Acta Chim. Slov. 2000, 47, 481-488. 481 Ni(II), Cu(II), Zn(II) AND Cd(II) COMPLEXES WITH DINEGATIVE N,N,0-TRIDENTATE URACIL-DERIVED HYDRAZONES Francisco Hueso-Urena, Nuria A. Illan-Cabeza, Miguel N. Moreno-Carretero* and Antonio L. Penas-Chamorro Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071-Jaén, Spain Received 9.10.2000 Abstract The synthesis and spectroscopic characterization of complexes of NiII, CuII, ZnII and CdII containing hydrazones derived from 6-amino-5-formyl-1,3-dimethyluracil and nicotinic and isonicotinic acid hydrazides are reported. In all cases, the complexes appear to be monomeric and four-coordinated, with three binding sites occupied by the dinegative tridentate ligand, which makes two five- and six-membered chelate rings and the fourth position occupied by either water or ammonia. The coordination of the organic ligand takes place through the deprotonated N6 atom from the 6-amino group, the N51 azomethine atom and the O52 oxygen from the hydrazide moiety. Experimental data indicate that neither carbonyl oxygen atoms from the uracil ring nor the endocyclic nitrogen atom from pyridine are involved in the coordination to the metal. Keywords: Complexes, hydrazones, Schiff bases, nicotinic acid, uracil Introduction Biological activity of complexes derived from hydrazones has been widely studied and contrasted, acting in processes such as antibacterial, antitumoral, antiviral, antimalarial and antituberculosis effects.1 A lot of complexes derived from hydrazones such as thiosemicarbazones have been reported;2-5 compounds of this type have a great biological activity as antitumoral and antiviral agents. They usually show an N,N,S coordinating mode. However, there are very little information about O,N,O or N,N,O hydrazone compounds in bibliography. F. Hueso-Ureha, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Pehas-Chamorro: Ni(II), Cu(II)... 482 Acta Chim. Slov. 2000, 47, 481-488. CH3 H In order to increase the knowledge about the coordination and bioinorganic chemistry of these compounds,6-14 two new hydrazone ligands (see Fig. 1) derived from 6-amino-5-formyl-1,3-dimethyluracil and nicotinoyl and isonicotinoyl hydrazides have been synthesized. The molecular structure of both ligands has been designed in a way that the activity of hydrazones with the uracil derivatives one has been tried to join with. Thus, the coordinating capacity through both the azomethinic nitrogen and carbonylic oxygen atoms of hydrazones has been enhanced with two new basic atoms (O4 and N6) available for metal ligation from the five-substituted uracil derivative. Furthermore, the presence of uracil ring may contribute to the resulting compounds with an structural analogy with the species found in biological systems, being this fact useful to their potential pharmacologic applications due to the azomethinic bond may be hydrolized in the acid pH of cancer cells, liberating the uracil derivative, which may act as an efficient alkylating or antimetabolite drug. Experimental Apparatus: C, H, N and S microanalyses were performed on a Fisons EA1108 apparatus. Conductivity measurements have been carried out using 10-3 M freshly prepared DMF solutions on a Hanna HI8820 instrument. IR spectra were measured on Perkin-Elmer FT-IR 1760-X (KBr pellets, 4000 - 400 cm-1) and FT-IR Bruker Vector-22 spectrophotometer (polyethylene pellets, 600 - 220 cm-1). 13C and 1H-NMR spectra were recorded using a Bruker AM-300 apparatus (DMSO-d6 solutions). Electronic spectra (diffuse relectance, 240 - 1500 nm) were recorded on a Perkin-Elmer UV/VIS/NIR F. Hueso-Urena, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Penas-Chamorro: Ni(II), Cu(II)... Acta Chim. Slov. 2000, 47, 481-488. 