Effect of hydrogen migration on the electronic structure of phenol derivatives observed by single-molecule conductance

Domain: physics
Published: 2025-12-03
Editorial outcome: major_revision

Abstract
The regulation of the electronic structure of an aromatic system significantly influences its chemical reactivity, optical behavior, and electrical property. A comprehensive understanding of the impact of hydrogen atom states on the electronic structure of phenol derivatives and the ability to regulate these effects is crucial for the design and development of functional materials. Here, we employ a single-molecule junction technology to simultaneously monitor and regulate a single hydrogen atom’s state in phenol derivatives. We show that the combined effects of the applied electric field and the acid-base environment in molecular solutions enable hydrogen bonding interactions to precisely control the movement of the hydrogen atom on phenol derivatives, drawing it closer to or farther away from the oxygen atom depending on the external stimuli. Complementary theoretical calculations reveal how these state changes alter electron distribution and charge transport pathways, consequently impacting molecular conductance. This study provides insights for developing controllable molecular devices.

Introduction
Precise regulation of the electronic structure of aromatic systems directly determines the physicochemical properties, reaction activities, and optoelectronic functional characteristics of molecules1–3. The study of such regulation mechanisms plays a key role in interdisciplinary fields such as chemistry, physics, material science, and nanotechnology. Among these, hydrogen (H) migration4–11, as an important strategy for modulating molecular electronic structures, not only governs the internal electron transfer and rearrangement processes of molecules, but can also achieve dynamic regulation through external stimuli like light12,13, heat8,14, force7, and electric fields4,5. Currently, various spectroscopic techniques, such as ultraviolet-visible spectroscopy15, X-ray photoelectron spectroscopy16, and photoluminescence spectroscopy (PL)17, are employed to monitor the changes in molecular electronic structures by analyzing characteristic electron transitions, binding energy, and emission wavelengths. Although these techniques generally reveal the overall characteristics of the molecular electronic structures, they possess the limited capacity to probe the dynamic changes in the electronic structure of individual molecules. Therefore, there is a pressing need to undertake studies at the single-molecule level, incorporating electrical methods attuned to electronic structures.

The single-molecule junction technology18–22 has made significant breakthroughs in revealing the intrinsic properties of molecules23–25 and has been successfully applied to the study of H migration-induced isomerization in systems such as porphyrins5 and enol-keto4. However, it is important to note that systems like porphyrins, which involve degenerate or quasi-degenerate states, have an isomerization barrier of less than 20 kJ mol−1, resulting in the isomerization process always being in a dynamic equilibrium. This thermodynamically driven spontaneous transformation can only be observed under ≈6 K and high vacuum conditions5,6, making it challenging to stably distinguish the “on/off” states of molecular switches at room temperature and pressure. On the other hand, while certain non-degenerate systems achieve stable bistability by constructing high isomerization barriers4, the high barriers (≈250 kJ mol−1) require large external stimuli for state switching, severely limiting the operability of the device in practical applications.

To address the aforementioned research challenges, a design of a molecular system featuring a hydroxy-benzothiazole core is proposed in this study. This structure effectively stabilizes the transition state during the H migration process by utilizing the delocalization effect of the π-conjugated system, in combination with the synergistic electronegativity of nitrogen (N) and sulfur (S) atoms, thereby precisely tuning the isomerization barrier to an intermediate range. This design concept breaks through the traditional dichotomy of “low-barrier dynamic imbalance” and “high-barrier inoperability” in conventional systems. More importantly, in the study of H migration at the single-molecule level, the dynamic response to external environmental conditions is achieved. By adjusting the acid-base environment of the solution, the positioning of H atoms at adjacent oxygen (O) sites can be precisely controlled. This single-atom-level spatial displacement causes substantial changes in the conjugation of the aromatic system, thereby modulating its electronic structure characteristics. This precise control mechanism based on single-atom migration provides a paradigm for developing intelligent molecular devices with environmental responsiveness, showing broad application prospects in the field such as molecular sensors and programmable materials.

Results
Design of the molecule
Based on the design principles of molecular engineering, the O−H⋯N structure of hydroxy-benzothiazole satisfies the requirements for intramolecular hydrogen bonding necessary for H migration, and restricts the rotation of the thiazole ring (Fig. 1a, b). The intramolecular tautomerism occurs as the H atom moves closer to or farther away from the O atom, thereby regulating the electronic structure of the aromatic system. To quantify the impact of H migration, theoretical calculations are performed on the orbital distribution of the aromatic system before and after H migration (Fig. 1c, d). We designate the initial state, where H is closer to O, as M-OH, and the final state, where H is closer to N, as M-NH. The transition from the initial state to the final state involves the transfer of an intramolecular H atom between the O atom and the N atom. This change in the position of the H atom can regulate the electronic orbital distribution of the molecule. In comparison with the initial state M-OH, the final state M-NH exhibits an extended conjugation effect on the molecular framework while reducing the π delocalization within the core ring (Fig. 1c, d), which may lead to the different electronic properties.

Electronic characteristics of single-molecule junctions
To enhance the anchoring strength between the molecule and the gold (Au) electrodes, phenylthioacetate (PhSAc) is introduced at both ends of hydroxy-benzothiazole. In addition, a control molecule M-OCH3, which lacks active H atom, is synthesized. The specifics synthesis route is detailed in the Supplementary information (Supplementary Figs. 1–6). Using propylene carbonate (PC) as the solvent and adding tetrabutylammonium hydroxide (TBAOH) to deprotect the thioacetyl groups (−SAc, details are provided in Methods), stable Au-S covalent bonds are formed directly with the Au electrodes, thereby constructing stable single-molecule junctions (Fig. 2a, d). We firstly performed Scanning Tunneling Microscopy Break Junction (STM-BJ) measurements in pure solvent PC (Supplementary Fig. 7) to ensure that PC itself does not exhibit any significant conductance plateau before proceeding with conductance measurements of the target molecules. Then, at room temperature, the H migration in the molecule is monitored by using the STM-BJ technique with a 1 mM solution of the target molecule. At a bias voltage of 0.1 V, thousands of conductance traces are used to construct two-dimensional (2D) conductance-displacement histograms (Fig. 2b, e). These histograms exhibit the quantum conductance of Au-Au atomic point contacts G0 (G0 = 2e2/h, 77500 nS) and distinct molecular signals below G0. M-OH displays two distinct conductance plateaus (Fig. 2b), with Gaussian-fitted conductance peaks in the corresponding one-dimensional (1D) conductance histogram at ≈0.35×10−3 G0 (≈27.50 nS) and 0.55×10−5 G0 (≈0.43 nS) (Fig. 2c). In contrast, M-OCH3 shows only one distinct conductance plateau (Fig. 2e), with a Gaussian-fitted conductance peak in the 1D conductance histogram at ≈0.35×10−5 G0 (≈0.27 nS) (Fig. 2f), which is similar with the low conductance value of M-OH. The conductance-time (G–t) measurements of the conductance as a function of time in the hover experiment yielded similar results (Supplementary Fig. 8).

The typical single-molecule conductance traces for M-OH and M-OCH3 are shown in the insets of Fig. 2b, e, respectively. The black curves represent the tunneling decay after the rupture of the Au atomic contacts in pure solvent, while conductance plateaus corresponding to molecular conductance are observed in the solution containing the target molecules. The red and blue curves are associated with the low conductance (GL) and the high conductance (GH) states, respectively. Their stochastic occurrence, independent existence, and ability to interconvert (as shown by the green curve) indicate a dynamic equilibrium between two distinct configurations. To determine the origin of the different conductance states, the lengths of the molecular conductance plateaus are statistically analyzed (insets of Fig. 2c, f). The plateau-length-distribution histogram of M-OH shows that the GH and GL states have nearly identical plateau lengths (inset of Fig. 2c). By adding the Au-Au snap-back distance (0.5 nm) to the conductance plateau statistics, the lengths of the molecular junctions in the GH and GL states are both ≈1.50 nm, which are consistent with the molecular length. This further indicates that the GH and GL states of the M-OH molecule could originate from different conformations of the same molecule, specifically due to the structural changes in the hydroxy-benzothiazole in the M-OH molecule, instead of variations in the anchoring points. Furthermore, the conductance value of ≈0.35×10−5 G0 and the plateau length of 1.55 nm (sum including Au-Au snap-back distance) for the M-OCH3 molecule (inset of Fig. 2f) suggest that the GL state of the M-OH molecule and the M-OCH3 molecule may share the similar structures. When comparing this with the experimental results of the M-OCH3 molecule, it can be speculated that the GH state of the M-OH molecule originates from the M-NH configuration, where the H atom migrates closer to the N atom.

Regulation mechanisms of electronic structures
To elucidate the origins of the GH and GL states in the M-OH molecule, theoretical calculations are performed on the charge transport capabilities of the M-OH, M-NH, and M-OCH3 configurations using Quantum ATK, based on the structures optimized by Gaussian. In addition, the structures optimized in the presence of the solvent molecules showed negligible differences (Supplementary Fig. 9). The transmission spectra of both M-OH and M-NH reveal that the conductance of these configurations is HOMO-dominated (Fig. 3a). The y-axis of the electron transmission spectra represents the electron transmission coefficient of the molecular junction, the magnitude of which indirectly reflects the charge transport capability of the junction. At EF = 0, the transmission coefficient of M-NH is nearly an order of magnitude higher than that of M-OH. In addition, potential energy scans are performed on these two molecules (M-OH and M-OCH3), and all stable conformers are subjected to calculations on structural optimization and transmission spectra. These results show that conductance fluctuation induced by conformational variations arising from the rotation of the benzothiazole ring is negligible, and the transmission coefficient of M-OCH3 is slightly lower than that of M-OH (Supplementary Fig. 10), which is consistent with the conductance trend shown in Fig. 2. Therefore, it can be inferred that the GH and GL states correspond to the M-NH and M-OH configurations, respectively.

To further reveal the working mechanism of the superior charge transport capability in M-NH configuration, an analysis on the transmission pathways of M-OH and M-NH configurations is conducted (Fig. 3b, c). The cyan lines represent the electron paths transmitting from the left electrode to the right electrode, while the purple lines denote the opposite direction. The thickness of these lines corresponds to the transmission coefficient between two incident atoms, normalized to the highest transmission coefficient in each molecule. For M-OH, a complex loop current is observed in the aromatic system (Fig. 3b and Supplementary Fig. 11a) due to the presence of a significant destructive quantum interference (DQI) effect. This is consistent with the DQI effect observed in meta-connected benzene configurations26–30. Similarly, a complex loop current is also observed in M-OCH3 (Supplementary Fig. 11c). For M-NH, the extended conjugation effect reduces the HOMO-LUMO energy gap, bringing the HOMO closer to the EF (Fig. 3a), while weakening the DQI effect (Fig. 3c, Supplementary Fig. 11b). This observation further implies that the state of the H atom in the M-OH molecule has changed: the GL state originates from a structure where the H is closer to the O atom, while the GH state originates from a structure where the H is closer to the N atom, with this process being reversible (Fig. 3d). Furthermore, a significant difference in the HOMO distributions between the two structures is observed (refer to Supplementary Fig. 12 for more details of the orbital distribution). In comparison with M-OH (Fig. 3e), M-NH exhibits a more delocalized electronic structure at the center of the aromatic system (Fig. 3f), which may also contribute to the superior charge transport capability of the M-NH configuration. However, the HOMO distribution of M-OCH3 is similar to that of M-OH (Supplementary Fig. 12), which could also account for their similar conductance values. In addition, the frontier orbitals obtained from ATK calculations exhibit similar patterns (Supplementary Fig. 13).

Electric-field manipulation of the single H atom state
To further explore the effect of the electric field on the state of the H atom, the evolution of the current of single-molecule junctions is recorded as the voltage is progressively varied (for details, see Methods). Among the thousands of current-voltage (I–V) curves recorded in the hovering stationary state, 50% exhibit significant current jumps without a fixed threshold bias (Fig. 4a and Supplementary Fig. 14). However, in a typical trace (yellow curve in Fig. 4a), it can be clearly seen that the probability of a current jump is higher at around 0.75 V. The corresponding 2D conductance-voltage (G–V) histogram also demonstrates that the conductance of the molecule undergoes minimal changes at lower voltages, but experiences a sudden shift when the voltage exceeds ≈0.75 V (Fig. 4b). Conversely, the current and conductance of the M-OCH3 molecule rise proportionally with the increasing bias voltage, without manifesting additional conductance jumps (Supplementary Fig. 15). Furthermore, the linear analysis of the typical I–V curve (Fig. 4c) suggests that a stochastic jump can occur between the GH and GL states, a phenomenon with potential applications in single-molecule switches. To further reveal the underlying causes for the atom state of H driven by the electric field, theoretical calculations of the potential barriers are conducted throughout the entire H migration process. The results show that under zero electric field, there is a relatively large energy barrier difference between the final state (M-NH) and the initial state (M-OH). However, under a high electric field, the energy barrier difference between M-NH and M-OH decreases and becomes insensitive to the electric field direction (Fig. 4d and Supplementary Fig. 16). This indicates that the H transfer process is not entirely governed by electric-field-induced barrier modulation. As reported in refs. 31–34, a bias-induced electron-excitation mechanism can render the I–V curve symmetric at zero bias. Therefore, another possibility is the involvement of inelastic electronic excitation processes, which leads to symmetric switching. This involvement can be characterized by abrupt changes in tunneling current as the bias increases35, consistent with the experimental results of this work. Moreover, under the influence of an applied electric field, the M-NH configuration becomes more stable, thereby favoring the capture of the M-NH state at high bias voltages.

