Dirhenium Compound Research Articles

New formulation and activity of rhenium-platinum antitumor system

Two-component Rhenium-Platinum system (Re-Pt system) is based on administration of a cluster dirhenium(III) compound and cisplatin to tumor bearing animals followed by a significant antitumor effect and decreased toxic effect of cisplatin on normal cells. The aim of this work was to obtain solid lipid nanoparticles (SLN) from surface lipids (waxes) of Chelidonium majus L. (Papaveraceae) leaves and to estimate whether capsulation of dirhenium(III) as a component of the Re-Pt system into SLN will affect its antitumor activity and red blood cells (RBC) morphology in a rat model of Guerin’s carcinoma growth. Fourier-transform infrared spectroscopy, gas-liquid chromatography, microscopy, light scattering were used in the research. Solid lipid nanoparticles were obtained, characterized, loaded with cluster dirhenium(III) and being introduced together with cisplatin to rats with Guerin’s carcinoma resulted in RBC morphology preservation and a significant decrease in tumor weight. It was concluded that the lipid coating of the rhenium cluster compound did not reduce the antitumor effect of the Re-Pt system and protected RBC from toxic cisplatin influence­. A new formulation of the Re-Pt system is proposed. Keywords: carcinoma, rhenium cluster compound, rhenium-platinum antitumor system, solid lipid nanoparticles, surface lipids

Interaction of dirhenium(III) tryptophan complex compound with DNA and protein

We report about the interactions of dirhenium(III) compound cis-[Re2(Trp)2Cl4(CH3CN)2]Cl2 (I) with bovine serum protein (BSA) and guanine (G4) quadruplexes DNA by UV-Vis titration. Addition of I to BSA led to the interaction between these compounds with binding constant 5.6103 M–1 and hyperchromism (20.9%) of the main protein absorption band (280 nm). These results support our assumption about formation of the additional conjugated systems during the process of interaction with BSA. Stabilization of the quadruple bonded rhenium(III) complex compound was shown in the presence of BSA (the rate of destruction was reduced), that may be explained by interaction between amino acid residues of BSA and quadruple bond of dirhenium(III) complex compound. In addition, we have obtained data about strong hyperchromism (up to 100%) and significant shift of the maximum of absorption (blue shift) towards UV (2–9 nm) and visible (22 nm) regions in the spectra of mixtures G4s and I, that, in our opinion, correlated with a conformational change in DNA and with formation of additional conjugated systems around quadruple bond of I. In a whole, our work confirms the strong binding activity of a cluster dirhenium(III) compound towards G4 quadruplexes, that exceed the binding activity to proteins and witness to preferential interactions of I with G4 DNA in a living cell. These results may be used in DNA "silencing technology" and "antisense therapy".

The concentration of ceruloplasmin in blood of tumor-bearing rats after administration of a dirhenium(III) compound and cisplatin

The concentration of ceruloplasmin in blood of tumor-bearing rats after administration of a dirhenium(III) compound and cisplatin

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improved in vivo anticancer activity

Liposomes loaded with the rhenium compound (bis-dimethylsulfoxido-cis-tetrachlorodi-μ-pivalatodirhenium(III) (cis–Re2((CH3)3CCOO)2Cl4ċ2DMSO, I) and cisplatin in the molar ratio of 4:1 as well as those loaded only with I were synthesized and characterized by scanning electron microscopy, transmission electron microscopy, dynamic light scattering and electronic absorption spectroscopy. The relative stability of liposomes loaded with I is reflected by a minimal change in the electronic absorption spectra over a period of 8 days whereas the stability of those loaded with both drugs is lower, which we ascribe to the formation of new Re-Pt species inside the liposomes. Furthermore, the investigations of the co-encapsulation effects on the anticancer activity of the Re-Pt system were undertaken. Importantly, the co-encapsulated liposomes exhibit synergistic or additive anticancer activities in vivo, e.g. introduction of these liposomes into tumor-bearing rats demonstrated their antianemic, nephro- and hepato-protecting effects. These liposomes, which are active in cancer treatment, protect the dirhenium compounds from hydrolysis and preserve the biological properties of the Re-Pt hybrid. This study reveals the importance of combined therapy in nanotechnology and medicine.

