Advertisement

Theoretical investigation of the self-association of antitumor drug imexon

  • Hind GuemmourEmail author
  • Djaffar Kheffache
Original Paper
  • 12 Downloads

Abstract

The dimers resulting from self-association of oxo-imino, oxo-amino, and hydroxyl-imino tautomers of imexon, that present two hydrogen bonds, were fully optimized with the density functional methods B3LYP, M06-2X in conjunction with 6-311++G(d,p) basis set. Additionally, second-order Møller-Plesset (MP2) level in combination with 6-311++G(d,p) basis set was employed for comparison purpose. The thermodynamic stability of the self assembled structures in gaseous phase has been obtained according to the analyses of total electronic energies and hydrogen bonding interactions. The bulk water environment has been simulated using the universal solvation model based on solute electron density (SMD). Stability and structure of homochiral and heterochiral imexon dimers resulting from the three imexon tautomers have been carried out to investigate the chiral discrimination. The imexon dimer with heterochiral configuration resulting from self-assembling oxo-amino tautomer is found to be thermodynamically most stable in both gas and aqueous phases. The interaction energies for these self assembled structures were further evaluated with the basis set superposition error corrections. The so-called seven-point interaction energy which includes corrections for BSSE and deformation was calculated. The intermolecular interactions of the selected dimers have been analyzed by calculation of electron density (ρ) and Laplacian (∇2ρ) at the bond critical points (BCPs) using atoms-in-molecule (AIM) theory.

Keywords

Imexon Self-association Hydrogen bond DFT AIM method 

Notes

Supplementary material

11696_2019_1014_MOESM1_ESM.docx (32 kb)
Supplementary material 1 (DOCX 32 kb)