Acid-base manipulation of the single H atom state
The structure of the M-OH molecule suggests that the regulation of its electronic structure can be effectively achieved by introducing acids and bases. Therefore, to further regulate the state of H atom in the molecule, camphorsulfonic acid (CSA) as the H⁺ source and tetrabutylammonium hydroxide (TBAOH) as the OH⁻ source are employed to interact with the N and H atom in the M-OH molecule, respectively (Fig. 5a). Subsequently, the corresponding conductance testing is performed. Experimental results show that an increase in the concentration of acid results in a significant reduction in the proportion of the GH state. Specifically, when the ratio of CSA to M-OH is maintained at 10:10, the proportion of the GH state decreases to a mere 9.30% (Fig. 5b and Supplementary Fig. 17). On the contrary, in the alkaline environment, the proportion of the GH state exhibits a marked increase with the escalating concentration of the base. Notably, when the ratio of TBAOH to M-OH is adjusted to 10:1, the proportion of the GH state surges to 53.85% (Fig. 5c and Supplementary Fig. 18).

Theoretical calculations indicate that in an acidic environment, H⁺ accumulates on the N atom of the M-OH molecule. This accumulation diminishes the electronegativity of the N atom, subsequently undermining its attraction to the H atom within the molecule, and rendering the formation of hydrogen bonds between N and H challenging. As a result, the electronic structure at the center of the aromatic system within the M-OH molecule largely mirrors its initial state (Fig. 5d and Supplementary Fig. 19a). In contrast, in an alkaline environment, the attraction of OH⁻ to the H atom in the M-OH molecule prompts the H atom to distance itself from the O atom, resulting in the C-O bond on the aromatic system exhibiting partial double-bond characteristics (Fig. 5e and Supplementary Fig. 19b). Consequently, the electron-cloud distribution at the center of the aromatic system becomes more delocalized, which weakens the DQI effect and aligns the overall conductance of the structure to the final state M-NH, where the H atom resides closer to the N atom. The transmission coefficients at EF – EF = 0, derived from these two structures, are also consistent with the conductivity laws observed (Fig. 5b, c) in the experiment (as shown in Fig. 5f, with detailed information in Supplementary Fig. 20). Therefore, it can be concluded that both acidic and basic environments can regulate the state of the H atom in the M-OH molecule, albeit through divergent mechanisms. The H⁺ in the acid “locks” the N atom in the M-OH molecule, thereby reducing the probability of the H atom being closer to the N atom. Conversely, the OH⁻ in the base “locks” the H atom within the M-OH molecule, thereby amplifying the likelihood of the H atom moving away from the O atom.

In this study, the STM-BJ technique is employed to directly monitor and regulate the effect of a single H atom’s proximity to the O atom within a phenol derivative on the electronic structure of the aromatic system. Theoretical simulations elucidate noteworthy disparities in the electron cloud distribution and charge transport pathways within the aromatic system both prior to and subsequent to the migration of a single H atom, leading to changes in the molecular quantum interference transport characteristics. Moreover, by applying an electric field and modifying the acid-base environment of the molecular solution, the position of a single H atom in phenol derivative, either approaching or distancing from the O atom, can be manipulated. This work provides insights for the design and development of new functional materials and controllable smart devices.

Methods
Materials
We obtained Au wire with a purity of 99.99% and a diameter of 0.25 mm from Zhongnuo Advanced Materials (Beijing) Technology Co., Ltd. First, the Au wire was electrochemically etched to produce a STM tip. Then, a 10 nm layer of chromium was plated on a single crystal silicon wafer, followed by a 200 nm layer of Au on the chromium to obtain an Au substrate.

STM-BJ measurements
We prepared 1 mM M-OH and M-OCH3 molecular solutions using solvent PC, and then added 2 mM TBAOH solution to the molecular solutions for deprotection. After deprotection, the –SAC groups are converted to –SH, which subsequently undergoes dehydrogenation to form Au–S covalent bonds with Au. This process leads to the formation of Au–molecule–Au junctions. In the STM-BJ experiment, we first tested the conductivity of M-OH and M-OCH3 molecules, and finally added different proportions of CSA and TBAOH to test the effect of acid and base on the conductivity of M-OH molecules. The plateau length is determined by analyzing data points that fall at least half an order of magnitude below the minimum conductance value. Due to the high ductility of Au, a retraction of ≈0.5 nm occurs when the Au-Au junction breaks. Therefore, the statistically derived plateau length (ΔZ) plus 0.5 nm equals the molecular junction length. We repeatedly opened (contracted the tip) and closed (approached the tip) the junction while collecting a large number of conductance-displacement traces for analysis. The conductance is not measure data fixed electrode spacing. Instead, the formation of molecular junctions is automatically identified through characteristic conductance signals during the electrode separation process. The measurement of the single-molecule conductivity and the specific algorithm for extracting the conductance value are performed using the Xtech STM-BJ system developed by Professor Wenjing Hong’s team at Xiamen University36. The data analysis was performed using the XMe open-source code (https://github.com/Pilab-XMU/XMe_DataAnalysis).

I–V characterizations
An automatic control program running on the NI cRIO-9039 controller was used to determine the conductance plateau37,38. We set the conductance range and sampling points based on the conductance value of the target molecule for detection. If the number of sampling points exceeding a certain threshold within this range was detected, a conductance plateau appeared, and the piezoelectric motion paused to maintain the molecular junction within this conductance range. The distance between two electrodes is not fixed during the measurement; instead, it is automatically adjusted by the instrument upon detecting the formation of a conductance plateau within the predefined range. The measurement mode then switched to I–V measurements, which was completed within 200 ms, and the measured I–V curves were collected for subsequent statistical analysis. A 2D I–V histogram was plotted as a 150×150 array, and each column of the array was fitted with a Gaussian curve to obtain the fitting line.

