A computational study of intramolecular hydrogen bonds breaking/formation: impact on the structural flexibility of the ranitidine molecule

  • Mariana Kozlowska
  • Jakub Goclon
  • Pawel Rodziewicz
Original Paper

Abstract

Ranitidine is a histamine H2-receptor antagonist that reduces gastric acid secretion. We studied the flexibility of the ranitidine molecule with the special focus on the network of diverse intramolecular hydrogen bonds: N-H ⋯O, N-H ⋯N, C-H ⋯O, C-H ⋯N and N-H ⋯S. We performed static density functional theory calculations of global and local minima and analyzed their stability at finite temperature in the Car–Parrinello molecular dynamics simulations. We observed intramolecular H-bonds breaking/formation crucial for the structural rearrangements leading to the folding process. The lifetimes of the closed structures of ranitidine were also estimated. The existence of hydrogen bonds and their strength were confirmed on the basis of topological parameters in the bond critical points utilizing Quantum Theory of Atoms in Molecules.

Keywords

Ranitidine Intramolecular hydrogen bonds AIM analysis Car-Parrinello molecular dynamics Structural flexibility 

Supplementary material

894_2015_2591_MOESM1_ESM.pdf (2.5 mb)
(PDF 2.47 MB)

References

  1. 1.
    Ahmadi A, Ebrahimzadeh MA, Ahmad-Ashrafi S, Karami M, Mahdavi MR, Saravi SSS (2001) Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists. Fundam Clin Pharmacol 25:72CrossRefGoogle Scholar
  2. 2.
    Amin AS, Ahmed IS, Dessouki HA, Gouda EA (2003) Utility of oxidation-reduction reaction for the determination of ranitidine hydrochloride in pure form, in dosage forms and in the presence of its oxidative degradates. Spectrochim Acta 59:695CrossRefGoogle Scholar
  3. 3.
    Bader RFW (1990) Atoms in Molecules, A Quantum Theory. Oxford University Press, OxfordGoogle Scholar
  4. 4.
    Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic-behavior. Phys Rev A 38:3098CrossRefGoogle Scholar
  5. 5.
    Car R, Parrinello M (1985) Unified approach for molecular-dynamics and density-functional theory. Phys Rev Lett 55:2471CrossRefGoogle Scholar
  6. 6.
    Ching TL, Haenen GR, Bast A (1993) Cimetidine and other H2 receptor antagonists as powerful hydroxyl radical scavengers. Chem Biol Interact 86:119CrossRefGoogle Scholar
  7. 7.
    Fan JM, Liu L, Guo QX (2002) Substituent effects on the blue-shifted hydrogen bonds. Chem Phys Lett 365:464CrossRefGoogle Scholar
  8. 8.
    Ferretti V, Pretto L, Tabrizi MA, Gilli P (2006) Role of strong intramolecular N-H-N hydrogen bonds in determining the conformation of adenosine-receptor antagonists. ActaCryst B62:634Google Scholar
  9. 9.
    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 J A 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 NJ, 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 JB, Foresman JV, Cioslowski Ortiz J, Fox DJ (2009) Gaussian 09, Revision D.01. Gaussian, Inc., Wallingford CT.Google Scholar
  10. 10.
    Gao Y, Tian Y, Sun X, Yin XB, Xiang Q, Ma G, Wang E (2006) Determination of ranitidine in urine by capillary electrophoresis-electrochemiluminescent detection. J Chromatogr B 832:236CrossRefGoogle Scholar
  11. 11.
    Grabowski SJ (2011) Red- and blue-shifted hydrogen bonds: the bent rule from Quantum Theory of Atoms in Molecules perspective. J Phys Chem A 115:12789CrossRefGoogle Scholar
  12. 12.
    Grant SM, Langtry HD, Brogden RN (1989) Ranitidine Drugs 37(6):801CrossRefGoogle Scholar
  13. 13.
    Grimme S (2004) Accurate description of van der Waals complexes by density functional theory including empirical corrections. J Comput Chem 25(12):1463CrossRefGoogle Scholar
  14. 14.
    Gu Y, Kar T, Scheiner S (1999) Fundamental properties of the CH ⋯O interaction: Is it a true hydrogen bond. J Am Chem Soc 121:9411CrossRefGoogle Scholar
  15. 15.
    Hermansson K (2002) Blue-shifting hydrogen bonds. J Phys Chem A 106:4695CrossRefGoogle Scholar
  16. 16.
    Hoover WG (1985) Canonical dynamics — equilibrium phase-space distributions. Phys Rev A 31:1695CrossRefGoogle Scholar