References

  1. Alkorta I, Zborowski K, Elguero J (2006a) Self-aggregation as a source of chiral discrimination. Chem Phys Lett. 427(4):289–294.  https://doi.org/10.1016/j.cplett.2006.06.104 CrossRefGoogle Scholar
  2. Alkorta I, Picazo O, Elguero J (2006b) Theoretical studies on chiral discrimination. Curr Org Chem 10(7):695–714.  https://doi.org/10.2174/138527206776818955 CrossRefGoogle Scholar
  3. Bader RFW (1985) Atoms in molecules. Acc Chem Res 18:9–15.  https://doi.org/10.1021/ar00109a003 CrossRefGoogle Scholar
  4. Becke AD (1993) Density-functional thermochemistry III. The role of exact exchange. J Chem Phys 98(7):5648–5652.  https://doi.org/10.1063/1.464913 CrossRefGoogle Scholar
  5. Boys SF, Bernardi F (1970) The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol Phys 19(4):553–566.  https://doi.org/10.1080/00268977000101561 CrossRefGoogle Scholar
  6. Carroll MT, Bader RFW (1988) An analysis of the hydrogen bond in BASE-HF complexes using the theory of atoms in molecules. Mol Phys 65:695–722.  https://doi.org/10.1080/00268978800101351 CrossRefGoogle Scholar
  7. Den Brok MWJ, Nuijen B, Hillebrand MJX, Lutz C, Opitz H, Beijnen JH (2005) LC-UV Method development and validation for the investigational anticancer agent Imexon and identification of its degradation products. J Pharm Biomed Anal 38(4):686–694.  https://doi.org/10.1016/j.jpba.2005.02.012 CrossRefGoogle Scholar
  8. Espinosa E, Molins E, Lecomte C (1998) Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities. Chem Phys Lett 285:170–173.  https://doi.org/10.1016/S0009-2614(98)00036-0 CrossRefGoogle Scholar
  9. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA, Jr, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2016) Gaussian 16, Revision A.03, Gaussian, Inc., Wallingford CTGoogle Scholar
  10. Huisken F, Pertsch T (1988) Infrared photodissociation of size-selected small ammonia clusters. Chem Phys 126(1):215–228.  https://doi.org/10.1016/0301-0104(88)85034-1 CrossRefGoogle Scholar
  11. Kheffache D, Ouamerali O (2010) What is the real existing form of imexon? Quantum chemical studies. J Mol Struct THEOCHEM 945(1):39–44.  https://doi.org/10.1016/j.theochem.2010.01.010 CrossRefGoogle Scholar
  12. Kheffache D, Guemmour H, Ouamerali O (2012) Prototropic tautomerism and microsolvation in antitumor drug imexon: a DFT study. Struct Chem 23(5):1547–1557.  https://doi.org/10.1007/s11224-012-9968-3 CrossRefGoogle Scholar
  13. Koch U, Popelier PLA (1995) Characterization of C–H–O hydrogen bonds on the basis of the charge density. J Phys Chem 99:9747–9754.  https://doi.org/10.1021/j100024a016 CrossRefGoogle Scholar
  14. Kuehl PJ, Carducci MD, Myrdal PB (2006) 4-Imino-1,3-diaza-bicyclo-[3.1.0]hexan-2-one. Acta Crystallogr Sect E 62:o3688–o3690.  https://doi.org/10.1107/S1600536806029412 CrossRefGoogle Scholar
  15. 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 37:785–789.  https://doi.org/10.1103/PhysRevB.37.785 CrossRefGoogle Scholar
  16. Lu T, Chen F (2012) Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem 33:580–592.  https://doi.org/10.1002/jcc.22885 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113(18):6378–6396.  https://doi.org/10.1021/jp810292n CrossRefPubMedGoogle Scholar
  18. Matta CF, Boyd RJ (2007) In the quantum theory of atoms in molecules: from solid state to DNA and drug design. Wiley, WeinheimCrossRefGoogle Scholar
  19. Møller C, Plesset MS (1934) Note on an Approximation treatment for many-electron systems. Phys Rev 46:618–622.  https://doi.org/10.1103/PhysRev.46.618 CrossRefGoogle Scholar
  20. Moulder S, Dhillon N, Ng C, Hong D, Wheler J, Naing A, Tse S, La Paglia A, Dorr R, Hersh E, Boytim M, Kurzrock R (2010) A phase I trial of imexon, a pro-oxidant, in combination with docetaxel for the treatment of patients with advanced breast, non-small cell lung and prostate cancer. Invest New Drugs 28(5):634–640.  https://doi.org/10.1007/s10637-009-9273-1 CrossRefPubMedGoogle Scholar
  21. Popelier PLA (1998) Characterization of a Dihydrogen bond on the basis of the electron density. J Phys Chem A 102:873–1878.  https://doi.org/10.1021/jp9805048 CrossRefGoogle Scholar
  22. Remers WA, Dorr R (2012) Chemistry and pharmacology of Imexon and related Cyanoaziridines. Curr Med Chem 19(33):5745–5753.  https://doi.org/10.2174/092986712803988802 CrossRefPubMedGoogle Scholar
  23. Ribeiro RF, Marenich AV, Cramer CJ, Truhlar DG (2011) The solvation, partitioning, hydrogen bonding, and dimerization of nucleotide bases: a multifaceted challenge for quantum chemistry. Phys Chem Chem Phys 13(23):10908–10922.  https://doi.org/10.1039/c0cp02784g CrossRefPubMedGoogle Scholar
  24. Rode JE, Dobrowolski JC (2002) Theoretical studies on the oxetane··· HCl and thietane··· HCl complexes. Chem Phys Lett 360(1–2):123–132.  https://doi.org/10.1016/S0009-2614(02)00779-0 CrossRefGoogle Scholar
  25. Rode JE, Jamróz MH, Dobrowolski JC, Sadlej J (2012) On vibrational circular cichroism chirality transfer in electron donor-acceptor Complexes: a Prediction for the Quinine···BF3 system. J Phys Chem A 116(30):7916–7926.  https://doi.org/10.1021/jp304955v CrossRefPubMedGoogle Scholar
  26. Shainyan BA, Chipanina NN, Aksamentova TN, Oznobikhina LP, Rosentsveig GN, Rosentsveig IB (2010) Intramolecular hydrogen bonds in the sulfonamide derivatives of oxamide, dithiooxamide, and biuret. FT-IR and DFT study, AIM and NBO analysis. Tetrahedron 66(44):8551–8556.  https://doi.org/10.1016/j.tetlet.2010.08.076 CrossRefGoogle Scholar
  27. Sheveleva EV, Landowski TH, Samulitis BK, Bartholomeusz G, Powis G, Dorr RT (2012) Imexon induces an oxidative endoplasmic reticulum stress response in pancreatic cancer cells. Mol Cancer Res 10(3):392–400.  https://doi.org/10.1158/1541-7786.MCR-11-0359 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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. Theor Chem Acc 120:215–241.  https://doi.org/10.1007/s00214-007-0310-x CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2019

Authors and Affiliations

  1. 1.Chemistry Department of the Faculty of SciencesUniversity M’Hamed Bougara (UMBB)BoumerdesAlgeria
  2. 2.Laboratory of Macromolecular Synthesis and Thio-organic Macromolecular, Faculty of ChemistryUniversity of Sciences and Technology Houari Boumediene (USTHB)AlgiersAlgeria
  3. 3.Laboratory of Computational Chemistry and Photonics, Faculty of ChemistryUniversity of Sciences and Technology Houari Boumediene (USTHB)AlgiersAlgeria

Personalised recommendations