- Email: [email protected]
Preparation and structural characterisation of a novel palladium (II) binuclear complex containing triazole bisthiosemicarbazone bridges
Inorganic Chemistry Communications 5 (2002) 344–346 www.elsevier.com/locate/inoche
Preparation and structural characterisation of a novel palladium (II) binuclear complex containing triazole bisthiosemicarbazone bridges Pilar Souza b
a,*
, Ana I. Matesanz a, Cesar Pastor
b
a Departamento de Quımica Inorg anica, Facultad de Ciencias, Universidad Aut onoma de Madrid, Cantoblanco, Madrid 28049, Spain Servicio Interdepartamental de Apoyo a la Investigaci on, Facultad de Ciencias, Universidad Aut onoma de Madrid, Cantoblanco, Madrid 28049, Spain
Received 2 February 2002; accepted 21 February 2002
Abstract A new polidentate ligand, 3,5-diacyl-1,2,4-triazolebis(4-methylthiosemicarbazone), (H5 L) has been synthesised; complexation of this ligand with Li2 PdCl4 leads to a novel stable [Pd2 ðl-H3 LÞ2 ] macrocyclic cage which was characterised by X-ray crystallography. The ligand coordinates to the Pd atoms in a new tridentate fashion, forming a chelating and a bridging bonding modes. Ó 2002 Elsevier Science B.V. All rights reserved. Keywords: Palladium(II) complexes; Bis(thiosemicarbazone); 1,2,4-Triazoles; Crystal structure
Thiosemicarbazones are of considerable interest due to the many bioactivities which they possess. They were the first compounds to be found active in virus-infected animals. Furthermore, these compounds were the first to be effective in humans and placed in clinical medicine [1]. In recent times there is an extensive literature on the antitumor activity [2–4] of the thiosemicarbazones due to a well-established link exist between viruses and malignancy. Thiosemicarbazones have been also the focus of the first systematic studies on the relationship between chemical structure and biological activity [5]. It is well known that drug resistance represents the major limitation for the success of antitumor metal drug such cisplatin (cis-diamminedichloroplatinum (II)). It has been demonstrated that glutathione (GSH) is implicated in drug resistance by reacting with the metal centre to form inactive species. Some recent experiments have shown that metal drug containing Sbound molecules exhibit low reactivity toward glutathione [6].
*
Corresponding author. Fax: +34-913978433. E-mail address: [email protected] (P. Souza).
We have recently shown that thiosemicarbazone and bisthiosemicarbazone ligands coupled to Zn, Cd and Pd metal centres are able to circumvent resistance in cisplatin-resistant cells and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of GSH [7]. As part of a research programme aimed at the synthesis of compounds with antiviral and antitumor properties and their spectroscopic characterisation, here we report the novel cage, dimeric molecule, 3,5-diacyl1,2,4-triazole bis(4-methylthiosemicarbazonate) palladium(II) 1. We have been using 3,5-diacyl-1,2,4-triazole, previously synthesised [8], as building block in condensation reaction with 4-methylthiosemicarbazide [9] (Scheme 1). Reaction of the new ligand ðH5 LÞ 1 with Li2 PdCl4 gave what we believed to be the dimeric complex 1. The formulation of which is supported by it elemental 1
Ligand H5 L: This compound was prepared by reacting methanolic solutions of 3,5-diacyl-1,2,4-triazole and 4-methylthiosemicarbazide in 1:2 molar ratio, the reaction mixture was heated under reflux for 6 h on a water bath at 60 °C. The solid formed was filtered and washed with cold MeOH and Et2 O and dried in vacuo. Anal. Calc. for C10 H21 N9 O2 S2 : C, 33.05%; H, 5.80%; N, 34.70%; S, 17.65%. Found: C, 33.80%; H, 5.75%; N, 34.20%; S, 17.80%. Selected IR results: m ¼ 3287, 3193(s, NH); 2930(m, CH3 ); 1612, 1557(s, CN); 759 cm1 (m, CS-thioamide IV band). Electronic spectrum kmax ¼ 322 nm.
