Advertisement

Unraveling the Origin of Substituents Effects in π-Stacking Interactions

  • Steven E. WheelerEmail author
Chapter
First Online:
Part of the Challenges and Advances in Computational Chemistry and Physics book series (COCH, volume 19)

Abstract

Non-covalent interactions involving aromatic rings, which include π-stacking, anion-π, and cation-π interactions, among others, are central to modern chemical research. These interactions play vital roles in everything from protein-DNA interactions and the properties of organic electronic materials to stereoselective organocatalyzed reactions. We discuss recent efforts to understand the impact of substituents on the strength of π-stacking interactions through the application of modern tools of computational quantum chemistry. We first provide an account of previous efforts to develop qualitative physical models of these interactions, followed by apparent flaws in these previous models. We then present our local, direct interaction model of substituent effects in π-stacking interactions, and discuss recent extensions of this model based on the examination of electric fields of arenes. We also discuss related misconceptions regarding molecular electrostatic potentials (ESPs), and offer a simpler view of the origin of ESP differences arising from the incorporation of heteroatoms or substituents into aromatic rings. Finally, we conclude with an outlook for future advances in our understanding of π-stacking interactions.

Keywords

Molecular Electrostatic Potential Substituent Effect Benzene Dimer Local Dipole Moment Unsubstituted Ring 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Notes

Acknowledgment

This work was supported by the National Science Foundation (Grant CHE-1254897) and the Welch Foundation (Grant A-1776). We also thank the Texas A&M Supercomputing Center for providing computational resources and J. W. G. Bloom, R. K. Raju, K. N. Houk, D. A. Dougherty, C. Corminboeuf, H. M. Jaeger, F. A. Evangelista, B. L. Iverson, and J. S. Siegel for many fruitful discussions about π-stacking interactions.

