Thermal decomposition of a generation 4.5 PAMAM dendrimer platinum drug conjugate

A nanoscale multivalent platinum drug based on a poly(amidoamine) [PAMAM] dendrimer (generation 4.5, carboxylate surface) has been synthesized and fully characterized using a variety of spectroscopic, chromatographic and thermal methods. Treatment of the dendrimer with an aqueous solution containing an excess diaquo(cis-1,2-diaminocyclohexane)platinum(II) produces a conjugate containing approximately forty (diaminocyclohexane)platinum(II) moieties at the surface of the dendrimer. This material undergoes smooth two-stage thermal decomposition to provide residual platinum oxide reflecting the platinum loading in the drug.     

Noncovalent complexes of water-soluble polymers and organoplatinum compounds as potential time-release antitumor agents

The complexation of appropriate organoplatinum compounds by water-soluble polymers has the potential to provide a time-release formulation which might afford a substantial reduction in the severity of side effects associated with use of organoplatinum antitumor agents. Both poly-(N-vinylpyrrolidone)(PVP) and poly(N-vinyl-5-methyl-2-oxazolidone)(PVOM) form stable, biologically active, molecular complexes with organoplatinum compounds containing polar aromatic ligands. Platinum compounds suitable for complexation by these polymers include cis-dichloro(4-substituted o-phenylenediamine)platinum(II), 4-substitutedcatecholato(1,2-diaminocyclohexane)platinum(II), and 4-substitutedphthallato(1,2-diaminocyclohexane)-platinum(II) compounds.     

Solid state decomposition studies on metal salicylates. Thermal decomposition of some lanthanide salicylato complexes

The thermal stability and mechanism of thermal decomposition in air of the four lanthanide complexes of 2-hydroxybenzoic acid have been studied by TG, DSC, IR and MS techniques. An analysis of the prepared compounds show that Pr(III), Nd(III) and Tb(III) form anhydrous salicylato (Hsal)⁻ complexes while the corresponding holmium compound contains four water molecules. The TG curves show two (praseodymium, terbium), three (neodymium) or four (holmium) main stages of thermal decomposition. The most unstable among the complexes studied is Ho(Hsal)₃·4H₂O which releases four water molecules in an endothermic dehydration step. Ligand molecules decompose mainly in two stages of which the first is endothermic and is attributed to the release of the ligand acid and the second is a strongly exothermic decarboxylation process. The final decomposition product is the corresponding lanthanide(III) oxide, except in the case of terbium which decomposes to Tb₄O₇.     

New Oxaliplatin-Pyrophosphato Analogs with Improved In Vitro Cytotoxicity

Two new Pt(II)-pyrophosphato complexes containing the carrier ligands cis-1,3-diaminocyclohexane (cis-1,3-DACH) and trans-1,2-diamine-4-cyclohexene (1,2-DACHEX), variants of the 1R,2R-diaminocyclohexane ligand present in the clinically used Pt-drug oxaliplatin, have been synthesized with the aim of developing new potential antitumor drugs with high bone tropism. The complexes are more stable at physiological pH than in acid conditions, with Na₂[Pt(pyrophosphato)(cis-1,3-DACH)] (1) slightly more stable than [Pt(dihydrogenpyrophosphato)(1,2-DACHEX)] (2). The greater reactivity at acidic pH ensures a greater efficacy at the tumor site. Preliminary NMR studies indicate that 1 and 2 react slowly with 5’-GMP (used as a model of nucleic acids), releasing the pyrophosphate ligand and affording the bis 5’-GMP adduct. In vitro cytotoxicity assays performed against a panel of four human cancer cell lines have shown that both compounds are more active than oxaliplatin. Flow cytometry studies on HCT116 cells showed that the pyrophosphato compounds with the non-classical 1,3- and 1,4-diaminocyclohexane ligands (1 and 4) are the most capable to induce cells’ death by apoptosis and necrosis.     

(1,4,7,10-Tetraazacyclododecane) (diamine or alanine)-Cobalt(III) complexes

(1,4,7,10-Tetraazacyclododecane) [diamine or (S)-alanine]-cobalt(III) complexes [diamine = ethylenediamine, 2-(aminomethyl)pyridine, (R)-1,2-propanediamine, (R,R)-1,2-diaminocyclohexane, trimethylenediamine and 2-methyl-1,3-diaminopropane] are prepared and characterized spectroscopically. The ligand field transitions occur at lower energies than those of the corresponding tetraamine analogues. Severe distortions caused by the too small size of the cyclic ligand are one of the origins. The distortions also exert influence upon circular dichroism spectra.     

