Synthesis and characterization of polypyridineruthenium(II) complexes containing a linear ambidentate ligand, NCO or NCS, and reaction of isocyanato complexes under acidic conditions

Isocyanato and isothiocyanatopolypyridineruthenium complexes, [Ru(NCX)Y(bpy)(py)₂]ⁿ⁺ (bpy=2,2′-bipyridine, PY=pyridine; X=O, Y=NO₂ for n=0, and Y=py for n=1; X=S, Y=NO₂ for n=0, Y=NO for n=2, and Y=py for n=1), were synthesized by the reaction of polypyridineruthenium complexes with potassium cyanate or sodium thiocyanate salt. Isocyanatoruthenium(II) complexes, [Ru(NCO)(NO₂)(bpy)(py)₂] and [Ru(NCO)(bpy)(py)₃]⁺, react under acidic conditions to form the corresponding ammineruthenium complexes, [Ru(NO)(NH₃)(bpy)(py)₂]³⁺. The molecular structures of [Ru(NCO)(bpy)(py)₃]ClO₄, [Ru(NCS)(NO)(bpy)(py)₂](PF₆)₂ and [Ru(NO)(NH₃)(bpy)(py)₂](PF₆)₃ were determined by X-ray crystallography.     

Nitrogen, sulfur and oxygen donor adducts with copper(II) complexes of antitumor 2-formylpyridinethiosemicarbazone analogs: Physicochemical and cytotoxic studies

The preparation of N-, S- and O-donor ligand adducts with CuX⁺(HX=6-methyl-2-formylpyridinethiosemicarbazone (6HL); 2-formylpyridine-2^′-methylthiosemicarbazone (2′L); 2-formylpyridine-4′-methylthiosemicarbazone (4′HL)) is described. The N-donors, 2,2′-bipyridyl (bipy), 4-dimethylaminopyridine (dmap) give the complexes [Cu(6L)(bipy)]PF₆, [Cu(6L)(bipy)]Cl·5H₂O, [Cu(4′L)(bipy)]PF₆, [Cu(6L)(dmap)₂]PF₆·2.5 H₂O and [Cu(4′L)(dmap)₂]PF₆·H₂O which have been characterized by physical and spectroscopic techniques. Pentafluorothiophenolate (pftp) gives S-donor complexes [CuX(pftp)] (X=6L and 4′L) and thiolato co-ordination is proposed on the basis of spectroscopic evidence. Paratritylphenolate (ptp) and HPO²⁻₄ give O-donor complexes [Cu(6L)(ptp)], [Cu(4′L)(ptp)], [{Cu(6L)}₂HPO₄]·4H₂O, and [{Cu(4^′L)}₂HPO₄]·5H₂O which have been characterized by physical and spectroscopic techniques, as have the precursor complexes [Cu(6L)(CH₃COO)]·H₂O, [Cu(4′L)(CH₃COO)], Cu(6HL)(CF₃COO)](CF₃COO)·0.5H₂O, [Cu(4′HL)(CF₃COO)](CF₃COO), [Cu(2′L)Cl₂] and [Cu(2′L)(NO₃)₂]. Protonation constants for the ligands and some of their complexes have been determined. 2-Formylpyridinethiosemicarbazone (HL) complexes of silver, gold, zinc, mercury, cadmium and lead are also discussed. Cytotoxicity against the human tumor cell line HCT-8 and antiviral data for selected compounds are presented.     

Reactions of the haloalcohols HO(CH2)nCl (n = 2, 3) with platinum(II) - alkynyl and -alkyne complexes. X-ray crystal structure of trans-[Pt(Me) {C(OCH2CH2Cl) (CH2Ph)} (PPh3)2] [BF4]

