Biomedical subjects
Publications and source records attributed to Carlos A Murillo.
We report a dirhodium paddlewheel compound which has an Rh2(5+) core enveloped by four guanidinate ligands and an axially coordinated bromine atom; Rh2(hpp)4Br crystallizes as a 1-D chain with a Rh-Rh distance of 2.430(3) è and a Rh-Rh bond order of 1.5 (hpp = the anion of 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2a]pyrimidine).
Two enantiopure molecular loops, RR-[cis-Rh2(C6H4PPh2)2(py)2O2C(CF2)(n)CO2]2 (1, n = 2 and 2, n = 3) have been made from the reaction in CH2Cl2 and CH3OH of the inherently chiral dirhodium compound, R-[cis-Rh2(C6H4PPh2)2(CH3CN)6](BF4)2, and HO2C(CF2)(n)CO2H in the presence of an excess of pyridine. Single-crystal structure analyses reveal that each of these compounds is composed of two R-cis-Rh2(C6H4PPh2)2(ax-py)2(2+) units, and two equatorial perfluorodicarboxylate linkers, which form a loop oligomer. The 1H, 19F, and 31P[1H] NMR spectra in CDCl3 and C5D5N indicate that only one type of highly symmetric species exists in each solution, which is consistent with the solid-state structures.
Enantiomers of the orthometalated dirhodium compound cis-Rh2(C6H4PPh2)2(OAc)2(HOAc)2 (R-1 and S-1) were prepared from carboxylate exchange reactions of the resolved diasteroisomers of cis-Rh2(C6H4PPh2)2(protos)2(H2O)2 (protos = N-4-methylphenylsulfonyl-l-proline anion) and acetic acid. These compounds react with excess Me3OBF4 in CH3CN, producing the enantiomers of [cis-Rh2(C6H4PPh2)2(CH3CN)6](BF4)2 (R-2 and S-2) which have six labile and replaceable CH3CN ligands in equatorial and axial positions. Reactions of R-2 and S-2 with tetraethylammonium salts of the linear dicarboxylic acids, terephthalic acid (HO2CC6H4CO2H), oxalic acid (HO2CCO2H), and 4,4'-diphenyl-dicarboxylic acid (HO2CC6H4C6H4CO2H) afford the enantiopure triangular supramolecules [cis-Rh2(C6H4PPh2)2(O2CC6H4CO2)(py)2]3, RRR-3 and SSS-3, Rh6(cis-C6H4PPh2)6(O2CCO2)3(py)5(CH2Cl2), RRR-4 and SSS-4, and Rh6(cis-C6H4PPh2)6(O2CC6H4C6H4CO2)3(py)4(CH2Cl2)2, RRR-5 and SSS-5, respectively. The absolute structures of each of the enantiomers of 1, 3, 4, and 5 were determined by X-ray diffraction analyses. The enantiomers of 3, 4, and 5 were found to be enantiomorphically isostructural, whereas R-1 and S-1 crystallized in different space groups. In 4 and 5, CH2Cl2 molecules coordinate to rhodium atoms in the axial positions. The 1H and 31P[1H] NMR spectra of all compounds are reported. The triangular compounds are redox-active, and their electrochemistry is also discussed. An assay of the catalytic activity/selectivity performance of the triangles for typical metal carbene transformation, using the model intermolecular cyclopropanation of styrene with ethyl diazoacetate in both homogeneous and heterogeneous phases, show that these chiral triangles are very active and have remarkable selectivity when compared with simple Rh2 paddle-wheel catalysts with chiral amidate ligands.
