Exploring the mechanism of olfactory recognition in the initial stage by modeling the emission spectrum of electron transfer

Autoři: Shu Liu aff001;  Rao Fu aff002;  Guangwu Li aff001
Působiště autorů: Department of Anatomy, Anhui Medical University, Hefei, Anhui, China aff001;  Department of Anatomy, School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0217665


Olfactory sense remains elusive regarding the primary reception mechanism. Some studies suggest that olfaction is a spectral sense, the olfactory event is triggered by electron transfer (ET) across the odorants at the active sites of odorant receptors (ORs). Herein we present a Donor-Bridge-Acceptor model, proposing that the ET process can be viewed as an electron hopping from the donor molecule to the odorant molecule (Bridge), then hopping off to the acceptor molecule, making the electronic state of the odorant molecule change along with vibrations (vibronic transition). The odorant specific parameter, Huang–Rhys factor can be derived from ab initio calculations, which make the simulation of ET spectra achievable. In this study, we revealed that the emission spectra (after Gaussian convolution) can be acted as odor characteristic spectra. Using the emission spectrum of ET, we were able to reasonably interpret the similar bitter-almond odors among hydrogen cyanide, benzaldehyde and nitrobenzene. In terms of isotope effects, we succeeded in explaining why subjects can easily distinguish cyclopentadecanone from its fully deuterated analogue cyclopentadecanone-d28 but not distinguishing acetophenone from acetophenone-d8.

Klíčová slova:

Emission spectra – Odorants – Smell – Vibration – Vibration engineering – Benzaldehydes – Nitrobenzenes – Electron transfer


1. Amoore JE (1963) Stereochemical Theory of Olfaction. Nature 199: 912–913.

2. Amoore JE (1964) Current Status of the Steric Theory of Odor. Ann N Y Acad Sci 116: 457–476. doi: 10.1111/j.1749-6632.1964.tb45075.x 14220538

3. Amoore JE, Johnston JW Jr., Rubin M (1964) The Sterochemical Theory of Odor. Sci Am 210: 42–49.

4. Mori K, Shepherd GM (1994) Emerging principles of molecular signal processing by mitral/tufted cells in the olfactory bulb. Semin Cell Biol 5: 65–74. doi: 10.1006/scel.1994.1009 8186397

5. Sell CS (2006) On the unpredictability of odor. Angew Chem Int Ed Engl 45: 6254–6261. doi: 10.1002/anie.200600782 16983730

6. Dyson GM (1928) Some aspects of the vibration theory of odor. Perfumery and Essential Oil Record 19: 456–459.

7. Dyson GM (1937) Raman effect and the concept of odour. Perfumery and Essential Oil Record 28: 13–19.

8. Wright RH (1954) Odour and molecular vibration. I. Quantum and thermodynamic considerations. Journal of Chemical Technology and Biotechnology 4: 611–615.

9. Wright RH, Reid C, Evans HGV (1956) Odour and molecular vibration. III A new theory of olfactory stimulation. Chemistry and Industry 37: 973–977.

10. Wright RH, Serenius RSE (1954) Odour and molecular vibration. II. Raman spectra of substances with the nitrobenzene odour. Journal of Chemical Technology and Biotechnology 4: 615–621.

11. Turin L (1996) A spectroscopic mechanism for primary olfactory reception. Chem Senses 21: 773–791. doi: 10.1093/chemse/21.6.773 8985605

12. Haffenden AM, Schiff KC, Goodale MA (2001) The dissociation between perception and action in the Ebbinghaus illusion: nonillusory effects of pictorial cues on grasp. Curr Biol 11: 177–181. doi: 10.1016/s0960-9822(01)00023-9 11231152

13. Turin L (2002) A method for the calculation of odor character from molecular structure. J Theor Biol 216: 367–385. doi: 10.1006/jtbi.2001.2504 12183125

14. Keller A, Vosshall LB (2004) A psychophysical test of the vibration theory of olfaction. Nat Neurosci 7: 337–338. doi: 10.1038/nn1215 15034588

15. Brookes JC, Hartoutsiou F, Horsfield AP, Stoneham AM (2007) Could humans recognize odor by phonon assisted tunneling? Phys Rev Lett 98: 038101. doi: 10.1103/PhysRevLett.98.038101 17358733

