Vibronic coupling is key to efficient energy flow in molecular systems and a critical component of most mechanisms invoking quantum effects in biological processes. Despite increasing evidence for coherent coupling of electronic states being mediated by vibrational motion, it is not clear how and to what degree properties associated with vibrational coherence such as phase and coupling of atomic motion can impact the efficiency of light-induced processes under natural, incoherent illumination. Here, we show that deuteration of the H11–C11=C12–H12 double-bond of the 11-cis retinal chromophore in the visual pigment rhodopsin significantly and unexpectedly alters the photoisomerization yield while inducing smaller changes in the ultrafast isomerization dynamics assignable to known isotope effects. Combination of these results with non-adiabatic molecular dynamics simulations reveals a vibrational phase-dependent isotope effect that we suggest is an intrinsic attribute of vibronically coherent photochemical processes.

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  1. 1.

    Born, M. & Oppenheimer, R. Zur Quantentheorie der Molekeln. Ann. Phys. 389, 457–484 (1927).

  2. 2.

    Butler, L. J. Chemical reaction dynamics beyond the Born–Oppenheimer approximation. Annu. Rev. Phys. Chem. 49, 125–171 (1998).

  3. 3.

    Brixner, T. et al. Two-dimensional spectroscopy of electronic couplings in photosynthesis. Nature 434, 625–628 (2005).

  4. 4.

    Engel, G. S. et al. Evidence for wavelike energy transfer through quantum coherence in photosynthetic systems. Nature 446, 782–786 (2007).

  5. 5.

    Lee, H., Cheng, Y.-C. & Fleming, G. R. Coherence dynamics in photosynthesis: protein protection of excitonic coherence. Science 316, 1462–1465 (2007).

  6. 6.

    Romero, E. et al. Quantum coherence in photosynthesis for efficient solar-energy conversion. Nat. Phys. 10, 676–682 (2014).

  7. 7.

    Dostál, J., Pšenčík, J. & Zigmantas, D. In situ mapping of the energy flow through the entire photosynthetic apparatus. Nat. Chem. 8, 705–710 (2016).

  8. 8.

    Delor, M. et al. On the mechanism of vibrational control of light-induced charge transfer in donor–bridge–acceptor assemblies. Nat. Chem. 7, 689–695 (2015).

  9. 9.

    Lim, J. S., Lee, Y. S. & Kim, S. K. Control of intramolecular orbital alignment in the photodissociation of thiophenol: conformational manipulation by chemical substitution. Angew. Chem. Int. Ed. 47, 1853–1856 (2008).

  10. 10.

    Lim, J. S. & Kim, S. K. Experimental probing of conical intersection dynamics in the photodissociation of thioanisole. Nat. Chem. 2, 627–632 (2010).

  11. 11.

    Polli, D. et al. Conical intersection dynamics of the primary photoisomerization event in vision. Nature 467, 440–443 (2010).

  12. 12.

    Kukura, P., McCamant, D. W., Yoon, S., Wandschneider, D. B. & Mathies, R. A. Structural observation of the primary isomerization in vision with femtosecond-stimulated Raman. Science 310, 1006–1009 (2005).

  13. 13.

    Schapiro, I. et al. The ultrafast photoisomerizations of rhodopsin and bathorhodopsin are modulated by bond length alternation and HOOP driven electronic effects. J. Am. Chem. Soc. 133, 3354–3364 (2011).

  14. 14.

    Frutos, L. M., Andruniów, T., Santoro, F., Ferré, N. & Olivucci, M. Tracking the excited-state time evolution of the visual pigment with multiconfigurational quantum chemistry. Proc. Natl Acad. Sci. USA 104, 7764–7769 (2007).

  15. 15.

    Strambi, A., Coto, P. B., Frutos, L. M., Ferré, N. & Olivucci, M. Relationship between the excited state relaxation paths of rhodopsin and isorhodopsin. J. Am. Chem. Soc. 130, 3382–3388 (2008).

  16. 16.

    Schnedermann, C., Liebel, M. & Kukura, P. Mode-specificity of vibrationally coherent internal conversion in rhodopsin during the primary visual event. J. Am. Chem. Soc. 137, 2886–2891 (2015).

  17. 17.

    Wang, Q., Schoenlein, R. W., Peteanu, L. A., Mathies, R. A. & Shank, C. V. Vibrationally coherent photochemistry in the femtosecond primary event of vision. Science 266, 422–424 (1994).

  18. 18.

    Johnson, P. J. M. et al. Local vibrational coherences drive the primary photochemistry of vision. Nat. Chem. 7, 980–986 (2015).

  19. 19.

    Mathies, R. A. Photochemistry: a coherent picture of vision. Nat. Chem. 7, 945–947 (2015).

  20. 20.

    Garavelli, M., Celani, P., Bernardi, F., Robb, M. A. & Olivucci, M. The C5H6NH2 + protonated Shiff base: an ab initio minimal model for retinal photoisomerization. J. Am. Chem. Soc. 119, 6891–6901 (1997).

