Moving Through Barriers in Science and Life.

This first serious attempt at an autobiographical accounting has forced me to sit still long enough to compile my thoughts about a long personal and scientific journey. I especially hope that my trajectory will be of interest and perhaps beneficial to much younger women who are just getting started in their careers. To paraphrase from Virginia Woolf's writings in A Room of One's Own at the beginning of the 20th century, "for most of history Anonymous was a Woman." However, Ms. Woolf is also quoted as saying "nothing has really happened until it has been described," a harbinger of the enormous historical changes that were about to be enacted and recorded by women in the sciences and other disciplines. The progress in my chosen field of study-the chemical basis of enzyme action-has also been remarkable, from the first description of an enzyme's 3D structure to a growing and deep understanding of the origins of enzyme catalysis.

The complexities of ligand/receptor interactions: Exploring the role of molecular vibrations and quantum tunnelling.

Molecular vibrations and quantum tunneling may link ligand binding to the function of pharmacological receptors. The well-established lock-and-key model explains a ligand's binding and recognition by a receptor; however, a general mechanism by which receptors translate binding into activation, inactivation, or modulation remains elusive. The Vibration Theory of Olfaction was proposed in the 1930s to explain this subset of receptor-mediated phenomena by correlating odorant molecular vibrations to smell, but a mechanism was lacking. In the 1990s, inelastic electron tunneling was proposed as a plausible mechanism for translating molecular vibration to odorant physiology. More recently, studies of ligands' vibrational spectra and the use of deuterated ligand analogs have provided helpful information to study this admittedly controversial hypothesis in metabotropic receptors other than olfactory receptors. In the present work, based in part on published experiments from our laboratory using planarians as an experimental organism, I will present a rationale and possible experimental approach for extending this idea to ligand-gated ion channels.

Development of an Artificially Intelligent Nanopore for High-Throughput DNA Sequencing with a Machine-Learning-Aided Quantum-Tunneling Approach.

Solid-state nanopore-based single-molecule DNA sequencing with quantum tunneling technology poses formidable challenges to achieve long-read sequencing and high-throughput analysis. Here, we propose a method for developing an artificially intelligent (AI) nanopore that does not require extraction of the signature transmission function for each nucleotide of the whole DNA strand by integrating supervised machine learning (ML) and transverse quantum transport technology with a graphene nanopore. The optimized ML model can predict the transmission function of all other nucleotides after training with data sets of all the orientations of any nucleotide inside the nanopore with a root-mean-square error (RMSE) of as low as 0.062. Further, up to 96.01% accuracy is achieved in classifying the unlabeled nucleotides with their transmission readouts. We envision that an AI nanopore can alleviate the experimental challenges of the quantum-tunneling method and pave the way for rapid and high-precision DNA sequencing by predicting their signature transmission functions.

A Playground for Heavy Atom Tunnelling: Neutral Substitutional Defect Rearrangement from Diamondoids to Diamonds.

Many diamond properties are defined by substitutional defects (i. e., a carbon atom replaced by another element), which may involve the formation of structural isomers that can interconvert. Herein, we analysed by computational means the structure, thermodynamics, and kinetics of substitutional nitrogen, boron, and oxygen from small diamondoids up to the diamond bulk, focusing on the possibility of heavy atom quantum tunnelling rearrangement between the isomers. The large range of threshold energies and bond lengths lead to a variety of intriguing behaviours, including cage size dependent thermally activated tunnelling of nitrogen, and quantum delocalization of boron. In addition, we predict that applying an external electric field makes it possible to control the rearrangement thermodynamics and kinetics through tunnelling, which lets us hypothesize that these systems can potentially be used as atomic memory devices.

Recent Developments in Kramers' Theory of Reaction Rates.

