Cyclopentadienyl Rhenium Tricarbonyl Research Articles

Reactions of pyridine-2-ethyl/methyl cyclopentadienes with metal carbonyls

Thermal treatment of pyridine-2-ethyl cyclopentadiene (1) with Fe(CO)5 and Ru3(CO)12 gave novel intramolecular C–H activated dinuclear products (3 and 5). In the case of Fe(CO)5, the reaction also afforded the normal bis(cyclopentadienyl) diiron complex (4). However, similar reaction of pyridine-2-methyl cyclopentadiene (2) with Fe(CO)5 and Ru3(CO)12 only afforded the normal bis(cyclopentadienyl) dinuclear metal complexes (7 and 8). For Ru3(CO)12, the reaction also yielded a pendant η1-pyridyl-coordinated product (9). In addition, the reactions of 1 and 2 with Re2(CO)10 formed the corresponding pyridylethyl/pyridylmethyl cyclopentadienyl rhenium tricarbonyl complexes 10 and 11, which further underwent pyridine to rhenium cyclization via photoirradiation to provide the rhenium dicarbonyl complexes 12 and 13. The molecular structures of 3, 5, 6, 7, 8, 9, and 12 were determined by X-ray diffraction.

Conformational preferences of heteronuclear Fischer carbene complexes of cymantrene and cyclopentadienyl rhenium tricarbonyl

Homo- and heteronuclear bimetallic carbene complexes of group VII transition metals (Mn and Re), with cymantrene or cyclopentadienyl rhenium tricarbonyl as the starting synthon, have been synthesized according to classic Fischer methodology. Crystal structures of the carbene complexes with general formula [RC5H4 M'(CO)2{C(OEt)(C5H4 M(CO)3)}], where M = M′ = Mn, R = H (1), R = Me (2); M = Mn, M′ = Re, R = H (3); M = M′ = Re, R = H (4); and M = Re, M′ = Mn, R = H (5), are reported. A density functional theory (DFT) study was undertaken to determine natural bonding orbitals (NBOs) and conformational as well as isomeric aspects of the binuclear complexes. Application of second-order perturbation theory (SOPT) of the NBO method revealed stabilizing interactions between the methylene C–H bonds and the carbonyl ligands of the carbene metal moiety. Energy calculations in the gas phase of the cis and trans conformations of the Cp rings relative to one another are comparable, with the trans conformation slightly lower in energy. The theoretical findings have also been confirmed with single-crystal X-ray diffraction, and all solid-state structures are found in the trans geometry.

Fluorine and Rhenium Substituted Ghrelin Analogues as Potential Imaging Probes for the Growth Hormone Secretagogue Receptor

In our effort to create imaging probes targeting the growth hormone secretagogue receptor (GHSR), we now report on the design and synthesis of fluorine and rhenium containing ghrelin analogues through modification of the n-octanoyl Ser-3 side chain. Fluorine analogues were designed whereby the fluorine atom is situated at the terminus of an aliphatic chain using diaminopropionic acid (Dpr) as residue-3. Truncated ghrelin(1-5) and ghrelin(1-14) fluorine-bearing analogues were prepared, the best of which had a 28 nM IC(50) for GHSR. Ghrelin(1-14) analogues were also prepared containing rhenium, as a surrogate metal for technetium-99m, with a cyclopentadienylrhenium tricarbonyl being situated at the terminus of the residue-3 side chain, yielding compounds the best of which had a 35 nM IC(50). This represents a rare case of incorporating rhenium into a peptide structure where the metal complex is required for biological activity. These fluorine and rhenium derivatives demonstrate the ability to modify the Ser-3 side chain of ghrelin in order to create imaging probes for the GHSR.

