Acta Chini. Slov. 2001, 48, 407-415. 407 New Transition Metal Complexes of J-L-glutamyl-5-(2-methoxy-/>-nitroanilide): Synthesis, Spectroscopic, Magnetic and Thermal Investigations. Leontin David, Cora Crachin, Cräita Bälan, Onuc Cozar Babes-Bolyai Univ., Dept. of Physics, 1 Kogalniceanu, 3400 Cluj-Napoca, Romania Letitia Ghizdavu, Carmen Bâtiu Babes-Bolyai Univ., Dept. of Chemistry, 10 Arany-Janos, 3400 Cluj-Napoca, Romania Received 23-10-2000 Abstract The CuL2-5H20, CoL2-4H20, MnL2-2H20 and FeL3-7H20 complexes for HL = y-L-glutamyl-5-(2-methoxy-p-nitroanilide) were synthesized and their spectral, magnetic and thermal properties were investigated. The thermal stability of the synthesized complexes was discussed in the 20-500 °C temperature range. In all the studied complexes y-L-glutamyl-5-(2-methoxy-p-nitroanilide) acts as a bidentate ligand with coordination involving the carboxylate oxygen and the nitrogen atom belonging to the amino group of they-L-glutamyl fragment. The local structure around the Cu(II) ion is pseudotetrahedral. In the Co(II), Mn(II) and Fe(III) complexes the metal ions are in the high-spin form, with an octahedral stereochemistry. Introduction Besides glutamic acid, its organic and inorganic derivatives also present a particular biological and pharmaceutical importance. The inorganic compounds of the glutamine and glutamic acid with metal ions have antitumoral activity. " In some previously synthesized metal complexes, the glutamic acid acts as a bidentate ligand and some of these complexes present cis-trans isomers. The metal complexes of the glutation were proved to be chemically very stable and to have a 02N CO,H 7 ÔCH3 Hv ^NH2 Figure 1. The ligand y-L-glutamyl-5-(2-methoxy-nitroanilide), HL L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... 408 Acta Chini. Slov. 2001, 48, 407-415. considerable antifungal activity. We have also tested y-L-glutamyl-5-(2-methoxy-p-nitroanilide) as a biochemical reagent for determination of y-glutamyl transferaza (y-GT) in the sanguine serum. Taking into account the important biochemical applications of y-L-glutamyl-5-(2-methoxy-/7-nitroanilide) (Figure 1), we report the synthesis and some physico-chemical properties of its coordinative complexes with the transition metals Cu(II), Co(II), Mn(II) and Fe(III). Results and discussion Thermal data The thermal behavior of the ligand and of the synthesized complexes is described in Table 1. Table 1. Thermal data of y-L-glutamyl-5-(2-methoxy-/?-nitroanilide) and its metal complexes Temperature range [°C] DTA peak (°C) Endo Exo TG weight loss (%) Cale. Exp. HL2H20 20-220 220-400 400 - 500 115 191 202 260 470 10.81 13.80 36.31 39.04 10.30 13.62 35.844 38.16 CuL25H20 20-220 220-400 400 - 500 108 195 207 243 450 12.06 12.33 28.79 39.87 12.18 12.10 28.48 41.23 CoL2-4H20 20-200 105 130 195 - 2.79 5.58 2.76 5.53 200-400 - 205 260 430 14.25 28.23 39.06 14.12 27.54 38.54 MnL22H20 20-200 200-400 400-500 160 202 206 248 438 5.58 14.77 29.91 40.44 6.31 14.52 30.28 38.94 FeL37H20 20-200 200-400 400 - 500 110 198 202 285 460 4.04 15.44 30.59 41.89 4.21 15.10 30.89 41.05 L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... Acta Chini. Slov. 2001, 48, 407-415. 