Understanding the Formation of Novel Hydrated Gallic Acid-Creatinine Molecular Salt: Crystal Structure, Hirshfeld Surface and DFT Studies

Abstract

Creatinine, an aliphatic hetero monocyclic compound, plays an important role in the protein metabolism and change in its physiological normal concentration leads to diabetic nephropathy, renal failure and muscle disorder. In this work, a novel molecular salt form (ionic cocrystal) of creatinine (CR) with gallic acid (GA) has been obtained and preliminarily characterized by PXRD, FTIR and the crystal structure was confirmed by X-ray diffraction method. The presence of a single C–O stretching band in the place of two stretching bands [C=O and C–O] in the infrared spectrum confirms the formation of molecular salt. The asymmetric unit of GA–CR ionic cocrystal [(C7H5O5) (C4H8N3O)+ 3(H2O)] comprises of a molecule of gallic acid, a molecule of creatinine and three water molecules. The structural analysis reveals the strong hydrogen bond DDAA environment of water molecules which confirms the presence of different supramolecular architectures. Thermal gravimetric analysis was carried out to investigate the presence of water/solvent molecules in the molecular salt. Further, the intermolecular interactions in stabilizing the molecular salt were analyzed using Hirshfeld surfaces. Furthermore, the coordinates of molecular salt were optimized by DFT calculations using APFD hybrid functional with 6-311 + G(d,p) level basis set. Frontier molecular orbitals, energy gap and related molecular properties were also analyzed. GA–CR pharmaceutical molecular salt form is found to be more reactive than CR and therefore offers an innovative approach for the futuristic drug design.

Graphic Abstract

Strong hydrogen-bond DDAA environment (D: donor, A: acceptor) exhibited by the water molecules in the GA–CR molecular salt play a major role in stabilizing the crystal structure.

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References

  1. 1.

    Schultheiss N, Newman A (2009) Cryst Growth Des 9:2950–2967

    CAS  Article  Google Scholar 

  2. 2.

    Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ (2006) J Pharm Sci 95:499–516

    CAS  Article  Google Scholar 

  3. 3.

    Lu J, Rohani S (2009) Curr Med Chem 16:884–905

    CAS  Article  Google Scholar 

  4. 4.

    Yadav AV, Shete AS, Dabke AP, Kulkarni PV, Sakhare SS (2009) Indian J Pharm Sci 71:359

    CAS  Article  Google Scholar 

  5. 5.

    Elder DP, Holm R, de Diego HL (2013) Int J Pharm 453:88–100

    CAS  Article  Google Scholar 

  6. 6.

    Stoimenovski J, MacFarlane DR, Bica K, Rogers RD (2010) Pharm Res 27:521–526

    CAS  Article  Google Scholar 

  7. 7.

    Blagden N, de Matas M, Gavan PT, York P (2007) Adv Drug Deliv Rev 59:617–630

    CAS  Article  Google Scholar 

  8. 8.

    Tsai HA, Syu MJ (2005) Biomaterials 26:2759–2766

    CAS  Article  Google Scholar 

  9. 9.

    Du Pre S, Mendel H (1955) Acta Crystallogr 8:311–313

    Article  Google Scholar 

  10. 10.

    Smith G, White JM (2001) Aust J Chem 54:97–100

    CAS  Article  Google Scholar 

  11. 11.

    Goswami S, Jana S, Hazra A, Fun HK, Anjum S (2006) Cryst Eng Commun 8:712–718

    CAS  Article  Google Scholar 

  12. 12.

    Rychkov D, Boldyreva EV, Tumanov NA (2013) Acta Crystallogr C 69:1055–1061

    CAS  Article  Google Scholar 

  13. 13.

    Shen FM, Lush SF (2010) Acta Crystallogr E 66:o2056–o2057

    CAS  Article  Google Scholar 

  14. 14.

    Su KM, Li ZH (2007) Acta Crystallogr E 63:o4512–o4512

    CAS  Article  Google Scholar 

  15. 15.