Theoretical calculations
We used Gaussian 1639 software to optimize the ground-state geometry of molecules by density functional theory. In the optimization process, the symmetry of molecular structure was not restricted, and the default values of the program were used for self-consistent field and convergence characterization. For M-OH, M-NH, and M-OCH3 molecules, we described all atoms using B3LYP functionals and 6-31G(d,p) basis set. The transition state shown in Fig. 4d was found using the B3LYP functional and the 6-31+G(d,p) basis set, while the IRC (intrinsic reaction coordinate) method used the 6-31+G(d,p) base group. The optimized Au-molecule-Au molecular junction was optimized and the non-equilibrium Green’s function combined with density functional theory (NEGF+DFT) was used for transmission analysis in ATK (Atomistix Toolkit)40,41. The left and right electrode regions used in Quantum ATK Q-2022.12 consisted of seven layers of Au(111)-(5*5) for M-OH, M-NH, and M-OCH3 molecules, while Au(111)-(6*6) for M-OH/CSA and M-OH/TBAOH. The model construction of the device was carried out on the basis of ref. 42. The Au electrode connected with the S atom was triangular in structure, and the S atom was the same distance from the three Au atoms, all of which were ≈2.5 Å. In the process of optimizing the device structure, we fixed the three-layer Au electrode connected to the molecular anchor, but the molecular coordinates were not restricted. The PBE commutative dependent functional was used, with the double-ζ basis set, DZ, used for Au atoms, and the double-ζ polarized basis set, DZP, used for the other atoms42–45. The k point value calculated by the transmission spectrum was 7×7. The transmission eigenvalues and eigenstates were analyzed at the peak positions in the transmission spectrum, while the isovalue is 0.1.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "In the manuscript, “Effect of hydrogen migration on the electronic structure with atomic precision” the authors design a hydroxy-benzothiazole-based molecule that utilizes intramolecular O-H···N hydrogen bonding to enable hydrogen atom migration, yielding two tautomers (M-OH and M-NH). They investigate and compare the conductance of M-OH and a reference molecule, M-OCH₃, which lacks the hydrogen bond. M-OH exhibits two conductance plateaus (high GH and low GL associated with the M-NH and M-OH form, respectively), while M-OCH₃ shows only the GL plateau, reflecting the absence of H atom migration. The authors demonstrate that single hydrogen migration can effectively modulate conductance. Transmission spectra, local current maps, and FMO analysis reveal that hydrogen position alters HOMO distribution and ring current, thus influencing transport. They further show that external stimuli such as electric fields or pH can control the tautomeric state, highlighting the system’s potential as a molecular switch. This work offers a compelling approach to tuning molecular transport via intramolecular hydrogen migration and could be considered for publication after addressing the following concerns.\n1. The authors state that “the unique O−H···N structure of hydroxy-benzothiazole satisfies the requirements for intramolecular hydrogen bonding necessary for H migration, and restricts the rotation of the thiazole ring.” Could the authors clarify the activation barrier associated with the rotation of the thiazole ring? Additionally, does the rotation around the C–C bond connecting the benzene and thiazole rings influence molecular conductance? Since M-OCH3 lacks intramolecular hydrogen bonding, is this molecule planar or non-planar? What is the energetic penalty for rotation in this case? There remains a possibility that the observed GL and GH conductance states may arise from differences in planarity rather than tautomerism. Including supporting data addressing this point would strengthen the interpretation.\n2. It would benefit the reader if the authors could include the transmission values at the Fermi energy from their theoretical calculations in the SI or in the plot itself. This will allow for quantitative comparison rather than simply the qualitative comparison that is available from examination of the plots. 3. In Figure 4d, what is represented on the X-axis? Is it the distance between the hydrogen atom and the oxygen or nitrogen atom (i.e., O–H or N–H distance)? Or generalized reaction coordinate? This was computed somehow so the axis should have a precise definition (and units). Further, it would be a useful sanity check to compare these results with a higher-level theory (larger basis set, dispersion corrected functional, wavefunction method etc.), as the transition-state likely has significant open-shell (singlet) character and thus is likely to be very sensitive to the level of theory.\n4. Figures 5d, 5e, and S15 show more than two colours in the molecular orbital isosurfaces. Could the authors explain the meaning of the colour gradients? How should they be interpreted? It is better to avoid bright red and bright green colours for the iso-surfaces for colourblind readers. Iso values should be mentioned in the caption.\n5. It would be helpful if the authors could provide the optimized geometries of the molecules in the presence of explicit solvent molecules, including important solvent–molecule intermolecular distances in SI or a data repository.\n6. The manuscript states, “In comparison with the initial state M-OH, the orbital distribution of the final state M-NH is more delocalized (Fig. 1b).” However, it may be more accurate to describe this as “extended conjugation,” since the benzene ring in M-OH appears to exhibit greater delocalization, while in M-NH, the presence of cross-conjugation due to the C=O group may reduce delocalization within the core ring. Incidentally orbital delocalisation is not a good measure of transmission/conductance but on the other hand, the narrowing of HOMO-LUMO gaps with extended conjugation length and resulting increase in transport is extremely well established (and what appears to be happening here).\n7. The interpretation about loop current in the following statements is incorrect and misleading. This is not a problem regarding the quality of the results or overall conclusions, simply the interpretation of the results and incorrect statements in the text. “For M-OH, a complex loop current across the aromatic system is observed, demonstrating a significant destructive quantum interference (DQI) effect (Fig. 3b).” and “The same DQI effect is also observed in M-OCH3 (Supplementary Fig. 8b). For M-NH, the number of loop currents across the aromatic system is significantly reduced, thereby weakening the DQI effect and enhancing its charge transport capability (Fig. 3c).” The DQI effect is indeed affected, but that cannot be interpreted from the local current circulation at a particular energy (ring current reversals are evidence of DQI not ring current at a particular energy). Rather, the observed variation in DQI appears to arise from differences in conjugation, specifically from the extended conjugation for the M-NH state, which reduces the cid:clip_image002.pngas compared to the M-OH state shifting both resonances and anti-resonances (this is clear from Figure 3a). These energy shifts ultimately modulate the transmission at the Fermi level, arguably with the HOMO energy shift being the dominant effect.\n8. It would be beneficial to include the bond lengths corresponding to O–H···N and O···H–N interactions in Figure 1.\n9. The caption for Section 7 in the Supporting Information appears to contain an error and should be revised.\n10. Authors could specify the exact linker used in the molecular junctions (i.e.,–C≡C–Ph–SAc).\n11. It would be better if the authors orient the ChemDraw structure and the isosurfaces in the same way in Figure 3 and Figure 5.", "reviewer_2": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts.", "reviewer_3": "Reviewer #3\n(Remarks to the Author)\nThis manuscript investigates the hydrogen tautomerization behavior of hydroxy-benzothiazole by introducing phenyl thioacetate groups at both ends of the molecule, enabling single-molecule electronic characterization using scanning tunneling microscopy break junction (STM-BJ) techniques. A methoxy-substituted control molecule (M-OCH₃) is also introduced for comparison.\nThe authors begin by using two-dimensional (2D) conductance–displacement histograms to identify two distinct molecular configurations: M-OH and M-NH. Through theoretical calculations of the transmission spectra, they attribute the higher conductance observed in the M-NH configuration to the weakening of destructive quantum interference (DQI). Furthermore, the authors perform I–V measurements on single-molecule junctions and combine these results with calculations of the proton transfer energy barrier. They conclude that the electric field modulates the energy barrier between the two tautomeric states, facilitating configuration switching. Finally, 2D conductance–displacement histograms are recorded under acidic and basic conditions. The observed differences in configuration populations are attributed to protonation and deprotonation effects, specifically the stabilization of the M-NH state by H⁺ binding to the nitrogen atom and stabilization of the M-OH state by OH⁻ locking the hydrogen atom.\nThe study presents an interesting and valuable contribution to the understanding of hydrogen tautomerization and electric-field-induced proton transfer at the single-molecule level. However, I have a few major concerns regarding the claim that the electric field modulates the proton transfer process. Here are my comments:\nMajor:\n1. In the section \"Electric-field manipulation of the single H atom state\", the authors propose that an electric field modulates the potential energy barrier between two configurations, thereby controlling the switching dynamics. However, if this modulation were truly due to an electric field effect, one would expect the conductance–voltage (G–V) curve to exhibit asymmetry with respect to bias polarity. This is because the field effect should influence the switching rate monotonically, regardless of the field direction. In contrast, Figure 4b shows a symmetric conductance change around ±0.75 V. This behavior is inconsistent with a pure electric-field-driven mechanism, especially considering the asymmetric structure of the molecule under study.\nMoreover, in Figure 4d, the authors only compare the transmission spectra at zero and high electric field strengths, without specifying the direction of the applied field or discussing the results for opposite field orientations. The authors should address this inconsistency and consider alternative explanations, such as bias-induced electron excitation, which is inherently symmetric with respect to zero bias. Relevant studies have previously attributed symmetric switching behavior to inelastic electron excitation processes:\n[1] J. Gaudioso and W. Ho, Angew. Chemie 113, 4204 (2001).\n[2] J. Gaudioso and W. Ho, J. Am. Chem. Soc. 123, 10095 (2001).\n[3] K. Motobayashi et al., Phys. Rev. Lett. 105, 076101 (2010).\n[4] J. Oh et al., Phys. Rev. Lett. 116, 056101 (2016).\n2. In lines 159–161, the authors attribute the weakening of destructive quantum interference (DQI) in the M-NH configuration to reduced loop currents. However, this conclusion is not clearly supported by Figures 3b and 3c.\nFirst, the black dotted circle in the figures is too small to interpret, even under high magnification.\nSecond, it is unclear which current loop the authors are referring to. From the figures, the main visible difference is that the M-NH configuration lacks a horizontal red line across two carbon atoms.\n3. In lines 111–132, the authors argue that differences in plateau lengths reflect distinct tautomeric configurations (M-OH vs. M-NH), rather than different adsorption geometries. However, the method for assigning plateau lengths to specific configurations (G_H and G_L) is not clearly defined.\nIf the molecule undergoes reversible switching, the plateau length alone cannot unambiguously indicate the configuration at the snapping point.\nThe authors should clarify how they distinguish between configurations, especially when switching may occur mid-plateau.\nMinor:\n1. Please clarify whether the orbital shown in Figure 1b corresponds to the HOMO or LUMO.\n2. The authors claim that Figure 1b shows two configurations and Figure 1e shows one. However, Figure 1b appears to show three configurations, and Figure 1e shows two, based on the circled areas. From context, it seems the authors refer to only the top two circles in 1b and the top one in 1e. Please clarify the status of the bottom configurations in both figures.\n3. The method used to generate Figures 1c and 1f is not described.\na. Were these obtained at a fixed displacement value?\nb. Or did the authors use an algorithm to extract plateau conductance from each trace?\nThis methodology should be clearly described—ideally in the Supplementary Information—and referenced in the main text.\n4. The x-axis label “Δz” is used in Figures 1b, 1e, 1c inset, and 1f inset, but it represents different quantities in different figures.\na. In Figures 1b and 1e, it indicates electrode displacement,\nb. While in the insets of Figures 1c and 1f, it appears to represent plateau length.\nThe authors should either clarify this distinction or use different labels to avoid confusion.\n5. The authors should explicitly identify Figure 3a as presenting the electron transmission spectra when it is first mentioned in the main text.\n6. The authors should specify the experimental conditions under which the data in Figure 4 were obtained, particularly regarding the electrode displacement. This is important for reproducibility and interpretation.", "reviewer_4": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts."}, "author_response": "Listed below are the major changes in the new version of the manuscript.\n1. We have added the molecule's potential-energy-barrier scan and transmission\nspectra under different stable states in the revised supplementary information\n(Supplementary Fig. 10), along with the related description in the revised main text.\nPlease see Pages 7 and 8 in the revised main text and Page S21 in the revised\nsupplementary information.\n2. We have added dashed guide lines to the transmission spectra in both the revised\nmain text and supplementary information, and provided the exact transmission\nvalues at the Fermi level in the figure captions.\nPlease see Pages 9 and 13 in the revised main text and Page S30 in the revised\nsupplementary information.\n3. We have changed the x-axis of Fig. 4d in the revised main text.\nPlease see Page 11 in the revised main text.\n4. We have standardized the colors of the HOMO-LUMO orbitals in the revised main\ntext and supplementary information, and labeled the isosurface values in the figure\ncaptions.\nPlease see Pages 4, 9, and 13 in the revised main text and Pages S22, S23, and S29\nin the revised supplementary information.\n5. We have added the structure optimization in the presence of solvent molecules in\nthe revised supplementary information (Supplementary Fig. 9), along with the\nrelated description in the revised main text.\nPlease see Page 7 in the revised main text and Page S20 in the revised\nsupplementary information.\n6. We have added an explanation of the relationship between the molecule's DQI\neffects and the loop current, as well as an explanation for the weakened DQI effects\nin the M-NH structure, in the revised main text. In addition, we have included\nmagnified versions of the loop-current maps in the revised Supplementary\nInformation (Supplementary Fig. S11).\nPlease see Pages 4 and 8 in the revised main text and Page S22 in the revised\nsupplementary information.\n7. We have added the hydrogen-bond lengths for O–H···N and O···H–N in the revised\nmain text.\nPlease see Page 4 in the revised main text.\n8. We have revised the caption of Section 10 in the revised Supplementary\nInformation.\nPlease see Page S29 in the revised supplementary information.\n9. We have added the process of molecular-junction formation, the method for\nstatistically analyzing plateau lengths, the measurement method for molecular\nconductance, and the I–V measurement method in the Methods section of the\nrevised main text.\nPlease see Pages 16 and 17 in the revised main text.