References

  1. 1.
    Meyer EA, Castellano RK, Diederich F (2003) Interactions with aromatic rings in chemical and biological recognition. Angew Chem Int Ed 42:1210–1250CrossRefGoogle Scholar
  2. 2.
    Salonen LM, Ellermann M, Diederich F (2011) Aromatic rings in chemical and biological recognition: energetics and structures. Angew Chem Int Ed 50:4808–4842CrossRefGoogle Scholar
  3. 3.
    Schneider H-J (2009) Binding mechanisms in supramolecular complexes. Angew Chem Int Ed 48:3924–3977CrossRefGoogle Scholar
  4. 4.
    Müller-Dethlefs K, Hobza P (2000) Noncovalent interactions: a challenge for experiment and theory. Chem Rev 100:143–168CrossRefGoogle Scholar
  5. 5.
    Kim KS, Tarakashwar P, Lee JY (2000) Molecular clusters of π-systems: theoretical studies of structures, spectra, and origin of interaction energies. Chem Rev 100:4145–4186CrossRefGoogle Scholar
  6. 6.
    Hunter CA, Sanders JKM (1990) The nature of π-π interactions. J Am Chem Soc 112:5525–5534CrossRefGoogle Scholar
  7. 7.
    Yakovchuk P, Protozanova E, Frank-Kamenetskii MD (2006) Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res 34:564–574CrossRefGoogle Scholar
  8. 8.
    Kool ET (2002) Replacing the nucleobases in DNA with designer molecules. Acc Chem Res 35:936–943CrossRefGoogle Scholar
  9. 9.
    Riley KE, Hobza P (2013) On the importance and origin of aromatic interactions in chemistry and biodisciplines. Acc Chem Res 46:927–936CrossRefGoogle Scholar
  10. 10.
    Cooper VR, Thonhauser T, Puzder A, Schröder E, Lundqvist BI, Langreth DC (2008) Stacking interactions and the twist of DNA. J Am Chem Soc 130:1304–1308CrossRefGoogle Scholar
  11. 11.
    Riley KE, Hobza P (2011) Noncovalent interactions in biochemistry. WIREs Comp Mol Sci 1:3–17CrossRefGoogle Scholar
  12. 12.
    Hargis JC, Schaefer HF, Houk KN, Wheeler SE (2010) Non-covalent interactions of a Benzo[a]pyrene diol epoxide with DNA base pairs: insight into the formation of adducts of (+)-BaP DE-2 with DNA. J Phys Chem A 114:2038–2044CrossRefGoogle Scholar
  13. 13.
    Knowles RR, Jacobsen EN (2010) Attractive noncovalent interactions in asymmetric catalysis: links between enzymes and small molecule catalysts. Proc Natl Acad Sci U S A 107:20678–20685CrossRefGoogle Scholar
  14. 14.
    Takenaka N, Chen JS, Captain B (2011) Helical chiral 2,2’-Bipyridine N-monoxides as catalysts in the enantioselective propargylation of aldehydes with allenyltrichlorosilane. Org Lett 13:1654–1657CrossRefGoogle Scholar
  15. 15.
    Lu T, Zhu R, An Y, Wheeler SE (2012) Origin of enantioselectivity in the propargylation of aromatic aldehydes catalyzed by helical N-Oxides. J Am Chem Soc 134:3095–3102CrossRefGoogle Scholar
  16. 16.
    Krenske EH, Houk KN (2013) Aromatic interactions as control elements in stereoselective organic reactions. Acc Chem Res 46:979–989CrossRefGoogle Scholar
  17. 17.
    Sinnokrot MO, Valeev EF, Sherrill CD (2002) Estimates of the Ab initio limit for π–π interactions: the benzene dimer. J Am Chem Soc 124:10887–10893CrossRefGoogle Scholar
  18. 18.
    Sinnokrot MO, Sherrill CD (2006) High-accuracy quantum mechanical studies of π-π interactions in benzene dimers. J Phys Chem A 110:10656–10668CrossRefGoogle Scholar
  19. 19.
    Grimme S (2008) Do special noncovalent π-π stacking interactions really exist? Angew Chem Int Ed 47:3430–3434CrossRefGoogle Scholar
  20. 20.
    Bloom JWG, Wheeler SE (2011) Taking aromaticity out of aromatic interactions. Angew Chem Int Ed 50:7847–7849CrossRefGoogle Scholar
  21. 21.
    Martinez CR, Iverson BL (2012) Rethinking the term “π-stacking”. Chem Sci 3:2191–2201CrossRefGoogle Scholar
  22. 22.