Synthesis and characterization of amidate bridged dimeric and oligomeric platinum complexes having short platinum-platinum interactions

A number of pivalamidate bridged dinuclear [PtII2(RNH2)4(NHCOtBu)2]2+, [PtIII2LL (RNH2)4(NHCOtBu)2]n+ (2RNH2 = 2NH3, 1,2-ethylenediamine, 1,2-diaminocyclohexane; L, L' = NO3-, H2O, or ketonate), trinuclear [{PtII(dap)(NHCOtBu)2}2PdIII]3+ (dap = 1,2-diaminopropane), tetranuclear [{PtII2(NH3)2(DACH)(NHCOtBu)2}2]4+ (DACH = 1,2-diaminocyclohexane), pentanuclear [{Pt2(C5H7O)(NH3)2Cl2(NHCOtBu)2}2PtCl4], and hexanuclear [Pt2(NH3)2(en)(NHCOtBu)2Pt(NO2)4]2 platinum complexes containing Pt(II)-Pt(II), Pt(II)-Pt(III), Pt(II)-Pd(III), and Pt(III)-Pt(III) interactions have been prepared and structurally characterized. The Pt-Pt interactions are characteristic of covalent, dative, or orbital symmetric Pt-Pt bonds. The dimeric Pt(III) complexes are able to activate C-H bonds of ketones to afford ketonate platinum(III) complexes. The Pt-Pt bonds are either doubly amidate-bridged or ligand unsupported. Their distances are 2.99-3.22 A for Pt(II)-Pt(II), 2.59-2.72 A for Pt(III)-Pt(III), 2.98 A for Pt(II)-Pt(III), and 2.66 A for Pt(II)-Pd(III) bonds depending on the oxidation states of the two metals and the ancillary ligands.     

Synthesis and thermal behavior of new ambazone complexes with some transitional cations

Ambazone is a pharmaceutical compound that possesses antiseptic activity and tested as well for anti-tumor properties. Metal complexes of Zn(II), Fe(III), and Cu(II) containing ambazone as ligand were synthesized using a molar ratio salt:ligand of 1:1, heating the mixture up to 50 °C for 6 h. Coordination compounds were characterized by thin-layer chromatography, FT-IR spectroscopy, elemental analysis, and thermal behavior. The non-isothermal experiments were carried out in order to investigate the thermal degradation process of these complexes and were performed in a dynamic air atmosphere at a heating rate β = 10 °C min^?1 from ambient temperature, up to 500 °C. It was revealed that decomposition process is a multistadial one.     

Synthesis,Crystal Structures and Spectrothermal Characterization of a Heptacoordinated Dimeric Salicylato Cadmium(II) Complex with 2,2′‐Azobispyridine (abpy), (µ‐abpy)[Cd(Hsal)2(abpy)]2

µ‐2,2′‐Azobispyridinebis[2,2′‐azobispyridinesalicylato(O)salicylato(O,O′) cadmium(II)], (µ‐abpy)[Cd(Hsal)₂(abpy)]₂ ( I ) was synthesized and characterized by IR and UV/ Vis spectroscopy, thermal analysis, and X‐ray diffraction techniques. Two abpy ligands and two salicylato ligands coordinate to the Cd²⁺ ion in a monocapped trigonal‐prismatic arrangement. The capping atom is the N3 atom. One of the two abpy ligands behaves as a “s‐frame” bridging ligand and adopts a s‐cis/ E/ s‐cis conformation, whereas the other one adopts as a s‐cis/ E/ s‐trans conformation. One of the two salicylato ligands acts as a monodentate ligand, which coordinates with the carboxylate oxygen atom, whereas the other one adopts bidentate coordination through two carboxylate oxygen atoms. The hydroxy groups of salicylato ligands, which coordinate in a monodentate fashion, are disordered over two positions, with occupancies of 0.52 for group A and 0.48 for group B. The decomposition reaction takes place in the temperature range 20–1000 °C under nitrogen. Thermal decomposition of the title complex proceeds in two stages.     

