Reductive Hydrogenation of Sulfido-Bridged Tantalum Alkyl Complexes: A Mechanistic Insight.

Hydrogenolysis of a series of alkyl sulfido-bridged tantalum(IV) dinuclear complexes [Ta(η5-C5Me5)R(µ-S)]2 [R = Me, nBu (1), Et, CH2SiMe3, C3H5, Ph, CH2Ph (2), p-MeC6H4CH2 (3)] has led quantitatively to the Ta(III) tetrametallic sulfide cluster [Ta(η5-C5Me5)(µ3-S)]4 (4) along with the corresponding alkane. Mechanistic information for the formation of the unique low-valent tetrametallic compound 4 was gathered by hydrogenation of the phenyl-substituted precursor [Ta(η5-C5Me5)Ph(µ-S)]2, which proceeds through a stepwise hydrogenation process, disclosing the formation of the intermediate tetranuclear hydride sulfide [Ta2(η5-C5Me5)2(H)Ph(µ-S)(µ3-S)]2 (5). Extending our studies toward tantalum alkyl precursors containing functional groups susceptible to hydrogenation, such as the allyl-and benzyl-substituted compounds [Ta(η5-C5Me5)(η3-C3H5)(µ-S)]2 and [Ta(η5-C5Me5)(CH2Ph)(µ-S)]2 (2), enables alternative reaction pathways en route to the formation of 4. In the former case, the dimetallic system undergoes selective hydrogenation of the unsaturated allyl moiety, forming the asymmetric complex [{Ta(η5-C5Me5)(η3-C3H5)}(µ-S)2{Ta(η5-C5Me5)(C3H7)}] (6) with only one propyl fragment. Species 2, in addition to the hydrogenation of one benzyl fragment and concomitant toluene release, also undergoes partial hydrogenation and dearomatization of the phenyl ring on the vicinal benzyl unity to give a η5-cyclohexadienyl complex [Ta2(η5-C5Me5)2(µ-CH2C6H6)(µ-S)2] (7). The mechanistic implications of the latter hydrogenation process are discussed by means of DFT calculations.

Low-Valent Titanium Species Stabilized with Aluminum/Boron Hydride Fragments.

Low-valent titanium species were prepared by reaction of [TiCp*X3 ] (Cp*=η5 -C5 Me5 ; X=Cl, Br, Me) with LiEH4 (E=Al, B) or BH3 (thf), and their structures elucidated by experimental and theoretical methods. The treatment of trihalides [TiCp*X3 ] with LiAlH4 in ethereal solvents (L) leads to the hydride-bridged heterometallic complexes [{TiCp*(µ-H)}2 {(µ-H)2 AlX(L)}2 ] (L=thf, X=Cl, Br; L=OEt2 , X=Cl). Density functional theory (DFT) calculations for those compounds reveal an open-shell singlet ground state with a Ti-Ti bond and can be described as titanium(II) species. The theoretical analyses also show strong interactions between the Ti-Ti bond and the empty s orbitals of the Al atom of the AlH2 XL fragments, which behave as σ-accepting (Z-type) ligands. Analogous reactions of [TiCp*X3 ] with LiBH4 (2 and 3 equiv.) in tetrahydrofuran at room temperature and at 85 °C lead to the titanium(III) compounds [{TiCp*(BH4 )(µ-X)}2 ] (X=Cl, Br) and [{TiCp*(BH4 )(µ-BH4 )}2 ], respectively. The treatment of [TiCp*Me3 ] with 4 and 5 equiv. of BH3 (thf) produces the diamagnetic [{TiCp*(BH3 Me)}2 (µ-B2 H6 )] and paramagnetic [{TiCp*(µ-B2 H6 )}2 ] complexes, respectively.

N═N Bond Cleavage by Tantalum Hydride Complexes: Mechanistic Insights and Reactivity.

The reaction of [TaCpRX4] (CpR = η5-C5Me5, η5-C5H4SiMe3, η5-C5HMe4; X = Cl, Br) with SiH3Ph resulted in the formation of the dinuclear hydride tantalum(IV) compounds [(TaCpRX2)2(µ-H)2], structurally identified by single-crystal X-ray analyses. These species react with azobenzene to give the mononuclear imide complex [TaCpRX2(NPh)] along with the release of molecular hydrogen. Analogous reactions between the [{Ta(η5-C5Me5)X2}2(µ-H)2] derivatives and the cyclic diazo reagent benzo[c]cinnoline afford the biphenyl-bridged (phenylimido)tantalum complexes [{Ta(η5-C5Me5)X2}2(µ-NC6H4C6H4N)] along with the release of molecular hydrogen. When the compounds [(TaCpRX2)2(µ-H)2] (CpR = η5-C5H4SiMe3, η5-C5HMe4; X = Cl, Br) were employed, we were able to trap the side-on-bound diazo derivatives [(TaCpRX)2{µ-(η2,η2-NC6H4C6H4N)}] (CpR = η5-C5H4SiMe3, η5-C5HMe4; X = Cl, Br) as intermediates in the N═N bond cleavage process. DFT calculations provide insights into the N═N cleavage mechanism, in which the ditantalum(IV) fragment can promote two-electron reductions of the N═N bond at two different metal-metal bond splitting stages.