    Sherrill CD, Takatani T, Hohenstein EG (2009) An assessment of theoretical methods for nonbonded interactions: comparison to complete basis set limit coupled-cluster potential energy curves for the benzene dimer, the methane dimer, benzene–methane, and benzene–H2S. J Phys Chem A 113:10146–10159CrossRefGoogle Scholar
  23. 23.
    Hohenstein EG, Sherrill CD (2012) Wavefunction methods for noncovalent interactions. WIREs Comp Mol Sci 2:304–326CrossRefGoogle Scholar
  24. 24.
    Dion M, Rydberg H, Schröder E, Langreth DC, Lundqvist BI (2004) Van der Waals density functional for general geometries. Phys Rev Lett 92:246401CrossRefGoogle Scholar
  25. 25.
    Grimme S (2004) Accurate description of van der Waals complexes by density functional theory including empirical corrections. J Comp Chem 25:1463–1473CrossRefGoogle Scholar
  26. 26.
    Grimme S (2006) Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J Comp Chem 27:1787–1799CrossRefGoogle Scholar
  27. 27.
    Grimme S, Antony J, Schwabe T, Mück-Lichtenfeld C (2007) Density functional theory with dispersion corrections for supramolecular structures, aggregates, and complexes of (bio)organic molecules. Org Biomol Chem 5:741–758CrossRefGoogle Scholar
  28. 28.
    Schwabe T, Grimme S (2008) Theoretical thermodynamics for large molecules: walking the thin line between accuracy and computational cost. Acc Chem Res 41:569–579CrossRefGoogle Scholar
  29. 29.
    Grimme S, Antony J, Ehrlich S, Krieg H (2010) A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J Chem Phys 132:154104CrossRefGoogle Scholar
  30. 30.
    Grimme S (2011) Density functional theory with London dispersion corrections. WIREs Comp Mol Sci 1:211–228CrossRefGoogle Scholar
  31. 31.
    Ehrlich S, Moellmann J, Grimme S (2013) Dispersion-corrected density functional theory for aromatic interactions in complex systems. Acc Chem Res 46:916–926CrossRefGoogle Scholar
  32. 32.
    Zhao Y, Schultz NE, Truhlar DG (2006) Design of density functionals by combining the method of constraint satisfaction with parametrization for thermochemistry, thermochemical kinetics, and noncovalent interactions. J Chem Theory Comput 2:364–382CrossRefGoogle Scholar
  33. 33.
    Zhao Y, Truhlar DG (2006) A new local density functional for main-group thermochemistry, transition metal bonding, thermochemical kinetics, and noncovalent interactions. J Chem Phys 125:194101CrossRefGoogle Scholar
  34. 34.
    Zhao Y, Truhlar DG (2007) Density functionals for noncovalent interaction energies of biological importance. J Chem Theory Comput 3:289–300CrossRefGoogle Scholar
  35. 35.
    Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four m06 functionals and twelve other functionals. Theor Chem Acc 120:215–241CrossRefGoogle Scholar
  36. 36.
    Zhao Y, Truhlar DG (2008) Density functionals with broad applicability in chemistry. Acc Chem Res 41:157–167CrossRefGoogle Scholar
  37. 37.
    Vydrov OA, Van Voorhis T (2009) Nonlocal van der Waals density functional made simple. Phys Rev Lett 103:063004CrossRefGoogle Scholar
  38. 38.
    Vydrov OA, Van Voorhis T (2012) Benchmark assessment of the accuracy of several van der Waals density functionals. J Chem Theory Comput 8:1929–1934CrossRefGoogle Scholar
  39. 39.
    Vydrov OA, Van Voorhis T (2010) Dispersion interactions from a local polarizability model. Phys Rev B 81:062708CrossRefGoogle Scholar
  40. 40.
    Becke A; Johnson ER (2005) Exchange-hole dipole moment and the dispersion interaction. J Chem Phys 122:154104CrossRefGoogle Scholar
  41. 41.
    Johnson ER, Mackie ID, DiLabio GA (2009) Dispersion interactions in density-functional theory. J Phys Org Chem 22:1127–1135CrossRefGoogle Scholar
  42. 42.
