A Small Change in Structure, a Big Change in Flexibility.

Studies of the rotational barrier energy of the amide bond using quantum computing and nuclear magnetic resonance (NMR) are focused mainly on its use as a model of the peptide bond. The results of these studies are valuable not only in terms of the fundamental conformational properties of amide bonds, but also in the design of molecular machines, which have recently attracted interest. We investigate the fluxionality of the amide and enamide bonds of compound 3-[(E)-(dimethylamino)methylidene]-1,1-dimethylurea using advanced dynamic NMR experiments and a theoretical evaluation of the density functional theory (DFT) calculation. The dynamic NMR study shows restricted rotation around the amide group (16.4 kcal/mol) and a very high barrier around the enamine group (18.6 kcal/mol). In a structurally similar compound, (E)-3-(dimethylamino)-N,N-dimethylacrylamide (N atom is replaced by CH), the amide barrier is 12.4 kcal/mol and the enamine barrier is 11.7 kcal/mol. The DFT studies of both compounds reveal the electronic origin of this phenomenon. Theoretical calculations reveal the origin of the higher enamine barrier. The better delocalization of the lone pair of electrons on the end nitrogen atom into the antibonding orbital of the neighboring C-N double bond leads to the better stabilization of the ground state, and this leads to a greater increase in the enamine barrier.

Chaperone-like effect of polyzwitterions on the interaction of C1q with IgG.

The amphiphilic polyzwitterion (PZ) poly(ethylene oxide-b-N,N-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate), zwitterionic surfactant (ZS) n-dodecyl-N,N-dimethyl-3-ammonium-1-propanesulfonate, and zwitterionic monomer (ZM) N,N-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate were analyzed for their suggested chaperone-like effect on the interaction of C1q and IgG. Our results proved that the PZ retarded the C1q interaction with IgG, demonstrating a specific protein-folding helper effect. The ZS enhanced this interaction, when the ZS concentration was lower than the critical micelle concentration (CMC), and retarded it, when the ZS concentration was above the CMC. The ZM, with no self-assembling ability, did not influence this interaction. These results support the hypothesis of a hydrophobic interaction between Pts and hydrophobic domains of partly denatured protein molecules. The amphiphilic self-assemblies, formed by polyzwitterionic macromolecules or zwitterionic surfactants, have the ability to transform the hydrophobic domains of the protein molecules into hydrophilic ones, covering them with their hydrophilic parts.

A case of 5F-ADB / FUB-AMB abuse: Drug-induced or drug-related death?

Synthetic cannabinoids (SCs) belong to the group of new psychoactive substances (NPS) which appear sprayed on herbal mixtures on the "street" drug market and are intended for smoking like marijuana. In the present report we discuss a fatal case of 18-years-old boy, who had smoked SCs since several months and an overuse of SCs during last 48 h of his life has been apprised. The autopsy findings revealed acute respiratory distress syndrome (ARDS). Both toxicological analysis of deceased blood and urine samples and chemical analysis of the herbal mixture seized revealed presence of two SCs - 5F-ADB and FUB-AMB. The amount of 5F-ADB in blood was found to be 3.7 ng/mL by standard addition method. Severe and irreversible morphology changes in lung specimen, leading to ischemic damage of all internal organs and tissues, were observed during histological examination. The present case can be discussed as an example of both drug-induced and drug-related death resulting from acute intoxication with 5F-ADB and FUB-AMB as well as from systematic use of both synthetic cannabinoids.

Verapamil hydrochloride release characteristics from new copolymer zwitterionic matrix tablets.

The aim of this study was to synthesize stable copolymer (vinyl acetate-co-3-dimethyl[methacryloyloxyethyl] ammonium propane sulfinate) zwitterionic latex with different compositions for the first time by emulsifier-free emulsion copolymerization. Throughout the course of the study, a proposal was made for the explanation of the relationship between the "overshooting" phenomenon (a swelling kinetics with a maximum) and the specific self-association of the zwitterionic copolymers. The zwitterionic monomer unit mole fraction, pH, and ionic strength effects on this relationship, on the swelling kinetics of the zwitterionic copolymers, and on the sustained verapamil hydrochloride release from the model tablets were established by the study's authors.

