Synthesis and characterization of Cu(II) complexes of proton transfer salts derived from piperazine derivatives and 5-sulfosalicylic acid


  • Nurgün Büyükkıdan Kütahya Dumlupınar University
  • Halil ilkimen Kütahya Dumlupınar University
  • Büşra Durmuş Kütahya Dumlupınar University
  • Aysel Gülbandılar Eskişehir Osmangazi University



5-Sulfosalicylic Acid, 1-Piperazine Derivatives, Proton Transfer Salt, Metal Complexes, Antimicrobial activity.


In this study, proton transfer salts (H2Etpip)(Hssa), (H2HOEtpip)(Hssa) and (HAcpip)(H2ssa), have been obtained by reactions between 1-ethylpiperazine (Etpip), 1-(2-hydroxyethyl)piperazine (HOEtpip) and 1‑acetylpiperazine (Acpip) and 5-sulfosalicylic acid (H3ssa). Also, Cu(II) complexes of proton transfer salts (H2Etpip)[Cu(Hssa)2]·5H2O, (H2HOEtpip)[Cu(Hssa)2]·5H2O and (H2Acpip)[Cu(Hssa)2]·5H2O) have been synthesized. The structures of proton transfer salts have been proposed by using FT-IR, 1H and 13C NMR spectroscopy, and elemental analysis. The structures of the amorphous metal complexes have been proposed by atomic absorption spectrometry, FT-IR, magnetic susceptibility, molar conductivity techniques, and elemental analysis. Antimicrobial activities of compounds have been tested against Staphylococcus aureus (ATCC 29213) (Gram-positive), Escherichia coli (ATCC 25922) (Gram-negative), Candida krusei (ATCC 6258) (yeast), and Candida parapsilosis (ATCC 22019) (yeast) microorganisms. For S. aureus, the minimum inhibitory concentration (MIC) values of the synthesized salts were between 31.25 and 62.50 µg/ml, and 15.60 µg/ml for complexes. The MIC values of salts and complexes for E. coli were in the range 125.00–500.00 µg/ml and 31.25–62.50 µg/ml, respectively. The MIC values of the salts for C. krusei were 62.50 µg/ml, and for the complexes in the range 15.60–31.25 µg/ml. For C. parapsilosis, these values were 31.25 µg/ml for all salts and in the range 15.60–62.50 µg/ml for complexes.


O. M. Yaghi, C. E. Davis, G. Li, H. Li. Selective guest binding by tailored channels in a 3-D porous zinc (II) benzene tricarboxylate network. J. Am. Chem. Soc. 119, 2861–2868 (1997). DOI: 10.1021/ja9639473.

C. Swiegers, T. Malefetse, New self-assembled structural motifs in coordination chemistry. Chem. Rev. 100, 3483–3538 (2000). DOI: 10.1021/cr990110s.

A. Cote, G. K. H. Shimizu, The supramolecular chemistry of the sulfonate group in extended solids. Coor. Chem. Rev. 245, 49–64 (2003).

DOI: 10.1016/S0010-8545(03)00033-X.

J.F. Song, Y. Chen, Z.G. Li, R.S. Zhou, X.Y. Xu, J. Q. Xu, T.G. Wang, Syntheses, supramolecular structures and properties of six coordination complexes based on 5-sulfosalicylic acid and bipyridyl-like chelates. Polyhedron 26, 4397–4410 (2007).

DOI: 10.1016/j.poly.2007.05.037.

A. Marzotto, D. A. Clemente, T. Gerola, G. Valle, Syn-thesis, molecular structure and reactivity of sodium 5-sulfosalicylate dihydrate and sodium [triaqua (5-sulfosalicylato) copper (II)] 2 hemihydrate. Polyhedron 20, 1079–1087 (2001).

DOI: 10.1016/S0277-5387(01)00765-3.

Z. G. Aliev, L. O. Atovmyan, Crystal structure of sodium sulfosalicylate dihydrate NaC7H5O6S.2H2O. J. Struct. Chem. 42, 506–508 (2001).

Y. Li, L. Deng, X. Zhou, S. Zhang, Q. Yang, The crystal structure and the second harmonic generation efficiency of the sulfosalicylate. Acta Phys.-Chim. Sin. 14, 778–783 (1998). DOI: 10.3866/PKU.WHXB19980903.

M. Hu, C. Geng, S. Li, Y. Du, Y. Jiang, L. Zhihong, Syntheses and crystal structures of three cesium salts: ce-sium 5-sulfosalicylate, cesium 3,5-dinitrosalicylate and cesium 2, 4-dinitrophenoxide monohydrate. J. Organ-omet. Chem. 690, 3118–3124 (2005).

DOI: 10.1016/j.jorganchem.2005.04.001.

