New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents

In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(II) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X = Cl or PF(6), were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs.     

Carbohydrate-appended 2,2'-dipicolylamine metal complexes as potential imaging agents

Three discrete carbohydrate-appended 2,2'-dipicolylamine ligands were complexed to the {M(CO)(3)}(+) (M = (99m)Tc/Re) core: 2-(bis(2-pyridinylmethyl)amino)ethyl-beta-d-glucopyranoside (L(1)()), 2-(bis(2-pyridinylmethyl)amino)ethyl-beta-D-xylopyranoside (L(2)()), and 2-(bis(2-pyridinylmethyl)amino)ethyl-alpha-d-mannopyranoside (L(3)). An ethylene spacer is used to separate the carbohydrate moiety and the dipicolylamine (DPA) function in all three ligands. The Re complexes [Re(L(1-3))(CO)(3)]Br were characterized by (1)H and (13)C 1D/2D NMR spectroscopies, which confirmed the pendant nature of the carbohydrate moieties in solution. NMR measurements also established the long-range asymmetric effect of the carbohydrate functions on the chelating portion of the ligand. One analogue, [Re(L(1))(CO)(3)]Cl, was characterized in the solid state by X-ray crystallography. Further characterization was provided by IR spectroscopy, elemental analysis, conductivity, and mass spectrometry. Radiolabeling of L(1)-L(3) with [(99m)Tc(H(2)O)(3)(CO)(3)](+) afforded high yield compounds of identical character to the Re analogues. The radiolabeled compounds were found to be stable toward ligand exchange in the presence of a large excess of either cysteine or histidine over a 24-h period.     

Transition metal ion complexes of thiosemicarbazones derived from 2-acetylpyridine. Part 7. Chemical and antifungal properties of 2-acetylpyridine4 N-ethylthiosemicarbazone and its metal complexes

Summary Spectral and thermal information, as well as activity againstAspergillus niger, have been obtained for 2-acetylpyridine⁴ N-ethylthiosemicarbazone and its iron(III), cobalt(II,III), nickel(II) and copper(II) complexes.     

Transition metal ion complexes of thiosemicarbazones derived from 2-acetylpyridine. Part 3. The 3-hexamethyleneimine derivative

Summary Metal ion complexes of the thiosemicarbazone, 3-hexamethyleneimine-3-thiocarboxylic acid-2-[1-(2-pyridyl)-ethylidene]hydrazide (HLhexim) have been prepared and spectrally characterized. HLhexim coordinates primarily as the deprotonated tridentate ligand (i.e., pyridylN, azomethineN, and thione sulphur). The air oxidised cobalt(III) complex, [Co(LHexim)₂] (BF₄), was isolated from the preparation with cobalt(II) tetrafluoroborate, but other cobalt(II) salts yielded tetrahedral cobalt(II) compounds. Planar nickel(II) and copper(II) complexes were isolated from preparations with halide salts. Significant differences in the spectral properties of the various complexes are observed when compared to other thiosemicarbazones prepared from 2-acetylpyridine.     

Transition metal ion complexes of thiosemicarbazones derived from 2-acetylpyridine. Part 4. The 3-piperidinyl derivative

Summary Metal ion complexes of the thiosemicarbazone, 3-piperidinyl-3-thiocarboxylic acid-2-[1-(2-pyridyl)ethylidene]hydrazide (HLpip) have been prepared and spectrally characterized. HLpip coordinates both as the deprotonated ligand (i.e., pyridylN, azomethineN, and thione sulphur) and the neutral ligand (i.e., pyridylN and azomethineN) with the sulphur possibly weakly coordinating in [Ni(HLpip)₂](BF₄)₂. All three preparative cobalt(II) salts yielded cobalt(III) cationic complexes. The nickel(II) and copper(II) chloride salts gave [M(Lpip)Cl] solids while complexes involving the neutral ligand were prepared with the corresponding bromide salts. Significant differences in the spectral properties of the various complexes are observed when compared to other thiosemicarbazones prepared from 2-acetylpyridine.     

