Synthesis and Antiproliferative Effect of Halogenated Coumarin Derivatives

A series of 6- and 6,8-halocoumarin derivatives have been investigated as potential antiproliferative compounds against a panel of tumor and normal cell lines. Cytotoxic effects were determined by the MTT method. To investigate the potential molecular mechanism involved in the cytotoxic effect, apoptosis assay, cell cycle analysis, reactive oxygen species (ROS), and reduced glutathione analysis were performed. Among the screened compounds, coumarins 6,8-dibromo-2-oxo-2H-chromene-3-carbonitrile 2h and 6,8-diiodo-2-oxo-2H-chromene-3-carbonitrile 2k exhibited the most antiproliferative effect in thyroid cancer-derived cells TPC-1. The apoptosis assay showed that both 2h and 2k induced apoptosis in TPC-1 thyroid cancer cells. According to these experiments, both coumarins induced a slight increase in TPC-1 cells in the G2/M phase and a decrease in the S phase. A significant increase in ROS levels was observed in TPC-1 treated with diiodocoumarin 2k, while the dibromocoumarin 2h induced a decrease in ROS in a dose and time-dependent manner.     

Polymeric photoinitiators based on side-chain benzoin methyl ether and tertiary amine moieties for fast UV curable coatings

The synthesis is reported of a new series of polymeric photoinitiators obtained by copolymerization of a-methylolbenzoin methyl ether acrylate (MBA) with different N,N-dialkylamino alkyl acrylates. The copolymers have been fully characterized and employed in the photoinitiated polymerization and crosslinking reactions of a standard acrylic formulation for clear curable coatings. The photoinitiation activity of the above systems has been measured by using microwave dielectrometry and differential photocalorimetry, and compared with that found for the corresponding low-molecular-weight models. The results clearly indicate that the copolymeric systems display a remarkable decrease of the induction period and an improved overall activity in the UV curing of the acrylic coatings. An interpretation of the experimental findings is also reported.     

6-Substituted-5H-pyrrolo[2,3-b]pyrazines via palladium-catalyzed heteroannulation from N-(3-chloropyrazin-2-yl)-methanesulfonamide and alkynes

We herein report the efficient and convenient synthesis of 6-substituted-5H-pyrrolo[2,3-b]pyrazines. The reaction is a palladium-catalyzed heteroannulation process followed by deprotection to yield the desired pyrrolo[2,3-b]pyrazine substrates. The reaction starts with readily accessible N-(3-chloropyrazin-2-yl)-methanesulfonamide and commercially available terminal alkynes and works with aryl- and alkylalkynes.     

The consistency of the postulates of special relativity

In a recent article in this journal, Kingsley has tried to show that the postulates of special relativity contradict each other. Here we show that the arguments of Kingsley are invalid because of an erroneous appeal to symmetry in a non-symmetric situation. The consistency of the postulates of special relativity and the relativistic kinematics deduced from them is restated.     

Conformal Generally Covariant Quantum Field Theory: The Scalar Field and its Wick Products

In this paper we generalize the construction of generally covariant quantum theories given in [BFV03] to encompass the conformal covariant case. After introducing the abstract framework, we discuss the massless conformally coupled Klein Gordon field theory, showing that its quantization corresponds to a functor between two certain categories. At the abstract level, the ordinary fields, could be thought of as natural transformations in the sense of category theory. We show that the Wick monomials without derivatives (Wick powers) can be interpreted as fields in this generalized sense, provided a non-trivial choice of the renormalization constants is given. A careful analysis shows that the transformation law of Wick powers is characterized by a weight, and it turns out that the sum of fields with different weights breaks the conformal covariance. At this point there is a difference between the previously given picture due to the presence of a bigger group of covariance. It is furthermore shown that the construction does not depend upon the scale μ appearing in the Hadamard parametrix, used to regularize the fields. Finally, we briefly discuss some further examples of more involved fields.     

