Biomedical subjects

Liat Avram

Publications and source records attributed to Liat Avram.

13 recordsLinked to original sources

PubMed2006

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 beta-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 beta-methyl d-glucopyranoside inside. The multiplicity of guest proton signals shows that the capsule provides an asymmetric magnetic environment that persists on the (1)H 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.

Calixarenes↗

PubMed2006

Molecules at close range: encapsulated solvent molecules in pyrogallol[4]arene hexameric capsules.

[reaction: see text] Pyrogallol[4]arenes form hexameric capsules with a large cavity and can be regarded as nanoreactors. The (1)H NMR signals of the encapsulated chloroform and benzene molecules are very complex, which may indicate that these encapsulated molecules are trapped in slightly different capsules. Co-encapsulation was found to be favored, and the ASIS effect was found to be enhanced, probably due to the close proximity and the higher molecular fraction of the benzene/chloroform complex in the capsule.

Journal Article↗

PubMed2005

Diffusion measurements for molecular capsules: pulse sequences effect on water signal decay.

Diffusion NMR and, more recently, diffusion ordered spectroscopy (DOSY) are gaining popularity as efficient tools for the characterization of supramolecular systems in solution. Here, using diffusion NMR of hydrogen-bond molecular capsules, we demonstrate that the use of different diffusion sequences may have a dramatic effect on exchanging peaks. In fact, we found that the signal decay of the water peak in [(1a)(6)(H(2)O)(8)] is monoexponential in the pulsed gradient spin-echo (PGSE) and stimulated echo (PGSTE) sequences and biexponential in the longitudinal eddy current delay (LED) and the bipolar longitudinal eddy current delay (BPLED) sequences, routinely used in modern DOSY experiments. By performing these diffusion measurements on molecular capsules, in which water is not part of the molecular capsules, we demonstrate that this phenomenon is observed only for water molecules that exchange between two sites that differ considerably in their diffusion coefficients. Degeneration of the LED or the BPLED sequences into PGSTE-type sequences by shortening the te period resulted in the disappearance of the extra slow diffusing component. The origin, as well as the implications of the different results obtained from conventional diffusion sequences, such as the PGSE and PGSTE as compared with the LED and BPLED sequences generally used in DOSY experiments, are briefly discussed.

Diffusion↗

PubMed2005

Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry: an old parameter--new insights.

Intermolecular interactions in solution play an important role in molecular recognition, which lies at the heart of supramolecular and combinatorial chemistry. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for simultaneously measuring diffusion coefficients of multicomponent systems. The diffusion coefficient reflects the effective size and shape of a molecular species. Applications of this technique include the estimation of association constants and mapping the intermolecular interactions in multicomponent systems as well as investigating aggregation, ion pairing, encapsulation, and the size and structure of labile systems. Diffusion NMR spectroscopy can also be used to virtually separate mixtures and screen for specific ligands of different receptors, and may assist in finding lead compounds.

Combinatorial Chemistry Techniques↗

PubMed2004

Self-recognition, structure, stability, and guest affinity of pyrogallol[4]arene and resorcin[4]arene capsules in solution.

In the present study, we used diffusion NMR to probe the structures and characteristics of the products obtained from the self-assembly of resorcin[4]arenes 1a and 1b and pyrogallol[4]arenes 2a and 2b in CDCl(3) solutions. It was found that all four molecules self-assemble into hexameric capsules. The hexameric capsules of pyrogallol[4]arenes 2a and 2b were found to be more stable than the capsules of resorcin[4]arenes 1a and 1b in polar media. We also studied the role of water molecules in the self-assembly of the different capsules and found that water molecules are part of the hexameric capsules of resorcin[4]arenes 1a and 1b but not in the capsules of pyrogallol[4]arenes 2a and 2b. It was found that the self-assembly process between the resorcin[4]arenes and pyrogallol[4]arenes proceeds with self-recognition. When mixing two macrocycles of different types in a chloroform solution, no heterohexamers are formed, only the capsule constructed from the same macrocycle is detected. However, when two resorcin[4]arenes (i.e., 1a and 1b) or two pyrogallol[4]arenes (i.e., 2a and 2b) are mixed, heterohexamers are formed over time. In addition, we found that resorcin[4]arenes and pyrogallol[4]arenes differ significantly in their guest affinity. The capsules of 1a and 1b can accommodate both the tertiary alkylamines and their respective ammonium salts, while the capsules of 2a and 2b encapsulate only the neutral tertiary alkylamines.