16. Franco MI, Turin L, Mershin A, Skoulakis EM (2011) Molecular vibration-sensing component in Drosophila melanogaster olfaction. Proc Natl Acad Sci U S A 108: 3797–3802. doi: 10.1073/pnas.1012293108 21321219

17. Hettinger TP (2011) Olfaction is a chemical sense, not a spectral sense. Proc Natl Acad Sci U S A 108: E349; author reply E350. doi: 10.1073/pnas.1103992108 21737743

18. Bittner ER, Madalan A, Czader A, Roman G (2012) Quantum origins of molecular recognition and olfaction in Drosophila. J Chem Phys 137: 22A551. doi: 10.1063/1.4767067 23249088

19. Brookes J, Horsfield A, Stoneham A (2012) The Swipe Card Model of Odorant Recognition. Sensors 12: 15709–15749. doi: 10.3390/s121115709 23202229

20. Solov'yov IA, Chang PY, Schulten K (2012) Vibrationally assisted electron transfer mechanism of olfaction: myth or reality? Phys Chem Chem Phys 14: 13861–13871. doi: 10.1039/c2cp41436h 22899100

21. Gane S, Georganakis D, Maniati K, Vamvakias M, Ragoussis N, et al. (2013) Molecular vibration-sensing component in human olfaction. PLoS One 8: e55780. doi: 10.1371/journal.pone.0055780 23372854

22. Gronenberg W, Raikhelkar A, Abshire E, Stevens J, Epstein E, et al. (2014) Honeybees (Apis mellifera) learn to discriminate the smell of organic compounds from their respective deuterated isotopomers. Proc Biol Sci 281: 20133089. doi: 10.1098/rspb.2013.3089 24452031

23. Block E, Jang S, Matsunami H, Sekharan S, Dethier B, et al. (2015) Implausibility of the vibrational theory of olfaction. Proc Natl Acad Sci U S A 112: E2766–2774. doi: 10.1073/pnas.1503054112 25901328

24. Hoehn RD, Nichols D, Neven H, Kais S (2015) Neuroreceptor activation by vibration-assisted tunneling. Sci Rep 5: 9990. doi: 10.1038/srep09990 25909758

25. Reese A, List NH, Kongsted J, Solov'yov IA (2016) How Far Does a Receptor Influence Vibrational Properties of an Odorant? PLoS One 11: e0152345. doi: 10.1371/journal.pone.0152345 27014869

26. Paoli M, Anesi A, Antolini R, Guella G, Vallortigara G, et al. (2016) Differential Odour Coding of Isotopomers in the Honeybee Brain. Sci Rep 6: 21893. doi: 10.1038/srep21893 26899989

27. Drimyli E, Gaitanidis A, Maniati K, Turin L, Skoulakis EM (2016) Differential Electrophysiological Responses to Odorant Isotopologues in Drosophilid Antennae. eNeuro 3.

28. Hoehn RD, Nichols DE, McCorvy JD, Neven H, Kais S (2017) Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation. Proc Natl Acad Sci U S A 114: 5595–5600. doi: 10.1073/pnas.1618422114 28500275

29. Horsfield AP, Haase A, Turin L (2017) Molecular recognition in olfaction. Advances in Physics: X 2: 937–977.

30. Hoehn RD, Nichols DE, Neven H, Kais S (2018) Status of the Vibrational Theory of Olfaction. Frontiers in Physics 6(25).

31. Thijssen JM, Zant HSJVD (2008) Charge transport and single-electron effects in nanoscale systems. Physica Status Solidi 245: 1455–1470.

32. Saidani MA, Benfredj A, Romdhane S, Kouki F, Bouchriha H (2012) Role of intermolecular coupling and electron-nuclear coupling in the photophysics of oligothiophenes. Physical Review B 86: 165315.

33. Frisch MJ, Trucks GW, Schlegel HB et al. Gaussian 09, Revision A.1, Gaussian, Inc., Wallingford CT, 2009.

34. Lu T, Chen F (2012) Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem 33: 580–592. doi: 10.1002/jcc.22885 22162017

35. Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev A Gen Phys 38: 3098–3100. doi: 10.1103/physreva.38.3098 9900728

36. Becke AD (1993) Density-Functional Thermochemistry. III. The Role of Exact Exchange. J Chem Phys 98: 5648–5652.

37. Becke AD (1997) Density-functional thermochemistry. V. Systematic optimization of exchange-correlation functionals. J Chem Phys 107: 8554–8561.

