High Fraction of Penta‐Coordinated Aluminum and Gallium in Lanthanum–Aluminum–Gallium Borates

This study is focused on structural changes induced by increasing treatment temperature of sol‐gel–derived La₂O₃?Al₂O₃?Ga₂O₃?5B₂O₃ system. The structure of samples heated for 30 min up to 900°C was investigated by X‐ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and magic‐angle spinning nuclear magnetic resonance (MAS‐NMR) analysis of ²⁷Al, ¹¹B, and ⁷¹Ga nuclei. The vitreous structure is preserved inclusively after 800°C treatment, and starting with 850°C the only crystalline phase evidenced in XRD patterns is of LaAl_2.03B₄O_10.54 type, of La(Al,Ga)_2.03B₄O_10.54 composition. The FTIR results point out the presence of BO₃, AlO₄, and AlO₆, and starting with 800°C treatment also of BO₄ and AlO₅ structural units, but more detailed information related to boron, aluminum, and gallium environments is obtained from the analysis of MAS‐NMR data. These data evidenced in both amorphous xerogels and in crystallized samples a high fraction of penta‐coordinated aluminum and gallium.     

Gallium Trichloride‐Promoted Ethynylation Reaction of 1,4‐Dienes

Cyclopentadienes and silylated 1,4‐dienes were deprotonated with gallium trichloride (GaCl₃), and the resultant pentadienylgalliums underwent an ethynylation reaction with chlorosilylethyne. The silyl substituent on the olefin had an effect to increase the acidity of the allylic protons.     

Gallium Trichloride‐Catalyzed Exhaustive α‐Ethynylation Reaction of 1‐Silylacetylenes

Gallium trichloride (GaCl₃) catalyzes the ethynylation reaction of a 1,4‐enyne with chlorosilylacetylene at the propargyl position giving a triethynylvinylmethane. This catalytic method can be applied to the exhaustive α‐ethynylation of 1‐silylacetylenes possessing less acidic propargyl protons, and mono‐, di‐, and triethynylated products are obtained depending on the structure of the starting materials.     

Expanding the Applicability of the Metal Labeling of Biomolecules by the RIKEN Click Reaction: A Case Study with Gallium‐68 Positron Emission Tomography

Radiolabeled biomolecules with short half‐life times are of increasing importance for positron emission tomography (PET) imaging studies. Herein, we demonstrate an improved and generalized method for synthesizing a [radiometal]‐unsaturated aldehyde as a lysine‐labeling probe that can be easily conjugated into various biomolecules through the RIKEN click reaction. As a case study, ⁶⁸Ga‐PET imaging of U87MG xenografted mice is demonstrated by using the ⁶⁸Ga‐DOTA‐RGDyK peptide, which is selective to α_Vβ₃ integrins.     

Phosphorus‐Carbon Bond Formation: Palladium‐Catalyzed Cross‐Coupling of H‐Phosphinates and Other P(O)H‐Containing Compounds

Two generally applicable systems have been developed for the cross‐coupling of P(O)H compounds with C_sp2 X and related partners. Palladium catalysis using a ligand/additive combination, typically either xantphos/ethylene glycol or 1,1′‐bis(diphenylphosphino)ferrocene/1,2‐dimethoxyethane, with diisopropylethylamine as the base, proved to be generally useful for the synthesis of numerous P C containing compounds. Routinely, 2 mol% of catalyst are employed (less than half the amount typically employed in most other literature reports). In most cases, excellent results are obtained with a variety of electrophiles (RX, where R=alkenyl, allyl, alkynyl, etc.). The full account of our studies is disclosed, including tandem hydrophosphinylation/coupling and coupling/coupling for doubly catalytic phosphorus‐carbon bond formation. The methodology compares favorably with any existing literature report. The use of an additive appears to be a generally useful strategy to control the reactivity of phosphinylidene compounds.     

