Comparison of [18F]F-CNBI and [18F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice

Glycogen synthase kinase-3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood-brain barrier (BBB) permeable positron emission tomography (PET) probe for imaging of GSK-3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, [¹⁸F]F-CNBI and [¹⁸F]F-CNPIFE, and evaluated their BBB permeability and affinity towards GSK-3α/β. [¹⁹F]F-CNPIFE showed higher in-vitro binding towards GSK-3α/β (IC₅₀=19.4±2.5 nM; n=3, for GSK-3α, IC₅₀=19.4±3.8 nM; n=3, for GSK-3β) compared to [¹⁹F]F-CNBI (IC₅₀=107.6±26.0 nM; n=4, for GSK-3α, IC₅₀=105.3±18.2 nM; n=3, for GSK-3β). [¹⁸F]F-CNPIFE showed 9.5-fold higher brain uptake than [¹⁸F]F-CNBI, in normal FVB/NJ mice, which was increased by additional 1.5-fold on co-administration of [¹⁹F]F-CNPIFE with respect to [¹⁸F]F-CNBI. Overall, [¹⁸F]F-CNPIFE is a promising PET probe for GSK-3α/β imaging and warrants further evaluation in an AD mouse model.     

An efficient synthesis of enamides from ketones

A new synthesis of enamides from ketones is disclosed that involves a phosphine-mediated reductive acylation of oximes. The resulting enamides are isolated in good yields (up to 89%) and excellent purity, permitting a subsequent hydrogenation to access enantiopure acetamides at catalyst loadings practical for large-scale applications.     

Computational prediction and experimental evaluation of a photoinduced electron-transfer sensor

An approach is presented for the design of photoinduced electron-transfer-based sensors. The approach relies on the computational and theoretical prediction of electron-transfer kinetics based on Rehm-Weller and Marcus theories. The approach allows evaluation of the photophysical behavior of a prototype fluorescent probe/sensor prior to the synthesis of the molecule. As a proof of concept, a prototype sensor for divalent metal ions is evaluated computationally, synthesized, and then analyzed spectroscopically for its fluorescence response to zinc. Calculations predicted that the system would show a competition between electron transfer and fluorescence in the free state. In the zinc-bound state, the compound was predicted to be more highly fluorescent, due to the inhibition of electron transfer. Both predictions were confirmed experimentally. A nonzero fluorescence signal was observed in the absence of zinc and an enhancement was observed in the presence of zinc. Specifically, a 56-fold enhancement was observed over a 10-fold increase in zinc concentration.     

Synthesis of beta-hydroxysulfides from alkenes under supramolecular catalysis in the presence of beta-cyclodextrin in water

An environmentally benign and highly efficient procedure has been developed for the direct one-pot synthesis of beta-hydroxysulfides in good yields under neutral conditions from alkenes and thiophenols in the presence of aerial oxygen using beta-cyclodextrin in water. This protocol tolerates a wide variety of functional groups or substrates and does not require the use of either acid or base catalysts. beta-Cyclodextrin can be recovered and reused for a number of runs without any loss of activity.     

Supramolecular catalysis of Strecker reaction in water under neutral conditions in the presence of beta-cyclodextrin

An environmentally benign and highly efficient procedure for the nucleophilic addition of trimethylsilyl cyanide to imines (Strecker reaction) has been developed under biomimetic conditions in water in the presence of beta-cyclodextrin to afford alpha-aminonitriles in quantitative yields. The use of cyclodextrin precludes the use of either acid or base, and the catalyst can be recycled a number of times without loss in activity.     