    Steinmann SN, Corminboeuf C (2010) A system-dependent density-based dispersion correction. J Chem Theory Comput 6:1990–2001CrossRefGoogle Scholar
  43. 43.
    Tkatchenko A, Scheffler M (2009) Accurate molecular van der Waals interactions from ground-state electron density and free-atom reference data. Phys Rev Lett 102:073005CrossRefGoogle Scholar
  44. 44.
    Becke A (1997) Density-functional thermochemistry. V. systematic optimization of exchange-correlation functionals. J Chem Phys 107:8554–8560CrossRefGoogle Scholar
  45. 45.
    Vázquez-Mayagoitia Á, Sherrill CD, Apra E, Sumpter BG (2010) An assessment of density functional methods for potential energy curves of nonbonded interactions: the XYG3 and B97-D approximations. J Chem Theory Comput 6:727–734CrossRefGoogle Scholar
  46. 46.
    Burns LA, Vázquez- Mayagoitia Á, Sumpter BG, Sherrill CD (2011) Density-functional approaches to noncovalent interactions: a comparison of dispersion corrections (DFT-D), exchange-hole dipole moment (XDM) theory, and specialized functionals. J Chem Phys 134:084107CrossRefGoogle Scholar
  47. 47.
    Jeziorski B, Moszyński R, Szalewicz K (1994) Perturbation theory approach to intermolecular potential energy surfaces of van der Waals complexes. Chem Rev 94:1887–1930CrossRefGoogle Scholar
  48. 48.
    Szalewicz K (2012) Symmetry-adapted perturbation theory of intermolecular forces. WIREs Comp Mol Sci 2:254–272CrossRefGoogle Scholar
  49. 49.
    Hohenstein EG, Sherrill CD (2010) Density fitting and Cholesky decomposition approximations in symmetry-adapted perturbation theory: implementation and application to probe the nature of π-π interactions in linear acenes. J Chem Phys 132:184111CrossRefGoogle Scholar
  50. 50.
    Hohenstein EG, Sherrill CD (2010) Efficient evaluation of triple excitations in symmetry-adapted perturbation theory via second-order Møller-Plesset perturbation theory natural orbitals. J Chem Phys 133:104107CrossRefGoogle Scholar
  51. 51.
    Hohenstein EG, Sherrill CD (2010) Density fitting of intramonomer correlation effects in symmetry-adapted perturbation theory. J Chem Phys 133:014101CrossRefGoogle Scholar
  52. 52.
    Parker TM, Burns LA, Parrish RM, Ryno AG, Sherrill CD (2014) Levels of symmetry adapted perturbation theory (SAPT). I. Efficiency and performance for interaction energies. J Chem Phys 140:094106CrossRefGoogle Scholar
  53. 53.
    Turney JM, Simmonett AC, Parrish RM, Hohenstein EG, Evangelista FA, Fermann JT, Mintz BJ, Wilke JJ, Abrams ML, Russ NJ et al (2012) Psi4: an open-source ab initio electronic structure program. WIREs Comp Mol Sci 2:556–565CrossRefGoogle Scholar
  54. 54.
    Raju RK, Bloom JWG, Wheeler SE (2013) Broad transferability of substituent effects in π-stacking interactions provides new insights into their origin. J Chem Theory Comput 9:3479–3490CrossRefGoogle Scholar
  55. 55.
    Hunter CA, Lawson KR, Perkins J, Urch CJ (2001) Aromatic interactions. J Chem Soc Perkin Trans 2:651–669CrossRefGoogle Scholar
  56. 56.
    Cockroft SL, Hunter CA, Lawson KR, Perkins J, Urch CJ (2005) Electrostatic control of aromatic stacking interactions. J Am Chem Soc 127:8594–8595CrossRefGoogle Scholar
  57. 57.
    Cockroft SL, Perkins J, Zonta C, Adams H, Spey SE, Low CMR, Vinter JG, Lawson KR, Urch CJ, Hunter CA (2007) Substituent effects on aromatic stacking interactions. Org Biomol Chem 5:1062–1080CrossRefGoogle Scholar
  58. 58.
    Cozzi F, Cinquini M, Annunziata R, Dwyer T, Siegel JS (1992) Polar/π interactions between stacked aryls in 1,8-Diarylnaphthalenes. J Am Chem Soc 114:5729–5733CrossRefGoogle Scholar
  59. 59.
    Cozzi F, Cinquini M, Annunziata R, Siegel JS (1993) Dominance of polar/π over charge-transfer effects in stacked phenyl interactions. J Am Chem Soc 115:5330–5331CrossRefGoogle Scholar
