Mechanism of Al(III)-catalyzed transamidation of unactivated secondary carboxamides

The carbon-nitrogen bond of secondary carboxamides is generally thermodynamically and kinetically unreactive; however, we recently discovered that the trisamidoaluminum(III) dimer Al2(NMe2)6 catalyzes facile transamidation between simple secondary carboxamides and primary amines under moderate conditions. The present report describes kinetic and spectroscopic studies that illuminate the mechanism of this unusual transformation. The catalytic reaction exhibits a bimolecular rate law with a first-order dependence on the Al(III) and amine concentrations. No rate dependence on the carboxamide concentration is observed. Spectroscopic studies (1H and 13C NMR, FTIR) support a catalyst resting state that consists of a mixture of tris-(kappa2-amidate)aluminum(III) complexes. These results, together with the presence of a significant kinetic isotope effect when deuterated amine substrate (RND2) is used, implicate a mechanism in which the amine undergoes preequilibrium coordination to aluminum and proton transfer to a kappa2-amidate ligand to yield an Al(kappa2-amidate)2(kappa1-carboxamide)(NHR) complex, followed by rate-limiting intramolecular delivery of the amido ligand (NHR) to the neutral Al(III)-activated kappa1-carboxamide. Noteworthy in this mechanism is the bifunctional character of Al(III), which is capable of activating both the amine nucleophile and the carboxamide electrophile in the reaction.     

Insights into brain microstructure from the T2 distribution

T2 weighting is particularly sensitive, but notoriously unspecific, to a wide range of brain pathologies. However, careful measurement and analysis of the T2 decay curve from brain tissue promise to provide much improved pathological specificity. In vivo T2 measurement requires accurate 180 pulses and appropriate manipulation of stimulated echoes; the most common approach is to acquire multiple echoes from a single slice. The T2 distribution, a plot of component amplitude as a function of T2, can be estimated using an algorithm capable of fitting a multi-exponential T2 decay with no a priori assumptions about the number of exponential components. T2 distributions from normal brain show peaks from myelin water, intra/extracellular water and cerebral spinal fluid; they can be used to provide estimates of total water content (total area under the T2 distribution) and myelin water fraction (MWF, fractional area under the myelin water peak), a measure believed to be related to myelin content. Experiments on bovine brain suggest that magnetization exchange between water pools plays a minor role in the T2 distribution. Different white matter structures have different MWFs. In normal white matter (NWM), MWF is not correlated with the magnetization transfer ratio (MTR) or the diffusion tensor fractional anisotropy (FA); hence it provides unique information about brain microstructure. Normal-appearing white matter (NAWM) in multiple sclerosis (MS) brain possesses a higher water content and lower MWF than controls, consistent with histopathological findings. Multiple sclerosis lesions demonstrate great heterogeneity in MWF, presumably due to varying myelin contents of these focal regions of pathology. Subjects with schizophrenia were found to have significantly reduced MWF in the minor forceps and genu of the corpus callosum when compared to controls, suggesting that reduced frontal lobe myelination plays a role in schizophrenia. In normal controls, frontal lobe myelination was positively correlated with both age and education; this result was not observed in subjects with schizophrenia. A strong correlation between MWF and the optical density from the luxol fast blue histological stain for myelin was observed in formalin-fixed brain, supporting the use of the MWF as an in vivo myelin marker.     

Helical peptoid mimics of lung surfactant protein C

Among the families of peptidomimetic foldamers under development as novel biomaterials and therapeutics, poly-N-substituted glycines (peptoids) with alpha-chiral side chains are of particular interest for their ability to adopt stable, helical secondary structure in organic and aqueous solution. Here, we show that a peptoid 22-mer with a biomimetic sequence of side chains and an amphipathic, helical secondary structure acts as an excellent mimic of surfactant protein C (SP-C), a small protein that plays an important role in surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome. When integrated into a lipid film, the helical peptoid SP mimic captures the essential surface-active behaviors of the natural protein. This work provides an example of how an abiological oligomer that closely mimics both the hydrophobic/polar sequence patterning and the fold of a natural protein can also mimic its biophysical function.     

