Molecular Interaction Studies of Doxycycline Hyclate in Aqueous Glycine or l-Alanine by Using Volumetric and Ultrasonic Parameters


The intermolecular interactions of the antibiotic drug doxycycline hyclate in water, aqueous solutions of glycine and aqueous solutions of l-alanine were determined by using volumetric and acoustic methods at four different temperatures (305.15, 310.15, 315.15 and 320.15) K. The limiting partial molar volume \((V_{\phi }^{{\text{o}}} )\), limiting standard partial molar volume of transfer \({(}\Delta_{{{\text{tr}}}} V_{\phi }^{{\text{o}}} )\), limiting partial molar adiabatic compressibility (\(\kappa_{\phi ,s}^{{\text{o}}} )\) and limiting partial molar adiabatic compressibility of transfer \({(}\Delta_{{{\text{tr}}}} \kappa_{\phi ,s}^{{\text{o}}} )\) were calculated from the density and ultrasonic velocity data at different temperatures and the results suggest strong solute–solvent interactions. The caging effect of doxycycline hyclate in water and in aqueous solutions of glycine and aqueous solutions of l-alanine was studied using the positive values of \(\left( {E_{\phi }^{{\text{o}}} = \frac{{{\updelta }V_{\phi }^{{\text{o}}} }}{{{\updelta }T}}} \right)\). The structure making behavior of doxycycline hyclate in water, aqueous solutions of glycine and aqueous solutions of l-alanine was analyzed from the positive values of Hepler’s constant i.e. \(\left( {\frac{{{\updelta }^{2} V_{\phi }^{{\text{o}}} }}{{{\updelta }T^{2} }}} \right)\). The limiting isobaric thermal expansion coefficient \(\left( {\alpha^{{\text{o}}} { } = \frac{{E_{\phi }^{{\text{o}}} }}{{V_{\phi }^{{\text{o}}} }}} \right)\), intermolecular free length (Lf) and acoustic impedance (Z) of doxycycline hyclate in water, aqueous solutions of glycine and aqueous solutions of l-alanine were also calculated at the studied temperatures.

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  1. 1.

    Yates, J.R., Petsko, G.A.: Analyzing molecular interactions. Curr. Protoc. Bioinform. (2011). Chap. 8.1

  2. 2.

    Teodorico, C.R., Elaine, F.F.C.: Thermodynamic framework of the interaction between protein and solvent drives protein folding. J. Biomol. Struct. Dyn. 28, 645–646 (2011)

    Article  Google Scholar 

  3. 3.

    Golemis, E.A., Tew, K.D., Dadke, D.: Protein interaction targeted drug discovery: evaluating critical issues. Bio. Tech. 32, 636–647 (2002)

    CAS  Google Scholar 

  4. 4.

    Bajpai, A.K., Shukla, S.K., Bhanu, S., Kankane, S.: Responsive polymers in controlled drug delivery. Prog. Poly. Sci. 33, 1088–1118 (2008)

    CAS  Article  Google Scholar 

  5. 5.

    Sinha, B., Sarkar, B.K., Roy, M.N.: Apparent molar volumes and viscosity B-coefficients of nicotinamide in aqueous tetrabutyl ammonium bromide solutions at T = (298.15, 308.15, and 318.15) K. J. Chem. Thermodyn. 40, 394–400 (2008)

    CAS  Article  Google Scholar 

  6. 6.

    Iqbal, M.J., Mahrukh, S.: Partial molar volume of mefenamic acid in alcohol at temperatures between T = 293.15 and T = 313.15 K. J. Braz. Chem. Soc. 17, 851–858 (2006)

    CAS  Article  Google Scholar 

  7. 7.

    Akram, M., Asif, H.M., Uzair, M., Akhtar, N., Madni, A., Shah Ali, S.M., Hasan, Z.U., Ullah, A.: Amino acids: a review article. J. Med. Plant. Res. 5, 3997–4000 (2011)

    CAS  Google Scholar 

  8. 8.

    Bakshi, M.S.: Nanoshape control tendency of phospholipids and proteins: protein nanoparticle composites, seeding, self-aggregation, and their applications in bionanotechnology and nanotoxicology. J. Phys. Chem. C. 115, 13947–13960 (2011)

    CAS  Article  Google Scholar 

  9. 9.

