Bis Thiosemicarbazone Complexes

The carcinostatic properties of these complexes have been summarized 

Consideration of the structure and reactivity of these complexes indicated that intracellular reduction was likely, the reduction potential (Eq = —120 mV at pH 6.6) being easily in the range of biological reducing agents [58]. A general reaction for thiols is  

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The Cu(II) bis(thiosemicarbazone) complex [Cu(KTS)] (28) (where KTS is 3-ethoxyl-2-oxobutyraldehyde-bisthiosemicarbazone) is a more... 

Figure 8 The X-ray crystal structure of a Ru bis thiosemicarbazonate) complex showing an unusual four-membered chelate ring...

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]. 

Bis(thiosemicarbazones) generally behave as dianionic, tetradentate N2S2 ligands that form planar [NiL] complexes (with loss of two protons upon coordination) or planar [NiL]X (with loss of... 

Zinc complexes of cyclohexane-1,2-dione bis(thiosemicarbazone) have been formed in the neutral and doubly deprotonated form. The X-ray structures show distorted square-based pyramidal geometries for both complexes [ZnL(OH2)] and [Zn(H2L)Cl]Cl with the water or chloride occupying the axial position.886 The binuclear complex bis[l-phenylglyoxal bis(3-piperidylthiose-micarbazone)zinc] was synthesized by electrochemical methods and reveals a Zn2L2 with two tetradentate bis-thiosemicarbazone ligands bridging the metal centers.887... 

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-... 

Fig. 2.9 Chemical formulas of crown thioether complexes and Cu(I I)bis-thiosemicarbazone. 

The coordination shell comprises three fac-S and three fac-N-donor atoms in [Fe(6mp)3] [FeClJCl, where 6mp = 6-thiopurine, (189). Both iron(II) and iron(III) complexes are included in a review of transition metal complexes of thiosemicarbazones. " 5,5 -Dimethyl-l,2,3-cyclohex-anetrione-l,2-dioxime-3-thiosemi-carbazone, dcdt (190), acts as an A, A, 5 -donor to Fe +, giving a bis-ligand complex (contrast [Fe(7V,7V -dcdt)3] with Fe " "). The Schiff bases from pyridine 2-carboxaldehyde and thiosemicarbazide or 4-phenyl thiosemicarbazide also act as A, VV, 5 -donors, both to Fe " " and to Fe " ". The antibacterial activity of these complexes was assessed, in... 

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-. ... 

Two classes of ligands, shown in Fignre 17, have been extensively investigated for complexation of copper bis(thiosemicarbazones), represented by diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) and pymvaldehyde bis-(N4-methylthiosemicarbazone) (PTSM) and macrocyclic ligands exemplified by 1,4,8,11-tetraaza-cyclotetradecane-A,A, A",A" -tetraacetic acid (TETA). 

Taylor, M. R., Gabe, E. J., Glusker, J. P., Minkin, J. A., and Patterson, A. L. The crystal structures of compounds with antitumor activity. 2-Keto-3-ethoxybutyraldehyde bis(thiosemicarbazone) and its cupric complex. J. Amer. Chem. Soc. 88, 1845-1846 (1966). 

Bis(thiosemicarbazones) have been made that display powerful activity against established solid tumours in rodents, and that are dependent upon the presence of copper in the host. The N2S2 metal coordination site in these ligands reacts with Cu to form highly stable complexes. Thus, ligand substitution reactions are unfavorable. As the number of alkyl groups increases, the redox potential declines as much as 100-200 mV, until it is out of range for... 

Copper bis(thiosemicarbazones) are neutral complexes that also display a range of partition coefficients between nonpolar solvents and water. For... 

The thiosemicarbazone 88 gave the 1,3,4-thiadiazole 89 with FeCh or the dihydrothiadiazole 90 on acetylation. Similar reactions have been reported for D-galactosyl, D-glucosyl and D-mannosyl thiosemicarbazones. Tetradentate metal ion and Pd " ) complexes of the l,2-bis(thiosemicarbazone) 91... 

Tetradentate Cu, Pt and Pd complexes of the l,2-bis(thiosemicarbazone) derived from 3-deoxy-D-eryrhro-hexos-2-ulose have been prepared, and some sugar analogues of cisplatin which incorporate a mono-N-sugar-substituted ethylene diamine unit have been synthesized. ... 

Table 17 Skeletal mode assignments for copper(II) complexes of pyridyl bis(thiosemicarbazones) (/cm )...

Complexes based on thiosemicarbazones and bis(thiosemicarbazones), which represent a mixed N,S donor set of ligands. 

One of the few crystal structures solved for a metal complex of a heterocyclic thiosemicarbazone is bis(l-formylisoquinoline thiosemicarbazone) nickel(II) monohydrate, [Ni(21-H)2] (Fig. 5) [208]. The nickel(II) center was found to be NNS coordinated by two approximately planar thiosemicarbazone ligands. 

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