Novel Synthesis of 2‐Alkylquinolizinium‐1‐olates and Their 1,3‐Dipolar Cycloaddition Reactions with Acetylenes

Several 2‐alkylquinolizinium‐1‐olates 9 , i.e., heterobetaines, were prepared from ketone 11 , the latter being readily available either from pyridine‐2‐carbaldehyde via a Grignard reaction, followed by oxidation with MnO₂, or from 2‐picolinic acid (=pyridine‐2‐carboxylic acid) via the corresponding Weinreb amide and subsequent Grignard reaction. Mesoionic heterobetaines such as quinolizinium derivatives have the potential to undergo cycloaddition reactions with double and triple bonds, e.g., 1,3‐dipolar cycloadditions or Diels? Alder reactions. We here report on the scope and limitations of cycloaddition reactions of 2‐alkylquinolizinium‐1‐olates 9 with electron‐poor acetylene derivatives. As main products of the reaction, 5‐oxopyrrolo[2,1,5‐de]quinolizines (=‘[2.3.3]cyclazin‐5‐ones’) 19 were formed via a regioselective [2+3] cycloaddition, and cyclohexadienone derivatives, formed via a Diels? Alder reaction, were obtained as side products. The structures of 2‐benzylquinolizinium‐1‐olate ( 9a ) and two ‘[2.3.3]cyclazin‐5‐ones’ 19i and 19l were established by X‐ray crystallography.     

The Hydrogen Evolution Reaction in Alkaline Solution: From Theory,Single Crystal Models,to Practical Electrocatalysts

The hydrogen evolution reaction (HER) is a fundamental process in electrocatalysis and plays an important role in energy conversion for the development of hydrogen‐based energy sources. However, the considerably slow rate of the HER in alkaline conditions has hindered advances in water splitting techniques for high‐purity hydrogen production. Differing from well documented acidic HER, the mechanistic aspects of alkaline HER are yet to be settled. A critical appraisal of alkaline HER electrocatalysis is presented, with a special emphasis on the connection between fundamental surface electrochemistry on single‐crystal models and the derived molecular design principle for real‐world electrocatalysts. By presenting some typical examples across theoretical calculations, surface characterization, and electrochemical experiments, we try to address some key ongoing debates to deliver a better understanding of alkaline HER at the atomic level.     

(E)‐6‐Methoxy‐3‐(α‐methoxybenzyl­idene)benzo[b]furan‐2(3H)‐one at 173 K

The title compound, C₁₇H₁₄O₄, is an unprecedented new synthetic isoaurone‐type enol ether that has the E configuration. The planar furanone ring is fused to a methoxy­benzene ring system, with an interplanar angle of 175.7 (1)°. Due to this ring fusion, the six‐membered ring has a significant amount of ring strain, as shown by the internal ring angle range of 115.8 (1)–124.7 (1)°, whereas the vinylic phenyl ring has internal angles between 119.7 (1) and 120.2 (1)°. The mol­ecules form infinite hydrogen‐bonding layers along the b direction of the form C—H?O, where the keto O atom acts as a bifurcated acceptor. These layers are connected along the c direction by another hydrogen bond with a methoxy H atom as donor. In addition to this connection, the layers are stacked via centres of symmetry by a pair of symmetry‐related benzo­furan­one ring systems.     

An implantable biochip to influence patient outcomes following trauma-induced hemorrhage

Following hemorrhage-causing injury, lactate levels rise and correlate with the severity of injury and are a surrogate of oxygen debt. Posttraumatic injury also includes hyperglycemia, with continuously elevated glucose levels leading to extensive tissue damage, septicemia, and multiple organ dysfunction syndrome. A temporary, implantable, integrated glucose and lactate biosensor and communications biochip for physiological status monitoring during hemorrhage and for intensive care unit stays has been developed. The dual responsive, amperometric biotransducer uses the microdisc electrode array format upon which were separately immobilized glucose oxidase and lactate oxidase within biorecognition layers, 1.0–5.0 μm thick, of 3 mol% tetraethyleneglycol diacrylate cross-linked p(HEMA-co-PEGMA-co-HMMA-co-SPA)-p(Py-co-PyBA) electroconductive hydrogels. The device was then coated with a bioactive hydrogel layer containing phosphoryl choline and polyethylene glycol pendant moieties [p(HEMA-co-PEGMA-co-HMMA-co-MPC)] for indwelling biocompatibility. In vitro cell proliferation and viability studies confirmed both polymers to be non-cytotoxic; however, PPy-based electroconductive hydrogels showed greater RMS 13 and PC12 proliferation compared to controls. The glucose and lactate biotransducers exhibited linear dynamic ranges of 0.10–13.0 mM glucose and 1.0–7.0 mM and response times (t ₉₅) of 50 and 35–40 s, respectively. Operational stability gave 80% of the initial biosensor response after 5 days of continuous operation at 37 °C. Preliminary in vivo studies in a Sprague–Dawley hemorrhage model showed tissue lactate levels to rise more rapidly than systematic lactate. The potential for an implantable biochip that supports telemetric reporting of intramuscular lactate and glucose levels allows the refinement of resuscitation approaches for civilian and combat trauma victims.     