483 Lambda-19 machine using a BaSO4 pellet as reference. EPR spectra were obtained in the X-band at room temperature on a Bruker ESP 300E spectrometer, with a microwave frequency of 9.79 GHz and a modulation frecuency of 100 kHz. Magnetic susceptibility measurements (70-290 K) were carried out on a Manics DSM-8 system. Synthetic procedures: Comercial grade chemicals were used without further purification. The Schiff bases were prepared by reacting equimolar amounts (10 mmol) of 6-amino-5-formyl-1,3-dimethyluracil with nicotinoyl hydrazide (H2NDO "H2O) and isonicotinoyl hydrazide (H2INDO) in EtOH medium (ca. 100 cm3) containing a few drops of glacial AcOH; after stirring the resulting solution for several hours, the Schiff bases were filtered off, washed with EtOH and Et2O and air dried (yields ca. 80%). Characterizational data were as follows: H2NDO"H2O; Found: C, 50.2; H, 4.9; N, 26.8. C13H15N6O3.5 calcd.: C, 50.1; H, 4.8; N, 27.0%. 13C{1H}-n.m.r.: 29.3 (C1), 27.5 (C3), 150.1 (C2), 153.5 (C4), 82.7 (C5), 160.0 (C6), 146.8 (C51), 160.9 (C52), 129.2 (C1 py), 147.8 (C2 py), 123.8 (C4 py), 136.0 (C5 py), 151.2 (C6 py); 1H-n.m.r.: 3.12 and 3.35 (N-CH3), 8.68 (H51), 8.23 and 9.90 (C6-NH2), 11.88 (H52); 9.08 (H2 py, singlet), 7.59 (H4 py, double doublet), 8.31 (H5 py, multiplet), 8.76 (H6 py, doublet). H2INDO; Found: C, 51.2; H, 4.5; N, 27.4. C13H14N6O3 calcd.: C, 51.6; H, 4.6, N, 27.8%. 13C{ 1H}-n.m.r.: 29.4 (C1), 27.6 (C3), 150.2 (C2), 153.6 (C4), 82.8 (C5), 160.2 (C6), 147.4 (C51), 161.0 (C52), 140.3 (C1 py), 121.4 (C2 and C6 py), 150.2 (C3 and C5 py); 1H-n.m.r.: 3.15 and 3.27 (N-CH3), 8.73 (H51), 8.22 (C6-NH2), 9.92 (H52); 7.81 (H2 and H6 py, doublet), 7.45 (H3 and H5 py, doublet). The structure of ligands is depicted in the Fig. 1. Preparation of the complexes: The complexes were synthesized by reacting 0.5 mmol of ligand (H2NDO"H2O or H2INDO) with 0.5 mmol of Ni(NO3)2-6H2O, Cu(NO3)2-3H2O, Zn(NO3)2-6H2O and CdCl2-2"H2O, respectively, in 50 ml of conc. aqueous NH3 , with the exception of Cu(NDO)-2H2O (H2O, 40 cm3). In all the cases, a suspension of the reaction product was obtained which was heated at and stirred for about one hour and left to cool at room temperature before getting filtered off. The solids were washed with EtOH and Et2O and air dried: Ni(NDO)2H2ONH3 (orange, A M=10 F. Hueso-Urena, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Penas-Chamorro: Ni(II), Cu(II)... 484 Acta Chim. Slov. 2000, 47, 481-488. Table 1. Selected infrared data ( cm-1) Compound v(N-H) v(C=0) v(N-N) Amide II v(M-N) H2NDO 3350, 3323 1701, 1676 1662 953 1543 - Ni(NDO)-2H2ONH3 3540, 3461 3386, 3291 1682 963 1554 436 Cu(NDO)-2H20 3467, 3377 1700 966 1547 440 Zn(NDO)l"H201"NH3 3376, 3333 3235 1669 978 1552 371 Cd(NDO)-2"H2ONH3 3494, 3340 1667 973 1547 431 H2INDO 3418, 3297 1703, 1682 971 1552 - Ni(INDO)H20"NH3 3437, 3396 3289 1700 972 1514 457 Cu(INDO)-2H2ONH3 3335 1698 965 1540 434 ohm^cm^mol1), found: C, 38.2; H, 4.3; N, 23.4%. NiCi3Hi9N705 calcd.: C, 37.9; H, 4.6; N, 23.8. Cu(NDO>2H20 (grey, AM=5 ohm^-cm^mol"1), found: C, 38.8; H, 3.6; N, 21.3%. CuCi3Hi6N605 calcd.: C, 39.0; H, 4.0; N, 21.0%. Zn(NDO)l'H201"NH3 (yellow, AM=2 ohm^-cm^mol"1), found: C, 36.9; H, 4.7; N, 25.0%. ZnC13H19.5N7.5O45 calcd.: C, 37.3; H, 4.7; N, 25.1%. Cd(NDO>2"H2ONH3 (yellow, AM=2 ohm^cm^mol x), found: C, 32.5; H, 3.8; N, 20.3%. CdCi3H20N7O5.5 calcd.: C, 32.9; H, 4.2; N, 20.6%. Cu(INDO>2H2ONH3 (brown, A M=13 ohm^-cm^mol"1), found: C, 38.3; H, 4.3; N, 23.1%. CUC13H19N7O5 calcd.: C, 37.4; H, 4.6; N, 23.5%. Ni(INDO)H20 "NH3 (orange, AM=30 ohm^-cm^mol"1), found: C, 40.2; H, 4.4; N, 23.7%. NiC13H15.5N6.5O4 calcd.: C, 40.5; H, 4.1; N, 23.6%. N.m.r. data of Zn(NDO)l"H201 "NH3 complex display the following signals: "Cl'Hj-ara.r.: 27.7 (CI), 27.0 (C3), 150.5 (C2), 155.5 (C4), 83.5 (C5), 161.6 (C6), 151.2 (C51), 163.9 (C52); ^-n.m.r.: 3.14 and 3.32 (N-CH3), 8.85 (H51), 6.12 (H6). It was not possible to record the Cd(NDO)-2"H20-NH3 spectra due to the low solubility in DMSO of this complex. Results and discussion The conductivity values have clearly shown the non-electrolyte character of the complexes. In all the complexes, the presence of water and/or ammonia molecules has F. Hueso-Urefia, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Perias-Chamorro: Ni(II), Cu(II)... Acta Chim. Slov. 2000, 47, 481-488. 