Microwave catalysis through rotationally hot reactive species

In this contribution we propose a novel physical mechanism for microwave catalysis based on rotationally excited reactive species and verify its validity through a computer simulation of a realistic chemical reaction-neutral ester hydrolysis. This nonequilibrium system is formally described by introducing rotational temperature, which is higher than the translational temperature. A Born-Oppenheimer surface was constructed on the density functional theory level and applied to a modified Monte Carlo scheme. The simulation gave a reduced activation free energy when the rotational temperature was higher than the translational temperature, which constitutes a catalytic effect. For example, our calculation predicts that with rotational and translational temperatures of 310 and 300 K, respectively, the reaction should proceed 4.5 times faster than when both temperatures are 300 K. Moreover, this microwave catalytic effect is less pronounced at higher temperatures, which may have serious implications for the interaction of microwaves with living organisms in the context of widespread mobile telephony.     

Comprehensive study of the parameters influencing the detection of organotin compounds by a pulsed flame photometric detector in sewage sludge

An investigation of the operating conditions of a pulsed flame photometric detection (PFPD) system for the determination of organotin compounds (OTCs) in sewage sludge is reported. During the analyses, some spectral interferences were observed. For their elimination detector parameters such as gate delay and gate width were investigated. In addition, the applicability of three different internal standards was evaluated. Under optimised analytical conditions (gate delay 3 ms, gate width 2 ms, tripropyltin as internal standard) limits of detection (LOD) were determined. The LOD for butyltins ranged between 8 and 16 ng Sn g(-1), for phenyltins around 8 ng Sn g(-1) and for octyltins between 5 and 10 ng Sn g(-1). Since there is no certified reference material (CRM) available for sewage sludge, the accuracy of the analytical procedure was checked by the analysis of CRM PACS-2 (marine sediment) and a spiked sludge sample. Good agreement between determined and certified values was obtained. Sewage sludge from a local wastewater treatment plant was analysed and the results compared with data from the literature.     

Concise and highly efficient approach to three key pyrimidine precursors for rosuvastatin synthesis

We report the synthesis of 5-formyl-, 5-(hydroxymethyl)-, and 5-(bromomethyl) substituted N-[4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide. The presented synthetic approach is based on highly efficient three step preparation of functionalized 5-methylpyrimidine. The methyl group is selectively brominated by NBS with irradiation into the bromomethyl derivative, which is then transformed into the hydroxymethyl or formyl groups in nearly quantitative yields. This approach is superior to the existing methodologies for the preparation of the key pyrimidine precursors used in the synthesis of rosuvastatin since no metal catalysis and no cryogenic reaction conditions are involved.     

Synthesis, structural and conformational studies of Z- and E-isomers of fluorinated C-6 isobutenyl N-methyl thymine derivatives

A new series of conformationally restricted pyrimidine derivatives bearing C-6 isobutenyl side-chain (2-9) has been prepared. The novel fluoroalkenyl pyrimidine nucleoside mimetic 3 as model compound for development of tracer molecule in positron emission tomography (PET) was synthesized by fluorination reaction of methoxytritylated pyrimidine derivative using diethylaminosulfur trifluoride (DAST). Conversion of one hydroxyl group to methoxytritylated, fluorinated, mesylated and acetylated pyrimidine derivatives (2, 3, 5-7 and 9) afforded a mixture of Z- and E-isomers in which Z-isomers were predominant. Conformational study of 1, and its fluorinated structural congeners 3 and 4 by the use of NOE experiments revealed predominant conformation of compounds where vinyl H-1′ proton is spatially close to N-1 methyl and H-3′b methylene protons and on the other hand H-3′a methylene protons are close to C-5 methyl protons. The stereostructure of 1,3-dihydroxyisobutenyl N-methyl thymine 1 was unambiguously confirmed by X-ray crystal structure analysis.     

Nonpeptidic Selective Inhibitors of the Chymotrypsin‐Like (β5 i) Subunit of the Immunoproteasome

Elevated expression of the immunoproteasome has been associated with autoimmune diseases, inflammatory diseases, and various types of cancer. Selective inhibitors of the immunoproteasome are not only scarce, but also almost entirely restricted to peptide‐based compounds. Herein, we describe nonpeptidic reversible inhibitors that selectively block the chymotrypsin‐like (β5i) subunit of the human immunoproteasome in the low micromolar range. The most potent of the reversibly acting compounds were then converted into covalent, irreversible, nonpeptidic inhibitors that retained selectivity for the β5i subunit. In addition, these inhibitors discriminate between the immunoproteasome and the constitutive proteasome in cell‐based assays. Along with their lack of cytotoxicity, these data point to these nonpeptidic compounds being suitable for further investigation as β5i‐selective probes for possible application in noncancer diseases related to the immunoproteasome.     