We present the synthesis, as well as the structural and magnetic characterization, of [Ru2(D(3,5-Cl2Ph)F)4Cl(0.5H2O)].C6H14 (D(3,5-Cl2Ph)F = N,N'-di(3,5-dichlorophenyl)formamidinate), a Ru2(5+) compound having a 4B(2u) ground state derived from a sigma2pi4delta2pi2delta electron configuration. The persistence of this configuration from 27 to 300 K is shown by the invariance of the Ru-Ru distance. Orientation-dependent magnetic susceptibility (chiT) and magnetization (M(H)) data are in accord with a spin quartet ground state with large magnetocrystalline anisotropy associated with a large axial zero-field splitting (D) parameter. Theoretical fits to chiT and M(H) plots yielded D/kB = +114 K, implying an S = +/-1/2 Kramers doublet ground state at low temperature. Single-crystal and powder EPR data are consistent with this result, as the only observed transition is between the M(s) = +/1/2 Zeeman levels. The g values are g(perpendicular) = 2.182, g(parallel) = 1.970, and D = 79.8 cm(-1). The totality of the results demands D >> 0.
A carceplex with T symmetry of the type A(4)B(6) has been synthesized enantiospecifically by employing the trianion of benzene-1,3,5-tricarboxylic (trimesic) acid as A and the R-cis-Rh(2)(C(6)H(4)PPh(2))(2)(2+) cation as B. The chiral (C(2)) B units abolish the symmetry planes required for T(d) symmetry, thus leaving only the eight C(3) and three C(2) rotations of the group T. Racemization is impossible under any chemically interesting conditions. This would appear to be only the third case where both preselection of the desired enantiomer and enantiostability based on covalent bonding are achieved.
Reactions of Pd3(OAc)6 with lithium salts of mononegative bidentate N,N-ligands, L, of various types, such as formamidinates, benzamidinates, triazinates, and guanidinates, were investigated in a search for ways to obtain Pd2(4+) compounds that could serve as precursors to paddlewheel complexes with a metal-metal bond and a Pd2(5+) core. It was found that the reactions are complex and that either square planar mononuclear or dinuclear species may be formed depending on the reaction conditions or the method of isolation. For Pd2L4 compounds, alpha and beta isomers were sometimes obtainable. In the alpha isomer, all N,N-ligands serve as bridges, whereas in the beta isomer, two ligands bridge the Pd2(4+) unit and each of the other two chelate to a metal atom. Electrochemistry shows that the paddlewheel compounds Pd2(TolNC(H)NTol)4, Pd2(PhNC(Ph)NPh)4, and Pd2(PhNC(Ph)NPh)3(OAc) and the orthometalated complex cis-Pd2[eta2-C6H4NC(Ph)N(H)Ph]2(mu-OAc)2 have reversible oxidation waves between 0.70 and 0.92 V vs Ag/AgCl, which makes them good candidates for chemical oxidation.
A new synthetic path, far superior to either of those previously available, to the W2(hpp)4 molecule (Hhpp = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) is reported. The reaction of W(CO)6 with Hhpp in o-dichlorobenzene at 200 degrees C produces W2(hpp)4Cl2 in a one-pot reaction in over 90% yield. This compound is stable and easily stored for further use, and it can be efficiently reduced in a one-step reaction to the title compound W2(hpp)4.
Reaction of activated palladium metal with a HNO3/acetic acid mixture produces both orange Pd3(OAc)6, 1, and purple Pd3(OAc)5(NO2), 2. Compound has a trinuclear structure derived from that of the well-known triangular complex 1 in which one acetate group has been replaced by a nitrite group which is bonded to one palladium atom by the nitrogen atom and to another Pd atom using one of the oxygen atoms. Highly pure 1 can be made by continuous removal of the nitric oxides from the reaction mixture using a flow of N2. 1H NMR spectra of solutions of 1 in CDCl3 and C6D6 show several signals of various intensities when a small amount of water is present in the deuterated solvents but only one signal when the solvents are thoroughly dried. These results are consistent with the occurrence of one or more hydrolysis processes when the solvents contain water and suggest that hypotheses about various [Pd(OAc)2]n aggregates that have previously been brought forward in the literature to explain the complexity of the spectrum of 1 are unnecessary, especially for nonpolar solvents. Compound 2 does not hydrolyze, and in wet or dried solvents shows a 1H NMR spectrum that consists of five equal-intensity signals due to the five nonequivalent acetate groups.