S. Gao, L. H. Huo, Z. B. Zhu, J. R. Li, Catena-Poly[[[tetraaqua (3-carboxy-4-hydroxy-benzenesulfonato) strontium (II)]-μ3-3-carboxy-4-hydroxybenzenesulfonato] dihydrate]. Acta Cryst. E61, m417–m419 (2005).

DOI: 10.1107/S1600536805002801.

J. F. Ma, J. Yang, L. Li, G. L. Zheng, J. F. Liu, The first ladder structure containing three different squares: the structure of barium 3-carboxy-4-hydroxybenzenesulfonate. Inorg. Chem. Commun. 6, 581–583 (2003).

DOI: 10.1016/S1387-7003(03)00044-3.

Z. G. Aliev, L. O. Atovmyan, T. A. Baranova, S. B. Pirkes, Crystalline-structure of La(C6H3OHCOOHSO3)3.9H2O lanthanum, Russ. J. Coor. Chem. 17, 1282 (1991).

A. Rohde, W. Urland, Octaaquaytterbium(III) tris(3-carboxy-4-hydroxy-benzenesulfonate) monohydrate. Acta Cryst. E62, m1210–m1212 (2006).

DOI: 10.1107/S1600536806015583.

Z. G. Aliev, T. A. Baranova, L. O. Atovmyan, S. B. Pirkes, Synthesis, structure and properties of samarium sulfosalicilate SmH(C6H3OHCOOSO3)2ˑ6H2O. Russ. J. Coor. Chem. 20, 150–152 (1994).

X. Q. Wang, J. Zhang, Z. J. Li, Y. H. Wen, J. K. Cheng, Y. G. Yao, Poly[aquaneodymium(III)-μ5-2-oxido-5-sulfonatobenzoato]. Acta Cryst. C60, 657–658 (2004). DOI: 10.1107/S0108270104022280.

H. Y. Sun, C. H. Huang, X. H. Jin, G. X. Xu, The syn-thesis, crystal structure and synergistic fluorescence effect of a heteronuclear lanthanide complex (HLC){Na3TbLa2(C7H3SO6)4.26H2O}n. Polyhedron 14, 1201–1206 (1995).

DOI: 10.1016/0277-5387(94)00378-R.

H. Y. Sun, C. H. Huang, L. B. Gan, G. X. Xu, Z. S. Ma, N. C. Shi, The synthesis and crystal structure of hetero-nuclear complex of lanthanide with sulfo-salicylic acid [Na3YLa2(C7H3SO6)4·26H2O]n. Chin. J. Chem. 13, 150–155 (1995). DOI: 10.1002/cjoc.19950130209.

S. R. Fan, L. G. Zhu, H. P. Xiao, S. W. Ng, cis-Diaquabis (1,10-phenanthroline) manganese (II) 3-carboxylato-4-hydroxybenzenesulfonate tetrahydrate, Ac-ta Cryst. E61, m563–m565 (2005).

DOI: 10.1107/S1600536805004927/ww6357Isup2.hkl.

W. G. Wang, J. Zhang, L. J. Song, J. F. Ju, Ferromagnet-ic linear trinuclear copper(II) complex bridged by sulfosa-licylate ligand. Inorg. Chem. Commun. 7, 858–860 (2004). DOI: 10.1016/j.inoche.2004.05.006.

S. R. Fan, L. G. Zhu, Influence of the reaction conditions on the self-assembly of lead(II) 5-sulfosalicylate coordi-nation polymers with chelating amine ligands. Inorg. Chem. 45, 7935–7942 (2006).

DOI: 10.1021/ic060871v.

P. Starynowicz, Synthesis and crystal structure of europi-um(II) dihydrogen bis(sulfosalicylate) pentahydrate [Eu(C7H5O6S)2(H2O)5]∞. J. Alloys Comp. 305, 117–120 (2000). DOI: 10.1016/S0925-8388(00)00749-0.

P. V. Khadikar, S. Joshi, S. G. Kashkhedikar, B. D. Heda, Metal-complexes of 5-sulfosalicylic acid and their antimicrobial activity. Indian J. Pharm. Sci. 46, 209–215 (1984).

P. V. Khadikar, S. M. Ali, B. Pol, B. D. Heda, Effect of metal ions on the antimicrobial activity of 5-sulphosalicylic acid. Acta Microbio. Immun. Hung. 33, 97–102 (1986).

C. Yenikaya, N. Büyükkıdan, M. Sarı, R. Keşli, H. İlki-men, O. Büyükgüngör, Synthesis, characterization, and biological evaluation of Cu(II) complexes with the proton transfer salt of 2,6-pyridinedicarboxylic acid and 2-amino-4-methylpyridine. J. Coord. Chem. 64, 3353–3365 (2011).

