Synthesis, structure and reactivity of iridium complexes containing a bis-cyclometalated tridentate C

In an effort to synthesize cyclometalated iridium complexes containing a tridentate C^N^C ligand, transmetallation of [Hg(HC^N^C)Cl] (1) (H2C^N^C = 2,6-bis(4-tert-butylphenyl)pyridine) with various organoiridium starting materials has been studied. The treatment of 1 with [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) in acetonitrile at room temperature afforded a hexanuclear Ir4Hg2 complex, [Cl(κ2C,N-HC^N^C)(cod)IrHgIr(cod)Cl2]2 (2), which features Ir-Hg-Ir and Ir-Cl-Ir bridges. Refluxing 2 with sodium acetate in tetrahydrofuran (thf) resulted in cyclometalation of the bidentate HC^N^C ligand and formation of trinuclear [(C^N^C)(cod)IrHgIr(cod)Cl2] (3). On the other hand, refluxing [Ir(cod)Cl]2 with 1 and sodium acetate in thf yielded [Ir(C^N^C)(cod)(HgCl)] (4). Chlorination of 4 with PhICl2 gave [Ir(C^N^C)(cod)Cl]·HgCl2 (5·HgCl2) that reacted with tricyclohexylphosphine to yield Hg-free [Ir(C^N^C)(cod)Cl] (5). Chloride abstraction of 5 with silver(i) triflate (AgOTf) gave [Ir(C^N^C)(cod)(H2O)](OTf) (6) that can catalyze the cyclopropanation of styrene with ethyl diazoacetate. Reaction of 1 and [Ir(CO)2Cl(py)] (py = pyridine) with sodium acetate in refluxing thf afforded [Ir(C^N^C)(HgCl)(py)(CO)] (7), in which the carbonyl ligand is coplanar with the C^N^C ligand. On the other hand, refluxing 1 with (PPh4)[Ir(CO)2Cl2] and sodium acetate in acetonitrile gave [Ir(C^N^C)(κ2C,N-HC^N^C)(CO)] (8), the carbonyl ligand of which is trans to the pyridyl ring of the bidentate HC^N^C ligand. Upon irradiation with UV light 8 in thf was isomerized to 8', in which the carbonyl is trans to a phenyl group of the bidentate HC^N^C ligand. The isomer pair 8 and 8' exhibited emission at 548 and 514 nm in EtOH/MeOH at 77 K with lifetime of 84.0 and 64.6 µs, respectively. Protonation of 8 with p-toluenesulfonic acid (TsOH) afforded the bis(bidentate) tosylate complex [Ir(κ2C,N-HC^N^C)2(CO)(OTs)] (9) that could be reconverted to 8 upon treatment with sodium acetate. The electrochemistry of the Ir(C^N^C) complexes has been studied using cyclic voltammetry. Reaction of [Ir(PPh3)3Cl] with 1 and sodium acetate in refluxing thf led to isolation of the previously reported compound [Ir(κ2P,C-C6H4PPh2)2(PPh3)Cl] (10). The crystal structures of 2-5, 8, 8', 9 and 10 have been determined.

Oxidizing Cerium(IV) Alkoxide Complexes Supported by the Kläui Ligand [Co(η5-C5H5){P(O)(OEt)2}3]-: Synthesis, Structure, and Redox Reactivity.

Tetravalent cerium alkoxide complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){P(O)(OEt)2}3]- (LOEt-) have been synthesized, and their nucleophilic and redox reactivity have been studied. Treatment of the Ce(IV) oxo complex [CeIV(LOEt)2(O)(H2O)]·MeCONH2 (1) with iPrOH or reaction of [CeIV(LOEt)2Cl2] (2) with Ag2O in iPrOH afforded the Ce(IV) dialkoxide complex [CeIV(LOEt)2(OiPr)2] (3-iPr). The methoxide and ethoxide analogues [CeIV(LOEt)2(OR)2] (R = Me (3-Me), Et (3-Et)) have been prepared similarly from 2 and Ag2O in ROH. Reaction of 3-iPr with an equimolar amount of 2 yielded a new Ce(IV) complex that was formulated as the chloro-alkoxide complex [CeIV(LOEt)2(OiPr)Cl] (4). Treatment of 3-iPr with HX and methyl triflate (MeOTf) afforded [Ce(LOEt)2X2] (X- = Cl-, NO3-, PhO-) and [CeIV(LOEt)2(OTf)2], respectively, whereas treatment with excess CO2 in hexane led to isolation of the Ce(IV) carbonate [CeIV(LOEt)2(CO3)]. 3-iPr reacted with water in hexane to give a Ce(III) complex and a Ce(IV) species, presumably the reported tetranuclear oxo cluster [CeIV4(LOEt)4(O)5(OH)2]. The Ce(IV) alkoxide complexes are capable of oxidizing substituted phenols, possibly via a proton-coupled electron transfer pathway. Treatment of 3-iPr with ArOH afforded the Ce(III) aryloxide complexes [CeIII(LOEt)2(OAr)] (Ar = 2,4,6-tri-tert-butylphenyl (5), 2,6-diphenylphenyl (6)). On the other hand, a Ce(III) complex containing a monodeprotonated 2,2'-biphenol ligand, [CeIII(LOEt)2(tBu4C12H4O2H)] (7) (tBu4C12H4O2H2 = 4,4',6,6'-tetra-tert-butyl-2,2'-biphenol), was isolated from the reaction of 3-iPr with 2,4-di-tert-butylphenol. The crystal structures of complexes 3-iPr, 3-Me, 3-Et, and 5-7 have been determined.