Multi-site coordination of ferrocenylamido-naphthyridine conjugates [{(5,7-dimethyl-1,8-naphthyridin-2-yl)amino}carbonyl]ferrocene and 1,1′-bis[{(5,7-dimethyl-1,8-naphthyridin-2-yl)amino}carbonyl]ferrocene

Ferrocenylamido-naphthyridine conjugates [{(5,7-dimethyl-1,8-naphthyridin-2-yl)amino}carbonyl]ferrocene (L 1) and 1,1′-bis[{(5,7-dimethyl-1,8-naphthyridin-2-yl)amino}carbonyl]ferrocene (L 2) have been synthesized. Reaction of L 1 with [Cu(CH 3CN) 6][ClO 4] 2 affords [Cu(L 1) 2][ClO 4] 2 ( 1) demonstrating tridentate coordination of the ligand utilizing naphthyridine (NP) nitrogens and carbonyl oxygen. Hydroxo-bridged neutral dirhenium(I) compound [K⊂{{Re(CO) 3} 2(μ-OH)(Fc(CONHNP)(CO N ¯ NP)) 2}] ( 2) is reported in which the amido-NP arm of L 2 chelates a Re I, and a K + ion is encapsulated in a six-coordinate environment rendered by four NP nitrogens and two carbonyl oxygens involving all four arms of two L 2 ligands. Selective and reversible binding of K + ion by the organometallic host has been recognized from electrochemical and fluorescence experiments. Partial hydrolysis of L 2 has provided a neutral metallamacrocycle [{Re(CO) 3} 2{Fc(CO 2)(CONHNP)} 2] ( 3) consisting of alternate Fc and Re(CO) 3 units linked by carboxylate and amide-NP bridges. The rotational freedom of the ferrocenyl rings, the flexibility of the amide linker and the multi-site coordination of the ligands are demonstrated in the molecular structures of compounds 1– 3.

Syntheses and structural characterization of heterometallic bis(pyrazolyl)methane complexes of rhenium and platinum

The new heterometallic complex {μ-1,3,5-[CH(pz) 2] 3C 6H 3}[Re(CO) 3Br][Pt( p-tolyl) 2] 2 has been prepared by reaction of 1 equiv. of the dimer [Pt( p-tolyl) 2(μ-SEt 2)] 2 with the monometallic rhenium precursor {1,3,5-[CH(pz) 2] 3C 6H 3}Re(CO) 3Br, where 1,3,5-[CH(pz) 2] 3C 6H 3 is the tritopic, arene-linked bis(pyrazolyl)methane ligand 1,3,5-tris[bis(1-pyrazolyl)methyl]benzene. Similarly, the heterometallic complex {μ-1,3,5-[CH(pz) 2] 3C 6H 3}[Re(CO) 3Br] 2[Pt( p-tolyl) 2] has been made by the reaction of the dirhenium compound {μ-1,3,5-[CH(pz) 2] 3C 6H 3}[Re(CO) 3Br] 2 and one-half of an equivalent of [Pt( p-tolyl) 2(μ-SEt 2)] 2. X-ray crystallographic studies of the new compounds reveal significant noncovalent interactions in their molecular and supramolecular structures.

Synthesis, X-ray diffraction structure, and redox chemistry of Re2(CO)8(bmf)

The reaction between Re2(CO)8(μ-H)(μ-η1,η2-CH=CHBu) (1) and the diphosphine ligand 3,4-bis(diphenylphosphino)-5-methoxy-2(5H)-furanone (bmf) proceeds at room temperature to give the dirhenium compound Re2(CO)8(bmf) (2) as the sole observable product in good yield after 24 h. Re2(CO)8(bmf) has been isolated and characterized in solution by IR and NMR (31P and 1H) spectroscopies, and the molecular structure of Re2(CO)8(bmf) has been determined by X-ray crystallography. The solid-state structure of 2 reveals a bridging bmf ligand that spans the Re=Re vector and whose Re(CO)4 moieties exhibit a staggered rotational geometry about the equatorial phosphine and CO groups. The redox properties of Re2(CO)8(bmf) have been explored by cyclic voltammetry in CH2Cl2, where an irreversible oxidation was found at Epa = 1.04 V, along with a reversible, one-electron reduction at E1/2 = −1.23 V. These redox couples have been assigned to the oxidation of the Re=Re σ bond and electron occupation of the π∗ system associated with the furanone ring of Re2(CO)8(bmf), respectively. The electrochemical behavior is discussed relative to the nature of the HOMO and LUMO levels in the model compound Re2(CO)8(H4-bmf), whose HOMO and LUMO compositions have been established by extended Huckel MO calculations. The electrochemistry and MO data from Re2(CO)8(bmf) are contrasted with the structurally similar dirhenium compound Re2(CO)8(bma).