The chloro complexes trans-[Pt(Me)(Cl)(PPh₃)₂], after treatment with AgBF₄, react with 1-alkynes HC---C---R in the presence of NEt₃ to afford the corresponding acetylide derivatives trans-[Pt(Me) (C---C---R) (PPh₃)₂] (R = p-tolyl (1), Ph (2), C(CH₃)₃ (3)). These complexes, with the exception of the t-butylacetylide complex, react with the chloroalcohols HO(CH₂)_nCl (n = 2, 3) in the presence of 1 equiv. of HBF₄ to afford the alkyl(chloroalkoxy)carbene complexes trans-[Pt(Me) {C[O(CH₂)_nCl](CH₂R) } (PPh₃)₂][BF₄] (R = p-tolyl, N = 2 (4), N = 3 (5); R=Ph, N = 2 (6)). A similar reaction of the bis(acetylide) complex trans-[Pt(C---C---Ph)₂(PMe₂Ph)₂] with 2 equiv. HBF₄ and 3-chloro-1-propanol affords trans-[Pt(C---CPh) {C(OCH₂CH₂CH₂Cl)(CH₂Ph) } (PMe₂Ph)₂][BF₄] (7). T alkyl(chloroalkoxy)-carbene complex trans-[Pt(Me) {C(OCH₂CH₂Cl)(CH₂Ph) } (PPh₃)₂][BF₄] (8) is formed by reaction of trans-[Pt(Me)(Cl)(PPh₃)₂], after treatment with AgBF₄ in HOCH₂CH₂Cl, with phenylacetylene in the presence of 1 equiv. of n-BuLi. The reaction of the dimer [Pt(Cl)(μ-Cl)(PMe₂Ph)]₂ with p-tolylacetylene and 3-chloro-1-propanol yields cis-[PtCl₂{C(OCH₂CH₂CH₂Cl)(CH₂C₆H₄-p-Me}(PMe₂Ph)] (9). The X-ray molecular structure of (8) has been determined. It crystallizes in the orthorhombic system, space group Pna2₁, with a = 11.785(2), B = 29.418(4), C = 15.409(3) Å, V = 4889(1) ų and Z = 4. The carbene ligand is perpendicular to the Pt(II) coordination plane; the PtC(carbene) bond distance is 2.01(1) Å and the short C(carbene)-O bond distance of 1.30(1) Å suggests extensive electronic delocalization within the Pt---C(carbene)---O moietry.     

The dicarbonylation of diiodomethane to malonate esters catalysed by triethylphosphine complexes of rhodium

Rhodium complexes, in the presence or absence of PEt₃, catalyse the carbonylation of CH₂I₂ to dialkylmalonates in the presence of alcohols (ROH, R=Me, Et, Pr¹, Bu) with side products from reactions in EtOH being CH₂(OEt)₂, EtI and traces of EtCO₂Et and EtOAc. The active species when using PEt₃ is shown to be [RhI(CO)(PEt₃)₂], formed via [Rh(OAc)(CO)(PEt₃)₂] from [Rh₂(OAc)₄ · 2MeOH] and PEt₃. Mechanistic studies show that the first step of the catalytic cycle is oxidative addition of CH₂I₂ to give [Rh(CH₂I)I₂(CO)(PEt₃)₂], but that insertion of CO into the Rh---CH₂I bond gives an iodoacyl complex which is unstable. The analogous [Rh(COCH₂X)X₂(CO)(PEt₃)₂], (X=Cl or Br) have been synthesised by oxidative addition of XCH₂COX to [RhX(CO)(PEt₃)₂] and fully characterised (by X-ray crystallography, for X=Cl). [Rh(COCH₂Br)Br₂(CO)(PEt₃)₂] has also been formed from reaction of [Rh(COCH₂Cl)Cl₂(CO)(PEt₃)₂] with excess NaBr. However, the analogous reaction with NaI does not give the iodoethanoyl complex, but rather [RhI₃(CO)(PEt₃)₂] and its decomposition products. It is proposed that [Rh(COCH₂I)I₂(CO)(PEt₃)₂] is unstable towards loss of I⁻ to form the ketene complex, [RhI₂(CH₂=C=O)(CO)(PEt₃)₂]I, which is transformed into [Rh(COCH₂CO₂Et)I₂(CO)(PEt₃)] by nucleophilic attack of ethanol at the central C atom, followed by CO insertion into the Rh---C bond. An analogue, [Rh(COCH₂CO₂Et)Cl₂(CO)(PEt₃)₂], has been isolated by oxidative addition of EtO₂CCH₂COCl across [RhCl(CO)(PEt₃)₂], and characterised both spectroscopically and crystallographically. In refluxing ethanol, [Rh(COCH₂CO₂Et)Cl₂(CO)(PEt₃)₂] produces diethylmalonate and [RhCl(CO)(PEt₃)₂], thus completing the catalytic cycle. Possible pathways of deactivation of the catalyst to give [RhI₃(CO)(PEt₃)₂] are discussed. One involves the reaction of ketene with ethanol to give EtOAc, whilst the others involve protonation of the Rh---Z bond in [RhZI₂(CO)(PEt₃)₂] (where Z =CH₂I, CH₂CO₂Et or H) by HI. The isolation of CH₂DCO₂Et, when carrying out the reaction in EtOD, is consistent with all of these deactivation pathways except protonation of [RhHI₂(CO)(PEt₃)₂].     

