Profiling Hydrogen-Bond Conductance via Fixed-Gap Tunnelling Sensors in Physiological Solution
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Fabrication and Characterisation of the QMT Probe
2.3. Preparation of Flow Cell
2.4. Preparation of 4-MBA-Functionalised QMT Probes
2.5. Hydrogen-Bond Recognition Tunnelling Measurements
3. Results and Discussion
3.1. Functionalisation and Characterisation of QMT Probe
3.2. Conductance Measurement of 4-MBA Supramolecular Junctions
3.3. Solvent-Dependent Measurements of 4-MBA Supramolecular Junctions
3.4. Recognition Tunnelling via 4-MBA-Functionalised QMT Probe
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Liu, Y.; Wang, L.; Zhao, L.; Zhang, Y.; Li, Z.-T.; Huang, F. Multiple hydrogen bonding driven supramolecular architectures and their biomedical applications. Chem. Soc. Rev. 2024, 53, 1592–1623. [Google Scholar] [CrossRef] [PubMed]
- Steiner, T. The hydrogen bond in the solid state. Angew. Chem. Int. Ed. 2002, 41, 48–76. [Google Scholar] [CrossRef]
- Sun, T.; Nian, Q.; Ren, X.; Tao, Z. Hydrogen-bond chemistry in rechargeable batteries. Joule 2023, 7, 2700–2731. [Google Scholar] [CrossRef]
- Lin, R.-B.; He, Y.; Li, P.; Wang, H.; Zhou, W.; Chen, B. Multifunctional porous hydrogen-bonded organic framework materials. Chem. Soc. Rev. 2019, 48, 1362–1389. [Google Scholar] [CrossRef]
- Reek, J.N.H.; de Bruin, B.; Pullen, S.; Mooibroek, T.J.; Kluwer, A.M.; Caumes, X. Transition metal catalysis controlled by hydrogen bonding in the second coordination sphere. Chem. Rev. 2022, 122, 12308–12369. [Google Scholar] [CrossRef] [PubMed]
- Bondar, A.-N. Graphs of hydrogen-bond networks to dissect protein conformational dynamics. J. Phys. Chem. B 2022, 126, 3973–3984. [Google Scholar] [CrossRef] [PubMed]
- Bellissent-Funel, M.-C.; Hassanali, A.; Havenith, M.; Henchman, R.; Pohl, P.; Sterpone, F.; van der Spoel, D.; Xu, Y.; Garcia, A.E. Water determines the structure and dynamics of proteins. Chem. Rev. 2016, 116, 7673–7697. [Google Scholar] [CrossRef]
- Livshits, G.I.; Stern, A.; Rotem, D.; Borovok, N.; Eidelshtein, G.; Migliore, A.; Penzo, E.; Wind, S.J.; Di Felice, R.; Skourtis, S.S.; et al. Long-range charge transport in single G-quadruplex DNA molecules. Nat. Nanotechnol. 2014, 9, 1040–1046. [Google Scholar] [CrossRef]
- Cleland, W.W.; Kreevoy, M.M. Low-barrier hydrogen bonds and enzymic catalysis. Science 1994, 264, 1887–1890. [Google Scholar] [CrossRef]
- Ishikita, H.; Saito, K. Proton transfer reactions and hydrogen-bond networks in protein environments. J. R. Soc. Interface 2014, 11, 20130518. [Google Scholar] [CrossRef]
- Saito, K.; Rutherford, A.W.; Ishikita, H. Mechanism of proton-coupled quinone reduction in Photosystem II. Proc. Natl. Acad. Sci. USA 2012, 110, 954–959. [Google Scholar] [CrossRef] [PubMed]
- Jiang, T.; Zeng, B.-F.; Zhang, B.; Tang, L. Single-molecular protein-based bioelectronics via electronic transport: Fundamentals, devices and applications. Chem. Soc. Rev. 2023, 52, 5968–6002. [Google Scholar] [CrossRef]
- Kretsch, R.C.; Li, S.; Pintilie, G.; Palo, M.Z.; Case, D.A.; Das, R.; Zhang, K.; Chiu, W. Complex water networks visualized by cryogenic electron microscopy of RNA. Nature 2025, 642, 250–259. [Google Scholar] [CrossRef]
- Wang, C.; Geng, X.; Chen, J.; Wang, H.; Wei, Z.; Huang, B.; Liu, W.; Wu, X.; Hu, L.; Su, G.; et al. Multiple H-bonding cross-linked supramolecular solid–solid phase change materials for thermal energy storage and management. Adv. Mater. 2024, 36, e2309723. [Google Scholar] [CrossRef]
