Research on Chemical Intermediates

, Volume 46, Issue 1, pp 961–982 | Cite as

Harmine derivatives: a comprehensive quantum chemical investigation of the structural, electronic (FMO, NBO, and MEP), and spectroscopic (FT-IR and UV–Vis) properties

  • Goncagül SerdaroğluEmail author


The harmine derivatives were comprehensively investigated by computational tools to predict the structural, electronic, and spectroscopic properties as well as the chemical reactivity behavior. Physicochemical parameters showed that the harmine derivatives (H2 and H4) containing the –OH group at 2-position were more stabilized with the solvent dielectric constant than those of the other compounds (H1 and H3) including the –OCH3 substitution at 2-position. The PED analysis was used to assign the vibrational modes of all stable conformers of the harmine derivatives. TD-DFT simulations revealed that the lowest energy excitations were related to the H → L transition, which was mainly characterized by n → π* for H1 and H2 compounds and π → π* for H3 and H4 compounds. According to NBO analysis results, the highest contribution to the lowering of the molecular stabilization energy for all compounds was mainly due to the intramolecular charge transfer from the lone pair of the N atom as a donor orbital to π* as an acceptor orbital. Global reactivity descriptors obtained from B3LYP/6-311++G(d,p) level implied that the trans-conformers of the studied compounds could be relatively more effective in their interaction with DNA, while the cis-conformers of them could be more eager to interact with the BSA molecule.

Graphic abstract

Harmine derivatives are investigated by computational tools to predict the structural, electronic, and spectroscopic properties. Global reactivity descriptors implied that the trans-conformers of the compounds could be relatively more effective to interact with DNA, while the cis-conformers could be more eager to interact with the BSA molecule.


Harmine derivatives FT-IR UV–Vis NBO FMO Chemical reactivity 



This work was supported by Sivas Cumhuriyet University, Scientific Research Projects Department (CUBAP: EĞT-053 and EĞT-066). All calculations were performed out at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR-Grid e-Infrastructure).

Supplementary material

11164_2019_4020_MOESM1_ESM.docx (262 kb)
Supplementary material 1 (DOCX 261 kb)


