Acta Chim. Slov. 2005, 52, 317–322 317 Scientific Paper Potentiometric and Theoretical Studies of Stability Constants of Glyoxime Derivatives and their Nickel, Copper, Cobalt and Zine Complexes Hayati Sari,a* Muzaffer Can,a and Mustafa Macitb 1 Gaziosmanpaşa University, Faculty of Art and Sciences, Department of Chemistry, 60250, Tokat, Turkey. E-mail: hsari@gop.edu.tr b Ondokuzmayis University, Department of Chemistry, 55139 Samsun, Turkey Received 11-02-2005 Abstract The dissociation constants of l,2-bis(4-methylpiperazine)glyoxime (BMPGH2) and l,2-bis(4-benzylpiperazine)gly oxime (BBPGH2) were determined in 0.1 mol dnr3 NaCl and 0.001 mol dnr3 HC1 at 25 °C potentiometricalh/. pKa values of BMPGH2 and BBPGH2 were obtained as 2.91, 6.79, 7.97, 10.00 and 3.46, 5.89, 6.77, 9.76, respeetiveh/. The protonation order of nitrogen atoms in the BMPGH2 and BBPGH2 were determined using Semi-empirical AM1 method. In various pH conditions, the different complexes formulated as MH6T2, MH5T2, MH4L2, MH3T2, MH2T2, MHT2, MT2, MH^Lj, and MH_2T2 were formed with titration of ligand and Cu, Co, Ni and Zn ions. Key words: l,2-bis(4’-methylpiperazine)glyoxime, l,2-bis(4’-benzylpiperazine)glyoxime, dissociation constant, stability constants, SUPEROUAD, AM1 method Introduction Recently, the high stability of the complexes prepared with v/odioxime ligands have been extensively used for various purposes including model compounds for vitamin B12 analytical and medicinal chemistry, pigments.1'2 Schrauzer has found that this kind of complexes exhibits semiconduetor property.3 An investigation4 has been done about spectrometric and potentiometric characterizations of these kinds of compounds and stability constants with divalent metal ions. Stability constants of metals complexes have been determined by many different methods sueh as spectroscopy5 and potentiometry.4 It is well-known that the simplest electroanalytical technique for determination of stability constants is potentiometric titration system used for the glass electrode. SUPERQUAD,6 a powerful computer program, was used in the evaluation of data obtained from this technique. In the literature, the synthesis of v/odioximes and their various derivatives have been a subject of study for a long period of time.7 In these studies, it is reported that v/odioximes have three isomers, syn-, anti-, and amphi- forms, depending on the position of -OH groups in molecule.79 In the present work, we investigated the dissociation constants of l,2-bis(4-methylpiperazinegl yoxime), (BMPGH2) and l,2-bis(4-benzylpierazinegly oxime); (BBPGH2) and the stability constants of their complexes with Ni, Cu, Co and Zn potentiometricalh/ and theoretically (AM1 method). Results and Discussion Dissociation Constants The structures of BMPGH2 and BBPGH2 compounds are given in Scheme 1a and 1b. Potentiometric titrations of these compounds with NaOH were performed in 0.1 mol dm–3 NaCl at 25 °C. The titration curves of the ligands are given in Figure 1. Four pKa values for each protonated ligand have been calculated by SUPERQUAD using titration data (Table 1). pKa values of the