  21. 21.

    Sinicropi, A., Migani, A., De Vico, L. & Olivucci, M. Photoisomerization acceleration in retinal protonated Schiff-base models. Photochem. Photobiol. Sci. 2, 1250 (2003).

  22. 22.

    Garavelli, M. et al. Photoisomerization path for a realistic retinal chromophore model: the nonatetraeniminium cation. J. Am. Chem. Soc. 120, 1285–1288 (1998).

  23. 23.

    Gozem, S. et al. Mapping the excited state potential energy surface of a retinal chromophore model with multireference and equation-of-motion coupled-cluster methods. J. Chem. Theory Comput. 9, 4495–4506 (2013).

  24. 24.

    Weingart, O. & Garavelli, M. Modelling vibrational coherence in the primary rhodopsin photoproduct. J. Chem. Phys. 137, 22A523 (2012).

  25. 25.

    Weingart, O. et al. Product formation in rhodopsin by fast hydrogen motions. Phys. Chem. Chem. Phys. 13, 3645–3648 (2011).

  26. 26.

    Duan, H.-G., Miller, R. J. D. & Thorwart, M. Impact of vibrational coherence on the quantum yield at a conical intersection. J. Phys. Chem. Lett. 7, 3491–3496 (2016).

  27. 27.

    Qi, D.-L., Duan, H.-G., Sun, Z.-R., Miller, R. J. D. & Thorwart, M. Tracking an electronic wave packet in the vicinity of a conical intersection. J. Chem. Phys. 147, 74101 (2017).

  28. 28.

    Mathies, R. A. & Lugtenburg, J. Chapter 2. The primary photoreaction of rhodopsin. Handb. Biol. Phys. 3, 55–90 (2000).

  29. 29.

    Laptenok, S. P. et al. Complete proton transfer cycle in GFP and its T203V and S205V mutants. Angew. Chem. Int. Ed. 54, 9303–9307 (2015).

  30. 30.

    Klinman, J. P. & Kohen, A. Hydrogen tunneling links protein dynamics to enzyme catalysis. Annu. Rev. Biochem 82, 471–496 (2013).

  31. 31.

    Peters, K., Applebury, M. L. & Rentzepis, P. M. Primary photochemical event in vision: proton translocation. Proc. Natl Acad. Sci. USA 74, 3119–3123 (1977).

  32. 32.

    Fransen, M. R. et al. Structure of the chromophoric group in bathorhodopsin. Nature 260, 726–727 (1976).

  33. 33.

    Kim, J. E., Tauber, M. J. & Mathies, R. A. wavelength dependent cistrans isomerization in vision. Biochemistry 40, 13774–13778 (2001).

  34. 34.

    Kochendoerfer, G. G., Verdegem, P. J., van der Hoef, I., Lugtenburg, J. & Mathies, R. A. Retinal analog study of the role of steric interactions in the excited state isomerization dynamics of rhodopsin. Biochemistry 35, 16230–16240 (1996).

  35. 35.

    Lin, S. W. et al. Vibrational assignment of torsional normal modes of rhodopsin: probing excited-state isomerization dynamics along the reactive C11=C12 torsion coordinate. J. Phys. Chem. B 102, 2787–2806 (1998).

  36. 36.

    Liebel, M., Schnedermann, C., Wende, T. & Kukura, P. Principles and applications of broadband impulsive vibrational spectroscopy. J. Phys. Chem. A 119, 9506–9517 (2015).

  37. 37.

    Bassolino, G. et al. Barrierless photoisomerization of 11-cis retinal protonated Schiff base in solution. J. Am. Chem. Soc. 137, 12434–12437 (2015).

  38. 38.

    Kovalenko, S. A., Dobryakov, A. L., Ruthmann, J. & Ernsting, N. P. Femtosecond spectroscopy of condensed phases with chirped supercontinuum probing. Phys. Rev. A 59, 2369–2384 (1999).

  39. 39.

    Schoenlein, R. W., Peteanu, L. A., Mathies, R. A. & Shank, C. V. The first step in vision: femtosecond isomerization of rhodopsin. Science 254, 412–415 (1991).

  40. 40.

    Dobryakov, A. L. et al. Femtosecond pump/supercontinuum-probe spectroscopy: optimized setup and signal analysis for single-shot spectral referencing. Rev. Sci. Instrum. 81, 113106 (2010).

  41. 41.

    Zener, C. Non-adiabatic crossing of energy levels. Proc. R. Soc. A 137, 696–702 (1932).

  42. 42.

    Landau, L. D. On the theory of transfer of energy at collisions II. Phys. Z. Sowjetunion 2, 7 (1932).

  43. 43.

