A Mixed-Valence Ti(II)/Ti(III) Inverted Sandwich Compound as a Regioselective Catalyst for the Uncommon 1,3,5-Alkyne Cyclotrimerization.

The synthesis, structure, and catalytic activity of a Ti(II)/Ti(III) inverted sandwich compound are presented in this study. Synthesis of the arene-bridged dititanium compound begins with the preparation of the titanium(IV) precursor [TiCl2(MesPDA)(thf)2] (MesPDA = N,N'-bis(2,4,6-trimethylphenyl)-o-phenylenediamide) (2). The reduction of 2 with sodium metal results in species [{Ti(MesPDA)(thf)}2(µ-Cl)3{Na}] (3) in oxidation state III. To achieve the lower oxidation state II, 2 undergoes reduction through alkylation with lithium cyclopentyl. This alkylation approach triggers a cascade of reactions, including ß-hydride abstraction/elimination, hydrogen evolution, and chemical reduction, to generate the Ti(II)/Ti(III) compound [Li(thf)4][(TiMesPDA)2(µ-η6: η6-C6H6)] (4). X-ray and EPR characterization confirms the mixed-valence states of the titanium species. Compound 4 catalyzes a mild, efficient, and regiospecific cyclotrimerization of alkynes to form 1,3,5-substituted arenes. Kinetic data support a mechanism involving a binuclear titanium arene compound, similar to compound 4, as the resting state. The active catalyst promotes the oxidative coupling of two alkynes in the rate-limiting step, followed by a rapid [4 + 2] cycloaddition to form the arene product. Computational analysis of the resting state for the cycloaddition of trimethylsilylacetylene indicates a thermodynamic preference for stabilizing the 1,3,5-arene within the space between the two [TiMesPDA] fragments, consistent with the observed regioselectivity.

Ti(III) Catalysts for CO2/Epoxide Copolymerization at Unusual Ambient Pressure Conditions.

Titanium compounds in low oxidation states are highly reducing species and hence powerful tools for the functionalization of small molecules. However, their potential has not yet been fully realized because harnessing these highly reactive complexes for productive reactivity is generally challenging. Advancing this field, herein we provide a detailed route for the formation of titanium(III) orthophenylendiamido (PDA) species using [LiBHEt3] as a reducing agent. Initially, the corresponding lithium PDA compounds [Li2(ArPDA)(thf)3] (Ar = 2,4,6-trimethylphenyl (MesPDA), 2,6-diisopropylphenyl (iPrPDA)) are combined with [TiCl4(thf)2] to form the heterobimetallic complexes [{TiCl(ArPDA)}(µ-ArPDA){Li(thf)n}] (n = 1, Ar = iPr 3 and n = 2, Ar = Mes 4). Compound 4 evolves to species [Ti(MesPDA)2] (6) via thermal treatment. In contrast, the transformation of 3 into [Ti(iPrPDA)2] (5) only occurs in the presence of [LiNMe2], through a lithium-assisted process, as revealed by density functional theory (DFT). Finally, the Ti(IV) compounds 3-6 react with [LiBHEt3] to give rise to the Ti(III) species [Li(thf)4][Ti(ArPDA)2] (Ar = iPr 8, Mes 9). These low-valent compounds in combination with [PPN]Cl (PPN = bis(triphenylphosphine)iminium) are proved to be highly selective catalysts for the copolymerization of CO2 and cyclohexene epoxide. Reactions occur at 1 bar pressure with activity/selectivity levels similar to Salen-Cr(III) compounds.

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.

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.

Severe pembrolizumab-induced gastritis in a patient with lung adenocarcinoma.

Cancer immunotherapy is an increasingly common treatment option based on anti-tumor immune response. However, a challenge is arising regarding its potential, which is the poorly understood recognized immune-mediated adverse effects.

Lymph Node Ratio, Perineural Invasion and R1 Resection as Independent Prognostic Factors in Pancreatic Adenocarcinoma: A Retrospective Cohort Study.

INTRODUCTION: The prognosis of pancreatic ductal adenocarcinoma has been associated with several factors. The aim of the present study was to correlate tumor-related factors and pathological findings with disease-free survival (DFS) and overall survival (OS) in patients undergoing pancreaticoduodenectomy. MATERIAL AND METHODS: From a prospectively maintained database, we reviewed 89 pancreatic ductal adenocarcinomas in patients who underwent pancreaticoduodenectomy from 2010 to 2014. The impact of histopathologic or tumor-related data, including a lymph node ratio greater than 15% (LNR15), on survival was analyzed. RESULTS: Univariate analysis of DFS and OS showed that vascular resection, pT, pN, LNR15, microvascular, lymphatic, and perineural invasion, and R1 resection influenced survival. Only LNR15, perineural invasion and R1 resection were independent predictors for both DFS (HR 6.39, p = 0.011; HR 8.53, p = 0.003; HR 9.68, p = 0.002, respectively) and OS (HR 4.21, p = 0.039; HR 5.41, p = 0.020; HR 4.41, p = 0.036, respectively). CONCLUSIONS: This study demonstrates that LNR15, perineural invasion and R1 resection are independently associated with DFS and OS.