ligands are expected to be similar to each other because of having similar chemical structures, except for benzyl and methyl groups. But, there is a small difference among pKa values because of different inductive properties of benzyl and methyl groups. Four protonated species formulated as LH4, LH3, LH2 and LH were observed during titration processes. The species distribution curves of BMPGH2 and BBPGH2 are shown in Figure 2a and 2b. All species have broad protonation space between pH 2–10 except for LH2. When pH increases, the protonated ligands lose the protons and convert to the other forms as seen in Figure 2. The concentration levels of LH4, LH3, LH and L form above 90%, while LH2 is 50%. The free ligand (L) starts to form at pH 8 and reaches its maximum at pH 11 (90–95%). Sari et al. Stability Constants of Glyoxime Derivatives 318 Acta Chim. Slov. 2005, 52, 317–322 1/ CH3—N \ 2 3 N—C=N—OH \ / 1/ CH2—N \ 2 3 N—C=N—OH HO—N=C—N N—CH3 4 5\-----/6 HO—N=C—N N—CH2 4 5\-----/6 / \ a b 1,2-Bis(4-methylpiperazine)glyoxime (BMPGH2) 1,2-Bis(4-benzylpiperazine)glyoxime (BBPGH2) Sheme 1 Table 1. Dissociation constants (pKa) of the ligands studied at 25 °C in aqueous NaCl (I = 0.100 mol dm–3). Figure 1. Potentiometric titration curve of the ligands. 80- \H* / lh/ \ L/ 60- 40- LEif\ LH,/^ 20-n- 10 pH (a) Ligand BMPGH2 BBPGH2 Species (b) pKa Values LH4 2.91±0.06 LH3 6.79±0.06 LH2 7.97 ±0.06 LH 10.00±0.04 LH4 3.46±0.03 LH3 5.89±0.01 LH2 6.77±0.01 LH 9.76±0.01 Figure 2. Distribution curves of a) BMPGH2 and b) BBPGH2. There are six nitrogens and two hydroxyl groups in the BBPGH2 and the BMPGH2 as seen in Scheme 1. The pKa values of BMPGH2 (2.91, 6.79, 7.97 and 10.00) and BBPGH2 (3.46, 5.89, 6.77 and 9.76) belong to the nitrogen atoms in the ligands. However, there is no information about pKa values for hydroxide groups of glyoximes.10~14 Theoretical Calculation The determination of the protonation order of these compounds is not possible with experimental methods such as NMR, IR, and UV. So, in this study, theoretical calculations were done to determine Table 2. The calculated Hf and TE values with AM1 method for BBPGH2 and BMPGH2 (their monoprotonated forms). BMPGH2 BBPGH2 Total Energy Hf Total Energy Hf (kcal/mol) (kcal/mol) 1N-H -86549.22 190.41 -124512.08 230.13 2N-H -86546.02 193.61 -124489.75 253.45 3N-H -86553.30 186.32 -124486.09 257.11 protonation order of nitrogen atoms in the ligands. The formation heats (Hf) and the total energies (TE) of various protonated species of ligands were calculated by Semi-Empirical AM1 method and given in Table 2. Sari et al. Stability Constants of Glyoxime Derivatives Acta Chim. Slov. 2005, 52, 317–322 319 Table 3. The calculated Hf and TE values with AM1 method for BMPGH2 and BBPGH2; a) diprotonated forms, b) tri protonated forms and c) four protonated forms. BMPGH2 BBPGH2 T.E. (kcal/mol) Hf TE (kcal/mol) Hf a) 3N-1N -86640.87 413.67 1N-2N -124579.55 478.56 3N-2N -86590.83 463.70 1N-3N -124595.94 462.17 3N-4N -86631.59 422.94 1N-4N -124619.29 438.82 3N-5N -86638.75 415.79 1N-5N -124618.25 439.86 3N-6N -86661.84 392.69 1N-6N -124632.91 425.20 b) 