1387-7003/02/$ - see front matter Ó 2002 Elsevier Science B.V. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 ( 0 2 ) 0 0 3 9 6 - 9
P. Souza et al. / Inorganic Chemistry Communications 5 (2002) 344–346
345
Scheme 1.
analysis, IR, 1 HNMR and FAB mass spectrum. 2 Numerous attempts at crystallisation were necessary before good quality orange crystals suitable for X-ray diffraction analysis were obtained by recrystallisation in DMSO, a single crystal X-ray structure determination was carried out to determine the structure unambiguously. 3 To our knowledge this is the first time that a single crystal structure of a 3,5-diacyl-1,2,4-triazole bis(thiosemicarbazone) derivative has been reported. The 1 HNMR spectrum of complex 1 shows pronounced changes with respect to the free ligand (H5 L), the signal assigned to the triazole proton disappear as a consequence of deprotonation. The protons of the terminal secondary amine groups are shifted downfield as expected after metal coordination, also it is possible to observe the loss of the original equivalence between the two ligand molecules as a result of the different arrangements of their two arms in the complex. This arrangement appears to be favoured since it minimises the interligand steric interactions. Hence, it appears that the solid-state structures are clearly preserved in solution. A drawing of complex 12DMSO with the atomic numbering scheme (for N, Pd and S atoms) is shown in Fig. 1, the binuclear ½Pd2 ðl-H3 LÞ2 molecule has crystallographically imposed 2-fold symmetry. Palladium (II) atom is square-planar four coordinate with two nitrogen atoms (N(1) and N(4)) and two sulphur atoms
(S(1) and S(2)), see Fig. 1 for labelling, in cis-position, the planes formed have an interplane separation of 3.400 and an intermetallic separation of 6.138 A . Each A dideprotonated ligand ðH3 LÞ coordinates to the Pd atoms in a new tridentate fashion, forming a chelating and a bridging bonding modes. The coordination result in the formation of two five membered [PdSCNN, PdNCCN] chelate rings for each palladium (II) ion which are coplanar with the deprotonate triazole ring, the conformation adopted by the metal complex is stablised by intramolecular N(7)–H(7) N(6A) (at x, hydrogen bonds. y, 0:5 z) 2.02 A A careful examination of the bond length data show ], Pd–N(4) [2.050(7) A ], Pd– that the Pd–N(1) [1.989(7) A ] and Pd–S(2) [2.306(3) A ] distances are S(1) [2.263(3) A comparable with those reported with strong Pd–N and Pd–S coordination [10]. The loss of the proton originally bonded to N(2) produces a negative charge delocalised in the ligand system which is consistent with the bond intermediate between length C(2)–N(2) 1.307(11) A formal single and double bond. The C–S distances and C(9)–S(2) 1.727(10) A ] are in [C(2)–S(1) 1.774(10) A the range of single bond character (typical bond lengths in ðMeSÞ C@CðSMeÞ and C@S being C(sp2 )–S 1.706 A 2 2 1.630 A in naphthylphenylthioketone) [11]. This substantiates the displacement of the tautomeric equilibrium to the thiol form in the CS groups in the complex.