4-Coordinated, 14-electron ruthenium(ii) chalcogenolate complexes: synthesis, electronic structure and reactions with PhICl2 and organic azides.

The 4-coordinated RuII chalcogenolate complexes [Ru(STipp)2(PPh3)2] (Tipp = 2,4,6-triisopropylphenyl, 1) and [Ru(SeMes)2(PPh3)2] (Mes = 2,4,6-trimethylphenyl, 2) have been synthesized, and their reactions with PhICl2 and organic azides have been studied. Complex 2 synthesized from [RuII(PPh3)3Cl2] and NaSeMes displays a seesaw structure with P-Ru-P and Se-Ru-Se bond angles of 103.43(13) and 145.26(6)°, respectively. Natural bond order analyses revealed that in each of 1 and 2, there are two n →σ* (donor-acceptor) π interactions between the chalcogen lone pairs and the Ru-P antibonding molecular orbitals. The calculated second-order perturbation interaction energies of the two interactions for 1 (20.5 and 18.3 kcal mol-1) are stronger than those of 2 (13.6 and 11.0 kcal mol-1), suggesting the thiolate ligand (TippS-) is a stronger π-donor than the selenolate ligand (MesSe-) with respect to RuII. Chlorination of 1 with PhICl2 afforded the dichloride complex [Ru(STipp)2Cl2(PPh3)] (3), which was hydrolyzed to the hydroxo complex [Ru(STipp)2(OH)Cl(PPh3)] (4) after column chromatography on silica in air. Treatment of 4 with HCl and methyl triflate gave 3 and [Ru(STipp)2(OH)(OTf)(PPh3)] (OTf = triflate, 5), respectively. Reactions of 1 and 2 with p-tolyl azide (p-tolN3) afforded the tetrazene complexes [Ru{N4(p-tol)2}(ER)2(PPh3)] (ER = STipp (6), SeMes (7)), whereas that with tosyl azide (TsN3) gave the imido complexes [Ru(κ2-NTs)(STipp)2(PPh3)] (ER = STipp (8), SeMes (10)). The short Ru-Nimido distances in 8 [1.883(3) Å] and 10 [1.892(2) Å] are indicative of multiple bond character. Treatment of 8 with TsN3 afforded the tetrazene complex [Ru(N4Ts2)(STipp)2(PPh3)] (9), but no cycloaddition was found between 10 and TsN3. Nucleophilic attack of the imido ligand in 10 with methyl triflate yielded the amido complex [Ru(κ2-NMeTs)(SeMes)2(PPh3)](OTf) (11). The crystal structures of 2, 4, 6, and 8-11 have been determined.

Reactions of cerium complexes with transition metal nitrides: synthesis and structure of heterometallic cerium complexes containing bridging catecholate ligands.