Reaction of 1,2-bis(diphenylphosphino)cyclobutenedione (bpcbd) with fac-BrRe(CO)3(THF)2: X-ray diffraction structure of the dimeric complex [BrRe(CO)3]2(bpcbd) Ch2Cl2

Treatment of the diphosphine ligand 1,2-bis(diphenylphosphino)cyclobutenedione (bpcbd) with the THF adduct fac-BrRe(CO)3(THF)2 at room temperature furnishes the new dirhenium compound [BrRe(CO)3]2(bpcbd) instead of the expected mononuclear compound fac-BrRe(CO)3(bpcbd). [BrRe(CO)3]2(bpcbd) was characterized in solution by IR spectroscopy, and the solid-state structure was solved by X-ray crystallography. [BrRe(CO)3]2(bpcbd), as the CH2Cl2 solvate, crystallizes in the space group P\(\overline {\text{1}} \), a = 11.173(1), b = 13.362(1), c = 15.250(1) A, α = 108.973(7)°, β = 99.477(8)°, γ = 110.466(7)°, V = 1915.0(3) A3, Z = 2, and dcalc = 2.143 g-cm−3. The structure of [BrRe(CO)3]2(bpcbd) consists of two rhenium centers that are six-coordinate and possess nearly ideal octahedral geometry. The two Re(CO)3 units are linked together by the bridging diphosphine ligand and two bridging bromide groups.

Unusual chemical reactivity in the reactions of Re 2(CO) 8(μ-H)(μ-η 1,η 2-CHCHBu) with 2,3-bis(diphenylphosphino)maleic anhydride (bma) and Re 2(CO) 8(bma) with Ni(cod) 2: X-ray diffraction structures of Re 2(CO) 8(bma), zwitterionic Re(CO) 4[Re(CO) 4(bma)], and the phosphido-bridged complex Re 2(CO) 8[μ-η 1,η 1- (O)](μ-PPh 2)

The reaction between Re 2(CO) 8(μ-H)( ν-η 1,η 2-CHCHBu) ( 1) and the diphosphine ligand 2,3-bis(diphenylphosphino)maleic anhydride (bma) proceeds slowly at room temperature to furnish the expected dirhenium compound Re 2(CO) 8(bma) ( 2) and the zwitterionic compound Re(CO) 4[Re(CO) 4(bma)] ( 3). Both 2 and 3 have been isolated and characterized in solution by IR and 31P NMR spectroscopy, in addition to X-ray crystallography. The solid-state structure of 2 reveals a bridging bma ligand that spans the Re–Re vector and whose Re(CO) 4 moieties exhibit a staggered rotational geometry. 3 consists of a Re(CO) 4 unit that is coordinated to the bma ligand in a chelating fashion by the two PPh 2 moieties, with the other Re(CO) 4 unit being π-bound to the alkene bond of the bma ligand. Thermolysis of Re 2(CO) 8(bma) in the presence of added Ni(cod) 2 affords the phosphido-bridged complex Re 2(CO) 8[μ-η 1,η 1- ▪(O)](μ-PPh 2) ( 4), whose identity has been established by solution spectroscopic methods and X-ray diffraction analysis. The redox properties of Re 2(CO) 8(bma) have been examined in detailed by cyclic voltammetry and constant-potential coulometry, where two fully reversible, one-electron reductions (0/1 − and 1 −/2 −) were observed at E 1/2=−0.38 V and E 1/2=−1.29 V in CH 2Cl 2. The reduction behavior is discussed relative to the nature of the LUMO level, which has been determined by extended Hückel MO calculations. The redox chemistry and the LUMO in Re 2(CO) 8(bma) are contrasted with the known redox chemistry and the LUMO composition of the mononuclear species BrRe(CO) 3(bma) and related bma-substituted complexes. The MO calculations on Re(CO) 4[Re(CO) 4(bma)] ( 3) reveal that the HOMO and LUMO levels are formed from the HOMO of the d 8-ML 4 fragment Re(CO) 4 − and its interaction with the ψ 4π * antibonding MO of the bma ligand on the [Re(CO) 4(bma)] + fragment.