Elucidating the Catalytic Subunit Composition of Distinct Proteasome Subtypes: A Crosslinking Approach Employing Bifunctional Activity‐Based Probes

In addition to two well‐recognized proteasome subtypes—constitutive proteasomes and immunoproteasomes—mounting evidence also suggests the existence of intermediate proteasome subtypes containing unconventional mixtures of catalytic subunits. Although they appear to play unique biological roles, the lack of practical methods for detecting distinct proteasome subtypes has limited functional investigations. Here, we report the development of activity‐based probes that crosslink two catalytic subunits within intact proteasome complexes. Identification of the crosslinked subunit pairs provides direct evidence of the catalytic subunit composition of proteasomes. Using these probes, we found that U266 multiple myeloma cells contain intermediate proteasomes comprising both β1i and β2, but not β1 and β2i, consistent with previous findings with other cell types. Our bifunctional probes can be utilized in functional investigations of distinct proteasome subtypes in various biological settings.     

Fischer‐Tropsch Synthesis: Modeling and Performance Study for Fe‐HZSM5 Bifunctional Catalyst

A water‐cooled fixed bed Fischer‐Tropsch reactor packed with Fe‐HZSM5 catalyst has been modeled in two dimensions (radial and axial) using the intrinsic reaction rates previously developed at RIPI. The reactor is used for production of high‐octane gasoline from synthesis gas. The Fischer‐Tropsch synthesis reactor was a shell and tube type with high pressure boiling water circulating on the shell side. By the use of a two‐dimensional model, the effects of some important operating parameters such as cooling temperature, H₂/CO ratio in syngas and reactor tube diameter on the performance capability of the reactor were investigated. Based on these results, the optimum operating conditions and the tube specification were determined. The model has been used to estimate the optimum operating conditions for the pilot plant to be operated in RIPI.     

A Bifunctional Cinchona Alkaloid‐Squaramide Catalyst for the Highly Enantioselective Conjugate Addition of Thiols to trans‐Chalcones

A chiral squaramide catalysts‐promoted asymmetric sulfa‐Michael conjugated addition of thiols to trans‐chalcones is presented. Moderate to excellent yields and high enantioselectivities (up to 99% ee) were achieved under mild conditions.     

A Compact and Synthetically Accessible Fluorine‐18 Labelled Cyclooctyne Prosthetic Group for Labelling of Biomolecules by Copper‐Free Click Chemistry

A new fluorine‐containing azadibenzocyclooctyne (ADIBO‐F) was designed using a synthetically accessible pathway. The fluorine‐18 prosthetic group was prepared from its toluenesulfonate precursor and isolated in 21–35 % radiochemical yield in 30 minutes of synthetic time. ADIBO‐F has been incorporated into azide‐functionalized, cancer‐targeting peptides through a strain‐promoted alkyne–azide cycloaddition with high radiochemical yields and purities. The final products are novel peptide‐based positron emission tomography (PET) imaging agents that possess high affinities for their targets, growth hormone secretagogue receptor 1a (GHSR‐1a) and gastrin‐releasing peptide receptor (GRPR), with IC₅₀ values of 9.7 and 0.50 nm , respectively. This is a new and rapid labelling option for the incorporation of fluorine‐18 into biomolecules for PET imaging.     

A Tuneable Bifunctional Water‐Compatible Heterogeneous Catalyst for the Selective Aqueous Hydrogenation of Phenols

A water‐tolerant bifunctional heterogeneous catalyst is able to effectively catalyse the selective hydrogenation of phenol to cyclohexanone in water at atmospheric pressure and room temperature with >99.9% selectivity to cyclohexanone at phenol conversions >99.9%. The catalyst was found to be highly active and reusable, giving identical activities and selectivities after >5 uses. Moreover, this reported simple bifunctional catalyst is also able to hydrogenate a range of substituted phenols in high yields under the investigated aqueous conditions.     

