Heterocyclization of 3-deoxy-D-erythro-hexos-2-ulose-1,2-bis(thiosemicarbazone). Crystal structure of the major diastereomer

Both thiosemicarbazone groups of the derivative 1 of 3-deoxy-D-erythro-hexos-2-ulose underwent, on acetylation, a heterocyclization process to give (5R,5'R)-2,2'-diacetamido-4,4'-di-N-acetyl-5'-(1-deoxy-2,3,4-tri-O-acetyl-D-erythritol-1-yl)-5,5'-bis(1,3,4-thiadiazoline) (2) as a major product. The X-ray diffraction data of a single crystal of 2 indicated the R,R configuration for the stereocenters of the thiadiazoline rings (C-5 and C-5'). In the solid state, 2 adopts a sickle conformation (by clockwise rotation of the C-2-C-3 axis of the sugar chain) which has a S//O 1,3-parallel interaction. In solution, as determined by (1)H NMR spectroscopy which included NOE experiments, a similar sickle conformation was observed. From the reaction mixture of acetylation of 1 was isolated the bis(thiadiazoline) 3 as a by-product. The configuration of the C-5 and C-5' stereocenters of 3 were respectively assigned as S,R by comparison of the physical and spectroscopic data of this compound with those of 2.     

Copper(I) bromide complexes from 1,2-bis(diphenylphosphano) benzene and some heterocyclic thiones

The synthesis, characterization and solid state emission properties of a series of mixed-ligand copper(I)bromide complexes containing 1,2-bis(diphenylphosphano)benzene (dppbz) and some heterocyclic thiones (L) are reported. The complexes are readily synthesized by the addition of the appropriate thione to a CuBr-diphosphane adduct in acetonitrile/methanol or acetone solution. The molecular structures of [CuBr(dppbz)(py2SH)], [CuBr(dppbz)(pymtH)] and [CuBr(dppbz)(imdtH₂)] were established by single-crystal X-ray diffraction. Each of these structures features a tetrahedral copper(I) centre with two phosphorus atoms from the chelating diphos ligand, one bromine and the exocyclic sulfur atom of the heterocyclic thioamide unit. Slow decomposition of the mixed-ligand complexes via ligand dissociation occurs when their chloroform solutions are left to stand at room temperature for several weeks. On the basis of elemental analysis, NMR and IR spectra, the resulting coloured crystals are found to contain phosphane-free coordination polymers of composition [CuBr(L)]. At room temperature, some of the molecular complexes in the solid state exhibit strong emission assigned to a metal-ligand charge transfer of type Cu(I) → π*(PPh₂).     

Palladium(II) complexes obtained from 3,4-bis(cyanamido)cyclobutane-1,2-dione dianion

Three palladium(II) complexes have been synthesized, using 3,4-bis(cyanamido) cyclobutane-1,2-dione dianion (3,4-bis(cyanamido)squarate or 3,4-NCNsq²⁻): [Pd(en)(3,4-NCNsq)] · 1.5H₂O (1) (en=1,2-diaminoethane), [Pd(en)(3,4-(NC(O)NH₂)sq)] · 0.5H₂O (2) and K₃Na[Pd₂(3,4-(NCN)₂sq)₄] · 5H₂O (3). Complex 1 has been characterized by elemental analysis, IR and ¹³C NMR spectroscopies. Complexes 2 and 3 have been characterized by single-crystal X-ray diffraction. In complex 2, the unusual hydration of the cyanamido ligand was observed, it proceeds in the coordination sphere of the palladium and leads to a chelating urea squarate ligand. Complex 3 is an anionic dinuclear complex containing four bridging cyanamido squarate ligands. In complexes 2 and 3, the 3,4-NCNsq²⁻ ligand (hydrated or not) is, for the first time, coordinated to the metal atom by the two amido nitrogen atoms, either in a chelating mode (complex 2) or in a bridging mode giving a short Pd ? Pd distance of 2.8866(15) Å (complex 3). Electrochemical studies in acetonitrile and dmf solutions have been performed on complexes 1 and 3.     

Synthesis and characterisation of Pd(II) allyl complexes derived from the diterpene carvone

A series of cationic allyl complexes of Pd(II) derived from the diterpene carvone have been synthesised and characterised using the chelating ligands, bipyridine, 1,8-phenanthroline, neocuproin, S,S (-)-Chiraphos and R (+)-Binap as co-ligands. These complexes can be readily converted to new organic products in which one C---H bond of the allyl methyl has been substituted. The structure of a bipyridyl complex as its tetraphenyl borate salt has been determined via X-ray diffraction. 2-D NOESY studies on the Chiraphos and Binap complexes are reported. The Binap, but not the Chiraphos, complex reveals η³-η³η³ isomerisation at ambient temperature.     