Intramolecular and intermolecular C-H activation at a cationic Pt center

Syntheses and C-H bond activation reactions of the novel electrophilic Pt^II complexes [(tmeda)Pt(CH₃)(OEt₂)][BAr₁], [(tmeda)Pt(CH₃)(THF)][BAr_f], and [(tmeda)Pt(CH₃)(NC₅F₅)][BAr_f] are described {[BAr_f]⁻ = [(3,5-C₆H₃(CF₃)₂)₄B]⁻} (tmeda is N,N,N′,N′-tetramethylethylenediamine), [(tmeda)Pt(CH₃)(OEt₂)][BAr_f] and [(tmeda)Pt(CH₃)(THF)][BAr_f] are unstable at room temperature, yielding methane and the Fischer carbene Pt^II hydrides, [(tmeda)Pt(=C(CH₃)(OCH₂CH₃))(H)][BAr_f] and . The methane liberated from [(tmeda)Pt(CH₃)(OEt₂-d₁₀)][BAr_f] consists of an isotopomeric mixture, (CH₄, CH₃D, CH₂D₂ and CHD₃), indicating a multiple H/D exchange reaction following the C-D activation and prior to methane loss. [(tmeda)Pt(CH₃)(THF-d₈)][BAr] liberates CH₄ and CH₃D. Methane-¹³C, cyclohexane, toluene, and benzene react with [(tmeda)Pt(CH₃)(NC₅F₅)][BAr_f] to yield methane and new organoplatinum complexes. Deuterated alkanes and arenes react with [(tmeda)Pt(CH₃)(NC₅F₅] [BAr_f] to give a mixture of methane isotopomers. The relevance of these results to the oxidation of alkanes by aqueous platinum complexes is discussed.     

The use of the borocaptate anion as a ligand. Synthesis and X-ray crystal structure of pentaammine (1-thiolato-closo-undecahydrododecaborane)ruthenium(III) dihydrate

The complex [Ru(SB₁₂H₁₁)(NH₃)₅]·2H₂O has been prepared by the reaction of Cs₂B₁₂H₁₁SH with [RuCl(NH₃)₅]Cl₂ in aqueous solution. The complex represents the first reported example of the borocaptate anion acting as a ligand. The structure of the complex has been determined by single crystal X-ray diffraction analysis. The crystal parameters are monoclinic, space group P2₁/c, A = 8.056(1), B = 14.240(2), C = 15.172(2) Å, β=98.48° and Z = 4. The ruthenium atom has a distorted octahedral coordination. The distortion is probably due to the high (3⁻) charge and the large bulk of the borocaptate ligand. These features can also be observed in the spectroscopic properties of the complex.     

Diplatinum(III) complexes with bridging 1-methylcytosinate ligands and variable axial ligands, including guanine nucleobases