409 DTG DTG 100 200 300 400 C 100 200 300 400t ________l__________l_________l________l________I I_________l_________l________l_________l_______ Or 20- 40-60-80- (a) (b) Figure 2. The derivatograms for L-2H20 (a) and CuL2-5H20 (b) compounds The DTA, TG and DTG curves have almost the same shape for all the investigated compounds, therefore Figure 2 presents the derivatograms recorded for the ligand and for its Cu(II) complex. The endo peak at 115 °C on the ligands derivatograme indicates the loss of two crystal water molecules. The anhydrous compound is stable up to 191 °C, where an endo peak marks its melting. The decomposing starts with the shoulder at ~200 °C, which was assigned to the losing of one -N02 group ' and it continues at 260 °C where the aniline rest is lost. The theoretic weight loss (50.11%) and the experimental one (50.54%) agree with the loss of 2-methoxy-p-nitroanilide residue. The slow weight loss process presenting an endo peak at 470°C indicates the pyrolysis of the remaining L-glutamic acid (C5H7O3N). The derivatograms recorded on CuL2-5H20 and FeL3-7H20 compounds present each two endo peaks at 105 °C and 108 °C, which were assigned to the loss of the hydrating water. In the case of CoL2-4H20 compound, a stepped dehydration reaction is observed, the two endo peaks at 98 °C and 150 °C corresponding to the loss of two moles of hydrating water and two moles of coordination water, respectively. L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... 410 Acta Chini. Slov. 2001, 48, 407-415. The dehydration of MnL2-2Ü20 compound is marked by an endo peak at 130 °C, corresponding to the loss of two coordination water molecules. The melting points for the coordinative compounds (in the 195-198 °C temperature range) are higher then the ligands (191 °C), confirming an increased thermal stability as complexation effect and the metal-nitrogen and metal-oxygen bondings formation. In the 200-400 °C temperature range, the stepped splitting of 2-methoxy-p-nitroanilide organic radical produces: the loss of nitro- and methoxy- groups takes place at -200 °C9'10 and the remaining aniline loss is marked by the exo peak between 265-280 °C. The pyrolysis of the remaining glutamic acid is marked by an exo peak in the temperature range 420-490 °C. The thermal data of the studied compounds agree well with the chemical analysis, confirming the metal:ligand:water combination ratio in the complexes. IR Spectra Table 2 presents some selected vibration bands for the ligand and for the synthesized compounds. A comparative study of these spectral data revealed the lowering of the ligand v(C=0) group frequency with 18^-45 cm"1, due to the II 17 -COO-metal bonding which is formed. ' Table 2. Some IR absorption bands (cm" ) for the ligand and its metal complexes derivatives HL2H20 CuL2-5H20 CoL2-4H20 MnL2-2H20 FeL3-7H20 v(O-H); v(O-H-O) 3385 3502 3428 3425 3410 v(NH2) 3192 3144 3075 3108 3132 v(OO) 1650 1632 1614 1605 1610 v(C-O) 1378 1364 1350 1372 1366 v(N02) 1628 1620 1618 1622 1623 P,(NH2) 1246 1220 1225 1231 1226 Pw(NH2) v(M-OH2) Ô(OO) 7t(O0) v(M-N) 1026 748 624 1055 726 612 456 1028 764 738 594 448 1036 762 736 598 437 1030 732 606 435 L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... Acta Chini. Slov. 2001, 48, 407-415. 411 The shift of v(N-H) absorption band with 48-^84 cm" in the metal complexes indicates the involvement of the nitrogen atom of the second amino group at the metal coordination. The v(M-N) stretchings are shifted to higher frequencies and the v(C=0) and v(NH2) stretchings are shifted to lower frequencies as the metal is changed in the order Fe(III) < Mn(II) < Co(II) < Cu(II). The IR data are in good agreement with Irving-Williams stability series of the studied divalent ion complexes. ' The broad bands over 3300 cm" appearing both in ligand and in the coordinative compounds suggest the presence of hydrogen bonds. This wide band is slightly shifted towards higher frequency values for complex salts, in connection with the increasing energy values of the hydrogen bonds. In the case of C0L24H2O and MnL2-2H20 compounds