A new synthesis of lysophosphatidylcholines and related derivatives. Use of p-toluenesulfonate for hydroxyl group protection

A new stereoselective synthesis of lysophosphatidylcholines is reported. The synthesis is based upon (1) the use of 3-p-toluenesulfonyl-sn-glycerol to provide the stereocenter for construction of the optically active lysophospholipid molecule, (2) tetrahydropyranylation of the secondary alcohol function to achieve orthogonal protection of the sn-2- and sn-3-glycerol positions, and (3) elaboration of the phosphodiester headgroup using a 2-chloro-1,3,2-dioxaphospholane/trimethylamine sequence. In the course of developing the synthesis it has been discovered that methoxyacetate displacement of the sn-3-p-toluenesulfonate yields a reactive methoxyacetyl ester, which in turn can be selectively cleaved with methanol/tert-butylamine, while the ester group at the sn-1-position remains unaffected. The sequence has been shown to be suitable for preparation of spectroscopically labeled lysophosphatidylcholines. One of these compounds was readily converted to a double-labeled mixed-chain phosphatidylcholine applicable for real-time fluorescence resonance energy transfer (FRET) assay of lipolytic enzymes. In addition, the work led to new synthetic strategies based on chemoselective manipulation of the tosyl group in the presence of other base-labile groups such as FMOC derivatives that are often used for the protection of amino and hydroxyl groups in syntheses.     

Femtosecond electronic relaxation of excited metalloporphyrins in the gas phase

A systematic study of the ultrafast decay of metalloporphyrins containing various transition metals with partially filled 3d shells and zinc (3d filled) is reported here after excitation in the second excited state of the system (Soret band). Both time-of-flight mass spectrometry and velocity map imaging have been used for detection. A general biexponential decay with a short time constant tau1 approximately 100 fs is observed for the transition metal porphyrins, followed by a tau2 approximately 1 ps time decay. This evolution is interpreted as a porphyrin-to-metal charge transfer, tau1, followed by a back transfer, tau2, which leads to an excited state (d,d*) localized on the metal. These conclusions stem from the different behaviors of zinc and the transition metal porphyrins. A porphyrin-to-metal charge transfer model is chosen to describe the relaxation mechanism, based upon the fact that transition metalloporphyrins can accept electrons on the metal site, in contrast to zinc porphyrins.     

A user-friendly, all-purpose Pd-NHC (NHC=N-heterocyclic carbene) precatalyst for the negishi reaction: a step towards a universal cross-coupling catalyst

We have developed the first user-friendly Negishi protocol capable of routinely cross-coupling all combinations of alkyl and aryl centers. The use of an easily synthesized, air stable, highly active, well-defined precatalyst PEPPSI-IPr (1; PEPPSI=pyridine-enhanced precatalyst preparation, stabilization and initiation; IPr=diisopropylphenylimidazolium derivative) substantially increases the scope, reliability, and ease-of-use of the Negishi reaction. All organohalides and routinely used pseudohalides were excellent coupling partners, with the use of chlorides, bromides, iodides, triflates, tosylates, and mesylates resulting in high yield of the coupled product. Furthermore, all reactions were performed by using general laboratory techniques, with no glove-box necessary as the precatalyst was weighed and stored in air. Utilization of this methodology allowed for the easy synthesis of an assortment of sterically encumbered biaryls and druglike heteroaromatics, demonstrating the value of the PEPPSI-IPr system. Furthermore, this is also the first time Pd-NHC (NHC=N-heterocyclic carbene) methodology has surpassed the related phosphine-ligated Negishi processes both in activity and use.     

