Controlled Radical Polymerization of Styrene and Methyl Acrylate in the Presence of Reversible Addition-Fragmentation Chain Transfer Agents, Phenylethyl Phenyl Dithioacetate and Phenyldithioacetic Acid

The use of phenyldithioacetic acid (PDA) in homopolymerizations of styrene or methyl acrylate produced only a small fraction of chains with dithioester end groups. The polymerizations using 1-phenylentyl phenyldithioacetate (PEPDTA) and PDA in the same reaction showed that PDA had little or no influence on the rate or molecular weight distribution even when a 1:1 ratio is used. The mechanistic pathway for the polymerizations in the presence of PDA seemed to be different for each monomer. Styrene favors addition of styrene to PDA via a Markovnikov type addition to form a reactive RAFT agent. The polymer was shown by double detection SEC to contain dithioester end groups over the whole distribution. This polymer was then used in a chain extension experiment and the M-n was close to theory. A unique feature of this work was that PDA could be used to form a RAFT agent in situ by heating a mixture of styrene and PDA for 24 h at 70 degrees C and then polymerizing in the presence of AIBN to give a linear increase in Mn and low values of PDI (< 1.14). In the case of the polymerization of MA with PDA, the mechanism was proposed to be via degradative chain transfer. (c) 2005 Wiley Periodicals, Inc.

Free volume and water uptake in a copolymer hydrogel series

A copolymer of X-hydroxyethyl methacrylate (HEMA) with 2-ethoxy ethyl methacrylate (EEMA) was synthesized and the molecular mobility, free volume, and density properties examined as a function of composition. These properties were correlated with the equilibrium water uptake in order to determine which of the properties were most influential in causing high water sorption, as these materials are suitable candidates for hydrogel systems. It was found that the polar HEMA repeat unit results in a rigid, glassy sample at room temperature due to the high degree of hydrogen bonding between chains whereas high EEMA content leads to rubbery samples with subambient glass transition temperatures. The free volume properties on the molecular scale measured by positron annihilation Lifetime spectroscopy (PALS) showed that higher HEMA content led to smaller, fewer holes and a lower free volume fraction than EEMA. Therefore the high water uptake of HEEMA-containing copolymers is largely related to the high polarity of the HEMA unit compared to EEMA, despite the low content of free volume into which the water can initially diffuse. Trends in density with copolymer composition, as measured on a macroscopic level, differs to that seen by PALS and indicates that the two techniques are measuring different scales of packing. (C) 1998 John Wiley & Sons, Inc.

Activation of beta(2)-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure

Background-Catecholamines hasten cardiac relaxation through beta-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of beta(1)- and beta(2)-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results-Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 mu mol/L) or zinterol (10 mu mol/L), mediated through beta(2)-adrenergic receptors, and of norepinephrine (10 mu mol/L), mediated through beta(1)-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17, Data did not differ between the 2 disease groups and were therefore pooled. Epinephrine, zinterol, and norepinephrine increased contractile force to approximately the same extent, hastened the onset of relaxation by 15+/-3%, 5+/-2%, and 20+/-3%, respectively, and reduced the time to half-relaxation by 26+/-3%, 21+/-3%, and 37+/-3%. These effects of epinephrine, zinterol, and norepinephrine were associated with phosphorylation (pmol phosphate/mg protein) of phospholamban 14+/-3, 12+/-4, and 12+/-3, troponin I 40+/-7, 33+/-7, and 31+/-6; and C-protein 7.2+/-1.9, 9.3 +/- 1.4, and 7.5 +/- 2.0. Phosphorylation of phospholamban occurred at both Ser16 and Thr17 residues through both beta(1)- and beta(2)-adrenergic receptors. Conclusions-Norepinephrine and epinephrine hasten human ventricular relaxation and promote phosphorylation of implicated proteins through both beta(1)- and beta(2)-adrenergic receptors, thereby potentially improving diastolic function.

A gene (Cargl) that regulates tissue resistance to Candida albicans maps to chromosome 14 of the mouse

Tissue susceptibility and resistance to infection with the yeast Candida albicans is genetically regulated. Analysis of the strain distribution pattern of the C. albicans resistance gene (Carg1) and additional gene and DNA segment markers in the AKXL recombinant inbred (RI) set showed that 13/15 RI strains were concordant for Carg1, Tcra and Rib1. Therefore, Carg1 is probably located within a 17 cM segment of chromosome 14, within approximately 4 cM of the other two genes. (C) 1998 Academic Press.

Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels

The omega-conotoxins are a set of structurally related, four-loop, six cysteine containing peptides, that have a range of selectivities for different subtypes of the voltage-sensitive calcium channel (VSCC). To investigate the basis of the selectivity displayed by these peptides, we have studied the binding affinities of two naturally occurring omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop hybrids using radioligand binding assays for N and P/Q-type Ca2+ channels in rat brain tissue. A selectivity profile was developed from the ratio of relative potencies at N-type VSCCs (using [I-125]GVIA radioligand binding assays) and P/Q-type VSCCs (using [I-125]MVIIC radioligand binding assays). in these peptides, loops 2 and 4 make the greatest contribution to VSCC subtype selectivity, while the effects of loops 1 and 3 are negligible. Peptides with homogenous combinations of loop 2 and 4 display clear selectivity preferences, while those with heterogeneous combinations of loops 2 and 4 are less discriminatory. H-1 NMR spectroscopy revealed that the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were similar; however, several differences in local structure were identified. Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin residues most Likely to interact with the N-type VSCC. (C) 1999 Academic Press.

Copolymer hydrogels of 2-hydroxyethyl methacrylate with n-butyl methacrylate and cyclohexyl methacrylate: synthesis, characterization and uptake of water

The bulk free radical copolymerizations of 2-hydroxyethyl methacrylate (HEMA) with n-butyl methacrylate (BMA) or cyclohexyl methacrylate (CHMA) were studied over the composition mole fraction interval of 0-1 for HEMA in the monomer feed. The C-13 NMR (125 MHz) spectra of the copolymers were analysed to determine the copolymer composition and the stereochemical configuration of the copolymers. The terminal model reactivity ratios of HEMA and BMA were found to be r(HEMA) = 1.73 and r(BMA) = 0.65 and for HEMA and CHMA, r(HEMA) = 1.26 and r(CHMA) = 0.31. The BMA and CHMA homopolymers were found to be predominantly syndiotactic with isotacticity parameters of theta(BB) = 0.18 and theta(CC) = 0.19, respectively. The copolymers were also found to be predominantly syndiotactic, indicating a strong tendency for racemic additions of the monomers in the formation of the copolymers. The diffusion of water into cylinders of poly(HEMA-co-BMA) and poly(HEMA-co-CHMA) was studied over a range of copolymer compositions and was found to be Fickian. The diffusion coefficients of water at 37 degrees C were determined from swelling measurements and were found to vary from 1.72 x 10(-11) m(2) s(-1) for polyHEMA to 0.97 x 10(-11) m(2) s(-1) for poly(HEMA-co-BMA) having a mole fraction F-HEMA = 0.80 and to 0.91 x 10(-11) m(2) s(-1) for a poly(HEMA-co-CHMA) also having F-HEMA = 0.80. The mass of water absorbed at equilibrium relative to the mass of dry polymer varied from 58.8 for polyHEMA to 27.2% for poly(HEMA-co-BMA) having F-HEMA = 0.85 and to 21.3% for poly(HEMA-co-CHMA) having F-HEMA = 0.80. (C) 1999 Elsevier Science Ltd. All rights reserved.

Embracing ligands. A synthetic strategy towards new nitrogen-thioether multidentate ligands and characterization of the cobalt(III) complexes

The synthesis of the hexadentate ligand 2,2,9,9-tetra(methyleneamine)-4,7-dithiadecane (EtN(4)S(2)amp) is reported. The ligand is of a type in which bifurcations of the chain occur at atoms other than donor atoms. The cobalt(III) complex [Co(EtN(4)S(2)amp)](3+) (1) was isolated and characterized. The synthetic methodology also results in a number of by-products, notably 2,9,9-tris(methyleneamine)-9-methylenehydroxy-4,7-dithiadecane (Et(HO)N(3)S(2)amp) and an eleven-membered pendant arm macrocyclic ligand 6,10-dimethyl-6,10-bis(methyleneamine)-1,4-dithia-8-azaacycloundec-7- ene (dmatue). The complexes [Co(Et(HO)N(3)S(2)amp)](3+) (2), in which the alcohol is coordinated to the metal ion, and [Co(dmatue)Cl](2+) (4) were isolated and characterized. Et(HO)N(3)S(2)amp also undergoes complexation with cobalt(III) to produce two isomers endo-[Co(Et(HO) N(3)S(2)amp)Cl](2+) (endo-3) and exo-[Co(Et(HO) N(3)S(2)amp)Cl](2+) (exo-3), both with an uncoordinated alcohol group. endo- 3 has the alcohol positioned cis, and exo-3 trans, to the sixth metal coordination site. Reaction of 1 with isobutyraldehyde, paraformaldehyde and base in dimethylformamide results in the encapsulated complex [Co(1,5,5,9,13,13-hexamethyl-18,21-dithia-3,7,11,15-tetraazabicyclo[7.7.6]docosa- 3,14-diene)](ClO4)(3) . 2H(2)O ([Co(Me(6)docosadieneN(4)S(2))](3+) ( 5). All complexes have been characterized by single crystal X-ray study. The low-temperature (11 K) absorption spectrum of 1 has been measured in Nafion films with spin-allowed (1)A(1g) --> T-1(1g) and (1)A(1g) --> T-1(2g) and spin forbidden (1)A(1g) --> T-3(1g) and (1)A(1g) --> T-3(2g) bands observed. The octahedral ligand-field parameters were determined (10Dq = 22570 cm(-1), B = 551 cm(-1); C = 3500 cm(-1)). For 5 10Dq and B were determined (20580 cm(-1); 516 cm(-1), respectively) and compared with those for similar expanded cavity complexes [Co(Me(8)tricosatrieneN(6))](3+) and [Co(Me(5)tricosatrieneN(6))](3+).