The magnetic and structural properties of two Ru2(DArF)4Cl compounds, where DArF is the anion of a diaryl formamidine, are presented here. The compounds with Ar = p-anisyl and m-anisyl both show temperature dependence of chiT (chi = molar magnetic susceptibility), but for different reasons. For the para compound, there is a Boltzmann distribution between a pi*3 ground state and a delta*pi*2 upper state, and this is confirmed by a temperature dependence of the Ru-Ru bond length: 2.4471(5) A at 23 K and 2.3968(5) A at 300 K. For the meta compound, a delta*pi*2 configuration persists over the range of 23-300 K as shown by an invariant Ru-Ru bond length, but the chiT drops with decreasing temperature owing to zero-field splitting of a 4B2u ground state.
The X-ray crystallographic structures, the magnetic susceptibilities from 2 to 300 K, and a theoretical analysis of the magnetism for a triangular and a tetranuclear molecule consisting of linked high-spin cobalt(II) centers are described. The interpretation of the magnetic data for the triangular compound [Co(depa)Cl](3) (depa is the anion of 2,2'-(bis-4-ethylpyridyl)amine), which has tetrahedrally coordinated Co(2+) ions, entails isotropic antiferromagnetic exchange interaction and antisymmetric exchange acting within the two low-lying spin doublets. Two strong isotropic ferromagnetic interactions have been modeled in the cuboidal compound Co(4)(DPM)(4)(CH(3)O)(4)(CH(3)OH)(4) (DPM represents the anion of dipivaloylmethane), which has octahedral coordination, and the system can be approximately considered as two weakly coupled S = 3 species.
The title compound, [Ru2(C2H3O2)4(C15H16N2O2)2], lies on a crystallographic inversion center and exhibits an Ru-Ru bond length of 2.2847 (8) A. There are weak intramolecular hydrogen-bonding interactions between the N1,N2-di-p-anisylformamidine (HDAniF) ligands and the bridging acetate ligands. The molecule is one of the few examples of a crystallographically characterized axial bis-adduct of a {Ru2}4+ complex with two N-donor ligands.
The title compound, [Ru2(C13H11N2)3(C2H3O2)(C2H3N)]BF4.0.5CH2Cl2 or [Ru2(mu-DPhF)3(mu-O2CMe)(MeCN)]BF4.0.5CH2Cl2, where DPhF is N,N'-diphenylformamidinate, crystallized as dark-blue block-shaped crystals. In the unit cell, the diruthenium cation lies on a general position, and the BF4- anions reside on two independent special positions with crystallographic twofold symmetry. Disorder was observed for one of the phenyl groups in the formamidinate ligand, the axial acetonitrile molecule and the interstitial dichloromethane molecule. The compound, which exhibits a long Ru-Ru bond of 2.4131 (5) A, is the first {Ru2}5+ formamidinate species that is both equatorially and axially functionalized so that it can be used as a precursor for polymeric paramagnetic supramolecular assemblies.
BACKGROUND: The phosphoinositide 3-kinase (PI3K/Akt) pathway transduces signals initiated from growth factors. Previously, we identified an important role for PI3K/Akt in colon cancer progression. The purpose of this study was to determine (1) whether short interfering RNA (siRNA) directed to PI3K/Akt components can render colon cancer cells sensitive to treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and (2) the cellular mechanisms contributing to the enhanced sensitivity. METHODS: Human colon cancer cells KM20 and KM12C (both TRAIL resistant) were transfected with siRNA directed against the PI3K p85alpha regulatory subunit Akt1 or nontargeting control sequence and then treated with TRAIL (100 ng/mL) or vehicle. A ribonuclease protection assay was performed to assess changes in TRAIL receptor expression. Protein was extracted and analyzed by Western blot for expression of cleavage of TRAIL receptors (death receptor (DR) 4 and 5), caspase-3, caspase-8, and BID. Apoptosis was measured by enzyme-linked immunosorbent assay of DNA fragmentation. RESULTS: Combination treatment with p85alpha or Akt1 siRNA and TRAIL increased apoptosis in KM20 and KM12C cells, compared with TRAIL alone; these results were corroborated further by complete inhibition of apoptosis by Z-acetyl-Asp-Glu-Val-Asp-(DEVD)-fmk, a caspase-3 inhibitor. Furthermore, siRNA-mediated PI3K pathway inhibition resulted in increased expression of the TRAIL death receptors 4 and 5. CONCLUSIONS: Inhibition of PI3K/Akt by RNA interference sensitizes resistant colon cancer cells to TRAIL-induced cell death through the induction of TRAIL receptors and activation of caspase-3 and caspase-8. Agents that selectively target the PI3K/Akt pathway may enhance the effects of chemotherapeutic agents and provide novel adjuvant treatment for selected colon cancers.