Synthesis and Evaluation of Bombesin Analogues Conjugated to Two Different Triazolyl‐Derived Chelators for 99mTc Labeling

Overexpression of the gastrin‐releasing peptide receptor (GRPR) in a variety of human carcinomas has provided a means of diagnosis and treatment. Previously we reported a metabolically stable (N^αHis)Ac‐βAla‐βAla‐[Cha¹³,Nle¹⁴]BBS(7–14) analogue with high affinity for the GRPR. We have also shown that the biodistribution pattern of this fairly lipophilic, radiolabeled peptide can be enhanced by glycation, which is easily carried out by Cu^I‐catalyzed cycloaddition. Herein, we further elaborate this “click approach” in the synthesis of a new series of triazole‐based chelating systems as alternatives to the (N^αHis)Ac chelator for labeling with the ^99mTc(CO)₃ core. The bombesin analogues, containing these new chelating systems, were evaluated with regard to their synthesis and in vitro and in vivo properties, and were compared with their (N^αHis)Ac counterparts. The influence of the chelator on biodistribution properties was less than that of glycation, which clearly improved the tumor‐to‐background ratios.     

New Iron(II) Complexes for Atom‐Transfer Radical Polymerization: The Ligand Design for Triazacyclononane Results in High Reactivity and Catalyst Performance

Mononuclear cordinatively unsaturated iron(II) complexes having a triazacyclononane ligand were developed as highly efficient and environmentally friendly catalysts for the atom‐transfer radical polymerization (ATRP). These iron catalysts showed high performance in the well‐controlled ATRP of styrene, methacrylates, and acrylates. The high reactivity of these catalysts led to well‐controlled polymerization and block copolymerization even with lower catalyst concentrations.     

The Cyclic Cystine Ladder of Theta‐Defensins as a Stable,Bifunctional Scaffold: A Proof‐of‐Concept Study Using the Integrin‐Binding RGD Motif.

Peptides have the specificity and size required to target the protein–protein interactions involved in many diseases. Some cyclic peptides have been utilised as scaffolds for peptide drugs because of their stability; however, other cyclic peptide scaffolds remain to be explored. θ‐Defensins are cyclic peptides from mammals; they are characterised by a cyclic cystine ladder motif and have low haemolytic and cytotoxic activity. Here we demonstrate the potential of the cyclic cystine ladder as a scaffold for peptide drug design by introducing the integrin‐binding Arg‐Gly‐Asp (RGD) motif into the θ‐defensin RTD‐1. The most active analogue had an IC₅₀ of 18 nM for the α_vβ₃ integrin as well as high serum stability, thus demonstrating that a desired bioactivity can be imparted to the cyclic cystine ladder. This study highlights how θ‐defensins can provide a stable and conformationally restrained scaffold for bioactive epitopes in a β‐strand or turn conformation. Furthermore, the symmetry of the cyclic cystine ladder presents the opportunity to design peptides with dual bioactive epitopes to increase activity and specificity.     

Asymmetric Synthesis of Dihydrocoumarins Containing Contiguous Quaternary and Tertiary Stereogenic Centers Catalyzed by a Cinchona‐Alkaloid‐Based Bifunctional Thiourea Derivative

A series of enantiomerically enriched 3,4‐dihydrocoumarins containing contiguous quaternary and tertiary stereogenic centers has been efficiently constructed via domino asymmetric Michael addition/transesterification reactions of azlactones with o‐hydroxychalcones using a quinine‐derived thiourea as bifunctional organocatalyst. Under mild reaction conditions, the optically active 3,4‐dihydrocoumarins were generally obtained in 63–96% yields with >20:1 dr and 81–96% ee.