β-Diketones derived from cyclopentadienyl rhenium tricarbonyl

The acetyl complex ( η 5–C 5H 4COCH 3)Re(CO) 3 reacts with KO t Bu and an excess of appropriate ester to provide cyrhetrenyl-β-diketones complexes ( η 5–C 5H 4COCH 2COR)Re(CO) 3 (R = CF 3, 1a; CH 3, 1b; Ph, 1c). These new 1,3-diketones exist predominantly as enol tautomer, although a enol/keto mixture of approx. 10:1 is present in complexes 1b– c, in chloroform-d solution. The complexes have been characterized by spectroscopic techniques IR, 1H and 13C NMR and mass spectrometry. X-ray crystallography of complex 1b shows that only the enol form occurs in the solid state. The O–C–C–C–O fragment of the molecule is planar with asymmetric enolisation in the direction furthest from the cyrhetrenyl group.

Metal complex SERMs (selective oestrogen receptor modulators). The influence of different metal units on breast cancer cell antiproliferative effects

The selective oestrogen receptor modulator tamoxifen is a leading agent in the adjuvant treatment of breast cancer. Several organometallic moieties have been vectorised with tamoxifen, in order to improve on the latter's antiproliferative properties by the addition of a potentially cytotoxic moiety, and have been evaluated versus both oestrogen receptor positive (MCF7) and oestrogen receptor negative (MDA-MB231) breast cancer cells. For tamoxifen analogues with ((R,R)-trans-1,2-diaminocyclohexane)platinum(II), cyclopentadienyl rhenium tricarbonyl, and ruthenocene tethers, there was no enhancement of the antiproliferative effect on oestrogen receptor positive cells, nor any cytotoxic effect on oestrogen receptor negative cells, while those containing cyclopentadienyl titanium dichloride showed an oestrogenic effect. However, compounds where ferrocene replaces tamoxifen's phenyl ring were strongly cytotoxic against both cell lines. The synthesis and biological results of these compounds is reviewed and placed in the historic context of inorganic compounds in therapy.

Selective estrogen-receptor modulators (SERMs) in the cyclopentadienylrhenium tricarbonyl series: synthesis and biological behaviour.

A series of organometallic antiestrogens based on the OH-tamoxifen (OH-Tam) skeleton and bearing the (eta(5)-C(5)H(4))Re(I)(CO)(3) unit has been prepared by using McMurry coupling for the purpose of studying their biological behaviour. The cyclopentadienylrhenium tricarbonyl moiety is indeed stable in biological media, compact, lipophilic and easy to handle. Furthermore, this study allowed us to select the best candidates for subsequent use as radiopharmaceuticals either for imaging or therapy by using appropriate radionucleides, namely (99m)Tc and (188)Re. In these molecules the beta-phenyl group of OH-Tam has been replaced by the (eta(5)-C(5)H(4))Re(CO)(3) moiety, and the length of the dimethylamino side chain --O(CH(2))(n)N(CH(3))(2) was varied (n=2, 3, 4, 5 and 8). The compounds 7 a-7 e were obtained as mixtures of their Z and E isomers, which could be separated by semipreparative HPLC. Unlike their ferrocene homologues, the compounds do not isomerise in solution. Structural identification was carried out with NMR spectroscopy by using the HMBC and NOE techniques and was confirmed by the X-ray structural determination of (E)-7 a (n=2). These molecules were more lipophilic than OH-Tam (log P(o/w)=4.5-6.3) and they were all reasonably well recognized by the two forms of the estrogen receptor (ERalpha and ERbeta). For example, (Z)-7 b (n=3) has high relative binding affinity (RBA) values of 31 % for ERalpha and 16.8 % for ERbeta. The antiproliferative effects of two pairs of isomers, (Z)- and (E)-7 b (n=3) and (Z)- and (E)-7 d (n=5), were studied at a molarity of 1 microM on two breast-cancer cell lines, MCF7 (ERalpha positive) and MDA-MB231 (ERalpha negative). These molecules had an antiproliferative effect on MCF7 cells slightly higher than that of OH-Tam and no effect on MDA-MB231 cells. Thus, the antiproliferative effect observed on the MCF7 cells seemed essentially to be linked to an antiestrogenic effect. Molecular modelling studies have allowed us to rationalise these effects and select the best compounds for future development of a radioactive series.