\n10. We have added the theoretical calculations of the hydrogen-migration process under\na high reverse electric field in the revised Supplementary Information\n(Supplementary Fig. 16), and included an explanation of the migration mechanism\nalong with relevant literature citations in the revised main text.\nPlease see Pages 10 and 15 in the revised main text and Page S26 in the revised\nsupplementary information.\n11. We have clarified in the revised main text that the orbital shown in Fig. 1b is the\nHOMO.\nPlease see Page 4 in the revised main text.\n12. We have added dashed boxes to the 2D conductance plots of Fig. 2 in the revised\nmain text, and included control experiments with pure solvent in the revised\nsupplementary Information (Supplementary Fig. 7).\nPlease see Pages 5 and 7 in the revised main text and Page S18 in the revised\nsupplementary information.\n13. We have added an explanation of the electron-transmission spectra in the revised\nmain text.\nPlease see Page 7 in the revised main text.\nA detailed point-by-point response to the comments of the reviewers is listed as\nfollows:\nResponse to Reviewer #1：\nIn the manuscript, “Effect of hydrogen migration on the electronic structure with atomic\nprecision” the authors design a hydroxy-benzothiazole-based molecule that utilizes\nintramolecular O-H···N hydrogen bonding to enable hydrogen atom migration,\nyielding two tautomers (M-OH and M-NH). They investigate and compare the\nconductance of M-OH and a reference molecule, M-OCH₃, which lacks the hydrogen\nbond. M-OH exhibits two conductance plateaus (high G and low G associated with\nH L\nthe M-NH and M-OH form, respectively), while M-OCH₃ shows only the G plateau,\nL\nreflecting the absence of H atom migration. The authors demonstrate that single\nhydrogen migration can effectively modulate conductance. Transmission spectra, local\ncurrent maps, and FMO analysis reveal that hydrogen position alters HOMO\ndistribution and ring current, thus influencing transport. They further show that external\nstimuli such as electric fields or pH can control the tautomeric state, highlighting the\nsystem’s potential as a molecular switch. This work offers a compelling approach to\ntuning molecular transport via intramolecular hydrogen migration and could be\nconsidered for publication after addressing the following concerns.\nReply: We deeply appreciate the reviewer’s pertinent and constructive feedbacks. In\nresponse to his/her highly relevant questions, we have provided substantial additional\nevidence that robustly strengthens the reliability of our conclusions. Accordingly, the\nmanuscript has been significantly enhanced following careful revisions based on these\ncomments.\nComment 1: The authors state that “the unique O−H···N structure of hydroxy-\nbenzothiazole satisfies the requirements for intramolecular hydrogen bonding\nnecessary for H migration, and restricts the rotation of the thiazole ring.” Could the\nauthors clarify the activation barrier associated with the rotation of the thiazole ring?\nAdditionally, does the rotation around the C–C bond connecting the benzene and\nthiazole rings influence molecular conductance? Since M-OCH lacks intramolecular\n3\nhydrogen bonding, is this molecule planar or non-planar? What is the energetic penalty\nfor rotation in this case? There remains a possibility that the observed G and G\nL H\nconductance states may arise from differences in planarity rather than tautomerism.\nIncluding supporting data addressing this point would strengthen the interpretation.\nReply: We sincerely appreciate the reviewer for raising these critical questions. To\naddress these concerns, we performed DFT calculations (B3LYP/6-311g(d,p)) to\nevaluate the rotational energy barriers of the benzothiazole ring in the M-OH and M-\nOCH₃ molecules. The results show that both M-OH and M-OCH₃ possess three stable\nconformers. The highest rotational energy barriers for the benzothiazole ring in these\nmolecules are approximately 50 kJ/mol for M-OH and 23 kJ/mol for M-OCH₃,\nrespectively (Fig. R1a). In addition, to quantitatively analyze the influence of C–C bond\nrotation on molecular conductance, we conducted calculations on structural\noptimization and transmission spectra for all stable conformations of both molecules.\nThe results indicate that the rotation of the C–C bond between the phenyl and thiazole\nrings shows a negligible effect on the molecular conductance (Figs. R1b and R1c). It is\ntrue that M-OCH₃ lacks an intramolecular hydrogen bond. The stable conformations of\nthis molecule include both planar (S3) and non-planar (S1 and S2) geometries (Fig.\nR1a). In the original manuscript, the M-OH structure was chosen as the lowest-energy\nconformer (S1). In summary, these results collectively confirm that the G and G\nL H\nconductance states in the M-OH molecule arise unambiguously from hydrogen-\ntransfer-induced tautomerization, rather than variations in molecular planarity.\nRevision: We have added the following sentence to the revised main text: “In addition,\npotential energy scans are performed on these two molecules (M-OH and M-OCH₃),\nand all stable conformers are subjected to calculations on structural optimization and\ntransmission spectra. These results show that conductance fluctuation induced by\nconformational variations arising from the rotation of the benzothiazole ring is\nnegligible,” (Pages 7 and 8, Lines 156–159). We have also added the following figure\nto the revised supplementary information (Supplementary Fig. 10).\nFig. R1 (Supplementary Fig. 10) | Theoretical calculation results of M-OH and M-\nOCH .a Rotational potential energy profiles of M-OH and M-OCH , showing that the\n3 3\nhighest rotational energy barriers for the benzothiazole ring in these molecules are\napproximately 50 kJ/mol for M-OH and 23 kJ/mol for M-OCH₃, respectively. b,c\nTransmission spectra of M-OH (b) and M-OCH (c) under different stable\n3\nconformations. The transmission values of M-OH at the stable conformations of S1, S2,\nand S3 are 10−3.67, 10−3.84, and 10−3.84, respectively. The transmission values of M-OCH\n3\nat stable conformations of S1, S2, and S3 are 10−4.49, 10−4.34, and 10−4.47, respectively.\nd,e Specific structures of M-OH (d) and M-OCH (e) under different stable states.\nvalues at the Fermi energy from their theoretical calculations in the SI or in the plot\nitself. This will allow for quantitative comparison rather than simply the qualitative\ncomparison that is available from examination of the plots.\nReply: We thank the reviewer very much for this constructive suggestion. In order to\nclearly illustrate the transmission values at the Fermi level, we have marked the\ntransmission spectra of Fig. 3a (Fig. R2), Fig. 5f (Fig. R3), and Supplementary Fig. 20\n(Fig. R4) with dotted lines, and we have provided the transmission values at the Fermi\nlevel in the figure captions.\nRevision: We replaced Fig. 3a and Fig. 5f in the revised main text, as well as\nSupplementary Fig. 20 in the revised supplementary information. We have added the\ncorresponding figure captions to the revised main text: “The transmission values of M-\nOH and M-NH are 10−3.67 and 10−3.14, respectively.” (Page 9, Lines 191 and 192) and\n“The transmission values of M-OH/CSA and M-OH/TBAOH are 10−4.11 and 10−3.16,\nrespectively.” (Page 13, Lines 268 and 269). We also added the following sentence in\nthe figure caption of the revised Supplementary Fig. 20: “The transmission values of\nM-OH, M-NH, M-OH/CSA, and M-OH/TBAOH are 10−3.67, 10−3.14, 10−4.11, and 10−3.16,\nrespectively.”\nFig. R2 (Fig. 3a) | Theoretical transmission spectra before (blue) and after (red) H\nmigration. The transmission values of M-OH and M-NH are 10−3.67 and 10−3.14,\nrespectively.\nFig. R3 (Fig. 5f) | Calculated transmission spectra based on these structures. The\ntransmission values of M-OH/CSA and M-OH/TBAOH are 10−4.11 and 10−3.16,\nrespectively.\nFig. R4 (Supplementary Fig. 20) | Transmission spectra. Calculated transmission\nspectra, represented in black, red, blue, and green, correspond to the stages prior to\nhydrogen migration, following hydrogen migration, after acidification with CSA, and\npost-alkalization with TBAOH, respectively. The transmission values of M-OH, M-NH,\nM-OH/CSA and M-OH/TBAOH are 10−3.67, 10−3.14, 10−4.11 and 10−3.16, respectively.\nComment 3: In Figure 4d, what is represented on the X-axis? Is it the distance between\nthe hydrogen atom and the oxygen or nitrogen atom (i.e., O–H or N–H distance)? Or\ngeneralized reaction coordinate? This was computed somehow so the axis should have\na precise definition (and units). Further, it would be a useful sanity check to compare\nthese results with a higher-level theory (larger basis set, dispersion corrected functional,\nwavefunction method etc.), as the transition-state likely has significant open-shell\n(singlet) character and thus is likely to be very sensitive to the level of theory.\nReply: We apologize for the ambiguity regarding the x-axis in the original Fig. 4d. The\nx-axis corresponds to the reaction path, defined as the intrinsic reaction coordinate\n(IRC)—the steepest descent path on the potential energy surface connecting the reactant\nand product via the transition state. This path objectively quantifies the degree of\nprogress as the system evolves from the transition state structure toward either the\nreactant or product configurations under zero initial kinetic energy, while accounting\nfor the collective motions of all nuclei and their mass effects. The O–H or N–H\ndistances quantify the progression along the reaction coordinate, with each geometric\nstate corresponding directly to an energy value on the y-axis. Thus, the x-axis inherently\nlacks conventional physical units. To clarify this representation, we have changed the\nx-axis of Fig. 4d in the main text to a dimensionless IRC, in accordance with its specific\nmethodological characteristics. In addition, while the calculations in the main text used\nthe 6-31+G(d) basis set, we further validated the transition states by recalculating with\nthe 6-31G(d) basis set. Although absolute energies show slight variations arising from\nbasis set differences, the overall energetic trends and barrier heights remain consistent\n(Fig. R5), confirming the robustness of the identified transition state. In addition, the\nmolecules tested in our work do not involve spin properties, so the issue of open-shell\ncharacter is not applicable.\nFig. R5 | Theoretical diagram of the potential energy associated with hydrogen\nmigration under the 6-31+G(d) basis set (black line) and 6-31G(d) basis set (red line).\nRevision: We have changed the x-axis of Fig. 4d in the main text to the intrinsic reaction\ncoordinate (IRC) (Page 11).\nFig. R6 (Fig. 4d) | Theoretical diagram of the potential energy associated with\nhydrogen migration under conditions of zero electric field (black line) and high electric\nfield (red line).\nComment 4: Figures 5d, 5e, and S15 show more than two colours in the molecular\norbital isosurfaces. Could the authors explain the meaning of the colour gradients? How\nshould they be interpreted? It is better to avoid bright red and bright green colours for\nthe iso-surfaces for colourblind readers. Iso values should be mentioned in the caption.\nReply: We thank the reviewer very much for this attention to these details. The color\ngradients in Figs. 5d, 5e, and S15 represent the phase of the molecular orbital\nwavefunctions. Variations in color intensity (e.g., from deep to shallow) correspond to\nthe differences in the probability density of the electron in those regions; areas with\nmore pronounced gradients indicate a more concentrated electron cloud distribution. To\nhelp readers better distinguish these color differences, we have standardized the color\nscheme for all HOMO–LUMO orbitals in Fig. 1b (Fig. R7), Figs. 3e and 3f (Fig. R8),\nFigs. 5d and 5e (Fig. R9) in the main text, as well as Supplementary Fig. 12 (Fig. R10),\nSupplementary Fig. 13 (Fig. R11), and Supplementary Fig. 19 (Fig. R12) in the\nsupplementary information. We have also annotated the iso values in the figure captions.\nRevision: We have replaced Fig. 1b, Figs. 3e and 3f, Figs. 5d, and 5e in the main text,\nand Supplementary Fig. 12, Supplementary Fig. 13, and Supplementary Fig. 19 in the\nsupplementary information. We have added the corresponding iso values to the figure\ncaptions in the revised main text: “with an isosurface of 0.02.” (Page 4, Line 91 and\nPage 9, Line 195), and “with an isosurface of 0.1.” (Page 13, Lines 267 and 268),\nrespectively. In the revised Supplementary Figs. 12, 13, and 19, we have added the\nfollowing sentences to the captions: “with an isosurface of 0.02.”, “with an isosurface\nof 0.05.” and “with an isosurface of 0.1.”, respectively.\nFig. R7 (Fig. 1b) | Theoretical distributions of the HOMO electron orbitals before (M-\nOH) and after hydrogen migration (M-NH) with an isosurface of 0.02.\nFig. R8 (Figs. 3e and 3f) | Theoretical distributions of the HOMO electron orbitals\nbefore (M-OH) and after hydrogen migration (M-NH) with an isosurface of 0.02.\nFig. R9 (Figs. 5d and 5e) | Influence of acids (d) and bases (e) on the HOMO structures\nof M-OH with an isosurface of 0.1.\nFig. R10 (Supplementary Fig. 12) | Theoretical calculation of the frontier orbitals.\nCalculated LUMO-orbital (up) and HOMO-orbital (down) diagrams of M-OCH (a),\nFig. R11 (Supplementary Fig. 13) | Molecular projected self–consistent\nHamiltonian (MPSH) eigenstate plots of M-OH. The LUMO (up) and HOMO (down)\norbital distributions before (a) and after (b) hydrogen migration with an isosurface of\n0.05.\nFig. R12 (Supplementary Fig. 19) | Theoretical calculation of molecular frontier\norbitals after acidification or alkalization. Calculated LUMO-orbital (up) and\nHOMO-orbital (down) diagrams of M-OH/CSA (a) and M-OH/TBAOH (b) with an\nisosurface of 0.1.\nComment 5: It would be helpful if the authors could provide the optimized geometries\nof the molecules in the presence of explicit solvent molecules, including important\nsolvent–molecule intermolecular distances in SI or a data repository.\nReply: Thank the reviewer very much for the good suggestion. Using the same basis\nset and functions, we incorporated both explicit and implicit parameters for the solvent\npropylene carbonate (PC) (electric permittivity of the solvent, ε = 24.5) and optimized\nthe molecular structures of M-OH and M-NH. The results are shown in Fig. R13. A\ncomparison of the optimized structures in the two cases reveals negligible differences.\nFig. R13 (Supplementary Fig. 9) | Optimization of molecular structures. The\noptimized structures of M-OH (a) and M-NH (c) in PC and the optimized structures of\nM-OH (b) and M-NH (d) in the absence of PC.\nRevision: We have added the following sentence to the revised main text: “In addition,\nthe structures optimized in the presence of the solvent molecules showed negligible\ndifferences (Supplementary Fig. 9).” (Page 7, Lines 149–151). We have also added\nSupplementary Fig. 9 to the revised supplementary information.\nComment 6: The manuscript states, “In comparison with the initial state M-OH, the\norbital distribution of the final state M-NH is more delocalized (Fig. 1b).” However, it\nmay be more accurate to describe this as “extended conjugation,” since the benzene\nring in M-OH appears to exhibit greater delocalization, while in M-NH, the presence\nof cross-conjugation due to the C=O group may reduce delocalization within the core\nring. Incidentally orbital delocalisation is not a good measure of\ntransmission/conductance but on the other hand, the narrowing of HOMO-LUMO gaps\nwith extended conjugation length and resulting increase in transport is extremely well\nestablished (and what appears to be happening here).\nReply: We sincerely thank the reviewer for this insightful comment. We agree that\ndescribing the change in electronic structure as “more delocalized” oversimplifies the\nsubtle conjugation effects. As the reviewer mentioned, the phenyl ring in M-OH\nexhibits stronger π-delocalization, whereas M-NH introduces cross-conjugation via the\nC=O group, which may reduce π-delocalization within the central ring. Accordingly,\nwe have revised the manuscript by replacing “more delocalized” with “extended\nconjugation.” Regarding the conductance mechanism, we fully agree with the view that\nmerely relying on the delocalization property of the orbitals is not sufficient to\naccurately predict the transport phenomenon. A critical insight is that the extended\nconjugation reduces π-delocalization within the central ring, leading to a narrowed\nHOMO-LUMO gap in the M-NH configuration (as seen in Fig. 3a), which in turn\nenhances the conductance.