  60. 60.
    Cozzi F, Ponzini F, Annunziata R, Cinquini M, Siegel JS (1995) Polar interactions between stacked π systems in fluorinated 1,8-Diarylnaphthalenes: importance of quadrupole moments in molecular recognition. Angew Chem Int Ed 34:1019–1020CrossRefGoogle Scholar
  61. 61.
    Cozzi F, Siegel JS (1995) Interaction between stacked aryl groups in 1,8-Diarylnaphthalenes: dominance of polar/π over charge-transfer effects. Pure Appl Chem 67:683–689CrossRefGoogle Scholar
  62. 62.
    Cozzi F, Annunziata R, Benaglia M, Cinquini M, Raimondi L, Baldridge KK, Siegel JS (2003) Through-space interactions between face-to-face, center-to-edge oriented arenes: importance of polar-π effects. Org Biomol Chem 1:157–162CrossRefGoogle Scholar
  63. 63.
    Cozzi F, Annunziata R, Benaglia M, Baldridge KK, Aguirre G, Estrada J, Sritana-Anant Y, Siegel JS (2008) Through-space interactions between parallel-offset arenes at the van der Waals distance: 1,8-diarylbiphenylene syntheses, structure and QM computations. Phys Chem Chem Phys 10:2686–2694CrossRefGoogle Scholar
  64. 64.
    Sinnokrot MO, Sherrill CD (2003) Unexpected substituent effects in face-to-face π-stacking interactions. J Phys Chem A 107:8377–8379CrossRefGoogle Scholar
  65. 65.
    Sinnokrot MO, Sherrill CD (2004) Substituent effects in π-π interactions: sandwich and T-shaped configurations. J Am Chem Soc 126:7690–7697CrossRefGoogle Scholar
  66. 66.
    Ringer AL, Sinnokrot MO, Lively RP, Sherrill CD (2006) The effect of multiple substituents on sandwich and T-Shaped π-π interactions. Chem Eur J 12:3821–3828CrossRefGoogle Scholar
  67. 67.
    Arnstein SA, Sherrill CD (2008) Substituent effects in parallel-displaced π-π interactions. Phys Chem Chem Phys 10:2646–2655CrossRefGoogle Scholar
  68. 68.
    Ringer AL, Sherrill CD (2009) Substituent effects in sandwich configurations of multiply substituted benzene dimers are not solely governed by electrostatic control. J Am Chem Soc 131:4574–4575CrossRefGoogle Scholar
  69. 69.
    Hohenstein EG, Duan J, Sherrill CD (2011) Origin of the surprising enhancement of electrostatic energies by electron-donating substituents in substituted benzene sandwich dimers. J Am Chem Soc 133:13244–13247CrossRefGoogle Scholar
  70. 70.
    Wheeler SE, Houk KN (2008) Substituent effects in the benzene dimer are due to direct interactions of the substituents with the unsubstituted benzene. J Am Chem Soc 130:10854–10855CrossRefGoogle Scholar
  71. 71.
    Wheeler SE, McNeil AJ, Müller P, Swager TM, Houk KN (2010) Probing substituent effects in aryl–aryl interactions using stereoselective Diels–Alder cycloadditions. J Am Chem Soc 132:3304–3311CrossRefGoogle Scholar
  72. 72.
    Raju RK, Bloom JWG, An Y, Wheeler SE (2011) Substituent effects in non-covalent interactions with aromatic rings: insights from computational chemistry. ChemPhysChem 12:3116–3130CrossRefGoogle Scholar
  73. 73.
    Wheeler SE (2011) Local nature of substituent effects in stacking interactions. J Am Chem Soc 133:10262–10274CrossRefGoogle Scholar
  74. 74.
    Wheeler SE (2013) Understanding substituent effects in non-covalent interactions involving aromatic rings. Acc Chem Res 46:1029–1038CrossRefGoogle Scholar
  75. 75.
    Lee EC, Kim D, Jurečka P, Tarakeshwar P, Hobza P, Kim KS (2007) Understanding of assembly phemona by aromatic-aromatic interactions: benzene dimer and the substituted systems. J Phys Chem A 111:3446–3457CrossRefGoogle Scholar
  76. 76.
    Seo J-I, Kim I, Lee YS (2009) π-π interaction energies in monosubstituted-benzene dimers in parallel- and antiparallel-displaced conformations. Chem Phys Lett 474:101–106CrossRefGoogle Scholar
