RuV -Acylimido Intermediate in [RuIV (Por)Cl2 ]-Catalyzed C-N Bond Formation: Spectroscopic Characterization, Reactivity, and Catalytic Reactions.

Metal-catalyzed C-N bond formation reactions via acylnitrene transfer have recently attracted much attention, but direct detection of the proposed acylnitrenoid/acylimido M(NCOR) (R=aryl or alkyl) species in these reactions poses a formidable challenge. Herein, we report on Ru(NCOR) intermediates in C-N bond formation catalyzed by [RuIV (Por)Cl2 ]/N3 COR, a catalytic method applicable to aziridine/oxazoline formation from alkenes, amination of substituted indoles, α-amino ketone formation from silyl enol ethers, amination of C(sp3 )-H bonds, and functionalization of natural products and carbohydrate derivatives (up to 99 % yield). Experimental studies, including HR-ESI-MS and EPR measurements, coupled with DFT calculations, lend evidence for the formulation of the Ru(NCOR) acylnitrenoids as a RuV -imido species.

Total Synthesis of Cryptotrione.

The total synthesis of cryptotrione (1) was enabled by substrate-controlled diastereoselective construction of the bicyclo[3.1.0]hexene framework through platinum-catalyzed enyne cycloisomerization and Lewis acid induced polyene cyclization to construct the abietane-type tricyclic diterpene skeleton. The stereogenic tertiary carbon center in the side chain was installed in a diastereodivergent manner by conjugate addition reactions.

Gold and silver catalysis: from organic transformation to bioconjugation.

This review focuses on gold (including gold(I) and gold(III) complexes, and gold nanoparticles) and silver(I) catalysis, including aerobic oxidation, activation of C-H bonds and activation of C-C multiple bonds, and their applications in the modification of biomolecules, including oligosaccharides, peptides and polypeptides, reported since the year 2000. Because of the high carbophilicity of gold and silver compounds, gold or silver-catalysed/mediated organic transformations feature high functional group tolerance, excellent regio-, diastereo- or enantioselectivity and/or high product turnover numbers under mild reaction conditions.

Elevated catalytic activity of ruthenium(II)-porphyrin-catalyzed carbene/nitrene transfer and insertion reactions with N-heterocyclic carbene ligands.

Bis(NHC)ruthenium(II)-porphyrin complexes were designed, synthesized, and characterized. Owing to the strong donor strength of axial NHC ligands in stabilizing the trans M=CRR'/M=NR moiety, these complexes showed unprecedently high catalytic activity towards alkene cyclopropanation, carbene C-H, N-H, S-H, and O-H insertion, alkene aziridination, and nitrene C-H insertion with turnover frequencies up to 1950 min(-1). The use of chiral [Ru(D4-Por)(BIMe)2] (1 g) as a catalyst led to highly enantioselective carbene/nitrene transfer and insertion reactions with up to 98% ee. Carbene modification of the N terminus of peptides at 37 °C was possible. DFT calculations revealed that the trans axial NHC ligand facilitates the decomposition of diazo compounds by stabilizing the metal-carbene reaction intermediate.

Effects of low temperature on growth and metabolism of larval green sturgeon (Acipenser medirostris) across early ontogeny.

Southern Distinct Population Segment (sDPS) green sturgeon spawn solely in one stretch of the Sacramento River in California. Management of this spawning habitat is complicated by cold water temperature requirements for the conservation of winter-run Chinook salmon. This study assessed whether low incubation and rearing temperatures resulted in carryover effects across embryo to early juvenile life stages on scaling relationships in growth and metabolism in northern DPS green sturgeon used as a proxy for sDPS green sturgeon. Fish were incubated and reared at 11 °C and 15 °C, with a subset experiencing a reciprocal temperature transfer post-hatch, to assess recovery from cold incubation or to simulate a cold-water dam release which would chill rearing larvae. Growth and metabolic rate of embryos and larvae were measured to 118 days post hatch. Reciprocal temperature transfers revealed a greater effect of low temperature exposure during larval rearing rather than during egg incubation. While 11 °C eggs hatched at a smaller length, log-transformed length-weight relationships showed that these differences in developmental trajectory dissipated as individuals achieved juvenile morphology. However, considerable size-at-age differences persisted between rearing temperatures, with 15 °C fish requiring 60 days post-hatch to achieve 1 g in mass, whereas 11 °C fish required 120 days to achieve 1 g, resulting in fish of the same age at the completion of the experiment with a ca. 37-fold difference in weight. Consequently, our study suggests that cold rearing temperatures have far more consequential downstream effects than cold embryo incubation temperatures. Growth delays from 11 °C rearing temperatures would greatly increase the period of vulnerability to predation in larval green sturgeon. The scaling relationship between log-transformed whole-body metabolism and mass exhibited a steeper slope and thus an increased oxygen requirement with size in 11 °C reared fish, potentially indicating an energetically unsustainable situation. Understanding how cold temperatures affect green sturgeon ontogeny is necessary to refine our larval recruitment estimations for this threatened species.