2 Complex 1. A suspension of H5 L (1 mmol in MeOH) was added with stirring to a solution of lithium tetrachloropalladate(II) prepared in situ from palladium chloride(II) (1.2 mmol) and lithium chloride (4.4 mmol) in MeOH. The reaction mixture was stirred for 15 h at room temperature, the result orange precipitated was filtered off, washed with MeOH and Et2 O and dried in vacuo. Anal. Calc. for C20 H46 N18 O8 Pd2 S4 : C, 23.85%; H, 4.55%; N, 25.00%; S, 12.70%. Found: C, 23.60%; H, 3.45%; N, 24.50%; S, 12.10%. MS (FABþ with m-nitrobenzyl alcohol matrix): m/z-8H2 O: 862.8. Selected IR results: m ¼ 3208 (s, NH); 2929(m CH3 ); 1587(s, CN), 744 cm1 (w, CSthioamide IV band). Electronic spectrum k ¼ 322, 421 and 487 nm. 3 Crystal data for 1: C24 H42 N18 O2 Pd2 S6 , M ¼ 1019:92, monoclinic, , b ¼ 12:3136ð8Þ A , space group C2/c, a ¼ 24:6639ð16Þ A , b ¼ 97:1550ð10Þ°, V ¼ 4129:8ð5Þ A 3 , T ¼ 296 K, c ¼ 13:7048ð9Þ A Z ¼ 4, Dc ¼ 1:640 Mg=m3 , F ð0 0 0Þ ¼ 2064, lðMo-KaÞ ¼ 1:224 mm1 , , 10,888 reflections measured, 4154 unique k ¼ 0:71073 A ðRint ¼ 0:0884Þ. The final agreement factors are R1 ¼ 0:0826 with F > 2rðF Þ and R1 ¼ 0:1264, wR2 ¼ 0:2115. CCDC reference number 173595.
Fig. 1. ORTEP drawing of 1, the two DMSO molecules and carbon labelling are omitted for clarity.
346
P. Souza et al. / Inorganic Chemistry Communications 5 (2002) 344–346
poor activity against this cell lines in comparison with the structural analogous Pd(II)benzyl bis(thiosemicarbazonate) recently published [7].
Acknowledgements We thank the Comisi on Interministerial de Ciencia y Tecnologıa (Spain) for financial support (project PM990008) and Professor D.W. West for his kind gift of 4methylthiosemicarbazide. C.P. also thanks Dr. Enrique Gutierrez Puebla for the technical and scientifical assistance in the X-ray structure determination.
References
Fig. 2. View showing the chains of 1 (running down the crystallographic a-axis) and their linkage via DMSO molecules.
An analysis of the packing diagram (Fig. 2) shows the existence of intermolecular hydrogen bonds involving the uncoordinated terminal nitrogen atoms of the molecule and the oxygen atoms of the two DMSO molecules which are responsible for the formation of the zig-zag strand along the crystallographic a-axis. This strong attachment explains the high stability of the crystal on exposure to air and moisture. The testing of the cytotoxic activity of the compound 1 against several human, monkey and murine cell lines sensitive (Hela, Vero and Pam 212) and resistant to cisDDP (Pam-ras) suggest that this compound has shown
[1] C.J. Pfau, Handb. Exp. Pharmacol. 61 (1982) 147, and references therein. [2] S.B. Padhye, G.B. Kauffman, Coord. Chem. Rev. 63 (1985) 127. [3] M. Peheva, T. Varadinova, Metal-Based Drugs 7 (2000) 129; I.H. Hall, B.J. Bernes, J.E. Rowell, K.A. Shaffer, S.E. Cho, D.X. West, A.M. Stark, Pharmazie 56 (8) (2001) 648; J. Easmon, G. Purstinger, G. Heinisch, T. Roth, H.H. Fiebig, W. Holzer, W. Jager, M. Jenny, J. Hofmann, J. Med. Chem. 44 (13) (2001) 2164; J.S. Lewis, T.L. Sharp, R. Laforest, Y. Fujibayashi, M.J. Welch, J. Nucl. Med. 42 (4) (2001) 655. [4] Z. Lakovidou, A. Papageorgiou, M.A. Demertzis, E. Mioglou, D. Mourelatos, A. Kotsis, P.N. Yadav, D. Kovala-Demertzi, Anticancer Drugs 12 (1) (2001) 65; I.H. Hall, C.B. Lackey, T.D. Kistler, R.W. Durham Jr., E.M. Jouad, M. Khan, X.D. Thanh, S. Djebbar-Sid, O. Benali-Baitich, G.M. Bouet, Pharmazie 55 (12) (2000) 937; L.J. Ackerman, D.X. West, C.J. Mathias, M.A. Green, Nucl. Med. Biol. 