    Ockenfels, A., Schapiro, I. & Gärtner, W. Rhodopsins carrying modified chromophores – the ‘making of’, structural modelling and their light-induced reactivity. Photochem. Photobiol. Sci. 15, 297–308 (2016).

  44. 44.

    Eyring, G., Curry, B., Broek, A., Lugtenburg, J. & Mathies, R. A. Assignment and interpretation of hydrogen out-of-plane vibrations in the resonance Raman spectra of rhodopsin and bathorhodopsin. Biochemistry 21, 384–393 (1982).

  45. 45.

    Gozem, S., Luk, H. L., Schapiro, I. & Olivucci, M. Theory and simulation of the ultrafast double-bond isomerization of biological chromophores. Chem. Rev. 117, 13502–13565 (2017).

  46. 46.

    Liebel, M., Schnedermann, C. & Kukura, P. Sub-10-fs pulses tunable from 480 to 980 nm from a NOPA pumped by an Yb:KGW source. Opt. Lett. 39, 4112–4115 (2014).

  47. 47.

    Sovdat, T. et al. Backbone modification of retinal induces protein-like excited state dynamics in solution. J. Am. Chem. Soc. 134, 8318–8320 (2012).

  48. 48.

    Okada, T. et al. The retinal conformation and its environment in rhodopsin in light of a new 2.2Å crystal structure. J. Mol. Biol. 342, 571–583 (2004).

  49. 49.

    Luk, H. L. et al. Modulation of thermal noise and spectral sensitivity in Lake Baikal cottoid fish rhodopsins. Sci. Rep. 6, 38425 (2016).

  50. 50.

    Cornell, W. D. et al. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 117, 5179–5197 (1995).

  51. 51.

    Manathunga, M. et al. Probing the photodynamics of rhodopsins with reduced retinal chromophores. J. Chem. Theory Comput. 12, 839–850 (2016).

  52. 52.

    Tully, J. C. Molecular dynamics with electronic transitions. J. Chem. Phys. 93, 1061–1071 (1990).

  53. 53.

    Granucci, G. & Persico, M. Critical appraisal of the fewest switches algorithm for surface hopping. J. Chem. Phys. 126, 134114 (2007).

  54. 54.

    Aquilante, F. et al. Molcas 8: new capabilities for multiconfigurational quantum chemical calculations across the periodic table. J. Comput. Chem. 37, 506–541 (2016).

  55. 55.

    Ponder, J. W. & Richards, F. M. Tinker molecular modeling package. J. Comput. Chem. 8, 1016–1024 (1987).

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We acknowledge support from the National Eye Institute for providing 11-cis retinal used to make the 11,12-H2 regenerated rhodopsin sample. P.K. was supported by the EPSRC (EP/K006630/1). M.O. is supported by the NSF (CHE-1710191) and HFSP (RGP0049/2012) and also thanks the Ohio Supercomputer Center for computer time. I.S. is supported by the ERC Starting Grant ‘PhotoMutant’ (678169). This work was supported in part by the Mathies Royalty Fund.

Author information

Author notes

    • C. Schnedermann

    Present address: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA

    • M. Liebel

    Present address: Institut de Ciencies Fotoniques, The Barcelona Institute of Science & Technology, Castelldefels, (Barcelona), Spain

    • K. M. Spillane

    Present address: Department of Physics, King’s College London, London, UK

    • I. Fernández

    Present address: International Flavors and Fragrances, Benicarló, Spain

    • A. Valentini

    Present address: Département de Chimie, Université de Liège, Liège, Belgium


  1. Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK

    • C. Schnedermann
    • , M. Liebel
    • , K. M. Spillane
    •  & P. Kukura
  2. Chemistry Department, Bowling Green State University, Bowling Green, OH, USA

    • X. Yang
    •  & M. Olivucci
  3. Chemistry Department, University of California, Berkeley, CA, USA

    • K. M. Spillane
    •  & R. A. Mathies
  4. Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands

    • J. Lugtenburg
    •  & I. Fernández
  5. Dipartimento di Biotecnologie, Chimica e Farmacia, Università di Siena, Siena, Italy

    • A. Valentini
    •  & M. Olivucci
  6. Fritz Haber Center for Molecular Dynamics Research, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

    • I. Schapiro
  7. University of Strasbourg, Institute for Advanced Studies, Strasbourg, France

    • M. Olivucci


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R.A.M. and J.L. conceived the project. P.K., C.S. and M.L. designed all experiments and analysed the data. J.L. and I.F. synthesized the isotopomers. M.O. and X.Y. carried out the molecular dynamics simulations and developed the proposed theoretical model. I.S. and A.V. wrote the isotope simulation code. K.M.S. prepared the rhodopsin samples for all measurements. C.S., P.K., M.O. and R.A.M. wrote the manuscript with contributions from all other authors.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to M. Olivucci or P. Kukura or R. A. Mathies.

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  1. Supplementary Information

    Supplementary Data and Analysis, Supplementary Figures 1–17, Tables 1–3

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