Structural, optical and electrical characterization of antimony-substituted tin oxide nanoparticles

Antimony-doped tin oxide (ATO) nanostructures were prepared using chemical precipitation technique starting from SnCl₂, SbCl₃ as precursor compounds. The antimony composition was varied from 5 to 20 wt%. The lower resistance was observed at composition of Sn:95 and Sb:05, when compared with undoped and higher doping concentration of antimony. The average crystalline size of undoped and doped tin oxide was calculated from the X-ray diffraction (XRD) pattern and found to be in the range of 30-11 nm and it was further confirmed from the transmission electron microscopy (TEM) studies. The scanning electron microscopy (SEM) analysis showed that the nanoparticles agglomerates forming spherical-shaped particles of few hundreds nanometers. The samples were further analyzed by energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and electrical resistance measurements.     

Sensitivity improvement in 19F NMR-based screening experiments: theoretical considerations and experimental applications

NMR-based binding and functional screening performed with FAXS (fluorine chemical shift anisotropy and exchange for screening) and 3-FABS (three fluorine atoms for biochemical screening) represents a potential alternative approach to high-throughput screening for the identification of novel potential drug candidates. The major limitation of this method in its current status is its intrinsic low sensitivity that limits the number of tested compounds. One approach for overcoming this problem is the use of a cryogenically cooled (19)F probe that reduces the thermal noise in the receiver circuitry. Sensitivity improvement in the two screening techniques achieved with the novel cryogenic (19)F probe technology permits an increased throughput, detection of weaker binders and inhibitors (relevant in a fragment-based lead discovery program), detection of slow binders, and reduction in protein and substrate consumption. These aspects are analyzed with theoretical simulations and experimental quantitative performance evaluation. Application of 3-FABS combined with the cryogenic (19)F probe technology to rapid screening at very low enzyme concentrations and the current detection limits reached with this approach are also presented.     

Synthesis and evaluation of a new non-fluorescent quencher in fluorogenic oligonucleotide probes for real-time PCR

A non-fluorescent quencher, based on the diaminoanthraquinone Disperse Blue 3, has been incorporated into oligonucleotides at the 5'-end, the 3'-end and internally as a thymidine derivative. Fluorimetry and fluorogenic real-time PCR experiments demonstrate that the quencher is effective with a wide range of fluorescent dyes. The anthraquinone moiety increases the melting temperature of DNA duplexes, thus allowing shorter, more discriminatory probes to be used. The quencher has been used in Scorpion primers and TaqMan probes for human DNA sequence recognition and mutation detection.     

Of the ortho effect in palladium/norbornene-catalyzed reactions: a theoretical investigation

Mechanistic questions concerning palladium and norbornene catalyzed aryl-aryl coupling reactions are treated in this paper: how aryl halides react with the intermediate palladacycles, formed by interaction of the two catalysts with an aryl halide, and what is the rational explanation of the "ortho effect" (caused by an ortho substituent in the starting aryl halide), which leads to aryl-aryl coupling with a second molecule of aryl halide rather than to aryl-norbornyl coupling. Two possible pathways have been proposed, one involving aryl halide oxidative addition to the palladacycle, the other passing through a palladium(II) transmetalation, also involving the palladacycle, as previously proposed by Cardenas and Echavarren. Our DFT calculations using M06 show that, in palladium-catalyzed reaction of aryl halides, not containing ortho substituents, and norbornene, the intermediate palladacycle formed has a good probability to undergo transmetalation, energetically favored over the oxidative addition leading to Pd(IV). The unselective sp(2)-sp(2) and sp(2)-sp(3) coupling, experimentally observed in this case, can be explained in the framework of the transmetalation pathway since the energetic difference between aryl attack onto the aryl or norbornyl carbon of the palladacycle intermediate is quite small. On the other hand, according to the experimentally observed "ortho effect", selective aryl-aryl coupling only occurs in the reactions of ortho-substituted metallacycles. The present work offers the first possible rationalization of this finding. These in situ formed palladacycles containing an ortho substituent could more easily undergo oxidative addition of an aryl halide rather than reductive elimination from the transmetalation intermediate as a result of a steric clash in the transition state of the latter. The now energetically accessible Pd(IV) intermediate, featuring a Y-distorted trigonal bipyramidal structure, can account for the reported selective aryl-aryl coupling through a reductive elimination which is easier than aryl-norbornyl coupling. Thus, the steric effect represents the main factor that dictates the energetic convenience of the system to follow the Pd(IV) or the transmetalation pathway. Ortho substituents cause a higher energy transition state for reductive elimination from the transmetalation intermediate than for oxidative addition to the metallacycle palladium(II) and the pathway based on the latter predominates.