M. Agotegaray, F. Gumilar, M. Boeris, R. Toso, A. Mi-netti, Enhanced analgesic properties and reduced ulcer-ogenic effect of a mononuclear copper(II) complex with fenoprofen in comparison to the parent drug: Promising insights in the treatment of chronic inflammatory diseases. BioMed. Res. Inter. 2014, 1–9 (2014).

DOI: 10.1155/2014/505987.

H. İlkimen, C. Yenikaya, A. Gülbandılar, M. Sarı, Syn-thesis and characterization of a novel proton salt of 2-amino-6-nitrobenzothiazole with 2,6-pyridinedicarboxylic acid and its metal complexes and their antimicrobial and antifungal activity studies. J. Mol. Struct. 1120, 25–33 (2016). DOI: 10.1016/j.molstruc.2016.04.068.

E. Soleimani, Synthesis, characterization and anti-microbial activity of a novel macrocyclic ligand derived from the reaction of 2,6-pyridinedicarboxylic acid with homopiperazine and its Co(II), Ni(II), Cu(II), and Zn(II) complexes. J. Mol. Struct. 995, 1–8 (2011).

DOI: 10.1016/j.molstruc.2011.01.002.

S. R. Fan, L. G. Zhu, Structural diversity and fluorescent properties of copper(II) complexes constructed by 5-sulfosalicylate and 2,2’-bipyridine. J. Mol. Struct. 827, 188–194 (2007). DOI: 10.1016/j.molstruc.2006.05.019.

H. İlkimen, Y. Tekşen, C. Yenikaya, İ. Turhan, T. Tunç. M. Sarı, Synthesis, characterization and pharmacological evaluation of the proton transfer salts of 2-aminobenzothiazole derivatives with 5-sulfosalicylic acid and their Cu(II) complexes. J. Coord. Chem. 71, 2831–2842 (2018).

DOI: 10.1080/00958972.2018.1504035.

M. Ghadermazi, J. Soleimannejad, S. Sheshmani, M. Shamsipur, M. Ghanbari, M. R. Eslami, Characterization, crystal structures and solution studies of Zn(II), Cd(II) and Mg(II) complexes obtained from a proton transfer compound including pyridine-2-carboxylic acid and pi-perazine. J. Iran. Chem. Soc. 9, 579–589 (2012). DOI: 10.1007/s13738-012-0071-x.

H. Aghabozorg, S. Daneshvar, E. Motyeian, F. Man-teghi, R. Khadivi, M. Ghadermazi, A. Shokrollahi, M. Ghaedi, S. Derki, M. Shamsipur, Synthesis and crystal structure of Mn(II) and Hg(II) compounds and solution studies of Mn(II), Zn(II), Cd(II) and Hg(II) compounds based on piperazinedium pyridine-2,3-dicarboxylate. J. Iran. Chem. Soc. 6, 620–637 (2009).

H. Aghabozorg, F. Manteghi, S. Sheshmani, A brief review on structural concepts of novel supramolecular proton transfer compounds and their metal complexes. J. Iran. Chem. Soc. 5,184–227 (2008).

N. Büyükkıdan, C. Yenikaya, H. İlkimen, C. Karahan, C. Darcan, E. Şahin, Synthesis, characterization and antimi-crobial activity of a novel proton salt and its Cu(II) com-plex. Russian J. Coord. Chem. 39, 96–103 (2013). DOI: 10.1134/S1070328412100028

K. Singh, H. H. Siddiqui, P. Shakya, P. Bagga, A. Ku-mar, M. Khalid, M. Arif, S. Alok, Piperazine – a biologi-cally active scaffold. Inter. J. Pharm. Sci. Res. 6, 4145–58 (2015).

DOI: 10.13040/IJPSR.0975-8232.6(10).4145-58.

W. CunicoI, C. R. B. GomesI, W. T. A. Harrison, M. Moreth, J. L. Wardell, S. M. S. V. WardellI, Structure of (2R,3S)-4-(aryl methyl)-1-(4-phenyl-3-amino-2-hydroxy butyl) piperazine, potential anti malarial agents. Z. Kristal-logr. 224, 461–470 (2009).

DOI: 10.1524/zkri.2009.1161.

M. Kimura, T. Masuda, K. Yamada, N. Kawakatsu, Anti-oxidative activities of novel diphenylalkyl piperazine de-rivatives with high affinities for the dopamine transporter. Bioorg. Med. Chem. Let. 14, 4287–4290 (2004). DOI: 10.1016/j.bmcl.2004.05.091.