Highly selective intramolecular carbene insertion into primary C-H bond of α-diazoacetamides mediated by a (p-cymene)ruthenium(II) carboxylate complex.

Complex [(p-cymene)Ru(η(1)-O(2)CCF(3))(2)(OH(2))] mediated transformation of α-diazoacetamides ArCH(2)N(C(CH(3))(3))C(O)CHN(2) to result in carbene insertion into the primary C-H bond exclusively, with the γ-lactam products being isolated in up to 98% yield. This unexpected reaction is striking in view of the presence of usually more reactive sites such as secondary C-H bonds in the substrates. DFT calculations based on proposed Ru-carbene species provide insight into this unique selectivity.

Gold-mediated bifunctional modification of oligosaccharides via a three-component coupling reaction.

An efficient modular approach for single-site incorporation of two independent functionalities (amines and alkynes) into aldehyde-containing oligosaccharides concurrently by using a one-pot gold-mediated three-component coupling reaction in aqueous medium under mild conditions has been developed.

Selective functionalisation of saturated C-H bonds with metalloporphyrin catalysts.

The recent surge of interest in metal-catalysed C-H bond functionalisation reactions reflects the importance of such reactions in biomimetic studies and organic synthesis. This critical review focuses on metalloporphyrin-catalysed saturated C-H bond functionalisation reported since the year 2000, including C-O, C-N and C-C bond formation via hydroxylation, amination and carbenoid insertion, respectively, together with a brief description of previous achievements in this area. Among the metalloporphyrin-catalysed reactions highlighted herein are the hydroxylation of steroids, cycloalkanes and benzylic hydrocarbons; intermolecular amination of steroids, cycloalkanes and benzylic or allylic hydrocarbons; intramolecular amination of sulfamate esters and organic azides; intermolecular carbenoid insertion into benzylic, allylic or alkane C-H bonds; and intramolecular carbenoid C-H insertion of tosylhydrazones. These metalloporphyrin-catalysed saturated C-H bond functionalisation reactions feature high regio-, diastereo- or enantioselectivity and/or high product turnover numbers. Mechanistic studies suggest the involvement of metal-oxo, -imido (or nitrene), and -carbene porphyrin complexes in the reactions. The reactivity of such metal-ligand multiple bonded species towards saturated C-H bonds, including mechanistic studies through both experimental and theoretical means, is also discussed (244 references).

The effect of temperature on specific dynamic action of juvenile fall-run Chinook salmon, Oncorhynchus tshawytscha.

Juvenile fall-run Chinook salmon (Oncorhynchus tshawytscha) in the Sacramento-San Joaquin River Basin experience temporally and spatially heterogenous temperature regimes, between cool upper tributaries and the warm channelized Delta, during freshwater rearing and outmigration. Limited water resources necessitate human management of dam releases, allowing temperature modifications. The objective of this study was to examine the effect of temperature on specific dynamic action (SDA), or the metabolic cost associated with feeding and digestion, which is thought to represent a substantial portion of fish energy budgets. Measuring SDA with respect to absolute aerobic scope (AAS), estimated by the difference between maximum metabolic rate (MMR) and standard metabolic rate (SMR), provides a snapshot of its respective energy allocation. Fish were acclimated to 16°C, raised or lowered to each acute temperature (13°C, 16°C, 19°C, 22°C or 24°C), then fed a meal of commercial pellets weighing 2% of their wet mass. We detected a significant positive effect of temperature on SMR and MMR, but not on AAS. As expected, there was no significant effect of temperature on the total O2 cost of digestion, but unlike other studies, we did not see a significant difference in duration, peak metabolic rate standardized to SMR, time to peak, percent of meal energy utilized, nor the ratio of peak O2 consumption to SMR. Peak O2 consumption represented 10.4-14.5% of AAS leaving a large amount of aerobic capacity available for other activities, and meal energy utilized for digestion ranged from 5.7% to 7.2%, leaving substantial remaining energy to potentially assimilate for growth. Our juvenile fall-run Chinook salmon exhibited thermal stability in their SDA response, which may play a role in maintaining homeostasis of digestive capability in a highly heterogeneous thermal environment where rapid growth is important for successful competition with conspecifics and for avoiding predation.