In an attempt to synthesize heterometallic cerium nitrido complexes, we studied the reactions of cerium complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){PO(OEt)2}3]- (LOEt-) with transition-metal nitrides. Whereas no reactions were found between Ce-LOEt complexes and [RuVI(LOEt)(N)Cl2] (2), treatment of the Ce(iv) oxo complex [CeIV(LOEt)2(O)(H2O)]·MeCONH2 (1) with 2 resulted in reduction of both the Ce(iv) and Ru(vi) complexes, and formation of a heterometallic Ce(iii)/Ru(iii) complex with a bridging deprotonated acetamide ligand, [(LOEt)2(H2O)CeIII{µ-O,N-MeC(O)NH}RuIII(LOEt)Cl2] (4), along with a minor product, [CeIII(LOEt)2(NO3)]. Ce(iv)-LOEt complexes such as [CeIV(LOEt)2Cl2] (3) can oxidize [ReV(LOEt)(N)(PPh3)Cl] to give the Re(vi) nitride [ReVI(LOEt)(N)(PPh3)Cl]+. Chloride abstraction of 3 by TlPF6 followed by reaction with [PPh4]2[MnV(N)(CN)4] afforded a diamagnetic red solid that is tentatively formulated as a heterometallic Ce(iv)/Mn(v) complex, [Ce(LOEt)2(H2O){Mn(N)(CN)4}] (5). Reactions of 3 with [nBu4N][MVI(N)(cat)2] (cat2- = catecholate(2-)) afforded the Ce(iii)/M(vi) complexes [(LOEt)2CeIII{(µ-cat)2MVI(N)}] [M = Ru (6), Os (7)], in which the Ce(iii) and M(vi) centers are bridged by two oxygen atoms of the two catecholate ligands. Similarly, the catecholate-bridged Ce(iii)/Re(v) complex [(LOEt)2CeIII{(µ-cat)2ReV(O)}] (8) was prepared from 3 and [Me4N][ReV(O)(cat)2]. In CH2Cl2, 8 was air-oxidized to the Ce(iii)/Re(vii) complex [CeIII(LOEt)2(H2O)2][cis-{ReVII(O)2(cat)2}] (9) with a cis-dioxo-Re(vii) counter-anion. The crystal structures of 4, 6, and 9 have been determined.

Iridium porphyrin complexes with µ-nitrido, hydroxo, hydrosulfido and alkynyl ligands.

Iridium porphyrin complexes containing µ-nitrido, hydroxo, hydrosulfido, and alkynyl ligands have been synthesized and structurally characterized, and their oxidation has been studied. The alkyl-IrIII porphyrin complex [Ir(tpp)R] (tpp2- = 5,10,15,20-tetraphenylporphyrin dianion; R = C8H13; 1) was synthesized by reaction of [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) with H2tpp in refluxing monoethylene glycol. Treatment of 1 with PPh3 and [(LOEt)Ru(N)Cl2] (LOEt- = [(η5-C5H5)Co{P(O)(OEt)2}3]-) gave [Ir(tpp)(R)(PPh3)] (2) and the µ-nitrido complex [R(tpp)Ir(µ-N)RuCl2(LOEt)] (3), respectively. The cyclic voltammogram of 3 exhibited a reversible oxidation couple at 0.44 V versus Fc+/0 (Fc = ferrocene). The oxidation of 3 with [(4-BrC6H4)3N](SbCl6) resulted in Ir-C bond homolysis and formation of the chloride complex [Cl(tpp)Ir(µ-N)RuCl2(LOEt)] (4). The short Ir-N(nitrido) bond distances in 3 [1.944(3) Å] and 4 [1.831(4) Å] are indicative of multiple bond character and thus these two µ-nitrido complexes can be described by the two resonance forms: IrIII-N[triple bond, length as m-dash]RuVI and IrV[double bond, length as m-dash]N[double bond, length as m-dash]RuIV. Similarly, the oxidation of 2 with [(4-BrC6H4)3N](SbCl6) yielded [Ir(tpp)Cl(PPh3)] (5). Chloride abstraction of 5 with TlPF6 in tetrahydrofuran (thf) afforded [Ir(tpp)(PPh3)(thf)](PF6) (6) that reacted with CsOH·H2O and Li2S to give the hydroxo [Ir(tpp)(OH)(PPh3)] (7) and hydrosulfido [Ir(tpp)(PPh3)(SH)] (8) complexes, respectively. Treatment of 6 with phenylacetylene in the presence of CuI and Et3N yielded the bimetallic complex [Ir(tpp)(PPh3)(µ-η1:η2-C[triple bond, length as m-dash]CPh)(CuI)] (9), whereas the transmetallation of 6 with LiC[triple bond, length as m-dash]CPh afforded the mononuclear alkynyl complex [Ir(tpp)(PPh3)(C[triple bond, length as m-dash]CPh)] (10). The electrochemistry of the Ir porphyrin complexes has been studied using cyclic voltammetry. On the basis of the measured redox potentials of [Ir(tpp)(PPh3)X], the ability of X- to stabilize the IrIV state is ranked in the order: R- > PhC[triple bond, length as m-dash]C- > Cl- ∼ OH-. Oxidation of 8 and 9 with [(4-BrC6H4)3N](SbCl6) led to isolation of 5 and [Ir(tpp)(PPh3)(H2O)]+, respectively. The crystal structures of complexes 3, 4, and 7-10 have been determined.

