Methoxymethyl (MOM) group nitrogen protection of pyrimidines bearing C-6 acyclic side-chains

Novel N-methoxymethylated (MOM) pyrimidine (4-13) and pyrimidine-2,4-diones (15-17) nucleoside mimetics in which an isobutyl side-chain is attached at the C-6 position of the pyrimidine moiety were synthesized. Synthetic methods via O-persilylated or N-anionic uracil derivatives have been evaluated for the synthesis of N-1- and/or N-3-MOM pyrimidine derivatives with C-6 acyclic side-chains. A synthetic approach using an activated N-anionic pyrimidine derivative afforded the desired N,N-1,3-diMOM and N-1-MOM pyrimidines 4 and 5 in good yield. Introduction of fluorine into the side-chain was performed with DAST as the fluorinating reagent to give a N,N-1,3-diMOM pyrimidine 13 with a 1-fluoro-3-hydroxyisobutyl moiety at C-6. Conformational study of the monotritylated N-1-MOM pyrimidine 12 by the use of the NOE experiments revealed the predominant conformation of the compound to be one where the hydroxymethyl group in the C-6 side-chain is close to the N-1-MOM moiety, while the OMTr is in proximity to the CH(3)-5 group. Contrary to this no NOE enhancements between the N-1-MOM group and hydroxymethyl or fluoromethyl protons in 13 were observed, which suggested a nonrestricted rotation along the C-6 side-chain. Fluorinated N,N-1,3-diMOM pyrimidine 13 emerged as a model compound for development of tracer molecules for non-invasive imaging of gene expression using positron emission tomography (PET).     

Beta-amyloid toxicity increases with hydrophobicity in the presence of metal ions

Abstract  

Alzheimer’s disease is a multifactorial neurodegenerative disorder characterized by the pathological brain deposition of neurofibrillary tangles and senile plaques. The latter consist mainly of insoluble β-amyloid (Aβ) fibril deposition. Aβ aggregation and deposition can be increased by several factors, including metal ions. In this study we investigated the role played by metal ions in affecting Aβ oligomerization in the presence and in the absence of its hydrophobic fragment Aβ_17–28. This was done not as a physiological investigation, but as a paradigmatic study to confirm the key role of Aβ superficial hydrophobicity as a relevant aggravating factor that contributes to the toxicity of Aβ and Aβ–metal complexes. The structural conformations of Aβ–metal complexes were monitored through fluorescence and turbidity measurements as well as transmission electron microscopy. Results reported herein indicate that various metals differentially influence Aβ conformation, with aluminum being the only metal ion for which we are able to determine a dramatic enhancement of peptide oligomer formation with a consequent toxic effect. This scenario was further enhanced by the presence of Aβ_17–28, which resulted in a marked toxicity in a neuroblastoma cell culture as a consequence of the enhancement of the hydrophobicity of the amyloid and amyloid–metal complexes.     

Integrable Mott insulators driven by a finite electric field

We develop a method for extracting the steady nonequilibrium current from studies of driven isolated systems, applying it to the model of a one-dimensional Mott insulator at high temperatures. While in the nonintegrable model the nonequilibrium conditions can be accounted for by internal heating, the integrability leads to a strongly nonlinear dc response with a vanishingly small dc conductivity in the linear-response regime. The finding is consistent with equilibrium results for the dc limit of the optical conductivity determined in the presence of a weak and decreasing perturbation.     

High-speed two-frame shadowgraphy for velocity measurements of laser-induced plasma and shock-wave evolution

We describe a high-speed, two-frame shadowgraph method for the two-dimensional visualization of an expanding laser-induced plasma and shock wave in two time instances. The developed experimental method uses a 30 ps, green-laser, polarized pulse for the direct and delayed illumination separated by a variable time delay in the range from 300 ps to 30 ns. Since the exposed images of a single event are captured with two CCD cameras, the established method enables velocity measurements of the fast laser-induced phenomena within the nanosecond excitation-laser pulse as well as at later times-when the excitation-laser radiation has already ended.     