Network formation and photoluminescence in copper(i) halide complexes with substituted piperazine ligands

The synthesis, X-ray structures and photophysics of ten complexes of CuX (X = I or Br) with bridging N-substituted and N,N'-disubstituted piperazines (Pip) are presented. Depending on the steric demand of the Pip substituents, the complexes fall into four categories: (CuX)(4)(Pip)(2), which are networks of linked Cu(4)X(4) cubane units, (CuX)(2)(Pip), which are chains of linked Cu(2)X(2) rhombs, and (CuX)(2)(Pip)(2) or (CuX)(4)(Pip)(4), which are simple rhomboid dimers and cubane tetramers. A combination of spectroscopic studies and DFT calculations was used to investigate the luminescence of the products. The results suggest that the relatively high energy emission seen in dimers is due to cluster-centred (XMLT/metal-centred) excitations for the aliphatic amines and MLCT (d →π*) for aromatic amines, and low energy emission seen in the tetramers is the result of cluster-centred transitions. The (CuI)(2)(Pip) complexes act as sensor materials, undergoing irreversible reaction with aliphatic and aromatic amines (Nu) in the vapour state, irreversibly producing cubanes (CuI)(4)Nu(4), with corresponding production of long wavelength emission.     

A Universality Property of Gaussian Analytic Functions

We consider random analytic functions defined on the unit disk of the complex plane f(z) = ?_n=0^￥ a_n X_n zⁿf(z) = \sum_{n=0}^{\infty} a_{n} X_{n} z^{n}, where the X _n ’s are i.i.d., complex-valued random variables with mean zero and unit variance. The coefficients a _n are chosen so that f(z) is defined on a domain of ℂ carrying a planar or hyperbolic geometry, and Ef(z)[`(f(w))]\mathbf{E}f(z)\overline{f(w)} is covariant with respect to the isometry group. The corresponding Gaussian analytic functions have been much studied, and their zero sets have been considered in detail in a monograph by Hough, Krishnapur, Peres, and Virág. We show that for non-Gaussian coefficients, the zero set converges in distribution to that of the Gaussian analytic functions as one transports isometrically to the boundary of the domain. The proof is elementary and general.     

Comparison of CID, ETD and metastable atom-activated dissociation (MAD) of doubly and triply charged phosphorylated tau peptides

The fragmentation behavior of the 2+ and 3+ charge states of eleven different phosphorylated tau peptides was studied using collision-induced dissociation (CID), electron transfer dissociation (ETD) and metastable atom-activated dissociation (MAD). The synthetic peptides studied contain up to two known phosphorylation sites on serine or threonine residues, at least two basic residues, and between four and eight potential sites of phosphorylation. CID produced mainly b-/y-type ions with abundant neutral losses of the phosphorylation modification. ETD produced c-/z-type ions in highest abundance but also showed numerous y-type ions at a frequency about 50% that of the z-type ions. The major peaks observed in the ETD spectra correspond to the charge-reduced product ions and small neutral losses from the charge-reduced peaks. ETD of the 2+ charge state of each peptide generally produced fewer backbone cleavages than the 3+ charge state, consistent with previous reports. Regardless of charge state, MAD achieved more extensive backbone cleavage than CID or ETD, while retaining the modification(s) in most cases. In all but one case, unambiguous modification site determination was achieved with MAD. MAD produced 15-20% better sequence coverage than CID and ETD for both the 2+ and 3+ charge states and very different fragmentation products indicating that the mechanism of fragmentation in MAD is unique and complementary to CID and ETD.     

Preparation,surface state and band structure studies of SrTi(1 − x)Fe(x)O(3 − δ) (x = 0–1) perovskite-type nano structure by X-ray and ultraviolet photoelectron spectroscopy