Products of the reactions of [Re 2X 8] 2– with 3,6-dithiaoctane (dto). Preparation and crystal structures of Re 2Cl 5(dto) 2, Re 2Br 5(dto) 2, and ( n-Bu 4N) 2Re 2(NCS) 8·dto

The reactions of the quadruply bonded complexes ( n-Bu 4N) 2Re 2X 8 (X=Cl, Br) with excess 3,6-dithiaoctane (CH 3CH 2SCH 2CH 2SCH 2CH 3 or dto) under forcing conditions lead to the compounds Re 2Cl 5(dto) 2 ( 1) and Re 2Br 5(dto) 2 ( 2) with Re–Re triple bonds. X-ray crystallographic studies of compounds 1 and 2 reveal a common staggered, unsymmetrical molecular geometry with both dto ligands chelated to the same metal atom. This Re atom is also bonded to a single axial halide ligand, while the other four halides surround the second Re atom. In contrast to the only previous example of this type of dirhenium compound, Re 2Cl 5(dithiahexane) 2, there is no sharing of axial chloride ligands between molecules in the crystal lattices of 1 and 2. The Re–Re bond distances are 2.2772(8) and 2.2826(6) Å in 1 and 2, respectively. Magnetic measurements, cyclic voltammetry, and IR, Vis and ESR spectra of 1 and 2 are reported. Addition of dto to a solution of ( n-Bu 4N) 2Re 2(NCS) 8 leads to the formation of ( n-Bu 4N) 2Re 2(NCS) 8·dto ( 3). Crystallographic studies show 3 to consist in the solid state of chains of [Re 2(NCS) 8] 2– units linked together by dto molecules with each dto sulfur atom weakly coordinated to axial sites on Re atoms of different anions. The Re–Re quadruple bond distance in 3 is 2.2854(3) Å.

Dirhenium complexes that contain the ligand 1,1-bis(diphenylphosphino)ethene (dppE). Synthesis, characterization and reactivity of Re2Cl4(μ-dppE)2

The dirhenium(II) compound Re2Cl4(μ-dppE)2 (1), where dppE=(Ph2P)2C=CH2, which contains an electron-rich triple bond, has been prepared by the reaction of (n-Bu4N)2Re2Cl8 with CH3CO2Na and dppE in refluxing ethanol. Its reactivity towards CO alone, and CO in combination with XylNC and 2,5-Me2-C6H3CN has been explored. The complexes Re2Cl4(μ-dppE)2(CO)2 (2) and [Re2Cl3(μ-dppE)2(CO)2(L)]O3SCF3, where L=CO (3), XylNC (4) or 2,5-Me2-C6H3CN (5) have been isolated and characterized by IR and NMR spectroscopy, cyclic voltammetry and X-ray crystallography. The complex trans-Re2(μ-O2CCH3)2Cl2(μ-dppE)2 (6) has been obtained by the reaction of Re2(μ-O2CCH3)4Cl2 with dppE. Crystal structure determinations on 1, 2, 4 and 6 reveal that the Re-Re distances are 2.2448(5), 2.5748(5), 2.5767(5) and 2.2861(6) Å, which are in accordance with Re-Re bond orders of 3, 2, 2 and 3, respectively.

A quadruply-bonded dirhenium complex bridged by two N 1/N 6 adenate ligands

The first structurally characterized example of a metal-metal bonded complex bridged by the DNA nucleobase adenine through the N1, N6 positions is reported. The new dirhenium compound, Re 2(O 2CCH 2CH 3) 2(9-EtA) 2Cl 2 · CH 3CH 2O · C 6H 14, binds to adenine at the sites where thymine normally engages in Watson-Crick base-pairing. Such chemistry, if it occurs in vivo, could play a role in the carcinostatic activity of tetrapropionatodirhenium complexes that are known to inhibit DNA replication.

CO substitution and diphosphine ligand chelation in the reaction between 4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (bpcd) and Re( 2(CO) 8( μ-H)( μ- η1, η2-C  CPh)

The reaction between the redox-active diphosphine ligand 4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (bpcd) and the dirhenium compound Re 2(CO) 8( μ-H)( μ- η 1, η 2-C  CPh) in CH 2Cl 2 at room temperature proceeds by CO loss to give the dirhenium complex Re 2(CO) 7(bpcd)( μ-H)( η 1-C  CPh) ( 1). This new complex was characterized in solution by IR and NMR ( 1H and 31P) spectroscopy and in the solid state by X-ray diffraction analysis. Re 2(CO) 7(bpcd)( μ-H)( η 1-C  CPh) crystallizes in the triclinic space group P 1: a = 11.3900(9), b = 13.3921(9), c = 14.275(1) A ̊ , α = 84.280(6)°, β = 89.678(6)° γ = 69.240(6)°, V = 2024.9(3) A ̊ 3, Z = 2, d calc = 1.862 g cm −3 R = 0.0221, R w = 0.243 for 4066 observed reflections. The bpcd ligand in 1 adopts a chelating mode with a linear phenylacetylide ligand being located on the adjacent rhenium center cis to the bpcd ligand. This complex represents the first structurally characterized example of a hydrido-bridged dirhenium complex possessing both a linear acetylide ligand and a chelating diphosphine ligand.

