Synthesis of monoalkylated calix[4]arenes via direct alkylation

A new one-step procedure for the synthesis of monoalkylated calix[4]arenes is presented. Reaction of calix[4]arene 1a or 1b with 1.2 equivalent of a weak base (K2CO3 in MeCN or CsF in DMF) and excess of alkylating agent affords the monoalkylated calix[4]arenes in moderate to good yield

Halogen-bonded architectures of multivalent calix[4]arenes

A small family of novel halogen-bonded crystalline supramolecular architectures of calixarenes was obtained by the co-crystallization of cone (1) and 1,3-alternate tetrakis(3-iodopropargyloxy)calix[4]arene (4) as tetradentate halogen donors with different multidentate acceptors. Particularly interesting is the interpenetrated diamondoid network of 4 with DABCO, which represents the first example of a 2D network of calixarene macrocycles where halogen bonding is the key interaction for self-organization

Calixarene-decorated liposomes for intracellular cargo delivery

Amphiphilic calix[4]arenes, functionalized with guanidinium groups, are used to decorate the outer surface of liposomes and significantly improve the cellular uptake of a cargo compared to plain liposomes. The improved uptake is elicited and mediated by the interaction between the cationic polar heads of the macrocycle units embedded in the liposome bilayer and anionic heparan-sulfate proteoglycans surrounding the exterior of cells

PdI2 as a simple and efficient catalyst for the hydroamination of arylacetylenes with anilines

The hydroamination reaction is a convenient alternative strategy for the formation of C– N bonds. Herein, we report a new versatile and convenient protocol for the hydroamination of arylacetylenes with anilines using palladium iodide in the absence of any added ligand as catalyst. Mild conditions, excellent regio-and stereoselectivity, and high functional group tolerance are the main features of this methodology. A subsequent reduction step gives access to a wide variety of secondary aromatic amines

Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as gene regulators by repressing translation or by inducing degradation of the target RNA transcripts. Altered expression of miRNAs may be involved in the pathogenesis of many severe human diseases, opening new avenues in the field of therapeutic strategies, i.e., miRNA targeting or miRNA mimicking. In this context, the efficient and non-toxic delivery of premiRNA and antimiRNA molecules might be of great interest. The aim of the present paper is to determine whether an argininocalix[4]arene is able to efficiently deliver miRNA, premiRNA, and antimiRNA molecules to target cells, preserving their biological activity. This study points out that (1) the toxicity of argininocalix[4]arene 1 is low, and it can be proposed for long-term treatment of target cells, being that this feature is a pre-requisite for the development of therapeutic protocols; (2) the delivery of premiRNA and antimiRNA molecules is efficient, being higher when compared with reference gold standards available; and (3) the biological activity of the premiRNAs and antimiRNAs is maintained. This was demonstrated using the argininocalix[4]arene 1 in miRNA therapeutic approaches performed on three well-described experimental model systems: (1) the induction of apoptosis by antimiR-221 in glioma U251 cells; (2) the induction of apoptosis by premiR-124 in U251 cells; and (3) the inhibition of pro-inflammatory IL-8 and IL-6 genes in cystic fibrosis IB3-1 cells. Our results demonstrate that the argininocalix[4]arene 1 should be considered a very useful delivery system for efficient transfer to target cells of both premiRNA and antimiRNA molecules, preserving their biological activity

Time Programmable Locking/Unlocking of the Calix[4]arene Scaffold by Means of Chemical Fuels

In this work, we report that 2-cyano-2-phenylpropanoic acid and its p-Cl, p-CH3 and p-OCH3 derivatives can be used as chemical fuels to control the geometry of the calix[4]arene scaffold in its cone conformation. It is shown that, under the action of the fuel, the cone calix[4]arene platform assumes a “locked” shape with two opposite aromatic rings strongly convergent and the other two strongly divergent (“pinched cone” conformation). Only when the fuel is exhausted, the cone calix[4]arene scaffold returns to its resting, “unlocked” shape. Remarkably, the duration of the “locked” state can be controlled at will by varying the fuel structure or amount. A kinetic study of the process shows that the consume of the fuel is catalyzed by the “unlocked” calixarene that behaves as an autocatalyst for its own production. A mechanism is proposed for the reaction of fuel consumption

Temporal Control of the Host-Guest Properties of a Calix[6]arene Receptor by the Use of a Chemical Fuel