    Shaikh, S.A., Ahmed, S.R., Jayaram, B.: A molecular thermodynamic view of DNA–drug interactions: a case study of 25 minor-groove binders. Arch. Biochem. Biophys. 429, 81–99 (2004)

    CAS  Article  Google Scholar 

  10. 10.

    Chakravarty, S., Yadava, V.S., Kumar, V., Kannan, K.K.: Drug protein interaction at the molecular level: a study of sulphonamide carbonic anhydrase complexes. J. Biosci. 8, 491–498 (1985)

    CAS  Article  Google Scholar 

  11. 11.

    Kumar, H., Kaur, K.: Interaction of antibacterial drug ampicillin with glycine and its dipeptides analyzed by volumetric and acoustic methods at different temperatures. Thermochim. Acta. 551, 40–45 (2013)

    CAS  Article  Google Scholar 

  12. 12.

    Sharma, S.K., Nathan, V., Kumar, D., Kishore, K.: Molecular interaction studies of antibiotic drug doxycycline hyclate with aqueous mannitol using volumetric and acoustic methods. J. Mol. Liq. 231, 647–654 (2017)

    CAS  Article  Google Scholar 

  13. 13.

    Sinha, B., Dakua, V.K., Roy, M.N.: Apparent molar volumes and viscosity B-coefficients of some amino acids in aqueous tetramethylammonium iodide solutions at 298.15 K. J. Chem. Eng. Data 52, 1768–1772 (2007)

    CAS  Article  Google Scholar 

  14. 14.

    Chauhan, S., Singh, K., Kumar, K., Neelakantan, S.G., Kumar, G.: Drug−amino acid interactions in aqueous medium: volumetric, compressibility, and viscometric studies. J. Chem. Eng. Data. 61, 788–796 (2016)

    CAS  Article  Google Scholar 

  15. 15.

    Nain, A.K., Chand, D.: Volumetric, ultrasonic, and viscometric behaviour of glycine, dl-alanine, and l-valine in aqueous 1,4-butanediol solutions at different temperatures. J. Chem. Thermodyn. 41, 243–249 (2009)

    CAS  Article  Google Scholar 

  16. 16.

    Banipal, T.S., Kaur, J., Banipal, P.K.: Interactions of some amino acids with aqueous manganese chloride tetrahydrate at T = (288.15 to 318.15) K: a volumetric and viscometric approach. J. Chem. Thermodyn. 48, 181–189 (2012)

    CAS  Article  Google Scholar 

  17. 17.

    Sastry, N.V., Valand, P.H., Macwan, P.M.: Effect of hydrophilic additives on volumetric and viscosity properties of amino acids in aqueous solutions at T = (283.15 to 333.15) K. J. Chem. Thermodyn. 49, 14–23 (2012)

    CAS  Article  Google Scholar 

  18. 18.

    Vraneš, M., Armakovic, S., Tot, A., Papovic, S., Zec, N., Armakovic, S., Banic, N., Abramovic, B., Gadzuric, S.: Structuring of water in the new generation ionic liquid—comparative experimental and theoretical study. J. Chem. Thermodyn. 93, 164–171 (2016)

    Article  Google Scholar 

  19. 19.

    Singla, M., Kumar, H., Jindal, R.: Solvation behaviour of biologically active compounds in aqueous solutions of antibacterial drug amoxicillin at different temperatures. J. Chem. Thermodyn. 76, 100–115 (2014)

    CAS  Article  Google Scholar 

  20. 20.

    Pal, A., Kumar, S.: Volumetric and ultrasonic studies of some amino acids in binary aqueous solutions of MgCl2·6H2O at 298.15 K. J. Mol. Liq. 121, 148–155 (2005)

    CAS  Article  Google Scholar 

  21. 21.

    Usmani, M.A., Riyazuddeen: Interactions in (l-alanine/l-threonine + aqueous glucose/aqueous sucrose) systems at (298.15–323.15) K. Thermochim. Acta 527, 112–117 (2012)

  22. 22.