Spectral nature,antifungal activity and molecular structure of metal complexes of acetylpyrazine 4N-substituted thiosemicarbazones

Summary Nickel(II) and copper(II) complexes of acetylpyrazine 3-azabicyclo[3.2.2]-nonylthiosemicarbazone and nickel(II) complexes of acetylpyrazine ⁴N-methyl-, ⁴N-dimethyl-, and 3-hexamethyleneiminylthiosemicarbazone have been synthesized and characterized by their spectral and physical properties. Crystal structures for the nickel(II) complexes of the ⁴N-methyl- and ⁴N-dimethyl-derivatives, with a chloro ligand in the fourth coordination position, are included. The growth inhibition by the four thiosemicarbazones and their metal complexes against two human pathogenic fungi, Aspergillus niger and Paecilomyces variotii, have been evaluated.     

Transition metal complexes of a potential anticancer quinazoline ligand

A new heterocycle, namely 2-(furyl)-3-(furfuralimino)-1,2-dihydroquinazolin-4(3H)-one (ffdq) was formed by the condensation of 2-aminobenzoylhydrazide with furfural and characterized by physico-chemical, spectroscopic, and single crystal X-ray diffraction studies. A series of complexes of ffdq have been synthesized and characterized by physico-chemical, spectroscopic, and thermal studies. According to the i.r. and ¹H-n.m.r. spectra ffdq behaves as a bidentate ligand coordinating through quinazoline oxygen and azomethine nitrogen. The FAB-mass spectrum of the Cd(II) complex indicates the monomeric nature of this complex. The X-band e.p.r. spectrum of the Cu(II) complex and thermal stabilities of the Co(II) and Ni(II) complexes are discussed.     

Transition metal complexes as molecular machine prototypes

The field of molecular machines, i.e. multicomponent systems able to undergo large amplitude motions under the action of an external signal, has experienced a spectacular development since the beginning of the 1990s. Transition metal complexes have played an important role in this context, often as components of catenanes and rotaxanes. The present tutorial review will discuss a few systems of this type, taken from the contributions of our group or from others. The stimulus responsible for the controlled motion of the machine can be chemical, electrochemical, or photochemical. Examples of these three categories will be considered.     

Transition metal complexes of 3-cyano- and 3-nitroformazans

The synthesis and characterization of six transition metal complexes of 3-cyano- and 3-nitroformazans are described. Three different formazans were reacted with nickel(II) to produce complexes with bidentate formazan ligands. Mononuclear NiL2 (L = deprotonated formazan) or binuclear hydroxo-bridged (LNi)2(mu-OH) 2 species were produced depending on the steric bulk on the formazan N-aromatic substituents. 1,5-Bis(2-methoxyphenyl)-3-cyanoformazan acts as a tetradentate monoanionic ligand in a copper(II) complex, whereas the analogous 1,5-bis(2-hydroxyphenyl)-3-cyanoformazan binds as a trianion in a tetradentate manner to Fe(III) and Co(III). Crystal structures-the first examples of metal complexes of cyano- or nitroformazans-as well as the electronic spectra of the complexes are discussed in relation to each other as well as that of the uncoordinated formazans.     

The synthesis of some 4-nitroisothiazoles as potential antifungal agents

5-Chloro-3-methyl-4-nitroisothiazole (III) was prepared by nitration of 5-chloro-3-methyliso-thiazole. Compound III was found to exhibit significant antifungal activity in vitro against a wide spectrum of fungi. The synthesis of 3-methyl-4-nitro-5-nitroamino, 5-carboxamido, 5-N,N-dimethylamino and 5-β-hydroxyethylaminoisothiazole are here reported. The synthesis of 3-methyl-4-nitroso-5-ethylthioisothiazole (IX) is reported via an unusual reaction of 5-bromo-3-methyl-4-nitroisothiazole (I) and sodium ethyl mercaptide. 5-Bromo-4-nitroisothiazole was prepared by nitration of 5-bromoisothiazole. The nitro group was shown to be essential for antifungal activity.     