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.

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.

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.

A flowgraph model for bladder carcinoma.

BACKGROUND: Superficial bladder cancer has been the subject of numerous studies for many years, but the evolution of the disease still remains not well understood. After the tumor has been surgically removed, it may reappear at a similar level of malignancy or progress to a higher level. The process may be reasonably modeled by means of a Markov process. However, in order to more completely model the evolution of the disease, this approach is insufficient. The semi-Markov framework allows a more realistic approach, but calculations become frequently intractable. In this context, flowgraph models provide an efficient approach to successfully manage the evolution of superficial bladder carcinoma. Our aim is to test this methodology in this particular case. RESULTS: We have built a successful model for a simple but representative case. CONCLUSION: The flowgraph approach is suitable for modeling of superficial bladder cancer.

Analysis and prediction of long-term survival using a clinically applicable risk score based on the Electronic Health Record.

BACKGROUND: The long-term survival of a population assigned to a hospital can be essential to anticipate, manage, and provide appropriate hospital healthcare resources or lead preventive actions for high-risk mortality individuals. In this study, we discriminate which electronic health record variables are most relevant to predict the long-term survival of a population, and apply the results to identify high-risk mortality groups. MATERIALS AND METHODS: A prospective cohort study was conducted on a population of 113,403 individuals alive on July 1st, 2018 from the General Hospital of Castellón (Spain). Considering electronic health record patients' variables and survival days from the start date of the study, a Kaplan-Meier analysis and a multivariate Cox regression model were performed, and a risk score based on Cox coefficients was applied to predict survival over 3 years. RESULTS: All significant covariates from the Cox model (91.5% c-index) were associated with increased mortality risk. Using the proposed risk score, Kaplan-Meier curves show that survival probability in the 3rd year is 99.23% (95% confidence interval (CI) 99.18-99.29) for the low-risk, 91.21% (95% CI 90.67-91.76) for medium-risk, 76.52% (95% CI 75.59-77.46) for the high-risk, and 48.61 % (95% CI 46.85-50.36) for the very high-risk groups. DISCUSSION: The Cox model obtained is highly predictive, and it has been found that some electronic health record variables little studied to date, such as Clinical Risk Groups, have a strong impact on survival. Regarding clinical application, the proposed risk score is particularly useful for identifying high-risk subpopulations within a large population.

Co-complexation of lithium gallates on the titanium molecular oxide {[Ti(η5-C5Me5)(µ-O)}3(µ3-CH)].

Amide and lithium aryloxide gallates [Li(+){RGaPh(3)}(-)] (R = NMe(2), O-2,6-Me(2)C(6)H(3)) react with the µ(3)-alkylidyne oxoderivative ligand [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ(3)-CH)] (1) to afford the gallium-lithium-titanium cubane complexes [{Ph(3)Ga(µ-R)Li}{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ(3)-CH)] [R = NMe(2) (3), O-2,6-Me(2)C(6)H(3) (4)]. The same complexes can be obtained by treatment of the [Ph(3)Ga(µ(3)-O)(3){Ti(η(5)-C(5)Me(5))}(3)(µ(3)-CH)] (2) adduct with the corresponding lithium amide or aryloxide, respectively. Complex 3 evolves with formation of 5 as a solvent-separated ion pair constituted by the lithium dicubane cationic species [Li{(µ(3)-O)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-CH)}(2)](+) together with the anionic [(GaPh(3))(2)(µ-NMe(2))](-) unit. On the other hand, the reaction of 1 with Li(p-MeC(6)H(4)) and GaPh(3) leads to the complex [Li{(µ(3)-O)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-CH)}(2)][GaLi(p-MeC(6)H(4))(2)Ph(3)] (6). X-ray diffraction studies were performed on 1, 2, 4, and 5, while trials to obtain crystals of 6 led to characterization of [Li{(µ(3)-O)(3)Ti(3)(η(5)-C(5)Me(5))(3)(µ(3)-CH)}(2)][PhLi(µ-C(6)H(5))(2)Ga(p-MeC(6)H(4))Ph] 6a.

Complications and diagnostic accuracy of CT-guided 18G tru-cut versus end-cut percutaneous core needle biopsy of solitary solid lung nodules.