485 been corroborated from the thermal studies. The pyrolitic degradation in the t.g. plots begins around 70°C due to the loss of the water and/or ammonia molecules. Each of these molecules causes an endothermic effect, being the NH3 ones at higher temperature since they must be coordinated to the metal because of their greater basicity if it is compared with the water ones. The pyrolitic degradations finish between 400 and 600°C, leaving as final residue the metallic oxide, which was corroborated by infrared spectroscopy. To carry out a comparative study of the IR spectra of the complexes and the free ligands is very difficult, due to the great number of bands; only general remarks can be made. The most interesting features are listed in Table 1. There is a general displacement due to the coordination process. The v(N-H) bands are displaced to upper wavenumber due to the coordination and the double deprotonation, because the two lost hydrogen to make the dianion are from 6-amino group (which becomes to an imino group)6,7,9 and the hydrazone nitrogen atom.12 So, bands of groups involved in the coordination are displaced too. As it has been found from X-ray diffraction studies,12 the more feasible predominant tautomeric form of the dinegative ligand in these complexes is the enolate one. The amide II band is displaced to lower wavenumber in the H2INDO complexes due to the electronic delocalization, but in the H2NDO ones, this displacement is to upper wavenumber; so, at least from the IR spectral point of view, it is not clear the predominant tautomeric form of these complexes. The v(N-N) bands are displaced to upper wavenumber, being this shift very characteristic for several hydrazone ligands coordinated through the azomethine nitrogen atom.15,16 In the 600-200 cm-1 range, the bands associated to M-N and terminal M-X vibrations have been assigned, and are in good accordance with the data found in the literature.17 On comparing the NMR spectra of Zn(NDO) 1"H2O 1"NH3 complex with those of free ligand, weak shifts (< 2 ppm) of the signals assigned to the C1 and C3 (downfield) and C2, C5 and C6 atoms (upfield) are observed; so, a stronger displacement is found in the C4 (upfield, 2 ppm). The C4 and C6 signals are equally modified, so it is not clear which of them is the metal binding site; however, we have characterized the similar complex [Pd4(TSDO)4]×4H2O×2DMF,9 whose ligand contains the same monodeprotonated uracil moiety, in which an analog F. Hueso-Urena, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Penas-Chamorro: Ni(II), Cu(II)... 486 Acta Chim. Slov. 2000, 47, 481-488. displacement is observed, but the crystallographic studies have clearly shown that the coordination takes place through the N6 atom. On the other hand, we have pointed out that when the 6-aminouracil derived ligand is not deprotonated, the coordination is established through the O4,8 so the deprotonation seems to be a decisive fact to assign the coordination pattern in these molecules. The signals assigned to the hydrogen attached to the N(6) atom display a strong change because the initial amino group becomes into an imino group as consequence of the deprotonation. So, it does not appears the H52 signal, due to its deprotonation. The shifts of the C(51), C(52) and H51 signals are in according to the loss of electronic density of the ligand through the M-L bonds. In the pyridine moiety there is long distance coupling between hydrogen atoms, which causes the presence of double doublets (H4 and H6) and doublets (H2). The electronic spectra of the copper(II) complexes show a single broad and poorly defined asymmetric band around 17500 cm-1 and the spectra of nickel(II) complexes show a band around 20000 cm-1. These results are consistent with square-planar structures, since the four lower orbitals are often so close together in energy, that individual transitions