A Nitrido-bridged Heterometallic Ruthenium(IV)/Iron(IV) Phthalocyanine Complex Supported by A Tripodal Oxygen Ligand, [Co(η5-C5H5){P(O)(OEt)2}3]-: Synthesis, Structure, and Its Oxidation to Give Phthalocyanine Cation Radical and Hydroxyphthalocyanine Complexes.

Dinuclear iron nitrido phthalocyanine complexes are of interest owing to their applications in catalytic oxidation of hydrocarbons. While nitrido-bridged diiron phthalocyanine complexes are well documented, the oxidation chemistry of heterodinuclear iron(IV) phthalocyanine nitrides has not been well explored. In this paper we report on the synthesis of a heterometallic FeIV/RuIV phthalocyanine nitride and its oxidation to yield phthalocyanine cation radical and hydroxyphthalocyanine complexes. Treatment of [FeII(Pc)] (Pc2- = phthalocyanine dianion) with [RuVI(LOEt)(N)Cl2] (LOEt- = [Co(η5-C5H5){P(O)(OEt)2}3]-) (1) afforded the heterometallic µ-nitrido complex [Cl2(LOEt)RuIV(µ-N)FeIV(Pc)(H2O)] (2) that contains an RuIV=N = FeIV linkage with the Ru-N and Fe-N distances of 1.689(6) and 1.677(6) Å, respectively, and Ru-N-Fe angle of 176.0(4)°. Substitution of 2 with 4- tert-butylpyridine (Bupy) gave [Cl2(LOEt)RuIV(µ-N)FeIV(Pc)(Bupy)]. The cyclic voltammogram of 2 displayed a reversible Pc-centered oxidation couple at +0.18 V versus Fc+/0 (Fc = ferrocene). The oxidation of 2 with [N(4-BrC6H4)3]SbCl6 led to isolation of the cationic complex [Cl2(LOEt)RuIV(µ-N)FeIV(Pc·+)(H2O)][SbCl6]0.85[SbCl5(OH)]0.15 (2[SbCl6]0.85[SbCl5(OH)]0.15), whereas that with PhICl2 yielded the chloride complex [Cl2(LOEt)RuIV(µ-N)FeIV(Pc·+)Cl] (3). Complexes 2[SbCl6]0.85[SbCl5(OH)]0.15 and 3 have been characterized by X-ray crystallography. The UV/visible spectra of 2+ (λmax = 515 and 747 nm) and 3 (λmax = 506 and 748 nm) displayed absorption bands that are characteristic of Pc cation radical. The EPR spectrum of 3 showed a signal with the g value of 2.0012 (width = 5 G) that is consistent with an organic radical. The spectroscopic data support the formulation of 2+ and 3 as RuIV-FeIV Pc cation radical complexes. The reaction of 2 with PhI(CF3CO2)2 in dried CH2Cl2 afforded a mixture of [Cl2(LOEt)RuIV(µ-N)FeIV(Pc·+)(CF3CO2)] (4) and a hydroxyphthalocyanine complex, [Cl2(LOEt)RuIV(µ-N)FeIV(Pc-OH)(H2O)](CF3CO2) (5), whereas that in wet CH2Cl2 (containing ca. 0.5% water) led to isolation of 5 as the sole product. Complex 4 was independently prepared by salt metathesis of 3 with AgCF3CO2.

Heterobimetallic Nitrido Complexes of Group 8 Metalloporphyrins.

Heterobimetallic nitrido porphyrin complexes with the [(L)(por)M-N-M'(LOEt)Cl2] formula {por2- = 5,10,15,20-tetraphenylporphyrin (TPP2-) or 5,10,15,20-tetra(p-tolyl)porphyrin (TTP2-) dianion; LOEt- = [Co(η5-C5H5){P(O)(OEt)2}3]-; M = Fe, Ru, or Os; M' = Ru or Os; L = H2O or pyridine} have been synthesized, and their electrochemistry has been studied. Treatment of trans-[Fe(TPP)(py)2] (py = pyridine) with Ru(VI) nitride [Ru(LOEt)(N)Cl2] (1) afforded Fe/Ru µ-nitrido complex [(py)(TPP)Fe(µ-N)Ru(LOEt)Cl2] (2). Similarly, Fe/Os analogue [(py)(TPP)Fe(µ-N)Os(LOEt)Cl2] (3) was obtained from trans-[Fe(TPP)(py)2] and [Os(LOEt)(N)Cl2]. However, no reaction was found between trans-[Fe(TPP)(py)2] and [Re(LOEt)(N)Cl(PPh3)]. Treatment of trans-[M(TPP)(CO)(EtOH)] with 1 afforded µ-nitrido complexes [(H2O)(TPP)M(µ-N)Ru(LOEt)Cl2] [M = Ru (4a) or Os (5)]. TTP analogue [(H2O)(TTP)Ru(µ-N)Ru(LOEt)Cl2] (4b) was prepared similarly from trans-[Ru(TTP)(CO)(EtOH)] and 1. Reaction of [(H2O)(por)M(µ-N)M(LOEt)Cl2] with pyridine gave adducts [(py)(por)M(µ-N)Ru(LOEt)Cl2] [por = TTP, and M = Ru (6); por = TPP, and M = Os (7)]. The diamagnetism and short (por)M-N(nitride) distances in 2 [Fe-N, 1.683(3) Å] and 4b [Ru-N, 1.743(3) Å] are indicative of the MIV═N═M'IV bonding description. The cyclic voltammograms of the Fe/Ru (2) and Ru/Ru (4b) complexes in CH2Cl2 displayed oxidation couples at approximately +0.29 and +0.35 V versus Fc+/0 (Fc = ferrocene) that are tentatively ascribed to the oxidation of the {LOEtRu} and {Ru(TTP)} moieties, respectively, whereas the Fe/Os (3) and Os/Ru (5) complexes exhibited Os-centered oxidation at approximately -0.06 and +0.05 V versus Fc+/0, respectively. The crystal structures of 2 and 4b have been determined.

