Synthesis of novel 4H-pyrimido[1,6-a]pyrimidines via a one-pot three-component condensation

Abstract  

Highly substituted novel 4H-pyrimido[1,6-a] pyrimidines were prepared by a trifluoromethanesulfonic acid catalyzed one-pot three-component condensation of 4-aminopyrimidines, aldehydes, and β-ketoesters. A preliminary feasibility study was undertaken on these compounds, to assess the potential production of a library of further diversified compounds by nucleophilic replacement of Cl (R¹) or by reaction of electrophiles with the NH₂ (R²) group.     

Towards a modular,versatile and portable sensor system for measurements in gaseous environments based on microcantilevers

Microfabricated silicon cantilever sensor arrays represent a powerful platform for sensing applications in physics, chemistry, material science, biology and medicine. The sensor response is mechanical bending due to absorption of molecules. In gaseous environment, polymer-coated microcantilevers are used as electronic nose for characterization of vapors, resulting in cantilever bending due to polymer swelling upon exposure. Medical applications involve fast characterization of exhaled patient's breath samples for detection of diseases, based on the presence of certain chemicals in breath. We present a portable, compact, modular microcantilever setup, which uses a micropump for aspiration and a bluetooth interface for remote data acquisition.     

Revealing the CO2 Conversion at Electrode/Electrolyte Interfaces in Li–CO2 Batteries via Nanoscale Visualization Methods

Lithium–carbon dioxide (Li–CO₂) battery technology presents a promising opportunity for carbon capture and energy storage. Despite tremendous efforts in Li–CO₂ batteries, the complex electrode/electrolyte/CO₂ triple-phase interfacial processes remain poorly understood, in particular at the nanoscale. Here, using in situ atomic force microscopy and laser confocal microscopy-differential interference contrast microscopy, we directly observed the CO₂ conversion processes in Li–CO₂ batteries at the nanoscale, and further revealed a laser-tuned reaction pathway based on the real-time observations. During discharge, a bi-component composite, Li₂CO₃/C, deposits as micron-sized clusters through a 3D progressive growth model, followed by a 3D decomposition pathway during the subsequent recharge. When the cell operates under laser (λ=405 nm) irradiation, densely packed Li₂CO₃/C flakes deposit rapidly during discharge. Upon the recharge, they predominantly decompose at the interfaces of the flake and electrode, detaching themselves from the electrode and causing irreversible capacity degradation. In situ Raman shows that the laser promotes the formation of poorly soluble intermediates, Li₂C₂O₄, which in turn affects growth/decomposition pathways of Li₂CO₃/C and the cell performance. Our findings provide mechanistic insights into interfacial evolution in Li–CO₂ batteries and the laser-tuned CO₂ conversion reactions, which can inspire strategies of monitoring and controlling the multistep and multiphase interfacial reactions in advanced electrochemical devices.     

MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2

MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.Subject terms: Translational research, Cell signalling     

Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever arrays

Free-standing cantilevers, which directly translate specific biochemical reactions into micromechanical motion, have recently attracted much attention as label-free biosensors and micro/nano robotic devices. To exploit this mechanochemical sensing technology, it is essential to develop a fundamental understanding of the origins of surface stress. Here we report a detailed study into the molecular basis of stress generation in aqueous environments focusing on the pH titration of model mercaptohexadecanoic acid self-assembled monolayers (SAMs), using in situ reference cantilevers coated with nonionizable hexadecanethiol SAMs. Semiautomated data analysis and a statistical model were developed to quantify cyclic deprotonation/protonation reactions on multiple arrays. In-plane force titrations were found to have the sensitivity to detect ionic hydrogen bond formation between protonated and nonprotonated carboxylic acid groups in the proximity of the surface pK1/2, which generated a mean tensile differential surface stress of +1.2 +/- 0.3 mN/m at pH 6.0, corresponding to 1 pN attractive force between two adjacent MHA molecules. Conversely, the magnitude of compressive differential surface stress was found to increase progressively with pH >/= 7.0, reaching a maximum of -14.5 +/- 0.5 mN/m at pH 9.0, attributed to enhanced electrostatic repulsion between deprotonated carboxylic acid groups. However, striking differences were observed in the micromechanical responses to different ionic strength and ion species present in the aqueous environment, highlighting the critical role of counter- and co-ions on surface stress. Our findings provide fundamental insights into the molecular mechanisms of in-plane mechanochemistry, which may be exploited for biosensing and nanoactuation applications.     