A series of diplatinum(III) complexes derived from cis-(NH₃)₂Pt^II and the model nucleobase 1-methylcytosine (1-MeC) has been prepared and X-ray structurally characterized, all of which contain two anionic base ligands (1-MeC⁻) in a head–tail (ht) arrangement: ht-cis-[(ONO₂)(NH₃)₂Pt(1-MeC⁻-N3,N4)₂Pt(NH₃)₂(ONO₂)](NO₃)₂·HNO₃·3H₂O (2b), ht-cis-[(NO₂) (NH₃)₂ Pt(1-MeC⁻-N3,N4)₂Pt(NH₃)₂(OH₂)](ClO₄)₃·3.5H₂O (3), ht-cis-[(OH₂)(NH₃)₂Pt(1-MeC⁻-N3,N4)₂Pt(NH₃)₂(OH₂)](ClO₄)₄·H₂O (4b), and ht-cis-[(9-EtGH-N7)(NH₃)₂Pt(1-MeC⁻-N3,N4)₂Pt (NH₃)₂(9-EtGH-N7)](NO₃)₄·9H₂O (7b) (9-EtGH=9-ethylguanine). Several other compounds, differing in the nature of the axial ligands, have been isolated and or observed in solution by ¹H and ¹⁹⁵Pt NMR spectroscopy. The chemistry of these diplatinum(III) compounds is dominated by facile substitution reactions of the axial ligands. Of particular interest in this context is the ready reaction of 2b or 3 with guanine nucleobases. Since similar compounds are not obtained with any of the other common nucleobases, 2b and 3 can be considered guanine-specific chemical probes.     

Second sphere coordination behavior of aquo and amine ligands bound to a η-benzeneruthenium(II) cation

The bis(oxazoline) ligand, 2,2-bis[4(R)-phenyl-1,3-oxazolon-2-yl]propane (bpop), was introduced to the η⁶-benzenemthenium(II) moiety on treatment with [Ru(η⁶-C₆H₆)Cl₂]₂ to give [Ru(η⁶-C₆H₆)(bpop)Cl]⁺. Aquo and amine complexes [Ru(η⁶-C₆H₆)(bpop)(L)]²⁺ (L = H₂O (1), NH₂R; R = H (2) , Me (3) , and n-Bu (4) ) were prepared by treating the chloride complex with AgBF₄ in the presence of L. X-ray structure determinations of 1 and 3 were carried out. Both complexes possessed a three-leg piano stool structure with the N or O donors located at the three comers of a pseudo octahedron. The aquo complex 1 exhibited a dynamic NMR feature in which two magnetically nonequivalent oxazoline parts observed at lower temperatures were interchanged with each other at higher temperatures. This observation was ascribed to the formation of a C₂-symmetric 16-electron intermediate via Ru-OH₂ cleavage, which is slower in acetone than in dichloromethane owing to more effective solvation by acetone around hydrogens of the coordinated water molecule. The two diastereotopic N-hydrogens of 4 underwent deuterium exchange with CD₃OD with greatly different rates from each other owing to different energy of NHO (D) (CD₃) interaction. Carboxylate and sulfonate ions (A⁻) formed second sphere complexes with 4 by means of NHA⁻ hydrogen bonding, as evidenced by continuous shift of NH₂ resonances with increasing amounts of the anions added.     

Monomeric and dimeric mixed-ligand copper(II) complexes of 2,2′-bipyridine/1,10-phenanthroline and 1-methylimidazole with imidazoles as catalysts for superoxide dismutation

Monomeric complexes [Cu(LL)(L′)(NO₃)₂] (where LL is 2,2′-bipyridine or 1,10-phenanthroline and L′ is 1-methylimidazole) and dimeric complexes [Cu₂(LL)₂(L″)]NO₃ (where L″ is an anion of imidazole or 2-methylimidazole) have been synthesized. These complexes show a d-d transition in the range of 600 to 710 nm. The infrared spectra of monomeric complexes show that the NO₃⁻ is coordinated to copper as a monodentate ligand through an oxygen atom. The ESR spectra of monomeric complexes indicate that the ligands are bonded in axial environment around copper (square pyramidal geometry) with three nitrogen donors occupying an equatorial plane. The ESR spectra of dimeric complexes show a broad signal at about G = 2 with an additional weak signal at about G = 4. This suggests that two copper atoms are in close proximity of < 7 Å. The ESR studies reveal that the formation of imidazolate-bridged binuclear copper(II) complexes from [Cu(LL)(L′)(NO₃)₂] and imidazole is pH dependent with apparent pK_a values of 8.25 to 8.30. The superoxide dismutase activity of ICu(phen)(L′)(NO₃)₂], [Cu(bipy)(L′)(NO₃)₂], and [Cu₂(bipy)₂(L′)₂(L″)]NO₃ has been measured and the latter two complexes show better activity than the former complex.     