Ruthenium chalcogenonitrosyl and bridged nitrido complexes containing chelating sulfur and oxygen ligands.

Ruthenium thio- and seleno-nitrosyl complexes containing chelating sulfur and oxygen ligands have been synthesised and their de-chalcogenation reactions have been studied. The reaction of mer-[Ru(N)Cl3(AsPh3)2] with elemental sulfur and selenium in tetrahydrofuran at reflux afforded the chalcogenonitrosyl complexes mer-[Ru(NX)Cl3(AsPh3)2] [X = S (1), Se (2)]. Treatment of 1 with KN(R2PS)2 afforded trans-[Ru(NS)Cl{N(R2PS)2}2] [R = Ph (3), Pr(i) (4), Bu(t) (5)]. Alternatively, the thionitrosyl complex 5 was obtained from [Bu(n)4N][Ru(N)Cl4] and KN(Bu(t)2PS)2, presumably via sulfur atom transfer from [N(Bu(t)2PS)2](-) to the nitride. Reactions of 1 and 2 with NaLOEt (LOEt(-) = [Co(η(5)-C5H5){P(O)(LOEt)2}3](-)) gave [Ru(NX)LOEtCl2] (X = S (8), Se (9)). Treatment of [Bu(n)4N][Ru(N)Cl4] with KN(R2PS)2 produced Ru(IV)-Ru(IV)µ-nitrido complexes [Ru2(µ-N){N(R2PS)2}4Cl] [R = Ph (6), Pr(i) (7)]. Reactions of 3 and 9 with PPh3 afforded 6 and [Ru(NPPh3)LOEtCl2], respectively. The desulfurisation of 5 with [Ni(cod)2] (cod = 1,5-cyclooctadiene) gave the mixed valance Ru(III)-Ru(IV)µ-nitrido complex [Ru2(µ-N){N(Bu(t)2PS)2}4] (10) that was oxidised by [Cp2Fe](PF6) to give the Ru(IV)-Ru(IV) complex [Ru2(µ-N){N(Bu(t)2PS)2}4](PF6) ([10]PF6). The crystal structures of 1, 2, 3, 7, 9 and 10 have been determined.

Heterobimetallic rhenium nitrido complexes containing the Kläui tripodal ligand [Co(η(5)-C5H5){P(O)(OEt)2}3](-).