Easily prepared air- and moisture-stable Pd-NHC (NHC=N-heterocyclic carbene) complexes: a reliable, user-friendly, highly active palladium precatalyst for the Suzuki-Miyaura reaction

The synthesis of NHC-PdCl(2)-3-chloropyridine (NHC=N-heterocyclic carbene) complexes from readily available starting materials in air is described. The 2,6-diisopropylphenyl derivative was found to be highly catalytically active in alkyl-alkyl Suzuki and Negishi cross-coupling reactions. The synthesis, ease-of-use, and activity of this complex are substantial improvements over in situ catalyst generation and all current Pd-NHC complexes. The utilization of complex 4 led to the development of a reliable, easily employed Suzuki-Miyama protocol. Employing various reaction conditions allowed a large array of hindered biaryl and drug-like heteroaromatic compounds to be synthesized without difficulty.     

Synthesis and Cytotoxic Evaluation of Novel 1,2,3‐Triazole‐4‐Linked (2E,6E)‐2‐Benzylidene‐6‐(4‐nitrobenzylidene)cyclohexanones

This work describes the synthesis of novel 1,2,3‐triazole‐4‐linked (2E,6E)‐2‐benzylidene‐6‐(4‐nitrobenzylidene)cyclo‐hexanones starting from cyclohexanone. 1‐(Cyclohex‐1‐en‐1‐yl)piperidine, the enamine from cyclohexanone and piperidine, reacted with 4‐nitrobenzaldehyde to obtain 2‐(4‐nitrobenzylidene)cyclohexanone. Condensation of the latter compound with (prop‐2‐yn‐1‐yloxy)benzaldehyde derivatives under acidic conditions gave (4‐nitrobenzylidene)‐[(prop‐2‐yn‐1‐yloxy)‐benzylidene]cyclohexanones. Finally, ‘click reaction’ of these derivatives and various organic azides led to the title compounds. All compounds were examined by MTT assay for cytotoxic activity in one human breast cancer cell line, MDA‐MB‐231.     

Body-centered-cubic structure as a basis for deriving the intermetallic crystal structures

Hyperfine Interactions - Dioximes as ligands are used as analytical reagents and serve as models for biological systems as well as catalysts in chemical processes. A number of novel mixed complexes...     

An AlGaN/GaN HEMT with reduced surface electric field and improved breakdown voltage

A reduced surface electric field in AlGaN/GaN high electron mobility transistor (HEMT) is investigated by employing a localized Mg-doped layer under the two-dimensional electron gas (2-DEG) channel as an electric field shaping layer. The electric field strength around the gate edge is effectively relieved and the surface electric field is distributed evenly as compared with those of HEMTs with conventional source-connected field plate and double field plate structures with the same device physical dimensions. Compared with the HEMTs with conventional source-connected field plate and double field plate, the HEMT with Mg-doped layer also shows that the breakdown location shifts from the surface of the gate edge to the bulk Mg-doped layer edge. By optimizing both the length of Mg-doped layer, L_m, and the doping concentration, a 5.5 times and 3 times the reduction in the peak electric field near the drain side gate edge is observed as compared with those of the HEMTs with source-connected field plate structure and double field plate structure, respectively. In a device with V_GS=-5 V, L_m=1.5 μm, a peak Mg doping concentration of 8× 10¹⁷ cm^-3 and a drift region length of 10 μm, the breakdown voltage is observed to increase from 560 V in a conventional device without field plate structure to over 900 V without any area overhead penalty.     

Nano- and micro-structure tin (IV) complexes bearing 4-pyridinecarbacylamidophosphate: Sonochemical synthesis,crystal structure,anti-cholinesterase activity,and docking studies