Convenient replacement of the hydroxy by an amino group in 4 hydroxycoumarin and 4-hydroxy-6-methyl-2-pyrone under microwave irradiation.

The reaction of 4-hydroxycoumarin (1) with some primary amines 2a-h and morpholine (2i) under microwave irradiation occurred without opening of the lactone ring to give N-substituted 4-aminocoumarins 3a-i in excellent yields. Under the same experimental conditions, 4-hydroxy-6-methyl-2-pyrone (4) reacted with benzylamine (2e) or 2-phenyl- ethylamine (2f) to give the corresponding N,N'-disubstituted 4-amino-6-methyl-2-pyridones 5e,f. The main advantages of this procedure are dramatically shortened reaction times, higher amine utilization and considerably improved yields.

Synthesis and characterization of Zwitterionic co-polymers as matrices for sustained metoprolol tartrate delivery.

Very stable co-polymer (vinyl acetate (VA)-co-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) (p(VA-co-DMAPS)) latexes with different compositions have been synthesized by emulsifier-free emulsion co-polymerization. The dry p(VA-co-DMAPS)s have been used in the preparation of drug tablets for sustained Metoprolol tartrate release. It has been shown that the tablet swelling depends on the mol fraction of DMAPS monomer units (m(DMAPS)), pH and ionic strength (I). An original explanation, based on the swelling behavior of p(VA-co-DMAPS), has been proposed for the "overshooting" phenomenon observed. It assumes the formation of hydrophilic domains with a higher m(DMAPS) in the co-polymer tablets. The formation of dipole-dipole clusters between the DMAPS units at different m(DMAPS) and I are the main cause for the established differences in both the swelling kinetics of the p(VA-co-DMAPS) matrices and Metoprolol tartrate release. The obtained results show that for p(VA-co-DMAPS) matrices-based tablets controlled sustained Metoprolol tartrate release can be realized just by varying two parameters, co-polymer composition and I.

Solid phase selective separation and preconcentration of Cu(II) by Cu(II)-imprinted polymethacrylic microbeads.

Ion-imprinted polymer (IIP) particles are prepared by copolymerization of methacrylic acid as monomer, trimethylolpropane trimethacrylate as crosslinking agent and 2,2'-azo-bis-isobutyronitrile as initiator in the presence of Cu(II), a Cu(II)-4-(2-pyridylazo)resorcinol (Cu(II)-PAR) complex, and PAR only. A batch procedure is used for the determination of the characteristics of the Cu(II) solid phase extraction from the IIP produced. The results obtained show that the Cu(II)-PAR IIP has the greatest adsorption capacity (37.4 micromol g(-1) of dry copolymer) among the IIPs investigated. The optimal pH value for the quantitative preconcentration is 7, and full desorption is achieved by 1 M HNO(3). The selectivity coefficients (S(Cu/Me)) for Me=Ni(II), Co(II) are 45.0 and 38.5, respectively. It is established that Cu(II)-PAR IIPs can be used repeatedly without a considerable adsorption capacity loss. The determination of Cu(II) ions in seawater shows that the interfering matrix does not influence the preconcentration and selectivity values of the Cu(II)-PAR IIPs. The detection and quantification limits are 0.001 micromol L(-1) (3sigma) and 0.003 micromol L(-1) (6sigma), respectively.

Self-assembly, antipolyelectrolyte effect, and nonbiofouling properties of polyzwitterions.

An explanation of the unique nonbiofouling properties of polyzwitterions (PZ) is proposed [in this paper, the term "polyzwitterion" is preferred to "polybetain"]. The existence of an osmotic component of the driving force of the antipolyelectrolyte effect (APE) and the parameters governing this phenomenon are quantitatively established. The correlation between this effect, which is specific of PZ only, and the PZ nonbiofouling properties is grounded.