Highly Enantioselective Synthesis Using Prolinol as a Chiral Auxiliary: Silver-Mediated Synthesis of Axially Chiral Vinylallenes and Subsequent (Hetero)-Diels-Alder Reactions.

Using (S)-prolinol as a chiral auxiliary, axially chiral vinylallenes with excellent enantiopurity (up to >99% enantiomeric excess (ee)) were readily prepared from optically pure propargylamines in the presence of AgNO3 under microwave irradiation. Subsequent (hetero)-Diels-Alder reaction of these axially chiral vinylallenes with azodicarboxylates or maleimides on water demonstrates excellent axial-to-point chirality transfer (up to 99% ee).

Luminescent ruffled iridium(iii) porphyrin complexes containing N-heterocyclic carbene ligands: structures, spectroscopies and potent antitumor activities under dark and light irradiation conditions.

A panel of iridium(iii) porphyrin complexes containing axial N-heterocyclic carbene (NHC) ligand(s) were synthesized and characterized. X-ray crystal structures of the bis-NHC complexes [IrIII(ttp)(IMe)2]+ (2a), [IrIII(oep)(BIMe)2]+ (2d), [IrIII(oep)(I i Pr)2]+ (2e) and [IrIII(F20tpp)(IMe)2]+ (2f) display ruffled porphyrin rings with mesocarbon displacements of 0.483-0.594 Å and long Ir-CNHC bonds of 2.100-2.152 Å. Variable-temperature 1H NMR analysis of 2a reveals that the macrocycle porphyrin ring inversion takes place in solution with an activation barrier of 40 ± 1 kJ mol-1. The UV-vis absorption spectra of IrIII(por)-NHC complexes display split Soret bands. TD-DFT calculations and resonance Raman experiments show that the higher-energy Soret band is derived from the 1MLCT dπ(Ir) → π*(por) transition. The near-infrared phosphorescence of IrIII(por)-NHC complexes from the porphyrin-based 3(π, π*) state features broad emission bands at 701-754 nm with low emission quantum yields and short lifetimes (Φ em < 0.01; τ < 4 µs). [IrIII(por)(IMe)2]+ complexes (por = ttp and oep) are efficient photosensitizers for 1O2 generation (Φ so = 0.64 and 0.88) and are catalytically active in the light-induced aerobic oxidation of secondary amines and arylboronic acid. The bis-NHC complexes exhibit potent dark cytotoxicity towards a panel of cancer cells with IC50 values at submicromolar levels. The cytotoxicity of these complexes could be further enhanced upon light irradiation with IC50 values as low as nanomolar levels in association with the light-induced generation of reactive oxygen species (ROS). Bioimaging of [IrIII(oep)(IMe)2]+ (2c) treated cells indicates that this Ir complex mainly targets the endoplasmic reticulum. [IrIII(oep)(IMe)2]+ catalyzes the photoinduced generation of singlet oxygen and triggers protein oxidation, cell cycle arrest, apoptosis and the inhibition of angiogenesis. It also causes pronounced photoinduced inhibition of tumor growth in a mouse model of human cancer.

Gold-catalyzed highly enantioselective synthesis of axially chiral allenes.

Axially chiral allenes are synthesized from chiral propargylamines catalyzed by KAuCl4 in high yields (up to 93% yield) and excellent enantioselectivities (up to 97% ee) in CH3CN at 40 degrees C. The reaction has been applied to the synthesis of novel allene-modified artemisinin derivatives with the delicate endoperoxide moieties remaining intact. A tentative mechanism regarding gold(I)-catalyzed intramolecular hydride transfer was proposed on the basis of deuterium-labeling experiments and ESI-MS analysis of the reaction mixture.