Preparation and characterisation of Ni(II), Pd(II) and Pt(II) complexes of 1-diphenylphosphino-2-bis (m -trifluoromethylphenyl)phosphinoethane,(m -CF3 P-P)

A series of four-coordinate, square-planar, dia- magnetic 1-diphenylphosphino-2-bis(_m-trifluoro- methylphenyl)phosphinoethane complexes of type cis-[MX₂(_m-CF₃P-P)] (M = Ni, Pd, Pt; X = Cl, Br, I or NCS) have been prepared. These complexes have been characterized by ³¹P {₁H} NMR, ¹H NMR, IR and UV spectroscopy, elemental analyses and magnetic susceptibility measurements. The effects of various substituents on the phenyl groups of the ditertiary phosphines on the solubility characteristics of the metal complexes are discussed.     

Syntheses and structures of photochromic molybdenum(II) and rhodium(II) complexes with 1,2-dicyano-1,2-bis(2,4,5-trimethyl-3-thienyl)ethene

Four novel Mo(II) and Rh(II) complexes with cis-1,2-dicyano-1,2-bis(2,4,5-trimethyl-3-thienyl)ethene (cis-dbe) or closed-dbe were synthesized and characterized. Employing [M(O₂CCF₃)₄] (M = Mo, Rh) with cis-dbe or closed-dbe afforded complex [Mo₂(O₂CCF₃)₄(cis-dbe)](benzene) (1), [Rh₂(O₂CCF₃)₄(cis-dbe)](benzene) (2), [{Mo₂(O₂CCF₃)₄}₂(closed-dbe)] (3), and [Rh₂(O₂CCF₃)₄(closed-dbe)](p-xylene) (4). The structures of four metal complexes were revealed by X-ray crystallographic analyses and the correlation between the crystal structures and the photochromic performance was discussed. In all complexes, two cyano groups of the ligand bridged two dimetal carboxylates to give a 1-D zigzag infinite chain structure. Upon irradiation with 405 nm light, complex 1 turned into reddish purple from yellow, and the color reverted to initial yellow on exposure to 563 nm light, indicating the reversible cyclization/ring-opening reaction in the crystalline phase. However, the Rh(II) complex 2 did not display similarities in reaction induced by light, which is attributable to the lower ratio of photoactive anti-parallel conformers compared with complex 1 and coordination effect of metal ions on photochromism of diarylethenes. The complexes of Rh(II) ions did not exhibit the expected reversible photoinduced behavior.     

Ni(II), Pd(II), and Pt(II) complexes of two new ditertiary phosphines, 1-diphenylphosphino-2-bis(m- or p-fluorophenyl) phosphinoethane

New complexes of the type cis-[MX₂(PP′)] (M= Ni, Pd and Pt; X=Cl, Br, I or NCS and PP′=(m- FC₆H₄)₂PCH₂CH₂PPh₂ or (p-FC₆H₄)₂PCH₂CH₂PPh₂) have been synthesized and characterized on the basis of ³¹P{¹H}NMR¹H NMR, IR and UV spectroscopy, elemental analysis and magnetic susceptibility measurements. All these complexes are found to be low spin, diamagnetic and square planar. ³¹P{¹H} spectra of these complexes exhibit extraordinarily large downfield coordination chemical shifts, J(³¹P³¹P′) and J(¹⁹⁵pt³¹P) couplings are discussed. Ring contribution (ΔR) values for palladium and platinum complexes are calculated from ³¹P NMR data.     

Zinc(II) complexes derived from pyridine-2-carbaldehyde thiosemicarbazone and (1E)-1-pyridin-2-ylethan-1-one thiosemicarbazone. Synthesis, crystal structures and antiproliferative activity of zinc(II) complexes