\nRevision: We have added the following sentence to the revised main text: “the final\nstate M-NH exhibits an extended conjugation effect on the molecular framework while\nreducing the π delocalization within the core ring” (Page 4, Lines 84–86) and “For M-\nNH, the extended conjugation effect reduces the HOMO-LUMO energy gap, bringing\nthe HOMO closer to the E (Fig. 3a), while weakening the DQI effect. As a result, the\nF\nloop current across the aromatic system is significantly attenuated, thereby enhancing\nits charge transport capability (Fig. 3c, Supplementary Fig. 11b).” (Page 8, Lines 173–\n177).\nComment 7: The interpretation about loop current in the following statements is\nincorrect and misleading. This is not a problem regarding the quality of the results or\noverall conclusions, simply the interpretation of the results and incorrect statements in\nthe text. “For M-OH, a complex loop current across the aromatic system is observed,\ndemonstrating a significant destructive quantum interference (DQI) effect (Fig. 3b).”\nand “The same DQI effect is also observed in M-OCH (Supplementary Fig. 8b). For\nthereby weakening the DQI effect and enhancing its charge transport capability (Fig.\n3c).” The DQI effect is indeed affected, but that cannot be interpreted from the local\ncurrent circulation at a particular energy (ring current reversals are evidence of DQI not\nring current at a particular energy). Rather, the observed variation in DQI appears to\narise from differences in conjugation, specifically from the extended conjugation for\nthe M-NH state, which reduces the cid:clip_image002.pngas compared to the M-OH\nstate shifting both resonances and anti-resonances (this is clear from Figure 3a). These\nenergy shifts ultimately modulate the transmission at the Fermi level, arguably with the\nHOMO energy shift being the dominant effect.\nReply: We sincerely appreciate the reviewer’s critical comments regarding our\ninterpretation of the DQI effect. Firstly, we fully agree that using the loop current as\ndirect proof of the DQI effect is misleading. The loop current should rather be regarded\nas a manifestation of the DQI effect. Accordingly, we have revised the causal\nrelationship in the manuscript. The original sentence, “For M-OH, a complex loop\ncurrent across the aromatic system is observed, demonstrating a significant destructive\nquantum interference (DQI) effect,” has been modified to: “For M-OH, a complex loop\ncurrent is observed in the aromatic system (Fig. 3b) due to the presence of a significant\nDQI effect.” Then, as noted by the reviewer, the reduction of the DQI effect in M-NH\nprimarily arises from the π-delocalization within the core ring, which is induced by the\nextended conjugation. The observed decrease in the loop current is a consequence of\nthis delocalization. We now emphasize: “The extended conjugation in M-NH reduces\nthe HOMO-LUMO gap, bringing the HOMO closer to the Fermi level (𝐸 ) (Fig. 3a).”\n𝐹\nThe loop currents depicted in Figs. 3b and 3c serve as schematic representations of\ncurrent transmission pathways and are not quantitative measures of the DQI effect.\nWe are grateful to the reviewer for correcting our misunderstanding of the role of loop\ncurrents. Indeed, the reduced DQI in M-NH is driven by the extended-conjugation-\ninduced narrowing of the HOMO-LUMO gap, which shifts the HOMO closer to 𝐸\n𝐹\n(Fig. 3a).\nRevision: We have added the following sentences to revise the main text: “For M-OH,\na complex loop current is observed in the aromatic system (Fig. 3b and Supplementary\nFig. 11a) due to the presence of a significant destructive quantum interference (DQI)\neffect.” (Page 8, Lines 169–171) and “Similarly, a complex loop current is also\nobserved in M-OCH₃ (Supplementary Fig. 11c). For M-NH, the extended conjugation\neffect reduces the HOMO-LUMO energy gap, bringing the HOMO closer to the E (Fig.\nF\n3a), while weakening the DQI effect. As a result, the loop current across the aromatic\nsystem is significantly attenuated, thereby enhancing its charge transport capability (Fig.\n3c, Supplementary Fig. 11b).” (Page 8, Lines 173–177).\nComment 8: It would be beneficial to include the bond lengths corresponding to O–\nH···N and O···H–N interactions in Figure 1.\nReply: We thank the reviewer very much for the valuable suggestion. We have added\nthe hydrogen bond lengths of O–H··N and O··H–N to the caption of Fig. 1.\nRevision: We have added the corresponding figure caption to the revised main text:\n“Hydrogen bond lengths are 1.75 Å (left) and 1.56 Å (right), respectively.” (Page 4,\nLines 91 and 92).\nComment 9: The caption for Section 7 in the Supporting Information appears to\ncontain an error and should be revised.\nReply: We thank the reviewer very much for pointing out this issue. We have corrected\nthe incorrect caption in Section 10 of the supplementary information from\n“Experimental conductance results of M-OH/CSA and M-OCH ” to “Theoretical\n3\ncalculation results of M-OH/CSA and M-OH/TBAOH”.\nRevision: We have added the following sentences to revise the caption for Section 10\nin the revised supplementary information: “Theoretical calculation results of M-\nOH/CSA and M-OH/TBAOH”.\nComment 10: Authors could specify the exact linker used in the molecular junctions\n(i.e.,–C≡C–Ph–SAc).\nReply: We sincerely appreciate the reviewer’s suggestion. In this study, both ends of\nthe molecular junction are connected by Au–S covalent bonds. Specifically, the target\nmolecules synthesized in this study are terminated with –SAC groups. As described in\nthe Methods section of the manuscript, we employed a well-established deprotection\nprocedure reported in the literature to convert –SAC to –SH (Tetrahedron Lett. 1998,\n39, 2693). The primary purpose of this conversion is to enable the formation of Au–S\ncovalent bonds through the dehydrogenation of –SH upon binding to gold electrodes, a\nprocess that has been widely documented in previous studies (Nat. Chem. 2019, 11,\n351).\nRevision: We have added the following sentences to revise the Methods section of the\nmain text: “After deprotection, the –SAC groups are converted to –SH, which\nsubsequently undergoes dehydrogenation to form Au–S covalent bonds with gold. This\nprocess leads to the formation of Au–molecule–Au junctions.” (Page 16, Lines 373–\n375).\nComment 11: It would be better if the authors orient the ChemDraw structure and the\nisosurfaces in the same way in Figure 3 and Figure 5.\nReply: We thank the reviewer very much for the suggestion. Since the orbital diagrams\nin the manuscript were calculated using different software programs, we selected\nappropriate isosurface values to ensure that the orbital distributions are clearly visible\nto readers. We also made an effort to standardize the color schemes for consistency.\nTherefore, we have standardized the color scheme for the HOMO and LUMO orbitals\nin Fig. 1b, Figs. 3e and 3f, Figs. 5d and 5e, Supplementary Figs. 12, 13, and 19, and\nindicated the isosurface in the figure captions.\nRevision: We have standardized the color scheme for the HOMO and LUMO orbitals\nin Fig. 1b, Figs. 3e and 3f, Figs. 5d and 5e, Supplementary Figs. 12, 13, and 19, and\nindicated the isosurface in the figure captions.\nThe specific revisions can be also found in Comment 4 for details.\nResponse to Reviewer #2:\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nReply: We sincerely appreciate the reviewer’s insightful and constructive feedbacks.\nAfter careful consideration and revision based on the comments, the manuscript has\nbeen significantly improved.\nResponse to Reviewer #3:\nThis manuscript investigates the hydrogen tautomerization behavior of\nhydroxybenzothiazole by introducing phenyl thioacetate groups at both ends of the\nmolecule, enabling single-molecule electronic characterization using scanning\ntunneling microscopy break junction (STM-BJ) techniques. A methoxy-substituted\ncontrol molecule (M-OCH₃) is also introduced for comparison.\nThe authors begin by using two-dimensional (2D) conductance–displacement\nhistograms to identify two distinct molecular configurations: M-OH and M-NH.\nThrough theoretical calculations of the transmission spectra, they attribute the higher\nconductance observed in the M-NH configuration to the weakening of destructive\nquantum interference (DQI). Furthermore, the authors perform I–V measurements on\nsingle-molecule junctions and combine these results with calculations of the proton\ntransfer energy barrier. They conclude that the electric field modulates the energy\nbarrier between the two tautomeric states, facilitating configuration switching. Finally,\n2D conductance–displacement histograms are recorded under acidic and basic\nconditions. The observed differences in configuration populations are attributed to\nprotonation and deprotonation effects, specifically the stabilization of the M-NH state\nby H⁺ binding to the nitrogen atom and stabilization of the M-OH state by OH⁻ locking\nthe hydrogen atom.\nThe study presents an interesting and valuable contribution to the understanding of\nhydrogen tautomerization and electric-field-induced proton transfer at the single-\nmolecule level. However, I have a few major concerns regarding the claim that the\nelectric field modulates the proton transfer process. Here are my comments:\nReply: We sincerely appreciate the reviewer’s positive evaluation and the constructive\nsuggestions. In response to the reviewer’s concerns regarding the electric-field-driven\nproton transfer process, we have included an intrinsic reaction coordinate (IRC) plot\nunder a strong electric field in the opposite direction (Fig. R14) to investigate the\nswitching dynamics under both positive and negative field directions. We found that\nwhile the electric field modulates switching dynamics, its asymmetric impact is less\npronounced than initially anticipated. This further supports the hypothesis that inelastic\nelectron excitation may also contribute to the observed symmetric switching behavior.\nThese thoughtful questions have significantly helped us improve the quality of the\nmanuscript. Our detailed responses are provided below.\nComment 1: In the section \"Electric-field manipulation of the single H atom state\", the\nauthors propose that an electric field modulates the potential energy barrier between\ntwo configurations, thereby controlling the switching dynamics. However, if this\nmodulation were truly due to an electric field effect, one would expect the conductance\nvoltage (G–V) curve to exhibit asymmetry with respect to bias polarity. This is because\nthe field effect should influence the switching rate monotonically, regardless of the field\ndirection. In contrast, Figure 4b shows a symmetric conductance change around ±0.75\nV. This behavior is inconsistent with a pure electric-field-driven mechanism, especially\nconsidering the asymmetric structure of the molecule under study. Moreover, in Figure\n4d, the authors only compare the transmission spectra at zero and high electric field\nstrengths, without specifying the direction of the applied field or discussing the results\nfor opposite field orientations. The authors should address this inconsistency and\nconsider alternative explanations, such as bias induced electron excitation, which is\ninherently symmetric with respect to zero bias. Relevant studies have previously\nattributed symmetric switching behavior to inelastic electron excitation processes:\n[1] J. Gaudioso and W. Ho, Angew. Chemie 113, 4204 (2001).\n[2] J. Gaudioso and W. Ho, J. Am. Chem. Soc. 123, 10095 (2001).\n[3] K. Motobayashi et al., Phys. Rev. Lett. 105, 076101 (2010).\n[4] J. Oh et al., Phys. Rev. Lett. 116, 056101 (2016).\nReply: We sincerely thank the reviewer for the insightful comments. Regarding the\nsymmetry of the conductance-voltage (G–V) curves: We agree with the reviewer that\nthe barrier modulation purely driven by the electric field would indeed result in\nasymmetry in the conductance curves with respect to bias polarity as the electric field\naffects the switching rate in a monotonic manner, regardless of its direction. However,\nthe symmetry observed in Fig. 4b suggests that this behavior is not solely governed by\nelectric-field-induced barrier modulation. As noted by the reviewer, a plausible\nexplanation involves inelastic electronic excitation processes, which may be\ncharacterized by abrupt changes in tunneling current as the bias increases (Phys. Rev.\nLett. 1996, 17, 1139), consistent with our experimental results. Regarding the\ndirectionality of the electric field, we agree that it is necessary to clarify the direction\nof the applied electric field. In our last submission, we did not explicitly address the\neffect of reversing the field direction. We have now included an IRC plot under a strong\nelectric field in the opposite direction (Fig. R14) to investigate the switching dynamics\nunder both positive and negative electric fields, and incorporated them into the revised\nmanuscript. We found that while the electric field modulates switching dynamics, its\nasymmetric impact is less pronounced than initially anticipated. It further supports the\nhypothesis that inelastic electronic excitations may also contribute to observed\nsymmetric switching behavior.\nRevision: We have added the following sentences to the revised main text: “The results\nshow that under zero electric field, there is a relatively large energy barrier difference\nbetween the final state (M-NH) and the initial state (M-OH). However, under a high\nelectric field, the energy barrier difference between M-NH and M-OH decreases and\nbecomes insensitive to the electric field direction (Fig. 4d and Supplementary Fig. 16).\nThis indicates that the hydrogen transfer process is not entirely governed by electric-\nfield-induced barrier modulation. As reported previously31−34, a bias-induced electron-\nexcitation mechanism can render the I–V curve symmetric at zero bias. Therefore,\nanother possibility is the involvement of inelastic electronic excitation processes, which\nleads to symmetric switching. This involvement can be characterized by abrupt changes\nin tunneling current as the bias increases35, consistent with the experimental results of\nthis work.” (Page 10, Lines 212–221). In addition, we have added references 31–35 in\nthe revised main text (Page 15, Lines 347–356), and Supplementary Fig. 16 to the\nrevised supplementary information.\nFig. R14 (Supplementary Fig. 16) | Theoretical calculation of the potential energy.\nTheoretical diagram of the potential energy associated with hydrogen migration under\na positive high electric field (black line) and a negative high electric field (red line).\nThe following references have been added in the main text accordingly:\nresistance in a single molecule. Angew. Chem. Int. Ed. 40, 4080−4082 (2001).\nelectronic conductivity of five-membered heterocycles. J. Am. Chem. Soc. 123,\n10095−10098 (2001).\nmotion and reactions through inelastic electron tunneling. Phys. Rev. Lett. 105,\n076101 (2010).\nexcitation. Phys. Rev. Lett. 116, 056101 (2016).\nRev. Lett. 17, 1139−1140 (1996).\nComment 2: In lines 159–161, the authors attribute the weakening of destructive\nquantum interference (DQI) in the M-NH configuration to reduced loop currents.\nHowever, this conclusion is not clearly supported by Figures 3b and 3c. First, the black\ndotted circle in the figures is too small to interpret, even under high magnification.\nSecond, it is unclear which current loop the authors are referring to. From the figures,\nthe main visible difference is that the M-NH configuration lacks a horizontal red line\nacross two carbon atoms.\nReply: We thank the reviewer very much for pointing out the ambiguity in Figs. 3b and\n3c. The original dashed ellipses were indeed insufficient to highlight the differences in\nring currents. To address the issue of clarity in Figs. 3b and 3c, we have enlarged the\nkey regions showing the ring currents and included them in Supplementary Fig. 11 (Fig.\nR15). In the M-NH structure, attenuation of the DQI effect stems from extended π-\nconjugation at the molecular center. This expansion reduces π-delocalization within the\ncore ring, narrowing the HOMO-LUMO gap and thereby weakening the DQI effect.