3N-6N-1N -86709.61 659.83 1N-6N-2N -124659.37 713.65 3N-6N-2N -86647.26 722.18 1N-6N-3N -124677.35 695.66 3N-6N-4N -86664.72 704.72 1N-6N-4N -124676.42 696.59 3N-6N-5N -86660.37 709.08 1N-6N-5N -124669.36 703.65 c) 3N-6N-1N-2N -86612.42 1071.92 1N-6N-3N-2N -124591.41 1096.51 3N-6N-1N-4N -86649.00 1035.34 1N-6N-3N-4N -124625.04 1062.88 3N-6N-1N-5N -86657.23 1027.12 1N-6N-3N-5N -124629.24 1058.68 According to the calculated H( and TE values, the first protonation of BMPGH2 and BBPGH2 are on 3N and IN, respectively. It was also determined the protonation orders for the second, third and fourth protonation with H( and TE values as shown in Table 3. According to the calculated results, the protonation orders of nitrogen atoms are 3N, 6N, IN and 5N for BMPGH21N and IN, 6N, 3N and 5N for BBPGH2. There are differences in these orders due to different inductive effects of benzvl and methvl groups in the ligands. In conclusion, according to the data obtained from the theoretical calculations, it can be proposed that the pKa values, 2.91 (LH4), 6.79 (LH3), 7.97 (LH2) and 10.00 (LH) belong to 3N, 6N, IN and 5N in BMPGH2, respectiveh/. Similarh/, 3.46 (LH4), 5.89 (LH3), 6.77 (LH2) and 9.76 (LH) belong to IN, 6N, 3N and 5N in BBPGH2, respectiveh/. Stability Constants of Metal Complexes The complex solutions were titrated with standard NaOH solution to determine the stabilitv constants of complexes formed by divalent metal ions (M) and the ligands (L). The titration curves are given in Figure 3a and 3b. There are two end points in the titration curves. Although the experimental conditions are similar, their end points are different from each other because of the various degree of hydrolysis of the metal ions. When the hydrolysis degree of M is increased, the end point of the complex system shifts to right.4 The interactions of M with L (1:2) lead to form ML2 type complexes. The same ratio was found betvveen M and similar ligands in literature.4'10'14'15 The data obtained from M-BMPGH2 and BBPGH2 titrations have been evaluated using SUPERQUAD program and the species distribution curves obtained from calculations are given in Figure 4a-4h. Various complexes formulated as MH6L2, MH5L2, MH4L2, MH3L2, MH2L2, MHL2 MH jL2, and MH 2L2 betvveen the ligands and the metal ions are formed depending on pH. In M-BMPGH2 system, the main complexes for Ni, Cu, Co and Zn are NiH5L2, CuH6L2 (and CuH2L2), CoH7L2 (and CoH2L2) and ZnH5L2 (and ZnL2) respectively. Their concentration ranges are about 90% except for ZnH5L2. Although Co, Zn, and Cu complexes are formed after pH 5, Ni complexes are formed after pH 2. The other intermediate complexes such as MH3L2, MH2L2 and MHL2 have also been observed due to smaller titrant additions (0.03-0.04 mL) in the titrations. Intermediate complexes NiH3L2, CuH3L2 and CoHL2 are at the lowest level (15-20%) betvveen pH 6-9. After pH 8, hydroxide group bound to M ions. Therefore, M(OH)L2 and M(OH)2L2 complexes formed, as seen in Figure 4. By increasing pH level, one nitrogen is protonated each time and the functional group bound the corresponding metal ions. The protonated