In this short review, we provide an update of recent developments in Kramers' theory of reaction rates. After a brief introduction stressing the importance of this theory initially developed for chemical reactions, we briefly present the main theoretical formalism starting from the generalized Langevin equation and continue by showing the main points of the modern Pollak, Grabert and Hänggi theory. Kramers' theory is then sketched for quantum and classical surface diffusion. As an illustration the surface diffusion of Na atoms on a Cu(110) surface is discussed showing escape rates, jump distributions and diffusion coefficients as a function of reduced friction. Finally, some very recent applications of turnover theory to different fields such as nanoparticle levitation, microcavity polariton dynamics and simulation of reaction in liquids are presented. We end with several open problems and future challenges faced up by Kramers turnover theory.

Quantum Tunneling Effect in CsPbBr3 Multiple Quantum Wells.

Two-dimensional (2D) lead halide perovskites (LHPs) have garnered incredible attention thanks to their exciting optoelectronic properties and intrinsic strong quantum confinement effect. Herein, we carefully investigate and decipher the charge carrier dynamics at the interface between CsPbBr3 multiple quantum wells (MQWs) as the photoactive layer and TiO2 and Spiro-OMeTAD as electron and hole transporting materials, respectively. The fabricated MQWs comprise three monolayers of CsPbBr3 separated by 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) as barriers. By varying the BCP thickness, we show that charge carrier extraction from MQWs to the corresponding extracting layer occurs through a quantum tunneling effect, as elaborated by steady-state and time-resolved photoluminescence measurements and further verified by femtosecond transient absorption experiments. Ultimately, we have investigated the impact of the barrier-thickness-dependent quantum tunneling effect on the photoelectric behavior of the synthesized QW photodetector devices. Our findings shed light on one of the most promising approaches for efficient carrier extraction in quantum-confined systems.

Accelerating Quantum Decay by Multiple Tunneling Barriers.

A quantum particle constrained between two high potential barriers provides a paradigmatic example of a system sustaining quasi-bound (or resonance) states. When the system is prepared in one of such quasi-bound states, the wave function approximately maintains its shape but decays in time in a nearly exponential manner radiating into the surrounding space, the lifetime being of the order of the reciprocal of the width of the resonance peak in the transmission spectrum. Naively, one could think that adding more lateral barriers would preferentially slow down or prevent the quantum decay since tunneling is expected to become less probable and due to quantum backflow induced by multiple scattering processes. However, this is not always the case and in the early stage of the dynamics quantum decay can be accelerated (rather than decelerated) by additional lateral barriers, even when the barrier heights are arbitrarily large. The decay acceleration originates from resonant tunneling effects and is associated to large deviations from an exponential decay law. We discuss such a counterintuitive phenomenon by considering the hopping dynamics of a quantum particle on a tight-binding lattice with on-site potential barriers.

Heavy-Atom Tunneling in Bicyclo[4.1.0]hepta-2,4,6-trienes.

Heavy-atom tunneling limits the lifetime and observability of bicyclo[4.1.0]hepta-2,4,6-triene, a key intermediate in the rearrangement of phenylcarbene. Bicyclo[4.1.0]hepta-2,4,6-triene had been proposed as the primary intermediate of the rearrangement of phenylcarbene, but despite many efforts evaded its characterization even in cryogenic matrices. By introducing fluorine substituents into the ortho-positions of the phenyl ring of phenylcarbene, the highly strained cyclopropene 1,5-difluorobicyclo[4.1.0]hepta-2,4,6-triene becomes stable enough to be characterized in argon matrices. However, even at 3 K this cyclopropene is only metastable and rearranges via heavy-atom tunneling to the corresponding cycloheptatetraene. Calculations suggest that fluorination is necessary to slow down the tunneling rearrangement of the bicycloheptatriene. The parent bicycloheptatriene rapidly rearranges via heavy-atom tunneling and therefore cannot be detected under matrix isolation conditions.

Hydrogen-Atom Tunneling in a Homochiral Environment.