Journal Article↗

PubMed2004

The effect of rotational angle and experimental parameters on the diffraction patterns and micro-structural information obtained from q-space diffusion NMR: implication for diffusion in white matter fibers.

Diffusion NMR may provide, under certain experimental conditions, micro-structural information about confined compartments totally non-invasively. The influence of the rotational angle, the pulse gradient length and the diffusion time on the diffusion diffraction patterns and q-space displacement distribution profiles was evaluated for ensembles of long cylinders having a diameter of 9 and 20 microm. It was found that the diffraction patterns are sensitive to the rotational angle (alpha) and are observed only when diffusion is measured nearly perpendicular to the long axis of the cylinders i.e., when alpha= 90 degrees +/- 5 degrees under our experimental conditions. More importantly, we also found that the structural information extracted from the displacement distribution profiles and from the diffraction patterns are very similar and in good agreement with the experimental values for cylinders of 20 microm or even 9 microm, when data is acquired with parameters that satisfy the short gradient pulse (SGP) approximation (i.e., delta -->0) and the long diffusion time limit. Since these experimental conditions are hardly met in in vitro diffusion MRI of excised organs, and cannot be met in clinical MRI scanners, we evaluated the effect of the pulse gradient duration and the diffusion time on the structural information extracted from q-space diffusion MR experiments. Indeed it was found that, as expected, accurate structural information, and diffraction patterns are observed when Delta is large enough so that the spins reach the cylinders' boundaries. In addition, it was found that large delta results in extraction of a compartment size, which is smaller than the real one. The relevance of these results to q-space MRI of neuronal tissues and fiber tracking is discussed.

Diffusion Magnetic Resonance Imaging↗

PubMed2003

Discrimination of guests encapsulation in large hexameric molecular capsules in solution: pyrogallol[4]arene versus resorcin[4]arene capsules.

NMR experiments demonstrate that, although 2b and 3b form hexameric capsules in chloroform solutions and despite the very similar building units of these hexamers, 3b encapsulates only the noncharged trialkylamines while 2b can encapsulate both the noncharged trialkylamines and the respective ammonium salts obtained by the addition of DCl. In fact, it was found that protonation that forms in situ the ammonium salt ejects the guest from the hexameric capsule of 3b. This is a general observation as it was found for guests containing alkyl chains of four, five, six, and eight carbons.

Journal Article↗

PubMed2003

Hexameric capsules of lipophilic pyrogallolarene and resorcinarene in solutions as probed by diffusion NMR: one hydroxyl makes the difference.

[reaction: see text] NMR diffusion measurements were used to characterize the self-assembled molecular capsule of pyrogallolarene 2c in CDCl(3) solutions. The results were compared with the characteristics of the hexameric capsule of 1b. Although both 2c and 1b self-assemble into hexameric capsules, the role of water in these capsules is rather different. It was also found that the capsule of 2c is more stable in polar media than that of 1b.

Journal Article↗

PubMed2003

Effect of a cationic guest on the characteristics of the molecular capsule of resorcinarene: a diffusion NMR study.

[reaction: see text] NMR diffusion measurements were used to probe the differences in the characteristics of the hexameric capsule of [c]-undecane resorcin[4]arene (1b) in a CDCl(3) solution in the absence and presence of tetrahexylammonium bromide (THABr). It was found that the nonencapsulated THABr forms a 1:1 complex with 1b, which is in fast exchange with its constituents. We found that water molecules seem not to participate in the construction of the THABr hexameric capsule of 1b in a CDCl(3) solution, in contrast to the finding in the absence of THABr, where the major species in CDCl(3) seems to be [(1b)(6)(H(2)O)(8)].