38. Hehre WJ, Ditchfield R, Pople JA (1972) Self-consistent molecular orbital methods. XII. Further extensions of Gaussian—Type basis sets for use in molecular orbital studies of organic molecules. J Chem Phys 56: 2257–2261.

39. Francl MM, Petro WJ, Hehre WJ, Binkley JS, Gordon MS, et al. (1982) Self-consistent molecular orbital methods. XXIII. A polarization type basis set for second-row elements. J Chem Phys 77: 3654–3665.

40. Dykstra CE, Frenking G, Kim KS, Scuseria GE Theory and Applications of Computational Chemistry The First Fourty Years. Elsevier, Amsterdam, The Netherlands, 2005.

41. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B: Condens Matter 37: 785–789.

42. Reimers JR (2001) A practical method for the use of curvilinear coordinates in calculations of normal-mode-projected displacements and Duschinsky rotation matrices for large molecules. J Chem Phys 115: 9103–9109.

43. Kroger A (1978) [Nobel prizes for medicine and chemistry 1978. Nobel prize for chemistry: energy transfer during electron transfer phosphorylation]. Fortschr Med 96: 2362–2363. 721014

44. Fukuzumi S (2003) New perspective of electron transfer chemistry. Org Biomol Chem 1: 609–620. doi: 10.1039/b300053b 12929444

45. Jortner J, Bixon M (1999) Electron Transfer—from Isolated Molecules to Biomolecules. Adv Chem Phys 106: 31–41.

46. Pope M, Swenberg CE (1999) Electronic Processes in Organic Crystals and Polymers. 2nd ed, Oxford University Press: New York.

47. Malagoli M, Brédas JL (2000) Density functional theory study of the geometric structure and energetics of triphenylamine-based hole-transporting molecules. Chem Phys Lett 327: 13–17.

48. May V, Kühn O (2000) Charge and Energy Transfer Dynamics in Molecular Systems. 2nd, Revised and Enlarged EditionWiley-VCH: Berlin.

49. Duschinsky F (1937) On the interpretation of electronic spectra of polyatomic molecules. Translated by Christian W Müller Acta Physicochim URSS 7: 551–566.

50. Mebel AM, Hayashi M, Liang KK, Lin SH (1999) Ab initio calculations of vibronic spectra and dynamics for small polyatomic molecules: Role of Duschinsky effect. J Phys Chem A 103: 10674–10690.

51. Shreve AP, Haroz EH, Bachilo SM, Weisman RB, Tretiak S, et al. (2007) Determination of exciton-phonon coupling elements in single-walled carbon nanotubes by Raman overtone analysis. Phys Rev Lett 98: 037405. doi: 10.1103/PhysRevLett.98.037405 17358727

52. Mok DKW, Lee EPF, Chau F-t, Dyke JM (2013) Simulated photodetachment spectra of AlH2−. J Chem Phys 139: 014301. doi: 10.1063/1.4811671 23822297

53. Sando GM, Spears KG (2001) Ab Initio Computation of the Duschinsky Mixing of Vibrations and Nonlinear Effects. The Journal of Physical Chemistry A 105: 5326–5333.

54. Schumm S, Gerhards M, Kleinermanns K (2000) Franck−Condon Simulation of the S1→ S0Spectrum of Phenol. The Journal of Physical Chemistry A 104: 10648–10655.

55. Hagler TW, Pakbaz K, Voss KF, Heeger AJ (1991) Enhanced order and electronic delocalization in conjugated polymers oriented by gel processing in polyethylene. Phys Rev B 44: 8652–8666.

56. Kanemoto K, Sudo T, Akai I, Hashimoto H, Karasawa T, et al. (2006) Intrachain photoluminescence properties of conjugated polymers as revealed by long oligothiophenes and polythiophenes diluted in an inactive solid matrix. Phys Rev B 73: 235203.

57. Wagner M (1964) Structural Form of Vibronic Bands in Crystals. J Chem Phys 31: 3939.

58. Liu GK, Chen XY, Huang J (2003) Intensity and bandwidth of multiphonon vibronic transitions of rare-earth ions in crystals. Mol Phys 101: 1029.

59. Bixon M, Jortner J (1999) Electron transfer–from isolated molecules to biomolecules. Adv Chem Phys 106: 35–202.

60. Jortner J (1976) Temperature dependent activation energy for electron transfer between biological molecules. J Chem Phys 64: 4860–4867.