PURPOSE: Percutaneous biopsy has demonstrated high accuracy in diagnosis of lung nodules, but the technique is not innocuous and a yield decrease in lesions smaller than 20 mm has been reported. We carried out a prospective study to evaluate and compare the complications and efficacy of percutaneous core needle biopsy (CNB) of solitary solid lung nodules, which were performed with two types of automatic guns. METHODS: 330 consecutive CT-guided CNB were included. Tru-cut or end-cut 18G devices were used alternatively. Nodules were categorized by their size: ≤10 mm, 11-20 mm and >20 mm. Incidence of complications such as pneumothorax or hemoptysis and factors influencing them (nodule size and depth within lung parenchyma) were evaluated. Diagnostic accuracy of CNB achieved in the three groups of nodules regarding the two different needles were calculated and statistically evaluated and compared. RESULTS: We performed 68 CNB in nodules ≤10 mm, 130 in 11-20 mm and 132 in >20 mm. Pneumothorax appeared in 24.2% of them, but only 5.7% required drainage. Hemoptysis was developed in 9.4% and abundant hemoptysis with hypoxemia was observed in only 4.2% of patients. Regarding appearance of complications between the two needle types, no significant differences were found. A higher risk of hemoptysis was observed in nodules ≤10 mm (OR = 3.87; 95% CI = 1.24-12.06, P = 0.019) and in those located deeper in pulmonary parenchyma (OR = 2.21; 95% CI = 1.04-4.69, P = 0.038). End-cut needles reached a diagnostic accuracy of 93.7%, 92.1% and 98.3%, in nodules sized ≤10 mm, 11-20 mm and >20 mm, respectively. Corresponding results for tru-cut were 84.7%, 88.5% and 92.1%. In spite of differences reaching up to 9% in smaller nodules, intra-group results were not significant. CONCLUSION: Both needles have similar complications rate. Despite not having observed statistically significant differences between the two types of needles, end-cut devices have demonstrated a higher diagnostic yield in the three groups of nodules and could be a more suitable option especially for CNB of nodules ≤10 mm.

Broad-ranging natural metabotype variation drives physiological plasticity in healthy control inbred rat strains.

Maintaining homeostasis in higher organisms involves a complex interplay of multiple ubiquitous and organ-specific molecular mechanisms that can be characterized using functional genomics technologies such as transcriptomics, proteomics, and metabonomics and dissected out through genetic investigations in healthy and diseased individuals. We characterized the genomic, metabolic, and physiological divergence of several inbred rat strains--Brown Norway, Lewis, Wistar Kyoto, Fisher (F344)--frequently used as healthy controls in genetic studies of the cardiometabolic syndrome. Hierarchical clustering of (1)H NMR-based metabolic profiles (n = 20 for urine, n = 16 for plasma) identified metabolic phenotype (metabotype) divergence patterns similar to the phylogenetic variability based on single nucleotide polymorphisms. However, the observed urinary metabotype variation exceeded that explainable by genetic polymorphisms. To understand further this natural variation, we used an integrative, knowledge-based network biology metabolic pathway analysis approach, coined Metabolite-Set Enrichment Analysis (MSEA). MSEA reveals that homeostasis and physiological plasticity can be achieved despite widespread divergences in glucose, lipid, amino acid, and energy metabolism in the host, together with different gut microbiota contributions suggestive of strain-specific transgenomic interactions. This work illustrates the concept of natural metabolomic variation, leading to physiologically stable albeit diverse strategies within the range of normality, all of which are highly relevant to animal model physiology, genetical genomics, and patient stratification in personalized healthcare.

Lithium aluminates on a molecular titanium oxide.

Lithium aluminates Li[Al(O-2,6-Me(2)C(6)H(3))R'(3)] (R' = Et, Ph) react with the µ(3)-alkylidyne oxoderivative ligands [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ(3)-CR)] [R = H (1), Me (2)] to afford the aluminum-lithium-titanium cubane complexes [{R'(3)Al(µ-O-2,6-Me(2)C(6)H(3))Li}(µ(3)-O)(3){Ti(η(5)-C(5)Me(5))}(3)(µ(3)-CR)] [R = H, R' = Et (5), Ph (7); R = Me, R' = Et (6), Ph (8)]. Complex 7 evolves with the formation of a lithium dicubane species and a Li{Al(µ-O-2,6-Me(2)C(6)H(3))Ph(3)}(2)] unit.

Ammonia activation by µ3-alkylidyne fragments supported on a titanium molecular oxide model.

