Synthesis, biochemical properties and molecular modelling studies of organometallic specific estrogen receptor modulators (SERMs), the ferrocifens and hydroxyferrocifens: evidence for an antiproliferative effect of hydroxyferrocifens on both hormone-dependent and hormone-independent breast cancer cell lines.

A series of ferrocene derivatives based upon the structure of the antiestrogenic drug tamoxifen or of its active metabolite hydroxytamoxifen has been prepared and named by analogy ferrocifens and hydroxyferrocifens. This series includes 1-[4-(O(CH(2))(n)NMe(2))phenyl]-1-phenyl-2-ferrocenyl-but-1-ene and 1-[4-(-O(CH(2))(n)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene, with n=2, 3, 5 and 8, and 1-[4-(-O(CH(2))(2)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenylethene. Most of these molecules have been synthesised by McMurry cross-coupling of the appropriate ketones, except for the ethene complexes, which were prepared by a four-step reaction sequence starting from the ferrocenylacetic acid. All these compounds were obtained as mixtures of Z and E isomers. The isomers were separated in the cases of the ferrocenyl derivatives of tamoxifen and hydroxytamoxifen (n=2). No isomerisation of the Z and E isomers occurred in DMSO after one day, while a 50:50 mixture of the isomers was obtained within one hour in chloroform. The X-ray structure of (E)-1-[4-(-O(CH(2))(2)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene has been determined. The relative binding affinity (RBA) values of the hydroxyferrocifens for the estrogen receptor alpha (ERalpha) was good to moderate, with values decreasing progressively with the length of the basic chain. The RBA values found for the estrogen receptor beta (ERbeta) are equal to or slightly less than those found for the alpha form. The lipophilicity of the hydroxyferrocifens are superior to the values found for estradiol and increase with lengthening of the chain. The antiproliferative effects of the four hydroxyferrocifens with n=2, 3, 5 and 8 were studied on four breast cancer cell lines (MCF7, MDA-MB231, RTx6 and TD5) possessing different levels of ERalpha. On MCF7 cells containing high levels of ERalpha, hydroxyferrocifens behave as antiestrogens. At a molarity of 1 microM the effect is close to that of hydroxytamoxifen (used for reference) when n=2 or 5, more marked when n=3, and weaker when n=8. Ferrocene alone has no effect. For the MDA-MB231 cells, classed as a hormone-independent breast cancer cell line, on the other hand, the hydroxyferrocifens show remarkable antiproliferative behaviour while the hydroxytamoxifen is completely inactive. Hydroxyferrocifens therefore show the unique property of being active both on hormone-dependent and on hormone-independent breast cancer cell lines. The molecular modelling study provides some clues for understanding of the antagonist effect of these molecules, while an additional cytotoxic effect due to the vectorised ferrocenyl unit is revealed in some occasions.

Formation study and X-ray structures of dinuclear beta-diketonate copper(I) complexes with conjugated ene-yne Lewis base. Implications for the use of (hfac)Cu(MHY) as a precursor for copper CVD.

Dinuclear [(hfac)Cu](2)(MHY) and [(hfac)Cu](2)(HY) species, where hfac = hexafluoroacetylacetonate, MHY = 2-methyl-1-hexen-3-yne, and HY = hex-3-yn-1-ene), are formed during copper chemical vapor deposition experiments when a bubbler containing the corresponding mononuclear species is used. These compounds and the so far unknown (hfac)Cu(HY) have been characterized by (1)H and (13)C NMR and IR spectroscopy and the two dinuclear species by X-ray crystallography and elemental analysis. As expected, in the structure of the dinuclear species, two roughly perpendicular Cu(hfac) moieties are bound to a single ene-yne: one to the C[triple bond]C, the other to the conjuguated double bond. Weak intra- and intermolecular Cu...Cu interactions have been detected in the solid. [(hfac)Cu](2)(HY) is more stable and more easily formed than [(hfac)Cu](2)(MHY) because of the hindrance character of the additional methyl groups. The formation of the dinuclear species from the mononuclear species is reversible as it has been demonstrated by (1)H NMR. The mononuclear species can be recovered from the dinuclear species when free ene-yne base is added. Crystallographic data for [(hfac)Cu](2)(MHY): C(17)H(12)O(4)F(12)Cu(2), triclinic, P1 (No. 2), Z = 4; at 298 K, a = 11.112(3) A, b = 13.472(4) A, c = 15.747(3) A, alpha = 94.95(2) degrees, beta = 98.15(2) degrees, gamma = 100.27(2) degrees; Crystallographic data for [(hfac)Cu](2)(HY): C(16)H(10)O(4)F(12)Cu(2), orthorhombic, Cc2a (No. 41, Aba2), Z = 8; at 230 K, a = 12.280(3) A, b = 13.531(3) A, c = 25.461(5) A.