Simultaneous integration of mixed quantum-classical systems by density matrix evolution equations using interaction representation and adaptive time step integrator

A density matrix evolution method [H. J. C. Berendsen and J. Mavri, J. Phys. Chem., 97, 13464 (1993)] to simulate the dynamics of quantum systems embedded in a classical environment is applied to study the inelastic collisions of a classical particle with a five-level quantum harmonic oscillator. We improved the numerical performance by rewriting the Liouville–von Neumann equation in the interaction representation and so eliminated the frequencies of the unperturbed oscillator. Furthermore, replacement of the fixed time step fourth-order Runge–Kutta integrator with an adaptive step size control fourth-order Runge–Kutta resulted in significantly lower computational effort at the same desired accuracy. © 1996 by John Wiley & Sons, Inc.     

The Interactions of Titanocene Dihalides with α-, β- and γ-cyclodextrin Host Molecules

The inclusion of titanocene dihalides (X = F, Cl) into -, - and -cyclodextrin hosts was studied by NMR spectroscopy, thermal analysis and mass spectrometry. It was found that -cyclodextrin does not form inclusion complexes with titanocene halides whereas - and -cyclodextrin do form such complexes. According to the changes in NMR spectra we propose that there is a shallow penetration of a guest molecule of titanocene dihalide into the cavity in the case of -cyclodextrin, but deeper penetration in the case of -cyclodextrin. The stability of the latter inclusion complexes was studied by NMR shift titration.     

A novel approach for speciation of airborne chromium by convective-interaction media fast-monolithic chromatography with electrothermal atomic-absorption spectrometric detection

A new analytical procedure using an anion-exchange separation support based on convective-interaction media (CIM) was developed for the speciation of chromium. The separation of Cr(VI) was performed on a weak anion-exchange CIM diethylamine (DEAE) fast-monolithic chromatographic disc. Buffer A (0.005 mol dm(-3) TRIS-HCl, pH 8.0) and buffer B (buffer A plus 3 mol dm(-3) NH4NO3) were employed in the separation procedure. The separated chromium species were determined 'off-line' by ETAAS in 0.5 cm3 fractions. The applicability of the CIM DEAE-ETAAS procedure was investigated for the determination of airborne Cr(VI) at a plasma cutting workplace. Aerosols were collected on polycarbonate membrane filters of 8 and 0.4 microm pore size (inhalable and respirable aerosols). Alkaline extraction of filters in a heated ultrasonic bath was applied to leach chromium. Good repeatability of measurement (+/-3.0%) of the alkaline extracts was obtained for Cr(VI). The LOD (3s) was found to be 0.30 microg m(-3) Cr(VI), when 0.25 m3 of air was collected on the filter. The validation of the procedure was performed by spiking filters with Cr(VI) and by the analysis of the standard reference material CRM 545, Cr(VI) in welding dust loaded on a filter. Good recoveries for spiked samples (101-102%) and good agreement between Cr(VI) found and the reported certified value for CRM 545 were obtained. The extracts were also analysed by the FPLC-ETAAS technique. Good agreement between two techniques (r2 = 0.9978) confirmed the reliability of the CIM DEAE-ETAAS procedure developed. The main advantage of the procedure lies in the speed of the chromatographic separation (chromatographic run completed in 15 min).     

Synthesis of 5H-pyridazino[4,5-b]indoles and their benzofurane analogues utilizing an intramolecular Heck-type reaction

The title ring systems were prepared from pyridazin-3(2H)-one precursors in novel, efficient pathways. 2-Methylbenzo[b]furo[2,3-d]pyridazin-1(2H)-one was synthesized via a regioselective nucleophilic substitution reaction of a 2-methyl-4,5-dihalopyridazin-3(2H)-one with phenol followed by an intramolecular Heck-type reaction. The same molecule and its 6-phenyl analogue were also prepared via reaction of 2-methyl-5-iodopyridazin-3(2H)-one or 2-methyl-5-chloro-6-phenylpyridazin-3(2H)-one, respectively, with 2-bromophenol or 2-iodophenol followed by Pd-catalyzed cyclodehydrohalogenation. Moreover, a new approach for the synthesis of 2-methyl-2,5-dihydro-1H-pyridazino[4,5-b]indol-1-ones was also elaborated utilizing a Heck-type ring closure reaction on 5-[(2-bromophenyl)amino]-2-methylpyridazin-3(2H)-ones which were obtained via Buchwald-Hartwig amination of 2-methyl-5-halopyridazin-3(2H)-ones with 2-bromoaniline.     

A New Pathway of DNA G‐Quadruplex Formation

A new folding intermediate of Oxytricha nova telomeric Oxy‐1.5 G‐quadruplex was characterized in aqueous solution using NMR spectroscopy, native gel electrophoresis, thermal differential spectra (TDS), CD spectroscopy, and differential scanning calorimetry (DSC). NMR experiments have revealed that this intermediate (i‐Oxy‐1.5) exists in two symmetric bimolecular forms in which all guanine bases are involved in GG N1‐carbonyl symmetric base pairs. Kinetic analysis of K⁺‐induced structural transitions shows that folding of Oxy‐1.5 G‐quadruplex from i‐Oxy‐1.5 is much faster and proceeds through less intermediates than folding from single strands. Therefore, a new folding pathway of Oxy‐1.5 G‐quadruplex is proposed. This study provides evidence that G‐rich DNA sequences can self‐assemble into specific pre‐organized DNA structures that are predisposed to fold into G‐quadruplex when interacting with cations such as potassium ions.