Multi-nuclear platinum complexes encapsulated in cucurbit[n]uril as an approach to reduce toxicity in cancer treatment

The dinuclear platinum complex trans-[[Pt(NH(3))(2)Cl](2)micro-dpzm](2+)(di-Pt) binds inside cucurbit[7]uril with slow exchange kinetics which does not significantly affect the cytotoxicity of the dinuclear complex but reactivity at the platinum centre is reduced.     

不对称大环双核铜(Ⅱ)配合物[Cu2(C23H26Cl2N4O2)](ClO4)2的合成、晶体结构及磁性

大环双核铜(Ⅱ)配合物由N,N′-二甲基-N,N′-二(3-甲酰基-5-氯水杨醛)乙二胺和1,3-丙二胺,与铜(Ⅱ)反应形成的,经过X-射线单晶衍射结果表明：a=0.871 05(16) nm,b=0.957 78(18) nm,c=1.810 4(3) nm,β=100.761(18)°,V=1.483 8(5) nm³,Z=2,D_c=1.762 Mg·m^-3,μ=1.85 mm^-1,F(000)=796,and final R₁=0.061,wR₂=0.126。晶体结构表明：两个铜离子位于双核大环中间,与大环的胺、亚胺以及酚羟基的氧进行配位。磁性结果表明配合物为反铁磁性。     

Crystal structure and ferromagnetic properties of the oxamidato-bridged Cu(II)–VO(IV) complex containing macrocyclic ligands

The novel oxamidato-bridged dinuclear [(CuL)VO(H₂O)(C₂O₄)] complex incorporating a macrocyclic oxamide has been synthesized, spectroscopically, structurally, and magnetically characterized, where (CuL = [5,6: 14,15-dibenzo-1,4,8,12- tetraazacyclopentadeca-7,13-diene-2,3-dione(2-)]copper(II)). Magnetic measurements indicate ferromagnetic interaction between Cu(II) and VO(IV) ions within the complex.     

Stacked platinum complexes of the magnus' salt type inside a coordination cage

Neatly wrapped up: alternately stacked square-planar platinum(II) complexes inside a dinuclear coordination cage were prepared to give a discrete and soluble Pt(5) -array of the Magnus' salt type. Characterization of the complex in solution was complemented by an X-ray crystal structure of {[Pt(pyridine)(4)]? [PtCl(4)](2) @Cage}; this structure showed the linear, pentanuclear array within the cages and their circular packing into a hollow tubular superstructure.     

Homotrinuclear lanthanide(III) arrays: assembly of and conversion from mononuclear and dinuclear units

The reactions of potentially hexadentate H2bbpen (N,N'-bis(2-hydroxybenzyl)-N,N'-bis(2-pyridylmethyl)-ethylenediamine, H2L1), H2(Cl)bbpen (N,N'-bis(5-chloro-2-hydroxybenzyl)-N,N'-bis(2-pyridylmethyl)ethylenediamine, H2L2), and H2(Br)bbpen (N,N'-bis(5-bromo-2-hydroxybenzyl)-N,N'-bis(2-pyridylmethyl)ethylenediamine, H2L3) with Ln(III) ions in the presence of a base in methanol resulted in three types of complexes: neutral mononuclear ([LnL(NO3)]), monocationic dinuclear ([Ln2L2(NO3)]+), and monocationic trinuclear ([Ln3L2(X)n(CH3OH)]+), where X = bridging (CH3COO-) and bidentate ligands (NO3-, CH3COO-, ClO4-) and n is 4. The formation of a complex depends on the base (hydroxide or acetate) and the size of the respective Ln(III) ion. All complexes were characterized by infrared spectroscopy, mass spectrometry, and elemental analyses; in some cases, X-ray diffraction studies were also performed. The structures of the neutral mononuclear [Yb(L1)(NO3)], dinuclear [Pr2(L1)2(NO3)(H2O)]NO3.CH3OH and [Gd2(L1)2(NO3)]NO3.CH3OH.3H2O, and trinuclear [Gd3(L3)2(CH3COO)4(CH3OH)]ClO4.5CH3OH and [Sm3(L1)2(CH3COO)2(NO3)2(CH3OH)]NO3.CH3OH.3.65H2O were solved by X-ray crystallography. The [LnL(NO3)] or [Ln2L2(NO3)]+ complexes could be converted to [Ln3L2(X)n(CH3OH)]+ complexes by the addition of 1 equiv of a Ln(III) salt and 2-3 equiv of sodium acetate in methanol. The trinuclear complexes were found to be the most stable of the three types, which was evident from the presence of the intact monocationic high molecular weight parent peaks ([Ln3L2(X)n]+) in the mass spectra of all the trinuclear complexes and from the ease of conversion from the mononuclear or dinuclear to the trinuclear species. The incompatibility of the ligand denticity with the coordination requirements of the Ln(III) ions was proven to be a useful tool in the construction of multinuclear Ln(III) metal ion arrays.     