Journal Article↗

PubMed2002

Spontaneous formation of hexameric resorcinarene capsule in chloroform solution as detected by diffusion NMR.

NMR diffusion measurements provide unequivocal proof that the resorcinarene 1b self-assembles spontaneously into a stable hexamer capsule in chloroform solution by encapsulating several chloroform molecules, which occupy different chemical positions. Although the affinity of tetrahexylammonium bromide (2a) toward the cavity of the hexamer is much higher than that of the chloroform molecules, it was found that the same amount of DMSO is needed to disrupt the two hexamers, thus suggesting similar stabilities for these two supramolecular capsules.

Journal Article↗

PubMed2002

The role of water molecules in a resorcinarene capsule as probed by NMR diffusion measurements.

[structure: see text] NMR diffusion measurements were used to probe the role of water molecules in a resorcinarene capsule in a CDCl(3) solution. It was found that the water/resorcinarene ratio affects both the chemical shift and the diffusion coefficient of the water molecules. From the NMR diffusion measurements we could conclude that the major species in the chloroform solution is the hexamer having eight water molecules that are in fast exchange, on the NMR time scale, with the bulk water.

Calixarenes↗

PubMed2002

Self-assembled, helically stacked anionic aggregates of 2,5,8,11-tetra-tert-butylcycloocta[1,2,3,4-def;5,6,7,8-d'e'f']bisbiphenylene, stabilized by electrostatic interactions.

Tetraanions of alkyl-substituted derivatives of cycloocta[1,2,3,4-def;5,6,7,8-d'e'f']bisbiphenylene (BPD) and their counter lithium cations self-assemble to form helically stacked assemblies, including a dimer, a trimer, and a tetramer. NMR self-diffusion measurements and unprecedented magnetic shielding effects for the sandwiched lithium cations support their aggregated nature. The D(2)-tetramer assembly is fully characterized by NMR spectroscopy, providing unequivocal evidence for a helix of four tetraanionic BPD layers with an estimated relative twist angle of about 45 degrees and interlayer spacing of ca. 4 A. The barrier for racemization through the in-plane inter-deck rotation is DeltaG(200)= 9.5 +/- 0.2 kcal mol(-1) in the dimer compared to >15 kcal mol(-1) in the tetramer.

Journal Article↗

PubMed2002

Complexation in pseudorotaxanes based on alpha-cyclodextrin and different alpha,omega-diaminoalkanes by NMR diffusion measurements.

The interactions of 1,4-diaminobutane (1), 1,6-diaminohexane (2), 1,8-diaminooctane (3), 1,10-diaminodecane (4), and 1,12-diaminododecane (5) with alpha-cyclodextrin (alpha-CD) were studied in aqueous solutions by NMR diffusion measurements before and after protonation. The correlation between the association constant and the length of the alkyl chain of the diamine unit was studied. The assumption that protonation on the amino groups can be used as a stopper and, as a result, to convert the pseudorotaxanes into rotaxanes was tested. In addition, other factors that can affect the pseudorotaxane stability, such as the effects of temperature, were tested. On the basis of these measurements, the following conclusions could be reached: (1) The association constant increases with the increase in the alkyl chain length. (2) For the salts (2b-5b), both in neutral and in acidic solutions, the binding constants increase as the number of CH(2) units increases. (3) The association constants of the complexes of the diaminoalkane salts and alpha-CD are lower than those of the corresponding neutral diaminoalkanes. (4) This difference between the binding constants of the diaminoalkanes and their respective salts decreases as the chain length increases. (5) By examining the effects of temperature on the (1)H NMR spectra, it was found that after addition of DCl the energy barrier for the threading-dethreading process of the salt of 5a is larger than that for the salt of 4a.

Alkanes↗