61. Zakarya D, Yahiaoui M, Fkiihtetouani S (1993) Structure-odor relations for bitter almond odorants. J phys Org Chem 6: 627–633.

62. Sumi H (1997) Electron transfer via a midway molecule as seen in primary processes in photosynthesis: Superexchange or sequential, or unified? J Electroanal Chem 438: 11–20.

63. Iversen G, Friis EP, Kharkats YI, Kuznetsov AM, Ulstru J (1998) Ulstrup,Sequential and coherent long-range electron transfer close to resonance with intermediate bridge groups, and new perspectives for in situ scanning tunnelling microscopy of adsorbed metalloproteins. J J Biol InorgChem 3: 229–235.

64. Zusman LD, Beratan DN (1999) Electron transfer in three-center chemical systems. J Chem Phys 110: 10468–10481.

65. Bixon M, Jortner J (1997) Electron Transfer via Bridges. J Chem Phys 107: 5154–5170.

66. Petrov EG, Shevchenko YV, Teslenko VI, May V (2001) Nonadiabatic donor-acceptor electron transfer mediated by a molecular bridge: A unified theoretical description of the superexchange and hopping mechanism. J Chem Phys 115: 7107–7122.

67. Sumi H, Kakitani T (1996) Electron transfer via a midway molecule as seen in primary processes in photosynthesis; a new process describable as superexchange or sequential in mutually opposite limits. Chem Phys Lett 252: 85–93.

68. Kim Y, Song H, Strigl F, Pernau HF, Lee T, et al. (2011) Conductance and vibrational states of single-molecule junctions controlled by mechanical stretching and material variation. Phys Rev Lett 106: 196804. doi: 10.1103/PhysRevLett.106.196804 21668188

69. Kushmerick JG, Lazorcik J, Patterson CH, Shashidhar R, Seferos DS, et al. (2004) Vibronic Contributions to Charge Transport Across Molecular Junctions. Nano Letters 4: 639–642.

70. Jiang J, Kula M, Lu W, Luo Y (2005) First-Principles Simulations of Inelastic Electron Tunneling Spectroscopy of Molecular Electronic Devices. Nano Lett: 1551–1555. doi: 10.1021/nl050789h 16089487

71. Troisi A, Beebe JM, Picraux LB, van Zee RD, Stewart DR, et al. (2007) Tracing electronic pathways in molecules by using inelastic tunneling spectroscopy. Proc Natl Acad Sci U S A 104: 14255–14259. doi: 10.1073/pnas.0704208104 17726099

72. Paulsson M, Frederiksen T, Ueba H, Lorente N, Brandbyge M (2008) Unified description of inelastic propensity rules for electron transport through nanoscale junctions. Phys Rev Lett 100: 226604. doi: 10.1103/PhysRevLett.100.226604 18643440

73. Sleigh AK, Phillips WA, Adkins CJ, Taylor ME (1986) A quantitative analysis of the inelastic electron tunnelling spectrum of the formate ion. J Phys C: 6645–6654.

74. Paulson BP, Miller JR, Gan WX, Closs G (2005) Superexchange and sequential mechanisms in charge transfer with a mediating state between the donor and acceptor. J Am Chem Soc 127: 4860–4868. doi: 10.1021/ja044946a 15796550

75. Bixon M, Jortner J, Michel-Beyerle ME (1995) A kinetic analysis of the primary charge separation in bacterial photosynthesis. Energy gaps and static heterogeneity. Chem Phys 197: 389–404.

76. Moya PR, Berg KA, Gutierrez-Hernandez MA, Saez-Briones P, Reyes-Parada M, et al. (2007) Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Pharmacol Exp Ther 321: 1054–1061. doi: 10.1124/jpet.106.117507 17337633

77. Ray TS (2010) Psychedelics and the human receptorome. PLoS One 5: e9019. doi: 10.1371/journal.pone.0009019 20126400

78. Pshenichnyuk SA, Rakhmeyev RG, Asfandiarov NL, Komolov AS, Modelli A, et al. (2018) Can the Electron-Accepting Properties of Odorants Be Involved in Their Recognition by the Olfactory System? J Phys Chem Lett 9: 2320–2325. doi: 10.1021/acs.jpclett.8b00704 29665679

79. Christophorou LG, McCorkle DL, Christodoulides AA (1984) Electron-Molecule Interactions and Their Applications. Academic Press, Orlando.

