Chiral organocatalysts based on lipopeptide micelles for aldol reactions in water.

A comprehensive study of the self-assembly in water of a lipopeptide consisting of a sequence of l-proline, l-arginine and l-tryptophan with a hydrocarbon chain has been performed. Fluorescence assays were used to determine the critical aggregation concentration. In situ small-angle X-ray scattering (SAXS) and molecular dynamics simulations showed the presence of spherical micelles with diameters around 6 nm. In agreement with these results, cryo-TEM images showed globular aggregates with diameters ranging from ≈4 nm up to ≈9 nm. Furthermore, the lipopeptide catalytic activity has been tested for the direct aldol reaction between cyclohexanone and p-nitrobenzaldehyde, and we have observed that the self-association of the organocatalyst played a critical role in the enhanced activity. Water affects the selectivity, and poor results are obtained under neat reaction conditions. The location of the catalytic groups at the lipopetide/water solvent interface also endowed unusual selectivity in the catalyzed aldol reactions. Under optimized reaction conditions, high yields (up to >99%), good enantioselectivity (ee up to 85%) and high diastereoselectivity (ds up to 92 : 8) were obtained.

Multifunctional biosensors based on peptide-polyelectrolyte conjugates.

A novel enzymatic platform for the sensing of H2O2 and glucose that uses L,L-diphenylalanine micro/nanostructures (FF-MNSs) as an enzyme support is shown. This platform is obtained by the self-assembly of poly(allylamine hydrochloride) (PAH), FF-MNSs, and microperoxidase-11 (MP11) anchored onto the peptide matrix, in two different crystal structures of FF-MNSs: hexagonal (P61) and orthorhombic (P22121). The electroactive area of the electrodes increases in the presence of FF-MNSs. We also demonstrate via theoretical calculations that the valence band energy of the orthorhombic structure allows it to be doped, similarly to p-type semiconductors, where PAH acts as a doping agent for the orthorhombic peptide structure, decreasing the band-gap by around 1 eV, which results in a smaller charge transfer resistance. These results are consistent with electrochemical impedance spectroscopy measurements, which further elucidate the role of the band structure of the orthorhombic FF-MNSs in the conductivity and electron transfer rates of the hybrid material. An effective communication between the electrode and the active site of a glucose oxidase enzyme through MP11-protein complexes occurs, paving the way for FF-MNSs in the orthorhombic phase for the future development of bioelectronics sensing devices.

Polycaprolactone fibers with self-assembled peptide micro/nanotubes: a practical route towards enhanced mechanical strength and drug delivery applications.

Peptide-based scaffolds are a frontier research area in materials science with widespread impact in biomedical engineering. In this paper, we describe a hybrid material formulated through the conjugation of electrospun polycaprolactone (PCL) fibers and micro/nanotubes of l,l-diphenylalanine (FF-MNTs). Morphology and crystallinity of the composite matrices are investigated using a wide range of analytical techniques including electron microscopy, thermal analyses, X-ray diffraction and micro-tomography. Peptide assemblies are found to produce deep modifications on the microstructure of PCL fibers, impacting average diameters, crystallinity degree and porous size in the polymer network. These changes are correlated with mechanical properties of the resulting scaffolds, whose strength is found to exhibit a brittle-to-ductile transition upon increasing the amount of FF-MNTs and lead to enhanced Young's moduli of polymer fibers. The PCL/FF-MNTs composites were tested for the drug delivery application of a lipophilic drug, benzocaine. In vitro permeation studies have shown that these polymer/peptide hybrids are able to produce a steady release of benzocaine over periods of up to ∼13 hours, much higher than commercially available gel formulations. Enzymatic tests have shown a significant increment in biodegradation rates in PCL/FF-MNTs hybrids containing higher peptide amounts, which exhibited almost 100% weight loss against only 10% found in pure PCL. Our findings indicate that using PCL/FF-MNTs materials is a simple route towards achieving enhanced mechanical strength of PCL networks that have the ability to promote controlled drug delivery from a completely biodegradable matrix.

Relaxation dynamics of deeply supercooled confined water in L,L-diphenylalanine micro/nanotubes.

The temperature dependence (10-290 K) of the low-frequency (20-150 cm(-1)) Raman-active phonon modes of deeply supercooled confined water in L,L-diphenylalanine micro/nanotubes was analyzed. The isolated dynamics of a specific geometry of a water cluster (pentamer) in a supercooled confined regime was studied in detail. A fragile-to-strong transition at 204 K was observed and related to the crossing of the Widom line. Analysis of peptide vibrational modes coupled to water hydrogen bonds indicated that hydrogen bond fluctuations play an irrelevant role in this system. Our results are in agreement with the second critical point of water existence hypothesis.

Mimics of copper proteins: structural and functional aspects.

The importance of copper as an essential element can be estimated by the wide range of copper proteins and enzymes playing different roles in biological systems. In the last decades many bioinorganic studies were developed on mimetic complexes of copper-dependent proteins, in order to verify the interrelations between structural and functional properties of active copper centers. Among the most studied copper ion ligand, diimine compounds have deserved special attention due their flexibility, facility of preparation, and ability to stabilize both oxidation states of this metal. In our laboratory, we have been investigating some Schiff base copper complexes as mimics of different proteins, with emphasis on functional aspects, trying to elucidate mechanisms of reaction, based on proposed intermediary species, in addition to molecular shapes. Particularly, mimics of the copper-zinc superoxide dismutase, and of monooxigenases and oxidases exhibiting dicopper sites are discussed in this work.

Ethical considerations in neuroclinical trials.

Ethical decision making in clinical trials has become increasingly emphasized at many levels of the review process. Ethical concepts applicable to Neuroclinical Trials (NCT) are reviewed. The discussion is directed towards ethical concerns that investigators must consider and justify prior to Institutional Review Board (IRB) submission. Risk-benefit analysis, methodology (randomization: placebo; design) and consent (informed; deferred; waived) are reviewed and Office for Protection from Research Risk (OPRR) guidelines are described. Our conclusions: Investigators proposing NCT face increasing ethical scrutiny by IRBs. Attention to ethical issues early in trial planning process is recommended.

Ethical considerations in clinical neuroscience. Current concepts in neuroclinical trials.

BACKGROUND: Ethical decision making in clinical trials has become increasingly emphasized at many levels of the review process. SUMMARY OF REVIEW: Ethical concepts applicable to neuroclinical trials are reviewed. The discussion is directed toward ethical concerns that investigators must consider and justify prior to institutional review board submission. Risk-benefit analysis, methodology (randomization, placebo, design), and consent (informed, deferred, waived) are reviewed and guidelines of the Office for Protection From Research Risk are described. CONCLUSIONS: Investigators proposing neuroclinical trials face increasing ethical scrutiny by institutional review boards. Attention to ethical issues early in the trial planning process is recommended.