  17. 17.
  18. 18.
    Humphrey W, Dalke A, Schulten K (1996) VMD — Visual Molecular Dynamics. J Molec Graphics 14:33CrossRefGoogle Scholar
  19. 19.
    Isidori M, Parrella A, Pistillo P, Temussi F (2009) Effects of ranitidine and its photoderivatives in the aquatic environment. Environ Int 35:821CrossRefGoogle Scholar
  20. 20.
    Jeffrey GA, Saenger W (1991) Hydrogen bonding in biological structures. SpringerGoogle Scholar
  21. 21.
    Karpfen A, Kryachko ES (2003) Blue-shifted hydrogen-bonded complexes cf3h-(hf)1¡n¡3. J Phys Chem A 107:9724CrossRefGoogle Scholar
  22. 22.
    Keith TA (2010) AIMAll (version 10.05.04, professional)Google Scholar
  23. 23.
    Khalil MM, Frag EYZ, Mohamed GG, Abed el Aziz GM (2013) Spectrophotometric studies using ion-pair formations of ranitidine hydrochloride in pure and in pharmaceutical forms with some dyestuff reagents. JAPS 3(04):092Google Scholar
  24. 24.
    Koch U, Popelier PLA (1995) Characterization of C-H-O hydrogen bonds on the basis of the charge density. J Phys Chem 99:9747CrossRefGoogle Scholar
  25. 25.
    Kokoletsi MX, Kafkala S, Tsiaganis M (2005) A novel gradient HPLC method for simultaneous determination of ranitidine, methylparaben and propylparaben in oral liquid pharmaceutical formulation. J Pharm Biomed Anal 38:763CrossRefGoogle Scholar
  26. 26.
    Kryachko ES, Zeegers-Huyskens Th (2001) Theoretical study of the ch ⋯o interaction in fluoromethanesh2o and chloromethanesh2o complex. J Phys Chem A 105:7118CrossRefGoogle Scholar
  27. 27.
    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 37:785CrossRefGoogle Scholar
  28. 28.
    Martins JL, Perez MA, Silva CH, Taft CA, Arissawa M, Longo E, Mello PC, Stamato F, Tostes JG (2002) Theoretical ab initio study of ranitidine. Int J Quantum Chem 90:575CrossRefGoogle Scholar
  29. 29.
    Martyna GJ, Tuckerman ME (1999) A reciprocal space based method for treating long range interactions in ab initio and force-field-based calculations in clusters. J Chem Phys 119:2810CrossRefGoogle Scholar
  30. 30.
    Nose S (1984) A unified formulation of the constant temperature molecular-dynamics methods. J Chem Phys 81:511CrossRefGoogle Scholar
  31. 31.
    Pfaffen V, Ortiz PI (2010) Alternative method with amperometric detection for ranitidine determination. Ind Eng Chem Res 49:4026CrossRefGoogle Scholar
  32. 32.
    Pimentel GC, McClellan AL (1971) Hydrogen bonding. Annu Rev Phys Chem 21:347CrossRefGoogle Scholar
  33. 33.
    Rodziewicz P, Meyer B (2014) Interplay between molecule—molecule and molecule—substrate interactions: first principles study of fluoroform aggregates on a hexagonal ice (0001) surface. Phys Chem Chem Phys 16:940CrossRefGoogle Scholar
  34. 34.
    Rodziewicz P, Rutkowski KS, Meyer B (2011) First-principles study of fluoroform adsorption on a hexagonal ice (0001) surface; weak hydrogen bonds–strong structural effects. Phys Chem Chem Phys 13:14101CrossRefGoogle Scholar
  35. 35.
    Rodziewicz P, Rutkowski KS, Melikova SM, Koll A (2005) Ab initio studies of electron acceptor–donor interactions with blue- and red-shifted hydrogen bonds. ChemPhysChem 6: 1282CrossRefGoogle Scholar
  36. 36.
    Van der Veken BJ, Herrebout WA, Szostak R, Shchepkin DN, Havlas Z, Hobza P (2001) The nature of improper, blue-shifting hydrogen bonding verified experimentally. J Am Chem Soc 123:12290CrossRefGoogle Scholar
  37. 37.
    Wojtulewski S, Grabowski SJ (2005) Blue-shifting C—H⋯Y intramolecular hydrogen bonds—DFT and AIM analyses. Chem. Phys. 309:183CrossRefGoogle Scholar
  38. 38.
    Wright R (1996) How Zantac became the best-selling drug in history, vol 16, p 4Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Mariana Kozlowska
    • 1
  • Jakub Goclon
    • 2
  • Pawel Rodziewicz
    • 1
  1. 1.Institute of ChemistryUniversity of BialystokBialystokPoland
  2. 2.Interdisciplinary Center for Molecular Materials (ICMM), and Computer-Chemistry-Center (CCC)Friedrich-Alexander-University Erlangen-NürnbergErlangenGermany

Personalised recommendations