Liat Avram

Resorcinarenes are hexameric capsules in solution

The host–guest complexes of resorcin[4]arenes with small molecules in organic solutions are examined using modern NMR spectroscopic methods. The complexation of glutaric acid and β-methyl d-glucopyranoside in chloroform were investigated through 2D COSY, 2D NOESY, 1D NOE, and diffusion-ordered NMR spectroscopy (DOSY) techniques. These methods indicate that the complex is a self-assembled capsule composed of six resorcinarenes that surround six guest molecules of glutaric acid or three molecules of β-methyl d-glucopyranoside inside. The multiplicity of guest proton signals shows that the capsule provides an asymmetric magnetic environment that persists on the 1H NMR time scale. The encapsulation of these guests and common solvents suggests that the phenomenon of reversible encapsulation in chemistry may be a century old.

Manganese‐Catalyzed Hydrogenation of Esters to Alcohols

Homogeneous catalytic hydrogenation of esters to alcohols is an industrially important, environmentally benign reaction. While precious metal-based catalysts for this reaction are now well known, only very few catalysts based on first-row metal complexes were reported. Here we present the hydrogenation of esters catalyzed by a complex of earth-abundant manganese. The reaction proceeds under mild conditions and insight into the mechanism is provided based on an NMR study and the synthesis of novel Mn complexes postulated as intermediates.

The effect of the diffusion time and pulse gradient duration ratio on the diffraction pattern and the structural information estimated from q-space diffusion MR: Experiments and simulations

q-Space diffusion MRI (QSI) provides a means of obtaining microstructural information about porous materials and neuronal tissues from diffusion data. However, the accuracy of this structural information depends on experimental parameters used to collect the MR data. q-Space diffusion MR performed on clinical scanners is generally collected with relatively long diffusion gradient pulses, in which the gradient pulse duration, delta, is comparable to the diffusion time, Delta. In this study, we used phantoms, consisting of ensembles of microtubes, and mathematical models to assess the effect of the ratio of the diffusion time and the duration of the diffusion pulse gradient, i.e., Delta/delta, on the MR signal attenuation vs. q, and on the measured structural information extracted therefrom. We found that for Delta/delta approximately 1, the diffraction pattern obtained from q-space MR data are shallower than when the short gradient pulse (SGP) approximation is satisfied. For long delta the estimated compartment size is, as expected, smaller than the real size. Interestingly, for Delta/delta approximately 1 the diffraction peaks are shifted to even higher q-values, even when delta is kept constant, giving the impression that the restricted compartments are even smaller than they are. When phantoms composed of microtubes of different diameters are used, it is more difficult to estimate the diameter distribution in this regime. Excellent agreement is found between the experimental results and simulations that explicitly account for the use of long duration gradient pulses. Using such experimental data and this mathematical framework, one can estimate the true compartment dimensions when long and finite gradient pulses are used even when Delta/delta approximately 1.

Manganese-Catalyzed N-Formylation of Amines by Methanol Liberating H2: A Catalytic and Mechanistic Study

The first example of a base metal (manganese) catalyzed acceptorless dehydrogenative coupling of methanol and amines to form formamides is reported herein. The novel pincer complex (iPr-PNH P)Mn(H)(CO)2 catalyzes the reaction under mild conditions in the absence of any additives, bases, or hydrogen acceptors. Mechanistic insight based on the observation of an intermediate and DFT calculations is also provided.

Encapsulated or Not Encapsulated? Mapping Alcohol Sites in Hexameric Capsules of Resorcin[4]arenes in Solution by Diffusion NMR Spectroscopy

Noncovalent molecular capsules are labile and dynamic molecular species. Thus, the probing of their structure in solution is challenging, especially as the number of building units of the supramolecular system increases. Different noncovalent interactions have been used to construct such molecular capsules, among which hydrogen bonds have played a pivotal role. Hydrogen-bonded molecular capsules have been studied in the solid state, in solution, 4] and recently also in the gas phase. A decade ago, it was demonstrated that diffusion NMR spectroscopy is a useful tool for probing encapsulation in solution. Diffusion NMR spectroscopy revealed for example that the resorcin[4]arenes 1a,b self-assembled spontaneously in organic solvents

Three-dimensional water diffusion in impermeable cylindrical tubes: theory versus experiments.