Dinitrogen Binding at a Trititanium Chloride Complex and Its Conversion to Ammonia under Ambient Conditions.

Reaction of [TiCp*Cl3 ] (Cp*=η5 -C5 Me5 ) with one equivalent of magnesium in tetrahydrofuran at room temperature affords the paramagnetic trinuclear complex [{TiCp*(µ-Cl)}3 (µ3 -Cl)], which reacts with dinitrogen under ambient conditions to give the diamagnetic derivative [{TiCp*(µ-Cl)}3 (µ3 -η1 : η2 : η2 -N2 )] and the titanium(III) dimer [{TiCp*Cl(µ-Cl)}2 ]. The structure of the trinuclear mixed-valence complexes has been studied by experimental and theoretical methods and the latter compound represents the first well-defined example of the µ3 -η1 : η2 : η2 coordination mode of the dinitrogen molecule. The reaction of [{TiCp*(µ-Cl)}3 (µ3 -η1 : η2 : η2 -N2 )] with excess HCl in tetrahydrofuran results in clean NH4 Cl formation with regeneration of the starting material [TiCp*Cl3 ]. Therefore, a cyclic ammonia synthesis under ambient conditions can be envisioned by alternating N2 /HCl atmospheres in a [TiCp*Cl3 ]/Mg(excess) reaction mixture in tetrahydrofuran.

Associations between Combined Influenza and Pneumococcal Pneumonia Vaccination and Cardiovascular Outcomes.

BACKGROUND: In 2017, the CDC listed heart disease as the leading cause of death, with pneumonia and influenza being the eighth cause of death. Several studies have suggested the protective effects of influenza vaccination on myocardial infarction (MI). Available evidence supports the use of influenza vaccination in decreasing cardiovascular events, and the Joint Commission considers influenza vaccination a metric of quality care for hospitalized patients. Our specific aim was to evaluate the combined use of pneumococcal pneumonia vaccine (PPV) and influenza vaccine on cardiovascular outcomes and mortality. METHODS: A retrospective observational study was conducted using the 2012-2015 US National Inpatient Sample (NIS) database, to compare cardiovascular events in adult patients who did and did not receive vaccination during their hospitalization. ICD-9 codes were used to extract data for specific variables. The outcomes included MI, transient ischemic attacks, cardiac arrest, stroke, heart failure, and death. Adjusted relative risks (RR) were calculated using survey-weighted generalized linear models after adjusting for gender, race, socioeconomic status, diabetes, hypertension, hyperlipidemia, smoking status, prior coronary artery disease, and cerebrovascular disease. The effect of vaccination on in-hospital mortality was assessed in each subgroup of cardiovascular events using RR regressions. RESULTS: This study included 22,634,643 hospitalizations, of which 21,929,592 did not receive immunization. Vaccination solely against influenza was associated with lower MI (RR = 0.84, 95% CI: 0.82-0.87, p < 0.001), TIA (RR = 0.93, 95% CI: 0.9-0.96, p < 0.001), cardiac arrest (RR = 0.36, 95% CI: 0.33-0.39, p < 0.001), stroke (RR = 0.94, 95% CI: 0.91-0.97, p < 0.001), and mortality (RR = 0.38, 95% CI: 0.36-0.4, p < 0.001). Vaccination with PPV alone was associated with MI (RR = 1.13, 95% CI: 1.11-1.16, p < 0.001), TIA (RR = 1.28, 95% CI: 1.26-1.31, p < 0.001), stroke (RR = 1.21, 95% CI: 1.18-1.24, p < 0.001), and lower mortality (RR = 0.47, 95% CI: 0.45-0.49, p < 0.001). Combined PPV and influenza vaccine was associated with lower mortality (2.21% vs. 1.03%, p < 0.001) and lower cardiac arrest (0.61% vs. 0.51%, p < 0.001). In the adjusted analysis, the RR was 0.46 (95% CI: 0.43, 0.49) for mortality in the combined vaccinated cohort. The combined vaccination group also had a significantly reduced risk of mortality among those admitted with MI (RR = 0.46), transient ischemic attacks (RR = 0.58), and stroke (RR = 0.42) compared to the nonvaccinated group. CONCLUSIONS: Our study shows a significantly reduced risk of mortality with influenza vaccine and PPV and with combined pneumococcal and influenza vaccination. These data suggest that in-hospital administration of pneumonia and influenza vaccines appears safe and supports the use of combined vaccination during hospitalization due to their cardiovascular benefits.