Two di- and triorganotin (IV) complexes, Sn (CH₃)₂Cl₂(4-PCAPh)₂ ( C ₁ ) and Sn(C₆H₅)₃Cl(4-PCAPh) ( C ₂ ); {4-PCAPh = 4-NC₅H₄C(O)NHP(O)(C₆H₁₂N)₂}, have been synthesized and characterized by elemental analysis, ¹H, ¹³C, ³¹P NMR and IR spectroscopy. The crystal structure of C ₁ has been confirmed by X-ray crystallography, which reveals an octahedral geometry surrounding Sn (IV). Both ligands function in an all-trans conformation, with an N-ligated mode for 4-PCAPh. Also, the complexes were prepared at nano- ( Ć ₁ ) and micro-size ( Ć ₂ ) by the sonochemical process. The role of reaction solvent and the concentration of initial reactants on the size and morphology of particles were studied and the products were characterized by X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). The activities and mechanism of complexes C ₁ , C ₂ , Ć ₁ , Ć ₂ and their corresponding ligand ( L ) on cholinesterase (ChE) were evaluated using a modified Ellman's method and Lineweaver-Burk plots. Nanosheet Ć ₁ showed the best activity against AChE and BChE with the IC₅₀ values being 73.08 ± 0.12 μM and 122.48 ± 0.69 μM, respectively, and the mixed-type mechanism. Molecular modeling simulation revealed the binding interaction template for Sn (CH₃)₂Cl₂(4-PCAPh)₂ with the ChE.     

Synthesis,structural characterization,density functional theory calculations and biological evaluation of a new organotin(IV) complex containing N‐isonicotinyl‐N',N″‐diaryl phosphorictriamide as N‐donor ligand

A new diorganotin(IV) complex with the formula SnCl₂(CH₃)₂L₂ ( C_1a ), L = 4‐NC₅H₄CONHPO(NCH₃CH₂C₆H₅)₂, was synthesized and characterized using ¹H NMR, ¹³C NMR, ³¹P NMR, ¹¹⁹Sn NMR and infrared spectroscopies. The molecular structure of C_1a was determined using X‐ray crystallography, revealing that C_1a contains hexa‐coordinated Sn(IV) centres with trans‐configuration of donor atoms around them. Each Sn(IV) atom is positioned in the centre of inversion of an octahedron. C_1a forms one‐dimensional chains via two equal intermolecular P?O…H? N hydrogen bonds. These hydrogen bonds produce centrosymmetric rings as a supramolecular hydrogen‐bonded pattern. In order to compare the relative stability of C_1a (with N‐ligated configuration) and its possible O‐ligated isomer, C_1b , density functional theory calculations were performed, the results showing a preference of C_1a over C_1b from an energy point of view. Also, natural bond orbital analysis was carried out to obtain detailed information on the electronic features of the optimized structures. The theoretical results show that intermolecular hydrogen bonding in the crystal structure has a significant role in the stabilization of C_1a , and Sn(IV) interacts more strongly with the N_py atom than the P?O functional group. Furthermore, the free ligand and its complex were tested against three human cancer cell lines, i.e. human cervical carcinoma (HeLa), human prostate cancer (PC‐3) and human breast adenocarcinoma cancer (MCF‐7). C_1a displays moderate to good cytotoxicity towards all three cancer cell lines. Moreover, antibacterial tests were carried out using the disc‐diffusion method, in which C_1a shows high activity against selected Gram‐negative and Gram‐positive bacteria. Copyright © 2015 John Wiley & Sons, Ltd.     

Characterization of gelatin/cellulose acetate nanofibrous scaffolds: Prediction and optimization by response surface methodology and artificial neural networks

Gelatin/cellulose acetate electrospun nanofibers are a good candidates for simulation of extracellular matrix (ECM). Electrospinning of the blend is controlled by many parameters such as applied voltage, gap distance, solvent composition, polymer composition and solution concentration. The individual and interactive effects of these parameters on pH, electrical conductivity (EC) and viscosity of solutions, and diameter and quality of fibers were investigated. Response surface methodology (RSM) and artificial neural networks (ANNs) were considered to model and optimize the responses. EC, pH and viscosity of solutions were dependent on the solution parameters. The solvent composition and solution concentration had an influence on the fiber diameter and quality. The optimum conditions for fabricating qualified nanofibers with minimum diameter were 16.9 kV, 15.3 cm, 77.5 wt % of gelatin, 88.9 vol % of acetic acid and solution concentration of 20 wt %/vol %. Uniform beadless nanofibers with a diameter of 284 nm were attained at this optimum condition.