Preparation and Structural Characterization of a Heterobimetallic Sulfide Cluster Compound [(η 5-C5Me5)WS3Au(dppms)]

A novel heterobimetallic sulfide cluster [( ⁵-C₅Me₅)WS₃Au(dppms)][dppms = bis(diphenylphosphino)methane monosulfide] was prepared by the reaction of [PPh₄][( ⁵-C₅Me₅)WS₃] with AuI and dppm [dppm = bis(diphenylphosphino)methane] in MeCN. The title compound was fully characterized by elemental analysis, i.r., u.v.–vis., ¹H-n.m.r. spectra, and by single crystal X-ray crystallography. In the molecular structure, the Au atom is trigonally coordinated by two bridging S atoms of a [( ⁵-C₅Me₅)WS₃]^– anion and a P atom of the dppms molecule. The formation mechanism for this compound is discussed.     

Helicenes Built from Silacyclopentadienes via Ring‐by‐Ring Knitting of the Helical Framework

Despite the apparent diversity of the protocols developed for the synthesis of helicenes, they essentially follow the same strategy: the closure of one, or several, internal rings in a key step. Herein, we report the synthesis of a new family of the heterohelicenes consisting of fused silacyclopentadiene rings formed via a facile and novel process. The treatment of oligo(alkynilydenesilylene) precursors of type H₂C=CH?(SiMe₂?C≡C)_n?R (n=3–7), bearing a vinyl group on the terminal silicon atom, with 9‐borabicyclononane leads first to 1,2‐hydroboration of the terminal double bond which then continues with a cascade of intramolecular 1,1‐carboboration reactions accompanied with the closure of a new silole ring after each step affording the target silahelicenes with, currently, up to seven condensed silole rings and with excellent yields. According XRD analysis, the seven fused silole rings of the heptacyclic compound 11 b form an almost complete turn of a helix. The presented one‐pot sequence of reactions is the first example of ring‐by‐ring knitting of a helical framework starting from easily available linear precursors.     

以醚胺为模板剂合成含二价金属杂原子的开放骨架磷酸铝化合物M(Ⅱ)-CJ50

在水热体系中, 以2,2'-(乙烯二氧)双(乙胺)为模板剂, 合成了3种含二价金属杂原子的开放骨架磷酸铝化合物M(Ⅱ)-CJ50(|C₆H₁₇N₂O₂| [MAl₃P₄O₁₆], 其中M=Mg, Mn和Fe). 单晶及粉末X射线衍射分析表明, 这3种化合物与以咪唑为模板剂合成的含三价金属杂原子的M(Ⅲ)-CJ50具有相似的骨架拓扑结构. 二者的区别在于: 由于使用了还原性较强的醚胺作模板剂, M(Ⅱ)-CJ50结构中的金属杂原子具有比M(Ⅲ)-CJ50更低的氧化态; M(Ⅱ)-CJ50中的金属杂原子与1个醚胺模板剂分子中的2个醚氧原子形成双齿配位, 而M(Ⅲ)-CJ50中的金属杂原子则与2个咪唑模板剂分别形成单齿配位. 此外, 磁性测试结果表明, 由于金属杂原子的氧化态以及配体模板剂分子的差异, 导致M(Ⅱ)-CJ50中的过渡金属杂原子处于电子高自旋态, 而M(Ⅲ)-CJ50中的杂原子则处于低自旋态.     

Beitrag zur Kenntnis der Viskosezersetzung. Die Dissoziationskonstante der Cellulosexanthogensäure

Zusammenfassung Nachdem plausibel gemacht werden konnte, daß bei verschiedenen Zersetzungs- bzw. Regenerationsprozessen als Zwischenprodukt freie Cellulosexanthogensäure (CXS.) auftritt und dieselbe z. B. in vorliegender Arbeit im frisch gesponnenen Faden tatsächlich nachweisbar war, wurde auch versucht, die Dissoziationskonstante derselben abzuschätzen. Die dabei auftretenden Schwierigkeiten — sowohl hinsichtlich der experimentellen Durchführung wie auch die durch das Fehlen einer Theorie polyvalenter Makroionen — werden diskutiert. Aus mehreren unabhängigen Messungen, unter Bedachtnahme auf Ergebnisse an Celluloseglycolsäureäther vonKagawa undKatsuura, wird wahrscheinlich gemacht, daß die Dissoziationskonstante der verdünnten Säure zwischen 2,1 und 5,5·10^–5 liegt. Mithin ist die Cellulosexanthogensäure etwas stärker als Essigsäure, die im verdünnten Zustand bekanntlich Na-Cellulosexanthogenat ziemlich unzersetzt läßt^{2, 9, 12}.Abschließend wurde noch das Röntgendiagramm von präzipitiertem Na-Cellulosexanthogenat wiedergegeben.Mit 4 AbbildungenHerrn Prof. Dr.A. Skrabal zum 75. Geburtstag gewidmet.