Thiosemicarbazones copper

The copper(II) complexes of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) and related compounds are active in vivo agents [151, 158, 159]. The metal complexes of 2-heterocyclic thiosemicarbazones were evaluated for their cytotoxicities [160, 161]. Further studies have revealed that these ligand s iron and copper complexes are effective inhibitors of DNA synthesis at much lower concentrations than the free thiosemicarbazones without apparent cytotoxicity [127]. Although the iron(III) complex of 2-isoformylquinoline thiosemicarbaz-one, 21, is considerably more active than free 21, the copper(II) complex is only moderately more active [127]. 

Early studies [170] of copper(II) complexes of thiosemicarbazones were 2-formylpyridine iV-methylthiosemicarbazone, 30, 6-methyl-2-formylpyridine Ai-methylthiosemicarbazone, 31, and 2-formylpyridine " JV-dimethylthiosemi-carbazone, 32. With copper(II) chloride and bromide, monomeric complexes of stoichiometry [Cu(L)A2] were isolated for each of these thiosemicarbazones. All six complexes had a band in the 14000-15000 cm spectral region, but their stereochemistry was not specified. 

The first copper(II) complexes prepared with a 2-acetylpyridine thiosemicarbazone were those of the 3-azabicyclononyl-derivative, 4, as well as the analogous selenosemicarbazone [175]. Monomeric [Cu(4-H) A] where A = Cl, Br, I, OAc and NO3 were characterized by their magnetic and spectral measurements. A second report [128] on copper(II) complexes of 4 included [Cu(4) (4-H)]BF4 as... 

Two copper(II) complexes of 2-acetylpyridine thiosemicarbazone, 8, were included in a study of complexes of 2-formylpyridine thiosemicarbazone [169]. [Cu(8-H)OAc] has a magnetic moment consistent with a monomeric copperfll) center and both it and [Cu(8)Cl2] have d,2-y2 ground state ESR spectra (Table 2). A d-d envelope and a magnetic moment of 1.68 B.M. have led others [178] to propose a distorted tetrahedral environment with metal-metal interaction for the brown complex, [Cu(8)Cl2]. 

Spectral results [180] for copper(II) complexes of 2-acetylpyridine N-dimethylthiosemicarbazone, 9, and 2-acetylpyridine 3-(4-methylpiperidine) thiosemicarbazone, 12, are included in Table 2. While the complexes of 9-H have spectral properties consistent with the other copper(II) complexes of Table 2, those of 12-H, with the exception of [Cu(12-H)F], show considerably higher values of g, and consequently higher values of k. These values indicate that there is little in-plane 7t-bonding, possibly due to the bulkiness of the 4-methylpiperidine group. 

Seven different copper(II) complexes [181] of 2-acetylpyridine iV-phenyl-thiosemicarbazone, 14, all having the general formula, [Cu(14-H)A] have been prepared and characterized. Their spectral data are included in Table 2 and g is similar to other copper(II) complexes of 2-acetylpyridine thiosemicarbazones. However, the d-d spectra all show two bands, suggesting planar stereochemistry these bands are of higher energy than the analogous complexes of the bicyclononyl derivative, 4 [128, 175]. 

A distorted tetrahedral copper(II) center has been proposed [185] for [Cu(37)Cl2] where 37 is 4-acetylpyridine thiosemicarbazone with the ring nitrogen not coordinated. 

Copper(II) complexes of 2,6-lutidylphenylketone thiosemicarbazone, 38, have been prepared from copper(II) chloride and copper(II) bromide [186]. Similar to 2-pyridyl thiosemicarbazones, 38-H coordinates via the ring nitrogen, the azomethine nitrogen and the thiol sulfur based on infrared spectral assignments. Magnetic susceptibilities and electron spin resonance spectra indicate dimeric complexes and both are formulated as [Cu(38-H)A]2 with bridging sulfur atoms. The electronic spectra of both halide complexes show band maxima at 14500-14200 cm with shoulders at 12100 cm S which is consistent with a square pyramidal stereochemistry for a dimeric copper(II) center. 

Copper(II) complexes have been prepared with the 2-acetylpyridine N-oxide 3-azabicyclo[3.2.2.]nonylthiosemicarbazone, 25, and bonding occurs via the pyridine N-oxide oxygen, azomethine nitrogen and thiol sulfur [128]. Based on electronic and ESR spectra, bonding to copper(II) of uninegative, tridentate 25-H is considerably weaker than the related 2-acetylpyridine thiosemicarbazone, 4-H. The other copper(II) complexes reported to date have been prepared... 

A copper(II) complexes of 5-phenylazo-3-methoxy salicylidene thiosemicarbazone has been shown to have promising growth inhibition activity against P388 lymphocytic leukemia cells sensitive and resistant to adriamycin [196], The complex involves ON coordination of two deprotonated ligands and v(CS) is reported to be unaltered in intensity and position in the complex from its position in the spectrum of the ligand. Inhibition studies with the uncomplexed thiosemicarbazone indicating an important role for the copper(II). 

The gallium and indium complexes of novel bis(thiosemicarbazones) have been investigated.71-73 Initial publications indicated a more complex stoichiometry where X-ray crystal structures suggested either dinuclear or trinuclear complexes. Whereas these complexes are quite interesting, they are less likely to result in useful nuclear medicine radiopharmaceuticals. The bis(thiosemi-carbazones) are quite useful as ligands for copper, and are discussed in more detail vide infra). 

Two distinct classes of ligand have been investigated for the complexation of copper the polyfunctional bis(thiosemicarbazones) and the macrocyclic ligands exemplified by 1,4,8,11-tetraaza-... 

Administration of copper dimethylglyoxime143), copper 2-keto-3-ethoxybutyralde-hyde bis(thiosemicabazone)144) or copper pyruvaldehyde bis(thiosemicarbazone)145) to rodents has led to inhibition of tumour growth. The copper(II) complex of 2-keto-3-ethoxybutyraldehyde bis(thiosemicarbazone) transports copper into neoplastic cells where it is deposited and inhibits a number of enzymes responsible for the synthesis of DNA146-. ... 

The other thiosemicarbazones are less well studied and as yet the link between antiviral action and chelation is not fully established. It has been proposed that the chelation of iron(II), a cofactor of ribonucleoside diphosphate reductase, could be the principal mode of action of the thiosemicarbazones300. However, other mechanisms are possible. Investigations of the ESR spectra of copper(II) complexes of thiosemicarbazones has been used to follow the intracellular reactions of the complexes - see Antholine et al.301 for a review. In Ehrlich cells the chelate becomes localized in the cell membrane302. This spectroscopic technique could also be used to monitor the antimala-rial action of 2-acetylpyridine thiosemicarbazones303. ... 

In a recent search for new antitumour chelates of thiosemicarbazones, Mohan et al.304 have examined the 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone chelates of cobalt(II), nickel(II), copper(II), zinc(II) and platinum(II) for antitumour properties but found antitumour activity absent. 

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