The complexes [ZnCl(2)(HFoTsc)xH(2)O], [Zn(FoTsc)(2)], [ZnCl(2)(HAcTsc)xH(2)O] and [Zn(AcTsc)(2)], where HFoTsc and HAcTsc is pyridine-2-carbaldehyde thiosemicarbazone and (1E)-1-pyridin-2-ylethan-1-one thiosemicarbazone respectively, have been prepared and structurally characterized by means vibrational, and NMR ((1)H and (13)C) spectroscopy. The crystal structures of the complexes [ZnCl(2)(HFoTsc)xH(2)O], [Zn(AcTsc)(2)] and [ZnCl(2)(HAcTsc)xH(2)O] have been determined by X-ray crystallography. The metal co-ordination geometry of [ZnCl(2)(HFoTsc)xH(2)O] and [ZnCl(2)(HAcTsc)xH(2)O] is described as distorted square pyramidal and the two complexes are self-assembled via pi-->pi stacking interactions and intermolecular hydrogen bonds. In these two cases molecular recognition of the hydrogen bonds leads to aggregation and a supramolecular assembly of infinite two-dimensional network. The metal co-ordination geometry of [Zn(AcTsc)(2)] is described as distorted octahedral configuration in a trans-N(2)-cis-N(1)-cis-S configuration. HFoTsc and HAcTsc and the zinc complexes have been evaluated for antiproliferative activity in vitro against the cells of two human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line) and a mouse fibroblast L-929 cell line. The cytotoxic activity shown by these compounds indicates that coupling of HFoTsc and HAcTsc to Zn(II) metal center result in metallic complexes with important biological properties since they display IC(50) values in a microM range similar to or better than that of the antitumor drug cis-platin and are considered as agents with potential antitumor activity candidates for further stages of screening in vitro and/or in vivo.     

Synthesis,characterization, DNA interaction,and cytotoxicity of novel Pd(II) and Pt(II) complexes

Four complexes [Pd(L)(bipy)Cl]·4H₂O (1), [Pd(L)(phen)Cl]·4H₂O (2), [Pt(L)(bipy)Cl]·4H₂O (3), and [Pt(L)(phen)Cl]·4H₂O (4), where L = quinolinic acid, bipy = 2,2’-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, ¹H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5?×?10⁴ M^?1, 3.9?×?10⁴ M^?1, 6.1?×?10⁴ M^?1, and 1.4?×?10⁵ M^?1, respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.     

Synthesis, X-ray crystal structure, DNA binding, antioxidant and cytotoxicity studies of Ni(ii) and Pd(ii) thiosemicarbazone complexes

New complexes, [Ni(HL)(PPh(3))]Cl (1), [Pd(L)(PPh(3))](2), and [Pd(L)(AsPh(3))](3), were synthesized from the reactions of 4-chloro-5-methyl-salicylaldehyde thiosemicarbazone [H(2)L] with [NiCl(2)(PPh(3))(2)], [PdCl(2)(PPh(3))(2)] and [PdCl(2)(AsPh(3))(2)]. They were characterized by IR, electronic, (1)H-NMR spectral data. Further, the structures of the complexes have been determined by single crystal X-ray diffraction. While the thiosemicarbazone coordinated as binegative tridentate (ONS) in complexes 2 and 3, it is coordinated as mono negative tridentate (ONS) in 1. The interactions of the new complexes with calf thymus DNA was examined by absorption and emission spectra, and viscosity measurements. Moreover, the antioxidant properties of the new complexes have also been tested against DPPH radical in which complex 1 exhibited better activity than that of the other two complexes 2 and 3. The in vitro cytotoxicity of complexes 1-3 against A549 and HepG2 cell lines was assayed, and the new complexes exhibited higher cytotoxic activity with lower IC(50) values indicating their efficiency in killing the cancer cells even at very low concentrations.     

(Dien)M(II) (M=Pd, Pt) and (NH3)3Pt(II) complexes of 1-methylcytosine: Linkage and rotational isomerism, metal-promoted deamination, and pathways to dinuclear species

Despite their structural similarity, [Pt(dien)(1-MeC-N3)](2+) (1), [Pd(dien)(1-MeC-N3)](2+) (2), and [Pt(NH(3))(3)(1-MeC-N3)](2+) (3) (with dien=diethylenetriamine and 1-MeC=neutral 1-methylcytosine) behave in part markedly different at strongly alkaline pH (12-13) and at room temperature. While 1 and 2, yet not 3 show linkage isomerization from N3 to N4, deamination of the cytosine nucleobase to 1-methyluracilate occurs with 1 and 3, yet not with 2. Pathways leading to N3,N4-diplatinated 1-MeC(-) complexes (1-MeC(-)=1-methylcytosine, deprotonated at exocyclic amino group N4) have been studied at high pH by starting from 1 and 3, respectively, and adding (dien)Pt(II). It appears that initial migration of the metal entity from N3 to N4, followed by binding of the second metal to the available N3 site, is favored over sequential coordination to N3 and then N4. X-ray crystal data of 1-3 density functional theory (DFT) calculations, and NMR ((1)H, (195)Pt) data are presented.     