One and Two-dimensional Structures of a New Oxamido Copper(Ⅱ) Complex with Phthalato Bridged

A new o-phthalato-bridged oxamide copper(Ⅱ) complex 1, {[Cu2(oxap)](pht)4H2O}n (oxap = N, N'-bis(2-aminopropyl)oxamide, pht = phthalate dianion), has been prepared and structurally characterized. It crystallizes in monoclinic, space group C2/c with a = 23.424(4), b = 7.9696(14), c = 15.727(3) (A), β = 129.617(2)°, C16H28Cu2N4O10, Mr = 563.50, V = 2261.6(7) (A)3, Z = 4, Dc = 1.655 g/cm3,μ(MoKα) = 1.939 mm 1, F(000) = 1160, the final R = 0.0393 and wR = 0.0928 for 1707 observed reflections with I ＞ 2σ(Ⅰ). Single-crystal X-ray analysis reveals that 1 displays a one-dimensional zigzag chain structure, in which each Cu(oxap) moiety adopting trans-conformation is connected by μ1,6-phthalate anion bridges, and these zigzag chains are further linked by anotherμ1,6-phthalate anion bridge to form a 2D sheet structure. The polar guest water molecules reside in the inter- and intrasheets to stabilize the whole crystal structure.     

A Redox‐Active Dinuclear Platinum Complex Exhibiting Multicolored Electrochromism and Luminescence

A redox series of cyclometalated platinum complexes based on a dinuclear motif linked by acetamidato (aam) bridging ligands, [Pt₂(μ‐aam)₂(ppy)₂] (ppy^?=2‐phenylpyridinate ion), has been synthesized. The complexes in this series are easily oxidized and reduced by both electrochemical and chemical methods, and this is accompanied by multistep changes in their optical properties, that is, multiple color changes and luminescence. Isolation of the complexes and the structural determination of three oxidation states, +2, +2.33, and +3, have been achieved. The mixed‐valent complex, with an average oxidation state of +2.33, forms a trimer based on the dinuclear motif. The mixed‐valent complex has a characteristic color owing to intervalence transitions in the platinum chain. In contrast, the divalent complex exhibits strong red phosphorescence originating from a triplet metal‐metal‐to‐ligand charge transfer (³MMLCT) state. This study demonstrates the unique chromic behavior of a redox‐active and luminescent platinum complex.     

Reactivity of a cytostatic active N,N-donor-containing dinuclear Pt(II) complex with biological relevant nucleophiles

A dinuclear platinum(II) complex that was recently investigated in our group was tested for its cytostatic activity and found to be active against HeLa S3 cells. The complex consists of a bidentate N,N-donor chelating ligand system in which the two platinum centers are connected by an aliphatic chain of 10 methylene groups. The complex [Pt(2)(N(1),N(10)-bis(2-pyridylmethyl)-1,10-decanediamine)(OH(2))(4)](4+) (10NNpy) is of further special interest, since only little is known about the substitution behavior of such dinuclear platinum complexes that contain a bidentate coordination sphere. The complex was investigated using different biologically relevant nucleophiles, such as thiourea (tu), L-methionine (L-Met), glutathione (GSH), and guanine-5'-monophosphate (5'-GMP), at two different pH values (2 and 7.4). The substitution of coordinated water by these nucleophiles was studied under pseudo-first-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The reactivity of 10NNpy with the selected nucleophiles was found to be tu ? 5'-GMP > L-Met > GSH at pH 2 and GSH > tu > L-Met at pH 7.4. The results for the dinuclear 10NNpy complex were compared to those for the corresponding mononuclear reference complex [Pt(aminomethylpyridine)(OH(2))(2)](2+), Pt(amp), studied before in our group, by which the effect of the addition of an aliphatic chain, an increase in the overall charge, and a shift in the pK(a) values of the coordinated water ligands could be investigated. The reactivity order for Pt(amp) was found to be tu > GSH > L-Met at pH 7.4.     