26 (5) (1999) 551; M.C. Miller III, C.N. Stineman, J.R. Vance, D.X. West, I.H. Hall, Anticancer Res. 18 (6A) (1998) 4131. [5] D.X. West, A.E. Liberta, S.B. Padhye, R.C. Chikate, P.B. Sonaware, A.S. Kumbar, R.G. Yerande, Coord. Chem. Rev. 123 (1993) 49. [6] Z. Guo, T.W. Hambley, P.S. Murdoch, P.S. Sadler, M. Frey, J. Chem. Soc., Dalton Trans. (1997) 468; E.L.M. Lempers, J. Reedijk, Adv. Inorg. Chem. 37 (1991) 175; B. Lippert, Coord. Chem. Rev. 200–202 (2000) 487. [7] J.M. Perez, V. Cerrillo, A.I. Matesanz, J.M. Millan, P. Navarro, C. Alonso, P. Souza, ChemBioChem. 2 (2001) 119; J.M. Perez, A.I. Matesanz, A. Martın-Ambite, P. Navarro, C. Alonso, P. Souza, J. Inorg. Biochem. 75 (1999) 255; A.I. Matesanz, J.M. Perez, P. Navarro, P. Souza, J. Inorg. Biochem. 76 (1999) 29. [8] J.M. Alonso, M.R. Martın, J. de Mendoza, T. Torres, J. Elguero, J. Heterocycles 26 (1987) 989; P. Souza, A.I. Matesanz, A. Arquero, V. Fernandez, Z. Naturforsch. 49b (1994) 665. [9] P. Souza, A.I. Matesanz, P. Navarro, J. Inorg. Biochem. 86 (2001) 439 (ICBIC 10 Florence 2001). [10] A. Bacchi, M. Carcelli, M. Cosla, P. Pelagatti, C. Pelizzi, G. Pelizzi, J. Chem. Soc., Dalton Trans. (1996) 4239; M. Bonamico, V. Fares, L. Petrilli, F. Tarli, G. Chiozzini, C. Riccucci, J. Chem. Soc., Dalton Trans. (1994) 3349. [11] P. Souza, A. Arquero, A. Garcıa-Onrubia, V. Fern andez, A.M. Leiva, U. M€ uller, Z. Naturforsch. 44b (1989) 946.
Preparation and structural characterisation of a novel palladium (II) binuclear complex containing triazole bisthiosemicarbazone bridges Pilar Souza b
a,*
, Ana I. Matesanz a, Cesar Pastor
b
a Departamento de Quımica Inorg anica, Facultad de Ciencias, Universidad Aut onoma de Madrid, Cantoblanco, Madrid 28049, Spain Servicio Interdepartamental de Apoyo a la Investigaci on, Facultad de Ciencias, Universidad Aut onoma de Madrid, Cantoblanco, Madrid 28049, Spain
Received 2 February 2002; accepted 21 February 2002
Abstract A new polidentate ligand, 3,5-diacyl-1,2,4-triazolebis(4-methylthiosemicarbazone), (H5 L) has been synthesised; complexation of this ligand with Li2 PdCl4 leads to a novel stable [Pd2 ðl-H3 LÞ2 ] macrocyclic cage which was characterised by X-ray crystallography. The ligand coordinates to the Pd atoms in a new tridentate fashion, forming a chelating and a bridging bonding modes. Ó 2002 Elsevier Science B.V. All rights reserved. Keywords: Palladium(II) complexes; Bis(thiosemicarbazone); 1,2,4-Triazoles; Crystal structure
Thiosemicarbazones are of considerable interest due to the many bioactivities which they possess. They were the first compounds to be found active in virus-infected animals. Furthermore, these compounds were the first to be effective in humans and placed in clinical medicine [1]. In recent times there is an extensive literature on the antitumor activity [2–4] of the thiosemicarbazones due to a well-established link exist between viruses and malignancy. Thiosemicarbazones have been also the focus of the first systematic studies on the relationship between chemical structure and biological activity [5]. It is well known that drug resistance represents the major limitation for the success of antitumor metal drug such cisplatin (cis-diamminedichloroplatinum (II)). It has been demonstrated that glutathione (GSH) is implicated in drug resistance by reacting with the metal centre to form inactive species. Some recent experiments have shown that metal drug containing Sbound molecules exhibit low reactivity toward glutathione [6].