Synthesis, spectroscopic properties and structural characterisation of Pd(II) and Pt(II) complexes with 1,3,5-pyrazole derived ligands. Rotation around the metal-N bond

Reactions of ligands 1-ethyl-5-methyl-3-phenyl-1H-pyrazole (L¹) and 5-methyl-1-octyl-3-phenyl-1H-pyrazole (L²) with [PdCl₂(CH₃CN)₂ and K₂PtCl₄ gave complexes trans-[MCl₂(L)₂] (L = L¹, L²). The new complexes were characterised by elemental analyses, conductivity measurements, infrared, ¹H and ¹³C{¹H} NMR spectroscopies and X-ray diffraction. The NMR study of the complex [PdCl₂(L¹)₂], in CDCl₃ solution, is consistent with a very slow rotation of ligands around the Pd-N bond, so that two conformational isomers can be observed in solution (syn and anti). Different behaviour is observed for complexes [PdCl₂(L²)₂] and [PtCl₂(L)₂] (L = L¹, L²), which present an isomer in solution at room temperature (anti). The crystal structure of [PdCl₂(L¹)₂] complex is described, where the Pd(II) presents a square planar geometry with the ligands coordinated in a trans disposition.     

Copper(I) halide complexes from cis-1,2-bis(diphenylphosphino) ethylene and some heterocyclic thiones

Reaction of copper(I) chloride or bromide with equimolar amounts of the diphos ligand cis-1,2-bis(diphenylphosphino)ethylene (dppet) and a heterocyclic thione (L) in acetonitrile/methanol solvent afforded mononuclear complexes of the type [CuX(dppet)(L)] with the diphosphine ligand acting as a chelating ligand. However, the same reaction carried out at higher temperatures proceeds, in some cases, with exclusion of the phosphine ligand from the coordination sphere leading to double-S-bridged dimers. In contrast, copper(I) iodide under the same conditions gave the thione-free dimeric compound [CuI(dppet)]₂ which contains double-bridging iodine atoms. A notable exception was for the reaction with 5-methyl-1,3,4-thiadiazole-2-thione (mtdztH) which, under the same conditions, gave rise to the unexpected, simultaneous formation of the monomer [CuI(dppet)(CH₃CN)] as well as the above mentioned dimeric [CuI(dppet)]₂. Furthermore treatment [CuX(dppet)(L)] with two equivalents of triphenylphosphine was found to cause replacement of the diphos ligand, while substitution of the chlorine atom under HCl elimination and formation of [Cu(dppet)(mftztH)₂] occured in the unique case of treating [CuCl(dppet)(mftztH)] with one additional equivalent of the same thione ligand. The structures of one representative for each of the above mentioned types of complexes, namely [CuBr(dppet)(mftztH)], [Cu(dppet)(mftztH)₂], [Cu(μ-I)(dppet)]₂ · [CuI(dppet)(CH₃CN)] and [CuBr{μ-S(pymtH)}(pymtH)]₂ have been established by single-crystal X-ray diffraction.     

Synthesis, characterization, and antitumor activity of 1,2-bis(diphenylphosphino) ethane platinum(II) and palladium(II) complexes

A number of 1,2-bis(diphenylphosphino)ethane monomeric platinum(II) and palladium(II) complexes have been synthesized in light of their potential antitumor activity. The metal center is coordinated with a number of carboxylate anions in the cis-configuration. These complexes have been characterized by elemental analysis, conductivity measurement, and various spectroscopic techniques [IR and 195Pt NMR]. In vivo screening tests for activity of these complexes were performed against the L1210/0 murine leukemia cancer model, but none displayed a significant level of antitumor activity.     

Spectral characterization of bimetallic complexes of thiosemicarbazone of monoacetylferrocene with Cu(II) halides

Monoacetylferrocenethiosemicarbazone (MAFTSC) has been investigated for its complexation behaviour towards Cu(II) halides. Two types of bimetallic complexes, MLX₂ and ML₂ (where L = MAFTSC) have been prepared and characterized through elemental analysis, conductivity measurements, UV, IR and ¹H NMR spectral techniques and by magnetic susceptibility measurements at room temperature. Conductance measurement in DMF indicated the complexes to be non-electrolytic in nature.     