An asymmetric dinuclear copper(II) complex with phenoxo and acetate bridges: Synthesis, structure and magnetic studies

The dinuclear (μ₂-acetate)bis(μ₂-phenoxide)di-copper(II) complex, 1 with a tetradentate ligand, L (L = 2,4-di-tert-butyl-6-{[(2-dimethylaminoethyl)-(2-hydroxybenzyl)-amino]-methyl}-phenol) has been synthesized and characterized. The single crystal X-ray structure of the dinuclear complex was determined. Variable temperature magnetic susceptibility measurement showed that the two copper(II) centres are strongly anti-ferromagnetically coupled. The structural study revealed that the Cu-Cu distance (2.911 Å) is very close to the distance observed in dinuclear copper(II) acetate. The average Cu-O-Cu angles (∼87°) are found to be the lowest amongst the examples reported so far.     

Cucurbituril binding of trans-[{PtCl(NH3)2}2(micro-NH2(CH2)8NH2)]2+ and the effect on the reaction with cysteine

The effect of encapsulation by cucurbiturils Q[7] and Q[8] on the rate of reaction of the anti-cancer dinuclear platinum complex trans-[{PtCl(NH3)2}2(micro-NH2(CH2)8NH2)]2+ with the model biological nucleophiles glutathione and cysteine has been examined by NMR spectroscopy. It was expected that the octamethylene linking chain would fold inside the cucurbituril host and hence position the reactive platinum centres close to the cucurbituril portals, and thereby, confer resistance to degradation by biological nucleophiles. The upfield shifts of the resonances from the methylene protons in the linking ligand observed in 1H NMR spectra of the platinum complex upon addition of either Q[7] or Q[8] indicate that the cucurbituril is positioned over the linking ligand, with the Pt(II) centres projecting out of the portal. Furthermore, the relative changes in chemical shift of the methylene resonances suggest that the octamethylene linking chain folds within the cucurbituril cavity, particularly in Q[8]. Simple molecular models, based on the observed relative changes in chemical shift, could be constructed that were consistent with the proposed folding of the linking ligand within the cucurbituril cavity. Encapsulation by Q[7] was found to reduce the rate of reaction of the platinum complex with glutathione. Encapsulation by Q[7] and Q[8] was also found to reduce the rate of reaction of the platinum complex with cysteine, with Q[8] slowing the reaction to a greater extent than Q[7], consistent with the inferred encapsulation geometries. Encapsulation of dinuclear platinum complexes within the cucurbituril cavity may provide a novel way of reducing the reactivity and degradation of these promising chemotherapeutic agents with blood plasma proteins.     

Novel dinuclear platinum(II) complexes containing mixed nitrogen-sulfur donor ligands

A series of novel dinuclear platinum(II) complexes were synthesized containing a mixed nitrogen-sulfur donor bidentate chelate system in which the two platinum centers are connected by an aliphatic chain of variable length. The bidentate chelating ligands were selected to stabilize the complex toward decomposition. The pK(a) values and reactivity of the four synthesized complexes, namely, [Pt(2)(S(1),S(4)-bis(2-pyridylmethyl)-1,4-butanedithioether)(OH(2))(4)](4+) (4NSpy), [Pt(2)(S(1),S(6)-bis(2-pyridylmethyl)-1,6-hexanedithioether)(OH(2))(4)](4+) (6NSpy), [Pt(2)(S(1),S(8)-bis(2-pyridylmethyl)-1,8-octanedithioether)(OH(2))(4)](4+) (8NSpy), and [Pt(2)(S(1),S(10)-bis(2-pyridylmethyl)-1,10-decanedithioether)(OH(2))(4)](4+) (10NSpy), were investigated. This system is of special interest because only little is known about the substitution behavior of dinuclear platinum complexes that contain a bidentate chelate that forms part of the aliphatic bridging ligand. Moreover, the ligands as well as the dinuclear complexes were examined in terms of their cytotoxic activity, and the 10NSpy complex was found to be active. Spectrophotometric acid-base titrations were performed to determine the pK(a) values of all the coordinated water molecules. The substitution of coordinated water by thiourea was studied under pseudo-first-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The results for the dinuclear complexes were compared to those for the corresponding mononuclear reference complex [Pt(methylthiomethylpyridine)(OH(2))(2)](2+) (Pt(mtp)), by which the effect of the increasing aliphatic chain length of the bridged complexes could be investigated. The results indicate that there is a clear interaction between the two platinum centers, which becomes weaker as the chain length between the metal centers increases. Furthermore, differences and similarities of the N,S-system were compared to the corresponding dinuclear N,N-system studied previously in our group. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data.     