*
Corresponding author. Fax: +34-913978433. E-mail address: [email protected] (P. Souza).
We have recently shown that thiosemicarbazone and bisthiosemicarbazone ligands coupled to Zn, Cd and Pd metal centres are able to circumvent resistance in cisplatin-resistant cells and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of GSH [7]. As part of a research programme aimed at the synthesis of compounds with antiviral and antitumor properties and their spectroscopic characterisation, here we report the novel cage, dimeric molecule, 3,5-diacyl1,2,4-triazole bis(4-methylthiosemicarbazonate) palladium(II) 1. We have been using 3,5-diacyl-1,2,4-triazole, previously synthesised [8], as building block in condensation reaction with 4-methylthiosemicarbazide [9] (Scheme 1). Reaction of the new ligand ðH5 LÞ 1 with Li2 PdCl4 gave what we believed to be the dimeric complex 1. The formulation of which is supported by it elemental 1
Ligand H5 L: This compound was prepared by reacting methanolic solutions of 3,5-diacyl-1,2,4-triazole and 4-methylthiosemicarbazide in 1:2 molar ratio, the reaction mixture was heated under reflux for 6 h on a water bath at 60 °C. The solid formed was filtered and washed with cold MeOH and Et2 O and dried in vacuo. Anal. Calc. for C10 H21 N9 O2 S2 : C, 33.05%; H, 5.80%; N, 34.70%; S, 17.65%. Found: C, 33.80%; H, 5.75%; N, 34.20%; S, 17.80%. Selected IR results: m ¼ 3287, 3193(s, NH); 2930(m, CH3 ); 1612, 1557(s, CN); 759 cm1 (m, CS-thioamide IV band). Electronic spectrum kmax ¼ 322 nm.
1387-7003/02/$ - see front matter Ó 2002 Elsevier Science B.V. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 ( 0 2 ) 0 0 3 9 6 - 9
P. Souza et al. / Inorganic Chemistry Communications 5 (2002) 344–346
345
Scheme 1.
analysis, IR, 1 HNMR and FAB mass spectrum. 2 Numerous attempts at crystallisation were necessary before good quality orange crystals suitable for X-ray diffraction analysis were obtained by recrystallisation in DMSO, a single crystal X-ray structure determination was carried out to determine the structure unambiguously. 3 To our knowledge this is the first time that a single crystal structure of a 3,5-diacyl-1,2,4-triazole bis(thiosemicarbazone) derivative has been reported. The 1 HNMR spectrum of complex 1 shows pronounced changes with respect to the free ligand (H5 L), the signal assigned to the triazole proton disappear as a consequence of deprotonation. The protons of the terminal secondary amine groups are shifted downfield as expected after metal coordination, also it is possible to observe the loss of the original equivalence between the two ligand molecules as a result of the different arrangements of their two arms in the complex. This arrangement appears to be favoured since it minimises the interligand steric interactions. Hence, it appears that the solid-state structures are clearly preserved in solution. A drawing of complex 12DMSO with the atomic numbering scheme (for N, Pd and S atoms) is shown in Fig. 1, the binuclear ½Pd2 ðl-H3 LÞ2 molecule has crystallographically imposed 2-fold symmetry. Palladium (II) atom is square-planar four coordinate with two nitrogen atoms (N(1) and N(4)) and two sulphur atoms
(S(1) and S(2)), see Fig. 1 for labelling, in cis-position, the planes formed have an interplane separation of 3.400 and an intermetallic separation of 6.138 A . Each A dideprotonated ligand ðH3 LÞ coordinates to the Pd atoms in a new tridentate fashion, forming a chelating and a bridging bonding modes. The coordination result in the formation of two five membered [PdSCNN, PdNCCN] chelate rings for each palladium (II) ion which are coplanar with the deprotonate triazole ring, the conformation adopted by the metal complex is stablised by intramolecular N(7)–H(7) N(6A) (at x, hydrogen bonds. y, 0:5 z) 2.02 A A careful examination of the bond length data show ], Pd–N(4) [2.050(7) A ], Pd– that the Pd–N(1) [1.989(7) A ] and Pd–S(2) [2.306(3) A ] distances are S(1) [2.263(3) A comparable with those reported with strong Pd–N and Pd–S coordination [10]. The loss of the proton originally bonded to N(2) produces a negative charge delocalised in the ligand system which is consistent with the bond intermediate between length C(2)–N(2) 1.307(11) A formal single and double bond. The C–S distances and C(9)–S(2) 1.727(10) A ] are in [C(2)–S(1) 1.774(10) A the range of single bond character (typical bond lengths in ðMeSÞ C@CðSMeÞ and C@S being C(sp2 )–S 1.706 A 2 2 1.630 A in naphthylphenylthioketone) [11]. This substantiates the displacement of the tautomeric equilibrium to the thiol form in the CS groups in the complex.