therefrom to the upper d level cannot be distinguished - hence the single absorption band.18 The nickel(II) complexes showed a diamagetic behaviour consistent with square-planar environment around the metal ion. Magnetic susceptibilities at different temperatures of the copper(II) compounds have been fitted to the Curie-Weiss law (l/Xm=(T-e)/C): Cu(NDO)-2H2O: C=0.239(6) cgsu-K-mol-1, 0=39(8) K, neff=1.72(5) BM; Cu(INDO)-2H2O-NH3: C=0.257(7) cgsu-K-mol-1, 0=36(8) K, \i eff=1.87(2) BM. The effective magnetic moments are in accordance with diluted monomeric units19 although the slightly high 0 value could indicate antiferromagnetic interactions between the metal atoms. Both copper(II) complexes display rhombic EPR powder spectra with g1=2.05, g2=2.07, g3=2.14 (Cu(NDO)-2H2O) and g1=2.03, g2=2.05, g3=2.17 (Cu(INDO)-2H2O-NH3) respectively.20 From these data, square-planar structures may be proposed for the nickel(II) and copper(II) complexes with the tridentate ligand and the fourth coordination position occupied by either an ammonia or water molecule, as depicted in fig. 2; a similar F. Hueso-Urena, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Penas-Chamorro: Ni(II), Cu(II)... Acta Chim. Slov. 2000, 47, 481-488. 487 structure has been observed from single-crystal X-ray diffraction studies for the related compounds aqua-[6-amino-l,3-dimethyl-uracilato-benzoylhydrazone(2-)-N6,N51,052]-copper(II) hydrate12 and several O-nitrito-6 and halide-complexes with monodeprotonated iV,iV,Z-tridentate hydrazones (Z = S or O) derived from 6-amino-5-formyl-l,3-dimethyluracil.13 A similar structure but tetrahedral may be suggested for the zinc(II) and cadmium(II) complexes. Figure 2. Computer-generated square-planar structure proposed for the nickel(II) and copper(II) complexes (solv = NH3 or H20). The two hydrogen lost to make the dianion are from N6 and N52 atoms. Acknowledgements The authors are indebted to Direction General de Ensehanza Superior e Investigation Científica (MEC, Spain) (project PB97-0786-C03-03) and Consejería de Educación y Ciencia (Junta de Andalucía, research group FQM-273). References 1. 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Hueso-Urefia, F.; Penas-Chamorro, A.L.; Moreno-Carretero, M.N.; Amigo, J.M.; Esteve, V.; Debaerdemaeker, T. Polyhedron 1999, 18, 2205. 9. Hueso-Urefia, F.; Illan-Cabeza, N.A.; Moreno-Carretero, M.N.; Perias-Chamorro, A.L.; Faure, R. Inorg. Chem. Commun. 1999, 2, 323. 10. Hueso-Urefia, F.; Penas-Chamorro, A.L.; Moreno-Carretero, M.N.; Amigo, J.M.; Esteve, V.; Debaerdemaeker, T. Polyhedron 1999, 18, 3629. 11. Hueso-Urefia, F.; Penas-Chamorro, A.L.; Moreno-Carretero, M.N.; Amigo, J.M.; Esteve, V.; Debaerdemaeker, T. Z Kristallogr. NCS 2000, 215, 155. 12. Hueso-Urefia, F.; Illan-Cabeza, N.A.; Penas-Chamorro, A.L.; Moreno-Carretero, M.N.; Faure, R. Polyhedron 2000, 19, 689. 13. Hueso-Urefia, F.; Illan-Cabeza, N.A.; Moreno-Carretero, M.N.; Perias-Chamorro, A.L. Transit. Met. Chem. in press. 14. Hueso-Urefia, F.; Penas-Chamorro, A.L.; Moreno-Carretero, M.N.; Amigo, J.M.; Esteve, V.; Debaerdemaeker, T. Z Kristallogr. NCS, in press. 15. Shetti, S.N.; Murty, A.S.; Tembe, G.L. Transit. Met. Chem. 1993, 18, 467. 16. West, D.X.; Makeever, R.M.; Scovill, J.P.; Klayman, D.L. Polyhedron 1984, 3, 947. 17. Ferraro, J.R. Low-Frequency Vibrations of Inorganic and Coordination Compounds, Plenum Press, New York, 1971, pp.156, 165, 222. 18. Lever, A.B.P. Inorganic Electronic Spectroscopy, 2nd ed., Elsevier, Amsterdam, 1984. 19. Carlin, R.L. Magnetochemistry, Springer-Verlag, Berlin, 1986. 20. Pilbrow, J.R. Transition Ion Electron Paramagnetic Resonance, Oxford Science Publications, Oxford, 1990. Povzetek Opisana je sinteza in spektroskopska karakterizacija kompleksov Ni(II), Cu(II), Zn(II) in Cd(II) s hidrazonom 6-amino-5-formil-l,3-dimetiluracila ter hidrazidoma nikotinske in izonikotinske kisline. F. Hueso-Urefia, N. A. Illan-Cabeza, M. N. Moreno-Carretero, A. L. Perias-Chamorro: Ni(II), Cu(II)...