Skip to main content
SpringerLink
Log in

Investigation of the effect of π–π stacking interaction on the properties of –CONH2 functional group of benzamide

  • Original Research
  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

The effect of π–π stacking between substituted benzene and benzamide on the properties of –CONH2 functional group, as an important unit in the drugs activities, was studied at the M06-2X/6-311++G(d,p) level of theory. All substituents enhanced the π–π interaction energies, where a reasonably good correlation was found between the interaction energies and Hammett constants of substituents. A linear correlation is observed between the sum of electron charge density at the cage critical point ∑ρ ccp obtained from the atoms in molecules (AIM) analysis and the interaction energies, where both values grow up with electron-withdrawing substituents (EWSs). The electrostatic potential around the O and N atoms, the natural charges, and the dipole moment of C=O bond have been calculated to predict the ability of functional group on the electrophilic and nucleophilic attacks. The charge transfer increases the electrostatic potential around the benzamide functional group in the presence of electron-donating substituents (EDSs). EWSs increase the acidity of the N atom of the –NH2 group; a linear relationship is observed between the acidity calculated with the molecular electrostatic potential around the N atom and the natural valence orbital energies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Scheme 2
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Meyer EA, Castellano RK, Diederich F (2003) Interactions with aromatic rings in chemical and biological recognition. Angew Chem Int Ed 42:1210–1250

    Article  CAS  Google Scholar 

  2. Muller-Dethlefs K, Hobza P (2000) Noncovalent interactions: a challenge for experiment and theory. Chem Rev 100:143–167

    Article  Google Scholar 

  3. Hunter CA, Lawson KR, Perkins J, Urch CJ (2001) Aromatic interactions. J Chem Soc Perkin Trans 2:651–669

    Article  Google Scholar 

  4. Waters ML (2002) Aromatic interactions in model systems. Curr Opin Chem Bio 6:736–741

    Article  CAS  Google Scholar 

  5. Pavel H (2008) Stacking interactions. Phys Chem Chem Phys 10:2581–2583

    Article  Google Scholar 

  6. Kryger G, Silman I, Sussman JL (1998) Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo Californica. J Physiol Paris 92:191–194

    Article  CAS  Google Scholar 

  7. Bhattacharyya R, Samanta U, Chakrabarti P (2002) Aromatic-aromatic interactions in and around α-helices. Protein Eng 15:91–100

    Article  CAS  Google Scholar 

  8. Rutledge LR, Campbell-Verduyn LS, Hunter KC, Wetmore SD (2006) Characterization of nucleobase-amino acid stacking interactions utilized by a DNA repair enzyme. J Phys Chem B 110:19652–19663

    Article  CAS  Google Scholar 

  9. Cysewski P (2008) A post-SCF complete basis set study on the recognition patterns of uracil and cytosine by aromatic and π-aromatic stacking interactions with amino acid residues. Phys Chem Chem Phys 10:2636–2645

    Article  CAS  Google Scholar 

  10. Sinnokrot MO, Sherrill CD (2006) High-accuracy quantum mechanical studies of π–π interactions in benzene dimers. J Phys Chem A 110:10656–10668

    Article  CAS  Google Scholar 

  11. Hunter CA, Sanders JKM (1990) The nature of π–π interactions. J Am Chem Soc 112:5525–5534

    Article  CAS  Google Scholar 

  12. Sinnokrot MO, Sherrill CD (2004) Substituent effects in π–π interactions: sandwich and T-shaped configurations. J Am Chem Soc 126:7690–7697

    Article  CAS  Google Scholar 

  13. 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 9:3479–3490

    Article  CAS  Google Scholar 

  14. Wheeler SE (2011) Local nature of substituent effects in stacking interactions. J Am Chem Soc 133:10262–10274

    Article  CAS  Google Scholar 

  15. Cozzi F, Cinquini M, Annuziata R, Siegel JS (1993) Dominance of polar/π over charge-transfer effects in stacked phenyl interactions. J Am Chem Soc 115:5330–5331

    Article  CAS  Google Scholar 

  16. Grimme S, Antony J, Schwabe T, Muck-Lichtenfeld C (2007) Density functional theory with dispersion corrections for supramolecular structures, aggregates, and complexes of (bio)organic molecules. Org Biomol Chem 5:741–758

    Article  CAS  Google Scholar 

  17. Lee EC, Kim D, Jurecka P, Tarakeshwar P, Hobza P, Kim KS (2007) Understanding of assembly phenomena by aromatic–aromatic interactions: benzene dimer and the substituted systems. J Phys Chem A 111:3446–3457

    Article  CAS  Google Scholar 

  18. Beg S, Waggoner K, Ahmad Y, Watt M, Lewis M (2008) Predicting face-to-face arene–arene binding energies. Chem Phys Lett 455:98–102

    Article  CAS  Google Scholar 

  19. Mignon P, Loverix S, Proft FD, Geerlings P (2004) Influence of stacking on hydrogen bonding: quantum chemical study on pyridine–benzene model complexes. J Phys Chem A 108:6038–6044

    Article  CAS  Google Scholar 

  20. Mignon P, Loverix S, Geerlings P (2005) Interplay between π–π interactions and the H-bonding ability of aromatic nitrogen bases. Chem Phys Lett 401:40–46

    Article  CAS  Google Scholar 

  21. Liu S, Pedersen LG (2009) Estimation of molecular acidity via electrostatic potential at the nucleus and valence natural atomic orbitals. J Phys Chem A 113:3648–3655