Synthesis and structure determination of some platinum (II) complexes with hydrophilic carboxylated tertiary phosphine ligands

[Pt(COD)Cl₂] (1) reacts with PPh₂(C₆H₄COOH) (2a,b,c), PPh₂(C₆H₄COONa) (2d), PPh(C₆H₄COOH)₂ (4b,c) and P(C₆H₄COOH)₃ (6b,c) with formation of the corresponding complexes [Pt(L)₂Cl₂] (3a,b,c,d, 5b,c, 7b,c). Halide abstraction from 3a by Ag⁺ promotes coordination of the ortho-carboxylate function to platinum, yielding [ -2)}{PPh₂(C₆H₄COOH-2)}Cl] (bd8) and [ovbar|{PPh₂(C₆H₄COO-2)}₂] (bd9). Reaction of 1 with CO and 2a or 2b gives [Pt(CO)(L)Cl₂] (10a,b), wherea 1 and 2,3-bis(diphenylphosphino) maleic anhydride yields

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(bd12) and [Pt{Ph₂PC(COOH)=C(COOMe)-PPh₂}Cl₂] (13). The ¹H, ¹³C and ³¹P NMR spectra are reported and discussed. The X-ray structural analysis of 3b showed the compound to be monoclinic, space group P2₁/n, Z=4, with a=1038.5(3), B=1792.6(4), C=2311.5(4) pm, β=91.6(2)° and D_calc=1.353 g cm⁻³. The structure was solved from 4832 observed reflections with F₀ > 4 σ(F₀) and refined to a final R value of 0.0743. The Pt atom is surrounded by two Cl and two P atoms in a square planar arrangement.     

Ammonia ruthenium complexes for the access to new hydrido, carbonyl and isocyanide ruthenium-alkynyl derivatives

The potential in preparative chemistry of the precursors trans-[Ru(NH₃)(CC---R¹)(Ph₂PCH₂CH₂PPh₂)₂]PF₆ (3) has been studied. They offer a convenient access, by NH₃ displacement, to new functional alkynyl-ruthenium derivatives. Complexes 3 react with alkynes HCC---R² to give unsymmetrical trans-Ru(---CC---R¹)(---CC---R²)(dppe)₂ compounds 4a-c, and with sodium methoxide in methanol they open the route to a variety of mixed hydride complexes 5a-c, trans-Ru(H)(---CC---R¹)(dppe)₂. In contrast, with carbon monoxide or isocyanides CN---R³ (R³:CH₂Ph, C₆H₁₁, Me₃C) they allow the preparation of cationic derivatives trans-(Ru(CO)(---CC---R¹)(dppe)₂]PF₆ (6a-c) or trans-[Ru(CNR³)(---CC---R¹)(dppe)₂]PF₆ (7a-d).     

Breast cancer inhibiting diastereomeric diacetato[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) derivatives: synthesis and studies on the relationship between reactivity and antitumor activity

Antitumor active [1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) diastereoisomers containing acetic acid derivatives as ‘leaving groups’ (acetate: meso/rac-4F-Pt(Ac)₂; monochloroacetate: meso/rac-4F-Pt(ClAc)₂; dichloroacetate: meso/rac-4F-Pt(Cl₂Ac)₂; trichloroacetate: meso/rac-4F-Pt(Cl₃Ac)₂; glycolate: meso/rac-4F-Pt(OHAc)₂; phenylacetate: meso/rac-4F-Pt(PhAc)₂) were synthesized and characterized by IR and ¹H NMR spectroscopy. In all complexes except meso/rac-4F-Pt(PhAc)₂, which exist as [meso/rac-4F-PtPhAc]⁺PhAc⁻, both carboxylic acid residues are coordinated to platinum. Kinetic studies on the reaction behavior of the title compounds with nucleophiles were performed by using iodide as nucleophile. The studies show that the new complexes react with nucleophiles predominantly via the ‘solvent path’ (i.e. via the reactive intermediates = Pt(X)(OH₂)⁺ and =Pt(OH₂)₂²⁺. Therefore the rates of reactions in which the reactive species are formed affect the antitumor activity of the complexes as well as their inactivation by bionucleophiles during the transport to the tumor. The extent of accumulation in the tumor cell, too, influences the antitumor activity of a complex. The rate constants are discussed in view of the activities of the respective complexes on the human MCF-7 breast cancer cell line. From the title compounds the Cl₂Ac and Cl₃Ac derivatives do not come close to the standard cisplatin, neither in chemical reactivity nor in biological activity. Meso/rac-4F-Pt(Ac)₂ and meso/rac-4F-Pt(ClAc)₂, respectively, show similar hydrolysis rates but lower antitumor activities than cisplatin, presumably due to a reduced drug uptake by the tumor cell. Meso/rac-4F-Pt(PhAc)₂ compare well with their standard carboplatin in respect to both properties. Other than the remaining, poorly water soluble title compounds, meso/rac-4F-Pt(OHAc)₂ equal their standard cisplatin in terms of water solubility and antitumor activity rac-4F-Pt(OHAc)₂ > meso-4F--Pt(OHAc)₂). However, they are markedly faster hydrolyzed than cisplatin. By use of rac-4F-Pt(Ac)₂ as an example it was confirmed that, in contrast to the parent compound rac-4F-PtCl₂, the new complex type is also active under in vivo conditions owing to its markedly lower reactivity (mainly due to the lack of a direct substitution by strong nucleophiles), which entails a reduced inactivation of the drug on its way to the tumor. The in vitro testing on tumor cell lines combined with the evaluation of the water solubility and with kinetic studies on the reaction with nucleophiles is a useful method for the preselection of potent platinum complexes deserving further thorough in vitro and in vivo investigations.     