Bromadiolone toxicokinetics: diagnosis and treatment implications.

INTRODUCTION: Ingestion of bromadiolone can lead to prolonged and life-threatening coagulopathy. Traditional treatment of bromadiolone intoxication relies on the coagulation profile. Currently, there is scanty information on bromadiolone elimination kinetics and half-life. CASE REPORT: We report a case of bromadiolone poisoning in a 40-year old female who, by history, ingested four 42.5-gram bags of rat poison (0.005% bromadiolone), equivalent to 8.5 mg bromadiolone (0.17 mg/kg body weight), four days prior to admission. On admission, her prothrombin time was 92.0 seconds, international normalized ratio was 5.7, and activated partial thromboplastin time was 50.2 seconds with no bleeding on clinical examination. The first plasma bromadiolone level (5 days post-ingestion) was 92 ng/mL. Serial measurement of plasma bromadiolone levels confirmed the diagnosis and demonstrated that bromadiolone obeys the elimination kinetic of a two-compartment model with a rapid, fairly steep decline phase (half-life 3.5 days) followed by a slower termination phase (half-life 24 days). Plasma bromadiolone level of less than 10 ng/mL in our patient was associated with a consistently normal coagulation profile without vitamin K1 therapy. CONCLUSIONS: There is a lack of information on the toxicodynamics and toxicokinetics of bromadiolone in humans; further studies are needed before the plasma bromadiolone level can serve as one of the logical and safe therapeutic endpoints for vitamin K1 therapy.

Gold(III) Salen complex-catalyzed synthesis of propargylamines via a three-component coupling reaction.

[reaction: see text] Propargylamines have been synthesized by a gold(III) salen complex-catalyzed three-component coupling reaction of aldehydes, amines, and alkynes in water in excellent yields at 40 degrees C. With chiral prolinol derivatives as the amine component, excellent diastereoselectivities (up to 99:1) have been attained. This coupling reaction has been applied to the synthesis of propargylamine-modified artemisinin derivatives with the delicate endoperoxide moieties remaining intact. Cytotoxicities with IC(50) values up to 1.1 microM against a human hepatocellular carcinoma cell line (HepG2) were exhibited by these artemisinin derivatives.

Gold-mediated selective cysteine modification of peptides using allenes.

A new approach for selective modification of cysteine-containing peptides through gold-mediated oxidative allene-thiol coupling reaction in aqueous medium is developed.

A spuriously 'normal' haemoglobin A1c result.

We report a case of spuriously 'normal' haemoglobin A1c (HbA1c) result due to misidentification of HbG Taipei as HbAo by the Variant II built-in retention time algorithm. The defect was circumvented effectively by the implementation of a chromatographic system specific internal quality control mechanism for peak identity verification. HbA1c and estimated average glucose results were corrected from 4.7% to 8.2%, and 4.9 to 10.5 mmol/L, respectively. The results were consistent with the patient's concurrent and previous fasting blood glucose concentrations and existence of diabetes mellitus dermopathy, indicating poor glycaemic control. A review of currently available analytical systems showed that other than mass spectrometry, HbA1c measurements by these systems were generally affected by the presence of haemoglobin variants. The same haemoglobin variant may affect different analytical systems differently, resulting in the deviation of HbA1c results from the true value to different extents. Including the analytical principle of HbA1c measurement in the laboratory report can avoid inappropriate comparison of results obtained by different analytical systems. Moreover, since individual haemoglobinopathy may affect the degree of glucose binding to haemoglobin in a different way, this uncertainty limits the general application of same decision cut-off of established guidelines for glycaemic control monitoring. Adoption of an individualized monitoring system based on the critical difference or reference change value of HbA1c can be considered.

Silver(I)-mediated highly enantioselective synthesis of axially chiral allenes under thermal and microwave-assisted conditions.

Silver(I) salts mediated stereospecific transformation of optically active propargylamines to axially chiral allenes with excellent enantioselectivities (17 examples with 96-99% ee; one substrate with 91% ee) without subsequent racemization.