\nThe resultant diminished ring current directly manifests this weakened quantum\ninterference. We have revised the main text accordingly. As the reviewer correctly noted,\nthe most apparent difference between the two configurations lies in the absence of a\nhorizontal red line between two carbon atoms in M-NH. Since both the M-OH and M-\nNH configurations exhibit DQI features, the overall ring current difference is not\npronounced. However, the DQI effect in M-NH is indeed weaker, resulting in a smaller\nring current compared to that of the M-OH configuration.\nRevision: We have added the following sentences to the revised main text: “For M-NH,\nthe extended conjugation effect reduces the HOMO-LUMO energy gap, bringing the\nHOMO closer to the E (Fig. 3a), while weakening the DQI effect. As a result, the loop\nF\ncurrent across the aromatic system is significantly attenuated, thereby enhancing its\ncharge transport capability (Fig. 3c, Supplementary Fig. 11b).” (Page 8, Lines 173–\n177). We also added Supplementary Fig. 11 to the revised supplementary information.\nFig. R15 (Supplementary Fig. 11) | Theoretical electron transport paths.\nTheoretical electron transport paths of the core parts of M-OH (a), M-NH (b), and M-\nOCH (c).\nreflect distinct tautomeric configurations (M-OH vs. M-NH), rather than different\nadsorption geometries. However, the method for assigning plateau lengths to specific\nconfigurations (G and G ) is not clearly defined. If the molecule undergoes reversible\nH L\nswitching, the plateau length alone cannot unambiguously indicate the configuration at\nthe snapping point. The authors should clarify how they distinguish between\nconfigurations, especially when switching may occur mid-plateau.\nReply: We thank the reviewer very much for pointing out the need to clarify\nmethodological details. The plateau length refers to the Au–molecule–Au distance,\nwhich reflects the overall length of the molecular junction. In this work, the plateau\nlength is determined by analyzing data points that fall at least half an order of magnitude\nbelow the minimum conductance value. We found that the intrinsic molecular length\nremains constant for both the M-OH and M-NH configurations. Therefore, the length\nhistogram exhibits a single pronounced peak. If molecular junctions of different lengths\nwere formed during the conductance measurements, multiple peaks should appear in\nthe length histogram. Indeed, many previous studies have employed this method to\ndistinguish molecular junctions of varying lengths (J. Am. Chem. Soc. 2012, 134, 2292;\nNat. Chem. 2022, 14, 1158). This further supports that, in our study, only one type of\nmolecular junction was consistently formed, anchored by Au–S covalent contacts at\nboth ends, representing the tunneling conductance of the intact molecule. Moreover,\nsince Supplementary Fig. 8 has ruled out the influence of different stable states of the\nmolecule on the conductance, it provides additional evidence that the observed high\nand low conductance states can only arise from two distinct configurations induced by\nproton transfer.\nRevision: We have added the following sentences to revise the method section of the\nmain text: “The plateau length is determined by analyzing data points that fall at least\nhalf an order of magnitude below the minimum conductance value.” (Page 16, Lines\n377–379).\nComment 4: Please clarify whether the orbital shown in Figure 1b corresponds to the\nHOMO or LUMO.\nReply: We thank the reviewer very much for the valuable comment. The orbital shown\nin Fig. 1b corresponds to the HOMO, and we have revised the manuscript accordingly.\nRevision: We have added the following sentences in the caption of Fig. 1: “Theoretical\ndistributions of the HOMO electron orbitals before (M-OH) and after hydrogen\nmigration (M-NH) with an isosurface of 0.02.” (Page 4, Lines 90 and 91).\nComment 5: The authors claim that Figure 1b shows two configurations and Figure 1e\nshows one. However, Figure 1b appears to show three configurations, and Figure 1e\nshows two, based on the circled areas. From context, it seems the authors refer to only\nthe top two circles in 1b and the top one in 1e. Please clarify the status of the bottom\nconfigurations in both figures.\nReply: We sincerely thank the reviewer for the careful reading and valuable suggestions.\nIn response, we have added the one-dimensional (1D) and two-dimensional (2D)\nconductance histograms of the pure solvent without molecules in Supplementary Fig.\n7 (Fig. R16). It is evident that in the absence of the target molecules, the 1D\nconductance histogram shows no molecular conductance peaks other than the quantum\nconductance peak at 0 corresponding to gold atoms, and any signals below 10−6 G are\n0\nattributed to instrumental background noise. The 2D conductance histogram only\nexhibits an exponentially decaying tunneling feature, with no evidence of molecular\nplateaus or electron cloud distribution.\nUpon introducing the target molecules, distinct conductance plateaus emerge\nbetween 10−0.3 G and 10−6 G , in addition to the gold quantum conductance and\n0 0\nbackground noise. The corresponding 1D histogram also displays pronounced\nconductance peaks, providing further evidence that M-OH and M-OCH₃ exhibit two\nand one conductance states, respectively. To clearly present the number of conductance\nstates, we have added explicit annotations in Fig. 2 (Fig. R17) of the main text.\nRevision: We have replaced Fig. 2 and added a corresponding caption in the revised\nmain text: “The dashed box indicates the conductance plateau.” (Page 7, Lines 142 and\n143), and we have added the following sentences to the revised main text: “We firstly\nperformed STM-BJ measurements in pure solvent PC (Supplementary Fig. 7) to ensure\nthat PC itself does not exhibit any significant conductance plateau before proceeding\nwith conductance measurements of the target molecules.” (Page 5, Lines 101–104). We\nhave also added Supplementary Fig. 7 to the revised supplementary information.\nFig. R16 (Supplementary Fig. 7) | Single-molecule electrical measurements of PC.\na 2D conductance-displacement histogram of PC at a bias voltage of 0.1 V. b 1D\nconductance histogram of PC.\nFig. R17 (Fig. 2) | Single-molecule electrical measurements of M-OH and M-OCH .\n3\na,d STM–BJ measurement diagrams of M-OH (a) and M-OCH (d) single-molecule\n3\njunctions. b,e 2D conductance-displacement histograms of M-OH (b) and M-OCH (e)\n3\njunctions at a bias voltage of 0.1 V. The dashed box indicates the conductance plateau.\nInset: individual conductance-displacement traces of molecular junctions (red, blue and\ngreen) and those of Au contacts in the pure solvent (black traces). c,f 1D conductance\nhistograms of M-OH (c) and M-OCH (f) junctions. Inset: corresponding plateau length\n3\nstatistics.\nComment 6: The method used to generate Figures 1c and 1f is not described. a.Were\nthese obtained at a fixed displacement value? b. Or did the authors use an algorithm to\nextract plateau conductance from each trace? This methodology should be clearly\ndescribed—ideally in the Supplementary Information—and referenced in the main text.\nReply: We sincerely appreciate the reviewer’s suggestion. We assume that you referred\nto the generation methods of Figs. 2c and 2f. Our instrument collects individual\nconductance traces, as illustrated in the inset of Fig. 2b. Thousands of such traces are\nused to construct the two-dimensional conductance histogram shown in Fig. 2b. The\none-dimensional (1D) conductance histograms presented in Figs. 2c and 2f are derived\nfrom the 2D histogram. Specifically, the x-axis represents the conductance values, while\nthe y-axis corresponds to the number of traces exhibiting those specific conductance\nvalues. By plotting the count of each conductance value continuously, we obtain the 1D\nconductance histograms shown in Figs. 2c and 2f. The red and blue peaks marked in\nthe figures are Gaussian fitting peaks obtained by applying Gaussian fitting to the\nrespective regions of the 1D histogram. The method is clearly described in Reference\n31 (Chin. J. Chem. 2024, 42, 317) cited in the main text.\nIn response to question (a), we assume that you asked us whether the conductance\nmeasurements were carried out at a fixed electrode separation during the experiment.\nOur conductance measurements were performed using the scanning tunneling\nmicroscopy break junction (STM-BJ) technique, which involves the relative motion of\nthe electrodes to form and break molecular junctions. As illustrated in Fig. R18 (Science,\n2003, 301, 1221), we take the measurement process of 4,4'-bipyridine as an example.\nAt the beginning of the measurement, the gold tip is slowly approached toward the gold\nsubstrate that is coated with the target molecules. When contact is made, a gold-gold\njunction is formed by mechanical indentation, and the conductance reaches a predefined\nthreshold. As the tip is retracted, the contact area gradually decreases due to the ductility\nof gold, eventually forming a single-atom Au–Au junction, as shown in Fig. R18a. At\nthis stage, a distinct conductance plateau is observed. As the tip continues to retract, the\nAu–Au junction breaks, and a molecular junction (Au-Molecule-Au) is formed via\ninteractions between the terminal gold atoms and the anchoring groups of the molecule,\nresulting in a molecular conductance plateau, as shown in Fig. R18c. With further\nretraction, the electrode separation becomes too large to maintain the molecular\njunction, leading to its rupture and the disappearance of the conductance plateau, as\nshown in Fig. R18e. Therefore, the conductance is not measured at a fixed electrode\nspacing. Instead, the formation of molecular junctions is identified automatically based\non characteristic conductance signals during the electrode separation process.\nFig. R18 | (a) Formation of the single-atom Au–Au junction and conductance tests. (b)\nConductance histogram of the single-atom Au–Au junction. (c) Formation of the Au–\nMolecule–Au molecular junction and conductance tests. (d) Conductance histogram of\nthe Au-Molecule-Au molecular junction. (e) Structure and corresponding conductance\nfor the junction without molecules. (f) Conductance histogram for the junction without\nmolecules. Copyright 2003 American Association for the Advancement of Science.\nIn response to question (b), we employed the built-in measurement and data\nacquisition methods provided by the instrument, which use a fixed algorithm to extract\nconductance plateaus from the traces. This method is clearly described in Reference 36\ncited in the main text, as detailed below: “The breaking traces. In general cases, the\noriginal conductance data collected from break junction measurements are continuous\nwave-like signals composed of consecutive open and close conductance curves, usually\nsaved as TDMS files. The first preprocessing step of the original data is to split the\ncontinuous signal into individual open and close traces. Since each individual open\ntrace is the repetition of the opening process of the electrodes, they should be aligned\nalong the time or displacement dimension. In our case, all traces are aligned by referring\nto a fixed conductance point that corresponds to the time points immediately after the\nrupture of the Au-Au single-atom contact. The reference conductance value was set to\n‒0.3 G , where G = 2 e2/h is the quantum conductance of the Au-Au atomic contact.\n0 0\nIt’s worth noting that formation and rupture of the Au-Au single-atom contact, which\nhas not occurred in the closing process, makes it more possible for the electrodes to\n‘catch’ a single molecule; for this reason, most of the subsequent statistical analyses are\nbased on the aligned breaking traces, rather than the closing traces.”\nRevision: We have added the following sentences to revise the Methods section of the\nmain text: “The conductance is not measured at a fixed electrode spacing. Instead, the\nformation of molecular junctions is automatically identified through characteristic\nconductance signals during the electrode separation process. The measurement of the\nsingle-molecule conductivity and the specific algorithm for extracting the conductance\nvalues are performed using the Xtech STM-BJ system developed by Professor Wenjing\nHong's team at Xiamen University36.” (Pages 16, Lines 383–388).\nComment 7: The x-axis label “Δz” is used in Figures 1b, 1e, 1c inset, and 1f inset, but\nit represents different quantities in different figures. a. In Figures 1b and 1e, it indicates\nelectrode displacement, b. While in the insets of Figures 1c and 1f, it appears to\nrepresent plateau length. The authors should either clarify this distinction or use\ndifferent labels to avoid confusion.\nReply：We sincerely appreciate the reviewer’s suggestion. We assume that you may\nrefer to the x-axis labels in Figs. 2b, 2c, 2e, and 2f. In all figures throughout the\nmanuscript, Δz denotes the same parameter. As mentioned above, our conductance\nmeasurements were performed using the STM-BJ technique, in which molecular\njunctions are formed through the relative motion of the electrodes. Δz represents the\nrelative displacement between the source and drain electrodes and indirectly reflects\nthe length of the molecular junction. Specifically, due to the high ductility of gold, a\nretraction (\"snap-back\") of approximately 0.5 nm occurs when the gold-gold junction\nbreaks. Therefore, the actual molecular junction length can be estimated as Δz + 0.5 nm.\nThis approach has been widely reported in the literature (Chem, 2020, 6, 2770).\nRevision：We have added the following sentences to revise the Methods section of the\nmain text: “Due to the high ductility of gold, a retraction of approximately 0.5\nnanometers occurs when the gold-gold junction breaks. Therefore, the statistically\nderived plateau length (Δz) plus 0.5 nm equals the molecular junction length.” (Page\n16, Lines 379–381).\nComment 8: The authors should explicitly identify Figure 3a as presenting the electron\ntransmission spectra when it is first mentioned in the main text.\nReply: We are grateful to the reviewer for bringing this important clarification\nrequirement to our attention. We have made the revisions in the main text.\nRevision: We have added the following sentences to the revised main text: “The y axis\nof the electron transmission spectra represents the electron transmission coefficient of\nthe molecular junction, the magnitude of which indirectly reflects the charge transport\ncapability of the junction.” (Page 7, Lines 152–154).\nComment 9: The authors should specify the experimental conditions under which the\ndata in Figure 4 were obtained, particularly regarding the electrode displacement. This\nis important for reproducibility and interpretation.\nReply: We are grateful to the reviewers for emphasizing the reproducibility of the\nexperiment. The test method for I−V in Fig. 4 has been elaborated in the Methods\nsection. Regarding the experimental conditions related to electrode displacement, we\nset the conductance range and sampling threshold based on the expected conductance\nof the target molecule. If the number of sampling points detected within this range\nexceeds a certain threshold, a conductance plateau is identified. At this point, the piezo\nmotion pauses to maintain the molecular junction within this conductance range. The\nmeasurement mode then switches to I–V acquisition, which is completed within 200\nmilliseconds, during which the I–V curves are collected for subsequent statistical\nanalysis. Therefore, the spacing between the two electrodes is not fixed during the\nmeasurement; rather, the system automatically adjusts it by detecting the formation of\na conductance plateau within the predefined range.\nRevision: We have added the following sentences to revise the Methods section of the\nmain text: “The distance between two electrodes is not fixed during the measurement;\ninstead, it is automatically adjusted by the instrument upon detecting the formation of\na conductance plateau within the predefined range.” (Page 17, Lines 396–398).\nResponse to Reviewer #4:\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nReply: We sincerely appreciate the reviewer’s insightful and constructive feedbacks.\nAfter carefully considering and revising the manuscript based on these comments, we\nhave significantly improved its quality.\nWe sincerely thank the reviewers for their invaluable time and constructive\ncomments, which have helped us significantly improve the manuscript.\nListed below are the major changes in the new version of the manuscript.\n1. We have deleted the following sentence in the revised main text: “As a result, the\nloop current across the aromatic system is significantly attenuated, thereby\nenhancing its charge transport capability.”