Exchange coupling in cyano-bridged homodinuclear Cu(II) and Ni(II) complexes: synthesis, structure, magnetism, and density functional theoretical study.

The synthesis and structural characterization of several new cyano-bridged copper(II) and nickel(II) homodinuclear complexes is presented. The measure of magnetic properties for these complexes is complemented with a computational study of the exchange coupling for several model structures representing this family of compounds. The influence of several factors on the coupling constant has been examined, coordination position occupied by the bridging ligand, distortions of the coordination environment, and relative disposition of the cyanide ion with respect to the M-M vector. Comparison of experimental and calculated coupling constants allows for the rationalization of the most relevant features of the exchange interaction between two identical metal ions through a cyano bridge.

Rational design of three-dimensional (3D) optically active molecule-based magnets: synthesis, structure, optical and magnetic properties of ([Ru(bpy)3](2+), ClO4(-), [Mn(II) Cr(III)(ox)3](-))n and ([Ru(bpy)2ppy](+), [M(II)Cr(III)(ox)3](-))n, with M(II) = Mn(II), Ni(II). X-ray structure of ([deltaRu(bpy)3](2+), ClO4(-), [deltaMn(II)DeltaCr(III)(ox)3](-))n and ([lambdaRu(bpy)2ppy)](+), [lambdaMn(II)lambdaCr(III)(ox)3](-))n.

To elucidate the relation between structural and magnetic properties, we have synthesized molecular materials having both Cotton effects and a ferromagnetic long range order. Such optically active 3D molecule-based magnets were rationally designed using the enantioselective template effect of optically active cations, namely Delta or Lambda [Ru(bpy)3, ClO4](+) or Delta or Lambda [Ru(bpy)3ppy](+) (bpy = bipyridine; ppy = phenylpyridine). Such cations are able to template the formation of optically active 3D anionic networks in which transition metal ions (Cr-Mn) and (Cr-Ni) are connected by oxalate ligands (ox). Following this strategy, we described the synthesis of ([Ru(bpy)3](2+), ClO4(-), [Mn(II)Cr(III)(ox)3](-))n and ([Ru(bpy)2ppy](+), [M(II)Cr(III)(ox)3](-))n with M(II) = Mn(II), Ni(II) in their optically active forms. In these 3D networks, all of the metallic centers have the same configuration, Delta or Lambda, as the template cation. We have determined the structure of ([DeltaRu(bpy)3][ClO4][DeltaMnDeltaCr(ox)3])n and ([LambdaRu(bpy)2ppy](+), [LambdaMn(II)LambdaCr(III)(ox)3](-))n by X-ray diffraction studies. These optically active networks show the Cotton effect and long-range ferromagnetic order at low temperatures. The magnetic circular dichroism of ([Ru(bpy)3](2+), ClO4(-), [Mn(II)Cr(III)(ox)3](-))n at 2 K is reported.

Clean oxidation of thiolates to sulfinates in a four-coordinate CoIII complex with a mixed carboxamido N-thiolato S donor set: relevance to nitrile hydratase.

A new [Co(N2(SO2)2)(CNtBu)2](Et4N) complex 6 was prepared from N,N'-(3-mercapto-3-methyl-butyryl)-o-phenylenediamine and completely characterized. While the starting square planar complex [Co(N2S2)](Et4N) 4 was destroyed by dioxirane, the Co ligated thiolates of the six-coordinate intermediate [Co(N2S2)(CNtBu)2](Et4N) complex 5 was readily oxidized to sulfinates with a stoichiometric amount of this oxidant. The resulting complex 6 crystallizes with an octahedral structure. The SO bonds of the SO2 groups are almost equivalent (approximately 1.483 and approximately 1.453 A). The isonitrile is linearly bonded to the cobalt with a Co-C-N angle of 177.5 degrees and a very short C-N(tBu) distance of 1.13 A, which has a triple bond character. As expected for six-coordinate CoIII complexes, 5 and 6 are diamagnetic in agreement with their 1H and 13C NMR spectra. The SO2 IR bands are located at 1210 cm(-1) (v(as)SO2) and 1070 cm(-1) (v(s)SO2), while the CN vibration of the isonitrile is observed at 2170 cm(-1) in 5 and 2210 cm(-1) in 6. Very recently, it has been reported in the literature that oxidation of the coordinated thiolates was required for activity of both Fe and Co nitrile hydratases. Complex 6, with two oxidized thiolates trans to two deprotonated carboxamido nitrogens, is the first to have an in-plane closely related to that of the Co-NHase active site.