The host-guest interaction of a 1,3,5-trisaminocalix[6]arene receptor with N-methylisoquinolinium trifluoromethanesulfonate (Kassof 500 ± 30 M-1in CD2Cl2) can be dissipatively driven by means of 2-cyano-2-(4′-chloro)phenylpropanoic acid used as a convenient chemical fuel. When the fuel is added to a dichloromethane solution containing the above complex, the host is induced to immediately release the guest in the bulk solution. Consumption of the fuel allows the guest to be re-uptaken by the host. The operation can be satisfactorily reiterated with four subsequent additions of fuel, producing four successive release-reuptake cycles. The percentage of the guest temporarily released in the bulk solution by the host and the time required for the reuptake process can be finely regulated by varying the quantities of added fuel

Liquid/Liquid Extraction Kinetics of Eu(III) and Am(III) by Extractants Designed for the Industrial Reprocessing of Nuclear Wastes

Results about the kinetics of extraction of Eu(III) and Am(III) by extractants designed for the industrial reprocessing of nuclear wastes are reported. They were obtained using the rotating membrane cell (RMC) technique. Extraction and stripping kinetic rate constants were determined for various compositions of the aqueous and organic phases. The transfer was studied at liquid/liquid interfaces between an aqueous nitric acid solution and an organic solvent containing the diglycolamide extractant molecule N,N,N′,N′-tetra-n-octyl-diglycolamide (TODGA) or a mixture of the bipyridine molecule CyMe4BTBP with TODGA (the latter being used as a phase-transfer catalyst), dissolved in an aliphatic diluent. In some experiments, an aqueous ligand (a sulfonated bis triazinyl pyridine, SO3-Ph-BTP, or a PyTri-diol) was added to the aqueous phase as a stripping agent. The diffusion coefficients of Eu(III) and Am(III), which are key in the analysis of the kinetic data, were measured using the RMC and the closed capillary technique. Whenever possible, mechanisms are proposed to interpret the experimental results

Unexpected Stereoselective Access to 2-Aminooxazolines from Propargyl Ureas by Silver Salts under Mild Conditions

Propargyl ureas can lead to a range of possible heterocyclic compounds, mainly depending on the employed catalyst. Silver salts are known to promote the N-5-exo-dig cyclization mode to imidazolidinone derivatives. Conversely, a versatile and stereoselective O-5-exo-dig cyclization of propargyl ureas to 2-aminooxazolines by Ag(I) catalysis is here disclosed. Good to excellent yields and complete stereoselectivity of the external double bond have been achieved under milder reaction conditions(50–60°C). A one-po protocol starting from the corresponding propargylic amines and isocyanates has been developed as well. N,N’-Dipropargyl ureas underwent a uncommon O-5-exo-dig/N-5-endo-dig double cyclization sequence. Finally, insights into the tautomeric equilibrium of 2-aminooxazoles and on their relative reactivity are provided

Reliability of voluntary step execution behavior under single and dual task conditions

<p>Abstract</p> <p>Background</p> <p>The current study investigated the repeatability (test-retest reliability) of ground reaction force parameters recorded during a voluntary step execution under single (motor task) and dual task (motor and cognitive task) conditions for healthy adults and elderly individuals as well as the number of trials required to produce repeatable results.</p> <p>Methods</p> <p>Twenty-four healthy adults (21–63 years old) and 16 elderly adults (66–87 years) performed a voluntary rapid step execution following a tap on their heel while standing on a force platform under single and dual task conditions on three separate occasions. The first two tests were performed 30–60 minutes apart and the third test was performed a week later. Variables analyzed from the ground reaction force data included onset latency of step initiation (initiation phase), preparation and swing phases, foot-off and foot-contact times.</p> <p>Results</p> <p>Intraclass correlation coefficients (ICC(2,1)) were good to excellent across all parameters and test conditions for the pooled population and for elderly (0.74–0.92 and 0.62–0.88, respectively) except for the swing phase duration where lower values were seen (0.54–0.60 and 0.32–0.64 respectively). Values were similar under single and dual task conditions.</p> <p>Conclusion</p> <p>A voluntary step execution test, performed under single and dual task conditions especially foot-off and foot-contact times, is a reliable outcome measure that may be a useful tool to asses dynamic balance function for diagnostic purposes as well as clinical intervention trials.</p