Embeddings of m-cycle systems and incomplete m-cycle systems: m<=14

In this paper we completely settle the embedding problem for m-cycle systems with m less than or equal to 14. We also solve the more general problem of finding m-cycle systems of K-v - K-u when m is an element of {4,6,7,8,10,12,14}.

Laboratory wear testing of polyurethane elastomers

A dry sand-rubber wheel abrasion test was used to investigate the wear behaviour of polyurethanes. The dry sand-rubber wheel abrasion test (DSRW test) is an approved ASTM test designed primarily for testing metals, therefore, in this study the set of test conditions was optimized for use with polyurethane elastomers. The wear performance of polyurethanes was assessed for the range of Shore hardness 85A to 65D, and a correlation was identified between the wear rate and the sample hardness. Polyurethane elastomers can be separated into three classes according to their hardness and wear performance, and each class shows a different dependence on the specimen temperature. This work has implications for use of the DSRW test for the prediction of field performance of polyurethanes. (C) Elsevier Science S.A.

Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons

The dependence of currents through the cyclic nucleotide-gated (CNG) channels of mammalian olfactory receptor neurons (ORNs) on the concentration of NaCl was studied in excised inside-out patches from their dendritic knobs using the patch-clamp technique. With a saturating concentration (100 mu M) of adenosine 3', 5'-cyclic monophosphate (cAMP), the changes in the reversal potential of macroscopic currents were studied at NaCl concentrations from 25 to 300 mM. In symmetrical NaCl solutions without the addition of divalent cations, the current-voltage relations were almost linear, reversing close to O mV. When the external NaCl concentration was maintained at 150 mM and the internal concentrations were varied, the reversal potentials of the cAMP-activated currents closely followed the Na+ equilibrium potential indicating that P-Cl/P-Na approximate to 0. However, at low external NaCl concentrations (less than or equal to 100 mM) there was some significant chloride permeability. Our results further indicated that Na+ currents through these channels: (i) did not obey the independence principle; (ii) showed saturation kinetics with K(m)s in the range of 100-150 mM and (iii) displayed a lack of voltage dependence of conductance in asymmetric solutions that suggested that ion-binding sites were situated midway along the channel. Together, these characteristics indicate that the permeation properties of the olfactory CNG channels are significantly different from those of photoreceptor CNG channels.

Impulse-response studies on tracer doses of [C-14]lignocaine and its multiple metabolites in the perfused rat liver

The outflow-concentration-time profiles for lignocaine (lidocaine) and its metabolites have been measured after bolus impulse administration of [C-14]lignocaine into the perfused rat liver. Livers from female Sprague-Dawley rats were perfused in a once-through fashion with red-blood-cell-free Krebs-Henseleit buffer containing 0 or 2% bovine serum albumin. Perfusate flow rates of 20 and 30 mL min(-1) were used and both normal and retrograde flow directions were employed. Significant amounts of metabolite were detected in the effluent perfusate soon after lignocaine injection. The early appearance of metabolite contributed to bimodal outflow profiles observed for total C-14 radioactivity. The lignocaine outflow profiles were well characterized by the two-compartment dispersion model, with efflux rate << influx rate. The profiles for lignocaine metabolites were also characterized in terms of a simplified two-compartment dispersion model. Lignocaine was found to be extensively metabolized under the experimental conditions with the hepatic availability ranging between 0.09 and 0.18. Generally lignocaine and metabolite availability showed no significant change with alterations in perfusate flow rate from 20 to 30 mt min(-1) or protein content from 0 to 2%. A significant increase in lignocaine availability occurred when 1200 mu M unlabelled lignocaine was added to the perfusate. Solute mean transit times generally decreased with increasing flow rate and with increasing perfusate protein content. The results confirm that lignocaine pharmacokinetics in the liver closely follow the predictions of the well-stirred model. The increase in lignocaine availability when 1200 mu M unlabelled lignocaine was added to the perfusate is consistent with saturation of the hydroxylation metabolic pathways of lignocaine metabolism.