Highly efficient DNA compaction mediated by an in vivo antitumor-active tetrazolato-bridged dinuclear platinum(II) complex

We investigated the effects of antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-tetrazolato-N(1),N(2))](2+) (1) and [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-tetrazolato-N(2),N(3))](2+) (2) on the higher-order structure of a large DNA molecule (T4 phage DNA, 166 kbp) in aqueous solution through single-molecule observation by fluorescence microscopy. Complexes 1 and 2 cause irreversible compaction of DNA through an intermediate state in which coil and compact parts coexist in a single DNA molecule. The potency of compaction is in the order 2 > 1 ? cisplatin. Transmission electron microscopic observation showed that both complexes collapsed DNA into an irregularly packed structure. Circular dichroism measurements revealed that the dinuclear platinum(II) complexes change the secondary structure of DNA from the B to C form. These characteristics of platinum(II) complexes are markedly different from those of the usual condensing agents such as spermidine(3+) and [Co(III)(NH(3))(6)](3+). The ability to cause DNA compaction by the platinum(II) complexes is discussed in relation to their potent antitumor activity.     

Reversible binding of dioxygen by the copper(I) complex with tris(2-dimethylaminoethyl)amine (Me6tren) ligand

At low temperatures, the mononuclear copper(I) complex of the tetradentate tripodal aliphatic amine Me(6)tren (Me(6)tren = tris(2-dimethylaminoethyl)amine) [Cu(I)(Me(6)tren)(RCN)](+) first reversibly binds dioxygen to form a 1:1 Cu-O(2) species which further reacts reversibly with a second [Cu(I)(Me(6)tren)(RCN)](+) ion to form the dinuclear 2:1 Cu(2)O(2) adduct. The reaction can be observed using low temperature stopped-flow techniques. The copper superoxo complex as well as the peroxo complex were characterized by resonance Raman spectroscopy. The spectral characteristics and full kinetic and thermodynamic results for the reaction of [Cu(I)(Me(6)tren)(RCN)](+) with dioxygen are reported.     

White emission from dinuclear cyclometalated platinum(II) complex in single-emitting layer PLEDs

A dinuclear platinum(II) complex of (dfppy)₂Pt₂(dipic) has been prepared, where dfppy is 2,4-difluorophenylpyridine and dipic is a biphenyl-bridged bi-picolinic acid derivative. Its physical and optoelectronic properties, as well as molecular orbitals calculation have been investigated and compared with those of its mono-nuclear (dfppy)Pt(pic) complex. Both platinum(II) complexes exhibited almost identical photoluminescence (PL) spectra with deep blue emission in dilute dichloro-methane (10⁻⁵ M) and different PL spectra with red emission in their neat films. Stable white emissions were obtained in the (dfppy)₂Pt₂(dipic)-doped polymer light-emitting devices using a blend of poly(vinylcarbazole) and 2-(4-biphenyl)-5-(4-tert-butyl-phenyl)-1,3,4-oxadiazole as a host matrix at dopant concentrations from 1 wt % to 10 wt %. In contrast, the (dfppy)Pt(pic)-doped devices exhibited orange-red emissions in the same device configuration. It indicates that dinuclear platinum(II) complex with a non-planar structure is an effective way to control formation excimers of platinum(II) complex and get white-emitting PLEDs with single dopant.     

Crystal structure of [Pt2I4(TEPOP)2] (TEPOP = tetraethyldiphosphite).

The structure of the dinuclear complex [Pt2I4(TEPOP)2] (TEPOP = tetraethyldiphosphite) was determined by X-ray diffraction. The two platinum atoms are doubly bridged by two (EtO)2POP(OEt)2 ligands and constitute an eight-membered ring. The platinum atoms have a square-planar geometry, which are completed by two phosphorous and two iodine atoms in a mutually cis arrangement.     

Thermodynamic and kinetic studies on novel dinuclear platinum(II) complexes containing bidentate N,N-donor ligands

A series of novel dinuclear platinum(II) complexes were synthesized with bidentate nitrogen donor ligands. The two platinum centers are connected by an aliphatic chain of variable length. The selected chelating ligand system should stabilize the complex toward decomposition. The pK(a) values and reactivity of four synthesized complexes, viz. [Pt(2)(N(1),N(4)-bis(2-pyridylmethyl)-1,4-butanediamine)(OH(2))(4)](4+) (4NNpy), [Pt(2)(N(1),N(6)-bis(2-pyridylmethyl)-1,6-hexanediamine)(OH(2))(4)](4+) (6NNpy), [Pt(2)(N(1),N(8)-bis(2-pyridylmethyl)-1,8-octanediamine)(OH(2))(4)](4+) (8NNpy), and [Pt(2)(N(1),N(10)-bis(2-pyridylmethyl)-1,10-decanediamine)(OH(2))(4)](4+) (10NNpy), were investigated. This system is of special interest because only little is known about the substitution behavior of dinuclear platinum complexes that contain a bidentate chelate that forms part of the aliphatic bridging ligand. Spectrophotometric acid-base titrations were performed to determine the pK(a) values of the coordinated water ligands. The substitution of coordinated water by thiourea was studied under pseudofirst-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The results for the dinuclear complexes were compared to those for the corresponding mononuclear reference complex [Pt(aminomethylpyridine)(OH(2))(2)](2+) (monoNNpy), by which the effect of increasing the aliphatic chain length on the bridged complexes could be investigated. The results indicated that there is a clear interaction between the two platinum centers, which becomes weaker as the chain length between the metal centers increases. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data.     