Successive Protonation and Methylation of Bridging Imido and Nitrido Ligands at Titanium Complexes.

The reactions of nitrido complexes [{Ti(η5-C5Me5)(µ-NH)}3(µ3-N)] (1) and [{Ti(η5-C5Me5)}4(µ3-N)4] (2) with electrophilic reagents ROTf (R = H, Me; OTf = OSO2CF3) in different molar ratios have allowed the structural characterization of a series of titanium intermediates en route to the formation of the ammonium salts [NR4]OTf and [NR4][Ti(η5-C5Me5)(OTf)4]. The treatment of the trinuclear imido-nitrido complex 1 with 5.5 equiv of triflic acid in toluene at room temperature led to the dinuclear complex [Ti2(η5-C5Me5)2(µ-N)(NH3)(µ-O2SOCF3)2(OTf)] (3) and [NH4]OTf. Compound 3, along with the ammonium salts [NMe4]OTf and [NMe4][Ti(η5-C5Me5)(OTf)4] (5), was also obtained in the reaction of 1 with 8 equiv of methyl triflate in toluene at 100 °C. The trinuclear complex [Ti3(η5-C5Me5)3(µ-N)(µ-NH)2(µ-O2SOCF3)(OTf)] (4), an intermediate in the formation of 3, was isolated in the treatment of 1 with 4 equiv of MeOTf, although compound 4 was prepared in better yield by treatment of 1 with Me3SiOTf (2 equiv). Addition of a large excess of MeOTf or HOTf reagents to solutions of 3 resulted in the clean formation of ammonium salts [NR4][Ti(η5-C5Me5)(OTf)4] (R = Me (5), H (6)). Treatment of the tetranuclear nitrido complex [{Ti(η5-C5Me5)}4(µ3-N)4] (2) with 1 equiv of ROTf in toluene afforded the precipitation of the ionic compounds [{Ti(η5-C5Me5)}4(µ3-N)3(µ3-NR)][OTf] (R = H (8), Me (9)), while a large excess of HOTf led to the formation of [{Ti(η5-C5Me5)}4(µ3-N)3(µ3-NH)][Ti(η5-C5Me5)(OTf)4(NH3)] (10) by rupture of a fraction of tetranuclear molecules. Complex 2 reacted with 1 equiv of [M(η5-C5H5)(CO)3H] (M = Mo, Cr) via hydrogenation of one nitrido ligand to give the molecular derivative [{Ti(η5-C5Me5)}4(µ3-N)3(µ3-NH)] (11) and [{M(η5-C5H5)(CO)3}2], while a second 1 equiv of [M(η5-C5H5)(CO)3H] produced the ionic compounds [{Ti(η5-C5Me5)}4(µ3-N)2(µ3-NH)2][M(η5-C5H5)(CO)3] (M = Mo (12), Cr (13)) by protonation of another nitrido group. The X-ray crystal structures of 3-5, 9, 10, and 13 were determined.

Preparation of Dimeric Monopentamethylcyclopentadienyltitanium(III) Dihalides and Related Derivatives.

The synthesis, crystal structure, and reactivity of a series of half-sandwich titanium(III) dihalide complexes [Ti(η5-C5Me5)X2] (X = Cl, Br, I) and several of its Lewis base derivatives were investigated. The reaction of the trihalides [Ti(η5-C5Me5)X3] (X = Cl (1), Br (2), I (3)) with LiAlH4 (≥1 equiv) in toluene at room temperature results in the formation of the halide-bridged dimers [{Ti(η5-C5Me5)X(µ-X)}2] (X = Cl (4), Br (5), I (6)). The treatment of 4 with [Li{N(SiMe3)2}] (≥2 equiv) at room temperature affords the precipitation of the amido titanium(III) complex [{Ti(η5-C5Me5)(µ-Cl){N(SiMe3)2}}2] (7), but analogous reactions of 4 with other lithium reagents [LiR] (R = Me, CH2SiMe3, NMe2) lead to disproportionation into titanium(IV) [Ti(η5-C5Me5)R3] and presumably titanium(II) derivatives. Similarly, complex 4 in solution at temperatures higher than 100 °C undergoes disproportionation as demonstrated by its reactions with cobaltocene and N-(4-methylbenzylidene)aniline yielding the ionic paramagnetic compound [Co(η5-C5H5)2][Ti(η5-C5Me5)Cl3] (8) and the diamagnetic diazatitanacyclopentane [Ti(η5-C5Me5)Cl{N(Ph)CH(p-tolyl)}2], respectively. Treatment of complex 4 with 2 equiv of 2,6-dimethylphenylisocyanide or tert-butylisocyanide in toluene at room temperature affords the paramagnetic titanium(III) dinuclear adducts [{Ti(η5-C5Me5)Cl(µ-Cl)(CNR)}2] (R = 2,6-Me2C6H3 (9), tBu (10)). Magnetic studies for polycrystalline 9 show that it displays a weak intramolecular antiferromagnetic coupling between the Ti ions, which is consistent with the long Ti-Ti distance of 3.857(1) Å determined by X-ray diffraction. The isocyanide ligands in complex 10 undergo a reductive coupling reaction in toluene to give the titanium(IV) iminoacyl derivative [{Ti(η5-C5Me5)Cl2}2(µ-η2:η2-tBuN═C-C═NtBu)] (11). Whereas an analogous dinuclear structure was found in the aqua titanium(III) complex [{Ti(η5-C5Me5)Cl(µ-Cl)(OH2)}2] (12), resulting from the reaction of 4 with adventitious amounts of water, compound 4 reacts with excess ammonia to give a mononuclear adduct [Ti(η5-C5Me5)Cl2(NH3)2] (13) with a robust layered pattern in the solid state.