Rhenium nitrido complexes containing the Kläui tripodal ligand [Co(η(5)-C5H5){P(O)(OEt)2}3](-) (LOEt(-)) have been synthesised and their reactions with [Ir(I)(cod)Cl]2 (cod = 1,5-cyclooctadiene) and [Rh(II)2(OAc)4] (OAc(-) = acetate) have been studied. The treatment of [Bu(n)4N][Re(VI)(N)Cl4] with NaLOEt in methanol afforded the Re(VI) nitride [Re(VI)(LOEt)(N)Cl(OMe)] (1). Reactions of 1 with [Ir(I)(cod)Cl]2 and [Rh(II)2(OAc)4] gave the µ-nitrido complexes [(LOEt)(OMe)ClRe(VI)(µ-N)Ir(I)(cod)Cl] (2) and [Rh(II)2(OAc)4{(µ-N)Re(VI)(LOEt)(OMe)Cl}2] (4), respectively. [(LOEt)Cl(PPh3)Re(V)(µ-N)Ir(I)(cod)Cl] (3) and [(LOEt)Cl(PPh3)Re(VI)(µ-N)Ir(I)(cod)Cl][PF6] (3·PF6) have been synthesised from the reactions of [Ir(I)(cod)Cl]2 with [Re(V)LOEt(N)Cl(PPh3)] and [Re(VI)LOEt(N)Cl(PPh3)](PF6), respectively. Similarly, the redox pair [Rh(II)2(OAc)4{(µ-N)Re(V)(LOEt)(PPh3)Cl}2] (5) and [Rh(II)2(OAc)4{(µ-N)Re(VI)(LOEt)(PPh3)Cl}2](PF6)2 (·(PF6)2) have been synthesised from the reactions of [Rh2(OAc)4] with [Re(V)LOEt(N)Cl(PPh3)] and [Re(VI)LOEt(N)Cl(PPh3)](PF6), respectively. While [(LOEt)Cl2Ru(VI)(µ-N)Ir(I)(cod)] (6) was obtained from [Ru(VI)(LOEt)(N)Cl2] and [Ir(I)(cod)Cl]2, the interaction between [Ru(VI)(LOEt)(N)Cl2] and [Rh(II)2(OAc)4] in CH2Cl2 is reversible. The crystal structures of complexes 2, 3, 3·PF6, 5, 5·(PF6)2 and 6 have been determined. X-ray crystallography indicates that the nitrido bridges in 2, 3, 3·PF6 and 6 can be described as MN-Ir (M = Re, Ru) showing Ir-N multiple bond character, whereas the interaction between Re≡N and Rh in 5 and 5·(PF6)2 is mostly of the donor-acceptor type. The electrochemistry of the Re nitrido complexes has been investigated by cyclic voltammetry.

Facile η5-η1 ring slippage of the cycloolefin ligands in osmocene and bis(η5-indenyl)ruthenium(II).

η(5)-η(1) ring slippage of [OsCp2] (Cp = η(5)-C5H5) and [Ru(η(5)-ind)2] (ind = indenyl) resulting from reaction with the ruthenium(VI) nitride [Ru(L(OEt))(N)Cl2] (1; L(OEt)(-) = [CoCp{P(O)(OEt)2}3](-)) is reported. The treatment of [OsCp2] or [Ru(η(5)-ind)2] with 1 resulted in η(5)-η(1) ring slippage of the cycloolefin ligands and formation of the trinuclear nitrido complexes [Cp(η(1)-C5H5)Os(NRuL(OEt)Cl2)2] (2) or [(η(5)-ind)(η(1)-ind)Ru(NRuL(OEt)Cl2)2] (3). No reactions were found between [OsCp2] and amines, such as pyridine and 2,2'-bipyridyl, or other metal nitrides, such as [Os(L(OEt))(N)Cl2], indicating that the electrophilic property of 1 is essential for ring slippage. The crystal structures of 2 and 3 have been determined. The short Os-N distances in 2 [1.833(5) and 1.817(5) Å] and the (ind)Ru-N distances in 3 [1.827(5) and 1.852(5) Å] are indicative of multiple bond character, consistent with density functional theory (DFT) calculations. Therefore, 2 and 3 may be described by two resonance forms: Ru(VI)-M(II)-Ru(VI) and Ru(IV)-M(VI)-Ru(IV) (M = Os, Ru). Also, DFT calculations indicate that for the reaction of 1 with [OsCp2] or [Ru(η(5)-ind)2], η(5)-η(1) ring slippage is energetically more favorable than the η(5)-η(3) counterpart. The driving force for η(5)-η(1) ring slippage is believed to be the formation of the strong M-N (M = Os, Ru) (multiple) bonds. By contrast, the same reaction with acetonitrile is energetically uphill, and thus no ring slippage occurs.

Dinuclear ruthenium nitrido complexes supported by an oxygen tripodal ligand.