mononuclear complexes undergo simple deprotonation reactions at high pH values. In M-BBPGH2 system, the main complexes were NiH3L2, CuH5L2 (and CuL2), CoH6L2 and ZnH6L2 (and ZnL2). Their concentration levels were above 80%. The other properties of complex species were similar to M-BMPGH2. However, only Cu complexes exist betvveen pH 3-5 in Cu-BBPGH2. After obtaining the dissociation constants for BMPGH2 and BBPGH2, overall stability constants have been calculated at the same way. The log/3 values obtained from these calculations for ali M-ligand complexes are given in Table 4. The stability constants of the complexes (ML2) decrease in the orders of Zn>Ni>Cu>Co for M-BMPGH2 system and Cu>Ni>Zn>Co for M-BBPGH2 system. Stability constants of M-BMPGH2 are higher than those of M-BMPGH2. A comparison of stability constants Sari et al. Stability Constants of Glyoxime Derivatives 320 Acta Chim. Slov. 2005, 52, 317–322 Table 4. Stability constant data for the complexation of Cu, Ni, Co and Zn with BMPGH2 and BBPGH2 at 25 °C (I = 0.100 mol dnf3) fi = [MLHJ/[M]'[l]'[H]'. Complex Ppqr Ni Cu Co in aqueous NaCl Zn M-BMPGH2 102 19.42±0.03 19.21±0.02 19.17±0.02 22.81±0.03 112 28.77 ±0.02 29.28±0.03 28.16±0.05 31.90 ±0.02 122 37.47 ±0.06 38.73 ±0.02 38.17±0.02 - 132 44.84 ±0.07 45.85±0.05 46.31±0.01 48.92±0.02 142 52.48 ±0.08 53.40±0.02 54.01±0.01 56.57±0.02 152 58.11 ±0.07 60.32 ±0.02 61.05±0.02 64.04±0.02 162 60.85 ±0.07 66.28 ±0.02 68.23±0.01 70.13±0.03 172 - - 74.07±0.02 73.13±0.02 1-22 0.37±0.01 -2.08 ±0.01 -1.53±0.03 2.18±0.03 M-BBPGH2 102 18.41±0.03 18.82±0.03 14.47±0.03 17.07±0.04 112 - 26.18±0.05 - 24.48 ±0.01 122 36.30 ±0.06 - 32.77±0.06 32.65±0.03 132 45.42 ±0.03 39.71±0.04 41.37±0.01 48.60±0.04 142 52.63 ±0.06 46.49±0.05 48.14±0.03 - 152 58.87 ±0.05 52.21 ±0.05 54.44±0.05 55.64±0.03 162 64.45 ±0.07 55.72 ±0.07 59.51±0.06 61.50±0.04 172 67.78 ±0.03 - - 65.16±0.05 1-12 8.73±0.02 9.42 ±0.03 3.99±0.04 7.66±0.04 1-22 -0.66±0.01 -0.88 ±0.02 -5.41±0.02 -2.56±0.03 * p: number of metal, q: number of hydrogens (positive values) or hydroxides (negative values) r: number of ligands in the complex. mL NaOH mL NaOH (a) M-BBPGH (b) M-BBPGH Figure 3. Titration curves for a) M-BBPGH2 and b) M-BMPGH2. of the Ni complexes with these two ligands (log/3[Ni-(BMPGH2)2] = 19.42, log/3 [Ni-(BBPGH)2] = 18.41) indicates that the imino groups (=N-OH) in the ligand plays an important role on the stability of mononuclear complex formation. Conclusions The dissociation constant values (pKa) were determined as 2.91, 6.79, 7.97 and 10.00 for BMPGH2 and 3.46, 5.89, 6.77 and 9.76 for BBPGH2 in acidic medium, respectivelv. The protonation order of nitrogen atoms in the BMPGH2 and BBPGH2 were determined using Semi-empirical AM1 method. The stabilitv constants of the various complexes from MH6L2 to MH 2L2 were calculated using SUPERQUAD. The relatively more stable complexes were formed between M and BMPGH2 in the bases of ML2 species. Experimental Reagents Ali reagents were of analytical quality and were used without further purification. BBMGH2 and BMPGH2 were synthesised and characterized according to Macit et al.16 