Ammonia-Borane Derived BN Fragments Trapped on Bi- and Trimetallic Titanium(III) Systems.

Titanium(III) complexes containing unprecedented (NH2 BH2 NHBH3 )2- and {N(BH3 )3 }3- ligands have been isolated, and their structures elucidated by a combination of experimental and theoretical methods. The treatment of the trimethyl derivative [TiCp*Me3 ] (Cp*=η5 -C5 Me5 ) with NH3 BH3 (3 equiv) at room temperature gives the paramagnetic dinuclear complex [{TiCp*(NH2 BH3 )}2 (µ-NH2 BH2 NHBH3 )], which at 80 °C leads to the trinuclear hydride derivative [{TiCp*(µ-H)}3 {µ3 -N(BH3 )3 }]. The bonding modes of the anionic BN fragments in those complexes, as well as the dimethylaminoborane group trapped on the analogous trinuclear [{TiCp*(µ-H)}3 (µ3 -H)(µ3 -NMe2 BH2 )], have been studied by X-ray crystallography and density functional theory (DFT) calculations.

Molecular Design of Cyclopentadienyl Tantalum Sulfide Complexes.

Use of (Me3Si)2S and [Ta(η5-C5Me5)Cl4] (1) in a 4:3 ratio afforded the trimetallic sulfide cluster [Ta3(η5-C5Me5)3Cl3(µ3-Cl)(µ-S)3(µ3-S)] (2) with loss of SiClMe3. A similar reaction between 1, TaCl5, and (Me3Si)2S in a 2:1:4 ratio resulted in the analogous complex [Ta3(η5-C5Me5)2Cl4(µ3-Cl)(µ-S)3(µ3-S)] (3). Single-crystal X-ray diffraction analyses of 2 and 3 showed in all cases trinuclear tantalum sulfide clusters. On the other hand, thermal treatment of 2 with SiH3Ph generated very cleanly the dinuclear tantalum(IV) sulfide complex [Ta2(η5-C5Me5)2Cl2(µ-S)2] (4) in a quantitative way. Likewise, we found that 4 was synthesized more easily by a one-pot reaction of 1, (Me3Si)2S, and SiH3Ph in toluene. Reactions of 4 with a series of alkylating reagents rendered the dinuclear peralkylated sulfide complexes [Ta2(η5-C5Me5)2R2(µ-S)2] (R = Me 5, Et 6, CH2SiMe3 7, C3H5 8, Ph 9). Single-crystal X-ray diffraction analyses of 4, 5, and 9 showed in all cases a trans disposition of the chloro or alkyl substituents. The short Ta-Ta distances (2.918(1)-2.951(1) Å) along with DFT calculations indicate a σ-Ta-Ta interaction. Complexes 5, 6, and 8 undergo trans- cis isomerization, and mechanistic proposals are discussed based on DFT calculations.

A Bridging bis-Allyl Titanium Complex: Mechanistic Insights into the Electronic Structure and Reactivity.