Variable temperature magnetic studies of the Ru(2)(6+) guanidinate compounds Ru(2)(hpp)(4)Cl(2) (1) and Ru(2)(hpp)(4)(CF(3)SO(3))(2) (2) show that they are paramagnetic with two unpaired electrons at room temperature and that they appear essentially diamagnetic at 2 K. In neither compound do the Ru-Ru distances vary by more than 0.008(1) A from 27 to 296 K. This argues strongly that the ground state electronic configuration remains constant over this temperature range and that the decrease in magnetism as the temperature is lowered must be attributable to zero-field splitting of the (3)A(2g) ground state arising from the electronic configuration sigma(2)pi(4)delta(2)pi(2). The Ru-Ru distance in 1 is about 0.04-0.05 A longer than that in 2 which indicates that the Ru(2)(hpp)(4)(2+) core is quite sensitive to the nature of the axial ligands. The electronic spectra show three absorption bands for each compound.
Reactions of Ru(2)(O(2)CMe)(4)Cl with two formamidines, HDXyl(2,6)F = N,N'-di(2,6-xylyl)formamidine and HDAniF = N,N'-di(p-anisyl)formamidine, have been investigated with the idea of synthesizing compounds with a mixed set of ligands having different labilities to be used as precursors of paramagnetic, higher-order assemblies. Depending on the formamidine and the reaction conditions, several Ru(2)(5+) compounds of the type Ru(2)(O(2)CMe)(4)(-)(n)(DArF)(n)Cl (DArF = anion of an N,N'-diarylformamidine) have been isolated. With the bulky formamidine HXyl(2,6)F, the compounds Ru(2)(O(2)CMe)(3)(DXyl(2,6)F)Cl (1) and trans-Ru(2)(O(2)CMe)(2)(DXyl(2,6)F)(2)Cl (2) were obtained. From reactions with appropriate amounts of HDAniF in THF and in the presence of NEt(3) and LiCl, complexes of the general type Ru(2)(O(2)CMe)(4)(-)(n)(DArF)(n)Cl (n = 1-4) were selectively obtained. For n = 2, only the cis isomer was obtained. The choice of solvent in reactions of Ru(2)(O(2)CMe)(4)Cl and HDAniF is of great importance. Toluene favored the formation of the fully substituted Ru(2)(5+) complex Ru(2)(DAniF)(4)Cl (3), whereas MeOH resulted in a disproportionation reaction that gave the edge-sharing bioctahedral Ru(3+)Ru(3+) complex [trans-Ru(2)(mu-OMe)(2)(mu-O(2)CMe)(2)(HDAniF)(4)]Cl(2) (6) and the Ru(2)(4+) complex Ru(2)(DAniF)(4) (7). Complexes 6 and 7 with an Ru(2)(6+) and Ru(2)(4+) core, respectively, are diamagnetic, whereas all Ru(2)(5+) complexes are paramagnetic with sigma(2)pi(4)delta(2)(pi*delta*)(3) ground-state electronic configurations and large zero-field splitting contributions. All compounds show rich and complex electrochemical behavior.