there is an additional band appearing at 764 and 762 cm" , respectively, due to the coordinative FbO-metal bondings.15 ESR and magnetic susceptibility measurements The powder ESR spectra of Q1L2 5H2O at room temperature (Figure 3) are typical for pseudotetrahedral monomeric species. The g|| = 2.417 and gi = 2.065 values correspond to a CUN2O2 cromophore.16 The powder ESR spectrum of MnL2-2H20 is characterized by a quasi-isotropic g tensor with principal values (g = 2.0018) close to the spin-only value. The ESR spectrum of FeL3-7H20 is almost isotropic (g = 2.002). The presence of a weak signal atg«4 suggests a small distortion of the octahedral symmetry around the metal ion. The magnetic susceptibility measurements indicate a Curie-Weiss behavior (Figure 4), with values of magnetic moments specific for monomeric species. The values of the magnetic moments were calculated considering also the temperature independent contribution. In the case of Cu(II) complexes the magnetic moment (jj,eff = 1.92 |Ub) is in the normally observed range for pseudotetrahedral species, while those corresponding to high-spin ions Co(II), Mn(II) and Fe(III) (jj,eff = 5.2 |Ub, L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... 412 Acta Chini. Slov. 2001, 48, 407-415. Figure 3. Powder spectrum of CuL2-5H20 at room temperature I 80 70 60 50 E 40 30 20 50 100 150 200 T (K) 250 300 Figure 4. Temperature dependence of l/%m for CoL2-4H20 5.87 |Ub and 5.25 |Ub, respectively) indicate local octahedral environments. The paramagnetic Curie temperatures (9 = -10.76 K, -10.05 K, and 35.97 K for Cu(II), Co(II) and Mn(II) complexes, respectively) indicate the presence of some exchange interactions between the metal ions, due to the formation of intermolecular hydrogen bonds 17 Conclusions Thermal and spectroscopic behavior of the synthesized metal complexes indicates that their stability range (CuI^EkO > C0L24H2O > Mnl^EkO ) obeys the Irving - Williams series. L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... Acta Chini. Slov. 2001, 48, 407-415. 413 The IR spectra show y-L-glutamyl-5-(2-methoxy-/?-nitroanilide) acting as a bidentate ligand with coordination involving the carboxylate oxygen and the nitrogen atom of the amino group belonging to the y-L-glutamyl molecular fragment. In the case of intermediate class Lewis acids Co(II) and Mn(II), two H2O molecules are involved in the metal ion coordination, resulting in an octahedral local structure. Three bidentate ligand molecules coordinate the a class Lewis acid Fe(III). The ESR spectra and magnetic data confirm the pseudotetrahedral (for Cu(II) ion) and octahedral (for Co(II), Mn(II), Fe(III) ions) local symmetries. The obtained structural data allow us to propose the following molecular formulas for the studied metal complexes: O. H2 • N L| ,M' )L N FL 2 Figure 5. Partial structures for the studied complexes. For the Cu(II)-complex, the positions 1 and 2 are occupied by oxygen atoms, for Co(II) and Mn(II) complexes these positions are ocupied by H20 molecules and for the Fe(III) compound, an oxygen atom is in position 1 and a nitrogen atom in position 2. Experimental The ligand y-L-glutamyl-5-(2-methoxy-p-nitroanilide) was prepared by reported procedure.5 The metal complexes were prepared by solvating 0.05 mole of the corresponding metal salts (CuS04-5H20, CoS04-7H20, MnS04-7H20 and Fe(NH4)(S04)2T2H20) in distilled water (3.5 ml) at high temperature. An aqueous solution (7 ml) was prepared from 0.05 mole L-glutamyl-5-(2-methoxy-/?