Microwave assisted IMDAF# reaction: microwave irradiation applied with success to cycloaddition reaction of N-propargyl-N-p-tolyl-N-2-furfurylamines

The new tertiary furfurylamine with triple bond as a dienophylic part i.e. N-(5-methyl-2-furfuryl)-N-prop-2-ynyl-p-toluidine (1) was prepared and the intramolecular Diels-Alder reaction of the amine (1) was performed under microwave irradiation conditions and by heating a benzene solution of the amine under nitrogen. Comparing the results of the usual thermal and the MAOS reaction, we confirmed our expectations that MAOS could promote the outcome of IMDA reaction of the suitably N-substituted tertiary 2-furfuryl-amines. In the present example, N-p-tolyl-5-methyl-5,7a-dihydro-5,7a-epoxyisoindoline was obtained in much better yield and of higher purity.     

A novel bis-phenanthridine triamine with pH controlled binding to nucleotides and nucleic acids

The new bis-phenanthridine triamine is characterised by three pK(a) values: 3.65; 6.0 and >7.5. A significant difference in the protonation state of at pH = 5 (four positive charges) and at pH = 7 (less than two positive charges) accounts for the strong dependence of -nucleotide binding constants on nucleotide charge under acidic conditions, whereas at neutral pH all -nucleotide complexes are of comparable stability. All experimental data point at intercalation as the dominant binding mode of to polynucleotides. However, there is no indication of bis-intercalation of the two phenanthridine subunits in binding to double stranded polynucleotides, the respective complexes being most likely mono-intercalative. Thermal stabilisation of calf thymus DNA (ct-DNA) and poly A-poly U duplexes upon addition of is significantly higher at pH = 5 than at neutral conditions. This is not the case with poly dA-poly dT, indicating that the specific secondary structure of the latter, most likely the shape of the minor groove, plays a key role in complex stability. At pH = 5 acts as a fluorimetric probe for poly G (emission quenching) as opposed to other ss-polynucleotides (emission increase), while at neutral conditions this specificity is lost. One order of magnitude higher cytotoxicity of compared to its "monomer" can be accounted for by cooperative action of two phenanthridinium units and the charged triamine linker. The results presented here are of interest to the development of e.g. sequence-selective cytostatic drugs, and in particular for the possibility to control the drug activity properties over binding to DNA and/or RNA by variation of the pH of its surrounding.     

Tunable external cavity quantum cascade laser for the simultaneous determination of glucose and lactate in aqueous phase

A room temperature operated pulsed external-cavity (EC) quantum cascade laser (QCL) was used for mid-infrared (mid-IR) transmission measurements of glucose and lactate in aqueous solution. The high spectral power density of the EC-QCL (ranging from 1-350 mW) over a wide tuning range (1030-1230 cm(-1)) allowed transmission measurements through optical paths of 130 μm and more. This is a significant improvement in terms of robustness of the measurement setup, especially when samples containing cells or other particles, as is the case for biofluids, are to be analyzed. The broad tuning range furthermore permitted multi-analyte detection based on multivariate calibrations. Promising results on the simultaneous determination of glucose (c = 0-800 mg dL(-1)) and sodium-lactate (c = 0-224 mg dL(-1)) in aqueous solutions in the presence of the interferents maltose and xylose are reported. A partial least squares (PLS) calibration model was calculated which was able to predict the glucose concentration with a root mean square error of prediction (RMSEP) of 9.4 mg dL(-1), as proved by external validation. Due to their small size and room temperature operation, EC-QCLs offer an attractive alternative regarding the way mid-IR measurements are carried out. This may be of special importance for new reagent-free bedside monitoring systems.     

EPR study of a copper impurity center in a single crystal of 2-thiothymine

EPR spectroscopy was used to study the complex formed in crystals of 5-methyl-2-thiouracil (2-thiothymine) containing traces of copper. The copper impurities, originally present as Cu(I)-complex of 2-thiothymine in the lattice of 2-thiothymine, are transformed into paramagnetic Cu(II)-complex by ionizing radiation. It was found that the complex is planar, the plane being defined by two pairs of S and N atoms, from two adjacent 2-thiothymine molecules. The structure of the complex suggests that a pair of hydrogen bonds between two neighboring molecules is replaced by a stronger Cu-coordination bonding, with two sulfur and two nitrogen atoms as ligands. The spectroscopic parameters (g-tensor, A(63Cu) and A(14N) tensors) are essentially similar to those earlier observed for copper planar centers in other systems.     

'Genome order index' should not be used for defining compositional constraints in nucleotide sequences

A “genome order index,” defined as S = a² + c² + t² + g², where a, c, t, and g are the nucleotide frequencies of A, C, T, and G, respectively, was used to suggest that there exist genome-specific constraints on nucleotide composition. We show that the “evidence” for constraint, S < 1/3, is in fact a mathematical property that is always true regardless of data. Moreover, we show that S is strictly equivalent to and derivable from the Shannon H-function and has no advantage over it.     