Treatment of the dinuclear compound [{Ti(η5-C5Me5)Cl2}2(µ-O)] with allylmagnesium chloride provides the formation of the allyltitanium(III) derivative [{Ti(η5-C5Me5)(µ-C3H5)}2(µ-O)] (1), structurally identified by single-crystal X-ray analysis. Density functional theory (DFT) calculations confirm that the electronic structure of 1 is a singlet state, and the molecular orbital analysis, along with the short Ti-Ti distance, reveal the presence of a metal-metal single bond between the two Ti(III) centers. Complex 1 reacts rapidly with organic azides, RN3 (R = Ph, SiMe3), to yield the allyl µ-imido derivatives [{Ti(η5-C5Me5)(CH2CH═CH2)2}2(µ-NR)(µ-O)] [R = Ph(2), SiMe3(3)] along with molecular nitrogen release. Reaction of 2 and 3 with H2 leads to the µ-imido propyl species [{Ti(η5-C5Me5)(CH2CH2CH3)2}2(µ-NR)(µ-O)] [R = Ph(4), SiMe3(5)]. Theoretical calculations were used to gain insight into the hydrogenation mechanism of complex 3 and rationalize the lower reactivity of 2. Initially, the µ-imido bridging group in these complexes activates the H2 molecule via addition to the Ti-N bonds. Subsequently, the titanium hydride intermediates induce a change in hapticity of the allyl ligands, and the nucleophilic attack of the hydride to the allyl groups leads to metallacyclopropane intermediates. Finally, the proton transfer from the amido group to the metallacyclopropane moieties affords the propyl complexes 4 and 5.

The Puzzling Monopentamethylcyclopentadienyltitanium(III) Dichloride Reagent: Structure and Properties.

Following the track of the useful titanocene [Ti(η5-C5H5)2Cl] reagent in organic synthesis, the related half-sandwich titanium(III) derivatives [Ti(η5-C5R5)Cl2] are receiving increasing attention in radical chemistry of many catalyzed transformations. However, the structure of the active titanium(III) species remains unknown in the literature. Herein, we describe the synthesis, crystal structure, and electronic structure of titanium(III) aggregates of composition [{Ti(η5-C5Me5)Cl2} n]. The thermolysis of [Ti(η5-C5Me5)Cl2Me] (1) in benzene or hexane at 180 °C results in the clean formation of [{Ti(η5-C5Me5)Cl(µ-Cl)}2] (2), methane, and ethene. The treatment of 1 with excess pinacolborane in hexane at 65 °C leads to a mixture of 2 and the paramagnetic trimer [{Ti(η5-C5Me5)(µ-Cl)2}3] (3). The X-ray crystal structures of compounds 2 and 3 show Ti-Ti distances of 3.267(1) and 3.219(12) Å, respectively. Computational studies (CASPT2//CASSCF and BS DFT methods) for dimer 2 reveal a singlet ground state and a relatively large singlet-triplet energy gap. Nuclear magnetic resonance spectroscopy of 2 in aromatic hydrocarbon solutions and DFT calculations for several [{Ti(η5-C5Me5)Cl2} n] aggregates are consistent with the existence of an equilibrium between the diamagnetic dimer [{Ti(η5-C5Me5)Cl(µ-Cl)}2] and a paramagnetic tetramer [{Ti(η5-C5Me5)(µ-Cl)2}4] in solution. In contrast, complex 2 readily dissolves in tetrahydrofuran to give a green-blue solution from which blue crystals of the mononuclear adduct [Ti(η5-C5Me5)Cl2(thf)] (4) were grown.

Cleavage of Dinitrogen from Forming Gas by a Titanium Molecular System under Ambient Conditions.

Simple exposure of a hexane solution of [TiCp*Me3 ] (Cp*=η5 -C5 Me5 ) to an atmosphere of commercially available and inexpensive forming gas (H2 /N2 mixture, 13.5-16.5 % of H2 ) at room temperature leads to the methylidene-methylidyne-nitrido cube-type complex [(TiCp*)4 (µ3 -CH)(µ3 -CH2 )(µ3 -N)2 ] via dinitrogen cleavage. This paramagnetic compound reacts with [D1 ]chloroform to give the titanium(IV) methylidyne-nitrido species [(TiCp*)4 (µ3 -CH)2 (µ3 -N)2 ], whereas its one-electron oxidation with AgOTf or [Fe(η5 -C5 H5 )2 ](OTf) (OTf=O3 SCF3 ) yields the diamagnetic ionic derivative [(TiCp*)4 (µ3 -CH)(µ3 -CH2 )(µ3 -N)2 ](OTf). The µ3 -nitrido ligands of the methylidyne-nitrido cubane complex can be protonated with [LutH](OTf) (Lut=2,6-lutidine) or hydrogenated with NH3 ⋅BH3 to afford µ3 -NH imido moieties.

An Effective Route to Dinuclear Niobium and Tantalum Imido Complexes.