    Atencio R, Chacón M, González T, Briceño A, Agrifoglio G, Sierraalta A (2004) Dalton Trans 4:505–513

    Article  Google Scholar 

  16. 16.

    Li YP, Yang P (2007) Chin J Chem 25:1715–1721

    CAS  Article  Google Scholar 

  17. 17.

    Perpétuo GJ, Janczak J (2008) J Mol Struct 891:429–436

    Article  CAS  Google Scholar 

  18. 18.

    Mekala R, Jagdish P, Mathammal R (2018) J Mol Struct 1164:501–515

    CAS  Article  Google Scholar 

  19. 19.

    Liu LD, Liu SL, Liu ZX, Hou GG (2016) Mol Struct 1112:1–8

    CAS  Article  Google Scholar 

  20. 20.

    Braga D, Maini L, Grepioni F (2013) Chem Soc Rev 42:7638–7648

    CAS  Article  Google Scholar 

  21. 21.

    Steed JW (2013) Trends Pharmacol Sci 34:185–193

    CAS  Article  Google Scholar 

  22. 22.

    Lee T, Wang PY (2010) Cryst Growth Des 10:1419–1434

    CAS  Article  Google Scholar 

  23. 23.

    Stanton MK, Bak A (2008) Cryst Growth Des 8:3856–3862

    CAS  Article  Google Scholar 

  24. 24.

    Grobelny P, Mukherjee A, Desiraju GR (2011) Cryst Eng Commun 13:4358–4364

    CAS  Article  Google Scholar 

  25. 25.

    Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JA, Puschmann H (2009) J Appl Cryst 42:339–341

    CAS  Article  Google Scholar 

  26. 26.

    Spek AL (1990) Acta Crystallogr A 46:c34–c34

    Google Scholar 

  27. 27.

    Macrae CF, Bruno IJ, Chisholm JA, Edgington PR, McCabe P, Pidcock E, Rodriguez-Monge L, Taylor R, Streek JV, Wood PA (2008) J Appl Crystallogr 41:466–470

    CAS  Article  Google Scholar 

  28. 28.

    Turner MJ, McKinnon JJ, Wolff SK, Grimwood DJ, Spackman PR, Jayatilaka D, Spackman MA (2018) CrystalExplorer. University of Western Australia, Perth

    Google Scholar 

  29. 29.

    BelhajSalah S, Abdelbaky MS, García-Granda S, Essalah K, Nasr CB, Mrad ML (2018) J Mol Struct 1152:276–286

    CAS  Article  Google Scholar 

  30. 30.

    Seth SK, Saha I, Estarellas C, Frontera A, Kar T, Mukhopadhyay S (2011) Cryst Growth Des 11:3250–3265

    CAS  Article  Google Scholar 

  31. 31.

    Luo YH, Zhang CG, Xu B, Sun BW (2012) Cryst Eng Commun 14:6860–6868

    CAS  Article  Google Scholar 

  32. 32.

    McKinnon JJ, Jayatilaka D, Spackman MA (2007) Chem Commun 37:3814–3816

    Article  CAS  Google Scholar 

  33. 33.

    Mackenzie CF, Spackman PR, Jayatilaka D, Spackman MA (2017) IUCrJ 4:575–587

    CAS  Article  Google Scholar 

  34. 34.

    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Fox DJ et al (2010) Gaussian 16, Revision B.01. Gaussian, Inc., Wallingford

  35. 35.

    Dennington R, Keith T, Millam J (2009) GaussView, version 5. Semichem Inc., Shawnee Mission, KS

    Google Scholar 

  36. 36.

    Koopmans T (1934) Physica 1:104–113

    Article  Google Scholar 

  37. 37.

    Qiao N, Li M, Schlindwein W, Malek N, Davies A, Trappitt G (2011) Int J Pharm 41:91–111

    Google Scholar 

  38. 38.

    Childs SL, Stahly GP, Park A (2007) Mol Pharm 4:323–338

    CAS  Article  Google Scholar 

  39. 39.