Dinuclear ruthenium nitrido complexes supported by the Kläui's tripodal ligand [CpCo{P(O)(OEt)(2)}(3)](-) (L(OEt)(-)) have been synthesized starting from the ruthenium(VI) nitrido precursor [L(OEt)Ru(VI)(N)Cl(2)] (1). Heating a solution of 1 in CCl(4) at reflux, followed by recrystallization from hexane under nitrogen, afforded the mixed-valence ruthenium(V)-ruthenium(IV) µ-nitrido complex [L(OEt)Cl(2)Ru(V)(µ-N)Ru(IV)Cl(2)L(OEt)] (2). The cyclic voltammogram of 2 exhibited reversible couples at 0.19 and 1.13 V versus Cp(2)Fe(+/0), which are assigned as the Ru(V)-Ru(IV)/Ru(IV)-Ru(IV) and Ru(V)-Ru(V)/Ru(V)-Ru(IV) couples, respectively. Recrystallization of 2 from Et(2)O/heptane in air yielded the diamagnetic Ru(IV)-Ru(IV) complex [H(13)O(6)][{L(OEt)Ru(IV)Cl(2)}(2)(µ-N)] ([H(13)O(6)][2]), which underwent cation exchange with n-Bu(4)NOH to give [n-Bu(4)N][2]. X-ray diffraction revealed that the complex anions in [H(13)O(6)][2] and [n-Bu(4)N][2] contain linear, symmetric Ru-N-Ru bridges. Treatment of 1 with [(η(6)-p-cymene)Ru(II)Cl(2)](2) in benzene afforded the tetranuclear ruthenium(IV) complex [L(OEt)Cl(2)Ru(IV)(µ-N)Ru(IV)(H(2)O)Cl(2)](2) (3) containing symmetric Ru(IV)-N-Ru(IV) bridges. The reaction of 1 with [Ru(II)(H)(Cl)(CO)(PCy(3))(2)] (Cy = cyclohexyl) gave the ruthenium(VI)-ruthenium(II) nitrido complex [L(OEt)Cl(2)Ru(VI)(µ-N)Ru(II)(H)Cl(CO)(PCy(3))(2)] (4). The observed short Ru(II)-N bond distance [1.915(5) Å] and high C-O stretching frequency (1985 cm(-1)) in 4 are suggestive of π interaction between Ru(II) and the nitride.

Torcetrapib produces endothelial dysfunction independent of cholesteryl ester transfer protein inhibition.

OBJECTIVE: Torcetrapib, a prototype cholesteryl ester transfer protein (CETP) inhibitor with potential for decreasing atherosclerotic disease, increased cardiovascular events in clinical trials. The identified hypertensive and aldosterone-elevating actions of torcetrapib may not fully account for this elevated cardiovascular risk. Therefore, we evaluated the effects of torcetrapib on endothelial mediated vasodilation in vivo. METHODS AND RESULTS: In vivo endothelial mediated vasodilation was assessed using ultrasound imaging of acetylcholine-induced changes in rabbit central ear artery diameter. Torcetrapib, in addition to producing hypertension and baseline vasoconstriction, markedly inhibited acetylcholine-induced vasodilation. A structurally distinct CETP inhibitor, JNJ-28545595, did not affect endothelial function despite producing similar degrees of CETP inhibition and high-density lipoprotein elevation. Nitroprusside normalized torcetrapib's basal vasoconstriction and elicited dose-dependent vasodilation of norepinephrine preconstricted arteries in torcetrapib-treated animals, indicating torcetrapib did not impair smooth muscle function. CONCLUSIONS: Torcetrapib significantly impairs endothelial function in vivo, independent of CETP inhibition and high-density lipoprotein elevation. Given the well-documented association of endothelial dysfunction with cardiovascular disease and risk, this activity of torcetrapib may have contributed to increased cardiovascular risk in clinical trials.

Pharmacological characterization of RWJ-676070, a dual vasopressin V(1A)/V(2) receptor antagonist.

The dysregulation of arginine vasopressin (AVP) release and activation of vasopressin V(1A) and V(2) receptors may play a role in disease. The in vitro and in vivo pharmacology of RWJ-676070, a potent, balanced antagonist of both the V(1A) and V(2) receptors is described. RWJ-676070 binding and intracellular functional antagonist activity was characterized using cells expressing V(1A), V(1B) or V(2) receptors. Its inhibition of V(1A) receptor-mediated contraction of vascular rings and platelet aggregation was determined. V(2) receptor-medated aquaresis was determined in rats, dogs and monkeys. V(1A) receptor-mediated inhibitory activity was assessed in vivo in a vasopressin-induced hypertension model and in normotensive rats and in two hypertensive rat models. RWJ-676070 inhibited AVP binding to human V(1A) and V(2) receptors (Ki=1 and 14 nM, respectively). RWJ-676070 inhibited V(1A) receptor-induced intracellular calcium mobilization and V(2) receptor-induced cAMP accumulation with Ki values of 14 nM and 13 nM, respectively. The compound was slightly less potent against rat V(1A) receptors. RWJ-676070 inhibited V(1A) receptor-mediated vasoconstriction in rat and dog vascular rings and AVP-induced human platelet aggregation. Dose dependent aquaresis was demonstrated in rats, dogs and monkeys following oral administration. RWJ-676070 inhibited AVP-induced hypertension in rats but had no effect on arterial pressure in normotensive and spontaneously hypertensive rats but did decrease arterial pressure in Dahl, salt-sensitive hypertensive rats. RWJ-676070 is a new, potent antagonist of V(1A) and V(2) receptors that may be useful for treatment of diseases benefiting from balanced inhibition of both V(1A) and V(2) receptors.