Chemistry of polynuclear metal complexes with bridging carbene or carbyne ligands. Part 70. Tetranuclear metal compounds with rhenium–molybdenum or –tungsten bonds. Crystal structures of [Mo2Re2(µ3-CC6H4Me-4)2(µ-CO)2(CO)7(η-C5H5)2]·1.5CH2Cl2and [W2Re2(µ-H)(µ3-σ:σ′:η2-CCH2)(µ3-CMe)(µ-CO)(CO)8(η-C5H5)2

Reactions between the compounds [M(CC6H4Me-4)(CO)2(η-C5H5)](M = Mo or W) and [Re2(µ-H)(µ-σ:η-CHCHBun)(CO)8] afford the tetranuclear metal complexes [M2Re2(µ3-CC6H4Me-4)2(µ-CO)2(CO)7(η-C5H5)2]. The corresponding reaction between [W(CMe)(CO)2(η-C5H5)] and the dirhenium compound yields a mixture of the cluster compounds [W2Re2(µ3-CMe)2(µ-CO)2(CO)7(η-C5H5)2], [W2Re2(µ-H)(µ3-σ:σ′:η2-CCH2)(µ3-CMe)(µ-CO)(CO)8(η-C5H5)2], and [WRe2(µ3CMe)(CO)10(η-C5H5)]. The molecular structures of [Mo2Re2(µ3-CC6H4Me-4)2(µ-CO)2(CO)7(η-C5H5)2]·1.5CH2Cl2 and [W2Re2(µ-H)(µ3-σ:σ′:η2-CCH2)(µ3-CMe)(µ-CO)(CO)8(η-C5H5)2] have been established by X-ray diffraction studies. Crystals of the former contain two very similar crystallographically independent molecules in the asymmetric unit and there are three molecules of CH2Cl2 of crystallisation. The structure has a tetrahedral core of metal atoms (mean metal–metal separations 2.914 A) with two of the faces of the tetrahedron capped by p-tolylmethylidyne ligands and two of the Mo–Re edges of the tetrahedron asymmetrically bridged by CO groups [Mo–C–O 155(3) and 157(3)°]. Each rhenium atom carries three orthogonal terminal CO ligands, with the remaining CO group being terminally attached to a molybdenum atom. As expected, the C5H5 moieties ligate the Mo atoms. In [W2Re2(µ-H)(µ3-σ:σ′:η2-CCH2)(µ3-CMe)(µ-CO)(CO)8(η-C5H5)2] the four metal atoms adopt a near-planar ‘butterfly’ arrangement, having a W–Re spine [2.923(1)A] and with a W and a Re atom at the wing-tip positions. The W2Re triangle is capped by a CMe group which lies perceptibly closer to the tungsten atoms than the rhenium. On the other side of the W2Re2 plane, the WRe2 triangle is triply bridged by the CCH2 group. The latter is σ bonded to the W and Re atoms which form the spine of the butterfly, and is η2-co-ordinated to the Re atom at the wing-tip position. A CO ligand asymmetrically bridges [W–C–O 159(2)°] the W–Re edge of the WRe2 triangle and, although not located by X-ray diffraction, the hydrido ligand must bridge the Re–Re edge [3.023(1)A], since the latter is perceptibly longer than the other metal–metal separations (mean 2.951 A). Each rhenium atom is ligated by three terminal CO groups, and the tungsten atom is co-ordinated by two such groups. There is a C5H5 ligand bonded to each tungsten centre. The 1H and 13C-{1H} n.m.r. spectra of the new compounds are reported and discussed.

ChemInform Abstract: Reactions of the Dirhenium(II) Complexes Re2X4(dppm)2 (X: Cl or Br; dppm: Ph2PCH2PPh2) with Isocyanides. Part 3. Dinuclear Species Containing Two or Three Isocyanide Ligands.

AbstractThe triply bonded dirhenium(II) compound (II) reacts with two equiv. tBuNC to yield two isomeric bis(isocyanide) species (I) and (III) depending on the reaction conditions.