In this report, SrTi_(1 ? x)Fe_(x)O_(3 ? δ) photocatalyst powder was synthesized by a high temperature solid state reaction method. The morphology, crystalline structures of obtained samples, was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM), respectively. The electronic properties and local structure of the perovskite STF_x (0 ≤ x ≤ 1) systems have been probed by extended X-ray absorption fine structure (EXAFS) spectroscopy. The effects of iron doping level x (x = 0–1) on the crystal structure and chemical state of the STF_x have been investigated by X-ray photoelectron spectroscopy and the valence band edges for electronic band gaps were obtained for STF_x by ultraviolet photoelectron spectroscopy (UPS). A single cubic perovskite phase of STF_x oxide was successfully obtained at 1200 °C for 24 h by the solid state reaction method. The XPS results showed that the iron present in the STF_x perovskite structure is composed of a mixture of Fe³⁺ and Fe⁴⁺ (SrTi_(1 ? x)[Fe³⁺, Fe⁴⁺]_(x)O_(3 ? δ)). When the content x of iron doping was increased, the amount of Fe³⁺ and Fe⁴⁺ increased significantly and the oxygen lattice decreased on the surface of STF_x oxide. The UPS data has confirmed that with more substitution of iron, the position of the valence band decreased.     

Adsorption of polyelectrolyte modified graphene to silica surfaces: monolayers and multilayers

Exfoliated graphene particles stabilised by the cationic polyelectrolyte polyethyleneimine (PEI) were used in conjunction with an anionic polyelectrolyte, poly(acrylic acid), to construct multilayers using the layer-by-layer technique on a silica substrate. In the first adsorption step, the surface excess of the cationic graphene was dependent on the overall charge on the nanoparticle which in turn can be tuned through modifying solution pH as PEI has weakly ionisable charged amine groups. The adsorbed amount onto the silica surface increased as the solution pH increased. Subsequently, a layer of PAA was adsorbed on top of the cationic graphene through electrostatic interaction. The multilayer could be assembled through this alternate deposition, with the influence of solution conditions investigated. The pH of the adsorbing solutions was the chief determinant of the overall adsorbed amounts, with more mass added at the elevated pH of 9 in comparison with pH 4. Atomic force microscopy confirmed that the graphene particles were adsorbed to the silica interface and that the surface coverage of the disc-like nanoparticles was complete after the deposition of five graphene-polyelectrolyte bi-layers. Furthermore, the graphene nanoparticles themselves could be modified through the consecutive addition of the oppositely charged polymers. A multilayered assembly of negatively charged graphene sheets modified with a bi-layer of PEI and PAA was also deposited on a silica surface with adsorbed PEI.     

Role of reversible dimerization in reactions of amphoteric aziridine aldehydes

Unprotected aziridine aldehydes belong to the amphoteric class of molecules by virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of these molecules, brought together by a weak and reversible aminal "connection", was found to be an important element of reactivity control. We present evidence that reversible dimer dissociation is instrumental in aziridine aldehyde transformations. We anticipate further developments that will unveil other synthetic consequences of remote control of selectivity through forging reversible covalent interactions.     

Comparison of CID,ETD and metastable atom‐activated dissociation (MAD) of doubly and triply charged phosphorylated tau peptides

The fragmentation behavior of the 2+ and 3+ charge states of eleven different phosphorylated tau peptides was studied using collision‐induced dissociation (CID), electron transfer dissociation (ETD) and metastable atom‐activated dissociation (MAD). The synthetic peptides studied contain up to two known phosphorylation sites on serine or threonine residues, at least two basic residues, and between four and eight potential sites of phosphorylation. CID produced mainly b‐/y‐type ions with abundant neutral losses of the phosphorylation modification. ETD produced c‐/z‐type ions in highest abundance but also showed numerous y‐type ions at a frequency about 50% that of the z‐type ions. The major peaks observed in the ETD spectra correspond to the charge‐reduced product ions and small neutral losses from the charge‐reduced peaks. ETD of the 2+ charge state of each peptide generally produced fewer backbone cleavages than the 3+ charge state, consistent with previous reports. Regardless of charge state, MAD achieved more extensive backbone cleavage than CID or ETD, while retaining the modification(s) in most cases. In all but one case, unambiguous modification site determination was achieved with MAD. MAD produced 15–20% better sequence coverage than CID and ETD for both the 2+ and 3+ charge states and very different fragmentation products indicating that the mechanism of fragmentation in MAD is unique and complementary to CID and ETD. Copyright © 2012 John Wiley & Sons, Ltd.