Mixed anion lanthanide(III) crown ether complexes: crystal structures of [LaCl2(NO3)(12-crown-4)]2, [La(NO3)(OH2)4-(12-crown-4)]Cl2·CH3CN and [LaCl2(NO3)(18-crown-6)]

Reaction of LaCl₃·7H₂O containing small amounts of La(NO₃)₃·7H₂O as an impurity with 12-crown-4 or 18-crown-6 in 3:1 CH₃CN:CH₃OH resulted in the isolation of the mixed anion complexes [LaCl₂(NO₃)(12-crown-4)]₂, [La(NO₃)(OH₂)₄(12-crown-4)]Cl₂·CH₃CN and [LaCl₂(NO₃)(18-crown-6)]. The nine-coordinate dimer, [LaCl₂(NO₃)(12-crown-4)]₂, has all of the anions in the inner coordination sphere and La³⁺ has a capped square antiprismatic geometry. It crystallizes in the orthorhombic space group Pbca with (at −150 °C) a = 12.938(6), B = 15.704(3), C = 13.962(2) Å, and D_calc = 2.08 g cm⁻³ for Z = 4. The second complex isolated from the same reaction, [La(NO₃)(OH₂)₄(12-crown-4)]Cl₂·CH₃CN, has the bidentate nitrate anion in the inner coordination sphere but the two chloride anions are in a hydrogen bonded outer sphere. This complex is ten-coordinate 4A,6B-expanded dodecahedral and crystallizes in the monoclinic space group P2₁ with (at 20 °C) A = 7.651(2), B = 11.704(7), C = 11.608(4) Å, β = 95.11(2)°, and D_calc = 1.80 g cm⁻³ for Z = 2. The 18-crown-6 complex, [LaCl₂(NO₃)(18-crown-6)], has all inner sphere anions and has ten-coordinate 4A,6B-expanded dodecahedral La³⁺ centers. It crystallizes in the orthorhombic space group Pbca with (at 20 °C) a = 14.122(7), B = 13.563(5), C = 19.311(9) Å, and D_calc = 1.89 g cm⁻³ for Z = 8.     

Reactions of PtII diamine anticancer complexes with trypanothione and octreotide

The products formed in reactions of the square-planar platinum(II) anticancer complexes, [Pt(en)Cl₂] and [Pt(R,R-dach)Cl₂] where en = ethylenediamine and dach = diaminocyclohexane, with trypanothione, a glutathione analogue found in some parasites, and octreotide, a synthetic analogue of the hormone somatostatin, have been investigated. Mononuclear and binuclear platinum adducts were formed in reactions of the cyclic disulfides in their oxidised and reduced forms, and were analysed by UV–visible spectroscopy and liquid chromatography–mass spectrometry (LC–MS). NMR and molecular modelling studies were carried out on the mononuclear adducts.     