Synthesis and characterization of dicyclopalladated complexes of azobenzene derivatives by experimental and computational methods

A series of doubly cyclopalladated complexes of azobenzene and its unsymmetrical substituted derivatives, namely, {LPdCl(mu-AZB)LPdCl}, where AZB is azobenzene, 4-methylazobenzene, 4-aminoazobenzene, or 4-(dimethylamino)-4'-nitroazobenzene, while L is N,N-dimethylformamide, dimethylsulfoxide, or pyridine, have been prepared. Their structural and spectroscopic properties were determined by X-ray diffraction analysis as well as by (1)H NMR, IR, UV-vis, and fluorimetric studies. Experimental results were rationalized by quantum chemical calculations. Crystal structures of several complexes have been resolved, and for the first time, it was demonstrated that the cyclopalladation may take place at the azobenzene aromatic ring having the strong electron-withdrawing substituent at the para position. In all cases, the metalated carbon and N,N-dimethylformamide or dimethylsulfoxide ligands are mutually trans, whereas the pyridine ligands are in the cis arrangement. cis/trans isomerism in the isolated compounds is explained by comparing the calculated energies of isomeric structures. All of the complexes absorb strongly in the visible region, and according to time-dependent density functional theory calculations, most of the absorptions can be attributed to intraligand pi --> pi* or metal-to-ligand charge-transfer transitions. The fluorescence emission was observed for the complexes with 4-aminoazobenzene or 4-(dimethylamino)-4'-nitroazobenzene. The aromaticity of palladacycles is evaluated by several aromaticity indices and related to relevant experimental findings.     

The Onset of Systemic Oxidative Stress Associated with the Accumulation of Lipid Peroxidation Product Acrolein in the Skin of Patients with Small-Vessel Vasculitis

Small-vessel vasculitis (SVV) is the inflammation of the vessel wall that can result in hemorrhage and/or ischemia. Among the histological findings in SVV are increased infiltrating neutrophils, which, due to their oxidative burst and myeloperoxidase activity, release excessive reactive oxygen species, triggering a chain reaction of lipid peroxidation and yielding reactive aldehydes such as acrolein. The implication of oxidative stress in the pathogenesis of SVV was studied, focusing on acrolein immunohistochemistry in the affected skin vessels and systemic stress response. Samples from SVV patients and healthy subjects were collected and analyzed for total serum peroxides, total antioxidant capacity, inflammatory and immunological parameters, as well as for the presence of acrolein–protein adducts in the skin tissue specimens. The obtained data showed that systemic redox homeostasis and iron metabolism are altered in SVV patients. Possible biomarkers in the evaluation of oxidative status, disease activity and prevalence were indicated. Furthermore, a strong correlation between the accumulation of acrolein–protein adducts in the skin and the progression of the disease was revealed. Thus, the results of this study demonstrate that SVV is not only associated with systemic oxidative stress but also with tissue-specific oxidative stress that promotes acrolein formation and protein modification correlating with the severity of cutaneous vasculitis.     

Simple route to the doubly ortho-palladated azobenzenes: building blocks for organometallic polymers and metallomesogens

A new class of doubly cyclopalladated complexes, {PdCl(dmf)}2(mu-azb) (1) and {PdCl(dmf)}2(mu-aazb) (2), has been prepared in dimethylformamide (dmf) by reaction of azobenzene (azb) and 4-aminoazobenzene (aazb), respectively, with an excess of PdCl2(CH3CN)2 complex. Recrystallization of 1 and 2 in dimethyl sulfoxide (dmso) yields complexes {PdCl(dmso)}2(mu-azb) (3) and {PdCl(dmso)}2(mu-aazb) (4), respectively. The crystal structures of 1 and 4 have been determined by X-ray diffraction. All complexes are characterized by 1H and 13C NMR spectra and elemental analysis. In both crystal structures, solvent molecules are bound to palladium through oxygen atoms and oriented trans to carbon. In view of greater preference of palladium to nitrogen and sulfur atoms, the experimental structures were rationalized by quantum-chemical calculations and confirmed as the most stable isomers.     

Plasma biomarker identification in S-adenosylhomocysteine hydrolase deficiency

S-Adenosylhomocysteine hydrolase (AHCY) deficiency is a rare congenital disorder in methionine metabolism clinically characterized by white matter atrophy, delayed myelination, slowly progressive myopathy, retarded psychomotor development and mildly active chronic hepatitis. In the present study, we utilized a comparative proteomics strategy based on 2-DE/MALDI-MS and LC/ESI-MS to analyze plasma proteins from three AHCY-deficient patients prior to and after receiving dietary treatment designed to alleviate disease symptoms. Obtained results revealed candidate biomarkers for the detection of myopathy specifically associated with AHCY deficiency, such as carbonic anhydrase 3, creatine kinase, and thrombospondin 4. Several proteins mediating T-cell activation and function were identified as well, including attractin and diacylglycerol kinase α. Further validation and functional analysis of identified proteins with clinical value would ensure that these biomarkers make their way into routine diagnosis and management of AHCY deficiency.