Chemical structure and glass transition temperature of non-ionic cellulose ethers

New zinc(II) propionate complexes (CH₃CH₂COO)₂Zn·Ln·xH₂O, where n=1-2, x=0 or 2, were prepared by reaction of zinc(II) propionate with heterocyclic ligands (L=theophylline, nicotinamide, methyl-3-pyridyl carbamate) and their thermal properties were studied. The prepared complex compounds were characterized by elemental analysis and IR spectra. TG/DTG and DTA measurements of the prepared compounds were performed in the air atmosphere under dynamic conditions. The thermal decomposition can be characterized as a multi-step process. The first step is attributed to the elimination of water or N-donor ligand molecules. It is followed by the decomposition of propionate anion when diethyl ketone and carbon dioxide were released. Zinc oxide was found as a final product of the thermal decomposition of the complex compounds under study. The volatile intermediate products of the thermal decomposition of zinc(II) propionate complexes were identified by IR-spectroscopy, qualitative chemical analyses and final solid product by X-ray powder diffraction method. Moreover, IR spectra suggest monodentate coordination of propionate anion to zinc. The complexes were tested against bacteria and filamentous fungi and show both antimicrobial activity and fungistatic effect towards pathogens as well as probiotic activity towards Lactobacillus paracasei.     

Synthesis, crystal structure, studies in solution and cytotoxicity of two new fluorescent platinum(II) compounds containing anthracene derivatives as a carrier ligand

Two new cytotoxic fluorescent platinum(II) compounds, cis-[Pt(A9opy)Cl2] (1) and cis-[Pt(A9pyp)(DMSO)Cl2] (2),have been designed, synthesized, and characterized by IR, 1H NMR, and 195Pt NMR spectroscopy; electrospray ionization mass spectrometry (ESI-MS); and single-crystal X-ray diffraction. The carrier ligands selected for thesynthesis of these fluorescent platinum(II) compounds are E-2-[1-(9-anthryl)-3-oxo-3-prop-2-enylpyridine] (abbreviatedas A9opy) and E-1-(9-anthryl)-3-(2-pyridyl)-2-propenone (abbreviated as A9pyp). The compound cis-[Pt(A9opy)Cl2](1) comprises a peculiar cis-platinum(II) organometallic compound, in which the platinum(II) ion is bound to the photoisomerizable carbon-carbon double bond of the carrier ligand. The effects of the metal-ion coordination on the photoisomerization of the carbon-carbon double bond of the ligand have been studied. In contrast, the carrier ligand A9pyp used for the synthesis of the cis-[Pt(A9pyp)(DMSO)Cl2] compound (2) does not undergo such anisomerization process and remains in the E conformation, while coordinated to the platinum(II) ion through the nitrogen of the pyridine ring. In addition to the synthesis and characterization, solution studies of both compounds have also been performed in detail, including NMR and ESI-MS spectroscopy. Moreover, a high degree of cytotoxicactivity of compound 1 was found, as compared to cisplatin and its corresponding platinum-free molecule, in a series of human tumor cell lines. Compound 2 was also found to be highly active against these cell lines but appeared less active compared to the platinum-free molecule.     

Interpretation of TG curves with help of high resolution mass spectrometry

The use of high resolution mass spectrometry for the determination of the thermal decomposition mechanisms of metal salicylato complexes, M(5-XHsal)₂ yH₂O (M is a divalent metal, 5-XH₂ sal is 5-substituted salicylic acid and y is the number of crystal water molecules), is discussed. The decomposition of these complexes involves dehydration and loss of ligand acid in two successive steps. The final product is the corresponding metal oxide. This study was conducted to shown that for the resolving of the detailed reaction mechanism, decomposition products both in gaseous and solid state phases must be analyzed.     

Thermal behavior of Mannich base N,N′-tetra(4-antipyrylmethyl)-1,2-diaminoethane (TAMEN) and its complexes

The thermal decomposition in air and in nitrogen atmosphere of binuclear complex compounds of Cu(II) and Co(II) containing the Mannich base N,N′-tetra(4-antipyrylmethyl)-1,2 diaminoethane (TAMEN) as a ligand, Cu₂(TAMEN)Cl₄ and Co₂(TAMEN)Cl₄, were investigated. X-ray powder diffractometry, infrared spectroscopy and simultaneous thermogravimetry-differential thermal analysis (TG-DTA), have been used to characterize and to study the thermal behavior of these compounds. The results provided information concerning the stoichiometry, crystallinity, thermal stability and decomposition mechanism of the compounds.     