Stopped-flow mechanistic study of bromide substitution by an organonitrile at an iron(II) phosphinic centre; a π-electron driven process

The kinetics of the displacement reactions of the bromide ligands of trans-[FeBr₂(depe)₂] (depe = Et₂PCH₂CH₂PEt₂) by the organonitrile NCCH₂C₆H₄OMe-4, in tetrahydrofuran (either in the absence or in the presence of added Br⁻), to give the corresponding mono- and dinitrile complexes trans-[FeBr(NCCH₂C₆H₄OMe-4)(depe)₂]⁺ and trans-[Fe(NCCH₂C₆H₄OMe-4)₂(depe)₂]²⁺, have been investigated by stopped-flow spectrophotometry. The substitution reaction occurs by a mechanism involving rate-limiting dissociation of bromo ligands to form the unsaturated intermediates [FeBr(depe)₂]⁺ (k₁ = 1.52 ± 0.02 s⁻¹) and [Fe(NCR)(depe)₂]²⁺ (k₃ = 0.063 ± 0.008 s⁻¹) which add the nitrile ligand to form those nitrile complexes. The competition between the nitrile and Br⁻ for such metal centres has also been investigated and a stronger inhibiting effect of added Br⁻ is observed for the substitution of the second bromo ligand relative to the first one. The kinetic data are rationalized in terms of π-electronic effects of these unsaturated metal centres and of the bromide and nitrile ligands.     

Crown ether mediated cadmium halide dimers and polymers

The reactions of cadmium halides with the 15-membered macrocyclic crown ethers, 15-crown-5 and benzo-15-crown-5, have been carried out and six new complexes have been isolated and structurally characterized. Metal to ligand stoichiometries of 1:1, 2:1, 3:1 and 3:2 have been observed with a variety of different formulations. Examples of charge separated ion pairs ([(NH₄)(benzo-15-crown-5)₂]₂[Cd₂I₆]), halogen bridged monomers, dimers or polymers ([Cd(15-crown-5)(OHMe)(μ-Br)CdBr₃], [Cd(15-crown-5)(μ-Br)₂CdBr(μ-Br)]₂(isolated from the same reaction mixture) and [(CdCl₂)₂CdCl₂(15-crown-5)]_n), and hydrogen bonded finite chains or polymers ([(Cd(OH₂)₂(15-crown-5)][CdI₃(OH₂)]₂·2(15-crown-5)·2CH₃CN and [CdI₂(OH₂)₂(THF)]·benzo-15-crown-5) have been isolated. Three different types of 15-crown-5 coordination modes have been observed in these complexes. In-cavity coordination resulting in pentagonal bipyramidal geometries about Cd²⁺ was observed in [(CdCl₂)₂CdCl₂(15-crown-5)]_n, [Cd(15-crown-5)(OHMe)(μ-Br)CdBr₃], and [Cd(OH₂)₂(15-crown-5)][CdI₃(OH₂)]₂·2(15-crown-5)·2CH₃CN, [Cd(15-crown-5)(μ-Br)₂CdBr(μ-Br)]₂ displays out-of-cavity coordination with one etheric donor distorted into an axial position of a distorted pentagonal bipyramid. The third coordination mode is secondary sphere coordination via hydrogen bonding which is observed for [Cd(OH₂)₂(15-crown-5)][CdI₃(OH₂)]₂·2(15-crown-5)·2CH₃CN. The good fit of Cd²⁺ within the cavity of 15-crown-5 results in shorter bonding contacts and a more narrow distribution in Cd---O values (2.273(7)-2.344(6) Å) than observed for cadmium halide complexes of 18-crown-6 (Cd---O = 2.69(1)–2.81(1) Å).     