The role-exchanging concerted torsional motion of two hydrogen atoms in the homochiral dimer of trans-1,2-cyclohexanediol was characterized through a combination of broadband rotational spectroscopy and theoretical modeling. The results reveal that the concerted tunneling motion of the hydrogen atoms leads to the inversion of the sign of the dipole moment components along the a and b principal axes, due to the interchange motion that cooperatively breaks and reforms one intermolecular hydrogen bond. This motion is also coupled with two acceptor switching motions. The energy difference between the two ground vibrational states arising from this tunneling motion was determined to be 29.003(2) MHz. The corresponding wavefunctions suggest that the two hydrogen atoms are evenly delocalized on two equivalent potential wells, which differs from the heterochiral case where the hydrogen atoms are confined in separate wells, as the permutation-inversion symmetry breaks down. This intriguing contrast in hydrogen-atom behavior between homochiral and heterochiral environments could further illuminate our understanding of the role of chirality in intermolecular interactions and dynamics.

Hybrid Approach to Fabricate Uniform and Active Molecular Junctions.

Molecules can serve as ultimate building blocks for extreme nanoscale devices. This requires their precise integration into functional heterojunctions, most commonly in the form of metal-molecule-metal architectures. Structural damage and nonuniformities caused by current fabrication techniques, however, limit their effective incorporation. Here, we present a hybrid fabrication approach enabling uniform and active molecular junctions. A template-stripping technique is developed to form electrodes with sub-nanometer smooth surfaces. Combined with dielectrophoretic trapping of colloidal nanorods, uniform sub-5 nm junctions are achieved. Uniquely, in our design, the top contact is mechanically free to move under an applied stimulus. Using this, we investigate the electromechanical tuning of the junction and its tunneling conduction. Here, the molecules help control sub-nanometer mechanical modulation, which is conventionally challenging due to instabilities caused by surface adhesive forces. Our versatile approach provides a platform to develop and study active molecular junctions for emerging applications in electronics, plasmonics, and electromechanical devices.

Molecular Platform for Fast Low-Voltage Nanoelectromechanical Switching.

The use of molecules as active components to build nanometer-scale devices inspires emerging device concepts that employ the intrinsic functionality of molecules to address longstanding challenges facing nanoelectronics. Using molecules as controllable-length nanosprings, here we report the design and operation of a nanoelectromechanical (NEM) switch which overcomes the typical challenges of high actuation voltages and slow switching speeds for previous NEM technologies. Our NEM switches are hierarchically assembled using a molecular spacer layer sandwiched between atomically smooth electrodes, which defines a nanometer-scale electrode gap and can be electrostatically compressed to repeatedly modulate the tunneling current. The molecular layer and the top electrode structure serve as two degrees of design freedom with which to independently tailor static and dynamic device characteristics, enabling simultaneous low turn-on voltages (sub-3 V) and short switching delays (2 ns). This molecular platform with inherent nanoscale modularity provides a versatile strategy for engineering diverse high-performance and energy-efficient electromechanical devices.

Gamow Temperature in Tsallis and Kaniadakis Statistics.

Relying on the quantum tunnelling concept and Maxwell-Boltzmann-Gibbs statistics, Gamow shows that the star-burning process happens at temperatures comparable to a critical value, called the Gamow temperature (T) and less than the prediction of the classical framework. In order to highlight the role of the equipartition theorem in the Gamow argument, a thermal length scale is defined, and then the effects of non-extensivity on the Gamow temperature have been investigated by focusing on the Tsallis and Kaniadakis statistics. The results attest that while the Gamow temperature decreases in the framework of Kaniadakis statistics, it can be bigger or smaller than T when Tsallis statistics are employed.

Quantum Chaos in the Dynamics of Molecules.