基于单颗粒气溶胶质谱的人体呼出颗粒物粒径分布与化学成分的分析方法研究

人体呼出气中内源性颗粒物和外源性颗粒物的粒径和化学成分信息可为肺部疾病诊断、环境暴露评价等研究提供参考。该文初步考察了单颗粒气溶胶质谱(Single particle aerosol mass spectrometry,SPAMS)同时获取人体呼出气中颗粒物(Exhaled breath particles,EBPs)粒径分布和化学成分的可行性。结果表明,健康成人的EBPs数浓度为227~1 043个/L,获取具有统计意义的粒径分布所需的EBPs检出限为2 500个颗粒物,粒径范围为200~1 000 nm,峰值出现在460 nm。与环境空气颗粒物的粒径分布相比,EBPs更多分布在200~300 nm和440~660 nm,从化学成分来看,这两段粒径范围内的EBPs含有更多的碳元素,不易在体内发生吸湿增长,提高了被呼出的概率。EBPs的化学成分可能反映内源性颗粒物和外源性颗粒物组成,如HSO_4~-、PO_3~-、CN~-、CNO~-和C_xH_yO_z~+(x=1~3,y=1~7,z=1~3)可能与内源性颗粒物中的蛋白含量、磷酸酯酰甘油等成分有关,碳簇峰C_3~-、C_4~-、C~+、C_3~+、C_3H~+和C_4~+推测与外源性颗粒物中的碳元素有关。     

Structure and function of a lignostilbene-α,β-dioxygenase orthologue from <Emphasis Type="Italic">Pseudomonas brassicacearum</Emphasis>

Background

Stilbene cleaving oxygenases (SCOs), also known as lignostilbene-α,β-dioxygenases (LSDs) mediate the oxidative cleavage of the olefinic double bonds of lignin-derived intermediate phenolic stilbenes, yielding small modified benzaldehyde compounds. SCOs represent one branch of the larger carotenoid cleavage oxygenases family. Here, we describe the structural and functional characterization of an SCO-like enzyme from the soil-born, bio-control agent Pseudomonas brassicacearum.

Methods

In vitro and in vivo assays relying on visual inspection, spectrophotometric quantification, as well as liquid-chormatographic and mass spectrometric characterization were applied for functional evaluation of the enzyme. X-ray crystallographic analyses and in silico modeling were applied for structural investigations.

Results

In vitro assays demonstrated preferential cleavage of resveratrol, while in vivo analyses detected putative cleavage of the straight chain carotenoid, lycopene. A high-resolution structure containing the seven-bladed β-propeller fold and conserved 4-His-Fe unit at the catalytic site, was obtained. Comparative structural alignments, as well as in silico modelling and docking, highlight potential molecular factors contributing to both the primary in vitro activity against resveratrol, as well as the putative subsidiary activities against carotenoids in vivo, for future validation.

Conclusions

The findings reported here provide validation of the SCO structure, and highlight enigmatic points with respect to the potential effect of the enzyme’s molecular environment on substrate specificities for future investigation.

     

MaxSynBio: Avenues Towards Creating Cells from the Bottom Up

A large German research consortium mainly within the Max Planck Society (“MaxSynBio”) was formed to investigate living systems from a fundamental perspective. The research program of MaxSynBio relies solely on the bottom‐up approach to synthetic biology. MaxSynBio focuses on the detailed analysis and understanding of essential processes of life through modular reconstitution in minimal synthetic systems. The ultimate goal is to construct a basic living unit entirely from non‐living components. The fundamental insights gained from the activities in MaxSynBio could eventually be utilized for establishing a new generation of biotechnological processes, which would be based on synthetic cell constructs that replace the natural cells currently used in conventional biotechnology.