Nickel(II) complexes of 5-phenyl and 5-furan-1,3,4-oxadiazole-2-thiones containing ethylenediamine: synthesis,spectral and X-ray characterization

The products obtained by the reactions of Ni(OAc)₂·4H₂O with Hpot (Hpot = 5-phenyl-1,3,4-oxadiazole-2-thione) and [K(H₂fchc)] (potassium N′-(furan-2-carbonyl) hydrazine carbodithioate), on treatment with excess of ethylenediamine (en), gave mixed ligand complexes [Ni(pot)₂(en)₂] (1) and [Ni(fot)₂(en)₂] (2) (fot = 5-furan-(1,3,4)-oxadiazole-2-thione). These complexes have been characterized with the aid of elemental analyses, IR, magnetic susceptibility and single crystal X-ray studies. In both complexes, the heterocyclic ligand coordinates through oxadiazole nitrogen, and the ligand exists as the thione form. The complexes 1 and 2 have distorted octahedral geometries around the centrosymmetric Ni(II) center with trans oxadiazole ligands. Both complexes show extended hydrogen bonding to give a supramolecular framework.     

Structural, optical and thermal studies of Eu ions in lithium fluoroborate glasses

Borate glasses doped with trivalent europium were prepared by the conventional melt quenching technique, in the chemical composition of (49.99-x)B₂O₃ + 25Li₂O + 25LiF+xEu₂O₃ by varying the concentration of the rare earth ion in the order 0.01, 0.1, 1, 2 and 3 wt% and their structural, luminescence and thermal behavior have been reported. The XRD and FTIR spectra reveal the glass structure and the functional groups. The UV–VIS, luminescence spectra and lifetime of the Eu³⁺ ions were measured. The local site symmetry around the Eu³⁺ ions were evaluated through the luminescence intensity ratio (R) of the ⁵D₀ → ⁷F₂ to ⁵D₀ → ⁷F₁ transitions. Optical measurements have been carried out to explore the optical properties such as bonding parameters, Judd–Ofelt parameters, stimulated emission cross-section, transition probability, branching ratio, radiative lifetime, etc. The lifetime measurements of the ⁵D₀ level as a function of the concentration of Eu³⁺ ion have been found and is comparable to other reported for Eu³⁺ doped borate, phosphate glasses and higher than that for the tellurite glasses. The thermal properties such as glass transition, crystallization and melting temperatures of the Eu³⁺ glasses were studied through the DSC traces in the temperature range of 30−1200 °C at a heating rate of 10 °C per minute. The change in optical properties with the variation of Eu³⁺ ion concentration have been discussed and compared with similar results.     

Neurotoxin (N-Oxalyl-L-α,β-Diamino Propionic Acid) Content in Different Plant Parts of Grass Pea (Lathyrus sativus L.) Spanning Seedling to Maturity Stage: Does It Increase over Time?

ODAP (N-oxalyl-L-2,3-diaminopropionic acid) is present in the seeds of grass pea. In this study, variation of total ODAP accumulation in leaves throughout the crop growth starting from 40 days after sowing to maturity, and the distribution pattern of ODAP in different plant parts including the seeds at the mature stage was analyzed. Five grass pea accessions were evaluated for two subsequent growing seasons in one location of ICARDA, Aleppo (Syria). The results found that the rate of accumulation of total ODAP varied during plant development. Increased rates of synthesis were noticed in young leaves of grass pea. The highest total ODAP content in leaves was noted in the early growth stage (40–50 days after sowing). Mean total ODAP content in leaves ranged from 0.17 to 0.96 percent during 2010–2011 and from 0.19 to 1.28 percent during 2011–2012. During maturity, the total ODAP content was lowest in the seeds than in leaves, stems, pod cover, seed coat, and cotyledons. The ranges of total ODAP content were 0.13 (seed)–0.34 (stem), 0.20 (seed)–1.01 (leaf), 0.22 (seed)–0.62 (leaf), 0.21 (seed)–0.66 (leaf), and 0.21 (seed)–0.78 (leaf) percent in B387, B222, B390, Bio-520, and B587 accessions, respectively, during maturity. The results indicated that the rate of accumulation and synthesis of total ODAP varied during the plant lifespan. The lowest total ODAP content of leaves was observed after 130 days of sowing. The lower total ODAP content after the early vegetative stage of grass pea plants makes them suitable as a feed.