-nitroanilide) solvated in NaOH (pH = 9.0) in excess (0.03 g) (molar ratio: 1:2 and 1:3, respectively) at room temperature. The precipitate formed by mixing the ligand solution with metal salts solutions was filtered off, washed in NaOH solution (pH = 9.0), then in cold water, dried in air (24-48h) and kept in dark bottles. L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... 414 Acta Chini. Slov. 2001, 48, 407-415. Table 3. Some physical and elemental analytical data of the synthesized metal compounds CuL2-5H20 CoL2-4H20 MnL2-2H20 FeL3-7H20 Colour pale-blue Pink-yellow white-yellow orange Melting point ( °C) 195 197 198 199 Elemental analysis: found (calculated) (%) Metal (%) 8.93 (8.51) 7.70 (8.14) 7.62 (8.04) 5.30 (5.48) C(%) 38.85 (38.63) 39.55 (39.84) 42.60 (42.17) 40.51 (40.27) H(%) 3.52 (3.78) 3.71 (3.90) 4.02 (4.13) 3.75 (3.94) N(%) 11.20 (11.26) 11.39 (11.61) 12.01 (12.29) 11.55 (11.74) Table 3 presents some physico-chemical and elemental analysis data of the synthesized metal complexes. The compounds are slightly soluble in water and insoluble in organic solvents as benzene, toluene, acetone, ether, chloroform and CCI4; they decompose in boiling DMF and DMSO. Thermal studies were performed on an OD-103 type Paulik-Erdely Derivatograph, in air atmosphere, in the temperature range of 20-500°C, at a rate of heating of 10°C/min, using 01-A12O3 as reference compound. IR spectra were recorded with a Karl Zeiss Jena UR-20 Spectrophotometer, in KBr pellets, in a range of 400-4000cm" . EPR spectra were recorded at 9.4 GHz (X band), using a standard JEOL-JES-3B equipment. Magnetic susceptibility measurements were made on powered samples using a Faraday type balance. References and Notes 1. Khakimov, Kh., Ahmkhodzhaeva, N. T., Khadzhaev, O. T.Koord. Khim. 1979, 5, 21. 2. Tewari, R. C, Svivastav, M. N. Indian J. Chem. 1974,12, 527. 3. Charlson, A. J., Trainer, K. E., Walton, E. C. J. Proc. R. Soc. N. S. W. 1975,108, 1. 4. Cristea, I, Mager, S., Bâtiu, C, Pie, G. Rev. Roum.Chim. 1994, 39, 1435. 5. Shirastava, H. P., Shirastava, R. K. J. Indian Chem. Soc. 1995, 72, 435. 6. Raha, K., Makashir, P. S, Kusian, E. W. J. Thermal Anal. 1989, 35, 1173. 7. Jazen, E. G. J. Am. Chem. Soc. 1965, 87, 3531. 8. Stefan, S. L. J. Thermal Anal. 1994, 42, 1299. 9. Olafsson, P. G., Bryan, A. M. Mikrochim. Acta 1970, 5, 871. 10. Liptay, G. Atlas ofThermoanalytical Curves; Akademiai Kiado, Budapest, 1973, pp. 95. L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of... Acta Chini. Slov. 2001, 48, 407-415. 415 11. Nakamoto, K. Infrared Spectra of Inorganic and Coordination Compounds, Wiley, New York, 1970, pp. 192-193. 12. Abuhijleh, A. L., Woods, C, Bogas, E., Le Guenniou, G.Inorg. Chim. Acta, 1992,195, 67. 13. Frausto da Silva, J. J. R., Williams, R. J. P. The Biological Chemistry of the Elements, Clarendon Press, Oxford, 1994, pp. 34-36. 14. Jensen, W. B. The Lewis acid-base concepts, Wiley, New York, 1980, pp. 26-33. 15. Stefan, S. L, El-Shetary, B. A., Hanna, W. G., El-Maraghy, S. B.Microchemical J., 1987, 35, 51. 16. Mabbs, F. E., Colisson, D. Electron Paramagnetic Resonance of d Transition Metal Compounds, Elsevier, Amsterdam, 1992, pp. 105. 17. Carlin, R. L. Magnetochemistry, Springer Verlag, Berlin, 1986, pp. 64-68. Povzetek Pripravili smo komplekse CuL2-5H20, CoL2-4H20, MnL2-2H20 in FeL3-7H20 , kjer je L = Y-L-glutamil-5-(2-metoksi-jD-nitroanilid) in raziskali njihove spektralne, magnetne in termiène lastnosti. V vseh raziskovanih kompleksih je ligand koordiniran s karboksilatnim kisikom in dušikom aminske skupine v y-L-glutamilnem fragmentu. Razporeditev ligandov okoli Cu(II) je psevdotetraederska, okoli Co(II), Mn(II) in Fe(III) pa oktaederska. L. David, C. Cräciun, C. Bälan, O. Cozar, L. Ghizdavu, C. Bâtiu: New Transition Metal Complexes of...