2 Complex 1. A suspension of H5 L (1 mmol in MeOH) was added with stirring to a solution of lithium tetrachloropalladate(II) prepared in situ from palladium chloride(II) (1.2 mmol) and lithium chloride (4.4 mmol) in MeOH. The reaction mixture was stirred for 15 h at room temperature, the result orange precipitated was filtered off, washed with MeOH and Et2 O and dried in vacuo. Anal. Calc. for C20 H46 N18 O8 Pd2 S4 : C, 23.85%; H, 4.55%; N, 25.00%; S, 12.70%. Found: C, 23.60%; H, 3.45%; N, 24.50%; S, 12.10%. MS (FABþ with m-nitrobenzyl alcohol matrix): m/z-8H2 O: 862.8. Selected IR results: m ¼ 3208 (s, NH); 2929(m CH3 ); 1587(s, CN), 744 cm1 (w, CSthioamide IV band). Electronic spectrum k ¼ 322, 421 and 487 nm. 3 Crystal data for 1: C24 H42 N18 O2 Pd2 S6 , M ¼ 1019:92, monoclinic, , b ¼ 12:3136ð8Þ A , space group C2/c, a ¼ 24:6639ð16Þ A , b ¼ 97:1550ð10Þ°, V ¼ 4129:8ð5Þ A 3 , T ¼ 296 K, c ¼ 13:7048ð9Þ A Z ¼ 4, Dc ¼ 1:640 Mg=m3 , F ð0 0 0Þ ¼ 2064, lðMo-KaÞ ¼ 1:224 mm1 , , 10,888 reflections measured, 4154 unique k ¼ 0:71073 A ðRint ¼ 0:0884Þ. The final agreement factors are R1 ¼ 0:0826 with F > 2rðF Þ and R1 ¼ 0:1264, wR2 ¼ 0:2115. CCDC reference number 173595.
Fig. 1. ORTEP drawing of 1, the two DMSO molecules and carbon labelling are omitted for clarity.
346
P. Souza et al. / Inorganic Chemistry Communications 5 (2002) 344–346
poor activity against this cell lines in comparison with the structural analogous Pd(II)benzyl bis(thiosemicarbazonate) recently published [7].
Acknowledgements We thank the Comisi on Interministerial de Ciencia y Tecnologıa (Spain) for financial support (project PM990008) and Professor D.W. West for his kind gift of 4methylthiosemicarbazide. C.P. also thanks Dr. Enrique Gutierrez Puebla for the technical and scientifical assistance in the X-ray structure determination.
References
Fig. 2. View showing the chains of 1 (running down the crystallographic a-axis) and their linkage via DMSO molecules.