Transition metal ion complexes of thiosemicarbazones derived from 2-acetylpyridineN-oxide. II. The4 N-dimethyl derivative

Summary Metal ion complexes of 2-acetylpyridineN-oxide⁴ N-dimethylthiosemicarbazone (HLO4DM), have been prepared and spectroscopically characterised. The presence of two alkyl groups at⁴ N facilitates loss of the hydrogen from² N since HLO4DM is found as the anionic ligand in the majority of its complexes. The anionic LO4DM bonds to the metal ions via theN-oxide oxygen, the azomethine nitrogen, and the thiol sulphur atoms. The infrared, electronic, and electron spin resonance spectra of these complexes are compared to 2-acetylpyridineN-oxide⁴ N-methylthiosemicarbazone as well as 2-acetylpyridine⁴ N-dimethylthiosemicarbazone.     

Transition metal ion complexes of thiosemicarbazones derived from 2-acetylpyridineN-oxide. I. The 4-methyl derivative

Summary TheN-methyl-2-[1-(2-pyridinyl-1-oxide)ethylidene]hydrazinecarbothioamide, HLO4M, has been used to prepare a series of Co^III, Ni^II and Cu^II complexes. Species with two deprotonated LO4M ligands, one LO4M and one HLO4M ligand, two HLO4M ligands and one HLO4M ligand with two small anionic ligands have been isolated. The deprotonated LO4M bonds as a tridentate ligandvia theN-oxide oxygen, the imine nitrogen (N¹ and the sulphur while the HLO4M ligand coordinates primarily as a bidentate ligandvia only the first two atoms listed above. I.r., electronic, mass and e.s.r. spectra have been used to determine the nature of these complexes. One of the more striking differences between these compounds and those prepared with other thiosemicarbazones of 2-acetylpyridine and 2-acetylpyridineN-oxide is that tetrahedral yellow [Ni(HL)X₂] rather than planar brown [NiLX] (X=Cl or Br) solids have been isolated with this ligand. Other differences in the nature of the coordination spheres of the various metal ions occur with this particular ligand when compared to previously studied thiosemicarbazone complexes.NATO Fellow, on leave from Medical Faculty, Istanbul University.     

Rhodium-105 complexes as potential radiotherapeutic agents

Rhodium-105 complexes have been investigated for their suitability as the basis of potential bifunctional chelating agents for therapeutic radiopharmaceuticals. Rhodium-105 is a reactor-produced therapeutic radionuclide that is available in high specific activity. The chemistry and biology of several six-coordinate Rh(III) complexes of the general form [RhCl2L]+, where L is a tetradentate ligand containing at least three thioethers donor atoms, is discussed. The backbone chain length of the acyclic or macrocyclic ligand determines the geometry about the Rh(III) centre (cis vs. trans), with the larger ligands preferentially forming trans-dichloro complexes. The stability of all of the 105Rh complexes is very high (>5 days) and the biological clearance properties of the complexes are consistent with their relative lipophilicities.     

Transition metal complexes in inorganic polymers as enzyme mimics

Features of a new family of catalytic systems which represent transition metal chelates entrapped within zeolite matrices are discussed. There exists strong similarity between the behavior of these catalysts and that of natural enzymes.     

Transition metal ion complexes of thiosemicarbazones derived from 2-acetylpyridine. Part 1. The4N-methyl derivative

Summary A series of metal ion complexes of the thiosemicarbazone,N-methyl-2[1-(2-pyridinyl)ethylidene]-hydrazinecarbothioamide (HL4M) has been prepared and spectrally characterized. HL4M coordinates either as a neutral bidentate ligand (i.e., pyridyl N and imine N) or as deprotonated tridentate ligand (i.e., pyridyl N, imine N and thiol sulphur). The cobalt(II) salts yield hexacoordinated cobalt(III) cations, and an isoelectronic species, [Ni(L4M)₂], has been formed from Ni(C₂H₃O₂)₂. The remaining nickel(II) complexes involve the neutral ligand, as do two of the three copper(II) complexes. HL4M possesses a weaker ligand field and has less covalency in its bonding than related thiosemicarbazones that possess anN-dialkyl-function.     

Transition metal complexes of thioalcanamines

Summary Thioalcanamines, in which the N and S atoms are separated by two carbons, induce remarkable schistosomicidal behaviour in laboratory mice infected with the disease, a biological action which might arise from complexation of these potential ligands with metal ions. A study showed that it is possible to obtain both mono- and trimetallic complexes, and the latter can be either homo- or heterometallic.