Quantum chaos is reviewed from the viewpoint of "what is molecule?", particularly placing emphasis on their dynamics. Molecules are composed of heavy nuclei and light electrons, and thereby the very basic molecular theory due to Born and Oppenheimer gives a view that quantum electronic states provide potential functions working on nuclei, which in turn are often treated classically or semiclassically. Therefore, the classic study of chaos in molecular science began with those nuclear dynamics particularly about the vibrational energy randomization within a molecule. Statistical laws in probabilities and rates of chemical reactions even for small molecules of several atoms are among the chemical phenomena requiring the notion of chaos. Particularly the dynamics behind unimolecular decomposition are referred to as Intra-molecular Vibrational energy Redistribution (IVR). Semiclassical mechanics is also one of the main research fields of quantum chaos. We herein demonstrate chaos that appears only in semiclassical and full quantum dynamics. A fundamental phenomenon possibly giving birth to quantum chaos is "bifurcation and merging" of quantum wavepackets, rather than "stretching and folding" of the baker's transformation and the horseshoe map as a geometrical foundation of classical chaos. Such wavepacket bifurcation and merging are indeed experimentally measurable as we showed before in the series of studies on real-time probing of nonadiabatic chemical reactions. After tracking these aspects of molecular chaos, we will explore quantum chaos found in nonadiabatic electron wavepacket dynamics, which emerges in the realm far beyond the Born-Oppenheimer paradigm. In this class of chaos, we propose a notion of Intra-molecular Nonadiabatic Electronic Energy Redistribution (INEER), which is a consequence of the chaotic fluxes of electrons and energy within a molecule.

Hydrogen Tunneling in Catalytic Hydrolysis and Alcoholysis of Silanes.

An unprecedented quantum tunneling effect has been observed in catalytic Si-H bond activations at room temperature. The cationic hydrido-silyl-iridium(III) complex, {Ir[SiMe(o-C6 H4 SMe)2 ](H)(PPh3 )(THF)}[BArF 4 ], has proven to be a highly efficient catalyst for the hydrolysis and the alcoholysis of organosilanes. When triethylsilane was used as a substrate, the system revealed the largest kinetic isotopic effect (KIESi-H/Si-D =346±4) ever reported for this type of reaction. This unexpectedly high KIE, measured at room temperature, together with the calculated Arrhenius preexponential factor ratio (AH /AD =0.0004) and difference in the observed activation energy [(E a D -E a H )=34.07 kJ mol-1 ] are consistent with the participation of quantum tunneling in the catalytic process. DFT calculations have been used to unravel the reaction pathway and identify the rate-determining step. Aditionally, isotopic effects were considered by different methods, and tunneling effects have been calculated to be crucial in the process.

Heavy-Atom Quantum Tunnelling in Spin Crossovers of Nitrenes.

We simulate two recent matrix-isolation experiments at cryogenic temperatures, in which a nitrene undergoes spin crossover from its triplet state to a singlet state via quantum tunnelling. We detail the failure of the commonly applied weak-coupling method (based on a linear approximation of the potentials) in describing these deep-tunnelling reactions. The more rigorous approach of semiclassical golden-rule instanton theory in conjunction with double-hybrid density-functional theory and multireference perturbation theory does, however, provide rate constants and kinetic isotope effects in good agreement with experiment. In addition, these calculations locate the optimal tunnelling pathways, which provide a molecular picture of the reaction mechanism. The reactions involve substantial heavy-atom quantum tunnelling of carbon, nitrogen and oxygen atoms, which unexpectedly even continues to play a role at room temperature.

Double Proton Transfer Across a Table: The Formic Acid Dimer-Fluorobenzene Complex.

Proton transfer via tunneling is a fundamental quantum-mechanical phenomenon. We report rotational spectroscopy measurements of this process in the complex of the formic acid dimer with fluorobenzene. The assignment of the spectrum indicates that this complex exists in the form of a π-π stacked structure. Each rotational transition of the parent isotopologue exhibits splitting. Isotopic substitution experiments show that the spectral splitting results from double-proton transfer tunneling in the formic acid dimer. Presence of fluorobenzene as a neighboring molecule does not quench the double proton transfer in the formic acid dimer but decreases its tunneling splitting from 341(3) MHz to 267.608(1) MHz. Calculations suggest that the presence of the weakly bounded fluorobenzene does not influence the activation energy of the proton transfer. The fluorobenzene is reoriented with respect to the formic acid dimer during the course of the reaction, slowing down the proton transfer motion.

