Functional Binding Surface of a β‐Hairpin VEGF Receptor Targeting Peptide Determined by NMR Spectroscopy in Living Cells

In this study, the functional interaction of HPLW peptide with VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) was determined by using fast ¹⁵N‐edited NMR spectroscopic experiments. To this aim, ¹⁵N uniformly labelled HPLW has been added to Porcine Aortic Endothelial Cells. The acquisition of isotope‐edited NMR spectroscopic experiments, including ¹⁵N relaxation measurements, allowed a precise characterization of the in‐cell HPLW epitope recognized by VEGFR2.     

The Cytotoxic Effect of α-Synuclein Aggregates

Parkinson's disease is a neurodegenerative disorder involving a functional protein, α-synuclein, whose primary function is related to vesicle trafficking. However, α-synuclein is prone to form aggregates, and these inclusions, known as Lewy bodies, are the hallmark of Parkinson's disease. α-synuclein can alter its conformation and acquire aggregating capacity, forming aggregates containing β-sheets. This protein's pathogenic importance is based on its ability to form oligomers that impair synaptic transmission and neuronal function by increasing membrane permeability and altering homeostasis, generating a deleterious effect over cells. First, we establish that oligomers interfere with the mechanical properties of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane, as demonstrated by nanoindentation curves. In contrast, nanoindentation revealed that the α-synuclein monomer's presence leads to a much more resistant lipid bilayer. Moreover, the oligomers’ interaction with cell membranes can promote lactate dehydrogenase (LDH) release, suggesting the activation of cytotoxic events.     

Convexity of Domains of Riemannian Manifolds

In this paper the problem of the geodesic connectedness and convexity ofincomplete Riemannian manifolds is analyzed. To this aim, a detailedstudy of the notion of convexity for the associated Cauchy boundary iscarried out. In particular, under widely discussed hypotheses,we prove the convexity of open domains (whose boundaries may benondifferentiable) of a complete Riemannian manifold. Variationalmethods are mainly used. Examples and applications are provided,including a result for dynamical systems on the existence oftrajectories with fixed energy.     

A generalization of an example by V. Ya. Ivrii

A well-known example by Ivrii concerning the operatorP=D _t ² −t^2lD _x ² +at^kD_x (a≠0), shows that there exists a delicate relation amongl, k and the Gevrey index of well-posedness of the Cauchy problem. In this paper we give a generalization to a class of pseudo-differential operators includingP.

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Sunto Un famoso esempio di Ivrii riguardante l'operatoreP=D _t ² −t^2lD _x ² +at^kD_x (a≠0), mostra che c'è una relazione sottile tral, k e l'indice di Gevrey di buona positura del problema di Cauchy. In questo articolo viene data una generalizzazione ad una classe di operatori pseudodifferenziali che comprendeP.

     

Conformational mobility of thianthrene-5-oxide

[reaction: see text] Data on the apparent dipole moment of thianthrene-5-oxide (1) and (1)H NMR spectra in different solvents support the conformational mobility of 1, which flaps between two limit boat conformations with the sulfinyl group in pseudoequatorial and pseudoaxial positions, respectively. The conformational equilibrium of 1 occurs too fast for the (1)H NMR (500 MHz) time-scale even at -130 degrees C, and the equilibrium constant has not been determined. The apparent dipole moments of 1 in n-hexane and 1,4-dioxane and the (1)H NMR spectra of 1 and the model compounds cis- and trans-thianthrene-5,10-dioxides (2) and thianthrene (5) in different solvents and at various temperatures confirm that the relative position of the conformational equilibrium of 1 is solvent-dependent, and more polar solvents favor the conformation with the sulfoxide group in the pseudoaxial position (1(')(ax)). Variable-temperature (1)H NMR spectra have established the interconversion barrier of trans-2 and confirmed that the conformational equilibrium of cis-2 is strongly displaced toward the conformation with both sulfinyl groups in the pseudoequatorial position. The (1)H NMR data support the transannular interaction of the functional groups in 1 and trans-2.     

Metal-directed synthesis and photophysical studies of trinuclear v-shaped and pentanuclear x-shaped ruthenium and osmium metallorods and metallostars based upon 4'-(3,5-dihydroxyphenyl)-2,2':6',2''-terpyridine divergent units

A new series of V-shaped trinuclear metallorods and X-shaped pentanuclear metallostars has been prepared by the reaction of metal complexes bearing pendant phenolic functionalities with complexes containing electrophilic ligands. Specifically, {M(tpy)2} motifs (M=Ru or Os; tpy=2,2':6',2'-terpyridine) bearing one or two pendant 3,5-dihydroxyphenyl substituents at the 4-position of the central ring of the tpy have been reacted with the complexes [Ru(tpy)(Xtpy)]2+ (X=Cl or Br) to form new ether-linked species. The energy transfer from ruthenium to osmium in these complexes has been investigated in detail and the efficiency of transfer shown to be highly temperature dependent; the energy transfer is highly efficient at low temperature, whereas at room temperature nonradiative and nontransfer deactivation of the excited {Ru(tpy)2}* domains is most significant.     

Baeyer-Villiger oxidation with potassium peroxomonosulfate supported on acidic silica gel

[reaction: see text] Potassium peroxomonosulfate deposited onto silica SiO2 x KHSO5 efficiently reacts with ketones in dichloromethane at room temperature to give the corresponding esters or lactones in quantitative yields. This method avoids hydrolysis of the reaction products. The Baeyer-Villiger reaction is catalyzed by potassium hydrogensulfate present in the supported reagent.     

Preserving the chromatographic integrity of high-speed supercritical fluid chromatography separations using time-of-flight mass spectrometry

The advantage of high-speed time-of-flight-mass spectrometry (TOF-MS) detection for ultrafast qualitative supercritical fluid chromatography/mass spectrometry (SFC/MS) applications allows the superior resolving power of SFC to be exploited in high-throughput analysis. A chromatographic comparison of quadrupole MS and TOF-MS shows high-speed TOF total ion current data point sampling to be more indicative of fast SFC separations and corresponding short (1-2 s) baseline peak widths. Results shown for analysis of a six-compound mixture with two peaks eluting at 0.86 and 0.89 min exhibit >50% resolution by high-speed TOF data sampling, whereas the same peaks appear to coelute using quadrupole MS data sampling. Additionally, a marked improvement in the peak baseline widths is afforded by fast TOF data acquisition of 0.1 s/spectrum, resulting in a reduction in the baseline width, 1.6 s, of sulfanilamide in a four-compound mixture that is more than 2-fold greater than that achieved at the slower data acquisition of 0.5 s/spectrum. The resulting increase in resolution and improved peak shapes allow automatic integration routines to perform more effectively. For most classes of compounds amenable to high performance liquid chromatography, including druglike species, steroids, and polymers, the union of SFC with TOF-MS provides the maximum density of chemical information per unit time available with any high-speed chromatographic/mass spectrometric method.