Reaction of racemic cis-Rh(2)(C(6)H(4)PPh(2))(2)(OAc)(2)(HOAc)(2) with excess Me(3)OBF(4) in CH(3)CN results in the formation of racemic cis-[Rh(2)(C(6)H(4)PPh(2))(2)(CH(3)CN)(6)](BF(4))(2).0.5H(2)O (1.0.5H(2)O), an ionic dirhodium complex which has two cisoid nonlabile orthometalated phosphine bridging anions and six labile CH(3)CN ligands in equatorial and axial positions. Reactions of 1 with tetraethylammonium salts of the linear dicarboxylates, oxalate, terephthalate, and 4,4'-biphenyl-dicarboxylate, in organic solvents, produced racemic crystals of the triangular compounds [Rh(2)(C(6)H(4)PPh(2))(2)](3)(C(2)O(4))(3)(py)(6).6MeOH.H(2)O (2.6MeOH.H(2)O), [Rh(2)(C(6)H(4)PPh(2))(2)](3)(O(2)CC(6)H(4)CO(2))(3)(DMF)(6).6.5DMF.0.5H(2)O (3.6.5DMF.0.5H(2)O), and [Rh(2)(C(6)H(4)PPh(2))(2)](3)(O(2)CC(6)H(4)C(6)H(4)CO(2))(3)(py)(6).4.5CH(3)OH.0.75H(2)O (4.4.5CH(3)OH.0.75H(2)O), respectively. All compounds are electrochemically active. The relative chiralities of the dirhodium units in each triangle have been established using a combination of data from X-ray crystallography and (31)P NMR spectroscopy.
Very strong electronic communication, manifested in a K(C) value of ca. 10(9), has been found in a system of three compounds separated by one electron oxidation where each compound contains two metal-metal bonded Mo(2)(n+) units linked by a dimethyloxamidate anion, CH(3)N(O)C-C(O)NCH(3)(2)(-). The Mo-Mo distances increase as the oxidation state increases and the bond order decreases, while the diamagnetic, doubly oxidized species becomes essentially planar and resembles a naphthalene molecule. Calculations at the DFT level indicate that a strong transition in the near-IR region, shown by the singly oxidized and paramagnetic species, is best described as a HOMO-1 --> SOMO transition.
Reactions of W(CO)(6) with formamidines contrast with those of Mo(CO)(6) and Cr(CO)(6) in that the former do not yield quadruply bonded dimetal species. From the reaction of W(CO)(6) with HDAniF (HDAniF = N,N'-di-p-anisylformamidine), several new ditungsten carbonyl compounds (W(2)(mu-CO)(2)(mu-DAniF)(2)(eta(2)-DAniF)(2) (1), W(2)(mu-CO)(2)(mu-DAniF)(2)(eta(2)-DAniF)(eta(2)-CH(2)DAniF) (2), and W(2)(mu-CO)(mu-CNC(6)H(4)OCH(3))(mu-DAniF)(2)(eta(2)-DAniF)(2) (3)) have been isolated and fully characterized. In 2, CH(2)DAniF represents a DAniF ligand in which a methylene group has been added to one of the nitrogen atoms. This ligand binds to the tungsten atom using a nitrogen and a carbon atom. Compound 1 has a tungsten-tungsten bond distance of 2.476(1) A and a planar W(2)(mu-CO)(2) core structure which has C(2)(h)() symmetry with short and long W-C bond distances (1.99(1) and 2.28(1) A, respectively). DFT calculations on a model of 1 indicate that (a) the C(2)(h)() instead of D(2)(h)() symmetry of the ditungsten core may be attributed to W --> CO pi back-bonding interactions and (b) the bond between the tungsten atoms may be formulated as a double bond. The new tetragonal paddlewheel compound W(2)(DAniF)(4) (4) and the edge-sharing bioctahedron W(2)(mu-O)(mu-NC(6)H(3)Cl(2))(mu-D(Cl)PhF)(2)(eta(2)-D(Cl)PhF)(2) (5) (D(Cl)PhF = N,N'-di-(3,5-dichlorophenyl)formamidinate) have also been prepared.