Chemical-Labeling-Assisted Detection of Nucleobase Modifications by Quantum-Tunneling-Based Single-Molecule Sensing.

Quantum-tunneling-based DNA sensing is a single-molecule technique that promises direct mapping of nucleobase modifications. However, its applicability is seriously limited because of the small difference in conductivity between modified and unmodified nucleobases. Herein, a chemical labeling strategy is presented that facilitates the detection of modified nucleotides by quantum tunneling. We used 5-Formyl-2'-deoxyuridine as a model compound and demonstrated that chemical labeling dramatically alters its molecular conductance compared with that of canonical nucleotides; thus, facilitating statistical discrimination, which is impeded in the unlabeled state. This work introduces a chemical strategy that overcomes the intrinsic difficulty in quantum-tunneling-based modification analysis-the similarity of the molecular conductance of the nucleobases of interest.

Charge Transport through Self-Assembled Monolayers of Monoterpenoids.

The nature of the processes at the origin of life that selected specific classes of molecules for broad incorporation into cells is controversial. Among those classes selected were polyisoprenoids and their derivatives. This paper tests the hypothesis that polyisoprenoids were early contributors to membranes in part because they (or their derivatives) could facilitate charge transport by quantum tunneling. It measures charge transport across self-assembled monolayers (SAMs) of carboxyl-terminated monoterpenoids (O2 C(C9 HX)) and alkanoates (O2 C(C7 HX)) with different degrees of unsaturation, supported on silver (AgTS ) bottom electrodes, with Ga2 O3 /EGaIn top electrodes. Measurements of current density of SAMs of linear length-matched hydrocarbons-both saturated and unsaturated-show that completely unsaturated molecules transport charge faster than those that are completely saturated by approximately a factor of ten. This increase in relative rates of charge transport correlates with the number of carbon-carbon double bonds, but not with the extent of conjugation. These results suggest that polyisoprenoids-even fully unsaturated-are not sufficiently good tunneling conductors for their conductivity to have favored them as building blocks in the prebiotic world.

Quantum Tunneling Mediated Interfacial Synthesis of a Benzofuran Derivative.

Reaction pathways involving quantum tunneling of protons are fundamental to chemistry and biology. They are responsible for essential aspects of interstellar synthesis, the degradation and isomerization of compounds, enzymatic activity, and protein dynamics. On-surface conditions have been demonstrated to open alternative routes for organic synthesis, often with intricate transformations not accessible in solution. Here, we investigate a hydroalkoxylation reaction of a molecular species adsorbed on a Ag(111) surface by scanning tunneling microscopy complemented by X-ray electron spectroscopy and density functional theory. The closure of the furan ring proceeds at low temperature (down to 150 K) and without detectable side reactions. We unravel a proton-tunneling-mediated pathway theoretically and confirm experimentally its dominant contribution through the kinetic isotope effect with the deuterated derivative.

Evidence for tunneling in base-catalyzed isomerization of glyceraldehyde to dihydroxyacetone by hydride shift under formose conditions.

Hydrogen atom transfer reactions between the aldose and ketose are key mechanistic features in formose chemistry by which formaldehyde is converted to higher sugars under credible prebiotic conditions. For one of these transformations, we have investigated whether hydrogen tunneling makes a significant contribution to the mechanism by examining the deuterium kinetic isotope effect associated with the hydrogen transfer during the isomerization of glyceraldehyde to the corresponding dihydroxyacetone. To do this, we developed a quantitative HPLC assay that allowed us to measure the apparent large intrinsic kinetic isotope effect. From the Arrhenius plot of the kinetic isotope effect, the ratio of the preexponential factors AH/AD was 0.28 and the difference in activation energies Ea(D) - Ea(H) was 9.1 kJ·mol(-1). All these results imply a significant quantum-mechanical tunneling component in the isomerization mechanism. This is supported by multidimensional tunneling calculations using POLYRATE with small curvature tunneling.