[Fe(Phen)(CN)4]-: a versatile building block for the design of heterometallic systems. Crystal structures and magnetic properties of PPh4[Fe(Phen)(CN)4]*2H2O and [[Fe(Phen)(CN)4]2M(H2O)2]*4H2O [Phen = 1,10-phenanthroline; M = Mn(II) and Zn(II)].

The mononuclear PPh4[Fe(phen)(CN)4]*2H2O (1) complex and the cyanide-bridged bimetallic [[Fe(phen)(CN)4]2M(H2O)2]*4H2O compounds [M = Mn(II) (2) and Zn(II) (3); phen = 1,10-phenanthroline; PPh4 = tetraphenylphosphonium cation] have been synthesized and structurally and magnetically characterized. Complex 1 crystallizes in the monoclinic system, space group P2(1)/c, with a = 9.364(4) A, b = 27.472(5) A, c = 14.301(3) A, beta = 97.68(2) degrees, and Z = 4. Complexes 2 and 3 are isostructural and they crystallize in the monoclinic system, space group P2(1)/n, with a = 7.5292(4) A, b = 15.6000(10) A, c = 15.4081(9) A, beta = 93.552(2) degrees, and Z = 2 for 2 and a = 7.440(1) A, b = 15.569(3) A, c = 15.344(6) A, beta = 93.63(2) degrees, and Z = 2 for 3. The structure of complex 1 is made up of mononuclear [Fe(phen)(CN)4]- anions, tetraphenyphosphonium cations, and water molecules of crystallization. The iron(III) is hexacoordinate with two nitrogen atoms of a chelating phen (2.018(6) and 2.021(6) A for Fe-N) and four carbon atoms of four terminal cyanide groups (Fe-C bond lengths varying in the range 1.906(8)-1.95(1) A) building a distorted octahedron around the metal atom. The structure of complexes 2 and 3 consists of neutral double zigzag chains of formula [[Fe(phen)(CN)4]2M(H2O)2] and crystallization water molecules. The [Fe(phen)(CN)4]- entity of 1 is present in 2 and 3 acting as a bridging ligand toward M(H2O)2 units [M = Mn(II) (2) and Zn(II) (3)] through two cyanide groups in cis positions, the other two cyanide remaining terminal. Two water molecules in trans positions and four cyanide-nitrogen atoms from four [Fe(phen)(CN)4]- units build a distorted octahedral surrounding Mn(II) (2) and Zn(II) (3). The M-O bond lengths are 2.185(3) (2) and 2.105(3) A (3), whereas the M-N bond distances vary in the ranges 2.210(3)-2.258(3) A (2) and 2.112(3)-2.186(3) A (3). The structure of the [Fe(phen)(CN)4]- complex ligand in 2 and 3 is as in 1. The shorter intrachain Fe-M distances through bridging cyano are 5.245(5) and 5.208(5) A in 2 and 5.187(1) and 5.132(1) A in 3. The magnetic properties of 1-3 have been investigated in the temperature range 2.0-300 K. Complex 1 is a low-spin iron(III) complex with an appreciable orbital contribution. The magnetic properties of 3 correspond to the sum of two magnetically isolated spin triplets, the magnetic coupling between the low-spin iron(III) centers through the -CN-Zn-NC- bridging skeleton (iron-iron separation larger than 10.2 A) being negligible. More interestingly, 2 exhibits one-dimensional ferrimagnetic behavior due to the noncompensation of the local interacting spins (S(Mn) = 5/2 and S(Fe) = 1/2) which interact antiferromagnetically through bridging cyano groups. A comparison between the magnetic properties of the isostructural compounds 2 and 3 allow us to check the antiferromagnetic coupling in 2.