- Ladenthin, J.N.; Frederiksen, T.; Persson, M.; Sharp, J.C.; Gawinkowski, S.; Waluk, J.; Kumagai, T. Force-induced tautomerization in a single molecule. Nat. Chem. 2016, 8, 935–940. [Google Scholar] [CrossRef]
- Zhang, J.; Chen, P.; Yuan, B.; Ji, W.; Cheng, Z.; Qiu, X. Real-space identification of intermolecular bonding with atomic force microscopy. Science 2013, 342, 611–614. [Google Scholar] [CrossRef]
- Pullanchery, S.; Kulik, S.; Rehl, B.; Hassanali, A.; Roke, S. Charge transfer across C–H⋅⋅⋅O hydrogen bonds stabilizes oil droplets in water. Science 2021, 374, 1366–1370. [Google Scholar] [CrossRef]
- Nishino, T.; Hayashi, N.; Bui, P.T. Direct measurement of electron transfer through a hydrogen bond between single molecules. J. Am. Chem. Soc. 2013, 135, 4592–4595. [Google Scholar] [CrossRef] [PubMed]
- Pirrotta, A.; De Vico, L.; Solomon, G.C.; Franco, I. Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes. J. Chem. Phys. 2017, 146, 092329. [Google Scholar] [CrossRef]
- Fang, J.H.; Zhao, Z.H.; Li, A.X.; Wang, L. Electron transport through hydrogen bonded single-molecule junctions. Chin. J. Chem. 2023, 41, 3433–3446. [Google Scholar] [CrossRef]
- Wang, J.; Wang, X.; Yao, C.; Xu, J.; Wang, D.; Zhao, X.; Li, X.; Liu, J.; Hong, W. Interface phenomena in molecular junctions through noncovalent interactions. Langmuir 2025, 41, 5705–5735. [Google Scholar] [CrossRef]
- Wimmer, M.; Palma, J.L.; Tarakeshwar, P.; Mujica, V. Single-molecule conductance through hydrogen bonds: The role of resonances. J. Phys. Chem. Lett. 2016, 7, 2977–2980. [Google Scholar] [CrossRef]
- Wang, L.; Gong, Z.L.; Li, S.Y.; Hong, W.; Zhong, Y.W.; Wang, D.; Wan, L.J. Molecular conductance through a quadruple-hydrogen-bond-bridged supramolecular junction. Angew. Chem. Int. Ed. 2016, 55, 12393–12397. [Google Scholar] [CrossRef]
- Zhou, C.; Li, X.X.; Gong, Z.L.; Jia, C.C.; Lin, Y.W.; Gu, C.H.; He, G.; Zhong, Y.W.; Yang, J.L.; Guo, X.F. Direct observation of single-molecule hydrogen-bond dynamics with single-bond resolution. Nat. Commun. 2018, 9, 807. [Google Scholar] [CrossRef]
- Chang, S.; Huang, S.; He, J.; Liang, F.; Zhang, P.; Li, S.; Chen, X.; Sankey, O.; Lindsay, S. Electronic signatures of all four DNA nucleosides in a tunneling gap. Nano Lett. 2010, 10, 1070–1075. [Google Scholar] [CrossRef]
- Chang, S.; He, J.; Kibel, A.; Lee, M.; Sankey, O.; Zhang, P.; Lindsay, S. Tunnelling readout of hydrogen-bonding-based recognition. Nat. Nanotechnol. 2009, 4, 297–301. [Google Scholar] [CrossRef]
- Tang, L.; Yi, L.; Jiang, T.; Ren, R.; Paulose Nadappuram, B.; Zhang, B.; Wu, J.; Liu, X.; Lindsay, S.; Edel, J.B.; et al. Measuring conductance switching in single proteins using quantum tunneling. Sci. Adv. 2022, 8, eabm8149. [Google Scholar] [CrossRef] [PubMed]
- Tang, L.; Nadappuram, B.P.; Cadinu, P.; Zhao, Z.; Xue, L.; Yi, L.; Ren, R.; Wang, J.; Ivanov, A.P.; Edel, J.B. Combined quantum tunnelling and dielectrophoretic trapping for molecular analysis at ultra-low analyte concentrations. Nat. Commun. 2021, 12, 913. [Google Scholar] [CrossRef] [PubMed]
- Jiang, T.; Yi, L.; Liu, X.; Ivanov, A.P.; Edel, J.B.; Tang, L. Fabrication of electron tunneling probes for measuring single-protein conductance. Nat. Protoc. 2023, 18, 2579–2599. [Google Scholar] [CrossRef]
- Simmons, J.G. Generalized formula for the electric tunnel effect between similar electrodes separated by a thin insulating film. J. Appl. Phys. 1963, 34, 1793–1803. [Google Scholar] [CrossRef]
