signals with a high on/off ratio.

Understanding the Suzuki–Miyaura coupling has witnessed tremendous attention from organic and organometallic chemists because of its mild reaction condition, ecological friendliness, availability of common boronic acid, and ultimately, it offers a reliable means of preparing a wide range of organic compounds using natural precursors ^[15][16][17][52,53,54]. However, despite this great attention, the full reaction pathway and specific reaction intermediate of Suzuki–Miyaura coupling remain elusive ^[18][19][20][55,56,57]. Contrary to the conventional analytical techniques that rely on taking averages of an ensemble to characterize the unstable fleeting intermediates, Yang et al. cleverly deployed label-free, high resolution, non-destructive, single-molecule junctions to monitor and unveil the full pathway and reaction intermediate of Suzuki–Miyaura coupling ^[21][58]. They covalently bound a single molecule of palladium catalyst between a nanogap of graphene electrodes. They reported distinct, sequential, and periodic electrical signals emanating from oxidative addition/ligand exchange, pretransmetallation, transmetallation, and reductive elimination. The periodic cycles comprised of three conductance states were revealed. The first conductance state corresponds to oxidative addition followed by an instantaneous ligand exchange that was not observable in the bulk catalytic process due to its short lifetime. After the first step, successive second and third conductance plateaus followed which translate to the transition from the ion exchange to the pretransmetallation and transmetallation stages. The results of their work decoupled the ambiguity in the Suzuki–Miyaura cross-coupling and clarified that ion exchange is a transient state that precedes the rate-dependent transmetallation step. A clear understanding of the specific reaction pathway and time trajectory of the intermediate stages of reactions is key to fostering the design of highly efficient and economical catalytic processes.

In 1987, the Nobel prize in chemistry was awarded to Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen for their landmark achievement in the development of a structure-specific assembly of molecules motivated by noncovalent interactions of defined selectivity called the “Host–Guest” systems ^[22][23][59,60]. Since then, research into the host–guest systems has become increasingly popular among chemists, physicists, advanced material scientists, and biologists as applied to drug delivery, nanomedicine, molecular electronics, sensors and actuators, catalysis, functional materials, and so on ^{[24][25][26][27][28]}[61,62,63,64,65]. Simple and complex supramolecular structures can be assembled when a “host” (macrocycles) molecule accommodates another “guest” molecule through any form of noncovalent interactions like π-π interaction, van der Waals interaction, electrostatic interactions, hydrophobic/hydrophilic interactions, and hydrogen bonding ^[29][66]. It has been shown that the robust SMJ techniques can also account for weak noncovalent interactions between the host and guest molecules ^[30][1].

A reduction and oxidation (redox) reaction involves the simultaneous transfer of electron(s) between chemical species (atoms, ions, molecules) taking part in a chemical reaction ^[31][70]. Due to the ubiquitous nature of redox reactions in many important areas, such as corrosion, catalysis, combustion, and photosynthesis, understanding the details of mechanistic processes of redox reactions and the rationalization of previously unknown electron and proton transfer phenomena of single molecules in electrochemical systems has attracted significant attention in recent years ^[32][33][71,72]. To this end, one of the productive foregoing directions is to exFMJ is often dominated by either coherent tunneling or incoherent hopping. Coherent tunneling is a phase retention, single-step process where the molecular core behaves as a scatterer. The Landauer formalism accurately predicts a zero-bias conductance G=G0T(EF), where quantum conductance G0=2e2/h=77.8 μS, and T(EF) is the transmission function of electrons at the Fermi energy of electrode EF. In an electrolytic environment, where the molecular core is undergoing a redox reaction by an electrochemical potential, the T(EF) changes ^[34][35][75,76]. This change alters the electron transmission efficiency of the system, resulting in a sudden current change around the electrochemical equilibrium potential of the molecule undergoing the redox reaction. In this regime, plotting the electrochemical response of the redox molecule against the conductance shows a sigmoidal shape at the center which connotes the potential at which the redox transition takes place ^[36][37][38][77,78,79]. Incoherent hopping, on the other hand, is considered a combination of multiple-step transport processes, with the molecular core accepting and releasing charges for a non-zero time. When a redox-active molecule is used as a hopping site for charges, the mechanism of the charge transport is semi-classical based on the Marcus theory with multiple rate constants ^[39][40][80,81]. A redox reaction occurs when a single electron travels from the source electrode to the drain electrode, leading to a rearrangement of the reaction energetics of the entire redox cell to accommodate the cascade electron-hopping processes ^[38][41][73,79]. The shift in the reaction energetics results in an enhancement of the charge transport efficiency at the equilibrium potential. Contrary to the sigmoidal-shaped signature of the conductance vs. electrochemical potential of the coherent tunneling transport, the incoherent hopping transport of redox-active molecules is bell-shaped with its maximum at the transition potential ^[42][43][82,83].

Several open and closed shell redox-active moieties, including benzodifuran ^[33][72], diazonium ^[44][84], metalloproteins ^[45][46][47][85,86,87], coronene ^[48][88], bipyridinium ^[38][43][79,83], anthraquinones ^[49][89], Cucurbit[n]uril ^[50][74], polyoxometalate ^[51][90], viologen ^[49][89], perylene tetracarboxylic acid ^[52][53][54][91,92,93], ferrocene ^[55][94], etc., have been studied at the single-molecule level by sweeping potentials in an electrochemical cell. During a potential sweep, they observed that the neutral state of ND showed a conductance 10⁻⁴ G₀ at −0.20 V which changed to 10^−3.3 G₀ at −1.50 V upon reduction to the first anionic radical (ND¹⁻) state. At −1.50 V, the conductance also increased to 10^−3.0 G₀ as a result of further reduction to the second anionic (ND^2-) state. In another experiment, Chen et al. added a positively charged electrostatic anchor formed from the Coulombic interaction between Au electrodes and positively charged pyridinium terminals to the existing anchor bank ^[56][96]. In their work, they also demonstrated redox switching sponsored by charge injection in neutral 4,4′-bipyridine (BIP), radical cationic bipyridine-methyl viologen (BIP-Me^•+), and dicationic BIP-Me²⁺. The conductance measurement in the three species shows two (low and high) distinct conductance plateaus. The low and high conductance states in the neutral state were attributed to the change in the contact geometry of the single-molecule junction during tip retraction. However, there is a significant increase in the bimodal conductance states of BIP-Me^•+ and dicationic BIP-Me²⁺ traceable to the key role of the anchor group in electron injection and extraction.