    Article  CAS  Google Scholar 

  22. Meng L, Wang Z, Zhang J, Zhou M, Wu WD (2014) Low energy conformations and gas phase acidity and basicity of pyrrolysine. J Phys Chem A 118:7085–7095

    Article  CAS  Google Scholar 

  23. Cosi C, Chopin P, Marien M (1996) Benzamide, an inhibitor of poly (ADP-ribose) polymerase, attenuates methamphetamine-induced dopamine neurotoxicity in the C57B1/6N mouse. Brain Res 735:343–348

    Article  CAS  Google Scholar 

  24. Brethous L, Garcia-Delgado N, Schwartz J, Bertrand S, Bertrand D, Reymond JL (2012) Synthesis and nicotinic receptor activity of chemical space analogues of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) and 1,4-diazabicyclo [3.2.2] nonane-4-carboxylic Acid 4-bromophenyle ester (SSR180711). J Med Chem 55:4605–4618

    Article  CAS  Google Scholar 

  25. Mao W, Ning M, Liu Z, Zhu Q, Leng Y, Zhang A (2012) Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. Bioorg Med Chem 20:2982–2991

    Article  CAS  Google Scholar 

  26. Zhao Y, Truhlar DG, Meta H (2004) Density functional theory methods for thermochemistry, thermochemical kinetics, and noncovalent interactions: the MPW1B95 and MPWB1K models and comparative assessments for hydrogen bonding and van der waals interactions. J Phys Chem A 108:6908–6918

    Article  CAS  Google Scholar 

  27. Kolar M, Hobza P (2007) Accurate theoretical determination of the structure of aromatic complexes is complicated: the phenol dimer and phenol…methanol cases. J Phys Chem A 111:5851–5854

    Article  CAS  Google Scholar 

  28. Zhao Y, Truhlar DG (2005) How well can new-generation density functional methods describe stacking interactions in biological systems? Phys Chem Chem Phys 7:2701–2705

    Article  CAS  Google Scholar 

  29. Zhao Y, Truhlar DG (2005) Design of density functionals that are broadly accurate for thermochemistry, thermochemical kinetics, and nonbonded interactions. J Phys Chem A 109:5656–5667

    Article  CAS  Google Scholar 

  30. Zhao Y, Schultz NE, Truhlar DG (2005) Exchange-correlation functional with broad accuracy for metallic and nonmetallic compounds, kinetics, and noncovalent interactions. J Chem Phys 123:161103

    Article  Google Scholar 

  31. 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 2:364–382

    Article  Google Scholar 

  32. 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 125:194101

    Article  Google Scholar 

  33. 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-class functionals and 12 other functionals. Chem Acc 120:215–241

    Article  CAS  Google Scholar 

  34. Zhao Y, Truhlar DG (2007) Density functionals for noncovalent interaction energies of biological importance. J Chem Theory Comput 3:289–300

    Article  CAS  Google Scholar 

  35. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, Revision C.01. Gaussian Inc., Wallingford

  36. Biegler Konig FW, Schonbohm J, Bayles D (2001) Software news and updates AIM2000. J Comput Chem 22:545–559

    Article  Google Scholar 

  37. Lu T (2013) Multiwfn: a multifunctional wave function analyzer, version 3.2

  38. Zhu W, Tan X, Shen J, Luo X, Cheng F, Mok PC, Ji R, Chen K, Jiang H (2003) A quantum chemistry study using density-functional theory and morokuma decomposition methods. J Phys Chem A 107:2296–2303

    Article  CAS  Google Scholar 

  39. 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 131:4574–4575

    Article  CAS  Google Scholar 

  40. Watt M, Hardebeck LKE, Kirkpatrick CC, Lewis M (2011) Face-to-face arene–arene binding energies: dominated by dispersion but predicted by electrostatic and dispersion/polarizability substituent constants. J Am Chem Soc 133:3854–3862

    Article  CAS  Google Scholar 

  41. Quinonero D, Frontera A, Deya PM, Alkorta I, Elguero J (2008) Interaction of positively and negatively charged aromatic hydrocarbons with benzene and triphenylene: towards a model of pure organic insulators. Chem Phys Lett 460:406–410

    Article  CAS  Google Scholar 

  42. Zhikol OA, Shishkin OV, Lyssenko KA, Leszczynski J (2005) Electron density distribution in stacked benzene dimers: a new approach towards the estimation of stacking interaction energies. J Chem Phys 122:144104–144108

    Article  Google Scholar 

  43. Alcami M, Mo O, Yanez M (1996) Modelling intrinsic basicities: the use of the electrostatic potentials and the atoms-in-molecules theory. Theor Comput Chem 3:407–455

    Article  CAS  Google Scholar 

  44. Suresh CH (2006) Molecular electrostatic potential approach to determining the steric effect of phosphine ligands in organometallic chemistry. Inorg Chem 45:4982–4986

    Article  CAS  Google Scholar 

  45. Hansch C, Leo A, Taft RW (1991) A survey of Hammett substituent constants and resonance and field parameters. Chem Rev 91:165–195

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Sistan and Baluchestan, P.O. Box 98135–674, Zahedan, Iran

    Z. Momeni & A. Ebrahimi

Authors
  1. Z. Momeni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Ebrahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Ebrahimi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Momeni, Z., Ebrahimi, A. Investigation of the effect of π–π stacking interaction on the properties of –CONH2 functional group of benzamide. Struct Chem 27, 731–737 (2016). https://doi.org/10.1007/s11224-015-0615-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-015-0615-7

Keywords

Search

Navigation