Mono- and polynuclear complexes of Pt(II) with polypyridyl ligands. Synthesis, spectroscopic and structural characterization and cytotoxic activity

An array of poly- and mononuclear complexes of Pt(II) with polypyridyl ligands is reported. The framework complexes [(PtCl(2))(2)(bpp)(2)(micro-PtCl(2))](H(2)O)(2) [bpp=2,3-bis(2-pyridyl)pyrazine], [PtCl(2)(micro-tptz)PtClNCPh]Cl [tptz=2,4,6-tris(2-pyridyl)-1,3,5-triazine], and mononuclear PtCl(2)(NH(2)dpt) [NH(2)dpt=4-amino-3,5-bis(2-pyridyl)-1,2,4-triazole] have been prepared and structurally characterized. Both neutral and ionic complexes are present, with bifunctional and monofunctional Pt(II) moieties, whose size and shape enable them to behave as novel scaffolds for DNA binding. Pt(II) complexes were tested for their biological activity. Cell viability assay and flow cytometric analysis demonstrated that these complexes, particularly [PtCl(2)(micro-tptz)PtClNCPh]Cl, were effective death inducers in human colon rectal carcinoma HT29 cells and their cytotoxic activity was higher than that exerted by cisplatin. Morphological analysis of treated HT29 cells, performed by fluorescence microscopy after Hoechst 33258 staining, showed the appearance of the typical features of apoptosis. Moreover, our results suggested that mitochondria are involved in apoptosis induced by Pt(II) complexes in HT29 cells as demonstrated by dissipation of mitochondrial transmembrane potential.     

Platinum(II), platinum(IV), and palladium (II) complexes of amino substituted phosphine oxides: synthesis, characterization, and antitumor activity

The complexes [Pt(dapo)2Cl2], [PtNH3(dapo)Cl2], [Pt(py)(dapo)Cl2], [Pt(mbpo)Cl2].H2O, [Pt(mbpo)(OH)2Cl2].H2O, [Pd(dapo)2Cl2], and [Pd(mbpo)Cl2], where dapo is dimethyl aminomethylphosphine oxide and mbpo is methyl bis(aminomethyl)phosphite oxide have been synthesized and characterized by elemental analyses, electric conductivity, infrared, 1H NMR and electronic spectra. The ligands are found to be coordinated only via the amino groups. The complexes are of cis-square planar configuration with the exception of [Pt(mbpo)(OH)2Cl2].H2O which is pseudo-octahedral. An in vivo antitumor screening of the complexes against Leukemia L1210 was performed. A considerable activity (T/C = 233%) was observed for [PtNH3(dapo)Cl2]. The activity of the remaining complexes was below the accepted criterion.     

Facile syntheses and characterization of pentaamminechromium(III) complexes with neutral O- and N-bound ligands

The ready substitution of coordinated trifluoromethanesulfonate on pentaamminechromium(III) has been applied to the facile synthesis of a range of complexes of neutral ligands, [Cr(NH₃)₅(L)]³⁺ (L = OH₂, OHCH₃, OS(CH₃)₂, OP(OCH₃)₃, OC(NH₂)₂, OC(NHCH₃)₂, OC(CH₃) · N(CH₃)₂, OCH · NH₂, OCH · N(CH₃)₂, NCCH₃, NH₃ and imidazole). The complexes have been characterized by microanalysis, electronic and infrared spectroscopy, and the lability of the neutral ligand towards acid hydrolysis determined, and compared with cobalt(III) analogues.     

New extracellular resistance mechanism for cisplatin

The HSQC NMR spectrum of ¹⁵N-cisplatin in cell growth media shows resonances corresponding to the monocarbonato complex, cis-[Pt(NH₃)₂(CO₃)Cl]⁻, 4, and the dicarbonato complex, cis-[Pt(NH₃)₂(CO₃)₂]⁻², 5, in addition to cisplatin itself, cis-[Pt(NH₃)₂Cl₂], 1. The presence of Jurkat cells reduces the amount of detectable carbonato species by (2.8 ± 0.7) fmol per cell and has little effect on species 1. Jurkat cells made resistant to cisplatin reduce the amount of detectable carbonato species by (7.9 ± 5.6) fmol per cell and also reduce the amount of 1 by (3.4 ± 0.9) fmol per cell. The amount of detectable carbonato species is also reduced by addition of the drug to medium that has previously been in contact with normal Jurkat cells (cells removed); the reduction is greater when drug is added to medium previously in contact with resistant Jurkat cells (cells removed). This shows that the platinum species are modified by a cell-produced substance that is released to the medium. Since the modified species have been shown not to enter or bind to cells, and since resistant cells modify more than non-resistant cells, the modification constitutes a new extracellular mechanism for cisplatin resistance which merits further attention.