    Singla, M., Jindal, R., Kumar, H.: Volumetric, acoustic, and UV absorption studies on solute–solvent interactions of dipeptides of glycine with aqueous amoxicillin solutions. Thermochim. Acta 591, 140–151 (2014)

    CAS  Article  Google Scholar 

  23. 23.

    Iqbal, M.J., Chaudhary, M.A.: Effect of temperature on volumetric and viscometric properties of some non-steroidal anti-inflammatory drugs in aprotic solvents. J. Chem. Thermodyn. 42, 951–956 (2010)

    CAS  Article  Google Scholar 

  24. 24.

    Torres, D.R., Blanco, L.H., Martinez, F., Vargas, E.F.: Apparent molal volumes of lidocaine·HCl and procaine·HCl in aqueous solution as a function of temperature. J. Chem. Eng. Data 52, 1700–1703 (2007)

    CAS  Article  Google Scholar 

  25. 25.

    Chadha, R., Kashid, N., Jain, D.V.S.: Microcalorimetric evaluation of the in vitro compatibility of amoxicillin/clavulanic acid and ampicillin/sulbactam with ciprofloxacin. J. Pharm. Biomed. Analysis 36, 295–307 (2004)

    CAS  Article  Google Scholar 

  26. 26.

    Fortin, T.J., Laesecke, A., Freund, M., Outcalt, S.: Advanced calibration, adjustment, and operation of a density and sound speed analyzer. J. Chem. Thermodyn. 57, 276–285 (2013)

    CAS  Article  Google Scholar 

  27. 27.

    Mishra, A.K., Ahluwalia, J.C.: Apparent molal volumes of amino acids, N-acetylamino acids, and peptides in aqueous solutions. J. Phys. Chem. 88, 86–92 (1984)

    CAS  Article  Google Scholar 

  28. 28.

    Iqbal, M.J., Chaudhary, M.A.: Thermodynamic study of phenyl salicylate solutions in aprotic solvents at different temperatures. J. Chem. Eng. Data 54, 338–341 (2009)

    CAS  Article  Google Scholar 

  29. 29.

    Ali, A., Bidhuri, P., Uzair, S.: Thermodynamic and spectroscopic studies of alanine and phenylalanine in aqueous b-cyclodextrin solutions. J. Saud. Chem. Soc. 21, S136–S142 (2017)

    CAS  Article  Google Scholar 

  30. 30.

    Lomesh, S.K., Kumar, D.: Temperature dependence of density, conductance and viscosity of zinc sulphate and copper sulphate solutions in aqueous medium in the presence of maltose and sodium chloride. J. Ind. Chem. Soc. 94, 397–408 (2017a)

    CAS  Google Scholar 

  31. 31.

    Sinha, B., Roy, P.K., Sarkar, B.K., Brahman, D., Roy, M.N.: Apparent molar volumes and viscosity B-coefficients of caffeine in aqueous thorium nitrate solutions at T = (298.15, 308.15, and 318.15) K. J. Chem. Thermodyn. 42, 380–386 (2010)

    CAS  Article  Google Scholar 

  32. 32.

    Sarkar, A., Pandit, B.K., Acharjee, K., Sinha, B.: Volumetric and viscometric behavior of ferrous sulfate in aqueous lactose solutions at different temperatures. Int. J. Am. Chem. Soc. 3, 219–229 (2015)

    CAS  Google Scholar 

  33. 33.

    Hepler, L.G.: Thermal expansion and structure in water and aqueous solutions. Can. J. Chem. 47, 4613–4617 (1969)

    CAS  Article  Google Scholar 

  34. 34.

    Roy, M.N., Dakua, V.K., Sinha, B.: Partial molar volumes, viscosity B-coefficients, and adiabatic compressibilities of sodium molybdate in aqueous 1,3-dioxolane mixtures from 303.15 to 323.15 K. Int. J. Thermophys. 28, 1275–1284 (2007)

    CAS  Article  Google Scholar 

  35. 35.

    Misra, P.R., Das, B., Parmar, M.L., Banyal, D.S.: Partial molar volumes, viscosity B-coefficients, and adiabatic compressibilities of sodium molybdate in aqueous 1,3-dioxolane mixtures from 303.15 to 323.15 K. Ind. J. Chem. 44A, 1582–1588 (2005)

    Google Scholar 

  36. 36.