N,N'-双(2-氨基丙基)草酰胺合铜(II)的铜(II)-锰(II)配合物的合成和磁性

合成和表征了两种新的异双核配合物[Cu(oxap)Mn(L)~2](ClO~4)~2, oxap表示N,N'-双(2-氨基丙基)草酰胺根阴离子, L表示1,10-邻菲咯啉(phen)和5-硝基-1,10-邻菲咯啉(NO~2-phen)。测定了配合物的变温磁化率(4.2-300K), 并用最小二乘法和从自旋Hamiltonian算符, ^^H=-2J^^S~1.^^S~2-D^^S~Z~1导出的磁方程拟合。求得交换积分为J=-74.72cm^-^1(phen)和J=-76.39cm^-^1(No~2-phen), 表明两个Cu(II)-Mn(II)双核配合物中有中等强度的反铁磁超交换作用。     

Dinuclear Pt(II)-bisphosphonate complexes: a scaffold for multinuclear or different oxidation state platinum drugs

Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}(2)(μ-AHBP-H(2))](+) (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H(2)) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}(3)(μ-AHBP)](+) (2), and a Pt(IV) adamantane-shaped dinuclear complex featuring an oxo-bridge, [{Pt(IV)(en)Cl}(2)(μ-O)(μ-AHBP-H(2))](+) (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at E(pc) = -0.84 V affording compound 1. Such a potential is far lower than that of glutathione (-0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the Pt(IV) dimer 3 is inactive up to a concentration of 50 μM, the two Pt(II) polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1.     

Novel platinum(II) ammine hydroxamate and hydroximate complexes and the platinum-assisted hydrolysis of hydroxamic acids

The 2-pyridinecarboxylate (2-pyca) platinum(IV) complex [2-pycaH2][PtCl4(2-pyca)].H2O, 1, has been synthesised from K2[PtCl4] following the hydrolysis of 2-pyridinehydroxamic acid (2-pyhaH) in the presence of H2O2, and directly from K2[PtCl6] and picolinic acid. Structural characterisation of 1 reveals octahedral geometry about platinum(IV) consisting of a (N,O)-bidentate pyridinecarboxylate ligand and four chloride ligands. A mechanism for the hydrolysis of 2-pyridinehydroxamic acid to 2-pyridinecarboxylic acid is proposed. Two novel coordination modes of hydroxamic acids to platinum(II) are also reported. The dinuclear platinum ammine hydroximato complex, [{cis-Pt(NH3)2}2(mu-2-pyhaH(-1))](ClO4)2.H2O, 3, has been synthesised where the two platinum(II) centres are bridged via(O,O) and (N,N) coordination. The latter coordination mode is via the hydroximate nitrogen and the pyridine nitrogen. The corresponding mononuclear platinum(II) pyridinehydroxamate complex, [cis-Pt(NH3)2(2-pyha)]ClO4, 4, has been synthesised. Spectroscopic studies indicate that the coordination mode is through the pyridine nitrogen and hydroxamate oxygen atoms (N,O).     

Structure and magnetism of the first strictly dinuclear compound containing paramagnetic 3d and 5f metal ions. Major influence of the Cu(II) ion coordination on the exchange Cu(II)-U(IV) interaction

The dinuclear compound [CuL2(py)U(acac)2] has been synthesized by treating [Cu(H2L2)] with U(acac)4 (L2 = N,N'-bis(3-hydroxysalicylidene)-2-methyl-1,2-propanediamine) and shows the antiferromagnetic Cu-U interaction; the distinct magnetic behaviour of the trinuclear complexes [(CuL2)2U] (antiferromagnetic) and [[CuL1(py)]U[CuL1]] (ferromagnetic) revealed the major influence of the Cu(II) ion coordination on the exchange interaction (L1 = N,N'-bis(3-hydroxysalicylidene)-2,2-dimethyl-1,3-propanediamine).