  1. 1.
    R.S. Kusurkar, S.K. Goswami, Tetrahedron 60, 5315 (2004)Google Scholar
  2. 2.
    A. Daoud, J. Song, F.Y. Xiao, J. Shang, Eur. J. Pharmacol. 724, 219 (2014)PubMedGoogle Scholar
  3. 3.
    R.S. Kusurkar, S.K. Goswami, S.M. Vyas, Tetrahedron Lett. 44, 4761 (2003)Google Scholar
  4. 4.
    M.R. Prinsep, J.W. Blunt, M.H.G. Munro, J. Nat. Prod. 54(4), 1068 (1991)PubMedGoogle Scholar
  5. 5.
    R. Cao, W. Peng, H. Chen, X. Hou, H. Guan, Q. Chen, Y. Ma, A. Xu, Eur. J. Med. Chem. 40, 249 (2005)PubMedGoogle Scholar
  6. 6.
    H. Song, Y. Liu, Y. Liu, L. Wang, Q. Wang, J. Agric. Food Chem. 62, 1010 (2014)PubMedGoogle Scholar
  7. 7.
    Y. Zeng, Y. Zhang, Q. Weng, M. Hu, G. Zhong, Molecules 15, 7775 (2010)PubMedPubMedCentralGoogle Scholar
  8. 8.
    R. Otto, R. Penzis, F. Gaube, T. Winckler, D. Appenroth, C. Fleck, C. Trankle, J. Lehmann, C. Enzensperger, Eur. J. Med. Chem. 87, 63 (2014)PubMedGoogle Scholar
  9. 9.
    Q. Chen, R. Chao, H. Chen, X. Hou, H. Yan, S. Zhou, W. Peng, A. Xu, Int. J. Cancer 114, 675 (2004)Google Scholar
  10. 10.
    R. Cao, W. Peng, H. Chen, Y. Ma, X. Liu, X. Hou, H. Guan, A. Xu, Biochem. Biophys. Res. Commun. 338, 1557 (2005)PubMedGoogle Scholar
  11. 11.
    R. Cao, W. Fan, L. Guo, Q. Ma, G. Zhang, J. Li, X. Chen, Z. Ren, L. Qiu, Eur. J. Med. Chem. 60, 135 (2013)PubMedGoogle Scholar
  12. 12.
    J. Jimenez, L. Riveron-Negrete, F. Abdullaev, J. Espinosa-Aguirrec, R. Rodriguez-Arnaiz, Exp. Toxicol. Pathol. 60, 381 (2008)PubMedGoogle Scholar
  13. 13.
    S. Nafisi, M. Bonsaii, P. Maali, M.A. Khalilzadeh, F. Manouchehri, J. Photochem. Photobiol., B 100, 84 (2010)Google Scholar
  14. 14.
    S. Nafisi, A. Panahyab, G.B. Sadeghi, J. Lumin. 132, 2361 (2012)Google Scholar
  15. 15.
    J.R. Sanchez-Ramos, Clin. Neuropharmacol. 14(5), 391 (1991)PubMedGoogle Scholar
  16. 16.
    O.I. Tarzi, R. Erra-Balsells, J. Photochem. Photobiol., B 82, 79 (2006)Google Scholar
  17. 17.
    H. Guan, X. Liu, W. Peng, R. Cao, Y. Ma, H. Chen, A. Xu, Biochem. Biophys. Res. Commun. 342, 894 (2006)PubMedGoogle Scholar
  18. 18.
    O.I. Tarzi, R. Erra-Balsells, J. Photochem. Photobiol., B 80, 29 (2005)Google Scholar
  19. 19.
    G. Bahlakeh, B. Ramezanzadeh, A. Dehghani, M. Ramezanzadeh, J. Mol. Liq. 283, 174 (2019)Google Scholar
  20. 20.
    A.D. Becke, J. Chem. Phys. 98, 1372 (1993)Google Scholar
  21. 21.
    C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37, 785 (1988)Google Scholar
  22. 22.
    J.B. Foresman, T.A. Keith, K.B. Wiberg, J. Snoonian, M.J. Frisch, J. Phys. Chem. 100, 16098 (1996)Google Scholar
  23. 23.
    J. Tomasi, B. Mennuci, R. Cammi, Chem. Rev. 105, 2999 (2005)Google Scholar
  24. 24.
    M. H. Jamroz, Vibrational Energy Distribution Analysis VEDA 4, 2004-2010, WarsawGoogle Scholar
  25. 25.
    M. E. Casida, Time-Dependent Density Functional Response Theory for Molecules. Recent Advances in Density Functional Methods, World Scientific, Chapter 5 (1995) p. 155Google Scholar
  26. 26.
    K. Burke, J. Werschnik, E.K. Gross, J. Chem. Phys. 123(6), 62206 (2005)PubMedGoogle Scholar
  27. 27.
    R. Importa, C. Ferrante, R. Bozioc, V. Barone, Phys. Chem. Chem. Phys. 11, 4664 (2009)Google Scholar
  28. 28.
    T. Koopmans, Physica 1, 104 (1934)Google Scholar
  29. 29.
    R.G. Parr, R.G. Pearson, J. Am. Chem. Soc. 105, 7512 (1983)Google Scholar
  30. 30.
    R.G. Pearson, Proc. Natl. Acad. Sci. 83, 8440 (1986)PubMedPubMedCentralGoogle Scholar
  31. 31.
    R.G. Parr, L.V. Szentpaly, S. Liu, J. Am. Chem. Soc. 121, 1922 (1999)Google Scholar
  32. 32.
    F. Weinhold, C.R. Landis, E.D. Glendening, Int. Rev. Phys. Chem. 35(3), 399 (2016)Google Scholar
  33. 33.
    A.E. Reed, L.A. Curtiss, F. Weinhold, Chem. Rev. 88(6), 899 (1988)Google Scholar
  34. 34.
    F. Weinhold, C. Landis, Valency and Bonding: A Natural Bond Orbital Donor-Acceptor perspective, (Cambridge University Press, Cambridge, Chapter 1, 2005) p. 19Google Scholar
  35. 35.
    M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian, Inc., Wallingford CT, 2013Google Scholar
  36. 36.
    GaussView 6.0, Gaussian, Inc, Wallingford CT, 2016Google Scholar
  37. 37.
    G. Shakila, H. Saleem, N. Sundaraganesan, World Sci. News 61(2), 150 (2017)Google Scholar
  38. 38.
    G. Serdaroglu, N. Uludag, Bulg. Chem. Commun. 50, 25 (2018)Google Scholar
  39. 39.
    G. Serdaroglu, N. Uludag, J. Mol. Struct. 1166, 286 (2018)Google Scholar
  40. 40.
    N. Uludag, G. Serdaroglu, A. Yinanc, J. Mol. Struct. 1161, 152 (2018)Google Scholar
  41. 41.
    S. Selvaraja, P. Rajkumara, K. Thirunavukkarasua, S. Gunasekaranb, S. Kumaresan, Vib. Spectrosc. 95, 16 (2018)Google Scholar
  42. 42.
    B.D. Joshi, A. Srivastava, P. Tandon, S. Jain, A.P. Ayal, Spectrochim. Acta A 191, 249 (2018)Google Scholar
  43. 43.
    K. Sayin, D. Karakaş, Spectrochim. Acta A 202, 276 (2018)Google Scholar
  44. 44.
    K. Sayin, D. Karakas, J. Mol. Struct. 1158, 57 (2018)Google Scholar
  45. 45.
    P. Agarwala, N. Choudharya, A. Gupta, P. Tandon, Vib. Spectrosc. 64, 134 (2013)Google Scholar
  46. 46.
    G. Serdaroğlu, N. Şahin, J. Mol. Struct. 1178, 212 (2019)Google Scholar
  47. 47.
    T. Herraiz, D. González, C. Ancín-Azpilicueta, V.J. Arán, H. Guillén, Food Chem. Toxicol. 48, 839 (2010)PubMedGoogle Scholar
  48. 48.
    J. Aihara, Theor. Chem. Acc. 102, 134 (1999)Google Scholar
  49. 49.
    J. Aihara, J. Phys. Chem. A 103, 7487 (1999)Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Mathematics and Science Education, Faculty of EducationSivas Cumhuriyet UniversitySivasTurkey

Personalised recommendations