Thermal degradation behaviour of some metal chelate polymer compounds with bis(bidentate) ligand by TG/DTG/DTA

Seven novel divalent transitional metal chelate polymers compounds (commonly known as chelate compounds or metal coordination complexes or polymer complexes) have been characterized by thermogravimetry (TG), differential thermal gravimetry (DTG) and differential thermal analysis (DTA) methods. Thermal decomposition behaviour of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) polymers with terphthaoyl-bis(p-methoxyphenylcarbamide) has been investigated by thermogravimetric analysis (TGA) at heating rate 10 °C min^?1 under nitrogen atmosphere. TG/DTA of chelate compounds were shown to be a stable compound against thermal decomposition which was measured on the basis of final decomposing temperature, but it is observed in some curves that decomposition takes place at low temperature due to the lattice water, which is always placed at outer coordination sphere of the central metal ion. The presence of both lattice and coordinated water were noteworthy investigated in Co(II), Ni(II) and Cu(II) chelate polymer compounds, whereas lattice water found in Zn(II), Cd(II) and Hg(II). However, Mn(II) showed only coordinated water. Thermal stabilities for release of lattice water, coordinated water and organic moiety that occur in sequential decomposition of chelate compounds are explained on the basis of ionic size effect and electronegativity. The processes of thermal degradation taking place in seven chelate polymers were studied comparatively by TG/DTG/DTA curves which indicating the difference in the thermal decomposition. Coats–Redfern integral method is used to determine the kinetic parameters for the successive steps in the decomposition sequence of TG curves. Scanning electron microscope images of some chelate polymers were shown in previous publication revealed that particle sizes of chelate polymers were found to be of nanomaterial level therefore, resulting chelate compounds might be called as nanomaterial.     

Ligating properties of tertiary phosphine/arsine sulphides or selenides,part V. Complexes of ditertiaryphosphine disulphides and diselenides with platinum(II) and platinum(IV) halides

Summary Platinum(IV)/platinum(II) chloride and bromide form 1 : 1, 1 : 2 or 3 : 2 (metal: ligand) addition compounds with 1,2-ethylene-, 1,3-propylene-and 1,4-butylene-bisdiphenyl-phosphine sulphide or selenide and 1,6-hexamethylene-bisdiphenylphosphine selenide. The adducts have been characterized by elemental analysis, i.r. and reflectance spectra, and molar conductance data. All adducts have been assigned bridged square planar or octahedral arrangements around platinum(II) or platinum(IV) ions respectively. Both oxidation states of platinum conform to class b behaviour with respect to the soft donor sulphur and selenium atoms of the ligands.Reprints of this article are not available.     

Thermal and Structural Investigation of The Reaction Between 1,2-propanediol and Ni(NO3)2⋅6H2O

The authors present the results of an investigation concerning the reaction between 1,2-propanediol and Ni(NO₃)₂6H₂O, leading to a complex containing as ligand the lactate anion (L), suggesting that the oxidation of 1,2-propanediol occurs at the primary hydroxyl group. The obtained solid homopolynuclear combination, [Ni₂(OH)₂L₂(H₂O)₂0.5H₂O]_n, has been investigated by thermal analysis, electron and IR spectroscopy,and magnetic methods. Nickel oxide obtained by thermolysis of this complex compound was characterized by IR, X-ray spectroscopy and elemental analysis. All the investigations lead to the conclusion that the complex compound is characterized by pseudooctahedral configuration of the nickel(II) ion. Thermal analysis of the homopolynuclear complex compound enabled to prove the thermal decomposition mechanism.This revised version was published online in November 2005 with corrections to the Cover Date.     

Crystallization of polypropylenewith a minute amount of β-nucleator

Triammonium-N-dithiocarboxyiminodiacetate, (NH₄)₃L, a new dithiocarbamato derivative of iminodiacetate, has been synthesized. The coordination properties of the ligand were tested in reactions with copper(II), nickel(II) and palladium(II) salts in acidic solutions. Complexes with a general formula M(H₂L)₂ were obtained, with the coordination taking place through the sulfur atoms of the dithiocarbamate moiety. The new compounds were characterized by elemental analysis, UV/VIS and IR spectroscopy, thermal analysis and magnetic measurements. In addition, the ligand was characterized by ¹H- and ¹³C-NMR spectroscopy and molar conductivity measurements. The copper(II) complex is paramagnetic, while the nickel(II) and palladium(II) compounds are diamagnetic. The thermal decomposition of all compounds is continuous and the thermal stability of the complexes is higher than that of the ligand, as expected.     