Thermal treatment of the trichloro complexes [MCl3(NR)py2] (R = tBu, Xyl; M = Nb, Ta) (Xyl = 2,6-Me2C6H3) under vacuum affords the dinuclear imido species [MCl2(µ-Cl)(NR)py]2 (R = tBu, Xyl; M = Nb 1, 3; Ta 2, 4) with loss of pyridine. Complexes 1-4 can be easily transformed to the mononuclear starting materials [MCl3(NR)py2] (R = tBu, Xyl; M = Nb, Ta) upon reaction with pyridine. While reactions of compounds 1 and 2 with a series of alkylating reagents render the mononuclear peralkylated imido complexes [MR3(NtBu)] (R = Me, CH2Ph, CH2CMe3, CH2CMePh, CH2SiMe3), the analogous treatment with allylmagnesium chloride results in the formation of the dinuclear niobium(IV) derivative [(NtBu)(η3-C3H5)M(µ-C3H5)(µ-Cl)2M(NtBu)py2] (5). Additionally, the treatment of the starting materials 1 and 2 with the organosilicon reductant 1,4-bis(trimethylsilyl)-1,4-diaza-2,5-cyclohexadiene yields the pyridyl-bridged dinuclear derivatives [M2Cl2(µ-Cl)2(NtBu)2py2]2(µ-NC4H4N)2 (M = Nb 6, Ta 7). Controlled hydrolysis reaction of 1 and 2 affords the oxo chlorido-bridged products [MCl(µ-Cl)(NtBu)py]2(µ-O) (M = Nb 8, Ta 9) in a quantitative way, while the treatment of these latter with one more equivalent of pyridine led to complexes [MCl2(NtBu)py2]2(µ-O) (M = Nb 10, Ta 11). Structural study of these dinuclear imido derivatives has been also performed by X-ray crystallography.

Group 4 Half-Sandwich Tris(trimethylsilylmethyl) Complexes: Thermal Decomposition and Reactivity with N,N-Dimethylamine-Borane.

The thermal decomposition of group 4 trimethylsilylmethyl derivatives [M(η5-C5Me5)(CH2SiMe3)3] (M = Ti (1), Zr (2), Hf (3)) in solution and their reactivity with N,N-dimethylamine-borane were investigated. Heating of hydrocarbon solutions of compounds 2 and 3 at 130-200 °C results in the elimination of SiMe4 and the clean formation of the singular alkylidene-alkylidyne zirconium and hafnium compounds [{M(η5-C5Me5)}3{(µ-CH)3SiMe}(µ3-CSiMe3)] (M = Zr (4), Hf (5)). The reaction of 2 and 3 with NHMe2BH3 (≥1 equiv) at room temperature affords the dialkyl(dimethylamidoborane) complexes [M(η5-C5Me5)(CH2SiMe3)2(NMe2BH3)] (M = Zr (6), Hf (7)). Compounds 6 and 7 are unstable in solution and decompose with formation of the alkyl(dimethylamino)borane [B(CH2SiMe3)H(NMe2)] (8), SiMe4, and other minor byproducts, including the tetranuclear zirconium(III) octahydride complex [{Zr(η5-C5Me5)}4(µ-H)8] (9) in the decomposition of 6. Addition of NHMe2BH3 to the titanium tris(trimethylsilylmethyl) derivative 1 gives the trinuclear mixed valence Ti(II)/Ti(III) tetrahydride complex [{Ti(η5-C5Me5)(µ-H)}3(µ3-H)(µ3-NMe2BH2)] (10) at 45-65 °C. While the complete conversion of 1 under argon atmosphere requires excess NHMe2BH3 (up to 15 equiv), complex 10 is readily prepared with 3 equiv of NHMe2BH3 under a hydrogen atmosphere indicating that the formation of 10 involves hydrogenolysis of 1 in the presence of (NMe2BH2)2. In absence of amine-borane, the reaction of 1 with H2 leads to the tetranuclear titanium(III) octahydride [{Ti(η5-C5Me5)}4(µ-H)8] (11), which upon addition of NHMe2BH3 and subsequent heating at 65 °C affords complex 10. The X-ray crystal structures of 2, 4, 5, 10, and 11 were determined.

Systematic Approach for the Construction of Niobium and Tantalum Sulfide Clusters.

Treatment of the imido complexes [MCl3(NR)py2] (R = (t)Bu, 2,6-Me2C6H3; M = Nb 1, 3; Ta 2, 4) (Xyl = 2,6-Me2C6H3) with (Me3Si)2S in a 1:1 ratio afforded the new cube-type sulfide clusters [MCl(NR)py(µ3-S)]4 (R = (t)Bu, 2,6-Me2C6H3; M = Nb 5, 7; Ta 6, 8) with loss of Me3SiCl. Reactions of 5 and 6 with cyclopentadienyllithium in 1:4 ratio resulted in the rupture of the coordinative M-S bonds and the replacement of a pyridine molecule and a chlorine atom by an η(5)-cyclopentadienyl group in each metal center, affording the compounds [M(η(5)-C5H5)(N(t)Bu)(µ-S)]4 (M = Nb 9, Ta 10). These processes may develop through formation of the complexes [M4(η(5)-C5H5)2(µ-Cl)(N(t)Bu)4py2(µ3-S)2(µ-S)2](C5H5) (M = Nb 11, Ta 12), also obtained by reaction of 5 and 6 with cyclopentadienyllithium in 1:3 ratio. As further evidence, 11 and 12 led to complexes 9 and 10 by treatment with one more equivalent of the lithium reagent. The structural study of these metal sulfide clusters has been also performed by X-ray crystallography.