Ruthenium complexes with tetraphenylimidodiphosphinate: syntheses, structures, and applications to catalytic organic oxidation.

Treatment of Ru(PPh3)3Cl2 with K(tpip) (tpip(-)=[N(Ph2PO)2](-)) afforded Ru(tpip)(PPh3)2Cl (1), which reacted with 4- t-Bu-C6H4CN, SO2(g), and NH 3(g) to give Ru(tpip)(PPh3)2Cl(4- t-BuC6H4CN) (2), Ru(tpip)(PPh3)2Cl(SO2) (3), and fac-[Ru(NH3)3(PPh3)2Cl][tpip] (4), respectively. Reaction of [Ru(CO)2Cl2] x with K(tpip) in refluxing tetrahydrofuran (THF) led to isolation of the K/Ru bimetallic compound K 2Ru2(tpip)4(CO)4Cl2 (5). Photolysis of cis-Ru(tpip) 2(NO)Cl in MeCN and wet CH 2Cl 2 afforded cis-Ru(tpip) 2(MeCN)Cl ( 6) and cis-Ru(tpip)2(H2O)Cl (7), respectively. Refluxing 6 in neat THF yielded Ru(tpip) 2(THF)Cl (8). Treatment of Ru(CHR)Cl2(PCy3)2 (Cy=cyclohexyl) with [Ag(tpip)] 4 afforded cis-Ru(tpip)2(CHR)(PCy3) [R=Ph (9), OEt (10)]. Complex 9 is capable of catalyzing oxidation of alcohols and olefins with N-methylmorpholine N-oxide and iodosylbenzene, respectively. The crystal structures of 2-7 and 9 were determined.

Synthesis, crystal structures, and reactivity of osmium(II) and -(IV) complexes containing a dithioimidodiphosphinate ligand.

Reduction of trans-[OsL2(O)2] (1) (L-=[N(i-Pr2PS)2]-) with hydrazine hydrate afforded a dinitrogen complex 2, possibly "[OsL2(N2)(solv)]" (solv=H2O or THF), which reacted with RCN, R'NC, and SO2 to give trans-[OsL2(RCN)2] (R=Ph (3), 4-tolyl (4), 4-t-BuC6H4 (5)), trans-[OsL2(R'NC)2] (R'=2,6-Me2C6H3 (xyl) (6), t-Bu (7)), and [Os(L)2(SO2)(H2O)] (8) complexes, respectively. Protonation of compounds 2, 3, and 6 with HBF4 led to formation of dicationic trans-[Os(LH)2(N2)(H2O)][BF4]2 (9), trans-[Os(LH)2(PhCN)2][BF4]2 (10), and trans-[Os(LH)2(xylNC)2][BF4]2 (11), respectively. Treatment of 1 with phenylhydrazine and SnCl2 afforded trans-[OsL2(N2Ph)2] (12) and trans-[OsL2Cl2] (13), respectively. Air oxidation of compound 2 in hexane/MeOH gave the dimethoxy complex trans-[OsL2(OMe)2] (14), which in CH2Cl2 solution was readily air oxidized to 1. Compound 1 is capable of catalyzing aerobic oxidation of PPh3, possibly via an Os(IV) intermediate. The formal potentials for the Os-L complexes have been determined by cyclic voltammetry. The solid-state structures of compounds 4, 6, cis-8, 13, and 14 have been established by X-ray crystallography.

Novel indolylindazolylmaleimides as inhibitors of protein kinase C-beta: synthesis, biological activity, and cardiovascular safety.

Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-betaII (IC(50) = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.

Is there any difference in pregnancy and implantation rates when nurses perform embryo transfer in an IVF-ET program?

A retrospective analysis of fresh in vitro fertilization treatment cycles and frozen embryo transfer (FET) cycles from mid-1995 to December 31, 1998, was undertaken. Nurses performed embryo transfer (ET) for government-funded cycles, whereas doctors performed ET for self-funded cycles. During the study period, fresh ET was performed in 1,165 treatment cycles. There were no significant differences in demographic data, ovarian responses and the number of embryos replaced between ET cycles performed by nurses and doctors. Pregnancy rates for ETs performed by nurses and doctors were 16.7 and 15.8% per transfer, respectively, whereas the corresponding implantation rates were 8.3 and 6.9%, respectively. Similar pregnancy and implantation rates were encountered in FET cycles whether ET was performed by nurses or doctors.