Thiosemicarbazone complexes

The metal dependence of ribonucleotide reductase is cobalt as vitamin Bi2 (prokaryotes) and iron (eukaryotes), with some evidence for manganese as cofactor [66]. The reader is referred to Ref. [66] for a recent discussion on the mechanism of these interesting enzymes. In essence, the reaction can be described  

The role of the metal ion is believed to be to generate and stabilize radicals which mediate the hydrogen transfer from a cysteine-SH to the ribonucleotide substrate. 

The carboxaldehyde thiosemicarbazones are the most active inhibitors of the mammalian reductases [66]. Originally, it was proposed that the ligand simply masked the enzyme site, but more recent results suggest that the complex formed from iron and the ligand is the active species, destroying (in an oxygen-dependent reaction) the enzyme s free radical, which is essential to the catalytic process [67]. These results explain the fact that inhibition increases with added iron [68, 69] whereas iron chelators [70, 71] and added dithiol [68, 72] decrease the potency of inhibition. 

The recognition of ribonucleotide reductase as a barrier for cellular proliferation should be of considerable interest for the design of other 

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Table 1. ESR parameters for iron(III) thiosemicarbazone complexes at 77 K as powders...

Iron(III) complexes have also been prepared with 2-acetylpyridine N-phenylthiosemicarbazone [142], 14. Three have been formulated as square pyramidal [Fe(14-H)A2] (A = Cl, NCS and NOj) based, in part, on molar conductivities of 37-62 ohm cm mol . Their ESR spectra in frozen DMF are essentially the same as for other Af-substituted species, which likely indicates the presence of [FeL2] ions. More recently [138], [Fe(14-H)2]C104 has been isolated and its solid ESR spectrum is reported to be axial with g > g - Table 1 summarizes the g-values of iron(III) heterocyclic thiosemicarbazone complexes. 

Preparations of heterocyclic thiosemicarbazone complexes with cobalt(II) salts of weakly coordinating anions (e.g., perchlorate and tetrafluoroborate) often result in cobalt(III) complexes due to air oxidation. The first 2-acetylpyridine thiosemicarbazone cobalt(III) complex was the diamagnetic [Co(15b-H)2]C104... 

Introduction of an organometallic moiety has been achieved by coupling ferrocenecarbaldehyde with thiosemicarbazide, with the resulting thiosemicarbazone (fctsc) forming the presumably octahedral cobalt(II) complex Co(fctsc)2Cl2,491 which showed antibacterial activity. Acetylferro-cene thiosemicarbazone complexes of Co were reported earlier,492 including a species of the same form as that given above. 

Fig. 9. The molecular structure of the salicylaldehyde thiosemicarbazone complex 239 clearly shows displacement of the NMe2 group of the damp ligand, which is monodentate and C-bonded. The N-H proton shows an intramolecular hydrogen bond to the chlorine atom.

Thomas AM, Naik AD, Nethaji M, Chakravarty AR. Synthesis, crystal structure and photoinduced DNA cleavage activity of ternary copper(II)-thiosemicarbazone complexes having heterocyclic bases. Inorg Chim Acta 2004 357 2315-23. 

Homogeneous uncatalysed reactions (e.g. the formation of the Co-salicylaldehyde thiosemicarbazone complex, which requires the prior oxidation of Co(ll) to Co(lll)) are less markedly affected by US than are homogeneous catalysed reactions (e.g. the oopper-catalysed oxidation of 2,2 -dipyridylketone hydrazone by hydrogen peroxide). The yield of these reactions increases by 28 and 300%, respectively, relative to unsonicated blanks. 

The thiosemicarbazone complexes CuPTSM and CuA-TSM, Fig. , have been used to image perfusion and hypoxia, respectively (36). It is believed that these compounds freely diffuse into cells. Reduction from Cu(II) to Cu(I) inside the cell causes the complex to faU apart, and the copper is trapped inside the ceU. The redox potential of CuATSM is lower than that of CuPTSM, and this redox potential is believed to be the root of the selectivity of CuATSM for hypoxic tissue. 

Parallel to the behavior previously described for the corresponding cobalt, nickel, copper, and zinc complexes, the thiosemicarbazonate complex C5H4CHN(N) = C(S)NH2)]2Cd also undergoes a reversible, ferrocenyl-centered, two-electron oxidation E° = -t-0.46 V) in acetonitrile [120],... 

Aryl tellurium trichlorides treated with the thiosemicarbazides ofbenzaldehydes or methyl phenyl ketones produced the thiosemicarbazone complexes of the aryl tellurium monochlorides . 

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...

Determination is based on the Cu-thiosemicarbazone complex formation and its extraction into benzene. Ethanol is used for dilution. 

Aldehyde, R = aryl Ru(II) pyridoxal thiosemicarbazone complex NH2OHHC1 NaHC03 (1 equiv.), CH3CN, 5 h 66-91 [93]... 

Rodrfguez-Arguelles MC, Villalonga R, Serra C, Cao R, Sanroman MA, Longo MA. A copper(II) thiosemicarbazone complex built on gold for the immobilization of lipase and laccase. J Colloid Interface Sci 2010 348 96-100. 

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