    Mohamed S, Tocher DA, Vickers M, Karamertzanis PG, Price SL (2009) Cryst Growth Des 9:2881–2889

    CAS  Article  Google Scholar 

  40. 40.

    Lee SM, Halcovitch NR, Jotani MM, Tiekink ER (2017) Acta Crystallogr E 73:630–636

    CAS  Article  Google Scholar 

  41. 41.

    Biswas S, Saha R, Steele IM, Kumar S, Dey K (2013) J Chem Crystallogr 43:493–501

    CAS  Article  Google Scholar 

  42. 42.

    Jyothi KL, Gautam R, Swain D, Guru Row TN, Lokanath NK (2019) Cryst Res Technol 54:1900016

    Article  CAS  Google Scholar 

  43. 43.

    Chen PY, Zhang L, Zhu SG, Cheng GB (2015) Crystals 5:346–354

    CAS  Article  Google Scholar 

  44. 44.

    Hema MK, Karthik CS, Manukumar HN, Kumara K, Pampa KJ, Lingappa M, Mallu P, Lokanath NK (2019) Inorg Chim Acta 484:227–236

    Article  CAS  Google Scholar 

  45. 45.

    Rychkov D, Arkhipov S, Boldyreva E (2016) Acta Crystallogr B 72:160–163

    CAS  Article  Google Scholar 

  46. 46.

    Thomas SP, Shi MW, Koutsantonis GA, Jayatilaka D, Edwards AJ, Spackman MA (2017) Angew Chem 56:8468–8472

    CAS  Article  Google Scholar 

  47. 47.

    Hema MK, Karthik CS, Pampa KJ, Manukumar HM, Mallu P, Warad I, Lokanath NK (2019) Polyhedron 168:127–137

    CAS  Article  Google Scholar 

  48. 48.

    Rybarczyk-Pirek AJ, Checinska L, Małecka M, Wojtulewski S (2013) Cryst Growth Des 13:3913–3924

    CAS  Article  Google Scholar 

  49. 49.

    Chethan Prathap KN, Lokanath NK (2018) J Mol Struct 1171:564–577

    CAS  Article  Google Scholar 

  50. 50.

    Kumara K, Kumar AD, Naveen S, Kumar KA, Lokanath NK (2018) J Mol Struct 1161:285–298

    CAS  Article  Google Scholar 

  51. 51.

    Jasmine NJ, Arunagiri C, Subashini A, Stanley N, Muthiah PT (2017) J Mol Struct 1130:244–250

    Article  CAS  Google Scholar 

  52. 52.

    Marinescu M, Tudorache DG, Marton GI, Zalaru CM, Popa M, Chifiriuc MC, Stavarache CE, Constantinescu C (2017) J Mol Struct 1130:463–471

    CAS  Article  Google Scholar 

  53. 53.

    Ramachandran S, Velraj G (2013) Rom J Phys 58:305–318

    CAS  Google Scholar 

  54. 54.

    Kaur R, Ponraj B, Swain D, Varma KB, Guru Row TN (2015) Cryst Growth Des 15:4171–4176

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Authors would like to thank the National Single Crystal diffractometer Facility, UGC-MRP project (MRP-Phys2013-32718), Department of Studies in Physics, University of Mysore, Mysuru for providing computational facilities. Authors also thank the Solid State and Structural Chemistry Unit, Indian Institute of Science, Bengaluru for providing infrastructure and instrumentation facilities.

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Correspondence to N. K. Lokanath.

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Jyothi, K.L., Mahesha & Lokanath, N.K. Understanding the Formation of Novel Hydrated Gallic Acid-Creatinine Molecular Salt: Crystal Structure, Hirshfeld Surface and DFT Studies. J Chem Crystallogr 50, 410–421 (2020). https://doi.org/10.1007/s10870-019-00814-4

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Keywords

  • Molecular salt
  • Supramolecular architectures
  • Hirshfeld surface
  • Density functional theory