\nPlease refer to Page 8 in the revised main text.\n2. We have used thinner purple and cyan lines to represent the ‘complex loops’ in both\nthe revised main text (Fig. 3) and the supplementary information (Supplementary\nFig. 11), and we have also added relevant explanations in the revised main text.\nPlease refer to Pages 8 and 9 in the revised main text and Page S22 in the revised\nsupplementary information.\n3. We have standardized the colors of the 2D conductance-displacement histograms\nin the revised main text (Figs. 2 and 5) and supplementary information\n(Supplementary Figs. 17 and 18).\nPlease refer to Pages 7 and 13 in the revised main text and Pages S27 and S28 in\nthe revised supplementary information.\n4. We have added a discussion in the main text to address the origin of the random\noccurrence of molecular conductance states.\nPlease refer to Pages 5 and 6 in the revised main text.\nA detailed point-by-point response to the comments of the reviewers is listed as\nfollows:\nResponse to Reviewer #1：\nIn the revised version, the authors have addressed most of the concerns, which\nstrengthened their claims significantly. Only a few minor comments and suggestions\ncan be addressed, but we believe this is optional.\nReply: We are very grateful to the reviewer for his/her pertinent and constructive\ncomments. In response, we have carefully revised the manuscript, and these changes\nhave significantly improved its quality.\nComment 1: The authors have tested their transition state in Fig. R5 with a lower basis\nset 6-31g(d), but it would be very nice if they could check with a higher basis set (e.g.,\ntriple zeta polarised basis set) and also with dispersion correction added with the\nfunctional.\nReply: We thank the reviewer very much for the suggestion. We recalculated the IRC\nusing a larger basis set 6-311G(d,p), with empirical dispersion correction (GD3BJ). As\nshown in Fig. R1, although slight changes in absolute energies are observed due to the\ndifference in basis sets, the overall energy profiles and barrier heights remain consistent,\nconfirming the robustness of the identified transition state.\nFig. R1 | Theoretical diagram of the potential energies associated with hydrogen\nmigration under the 6-31+G(d) basis set (black), 6-31G(d) basis set (red), and 6-\n311G(d,p) basis set (blue).\nComment 2: We agree with most of the additions regarding the discussion of extended\nconjugation and DQI but the sentence in Line 175: “As a result, the loop current across\nthe aromatic system is significantly attenuated, thereby enhancing its charge transport\ncapability” could be removed. In our opinion this is not true (at least as we understand\nthe statement) because it implies that the ring current is somehow responsible for DQI\n(rather than just being a symptom) and that the magnitude controls the magnitude of\ntransport.\nReply: We thank the reviewer very much for this insightful comment and explanation.\nWe agree with the reviewer that the original sentence in Line 175 could misleadingly\nimply a causal relationship between the weakening of the aromatic ring current and the\nsuppression of destructive quantum interference (DQI). To avoid confusion, we have\nremoved this sentence in the revised manuscript.\nRevision: We have deleted the following sentence on original Page 8 of the revised\nmain text: “As a result, the loop current across the aromatic system is significantly\nattenuated, thereby enhancing its charge transport capability”.\nResponse to Reviewer #2：\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nReply: We sincerely appreciate the reviewer’s insightful and constructive feedbacks.\nAfter careful consideration and revision based on the comments, the manuscript has\nbeen significantly improved.\nResponse to Reviewer #3：\nThe authors have addressed some of my previous comments and questions, however,\nthere are still a few issues the author should discuss to further strengthen the\npresentation.\nReply: We sincerely appreciate the reviewer’s insightful and constructive comments.\nWe have carefully addressed each point and incorporated the suggestions into the\nrevised manuscript, which has substantially enhanced its overall quality.\nComment 1: Regarding Previous Comment 2 In the revised manuscript (line 168), do\nyou mean line thickness when referring to “the diameters of these lines”? If so, could\nyou instead use a thin line (with a color other than blue or red) to indicate the “complex\nloop”?\nReply: We thank the reviewer very much for pointing this out. Indeed, in the revised\nmanuscript (Line 168), the phrase “the diameters of these lines” originally referred to\nthe thickness of the lines. To express this more accurately, we have replaced “diameter”\nwith “thickness.” In addition, to better distinguish the complex ring currents, we now\nuse thinner purple and cyan lines to represent the complex loops.\nRevision: We have added the following sentence to the revised main text: “The cyan\nlines represent the electron paths transmitting from the left electrode to the right\nelectrode, while the purple lines denote the opposite direction. The thickness of these\nlines corresponds to the transmission coefficient between two incident atoms,\nnormalized to the highest transmission coefficient in each molecule.” (Page 8, Lines\n166–170) We have also replaced Figs. 3b and 3c in the revised main text (Page 9) and\nSupplementary Fig. 11 in the revised supplementary information.\nFig. R2 (Fig. 3) | Regulation mechanism of a single H atom on the electronic\nstructure of the aromatic system. a Theoretical transmission spectra before (blue) and\nafter (red) H migration. The transmission values of M-OH and M-NH are 10−3.67 and\n10−3.14, respectively. b,c Theoretical electron transport paths before (b) and after (c) H\nmigration. d Schematic diagram demonstrating the tautomerism of H migration in M-\nOH. e,f Theoretical distributions of the HOMO electron orbitals before (M-OH) and\nafter hydrogen migration (M-NH) with an isosurface of 0.02.\nFig. R3 (Supplementary Fig. 11) | Theoretical electron transport paths. Theoretical\nelectron transport paths of the core parts of M-OH (a), M-NH (b), and M-OCH3 (c).\nComment 2: Regarding Previous Comment 5 The newly added dashed circles make\nthe configurations much clearer. I now also see why the initial confusion arose: white\nis used to represent both very high counts and very low counts. This makes it difficult\nto distinguish whether a white region corresponds to an absence of data or the highest\nprobability. I suggest adopting a different color scale that separates low and high counts\nmore clearly. A good example is in Figures 4a and 4b, where white denotes low counts\nand black denotes high counts. The figures affected by this ambiguity include Figures\n2b, 2c, 5b, and 5c.\nReply: We thank the reviewer very much for carefully pointing out the ambiguity\ncaused by the original color scales. We fully agree that using white to represent both\nlow and high counts could be misleading. Following the reviewer’s suggestion, we have\nrevised the color scales in Figs. 2b, 2e, 5b, and 5c in the main text, as well as Figs. S17\nand S18 in the supplementary information. This ensures a clearer distinction between\nlow and high counts.\nRevision: We have replaced Figs. 2b, 2e, 5b, and 5c in the main text (Pages 7 and 13),\nand Supplementary Figs. 17 and 18 as follows:\nFig. R4 (Fig. 2) | Single-molecule electrical measurements of M-OH and M-OCH .\n3\na,d STM-BJ measurement diagrams of M-OH (a) and M-OCH (d) single-molecule\n3\njunctions. b,e 2D conductance-displacement histograms of M-OH (b) and M-OCH (e)\n3\njunctions at a bias voltage of 0.1 V. The dashed box indicates the conductance plateau.\nInset: individual conductance-displacement traces of molecular junctions (red, blue and\ngreen) and those of Au contacts in the pure solvent (black traces). c,f 1D conductance\nhistograms of M-OH (c) and M-OCH (f) junctions. Inset: corresponding plateau length\n3\nstatistics.\nFig. R5 (Fig. 5) | Effects of acids and bases on the state of a single H atom in M-\nOH. a Regulatory mechanism of the H atom state by acids and bases. b,c 2D\nconductance-displacement histograms of M-OH/CSA 10:10 (b) and M-OH/TBAOH\n1:10 (c) at a bias voltage of 0.1 V. Inset: corresponding 1D conductance histograms. d,e\nInfluence of acids (d) and bases (e) on the HOMO structures of M-OH with an\nisosurface of 0.1. f Calculated transmission spectra based on these structures. The\ntransmission values of M-OH/CSA and M-OH/TBAOH are 10−4.11 and 10−3.16,\nrespectively.\nFig. R6 (Supplementary Fig. 17) | Experimental conductance results of M-OH\nmolecules acidized with CSA in different concentrations. 2D conductance-\ndisplacement histograms (up) and 1D conductance histograms (down) of M-OH/CSA\n10:1 (a, d), 10:5 (b, e) and 10:10 (c, f) at a bias voltage of 0.1 V.\nFig. R7 (Supplementary Fig. 18) | Experimental conductance results of M-OH\nmolecules alkalified with TBAOH in different concentrations. 2D conductance-\ndisplacement histograms (up) and 1D conductance histograms (down) of M-\nOH/TBAOH 1:1 (a, d), 1:5 (b, e) and 1:10 (c, f) at a bias voltage of 0.1 V.\nComment 3: Additional follow-up Comments related to previous Comment 3 and\nComment 5 Why does the second tautomeric configuration, M-OH (–3.45), only appear\nafter ΔZ exceeds a certain value in Figure 2b? How does Z modulate the potential of\nthe two tautomeric configurations? This mechanically related chemical tuning is quite\ninteresting. Could the authors add a paragraph discussing this point? Are Figures 2c and\n2f statistical analyses of Figures 2b and 2e, respectively? The use of two-Gaussian/one-\nGaussian fitting suggests that the authors assume the conductance of both\nconfigurations remains constant across all ΔZ values. However, this assumption does\nnot seem reasonable, since Figure 2b clearly shows that Z affects the conductance of\neach configuration. I suggest that the authors perform the analysis at specific Z values\nand repeat it for multiple Z values, rather than pooling all Z values together. This\napproach may even allow the authors to identify how the conductance of each\nconfiguration evolves with ΔZ, instead of assigning a fixed value across all Z.\nReply: We sincerely thank the reviewer for the valuable comments and would like to\nclarify the possible misunderstandings as follows.\nFirstly, based on our experimental results, we provide a brief introduction to the\nSTM-BJ technique. A typical breaking process is illustrated in Fig. R8a (Chem. Soc.\nRev., 2015, 44, 889–901). Initially, the metallic wire is connected (a). As stretching\nproceeds, the contact area gradually decreases until a single-atom point contact is\nformed (b), corresponding to the conductance plateau (1) in Fig. R8b, i.e., the single-\natom contact state. Further stretching breaks the final metal–metal bond, allowing the\nmolecule—anchored by its terminal groups (or weak interactions) — to slide into the\nnanogap and adopt a partially coiled configuration (c). This stage corresponds to\nconductance plateaus (2) and (3). Since the M-NH and M-OH configurations exhibit\nsimilar lengths and undergo random switching, plateaus (2) and (3) do not follow a\nfixed sequence. Continued stretching straightens the molecule, leading to an extended\nconfiguration (d and e). Stages c–e all reflect the molecular conductance, resulting in\nGaussian peaks with finite half-widths in the statistical analyses. Further stretching\nbreaks the molecular junction at the electrode–molecule contact (f), corresponding to\nthe conductance decay below –6 G in Fig. R8b. Reversing the operation from state f\n0\nre-establishes the electrode contact. By repeatedly performing this stretching–retracting\ncycle, numerous nanogaps are dynamically generated for molecular junction formation,\nenabling sufficient statistical data collection for conductance analyses.\nTherefore, the reviewer’s concern—“why conductance states only appear when ΔZ\nexceeds a certain value”—stems from the inherent stepwise nature of the STM-BJ\nstretching–breaking process. While ΔZ may influence the potential energy of molecular\nconformations, the present experiments were conducted under consistent conditions\nwithout force modulation. The transitions between the two conductance states occur\nrandomly and are independent of the external force. According to the fundamental\nprinciple of STM-BJ, the plateau length reflects the intrinsic molecular length rather\nthan any force effect.\nFigs. 2c and 2f represent the statistical analyses corresponding to Figs. 2b and 2e,\nrespectively. The reviewer’s suggestion to analyze conductance at specific ΔZ values is\nconstructive. However, in STM-BJ experiments as noted above, stretching corresponds\nto increasing the electrode separation, and the associated conductance evolution follows\nthe sequence: quantum conductance through metallic atomic contact→ molecular\nbridge conductance plateaus → exponential tunneling decay after rupture. For this\nreason, the conductance-plateau-based statistical method has been widely adopted in\nthe field, as it provides a more comprehensive representation of the molecular transport\ncharacteristics. Such data processing and analytical methods are well established and\npresent standard practice in this research area (Science, 2003, 301, 1221; Nature, 2006,\n442, 904–907; Nature, 2018, 558, 415–419).\nFig. R8 | Molecular junction evolution and conductance characterization. (a)\nSchematic of the molecular junction stretching process during STM-BJ measurements.\n(b) 2D conductance-displacement histograms of M-OH at a bias voltage of 0.1 V.\nRevision: We have added the following sentences to the main text: “The red and blue\ncurves are associated with the low conductance (G ) and the high conductance (G )\nL H\nstates, respectively. Their stochastic occurrence, independent existence, and ability to\ninterconvert (as shown by the green curve) indicate a dynamic equilibrium between two\ndistinct configurations.” (Pages 5 and 6, Lines 121–124).\nResponse to Reviewer #4:\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nReply: We thank the reviewer for their insightful and constructive feedback, which\nhave significantly enhanced the quality of our manuscript.\nWe sincerely thank all the reviewers for their invaluable time and constructive\ncomments, which have helped us significantly improve the manuscript."}, {"round": 2, "reviewer_comments": {"reviewer_1": "In the revised version, the authors have addressed most of the concerns, which strengthened their claims significantly. Only a few minor comments and suggestions can be addressed, but we believe this is optional.\n1. The authors have tested their transition state in Fig. R5 with a lower basis set 6-31g(d), but it would be very nice if they could check with a higher basis set (e.g., triple zeta polarised basis set) and also with dispersion correction added with the functional.\n2. We agree with most of the additions regarding the discussion of extended conjugation and DQI but the sentence in Line 175: “As a result, the loop current across the aromatic system is significantly attenuated, thereby enhancing its charge transport capability” could be removed. In our opinion this is not true (at least as we understand the statement) because it implies that the ring current is somehow responsible for DQI (rather than just being a symptom) and that the magnitude controls the magnitude of transport.", "reviewer_2": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts.", "reviewer_3": "The authors have addressed some of my previous comments and questions, however, there are still a few issues the author should discuss to further strengthen the presentation.\nRegarding Previous Comment 2\nIn the revised manuscript (line 168), do you mean line thickness when referring to “the diameters of these lines”? If so, could you instead use a thin line (with a color other than blue or red) to indicate the “complex loop”?\nRegarding Previous Comment 5\nThe newly added dashed circles make the configurations much clearer. I now also see why the initial confusion arose: white is used to represent both very high counts and very low counts. This makes it difficult to distinguish whether a white region corresponds to an absence of data or the highest probability. I suggest adopting a different color scale that separates low and high counts more clearly. A good example is in Figures 4a and 4b, where white denotes low counts and black denotes high counts. The figures affected by this ambiguity include Figures 2b, 2c, 5b, and 5c.