Synthesis of various stimuli‐responsive gradient copolymers by living cationic polymerization and their thermally or solvent induced association behavior

Stimuli‐responsive gradient copolymers, composed of various monomers, were synthesized by living cationic polymerization in the presence of base. The monomers included thermosensitive 2‐ethoxyethyl vinyl ether (EOVE) and 2‐methoxyethyl vinyl ether (MOVE), hydrophobic isobutyl vinyl ether (IBVE) and 2‐phenoxyethyl vinyl ether (PhOVE), crystalline octadecyl vinyl ether (ODVE), and hydrophilic 2‐hydroxyethyl vinyl ether (HOVE). The synthesis of gradient copolymers was conducted using a semibatch reaction method. Living cationic polymerization of the first monomer was initiated using a conventional syringe technique, followed by an immediate and continuous addition of a second monomer using a syringe pump at regulated feed rates. This simple method permitted precise control of the sequence distribution of gradient copolymers, even for a pair of monomers with very different relative monomer reactivities. The stimuli‐responsive gradient, block and random copolymers exhibited different self‐association behavior. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6444–6454, 2008     

Reaction control in radical polymerization of di‐n‐butyl itaconate utilizing a hydrogen‐bonding interaction

We have reported that intramolecular chain‐transfer reaction takes place in radical polymerization of itaconates at high temperatures and/or at low monomer concentrations. In this article, radical polymerizations of di‐n‐butyl itaconate (DBI) were carried out in toluene at 60 °C in the presence of amide compounds. The ¹³C‐NMR spectra of the obtained poly(DBI)s indicated that the intramolecular chain‐transfer reaction was suppressed as compared with in the absence of amide compounds. The NMR analysis of DBI and N‐ethylacetamide demonstrated both 1:1 complex and 1:2 complex were formed at 60 °C through a hydrogen‐bonding interaction. The ESR analysis of radical polymerization of diisopropyl itaconate (DiPI) was conducted in addition to the NMR analysis of the obtained poly(DiPI). It was suggested that the suppression of the intramolecular chain‐transfer reaction with the hydrogen‐bonding interaction was achieved by controlling the conformation of the side chain at the penultimate monomeric unit of the propagating radical with an isotactic stereosequence. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4895–4905, 2004     

High-throughput and simultaneous analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography–tandem mass spectrometry in the positive and negative ionization modes

In this report, a high-throughput and sensitive method for analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) in the positive and negative ionization modes using tolbutamide as internal standard is presented. After pretreatment of a plasma sample by solid-phase extraction with an Oasis HLB cartridge, muscle relaxants were analyzed by UPLC with Acquity UPLC BEH C₁₈ column and Acquity TQD tandem quadrupole mass spectrometer equipped with an electrospray ionization interface. The calibration curves for muscle relaxants spiked into human plasma equally showed good linearities in the nanogram per milliliter order range. The detection limits (signal-to-noise ratio = 3) was as low as 0.1–2 ng/mL. The method gave satisfactory recovery rates, accuracy, and precision for quality control samples spiked with muscle relaxants. To further validate the present method, 250 mg of chlorphenesin carbamate was orally administered to a healthy male volunteer, and the concentrations of chlorphenesin carbamate in plasma were measured 0.5, 1, 2, 4, 6, and 8 h after dosing; their concentrations in human plasma were between 0.62 and 2.44 μg/mL. To our knowledge, this is the first report describing simultaneous analysis of over more than two central-acting muscle relaxants by liquid chromatography–tandem mass spectrometry. This has been realized by the capability of our instrument for simultaneous multiple reaction monitoring of the target compounds in both positive and negative ionization modes. Therefore, the present method seems very useful in forensic and clinical toxicology and pharmacokinetic studies.     