- Albrecht, T. Electrochemical tunnelling sensors and their potential applications. Nat. Commun. 2012, 3, 829. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.X.; Käll, M. Surface-plasmon-enhanced optical forces in silver nanoaggregates. Phys. Rev. Lett. 2002, 89, 246802. [Google Scholar] [CrossRef]
- Zeng, B.-F.; Deng, R.; Zou, Y.-L.; Huo, C.-A.; Wang, J.-Y.; Yang, W.-M.; Liang, Q.-M.; Qiu, S.-J.; Feng, A.; Shi, J.; et al. Optical trapping of a single Molecule of length sub-1 nm in solution. CCS Chem. 2023, 5, 830–840. [Google Scholar] [CrossRef]
- Huang, S.C.; Wang, X.; Zhao, Q.Q.; Zhu, J.F.; Li, C.W.; He, Y.H.; Hu, S.; Sartin, M.M.; Yan, S.; Ren, B. Probing nanoscale spatial distribution of plasmonically excited hot carriers. Nat. Commun. 2020, 11, 4211. [Google Scholar] [CrossRef]
- Huh, H.; Trinh, H.D.; Lee, D.; Yoon, S. How does a plasmon-induced hot charge carrier break a C-C bond? ACS Appl. Mater. Interfaces 2019, 11, 24715–24724. [Google Scholar] [CrossRef]
- Needham, L.M.; Saavedra, C.; Rasch, J.K.; Sole-Barber, D.; Schweitzer, B.S.; Fairhall, A.J.; Vollbrecht, C.H.; Wan, S.S.; Podorova, Y.; Bergsten, A.J.; et al. Label-free detection and profiling of individual solution-phase molecules. Nature 2024, 629, 1062–1068. [Google Scholar] [CrossRef]
- Dief, E.M.; Low, P.J.; Díez-Pérez, I.; Darwish, N. Advances in single-molecule junctions as tools for chemical and biochemical analysis. Nat. Chem. 2023, 15, 600–614. [Google Scholar] [CrossRef]
- Bui, P.T.; Nishino, T. Electron transfer through coordination bond interaction between single molecules: Conductance switching by a metal ion. Phys. Chem. Chem. Phys. 2014, 16, 5490–5494. [Google Scholar] [CrossRef]
- Lindsay, S.; He, J.; Sankey, O.; Hapala, P.; Jelinek, P.; Zhang, P.; Chang, S.; Huang, S. Recognition tunneling. Nanotechnology 2010, 21, 262001. [Google Scholar] [CrossRef] [PubMed]
- Ma, T.; Guo, J.; Chang, S.; Wang, X.; Zhou, J.; Liang, F.; He, J. Modulating and probing the dynamic intermolecular interactions in plasmonic molecule-pair junctions. Phys. Chem. Chem. Phys. 2019, 21, 15940–15948. [Google Scholar] [CrossRef] [PubMed]
- Cook, J.L.; Hunter, C.A.; Low, C.M.R.; Perez-Velasco, A.; Vinter, J.G. Solvent effects on hydrogen bonding. Angew. Chem. Int. Ed. 2007, 46, 3706–3709. [Google Scholar] [CrossRef]
- Meredith, N.Y.; Borsley, S.; Smolyar, I.V.; Nichol, G.S.; Baker, C.M.; Ling, K.B.; Cockroft, S.L. Dissecting solvent effects on hydrogen bonding. Angew. Chem. Int. Ed. 2022, 61, e202206604. [Google Scholar] [CrossRef] [PubMed]
- Morris, D.T.J.; Wales, S.M.; Tilly, D.P.; Farrar, E.H.E.; Grayson, M.N.; Ward, J.W.; Clayden, J. A molecular communication channel consisting of a single reversible chain of hydrogen bonds in a conformationally flexible oligomer. Chem 2021, 7, 2460–2472. [Google Scholar] [CrossRef]
- Peng, C.S.; Baiz, C.R.; Tokmakoff, A. Direct observation of ground-state lactam–lactim tautomerization using temperature-jump transient 2D IR spectroscopy. Proc. Natl. Acad. Sci. USA 2013, 110, 9243–9248. [Google Scholar] [CrossRef]
- Kumagai, T.; Hanke, F.; Gawinkowski, S.; Sharp, J.; Kotsis, K.; Waluk, J.; Persson, M.; Grill, L. Controlling intramolecular hydrogen transfer in a porphycene molecule with single atoms or molecules located nearby. Nat. Chem. 2013, 6, 41–46. [Google Scholar] [CrossRef]
