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.
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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Schultheiss N, Newman A (2009) Cryst Growth Des 9:2950–2967
Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ (2006) J Pharm Sci 95:499–516
Lu J, Rohani S (2009) Curr Med Chem 16:884–905
Yadav AV, Shete AS, Dabke AP, Kulkarni PV, Sakhare SS (2009) Indian J Pharm Sci 71:359
Elder DP, Holm R, de Diego HL (2013) Int J Pharm 453:88–100
Stoimenovski J, MacFarlane DR, Bica K, Rogers RD (2010) Pharm Res 27:521–526
Blagden N, de Matas M, Gavan PT, York P (2007) Adv Drug Deliv Rev 59:617–630
Tsai HA, Syu MJ (2005) Biomaterials 26:2759–2766
Du Pre S, Mendel H (1955) Acta Crystallogr 8:311–313
Smith G, White JM (2001) Aust J Chem 54:97–100
Goswami S, Jana S, Hazra A, Fun HK, Anjum S (2006) Cryst Eng Commun 8:712–718
Rychkov D, Boldyreva EV, Tumanov NA (2013) Acta Crystallogr C 69:1055–1061
Shen FM, Lush SF (2010) Acta Crystallogr E 66:o2056–o2057
Su KM, Li ZH (2007) Acta Crystallogr E 63:o4512–o4512
Atencio R, Chacón M, González T, Briceño A, Agrifoglio G, Sierraalta A (2004) Dalton Trans 4:505–513
Li YP, Yang P (2007) Chin J Chem 25:1715–1721
Perpétuo GJ, Janczak J (2008) J Mol Struct 891:429–436
Mekala R, Jagdish P, Mathammal R (2018) J Mol Struct 1164:501–515
Liu LD, Liu SL, Liu ZX, Hou GG (2016) Mol Struct 1112:1–8
Braga D, Maini L, Grepioni F (2013) Chem Soc Rev 42:7638–7648
Steed JW (2013) Trends Pharmacol Sci 34:185–193
Lee T, Wang PY (2010) Cryst Growth Des 10:1419–1434
Stanton MK, Bak A (2008) Cryst Growth Des 8:3856–3862
Grobelny P, Mukherjee A, Desiraju GR (2011) Cryst Eng Commun 13:4358–4364
Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JA, Puschmann H (2009) J Appl Cryst 42:339–341
Spek AL (1990) Acta Crystallogr A 46:c34–c34
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
Turner MJ, McKinnon JJ, Wolff SK, Grimwood DJ, Spackman PR, Jayatilaka D, Spackman MA (2018) CrystalExplorer. University of Western Australia, Perth
BelhajSalah S, Abdelbaky MS, García-Granda S, Essalah K, Nasr CB, Mrad ML (2018) J Mol Struct 1152:276–286
Seth SK, Saha I, Estarellas C, Frontera A, Kar T, Mukhopadhyay S (2011) Cryst Growth Des 11:3250–3265
Luo YH, Zhang CG, Xu B, Sun BW (2012) Cryst Eng Commun 14:6860–6868
McKinnon JJ, Jayatilaka D, Spackman MA (2007) Chem Commun 37:3814–3816
Mackenzie CF, Spackman PR, Jayatilaka D, Spackman MA (2017) IUCrJ 4:575–587
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
Dennington R, Keith T, Millam J (2009) GaussView, version 5. Semichem Inc., Shawnee Mission, KS
Koopmans T (1934) Physica 1:104–113
Qiao N, Li M, Schlindwein W, Malek N, Davies A, Trappitt G (2011) Int J Pharm 41:91–111
Childs SL, Stahly GP, Park A (2007) Mol Pharm 4:323–338
Mohamed S, Tocher DA, Vickers M, Karamertzanis PG, Price SL (2009) Cryst Growth Des 9:2881–2889
Lee SM, Halcovitch NR, Jotani MM, Tiekink ER (2017) Acta Crystallogr E 73:630–636
Biswas S, Saha R, Steele IM, Kumar S, Dey K (2013) J Chem Crystallogr 43:493–501
Jyothi KL, Gautam R, Swain D, Guru Row TN, Lokanath NK (2019) Cryst Res Technol 54:1900016
Chen PY, Zhang L, Zhu SG, Cheng GB (2015) Crystals 5:346–354
Hema MK, Karthik CS, Manukumar HN, Kumara K, Pampa KJ, Lingappa M, Mallu P, Lokanath NK (2019) Inorg Chim Acta 484:227–236
Rychkov D, Arkhipov S, Boldyreva E (2016) Acta Crystallogr B 72:160–163
Thomas SP, Shi MW, Koutsantonis GA, Jayatilaka D, Edwards AJ, Spackman MA (2017) Angew Chem 56:8468–8472
Hema MK, Karthik CS, Pampa KJ, Manukumar HM, Mallu P, Warad I, Lokanath NK (2019) Polyhedron 168:127–137
Rybarczyk-Pirek AJ, Checinska L, Małecka M, Wojtulewski S (2013) Cryst Growth Des 13:3913–3924
Chethan Prathap KN, Lokanath NK (2018) J Mol Struct 1171:564–577
Kumara K, Kumar AD, Naveen S, Kumar KA, Lokanath NK (2018) J Mol Struct 1161:285–298
Jasmine NJ, Arunagiri C, Subashini A, Stanley N, Muthiah PT (2017) J Mol Struct 1130:244–250
Marinescu M, Tudorache DG, Marton GI, Zalaru CM, Popa M, Chifiriuc MC, Stavarache CE, Constantinescu C (2017) J Mol Struct 1130:463–471
Ramachandran S, Velraj G (2013) Rom J Phys 58:305–318
Kaur R, Ponraj B, Swain D, Varma KB, Guru Row TN (2015) Cryst Growth Des 15:4171–4176
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
About this article
Cite this article
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
- Molecular salt
- Supramolecular architectures
- Hirshfeld surface
- Density functional theory