V. Cecchetti, F. Schiaffella, 1,4-Benzothiazinyloxy al-kylpiperazine derivatives as potential antihypertensive agents. Bioorg. Med. Chem. Let. 10, 465–468 (2000). DOI: 10.1016/S0960-894X(00)00016-0.

H. T. Varghese, C. Y. Panicker, D. Philip, IR, Raman and SERS spectra of 5-sulphosalicylic acid dihydrate. J. Raman Spect. 38, 309–315 (2007).

DOI: 10.1002/jrs.1644.

R. Bhuvaneswari, K. S. Murugesan, Synthesis, growth, structural, dielectric, thermal, linear and nonlinear proper-ties of 8-hydroxyquinolinium 3-carboxy-4-hydroxy ben-zene sulfonate monohydrate single crystal. Opt. Mat. 98, 109431 (2019). DOI: 10.1016/j.optmat.2019.109431.

H. Aghabozorg, F. Mahfoozi, M. A. Sharif, A. Shokrollahi, S. Derkid, M. Shamsipur, H. R. Khavasi, A proton transfer self-associated compound from benzene-1,2,4,5-tetracarboxylic acid and piperazine and its co-balt(II) complex: Syntheses, crystal structures and solu-tion studies. J. Iran. Chem. Soc. 7, 727–739 (2010).

H. Aghabozorg, F. Manteghi, M. Ghadermazi, M. Mir-zaei, A. R. Salimi, H. Eshtiagh-Hosseini, Synthesis, X-ray characterization and molecular structure of a novel su-pramolecular compound of antimony(III): Theoretical ın-vestigation on molecular and electronic properties based on the ab initio HF and various DFT methods. J. Iran. Chem. Soc. 7, 500–509 (2010).

M. S. Nothenberg, A. R. Souza, J. R. Matos, Synthesis and physicochemical characterization of rhodium sulfosa-licylate. Polyhedron 19, 1305–1309 (2000).

DOI: 10.1016/S0277-5387(00)00394-6.

M. S. Gruzdev, L. E. Shmukler, N. O. Kudryakova, A. M. Kolker, Y. A. Sergeeva, L. P. Safonova, Triethanola-mine-based protic ionic liquids with various sulfonic ac-ids: Synthesis and properties. J. Mol. Liq. 242, 838–844 (2017). DOI: 10.1016/j.molliq.2017.07.078.

Y. Zhang, J. R. Price, I. Karatchevtseva, Y. K. L. Bongho, F Kadi, R. l. Gregory, L. Feng, Comparison of uranium(VI) and thorium(IV) coordination polymers with p-toluenesulfonic acid. Polyhedron 91, 98–103 (2015). DOI: 10.1016/j.poly.2015.03.002.

A. Golcu, M. Tumer, H. Demirelli, R. A. Wheatley, Cd(II) and Cu(II) complexes of polydentate Schiff base ligands: synthesis, characterization, properties and biolog-ical activity. Inorg. Chim. Acta 358, 1785–1797 (2005). DOI: 10.1016/j.ica.2004.11.026.1785.

H. İlkimen, N. Türken, A. Gülbandılar. Synthesis, char-acterization, antimicrobial and antifungal activity studies of two novel aminopyridine-sulfamoylbenzoic acid salts and their Cu(II) complexes. J. Iran. Chem. Soc. 18, 1941–1946 (2021). DOI: 10.1007/s13738-021-02157-4.

W. J. Geary, The use of conductivity measurements in organic solvents for the characterisation of coordination compounds. Coor. Chem. Rev. 7, 81–122 (1971).

DOI: 10.1016/S0010-8545(00)80009-0.

P. V. Khadikar, S. Joshi, S. G. Kashkhedikar, B. D. Heda, Metal-complexes of 5-sulfosalicylic acid and their antimicrobial activity. Indian J. Pharm. Sci. 46, 209–211 (1984).

B. D. Heda, P. V. Khadikar, S. G. Kaskedikar, Antifun-gal and antibacterial activities of cobalt II chelates of sali-cylic and substituted salicylic acids. Indian J. Pharm. Sci. 42, 174–175 (1980).

G. D. Bajju, G. Devi, S. Katoch, M. Bhagat, D. Ashu, S. Kundan, A. K. Sunil, Synthesis, spectroscopic and bio-logical studies on new zirconium(IV) porphyrins with ax-ial ligand. Bioinorg. Chem. Appl. 903616, (2013). DOI: 10.1155/2013/903616




How to Cite

Büyükkıdan, N., ilkimen, H., Durmuş, B., & Gülbandılar, A. (2021). Synthesis and characterization of Cu(II) complexes of proton transfer salts derived from piperazine derivatives and 5-sulfosalicylic acid. Macedonian Journal of Chemistry and Chemical Engineering, 40(2), 159–169.



Inorganic Chemistry