Cobalt-complexed conjugated diyne salts: a family of rigid masked dielectrophiles. Syntheses, structures, and double nucleophilic substitutions.

A family of dicationic diyne salts of the general formula [(Co2(CO)6)2-mu,eta2,eta2-(Nu-CH2C(triple bond)C-C(triple bond)CCH2-Nu)][BF4]2 [Nu = SMe2 (3); Nu = NC6H7, 3-picoline, (5); Nu = NC9H7, quinoline (7)] were prepared and fully characterized. Three X-ray molecular structures of 3, 5, and the neutral starting material 2,4-hexadiyne-1,6-diol complex [(Co2(CO)6)2-mu,eta2,eta2-(HO-CH2C(triple bond)C-C(triple bond)CCH2-OH)] (1) are presented. Complex 1 crystallizes in the triclinic space group P1 with a = 14.722(2) A, b = 14.571(3) A, c = 14.722(2) A, alpha = 105.17(1) degrees, beta = 113.30(1) degrees, gamma = 99.20(1) degrees, and Z = 4. Complex 3 crystallizes in the monoclinic space group P2(1)/n with a = 12.758(3) A, b = 13.360(3) A, c = 20.494(3) A, beta = 91.44(1) degrees, and Z = 4, and compound 5 also crystallizes in the monoclinic space group P2(1)/n with a = 9.426(2) A, b = 21.739(5) A, c = 18.704(3) A, beta = 94.86(1) degrees, and Z = 4. The X-ray structures provide us with valuable information on the arrangement of the Co2-alkyne units, which have a cis geometry and are in sharp contrast to that observed generally for diyne-tetracobalt compounds. Complex [(Co2(CO)6)2-mu,eta2,eta2-(Me2S-CH2C(triple bond)C-C(triple bond)CCH2-SMe2)][BF4]2 (3) reacts with N-, S-, and P-centered nucleophiles and affords the related substituted complexes in high yields. The stability and reactivity of the disulfonium diyne complex 3 toward nucleophiles are compared to those of the analogous disulfonium-yne complex [(Co2(CO)6)2-mu,eta2,eta2-(Me2S-CH2-C(triple bond)C-CH2-SMe2)][BF4]2 (4).

A Pentacoordinated Di-N-carboxamido-dithiolato-O-sulfinato-iron(III) Complex Related to the Metal Site of Nitrile Hydratase.

Postcoordination oxidation by dioxygen of one of the thiolate groups in a pentadentate N(2)S(3) ligand results in an iron(III) complex with two N-carboxamido, two thiolato, and one O-sulfinato ligands (see the CAMERON representation). This novel mixed coordination is similar to that determined for the inactive form of the nitrile hydratase from Rhodococcus sp. N-771, but differs by the O versus S binding of the sulfinato ligand.

Unusual Me-O Bond Cleavage in a Metalated Crown-Ether: X-ray Molecular Structure of (5-Methoxy-4,6-dimethyl-1,3-xylylene-2-one)-15 Crown-4 Complex of Pentamethylcyclopentadienyl Iridium.

The reaction of [(C(5)Me(5))Ir(Solvent)(3)][BF(4)](2) (1) with (2,5-dimethoxy-4,6-dimethyl-1,3-xylylene)-15 crown-4 (2) affords the metalated crown-ether complex [(eta(5)-C(5)Me(5))Ir(eta(6)-C(18)H(28)O(6))][BF(4)](2) (3) in 88% yield. Complex 3 undergoes a facile Me-O bond cleavage to give the related semiquinone form of the metalated crown-ether [(eta(5)-C(5)Me(5))Ir(eta(5)-C(17)H(25)O(6))][BF(4)] (4). A single-crystal X-ray structure determination of complex 4 is reported. Complex 4 crystallizes in the monoclinic space group P2(1)/m with a = 8.187(5) Å, b = 17.193(4) Å, and c = 10.900(3) Å, alpha = 90 degrees, beta = 109.68(1) degrees, gamma = 90 degrees, and Z = 2. The structure provides us with valuable information about the nature of the eta(5)-semiquinone form of the metalated crown-ether and reveals that, surprisingly, the Me-O unit close to the crown chain is the one that undergoes hydrolysis. A rationale consistent with the experimental results is advanced.