Unique properties of DNA interstrand cross-links of antitumor oxaliplatin and the effect of chirality of the carrier ligand

The different antitumor and other biological effects of the third-generation antitumor platinum drug oxaliplatin [(1R,2R-diamminocyclohexane)oxalatoplatinum(II)] in comparison with those of conventional cisplatin [cis-diamminedichloridoplatinum(II)] are often explained by the ability of oxaliplatin to form DNA adducts of different conformation and consequently to exhibit different cytotoxic effects. This work describes, for the first time, the structural and biochemical characteristics of the interstrand cross-links of oxaliplatin. We find that: 1) DNA bending, unwinding, thermal destabilization, and delocalization of the conformational alteration induced by the cross-link of oxaliplatin are greater than those observed with the cross-link of cisplatin; 2) the affinity of high-mobility-group proteins (which are known to mediate the antitumor activity of platinum complexes) for the interstrand cross-links of oxaliplatin is markedly lower than for those of cisplatin; and 3) the chirality at the carrier 1,2-diaminocyclohexane ligand can affect some important structural properties of the interstrand cross-links of cisplatin analogues. Thus, the information contained in the present work is also useful for a better understanding of how the stereochemistry of the carrier amine ligands of cisplatin analogues can modulate their anticancer and mutagenic properties. The significance of this study is also reinforced by the fact that, in general, interstrand cross-links formed by various compounds of biological significance result in greater cytotoxicity than is expected for monofunctional adducts or other intrastrand DNA lesions. Therefore, we suggest that the unique properties of the interstrand cross-links of oxaliplatin are at least partly responsible for this drug's unique antitumor effects.     

New half sandwich-type Ru(II) coordination compounds characterized by the fac-Ru(dmso-S)3 fragment: influence of the face-capping group on the chemical behavior and in vitro anticancer activity

The Ru(II) complex fac-[RuCl(dmso-S)(3)(dmso-O)(2)][PF(6)] (P2) was found to be an excellent precursor for the facile preparation in high yield of half sandwich-type compounds of the general formula fac-[RuCl(dmso-S)(3)(N)(2)][PF(6)] (e.g. (N)(2) = 1,2-diaminoethane (en, 4), trans-1,2-diaminocyclohexane (dach, 5), or 2 NH(3) (6)). Neutral half sandwich-type compounds of the general formula fac-[RuCl(dmso-S)(3)(N-O)] where N-O is an anionic chelating ligand (e.g. N-O = picolinate (pic, 7)) are best prepared from the universal Ru(II)-dmso precursor cis-[RuCl(2)(dmso)(4)] (P1). These complexes, that were fully characterized in solution and in the solid state, are structurally similar to the anticancer organometallic compounds [Ru(η(6)-arene)(chel)Cl][PF(6)](n) but, in place of a face-capping arene, have the fac-Ru(dmso-S)(3) fragment. In contrast to what observed for the corresponding arene compounds, that rapidly hydrolyze the Cl ligand upon dissolution in water, compounds 4-6 are very stable and inert in aqueous solution. Probably their inertness is the reason why they showed no significant cytotoxicity against the MDA-MB-231 cancer cell line.     

Syntheses and X-ray structures of Cu(II) and Zn(II) complexes of N,N′-dibenzyl-(R,R)-1,2-diaminocyclohexane and application to nitroaldol reaction

Chiral Cu(II) and Zn(II) complexes with N,N′-dibenzyl-(R,R)-1,2-diaminocyclohexane ligands were synthesized and characterized. X-ray crystal structures of these complexes reveal that Cu complex has the distorted square-planar geometry and the Zn one has the nearly tetrahedral pattern. The coordination of metals to the chiral diamine ligand leads to a 5-membered metallaheterocycle of (S,S)-configuration of nitrogen atoms. Their asymmetric catalytic activities to nitroaldol reaction of benzaldehyde and nitromethane were examined. The difference of the geometry around metals leads to the opposite preferential configuration of alcohol products using these chiral complexes as asymmetric catalysts in the presence of triethylamine or diisopropylethylamine.     

Thermal and structural studies of the chloro complexes of cobalt and copper with 2-amino-3-methylpyridine

The chloro complexes of 2-amino-3-methylpyridine with cobalt(II) and copper(II) have been prepared in ethanolic solution and solid compounds have been isolated. The compounds have stoichiometry ML₂Cl₂ whereM is Co²⁺ or Cu²⁺ and L is 2-amino-3-methylpyridine. Spectral and magnetic studies have been used to obtain information about the environment of the metal ion in these compounds. The compounds have tetrahedral structures. The thermal decomposition of each compound has been studied using thermogravimetry and differential thermal analysis. Thermogravimetry studies show that the cobalt complex forms an intermediate compound before the metal oxide is produced while the copper compound undergoes decomposition with loss of organic ligand and the formation of copper chloride which then decomposes to give an oxide of copper. The enthalpy of reaction for each of the processes has been calculated from the thermal analysis curves.