Characterizing diffusion of gases and liquids within pores is important in understanding numerous transport processes and affects a wide range of practical applications. Previous measurements of the pulsed gradient stimulated echo (PGSTE) signal attenuation, E(q), of water within nerves and impermeable cylindrical microcapillary tubes showed it to be exquisitely sensitive to the orientation of the applied wave vector, q, with respect to the tube axis in the high‐q regime. Here, we provide a simple three‐dimensional model to explain this angular dependence by decomposing the average propagator, which describes the net displacement of water molecules, into components parallel and perpendicular to the tube wall, in which axial diffusion is free and radial diffusion is restricted. The model faithfully predicts the experimental data, not only the observed diffraction peaks in E(q) when the diffusion gradients are approximately normal to the tube wall, but their sudden disappearance when the gradient orientation possesses a small axial component. The model also successfully predicts the dependence of E(q) on gradient pulse duration and on gradient strength as well as tube inner diameter. To account for the deviation from the narrow pulse approximation in the PGSTE sequence, we use Callaghans matrix operator framework, which this study validates experimentally for the first time. We also show how to combine average propagators derived for classical one‐dimensional and two‐dimensional models of restricted diffusion (e.g. between plates, within cylinders) to construct composite three‐dimensional models of diffusion in complex media containing pores (e.g. rectangular prisms and/or capped cylinders) having a distribution of orientations, sizes, and aspect ratios. This three‐dimensional modeling framework should aid in describing diffusion in numerous biological systems and in a myriad of materials sciences applications. Copyright

Self-assembly of resorcin[4]arene in the presence of small alkylammonium guests in solution.

We followed the self-assembly of C-alkyl-resorcin[4]arene (1a,1b) in the presence of tetraethylammonium salts (2). The X-ray structure of C-ethyl-resorcin[4]arene (1c) in the presence of TEABr (2b), showed a dimer encapsulating one guest. However, diffusion measurements reveal that two molecules of tetraethylammonium are encapsulated within the hexameric capsule of 1a,b in chloroform, regardless of the anion. Most importantly, the anion affects the role of water in the self-assembly and the nature of the formed capsules.

Hydrogen-Bonded Hexameric Capsules of Resorcin[4]arene, Pyrogallol[4]arene and Octahydroxypyridine[4]arene are Abundant Structures in Organic Solvents: A View from Diffusion NMR

Hydrogen-bond molecular capsules have attracted much interest in the last decade. In the present paper, we wish to describe new insights obtained from diffusion NMR when studying the self-assembly of resorcin[4]arenes (2), pyrogallol[4]arenes (3) and octahydroxypyridine[4]arenes (4) in solution. These diffusion NMR studies demonstrate that compounds 2 and 3 self-assemble spontaneously into hexameric capsules in organic solvents. For compound 4, both hexameric capsules and dimeric aggregates were identified. Diffusion NMR was found to be very useful in evaluating the relative stability of these capsules as well as in determining the role played by water molecules in the self-assembly of such systems. Moreover, diffusion NMR enabled us to establish whether the self-assembly of these capsules proceeds with self-sorting. We could demonstrate that the hexamers of 3 are more stable than the hexameric capsules of 2 and that the formation of such hexamers proceeds with self-sorting and no hetero-hexamers are formed when macrocycles of different classes are mixed. The hexameric capsules of 2 were found to self-assemble with eight water molecules, whereas water molecules are not required for the formation of the hexameric capsules of 3. Diffusion NMR helped in demonstrating that many of the previously evoked 1:1 and 1:2 host–guest complexes of 2 are in fact hexamers encapsulating a multiplicity of guests. This supports the notion that hexameric capsules of these systems are much more abundant species in organic solvents than previously thought. These studies also demonstrate that diffusion NMR is an extremely useful tool for studying and characterising supramolecular systems and molecular capsules in solution.

Direct Synthesis of Amides by Dehydrogenative Coupling of Amines with either Alcohols or Esters: Manganese Pincer Complex as Catalyst

The first example of base-metal-catalysed synthesis of amides from the coupling of primary amines with either alcohols or esters is reported. The reactions are catalysed by a new manganese pincer complex and generate hydrogen gas as the sole byproduct, thus making the overall process atom-economical and sustainable.

Alginate-coated magnetic nanoparticles for noninvasive MRI of extracellular calcium.

Nanoparticles (NPs) have great potential to increase the diagnostic capacity of many imaging modalities. MRI is currently regarded as the method of choice for the imaging of deep tissues, and metal ions, such as calcium ions (Ca2+), are essential ingredients for life. Despite the tremendous importance of Ca2+ for the well‐being of living systems, the noninvasive determination of the changes in Ca2+ levels in general, and extracellular Ca2+ levels in particular, in deep tissues remains a challenge. Here, we describe the preparation and contrast mechanism of a flexible easy to prepare and selective superparamagnetic iron oxide (SPIO) NPs for the noninvasive determination of changes in extracellular Ca2+ levels using conventional MRI. We show that SPIO NPs coated with monodisperse and purified alginate, having a specific molecular weight, provide a tool to selectively determine Ca2+ concentrations in the range of 250 µm to 2.5 mm, even in the presence of competitive ions. The alginate‐coated magnetic NPs (MNPs) aggregate in the presence of Ca2+, which, in turn, affects the T2 relaxation of the water protons in their vicinity. The new alginate‐coated SPIO NP formulations, which have no effect on cell viability for 24 h, allow the detection of Ca2+ levels secreted from ischemic cell cultures and the qualitative examination of the change in extracellular Ca2+ levels in vivo. These results demonstrate that alginate‐coated MNPs can be used, at least qualitatively, as a platform for the noninvasive MRI determination of extracellular Ca2+ levels in myriad in vitro and in vivo biomedical applications. Copyright