Ammonolysis of the µ(3)-alkylidyne derivatives [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ(3)-CR)] [R = H (1), Me (2)] produces a trinuclear oxonitride species, [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ(3)-N)] (3), via methane or ethane elimination, respectively. During the course of the reaction, the intermediates amido µ-alkylidene [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ-CHR)(NH(2))] [(R = H (4), Me (5)] and µ-imido ethyl species [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ-NH)Et] (6) were characterized and/or isolated. This achievement constitutes an example of characterization of the three steps of successive activation of N-H bonds in ammonia within the same transition-metal molecular system. The N-H σ-bond activation of ammonia by the µ(3)-alkylidyne titanium species has been theoretically investigated by DFT method on [{Ti(η(5)-C(5)H(5))(µ-O)}(3)(µ(3)-CH)] model complex. The calculations complement the characterization of the intermediates, showing the multiple bond character of the terminal amido and the bridging nature of imido ligand. They also indicate that the sequential ammonia N-H bonds activation process goes successively downhill in energy and occurs via direct hydron transfer to the alkylidyne group on organometallic oxides 1 and 2. The mechanism can be divided into three stages: (i) coordination of ammonia to a titanium center, in a trans disposition with respect to the alkylidyne group, and then the isomerization to adopt the cis arrangement, allowing the direct hydron migration to the µ(3)-alkylidyne group to yield the amido µ-alkylidene complexes 4 and 5, (ii) hydron migration from the amido moiety to the alkylidene group, and finally (iii) hydron migration from the µ-imido complex to the alkyl group to afford the oxo µ(3)-nitrido titanium complex 3 with alkane elimination.

Major Prehospital Trauma and In-Hospital Emergencies: Massive Transfusion Triggers.

BACKGROUND: Massive transfusion (MT) in trauma is initiated on the basis of factors of different natures and depending on protocols and scales used both in prehospital and in-hospital care areas. OBJECTIVE: The main goal was to analyze and relate factors and predictive variables for MT requirements considering both health care areas. METHOD: This was a retrospective cohort study that included patients who were treated either at the emergency department of a large hospital or through prehospital care before arrival at the hospital. The patients included were adults who received MT, defined as a blood bank request of 10 or more units of red cells in the first 24 hours or 5 or more within 4 hours of trauma, from January 1, 2009, to January 1, 2017. The variables included were individual characteristics and those associated with the trauma, clinical-analytical assessment, resuscitation, timing, and survival. RESULTS: A total of 52 patients who received MT were included. The average age of the patients was 41.23 ± 16.06 years, a mean of 19.56 ± 12.77 units was administered, and the mortality rate was 21.2%. DISCUSSION: Injury mechanism, clinical-analytical variables, and resuscitation strategies have a significant influence on the need for MT; therefore, early identification is fundamental for performing quality management and addressing avoidable factors during MT processes.

Incorporation of boron, aluminum, and gallium derivatives into [{Ti(η(5)-C5Me5)(µ-O)}3(µ3-CR)] (R = H, Me).

The synthesis and characterization of a family of alkyl and halide adducts of group 13 elements (B, Al, Ga), containing the µ(3)-alkylidyne oxo derivative ligands [{Ti(η(5)-C(5)Me(5))(µ-O)}(3)(µ(3)-CR)] [R = H (1), Me (2)], are presented. The compounds are synthesized by Lewis acid-base reactions involving equimolecular amounts of 1 or 2 and alkyl [AlR'(3)] (R' = Me, Et, Ph) or halide derivatives [MX(3)] (M = B, X = Br; M = Al, X = Cl, Br, I; M = Ga, X = Cl, Br). The novel species [{E(3)M}(µ(3)-O)(µ-O)(2){Ti(η(5)-C(5)Me(5))}(3)(µ(3)-CR)] (3-8 and 11-21; R = H, Me; M = B, Al, Ga; E = alkyl, halide) exhibit coordination of 1 or 2 through one of the three oxygen atoms of the Ti(3)O(3) ring to the metal center. In the case of the reaction of 2 with 2 equiv of [AlMe(3)], the complex [{MeAl}(µ(3)-O)(3){Ti(η(5)-C(5)Me(5))}(3)(µ(3)-CCH(2-))] (9) containing the naked carbanion µ(3)-CCH(2-) was isolated with methane elimination. On the other hand, the derivative [{Br(3)B}(µ(3)-O)(µ-O)(2){Ti(η(5)-C(5)Me(5))}(3)(µ(3)-CMe)] (11) undergoes cleavage of the trinuclear structure to give [TiBr(η(5)-C(5)Me(5))}(µ-O){Ti(η(5)-C(5)Me(5))}(MeCBO(2)){TiBr(2)(η(5)-C(5)Me(5))}] (22). The crystalline structures of some of these products are also included in this paper.