Sodium hydroxide (Merck), potassium hydrogen phthalate (Fluka), were dried at 110 °C before use. HC1, CuCl2, ZnCl2, CoCl2.6H20 and NiCl2.6H20 were purchased from Merck. For the solutions, C02-free deionized water was obtained with an aquaMAX™-[/&ra water purification system (Young Lin Inst.). Its resistivity was 18.2 MQcm4. Sari et al. Stability Constants of Glyoxime Derivatives Acta Chim. Slov. 2005, 52, 317–322 321 a) c) e) 23456789 pH 9 10 11 PH g) pH 60 pH b) Ni-BBPGH2 \NiHjLj NiHJ, / \ NiHjV /C \ NiLj / /NiHjLj \/ NiHjLj^-X / pH d) 6 7 8 9 pH f) NCoH^ \ A C0H3U/ / / \ CoH.1/ \ / \ °*w \ /V \ CoH^ 7 V A \ CqH2L-/ CoL, / A/ \/\ \Al 4 5 6 7 h) 8 9 PH 8 9 pH Figure 4. Species distribution curves for the following systems: a) Ni-BMPGH2, b) Ni-BBPGH2, c) Cu-BMPGH2, d) Cu-BBPGH2, e) Co-BMPGH2, f) Co-BBPGH2, g) Zn-BMPGH2 and h) Zn-BBPGH. Procedure First, the ligands were dissolved in ethyl alcohol and then the solutions obtained were diluted with deionized water. The final concentration of the ligands was 2.10~3 mol dirr3 and their final water-ethyl alcohol ratio (v/v) was 96:4. Stock 0.025 mol dirr3 sodium hydroxide and 0.1 mol dirr3 hvdrochloric acid solutions were prepared. Solutions of 0.001 mol dirr3 metals ions have been prepared from CuCl2, ZnCl2, CoCl2.6H20 and NiCl2.6H20. The ionic strength was adjusted at 0.1 mol dirf3 with sodium chloride. The potentiometric titrations were performed using Molspin pH meter™ with a Sentix 20 pH combination electrode (WTW, Weilheim). Temperature was controlled by a thermostat (DIGITERM 100, SELECTA) at 25.0 + 0.1 °C. The titration vessel is double-wall glass and placed on the magnetic stirrer. It was cleaned with distilled 100 100 80 80 60 60 40 40 20 20 0 0 10 5 6 7 8 9 0 100 00 80 80 60 60 40 40 20 20 0 0 4 5 0 11 6 7 8 12 100 100 CoBBPGH2 80 80 60 60 40 40 20 20 0 0 3 10 11 6 7 8 9 10 11 100 100 80 80 60 40 40 20 20 0 0 4 5 6 7 10 11 6 7 8 9 0 1 Sari et al. Stability Constants of Glyoxime Derivatives 322 Acta Chim. Slov. 2005, 52, 317–322 Table 5. Summary of the experimental parameters for the potentiometric stability constants measurements. System BBPGH2 and BMPGH2 with H, Cu, Ni, Co, and Zn in water Solution composition [L] range/mol dm–3 0.001–0.002 [M] range/mol dm–3 0.001 ionic strength/mol dm–3 0.1 electrolyte NaCl Experimental Method Potentiometric titration in range pH 3–11 logß00–1 –13.98 T/°C 25.0 nt„ta n,„b 250 3 Method of calculation SUPERQUAD Titration system MOLSPIN " Number of titration points per titration. b Number of titrations per metal-ligand system. M: Metal ion, L: ligand, /i: overall stability constant. water and dried with a tissue before and after each titration. The vessel was kept closed by the lid, which contained three holes for the electrode, glass tubing for nitrogen purging and plastic tubing for alkali from the burette. The electrode was calibrated according to the instructions in the Molspin manual.17 Air bubble was not allowed to syringe while filling with alkali solution. Before filling with solution, the syringe was washed several times with distilled water, and rinsed at least three times with the