An analysis of the packing diagram (Fig. 2) shows the existence of intermolecular hydrogen bonds involving the uncoordinated terminal nitrogen atoms of the molecule and the oxygen atoms of the two DMSO molecules which are responsible for the formation of the zig-zag strand along the crystallographic a-axis. This strong attachment explains the high stability of the crystal on exposure to air and moisture. The testing of the cytotoxic activity of the compound 1 against several human, monkey and murine cell lines sensitive (Hela, Vero and Pam 212) and resistant to cisDDP (Pam-ras) suggest that this compound has shown
[1] C.J. Pfau, Handb. Exp. Pharmacol. 61 (1982) 147, and references therein. [2] S.B. Padhye, G.B. Kauffman, Coord. Chem. Rev. 63 (1985) 127. [3] M. Peheva, T. Varadinova, Metal-Based Drugs 7 (2000) 129; I.H. Hall, B.J. Bernes, J.E. Rowell, K.A. Shaffer, S.E. Cho, D.X. West, A.M. Stark, Pharmazie 56 (8) (2001) 648; J. Easmon, G. Purstinger, G. Heinisch, T. Roth, H.H. Fiebig, W. Holzer, W. Jager, M. Jenny, J. Hofmann, J. Med. Chem. 44 (13) (2001) 2164; J.S. Lewis, T.L. Sharp, R. Laforest, Y. Fujibayashi, M.J. Welch, J. Nucl. Med. 42 (4) (2001) 655. [4] Z. Lakovidou, A. Papageorgiou, M.A. Demertzis, E. Mioglou, D. Mourelatos, A. Kotsis, P.N. Yadav, D. Kovala-Demertzi, Anticancer Drugs 12 (1) (2001) 65; I.H. Hall, C.B. Lackey, T.D. Kistler, R.W. Durham Jr., E.M. Jouad, M. Khan, X.D. Thanh, S. Djebbar-Sid, O. Benali-Baitich, G.M. Bouet, Pharmazie 55 (12) (2000) 937; L.J. Ackerman, D.X. West, C.J. Mathias, M.A. Green, Nucl. Med. Biol. 26 (5) (1999) 551; M.C. Miller III, C.N. Stineman, J.R. Vance, D.X. West, I.H. Hall, Anticancer Res. 18 (6A) (1998) 4131. [5] D.X. West, A.E. Liberta, S.B. Padhye, R.C. Chikate, P.B. Sonaware, A.S. Kumbar, R.G. Yerande, Coord. Chem. Rev. 123 (1993) 49. [6] Z. Guo, T.W. Hambley, P.S. Murdoch, P.S. Sadler, M. Frey, J. Chem. Soc., Dalton Trans. (1997) 468; E.L.M. Lempers, J. Reedijk, Adv. Inorg. Chem. 37 (1991) 175; B. Lippert, Coord. Chem. Rev. 200–202 (2000) 487. [7] J.M. Perez, V. Cerrillo, A.I. Matesanz, J.M. Millan, P. Navarro, C. Alonso, P. Souza, ChemBioChem. 2 (2001) 119; J.M. Perez, A.I. Matesanz, A. Martın-Ambite, P. Navarro, C. Alonso, P. Souza, J. Inorg. Biochem. 75 (1999) 255; A.I. Matesanz, J.M. Perez, P. Navarro, P. Souza, J. Inorg. Biochem. 76 (1999) 29. [8] J.M. Alonso, M.R. Martın, J. de Mendoza, T. Torres, J. Elguero, J. Heterocycles 26 (1987) 989; P. Souza, A.I. Matesanz, A. Arquero, V. Fernandez, Z. Naturforsch. 49b (1994) 665. [9] P. Souza, A.I. Matesanz, P. Navarro, J. Inorg. Biochem. 86 (2001) 439 (ICBIC 10 Florence 2001). [10] A. Bacchi, M. Carcelli, M. Cosla, P. Pelagatti, C. Pelizzi, G. Pelizzi, J. Chem. Soc., Dalton Trans. (1996) 4239; M. Bonamico, V. Fares, L. Petrilli, F. Tarli, G. Chiozzini, C. Riccucci, J. Chem. Soc., Dalton Trans. (1994) 3349. [11] P. Souza, A. Arquero, A. Garcıa-Onrubia, V. Fern andez, A.M. Leiva, U. M€ uller, Z. Naturforsch. 44b (1989) 946.