\nAdditional follow-up Comments related to previous Comment 3 and Comment 5\nWhy does the second tautomeric configuration, M–OH (–3.45), only appear after ΔZ exceeds a certain value in Figure 2b? How does Z modulate the potential of the two tautomeric configurations? This mechanically related chemical tuning is quite interesting. Could the authors add a paragraph discussing this point?\nAre Figures 2c and 2f statistical analyses of Figures 2b and 2e, respectively? The use of two-Gaussian/one-Gaussian fitting suggests that the authors assume the conductance of both configurations remains constant across all ΔZ values. However, this assumption does not seem reasonable, since Figure 2b clearly shows that Z affects the conductance of each configuration. I suggest that the authors perform the analysis at specific Z values and repeat it for multiple Z values, rather than pooling all Z values together. This approach may even allow the authors to identify how the conductance of each configuration evolves with ΔZ, instead of assigning a fixed value across all Z.", "reviewer_4": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts."}, "author_response": "Listed below are the major changes in the new version of the manuscript.\n1. We have deleted the following sentence in the revised main text: “As a result, the\nloop current across the aromatic system is significantly attenuated, thereby\nenhancing its charge transport capability.”\nPlease refer to Page 8 in the revised main text.\n2. We have used thinner purple and cyan lines to represent the ‘complex loops’ in both\nthe revised main text (Fig. 3) and the supplementary information (Supplementary\nFig. 11), and we have also added relevant explanations in the revised main text.\nPlease refer to Pages 8 and 9 in the revised main text and Page S22 in the revised\nsupplementary information.\n3. We have standardized the colors of the 2D conductance-displacement histograms\nin the revised main text (Figs. 2 and 5) and supplementary information\n(Supplementary Figs. 17 and 18).\nPlease refer to Pages 7 and 13 in the revised main text and Pages S27 and S28 in\nthe revised supplementary information.\n4. We have added a discussion in the main text to address the origin of the random\noccurrence of molecular conductance states.\nPlease refer to Pages 5 and 6 in the revised main text.\nA detailed point-by-point response to the comments of the reviewers is listed as\nfollows:\nResponse to Reviewer #1：\nIn the revised version, the authors have addressed most of the concerns, which\nstrengthened their claims significantly. Only a few minor comments and suggestions\ncan be addressed, but we believe this is optional.\nReply: We are very grateful to the reviewer for his/her pertinent and constructive\ncomments. In response, we have carefully revised the manuscript, and these changes\nhave significantly improved its quality.\nComment 1: The authors have tested their transition state in Fig. R5 with a lower basis\nset 6-31g(d), but it would be very nice if they could check with a higher basis set (e.g.,\ntriple zeta polarised basis set) and also with dispersion correction added with the\nfunctional.\nReply: We thank the reviewer very much for the suggestion. We recalculated the IRC\nusing a larger basis set 6-311G(d,p), with empirical dispersion correction (GD3BJ). As\nshown in Fig. R1, although slight changes in absolute energies are observed due to the\ndifference in basis sets, the overall energy profiles and barrier heights remain consistent,\nconfirming the robustness of the identified transition state.\nFig. R1 | Theoretical diagram of the potential energies associated with hydrogen\nmigration under the 6-31+G(d) basis set (black), 6-31G(d) basis set (red), and 6-\n311G(d,p) basis set (blue).\nComment 2: We agree with most of the additions regarding the discussion of extended\nconjugation and DQI but the sentence in Line 175: “As a result, the loop current across\nthe aromatic system is significantly attenuated, thereby enhancing its charge transport\ncapability” could be removed. In our opinion this is not true (at least as we understand\nthe statement) because it implies that the ring current is somehow responsible for DQI\n(rather than just being a symptom) and that the magnitude controls the magnitude of\ntransport.\nReply: We thank the reviewer very much for this insightful comment and explanation.\nWe agree with the reviewer that the original sentence in Line 175 could misleadingly\nimply a causal relationship between the weakening of the aromatic ring current and the\nsuppression of destructive quantum interference (DQI). To avoid confusion, we have\nremoved this sentence in the revised manuscript.\nRevision: We have deleted the following sentence on original Page 8 of the revised\nmain text: “As a result, the loop current across the aromatic system is significantly\nattenuated, thereby enhancing its charge transport capability”.\nResponse to Reviewer #2：\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nReply: We sincerely appreciate the reviewer’s insightful and constructive feedbacks.\nAfter careful consideration and revision based on the comments, the manuscript has\nbeen significantly improved.\nResponse to Reviewer #3：\nThe authors have addressed some of my previous comments and questions, however,\nthere are still a few issues the author should discuss to further strengthen the\npresentation.\nReply: We sincerely appreciate the reviewer’s insightful and constructive comments.\nWe have carefully addressed each point and incorporated the suggestions into the\nrevised manuscript, which has substantially enhanced its overall quality.\nComment 1: Regarding Previous Comment 2 In the revised manuscript (line 168), do\nyou mean line thickness when referring to “the diameters of these lines”? If so, could\nyou instead use a thin line (with a color other than blue or red) to indicate the “complex\nloop”?\nReply: We thank the reviewer very much for pointing this out. Indeed, in the revised\nmanuscript (Line 168), the phrase “the diameters of these lines” originally referred to\nthe thickness of the lines. To express this more accurately, we have replaced “diameter”\nwith “thickness.” In addition, to better distinguish the complex ring currents, we now\nuse thinner purple and cyan lines to represent the complex loops.\nRevision: We have added the following sentence to the revised main text: “The cyan\nlines represent the electron paths transmitting from the left electrode to the right\nelectrode, while the purple lines denote the opposite direction. The thickness of these\nlines corresponds to the transmission coefficient between two incident atoms,\nnormalized to the highest transmission coefficient in each molecule.” (Page 8, Lines\n166–170) We have also replaced Figs. 3b and 3c in the revised main text (Page 9) and\nSupplementary Fig. 11 in the revised supplementary information.\nFig. R2 (Fig. 3) | Regulation mechanism of a single H atom on the electronic\nstructure of the aromatic system. a Theoretical transmission spectra before (blue) and\nafter (red) H migration. The transmission values of M-OH and M-NH are 10−3.67 and\n10−3.14, respectively. b,c Theoretical electron transport paths before (b) and after (c) H\nmigration. d Schematic diagram demonstrating the tautomerism of H migration in M-\nOH. e,f Theoretical distributions of the HOMO electron orbitals before (M-OH) and\nafter hydrogen migration (M-NH) with an isosurface of 0.02.\nFig. R3 (Supplementary Fig. 11) | Theoretical electron transport paths. Theoretical\nelectron transport paths of the core parts of M-OH (a), M-NH (b), and M-OCH3 (c).\nComment 2: Regarding Previous Comment 5 The newly added dashed circles make\nthe configurations much clearer. I now also see why the initial confusion arose: white\nis used to represent both very high counts and very low counts. This makes it difficult\nto distinguish whether a white region corresponds to an absence of data or the highest\nprobability. I suggest adopting a different color scale that separates low and high counts\nmore clearly. A good example is in Figures 4a and 4b, where white denotes low counts\nand black denotes high counts. The figures affected by this ambiguity include Figures\n2b, 2c, 5b, and 5c.\nReply: We thank the reviewer very much for carefully pointing out the ambiguity\ncaused by the original color scales. We fully agree that using white to represent both\nlow and high counts could be misleading. Following the reviewer’s suggestion, we have\nrevised the color scales in Figs. 2b, 2e, 5b, and 5c in the main text, as well as Figs. S17\nand S18 in the supplementary information. This ensures a clearer distinction between\nlow and high counts.\nRevision: We have replaced Figs. 2b, 2e, 5b, and 5c in the main text (Pages 7 and 13),\nand Supplementary Figs. 17 and 18 as follows:\nFig. R4 (Fig. 2) | Single-molecule electrical measurements of M-OH and M-OCH .\n3\na,d STM-BJ measurement diagrams of M-OH (a) and M-OCH (d) single-molecule\n3\njunctions. b,e 2D conductance-displacement histograms of M-OH (b) and M-OCH (e)\n3\njunctions at a bias voltage of 0.1 V. The dashed box indicates the conductance plateau.\nInset: individual conductance-displacement traces of molecular junctions (red, blue and\ngreen) and those of Au contacts in the pure solvent (black traces). c,f 1D conductance\nhistograms of M-OH (c) and M-OCH (f) junctions. Inset: corresponding plateau length\n3\nstatistics.\nFig. R5 (Fig. 5) | Effects of acids and bases on the state of a single H atom in M-\nOH. a Regulatory mechanism of the H atom state by acids and bases. b,c 2D\nconductance-displacement histograms of M-OH/CSA 10:10 (b) and M-OH/TBAOH\n1:10 (c) at a bias voltage of 0.1 V. Inset: corresponding 1D conductance histograms. d,e\nInfluence of acids (d) and bases (e) on the HOMO structures of M-OH with an\nisosurface of 0.1. f Calculated transmission spectra based on these structures. The\ntransmission values of M-OH/CSA and M-OH/TBAOH are 10−4.11 and 10−3.16,\nrespectively.\nFig. R6 (Supplementary Fig. 17) | Experimental conductance results of M-OH\nmolecules acidized with CSA in different concentrations. 2D conductance-\ndisplacement histograms (up) and 1D conductance histograms (down) of M-OH/CSA\n10:1 (a, d), 10:5 (b, e) and 10:10 (c, f) at a bias voltage of 0.1 V.\nFig. R7 (Supplementary Fig. 18) | Experimental conductance results of M-OH\nmolecules alkalified with TBAOH in different concentrations. 2D conductance-\ndisplacement histograms (up) and 1D conductance histograms (down) of M-\nOH/TBAOH 1:1 (a, d), 1:5 (b, e) and 1:10 (c, f) at a bias voltage of 0.1 V.\nComment 3: Additional follow-up Comments related to previous Comment 3 and\nComment 5 Why does the second tautomeric configuration, M-OH (–3.45), only appear\nafter ΔZ exceeds a certain value in Figure 2b? How does Z modulate the potential of\nthe two tautomeric configurations? This mechanically related chemical tuning is quite\ninteresting. Could the authors add a paragraph discussing this point? Are Figures 2c and\n2f statistical analyses of Figures 2b and 2e, respectively? The use of two-Gaussian/one-\nGaussian fitting suggests that the authors assume the conductance of both\nconfigurations remains constant across all ΔZ values. However, this assumption does\nnot seem reasonable, since Figure 2b clearly shows that Z affects the conductance of\neach configuration. I suggest that the authors perform the analysis at specific Z values\nand repeat it for multiple Z values, rather than pooling all Z values together. This\napproach may even allow the authors to identify how the conductance of each\nconfiguration evolves with ΔZ, instead of assigning a fixed value across all Z.\nReply: We sincerely thank the reviewer for the valuable comments and would like to\nclarify the possible misunderstandings as follows.\nFirstly, based on our experimental results, we provide a brief introduction to the\nSTM-BJ technique. A typical breaking process is illustrated in Fig. R8a (Chem. Soc.\nRev., 2015, 44, 889–901). Initially, the metallic wire is connected (a). As stretching\nproceeds, the contact area gradually decreases until a single-atom point contact is\nformed (b), corresponding to the conductance plateau (1) in Fig. R8b, i.e., the single-\natom contact state. Further stretching breaks the final metal–metal bond, allowing the\nmolecule—anchored by its terminal groups (or weak interactions) — to slide into the\nnanogap and adopt a partially coiled configuration (c). This stage corresponds to\nconductance plateaus (2) and (3). Since the M-NH and M-OH configurations exhibit\nsimilar lengths and undergo random switching, plateaus (2) and (3) do not follow a\nfixed sequence. Continued stretching straightens the molecule, leading to an extended\nconfiguration (d and e). Stages c–e all reflect the molecular conductance, resulting in\nGaussian peaks with finite half-widths in the statistical analyses. Further stretching\nbreaks the molecular junction at the electrode–molecule contact (f), corresponding to\nthe conductance decay below –6 G in Fig. R8b. Reversing the operation from state f\n0\nre-establishes the electrode contact. By repeatedly performing this stretching–retracting\ncycle, numerous nanogaps are dynamically generated for molecular junction formation,\nenabling sufficient statistical data collection for conductance analyses.\nTherefore, the reviewer’s concern—“why conductance states only appear when ΔZ\nexceeds a certain value”—stems from the inherent stepwise nature of the STM-BJ\nstretching–breaking process. While ΔZ may influence the potential energy of molecular\nconformations, the present experiments were conducted under consistent conditions\nwithout force modulation. The transitions between the two conductance states occur\nrandomly and are independent of the external force. According to the fundamental\nprinciple of STM-BJ, the plateau length reflects the intrinsic molecular length rather\nthan any force effect.\nFigs. 2c and 2f represent the statistical analyses corresponding to Figs. 2b and 2e,\nrespectively. The reviewer’s suggestion to analyze conductance at specific ΔZ values is\nconstructive. However, in STM-BJ experiments as noted above, stretching corresponds\nto increasing the electrode separation, and the associated conductance evolution follows\nthe sequence: quantum conductance through metallic atomic contact→ molecular\nbridge conductance plateaus → exponential tunneling decay after rupture. For this\nreason, the conductance-plateau-based statistical method has been widely adopted in\nthe field, as it provides a more comprehensive representation of the molecular transport\ncharacteristics. Such data processing and analytical methods are well established and\npresent standard practice in this research area (Science, 2003, 301, 1221; Nature, 2006,\n442, 904–907; Nature, 2018, 558, 415–419).\nFig. R8 | Molecular junction evolution and conductance characterization. (a)\nSchematic of the molecular junction stretching process during STM-BJ measurements.\n(b) 2D conductance-displacement histograms of M-OH at a bias voltage of 0.1 V.\nRevision: We have added the following sentences to the main text: “The red and blue\ncurves are associated with the low conductance (G ) and the high conductance (G )\nL H\nstates, respectively. Their stochastic occurrence, independent existence, and ability to\ninterconvert (as shown by the green curve) indicate a dynamic equilibrium between two\ndistinct configurations.” (Pages 5 and 6, Lines 121–124).\nResponse to Reviewer #4:\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nReply: We thank the reviewer for their insightful and constructive feedback, which\nhave significantly enhanced the quality of our manuscript.\nWe sincerely thank all the reviewers for their invaluable time and constructive\ncomments, which have helped us significantly improve the manuscript."}, {"round": 3, "reviewer_comments": {"reviewer_1": "The authors have addressed all the points we have raised and we have no further comments. In our opinion the paper is now suitable for publication.", "reviewer_2": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts.", "reviewer_3": "The authors have addressed all my questions. I support the manuscript to be published ASIS.", "reviewer_4": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts."}, "author_response": ""}]

Decision letter