    Sinha, B., Sarkar, A., Roy, P., Brahman, D.: Physicochemical properties of L-alanine in aqueous silver sulphate solutions at (298.15, 308.15, and 318.15) K. Int. J. Thermophys. 32, 2062–2078 (2011)

    CAS  Article  Google Scholar 

  37. 37.

    Zhao, H.: Viscosity B-coefficients and standard partial molar volumes of amino acids, and their roles in interpreting the protein (enzyme) stabilization. J. Biophys. Chem. 122, 157–183 (2006)

    CAS  Article  Google Scholar 

  38. 38.

    Cibulka, I., Hnedkovsky, L., Sedlbauer, J.: Partial molar volumes of organic solutes in water. Glycine(aq) and l-alanine (aq) at temperatures (298 to 443) K and at pressures up to 30 MPa. J. Chem. Thermodyn. 42, 198–207 (2010)

  39. 39.

    Wadi, R.K., Ramasami, P.: Partial molal volumes and adiabatic compressibilities of transfer of glycine and DL-alanine from water to aqueous sodium sulfate at 288.15, 298.15 and 308.15 K. J. Chem. Soc. Faraday Trans. 93, 243–247 (1997)

  40. 40.

    Lomesh, S.K., Kumar, D.: Volumetric, viscosity and ultrasonic studies of solute–solute and solute–solvent interactions of glycine and diglycine in water and in aqueous citric acid at different temperatures. J. Mol. Liq. 241, 764–771 (2017b)

    CAS  Article  Google Scholar 

  41. 41.

    Chimankar, O.P., Shriwas, R., Tabhane, V.A.: Intermolecular interaction studies in some amino acids with aqueous NaOH. J. Chem. Pharm. Res. 3, 587–596 (2011)

    CAS  Google Scholar 

  42. 42.

    Syal, V.K., Thakur, S.K., Chauhan, S., Sharma, P.: Ultrasonic velocity studies of drug parvon-spas in mixed alcohol–water solvent systems at 25 °C. Int. J. Thermophys. 26, 807–826 (2005)

    CAS  Article  Google Scholar 

  43. 43.

    Kumar, H., Kaur, K.: Investigation on molecular interaction of amino acids in antibacterial drug ampicillin solutions with reference to volumetric and compressibility measurements. J. Mol. Liq. 173, 130–136 (2012)

    CAS  Article  Google Scholar 

  44. 44.

    Romero, C.M., Negrete, F.: Effect of temperature on partial molar volumes and viscosities of aqueous solutions of α-dl-aminobutyric acid, dl-norvaline and dl-norleucine. Phys. Chem. Liq. 42, 261–267 (2004)

    CAS  Article  Google Scholar 

  45. 45.

    Moatter Zafarani, M.T., Sarmad, S.: Effect of tri-potassium phosphate on volumetric, acoustic, and transport behaviour of aqueous solutions of 1-ethyl-3-methylimidazolium bromide at T = (298.15 to 318.15) K. J. Chem. Thermodyn. 42, 1213–1221 (2010)

  46. 46.

    Jacobson, B.: Intermolecular free lengths in the liquid state. I. Adiabatic and isothermal compressibilities. Acta Chem. Scand. 6, 1485–1498 (1952)

  47. 47.

    Baskaran, R., Kubendran, T.R.: Refractive indices, ultrasonic velocities, surface tension and thermo acoustical parameters of anisaldehyde + benzene at 313.15 K. Int. J. App. Sci. Eng. 5, 115–122 (2007)

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The author is grateful to CSIR New Delhi for the financial support in the beginning (sanction letter no. 09/237(0153)/2014-EMR-I) and Himachal Pradesh University for laboratory facilities.

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Sharma, S.K., Poonam Molecular Interaction Studies of Doxycycline Hyclate in Aqueous Glycine or l-Alanine by Using Volumetric and Ultrasonic Parameters. J Solution Chem (2021).

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  • Partial molar volume
  • Standard partial molar volume of transfer
  • Partial molar adiabatic compressibility
  • Doxycycline hyclate
  • Glycine and l-alanine