- Nibbering, E.T.J.; Elsaesser, T. Ultrafast vibrational dynamics of hydrogen bonds in the condensed phase. Chem. Rev. 2004, 104, 1887–1914. [Google Scholar] [CrossRef]
- Yi, L.; Jiang, T.; Ren, R.; Cao, J.; Edel, J.B.; Ivanov, A.P.; Tang, L. Quantum mechanical tunnelling probes with redox cycling for ultra-sensitive detection of biomolecules. Angew. Chem. Int. Ed. 2025, 64, e202501941. [Google Scholar] [CrossRef]
- Jaugstetter, M.; Blanc, N.; Kratz, M.; Tschulik, K. Electrochemistry under confinement. Chem. Soc. Rev. 2022, 51, 2491–2543. [Google Scholar] [CrossRef] [PubMed]
- Trushin, M.; Andreeva, D.V.; Peeters, F.M.; Novoselov, K.S. Structure and flow of low-dimensional water. Nat. Rev. Phys. 2025, 7, 502–513. [Google Scholar] [CrossRef]
- Xiao, S.; Wollman, Z.; Xie, Q.; Duan, C. Current monitoring in nanochannels. Microfluid. Nanofluid. 2022, 26, 86. [Google Scholar] [CrossRef]
- Schuster, R.; Kirchner, V.; Xia, X.H.; Bittner, A.M.; Ertl, G. Nanoscale electrochemistry. Phys. Rev. Lett. 1998, 80, 5599–5602. [Google Scholar] [CrossRef]
- Tsutsui, M.; Taniguchi, M.; Yokota, K.; Kawai, T. Identifying single nucleotides by tunnelling current. Nat. Nanotechnol. 2010, 5, 286–290. [Google Scholar] [CrossRef] [PubMed]
- Huang, S.; He, J.; Chang, S.; Zhang, P.; Liang, F.; Li, S.; Tuchband, M.; Fuhrmann, A.; Ros, R.; Lindsay, S. Identifying single bases in a DNA oligomer with electron tunnelling. Nat. Nanotechnol. 2010, 5, 868–873. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Ashcroft, B.; Zhang, P.; Liu, H.; Sen, S.; Song, W.; Im, J.; Gyarfas, B.; Manna, S.; Biswas, S.; et al. Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling. Nat. Nanotechnol. 2014, 9, 466–473. [Google Scholar] [CrossRef]
- Zhang, B.; Ryan, E.; Wang, X.; Song, W.; Lindsay, S. Electronic transport in molecular wires of precisely controlled length built from modular proteins. ACS Nano 2022, 16, 1671–1680. [Google Scholar] [CrossRef]
Solvent | Gap Distance (nm) | Bimodal Conductance Distribution (nS) | Trimodal Conductance Distribution (nS) | |||
---|---|---|---|---|---|---|
GBL* | GBH* | GTL* | GTM* | GTH* | ||
TCB | 1.40 | 363.11 ± 10.10 | 379.35 ± 8.15 | 365.11 ± 9.023 | 380.90 ± 8.50 | 390.11 ± 10.60 |
TCM | 1.57 | 433.43 ± 26.33 | 558.09 ± 29.07 | 469.38 ± 53.51 | 506.82 ± 20.65 | 588.84 ± 48.14 |
PBS | 1.64 | 459.62 ± 13.85 | 572.77 ± 19.35 | 484.82 ± 14.43 | 548.73 ± 18.42 | 582.61 ± 28.13 |
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Zeng, B.-F.; Yan, C.; Tian, Y.; Yang, Y.; Yi, L.; Fu, S.; Liu, X.; Kuang, C.; Tang, L. Profiling Hydrogen-Bond Conductance via Fixed-Gap Tunnelling Sensors in Physiological Solution. Chemosensors 2025, 13, 360. https://doi.org/10.3390/chemosensors13100360
Zeng B-F, Yan C, Tian Y, Yang Y, Yi L, Fu S, Liu X, Kuang C, Tang L. Profiling Hydrogen-Bond Conductance via Fixed-Gap Tunnelling Sensors in Physiological Solution. Chemosensors. 2025; 13(10):360. https://doi.org/10.3390/chemosensors13100360
Chicago/Turabian StyleZeng, Biao-Feng, Canyu Yan, Ye Tian, Yuxin Yang, Long Yi, Shiyang Fu, Xu Liu, Cuifang Kuang, and Longhua Tang. 2025. "Profiling Hydrogen-Bond Conductance via Fixed-Gap Tunnelling Sensors in Physiological Solution" Chemosensors 13, no. 10: 360. https://doi.org/10.3390/chemosensors13100360
APA StyleZeng, B.-F., Yan, C., Tian, Y., Yang, Y., Yi, L., Fu, S., Liu, X., Kuang, C., & Tang, L. (2025). Profiling Hydrogen-Bond Conductance via Fixed-Gap Tunnelling Sensors in Physiological Solution. Chemosensors, 13(10), 360. https://doi.org/10.3390/chemosensors13100360