Crystal structures of Pt(II) and Pd(II) complexes with the free radical 4-aminoTEMPO

Pt(II) and Pd(II) compounds containing the free radical 4-aminoTEMPO (4amTEMPO) were synthesized and characterised by X-ray diffraction methods. The disubstituted complexes cis- and trans-Pt(4amTEMPO)₂I₂ were studied. The trans isomer was prepared from the isomerisation of the cis analogue. The two Pd(II) compounds trans-Pd(4amTEMPO)₂X₂ (X = Cl and I) were also characterised by crystallographic methods. A mixed-ligand complex cis-Pt(DMSO)(4amTEMPO)Cl₂ was synthesized from the isomerisation of the trans isomer in hot water. Its crystal structure was also determined. In all the complexes, the 4amTEMPO ligand is bonded to the metal through the -NH₂ group, since the nitroxide O atom is not a good donor atom for the soft Pt(II) and Pd(II) metals. The conformation of the 4-aminoTEMPO ligand was compared to those of the few reported structures in the literature.     

Synthesis and spectroscopic properties of copper(II) complexes derived from thiophene-2-carbaldehyde thiosemicarbazone. Structure and biological activity of [Cu(C6H6N3S2)2].

The synthesis, structure and spectroscopic properties on complexes with the formula [Cu(Lm)2] (1) and Cu(NO3)2(HLm)2 (2), where HLm = thiophene-2-carbaldehyde thiosemicarbazone, have been developed. The molecular structure of compound 1 consists of monomeric entities. The copper(II) ions exhibit distorted square-planar geometry with both bidentate thiosemicarbazone ligands placed in a centrosymmetric way. Metal to ligand pi-backdonation is proposed to explain several structural and spectroscopic features in these complexes. The EPR spectra of compound 1 show an orthorhombic g tensor indicating the presence of weak magnetic exchange interactions. The reaction of compound 1 with glutathione causes the reduction of the metal ion and the substitution of the thiosemicarbazone ligand by the thiol ligand. This mechanism seems to be related to the cytotoxicity of this complex against Friend Erithroleukemia cells (FLC) and melanome B16F10 cells.     

Antiproliferative activity of Pt(II) and Pd(II) phosphine complexes with thymine and thymidine

Oxidative addition reactions between [M(PPh(3))(4)] (M=Pt and Pd) and N1-methylthymine (t)/3',5'-di-O-acetylthymidine (T) were carried out to give [M(II)(PPh(3))(2)Cl t (or T)] complexes, in which the metal is coordinated to the N3 of the base. All complexes were characterized by spectroscopic analyses (IR, NMR) and Fast Atom Bombardment mass spectrometry (FAB-MS); X-ray data for the thymine complexes and elemental analysis for the thymidine complexes are reported. The antiproliferative activity of the complexes was tested on human chronic myelogenous leukaemia K562 cells. Arrested polymerase-chain reaction analysis was carried on to correlate antiproliferative activity and inhibition of DNA replication. All Pd and Pt complexes exhibit antiproliferative activity, Pd complexes resulting always more active than Pt complexes. Arrested PCR data are strongly in agreement with the effects on cell growth, suggesting that inhibition of the DNA replication by the synthesized compounds is the major basis for their in vitro antiproliferative activity.     

Mixed complexes of Pt(II) and Pd(II) with ethylsarcosinedithiocarbamate and 2-/3-picoline as antitumor agents

The [M(ESDT)Cl](n) (M=Pt(II), Pd(II); ESDT=EtO(O)CCH(2)N(CH(3))CS(2)(-), ethylsarcosinedithiocarbamate ion) species have been reacted with 2- or 3-picoline in dichloromethane in order to obtain mixed ligand complexes of the type [M(ESDT)(L)Cl] (L=2-picoline, 3-picoline). The synthesized compounds have been isolated, purified and characterized by means of elemental analyses, (1)H-/(13)C-/(1)H(13)C-HMBC (heteronuclear multiple bonding coherence) NMR and FT-IR spectroscopy. The biological activity of the compounds reported here has been then determined in terms of cell growth inhibition, DNA synthesis inhibition, detection of interstrand cross-links and DNA-protein cross-links, and micronuclei (MN) detection on a panel of tumor cell lines both sensitive and resistant to cisplatin. On the basis of the experimental results, coordination in the above mentioned complexes takes place in a near square-planar geometry, the dithiocarbamate moiety acting as a chelating agent, whereas the two remaining coordination sites are occupied by a chlorine atom and an amino ligand. Above all, [Pt(ESDT)(2-picoline)Cl] complex has shown very encouraging cytotoxicity levels higher or, at least, comparable to those exerted by cisplatin in the same experimental conditions.