80. Illenberger E, Momigny J (1992) Gaseous Molecular Ions. Steinkopf Verlag, Darmstadt and Springer Verlag, New York.

81. Brookes JC (2017) Quantum effects in biology: golden rule in enzymes, olfaction, photosynthesis and magnetodetection. Proc Math Phys Eng Sci 473: 20160822. doi: 10.1098/rspa.2016.0822 28588400

82. Malnic B, Hirono J, Sato T, Buck LB (1999) Combinatorial receptor codes for odors. Cell 96: 713–723. doi: 10.1016/s0092-8674(00)80581-4 10089886

83. Turin L, Gane S, Georganakis D, Maniati K, Skoulakis EM (2015) Plausibility of the vibrational theory of olfaction. Proc Natl Acad Sci U S A 112: E3154. doi: 10.1073/pnas.1508035112 26045494

84. Sell C (2009) Odor cannot be predicted by molecular shape. Chem Senses 34: 181. doi: 10.1093/chemse/bjn069 19001463

85. Triller A, Boulden EA, Churchill A, Hatt H, Englund J, et al. (2008) Odorant-receptor interactions and odor percept: a chemical perspective. Chem Biodivers 5: 862–886. doi: 10.1002/cbdv.200890101 18618409

86. Kaupp UB (2010) Olfactory signalling in vertebrates and insects: differences and commonalities. Nat Rev Neurosci 11: 188–200. doi: 10.1038/nrn2789 20145624

87. Pellegrino M, Nakagawa T (2009) Smelling the difference: controversial ideas in insect olfaction. J Exp Biol 212: 1973–1979. doi: 10.1242/jeb.023036 19525421

88. Ernst OP, Lodowski DT, Elstner M, Hegemann P, Brown LS, et al. (2014) Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem Rev 114: 126–163. doi: 10.1021/cr4003769 24364740

89. Song L, El-Sayed MA, Lanyi JK (1993) Protein catalysis of the retinal subpicosecond photoisomerization in the primary process of bacteriorhodopsin photosynthesis. Science 261: 891–894. doi: 10.1126/science.261.5123.891 17783735

90. Schenkl S, van Mourik F, van der Zwan G, Haacke S, Chergui M (2005) Probing the ultrafast charge translocation of photoexcited retinal in bacteriorhodopsin. Science 309: 917–920. doi: 10.1126/science.1111482 16081732

91. Schenkl S, van Mourik F, Friedman N, Sheves M, Schlesinger R, et al. (2006) Insights into excited-state and isomerization dynamics of bacteriorhodopsin from ultrafast transient UV absorption. Proc Natl Acad Sci U S A 103: 4101–4106. doi: 10.1073/pnas.0506303103 16537491

92. Fedorov DG, Kitaura K (2007) Pair interaction energy decomposition analysis. J Comput Chem 28: 222–237. doi: 10.1002/jcc.20496 17109433

93. Fedorov DG, Kitaura K (2018) Pair Interaction Energy Decomposition Analysis for Density Functional Theory and Density-Functional Tight-Binding with an Evaluation of Energy Fluctuations in Molecular Dynamics. J Phys Chem A 122: 1781–1795. doi: 10.1021/acs.jpca.7b12000 29337557

94. Green MC, Fedorov DG, Kitaura K, Francisco JS, Slipchenko LV (2013) Open-shell pair interaction energy decomposition analysis (PIEDA): formulation and application to the hydrogen abstraction in tripeptides. J Chem Phys 138: 074111. doi: 10.1063/1.4790616 23445001

95. Phipps MJ, Fox T, Tautermann CS, Skylaris CK (2015) Energy decomposition analysis approaches and their evaluation on prototypical protein-drug interaction patterns. Chem Soc Rev 44: 3177–3211. doi: 10.1039/c4cs00375f 25811943

96. Gordon MS, Fedorov DG, Pruitt SR, Slipchenko LV (2012) Fragmentation methods: a route to accurate calculations on large systems. Chem Rev 112: 632–672. doi: 10.1021/cr200093j 21866983

97. Heifetz A, Chudyk EI, Gleave L, Aldeghi M, Cherezov V, et al. (2016) The Fragment Molecular Orbital Method Reveals New Insight into the Chemical Nature of GPCR-Ligand Interactions. J Chem Inf Model 56: 159–172. doi: 10.1021/acs.jcim.5b00644 26642258

Článek vyšel v časopise


2020 Číslo 1
Nejčtenější tento týden