     

Bifunctional cellulose derivatives for the removal of heavy‐metal ions and phenols: Synthesis and adsorption studies

In this article, we report a study of the design and synthesis of a bifunctional cellulose derivative on the removal of phenols and heavy‐metal ions in wastewater treatment. A radical polymerization was performed in an ionic liquid, 1‐allyl‐3‐methylimidazolium chloride, to graft two monomers, butyl methacrylate and 4‐vinyl pyridine, on the backbone of cellulose. The effects of the five reaction conditions on the yield of final products were evaluated. The grafted celluloses were characterized by means of Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis. Adsorption experiments were carried out on the cellulose‐g‐poly(butyl methacrylate‐co‐4‐vinyl pyridine) to evaluate the capacity of the removal of 2,4‐dichlorophenol (2,4‐DCP) and Cu(II) in water. The adsorption isotherms were measured at five temperatures and interpreted by a Langmuir model of adsorption. The thermodynamics of the adsorption suggested that the binding process was mildly exothermic for Cu(II) and endothermic for 2,4‐DCP. Kinetic studies were interpreted with a pseudo‐second‐order adsorption model. The process of the adsorption of 2,4‐DCP could be described overall by the model, whereas the adsorption of Cu(II) involved two processes. This was due to adsorption both on the surface and inside the adsorbent. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41830.     

6‐Methyluracil Derivatives as Bifunctional Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease

Novel 6‐methyluracil derivatives with ω‐(substituted benzylethylamino)alkyl chains at the nitrogen atoms of the pyrimidine ring were designed and synthesized. The numbers of methylene groups in the alkyl chains were varied along with the electron‐withdrawing substituents on the benzyl rings. The compounds are mixed‐type reversible inhibitors of cholinesterases, and some of them show remarkable selectivity for human acetylcholinesterase (hAChE), with inhibitory potency in the nanomolar range, more than 10 000‐fold higher than that for human butyrylcholinesterase (hBuChE). Molecular modeling studies indicate that these compounds are bifunctional AChE inhibitors, spanning the enzyme active site gorge and binding to its peripheral anionic site (PAS). In vivo experiments show that the 6‐methyluracil derivatives are able to penetrate the blood–brain barrier (BBB), inhibiting brain‐tissue AChE. The most potent AChE inhibitor, 3 d (1,3‐bis[5‐(o‐nitrobenzylethylamino)pentyl]‐6‐methyluracil), was found to improve working memory in scopolamine and transgenic APP/PS1 murine models of Alzheimer's disease, and to significantly decrease the number and area of β‐amyloid peptide plaques in the brain.     

Bifunctional Metal Organic Framework Catalysts for Multistep Reactions: MOF‐Cu(BTC)‐[Pd] Catalyst for One‐Pot Heteroannulation of Acetylenic Compounds

A bifunctional metal organic framework catalyst containing palladium and copper(II) benzene‐1,3,5‐tricarboxylate – MOF‐Cu(BTC)‐[Pd] – has been prepared. This catalyst enables the performance of the tandem Sonogashira/click reaction starting from 2‐iodobenzylbromide, sodium azide and alkynes to produce 8H‐[1,2,3]triazolo[5,1‐a]isoindoles with good yields under mild reaction conditions.     

Bifunctional Catalysts Stabilized on Nanocrystalline Magnesium Oxide for One‐Pot Synthesis of Chiral Diols

New bifunctional catalysts composed of PdCl₄²⁻, OsO₄²⁻ and OsO₄²⁻, WO₄²⁻ designed and prepared by a counterionic stabilization technique involving the reactions of Na₂PdCl₄‐K₂OsO₄ and K₂OsO₄‐Na₂WO₄ with nanocrystalline MgO are well characterized. These bifunctional catalysts, NAP‐Mg‐PdOs and NAP‐Mg‐OsW perform tandem Heck asymmetric dihydroxylation and asymmetric dihydroxylation‐N‐oxidation reactions, respectively, in the presence of the chiral ligand 1,4‐bis(9‐o‐dihydroquinidinyl)phthalazine [(DHQD)₂PHAL] in a single pot. It is quite impressive to note that H₂O₂ is used as a terminal oxidant to provide N‐methylmorpholine N‐oxide (NMO) in situ by the oxidation of N‐methylmorpholine (NMM) in the asymmetric dihydroxylation‐N‐oxidation catalyzed by NAP‐Mg‐OsW.