Moment Approximations for Set-Semidefinite Polynomials

The set of polynomials that are nonnegative over a subset of the nonnegative orthant (we call them set-semidefinite) have many uses in optimization. A common example of this type set is the set of copositive matrices, where we are effectively considering nonnegativity over the entire nonnegative orthant and are restricted to homogeneous polynomials of degree two. Lasserre (SIAM J. Optim., 21(3):864–885, 2011) has previously considered a method using moments in order to provide an outer approximation to this set, for nonnegativity over a general subset of the real space. In this paper, we shall show that, in the special case of considering nonnegativity over a subset of the nonnegative orthant, we can provide a new outer approximation hierarchy. This is based on restricting moment matrices to be completely positive, and it is at least as good as Lasserre’s method. This can then be relaxed to give tractable approximations that are still at least as good as Lasserre’s method. In doing this, we also provide interesting new insights into the use of moments in constructing these approximations.     

C and O stable isotopic signatures of fast-growing dripstones on alkaline substrates: reflection of growth mechanism,carbonate sources and environmental conditions

Secondary carbonate precipitates (dripstones) formed on concrete surfaces in four different environments – Mediterranean and continental open-space and indoor environments (inside a building and in a karstic cave) – were studied. The fabric of dripstones depends upon water supply, pH of mother solution and carbonate-resulting precipitation rate. Very low δ¹³C (average?28.2‰) and δ¹⁸O (average?18.4‰) values showed a strong positive correlation, typical for carbonate precipitated by rapid dissolution of CO₂ in a highly alkaline solution and consequent disequilibrium precipitation of CaCO₃. The main source of carbon is atmospheric or biogenic CO₂ in the poorly ventilated karstic cave, which is reflected in even lower δ¹³C values. Statistical analysis of δ¹³C and δ¹⁸O values of the four groups of samples showed that the governing factor of isotope fractionation is not the temperature, but rather the precipitation rate.     

75As N.Q.R. and 19F N.M.R. study of solid AsF3

The temperature dependence of the ⁷⁵As pure quadrupole resonance frequency in AsF₃ has been studied from 77 K to a temperature very close to the melting point. It is found that the effective electric field gradient at the As site does not shift much from the gas-phase value and that the temperature dependence of the ⁷⁵As N.Q.R. frequency seems to follow the Bayer-Kushida model. The occurrence of a line-width transition in the ¹⁹F N.M.R. spectrum between 200 and 150 K demonstrates the presence of low-frequency, large-amplitude molecular motions which are too slow to average out the ⁷⁵As quadrupole coupling.     

The Influence of Pressure in Paracetamol Tablet Compaction on 14N Nuclear Quadrupole Resonance Signal

¹⁴N nuclear quadrupole resonance (¹⁴N NQR) of several commercially available paracetamol tablets was measured. The spectra of two polymorphs are presented. The linewidths of the correspondent ¹⁴N NQR lines in all the measured samples containing the room-temperature stable monoclinic polymorph were noticeably different. We proved experimentally that the linewidth differences are the consequence of different compacting pressure in the production of tablets.     

Methodologies and applications for resilient global development from the aspect of SDI-SOR special issues of CJOR

Central European Journal of Operations Research - In this paper, we present the results of a bibliometric analysis of papers published in six SDI-SOR special issues that have been published since...     

Oxidation of sulfides including DBT using a new vanadyl complex of a non‐innocent o‐aminophenol benzoxazole based ligand

Reaction of a non‐innocent o‐aminophenol benzoxazole based ligand HL^BAP with VOCl₃ afforded a vanadyl complex, VOL^BIS (SQ), in which SQ is a 2,4‐di‐tert‐butylsemiquinone produced from hydrolysis of HL^BAP. The crystal structure of VOL^BIS (SQ) exhibits an octahedral geometry with the VO²⁺ center coordinated by two nitrogen and one oxygen atoms of L^BAP and two oxygen atoms of SQ. Electrochemical studies showed quasi‐reversible metal‐centered reduction and ligand‐centered oxidation of complex. The magnetic moment of VOL^BIS (SQ) is consistent with the spin‐only value expected for S = 1/2 system. The neutral species of VOL^BIS (SQ) is EPR active, which is consistent with a paramagnetic electronic ground state (S = 1/2). This result is in accordance with the vanadyl (IV) moiety surrounded by tridentate iminobenzosemiquinonate anion radical (HL^BIS)^?‐ and benzosemiquinone ligand (SQ)^?. The theoretical calculations confirm the experimental results. Furthermore, we present the optimal conditions for maximum efficiency of sulfide oxidation for oxidative desulfurization with hydrogen peroxide and 6 times reusability of catalyst for sulfoxidation of dibenzothiophene.