First anti-oestrogen in the cyclopentadienyl rhenium tricarbonyl series. Synthesis and study of antiproliferative effects

A route to the organometallic complex 8 is described, along with a study of its antiproliferative effects on breast cancer cell lines; in the examples studied, 8 behaves in a very similar manner to tamoxifen, suggesting new possibilities for applications in organometallic chemistry.

Microwave measurements of rhenium quadrupole coupling in cyclopentadienyl rhenium tricarbonyl

Microwave measurements of rotational transitions for cyclopentadienyl rhenium tricarbonyl were performed in the gas phase using pulsed beam Fourier transform microwave spectroscopy. One hundred and sixty five transitions were assigned to two isotopomers of rhenium. The location of the rhenium atom near the center of mass produced significant overlap between the spectra of the two isotopomers. The data were accurately fit using a symmetric top, rigid rotor Hamiltonian that included nuclear quadrupole coupling and centrifugal distortion constants. The rotational constants obtained were B(187Re) = 724.9794(2), B(185Re) = 724.9795(2). The quadrupole coupling constants obtained were eQq(187Re) = 614.464(12) and eQq(185Re) = 649.273(14) MHz. The successful fitting of the measured spectra to a symmetric top Hamiltonian indicates that the cyclopentadienyl group retains C5v symmetry, and the Re(CO)3 group C3v symmetry in the gas phase. The measured rotational constants are in reasonable agreement with those calculated from the structural parameters obtained in the earlier x-ray work. The Re quadrupole coupling constants obtained are compared with values for other complexes.

Catalytic hydrogenolysis of ?-cyclopentadienyl transition-metal complexes under mild conditions

1. Cymanthrene and its derivatives containing phosphines or a nitrosyl group as ligands at the metal atom or a substituent in the cyclopentadienyl ring undergo complete hydrogenolysis in acid medium with Pd/C catalyst at 1 atm H2 and temperatures up to 50°C to form cyclopentane and small amounts of cyclopentene. 2. The hydrogenolysis of azaferrocene proceeds under the same conditions, but cyclopenta-dienylrhenium tricarbonyl does not undergo this reaction.

Insertion of (Ph3P)2Pt into symmetrical mercury derivatives of cyclopentadienylmanganese tricarbonyl and cyclopentadienylrhenium tricarbonyl

The insertion of Pt(0)(PPh3)2 across the carbon-metal bond in mercury derivatives of cyclopentadienylmanganese tricarbonyl and cyclopentadienylrhenium tricarbonyl leads to compounds with a mercury-platinum bond, the dimercuration of which gives theσ-platinum derivatives of theseπ complexes.

Comparative study of low-frequency vibrational spectra of cyclopentadienylmanganese tricarbonyl and cyclopentadienylrhenium tricarbonyl derivatives

1. A study was made of the dependence of the frequencies of the completely symmetric metal-ring and metal-carbonyl stretching vibrations in cyclopentadienylmanganese tricarbonyl and cyclopentadienyl-rhenium tricarbonyl derivatives on the character of the substituent in the cyclopentadienyl ring. 2. The different type of frequency shifts for the manganese and rhenium derivatives is explained by the substantially greater role of dative interaction in the formation of the metal-ring bond for the cyclopentadienylmanganese tricarbonyl derivatives.

Comparative study of NMR spectea of monosubstituted (C5H4X)M(CO)3 (M=Mn, Re)

The electron density on theπ-cyclopentadienyl ligand in cyclopentadienylmanganese tricarbonyl derivatives is higher than in the corresponding cyclopentadienylrhenium tricarbonyl derivatives.

Isotopic exchange of hydrogen atoms of cyclopentadienylmanganese tricarbonyl and cyclopentadienylrhenium tricarbonyl in alkaline media

Isotopic exchange of hydrogen atoms of cyclopentadienylmanganese tricarbonyl and cyclopentadienylrhenium tricarbonyl in alkaline media