  77. 77.
    Watt M, Hardebeck LKE, Kirkpatrick CC, Lewis M (2011) Face-to-face arene-arene bidning energies: dominated by dispersion but predicted by electrostatic and dispersion/polarizability substituent constants. J Am Chem Soc 133:3854–3862CrossRefGoogle Scholar
  78. 78.
    Hunter CA (2004) Quantifying intermolecular interactions: guidelines for the molecular recognition toolbox. Angew Chem Int Ed 43:5310–5324CrossRefGoogle Scholar
  79. 79.
    Cockroft SL, Hunter CA (2007) Chemical double-mutant cycles: dissecting non-covalent interactions. Chem Soc Rev 36:172–188CrossRefGoogle Scholar
  80. 80.
    Cockroft SL, Hunter CA (2009) Desolvation and substituent effects in edge-to-face aromatic interactions. Chem Commun 3961–3963Google Scholar
  81. 81.
    Wheeler SE, Bloom JWG (2014) Toward a more complete understanding of non-covalent interactions involving aromatic rings. J Phys Chem A 118:6133–6147CrossRefGoogle Scholar
  82. 82.
    Tauer T, Sherrill CD (2005) Beyond the benzene dimer: an investigation of the additivity of π–π interactions. J Phys Chem A 109:10475–10478CrossRefGoogle Scholar
  83. 83.
    Hohenstein EG, Sherrill CD (2009) Effects of heteroatoms on aromatic π-π interactions: benzene-pyridine and pyridine dimer. J Phys Chem A 113:878–886CrossRefGoogle Scholar
  84. 84.
    Sherrill CD (2009) Computations of noncovalent pi interactions. In: Lipkowitz KB Cundari TR (eds) Reviews computational chemistry, vol 26. Wiley-VCH, New York, pp 1–38Google Scholar
  85. 85.
    Marshall MS, Burns LA, Sherrill CD (2011) Basis set convergence of the coupled-cluster correction, δ(MP2)(CCSD(T)): best practices for benchmarking non-covalent interactions and the attendant revision of the S22, NBC10, HBC6, and HSG databases. J Chem Phys 135:194102CrossRefGoogle Scholar
  86. 86.
    Beg S, Waggoner K, Ahmad Y, Watt M, Lewis M (2008) Predicting face-to-face arene-arene binding energies. Chem Phys Lett 455:98–102CrossRefGoogle Scholar
  87. 87.
    Gung BW, Emenike BU, Alvereza CN, Rakovan J, Kirschbaum K, Jain N (2010) Relative substituent position on the strength of π-π stacking interactions. Tetrahedron Lett 51:1648–1650CrossRefGoogle Scholar
  88. 88.
    Benitex Y, Baranger AM (2011) Control of the stability of a protein-RNA Complex by the position of fluorine in a base analog. J Am Chem Soc 133:3687–3689CrossRefGoogle Scholar
  89. 89.
    Wheeler SE (2012) Controlling the local arrangements of π-stacked polycyclic aromatic hydrocarbons through substituent effects. CrystEngComm 14:6140–6145CrossRefGoogle Scholar
  90. 90.
    Munusamy E, Wheeler SE (2013) Endohedral and exohedral complexes of cyclohexane and substituted benzenes with carbon nanotubes and graphene. J Chem Phys 139:094703CrossRefGoogle Scholar
  91. 91.
    Wheeler SE, Houk KN (2009) Through-space effects of substituents dominate molecular electrostatic potentials of substituted arenes. J Chem Theory Comput 5:2301–2312CrossRefGoogle Scholar
  92. 92.
    Wheeler SE, Bloom JWG (2014) Anion-π interactions and positive electrostatic potentials of N-heterocycles arise from the positions of the nuclei, not changes in the π-electron distribution. Chem Commun 50:11118–11121CrossRefGoogle Scholar
  93. 93.
    Hunter CA (1994) Meldola lecture. The role of aromatic interactions in molecular recognition. Chem Soc Rev 23:101CrossRefGoogle Scholar
  94. 94.
    Carver FJ, Hunter CA, Seward EM (1998) Structure-activity relationship for quantifying aromatic interactions. Chem Commun 775–776Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of ChemistryTexas A&M UniversityCollege StationUSA

Personalised recommendations

Cite chapter

Buy options