Carbon-nitrogen bond construction and carbon-oxygen double bond cleavage on a molecular titanium oxonitride: a combined experimental and computational study.

New carbon-nitrogen bonds were formed on addition of isocyanide and ketone reagents to the oxonitride species [{Ti(η(5)-C5Me5)(µ-O)}3(µ3-N)] (1). Reaction of 1 with XylNC (Xyl = 2,6-Me2C6H3) in a 1:3 molar ratio at room temperature leads to compound [{Ti(η(5)-C5Me5)(µ-O)}3(µ-XylNCCNXyl)(NCNXyl)] (2), after the addition of the nitrido group to one coordinated isocyanide and the carbon-carbon coupling of the other two isocyanide molecules have taken place. Thermolysis of 2 gives [{Ti(η(5)-C5Me5)(µ-O)}3(XylNCNXyl)(CN)] (3) where the heterocumulene [XylNCCNXyl] moiety and the carbodiimido [NCNXyl] fragment in 2 have undergone net transformations. Similarly, tert-butyl isocyanide (tBuNC) reacts with the starting material 1 under mild conditions to give the paramagnetic derivative [{Ti3(η(5)-C5Me5)3(µ-O)3(NCNtBu)}2(µ-CN)2] (4). However, compound 1 provides the oxo ketimide derivatives [{Ti3(η(5)-C5Me5)3(µ-O)4}(NCRPh)] [R = Ph (5), p-Me(C6H4) (6), o-Me(C6H4) (7)] upon reaction with benzophenone, p-methylbenzophenone, and o-methylbenzophenone, respectively. In these reactions, the carbon-oxygen double bond is completely ruptured, leading to the formation of a carbon-nitrogen and two metal-oxygen bonds. The molecular structures of complexes 2-4, 6, and 7 were determined by single-crystal X-ray diffraction analyses. Density functional theory calculations were performed on the incorporation of isocyanides and ketones to the model complex [{Ti(η(5)-C5H5)(µ-O)}3(µ3-N)] (1H). The mechanism involves the coordination of the substrates to one of the titanium metal centers, followed by an isomerization to place those substrates cis with respect to the apical nitrogen of 1H, where carbon-nitrogen bond formation occurs with a low-energy barrier. In the case of aryl isocyanides, the resulting complex incorporates additional isocyanide molecules leading to a carbon-carbon coupling. With ketones, the high oxophilicity of titanium promotes the unusual total cleavage of the carbon-oxygen double bond.

Partial hydrogenation of a tetranuclear titanium nitrido complex with ammonia borane.

The treatment of [{Ti(η(5)-C5Me5)}4(µ3-N)4] with NH3BH3 leads to the paramagnetic imidonitrido complex [{Ti(η(5)-C5Me5)}4(µ3-N)3(µ3-NH)], which can also be obtained by stepwise proton and electron transfer with HOTf and [K(C5Me5)].

[Update in the management of chronic thrombo-embolic pulmonary hypertension]. / Actualización del abordaje de la hipertensión pulmonar tromboembólica crónica.

Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a potentially curable form of pulmonary hypertension (PH) that develops in up to 3% of patients after pulmonary embolism (PE). In these patients, PE does not resolve, leading to organized fibrotic clots, with the development of precapillary PH as a result of the proximal obstruction of the pulmonary arteries. In addition, a distal microvasculopathy may also develop, contributing to the increase of pulmonary vascular resistance. Transthoracic echocardiography is the diagnostic tool that allows to establish the suspicion of PH. Ventilation-perfusion lung scintigraphy is the fundamental tool in the study of patients with suspected CTEPH; if it is normal, virtually rules out the diagnosis. Right heart catheterization is mandatory for the diagnosis of these patients. CTEPH is defined as the existence of symptoms, residual perfusion defects and precapillary PH after a minimum period of three months of anticoagulation. Pulmonary angiography helps determine the extent and surgical accessibility of thromboembolic lesions. CTEPH patients are candidates for long-term anticoagulation. Pulmonary endarterectomy is the treatment of choice, resulting in significant clinical and hemodynamic improvement. About 25% of patients have residual PH post-endarterectomy. Balloon pulmonary angioplasty is an endovascular technique that targets more distal lesions, being potentially useful for patients with inoperable CTEPH or persistent/recurrent PH post-endarterectomy. Both types of patients may also benefit from pharmacological treatment for PH. These three therapies are the cornerstone of CTEPH treatment, which has evolved towards a multimodal approach.

