Acetylpyridine Thiosemicarbazones and S-Alkyldithiocarbazates

Treatment via chelation has been observed for 2-acetylpyridine thiosemi-carbazone derivatives, which have been found to possess inhibitory activity for the RNA-polymerases of the influenza virus [133]. The iron(III) complexes were shown to be 3 to 6 times more active as inhibitors of partially purified ribonucleotide reductase (no added iron) compared to uncomplexed thiosemi-carbazone [128]. Raina and Srivastava [134] prepared and characterized low spin iron(III) complexes of 2-acetylpyridine thiosemicarbazone, [Fe(8-H)2A] (A = NO3, OH, Cl, N3, NCS or NO2), which were proposed as being seven-coordinate. However, all but the azide complex are 1 1 electrolytes in DMF and their solid ESR spectra are rhombic with the g-values being about 2.20,2.15 and 2.00. Of the six complexes, the azide ion seems to interact ihost strongly with the iron(III) center. 

There have been no reports of complexes of JV-substituted thiosemicarbazones derived from 2-formylpyridine, but 2-acetylpyridine JV-methyl-thiosemicarbazone, 3a, formed [Fe(3a-H)2]C104 and [Fe(3a-H)2]FeCl4 [117]. The nature of these two species was established by partial elemental analyses, molar conductivities, magnetic moments, electronic, infrared, mass and electron spin resonance spectra. A crystal structure of a related selenosemicarbazone complex confirmed the presence of a distorted octahedral iron(III) cation coordinated by two deprotonated anions so that each ligand is essentially planar and the azomethine nitrogens are trans to each other the pyridyl nitrogen and selenium donors are both cis. 

An iron(III) complex of 2-acetylpyridine 3-azabicyclononylthiosemi-carbazone, 4, the thiosemicarbazone that was found to have the most potent antimalarial activity of a large number of 2-acetylpyridine thiosemicarbazones tested [88], was originally formulated as 5-coordinate [Fe(4-H)Cl2], [135], but more recent studies have shown it to be [Fe(4-H)2] [FeCl4] [117]. This complex has similar antimalarial activity to that of the uncomplexed ligand, but possesses enhanced antitumor activity [136]. 

More recently additional iV-substituted thiosemicarbazones i.e., JV-di-methyl- [137, 138], 9 3-piperidinyl- [139], 10 3-hexamethyleneimine- [138, 140], 11 and 3-(4-methylpiperidinyl)- [138] 12 have all been found to yield complexes with [Fe(L-H)2] cations there is some variation in their solid state 

ESR spectra (Table 1). The JV-cyclohexylthiosemicarbazone, 13, complex formed the expected [Fe(13-H)2] with FeCl as the counterion [141]. However, [Fe(13) (13-H)H20]C104 was isolated from ethanol. Bulkiness of the cyclohexyl group, and the perchlorate ion s greater ability to hydrogen bond are probably both important to the stability of this cation. The iron(III) center is considered six-coordinate with a tridentate 13-H, bidentate 13, and a coordinated water molecule. 

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