Thromboxane A2 receptor antagonists. II. Synthesis and pharmacological activity of 6,6-dimethylbicyclo[3.1.1]heptane derivatives with the benzenesulfonylamino group

Various stereoisomers based on the alpha- and omega-side chain ring junctions of 6,6-dimethylbicyclo[3.1.1]heptane were synthesized. Their sodium salts 12, 18, 20, 30 and 37 were examined in vitro for their inhibitory activity toward aggregation of rabbit platelet-rich plasma and rat washed platelets. Their potency was very high and the partial agonist effect was small. The differences of the side chain ring junctions did not affect the activity very much. Homologation in the omega-side chain (as in 47) decreased the activity.     

Elementary reaction analysis of the radical polymerization of α‐ethyl β‐N‐(α′‐methylbenzyl)itaconamates carrying (RS)‐ and (S)‐α‐methylbenzylaminocarbonyl groups

The polymerizations of α‐ethyl β‐N‐(α′‐methylbenzyl)itaconamates carrying (RS)‐ and (S)‐α‐methylbenzylaminocarbonyl groups (RS‐EMBI and S‐EMBI) with dimethyl 2,2′‐azobisisobutyrate (MAIB) were studied in methanol (MeOH) and in benzene kinetically and with electron spin resonance (ESR) spectroscopy. The initial polymerization rate (R_p) at 60 °C was given by R_p = k[MAIB]^{0.58 ± 0.05}[RS‐EMBI]^{2.4 ± 0.l} and R_p = k[MAIB]^{0.61 ± 0.05}[S‐EMBI]^{2.3 ± 0.l} in MeOH and R_p = k[MAIB]^{0.54 ± 0.05}[RS‐EMBI]^{1.7 ± 0.l} in benzene. The rate constants of initiation (k_df), propagation (k_p), and termination (k_t) as elementary reactions were estimated by ESR, where k_d is the rate constant of MAIB decomposition and f is the initiator efficiency. The k_p values of RS‐EMBI (0.50–1.27 L/mol s) and S‐EMBI (0.42–1.32 L/mol s) in MeOH increased with increasing monomer concentrations, whereas the k_t values (0.20?7.78 × 10⁵ L/mol s for RS‐EMBI and 0.18?6.27 × 10⁵ L/mol s for S‐EMBI) decreased with increasing monomer concentrations. Such relations of R_p with k_p and k_t were responsible for the unusually high dependence of R_p on the monomer concentration. The activation energies of the elementary reactions were also determined from the values of k_df, k_p, and k_t at different temperatures. R_p and k_p of RS‐EMBI and S‐EMBI in benzene were considerably higher than those in MeOH. R_p of RS‐EMBI was somewhat higher than that of S‐EMBI in both MeOH and benzene. Such effects of the kinds of solvents and monomers on R_p were explicable in terms of the different monomer associations, as analyzed by ¹H NMR. The copolymerization of RS‐EMBI with styrene was examined at 60 °C in benzene. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1819–1830, 2003     

Formation of kink bands by compression of the extrudate of solid linear polyethylene

Extrudates of solid linear polyethylene prepared under proper pressure and temperature conditions have a high c axis orientation along the extrusion direction, with lamellar crystals and amorphous layers stacked alternately along the extrusion direction. Kink bands were formed by compressing the oriented extrudate at room temperature along the extrusion direction. Inspection of the kink bands by wide-angle and small-angle x-ray diffraction and electron microscopy revealed that the fiber axis was rotated from the original axis direction by 70–75° and that the lamellar crystals were inclined to the fiber axis in the kink band by 55–60° and stacked nearly parallel to the kink boundary. The superstructural change during the formation of the kink band could not be interpreted in terms of uniform c axis shear alone. In addition to such a mechanism, it was necessary to take into account intermicrofibril and/or intercrystallite slip.     

Total synthesis of a macrocyclic spermidine alkaloid,codonocarpine

Total synthesis of codonocarpine ($\text{5}$) and its regio-isomer ($\text{1}$$\text{5}$) utilizing a new cyclization procedure is described.