Copper(I) and silver(I) complexes supported by the tridentate [{Ti(η(5)-C5Me5)(µ-NH)}3(µ3-N)] metalloligand.

Copper(I) and silver(I) ionic compounds [(L)M{(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}][O(3)SCF(3)] containing [MTi(3)N(4)] cube-type cations have been prepared by reaction of [(CF(3)SO(2)O)M{(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}] (M = Cu (2), Ag (3)) with a variety of donor molecules L. Treatment of complexes 2 and 3 with NH(3) in toluene at room temperature gives the ammonia adducts [(H(3)N)M{(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}][O(3)SCF(3)] (M = Cu (4), Ag (5)), whose X-ray crystal structures reveal two cube-type cations associated through hydrogen bonding interactions between the ammine ligands and one oxygen atom of each trifluoromethanesulfonate anion. Analogous treatment of 2 and 3 with 1 equiv of pyridine, 2,6-dimethylphenylisocyanide, tert-butylisocyanide, or triphenylphosphane gives the ionic compounds [(L)M{(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}][O(3)SCF(3)] (L = py, M = Cu (6), Ag (7); L = CNAr, M = Cu (8), Ag (9); L = CNtBu, M = Cu (10), Ag (11); L = PPh(3), M = Cu (12), Ag (13)). The reactions of 2 and 3 with methylenebis(diphenylphosphane) (dppm) in a 1:1 ratio lead to the single-cube complexes [(dppm)M{(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}][O(3)SCF(3)] (M = Cu (14), Ag (15)), whereas in a 2:1 ratio give the bisphosphane-bridged double-cube compounds [{M(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}(2)(µ-dppm)][O(3)SCF(3)](2) (M = Cu (16), Ag (17)). Similarly, treatment of 2 or 3 with a half equivalent of ethane-1,2-diylbis(diphenylphosphane) (dppe) affords double-cube derivatives [{M(µ(3)-NH)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-N)}(2)(µ-dppe)][O(3)SCF(3)](2) (M = Cu (18), Ag (19)). The X-ray crystal structures of 4, 5, 10, 14, 15, and 18 have been determined.

Reactivity with electrophiles of imido groups supported on trinuclear titanium systems.

Several trinuclear titanium complexes bearing amido µ-NHR, imido µ-NR, and nitrido µn-N ligands have been prepared by reaction of [{Ti(η(5)-C5Me5)(µ-NH)}3(µ3-N)] (1) with 1 equiv of electrophilic reagents ROTf (R = H, Me, SiMe3; OTf = OSO2CF3). Treatment of 1 with triflic acid or methyl triflate in toluene at room temperature affords the precipitation of compounds [Ti3(η(5)-C5Me5)3(µ3-N)(µ-NH)2(µ-NH2)(OTf)] (2) or [Ti3(η(5)-C5Me5)3(µ3-N)(µ-NH)(µ-NH2)(µ-NMe)(OTf)] (3). Complexes 2 and 3 exhibit a fluxional behavior in solution consisting of proton exchange between µ-NH2 and µ-NH groups, assisted by the triflato ligand, as could be inferred from a dynamic NMR spectroscopy study. Monitoring by NMR spectroscopy the reaction course of 1 with MeOTf allows the characterization of the methylamido intermediate [Ti3(η(5)-C5Me5)3(µ3-N)(µ-NH)2(µ-NHMe)(OTf)] (4), which readily rearranges to give 3 by a proton migration from the NHMe amido group to the NH imido ligands. The treatment of 1 with 1 equiv of Me3SiOTf produces the stable ionic complex [Ti3(η(5)-C5Me5)3(µ3-N)(µ-NH)2(µ-NHSiMe3)][OTf] (5) with a disposition of the nitrogen ligands similar to that of 4. Complex 5 reacts with 1 equiv of [K{N(SiMe3)2}] at room temperature to give [Ti3(η(5)-C5Me5)3(µ3-N)(µ-N)(µ-NH)(µ-NHSiMe3)] (6), which at 85 °C rearranges to the trimethylsilylimido derivative [Ti3(η(5)-C5Me5)3(µ3-N)(µ-NH)2(µ-NSiMe3)] (7). Treatment of 7 with [K{N(SiMe3)2}] affords the potassium derivative [K{(µ3-N)(µ3-NH)(µ3-NSiMe3)Ti3(η(5)-C5Me5)3(µ3-N)}] (8), which upon addition of 18-crown-6 leads to the ion pair [K(18-crown-6)][Ti3(η(5)-C5Me5)3(µ3-N)(µ-N)(µ-NH)(µ-NSiMe3)] (9). The X-ray crystal structures of 2, 5, 6, and 8 have been determined.