alkali. Titration was performed in triplicate, and the SUPERQUAD computer program6 was used for calculation of protonation and stability constants. Summary of the experimental parameters for the potentiometric measurements were given in Table 5. Standard deviations quoted refer to random errors only. The pH data (250) were obtained after addition of 0.03 cm3 increments of standardized NaOH solution. The pKw values for the aqueous system at the ionic strength employed, defined as -log [H+][OH ], was obtained as 13.98. The theoretical calculations were performed by Semi-empirical(AMl) method.18~22 Acknowledgement The authors thank Research Fund of Gaziosmanpasa University for financial support. References 1. G. N. Schrauser, J. Kohnie, Chem. Ber. 1964, 97, 3056-3059. 2. S. Kuse, S. Motomizu, K. Toei, Anal. Chim. Acta 1974, 70, 65-76. 3. G. N. Schrauser, J. Windgassen,/. Am. Chem. Soc. 1967, 89, 143-147. 4. M. Can, H. Sari, M. Macit, ^4cto Chim. Slov. 2003, 50, 1-14. 5. K. Takacs-Novak, K. Y. Tam, Anal. Chim. Acta 2001, 434, 157-167. 6. G. Gans, A. Sabatini, A. Vacca, /. Chem. Soc, Dalton Trans. 1985, 1195-1200. 7. S. B. Pedersen, E. Larsen, Acta Chem. Scand. 1973, 27, 3291-3301. 8. Ö. Bekaroglu, S. Sanbasan, A. R. Koray, B. Nuber, K. Weidenhammer, J. Welss, M. L. Ziegler,^4cto. Cryst. 1978, B34, 3591-3593. 9. S. Sanbasan, Ö. Bekaroglu, H. Wyden, Thermochim. Acta 1978, 25, 349-356. 10. Y. Aydogdu, F. Yakuphanoglu, A. Aydogdu, E. Fas, A. Cukurovali, Solid State Sci. 2002, 4, 879-883. 11. E. Farkas, H. Csoka, S. Gama, M. A. Santos, Talanta 2002, 57, 935-943. 12. V. Bochkova, V. Peshkova, Zhur. Neorg. Khim. 1958, 3, 1132-1134. 13. G. C. S. Manku, Z. Anorg. Allg. Chem. 1971, 382, 202-208. 14. U. Dincer, F. Ercan, M. Macit, A. Gulce,^4cto. Cryst. 1996, C52, 2680-2682. 15. E. Ozcan, E. Karapmar, B. Demirtas, Transit. Metal Chem. 2002, 27, 557-561. 16. M. Macit, H. Bati, B. Bati, Synth. React. Inorg. Met-Org. Chem. 1998, 28, 833-841. 17. F. D. Pettit, “Molspin Softvvare for Molspin pH Meter”, Sourby Farm, Fimble, Otley, FS21 2PW, UK. 1992. 18. M. J. S. Dewar, E. G. Zoebisch, E. F. Healy, J. J. P. Stevvart, /. Am. Chem. Soc. 1985, 107, 3902-3909. 19. M. J. S. Dewar, K. M. Dieter, /. Am. Chem. Soc. 1986, 108, 8075-8086. 20. J. J. P. Stevvart, /. Comp. Aided Mol. Design 1990, 4, 1-105. 21. F. Nyulaszi, P. Varnai, F. Veszpremi, /. Mol. Struct. (Theochem) 1995, 358, 55-61. 22. G. A. Ibanez, A. C. Olivieri, G. M. Escandar, /. Chem. Soc, Faraday Trans. 1997, 93, 545-551. Povzetek Potenciometrično smo določili konstante disociacije 1,2-bis(4-methilpiperazin)glyoxima (BMPGH2) in 1,2-bis(4-benzilpiperazin)glyoxima (BBPGH2) v 0.1 mol dm–3 NaCl in v 0.1 mol dm–3 HCl pri 25 °C. Dobljene vrednosti pKa BMPGH2 in BBPGH2 so 2.91, 6.79, 7.97, 10.00 in 3.46, 5.89, 6.77, 9.76. S semiempirično AM1 metodo smo določili vrstni red protonacije dušikovih atomov v BMPGH2 in v BBPGH2. Ob titraciji liganda z Cu, Co, in Zn ioni pri različnih vrednostih pH v raztopini obstajajo različni kompleksi: MH6L2, MH5L2, MH4L2, MH3L2, MH2L2, MHL2, ML2, MH–1L2, in MH–2L2. Sari et al. Stability Constants of Glyoxime Derivatives