Stability of a novel hexapeptide, (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt, with neurotensin activity, in aqueous solution and in the solid state

The stability and some physicochemical properties of a novel hexapeptide, (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt (I), with neurotensin activity, were investigated. The degradation of I in aqueous solution was observed as a pseudo-first order reaction. By determining the degradation rate of I at various pH values, it was found that I was most stable at around pH 4. The activation energies of the degradation in aqueous solutions at pH 2.2, 6.1, 7.0 and 8.0 were 16.3, 22.2, 23.9 and 24.2 kcal/mol, respectively. The enzymatic hydrolysis of I was studied in vitro with a porcine liver esterase at 37 degrees C. The degradation of I in this system was observed as a pseudo-first order reaction. The degradation rate of I in the presence of the esterase was about 10000 times larger than the rate in a buffer solution. I in the solid state was stable under 65 degrees C and labilized by strong light and/or high humidity. The pKa1, pKa2 and pKa3 of I were 7.1, 10.0 and 11.3, respectively. The partition coefficients between n-octanol and the buffer solution at pH values ranging from 2 to 11 were measured. The partition coefficient increased with the increase of the pH value. But the value at pH 7.0 was 2.10 x 10(-2), which was very low. The solubility of I in aqueous solution was more than 10 mg/ml. From the results of the powder X-ray diffraction pattern, I in the solid state was found to be amorphous. The dissolution rates in the 1st and 2nd fluid of JPXI at 37 degrees C and 100 rpm were 19.4 and 9.0 mg/cm2.min, respectively.     

Synthesis and properties of new polyesters having tetrahydrofuran rings in their main chains

New polyesters 6a–6c consisting of 2,4-linked tetrahydrofuran rings were synthesized by bulk polycondensation of methyl trans- and cis-4-hydroxytetrahydrofuran-2-carboxylates ( 5a and 5b ) and a stereoisomeric mixture of methyl 4-hydroxy-5-methyltetrahydrofuran-2-carboxylate ( 5c ) at high temperature. These monomers were prepared from methyl glycolate or methyl lactate and diethyl maleate through a four-step reaction sequence. The polycondensation was carried out without solvent at different temperatures ranging from 150 to 220°C. Titanium isopropoxide was most effective among the catalysts examined, giving polyesters with number-average molecular weights up to 2 × 10⁴. Polyester 6a consisting of trans-2,4-linked tetrahydrofuran rings was soluble in trifluoroacetic acid and a mixed solvent of chloroform and methanol (10/1, v/v). Polyester 6b composed of cis-2,4-linked tetrahydrofuran rings was soluble in dimethyl sulfoxide and dimethylformamide in addition to the two solvents for 6a . Polyester 6c with 5-methyl-substituted tetrahydrofuran rings was composed of a mixture of stereoisomeric units and thus was soluble in a variety of solvents including chloroform, tetrahydrofuran, acetonitrile, dimethyl sulfoxide, and dimethylformamide. The glass transition temperatures of 6a, 6b , and 6c determined by DSC were 109, 88, and 66°C. These polyesters were found to be very slowly hydrolyzed in a neutral phosphate buffer solution at ambient temperature. © 1993 John Wiley & Sons, Inc.     

γ-irradiation of polypropylene in vacuum and in air

Polypropylene films were irradiated with ⁶⁰Co γ-rays in vacuum or in air and stored in air. Just after irradiation, the concentration of carbonyl group of the sample irradiated in air only increased with dose. The concentrations of both samples increased with storage time. The more the absorbed doses, the higher the increasing rates. The increasing rate of the concentration of carbonyl group during irradiation in air was higher than those during storage in air. Just after irradiation, the tensile strengths and the elongations of the both samples somewhat increased with dose at the doses less than 5 Mrad, but decreased at doses more than 13 Mrad. The tensile strength and the elongation of the sample irradiated in air decreased with storage time. Those of the sample irradiated in vacuum also decreased with storage time but the decreasing rates were much smaller than those in the sample irradiated in air. The gel fractions of the samples irradiated in vacuum and annealed in vacuum were somewhat higher than those irradiated in vacuum and not annealed. To elucidate high oxidation rate in the sample irradiated in air during and after irradiation, reaction mechanisms were discussed. To clarify the difference of mechanical properties between the samples irradiated in vacuum and in air, the effect of crosslink was considered, together with the oxidation.     

Simultaneous determination of tetrahydro-β-carbolines and β-carbolines

Summary Reversed-phase ion-pair HPLC with fluorimetric detectors connected in series was studied for the simultaneous determination of two tetrahydro--carbolines and two -carbolines. After additon of internal standards the samples were reacted with fluorescamine, and then subjected to serial extractions to remove their precursor (tryptamine) from the analytical system. This treatment not only suppressed the artefactual formation of tetrahydro--carbolines and -carbolines during analysis, but also effectively purified them. Under optimum conditions, using trifluoroacetic acid as counter ion, all analytes were separated within 14 min and without major interfering peaks. The quantitative ranges were 0.25–80.0 ng mL^–1 for both tetrahydro--carbolines and 0.1–30.0 ng mL^–1 for both -carbolines. Replicate spiking experiments showed that recovery from most of the samples tested was over 90% and the relative standard deviation ranged from 0.7 to 10.4% within and between assays. The proposed method was applicable to various materials such as soy sauce, vinegar, ketchup, tabasco, beer, wine, sake, whisky, brandy, cows' milk, coffee, cocoa, cheese, cigarette smoke and urine.     

Amphiphilic block copolymers of vinyl ethers by living cationic polymerization. II. Synthesis and surface activity of macromolecular amphiphiles with pendant amino groups

Amphiphilic block polymers of vinyl ethers (VEs). $\rlap{--} [{\rm CH}_{\rm 2} {\rm CH}\left( {{\rm OCH}_{\rm 2} {\rm CH}_{\rm 2} {\rm NH}_{\rm 2} } \right)\rlap{--} ]_m \rlap{--} [{\rm CH}_{\rm 2} {\rm CH}\left( {{\rm OR}} \right)\rlap{--} ]_n \left( {{\rm R: }n{\rm - C}_{{\rm 16}} {\rm H}_{{\rm 33}} ,{\rm }n{\rm - C}_{\rm 4} {\rm H}_{\rm 9} ;m \simeq 40,{\rm n} = 1 - 10} \right)$ were prepared, each of which consists of a hydrophilic segment with pendant primary amino groups and a hydrophobic poly(alkyl VE) segment. Their precursors were obtained by the HI/I₂-initiated sequential living cationic polymerization of an alkyl VE and a VE with a phthalimide pendant (CH₂ = CHOCH₂CH₂Im; Im; phthalimide group), where the segment molecular weights and compositions (m/n ratio) could be controlled by regulating the feed ratio of two monomers and the concentration of hydrogen iodide. Hydrazinolysis of the imide functions gave the target polymers which were readily soluble in water under neutral conditions at room temperature. These amphiphilic block polymers lowered the surface tension of their aqueous solutions (0.1 wt%, 25°C) to a minimum ? 30 dyn/cm when the hydrophobic pendant R was n-C₄H₉ (n = 4–9). The polymers with n-C₄H₉ pendants in the hydrophobic segment exhibited a higher surface activity than those with n-C₁₆ H₃₃ pendants. The surface activity of the polymers also depended on the pH of the polymer solutions; the surface activity increased in more basic solutions where the ionization of the amino group (? NH₂)2? NH₃^⊕) is suppressed.     

Reactions of 1,2‐dihydro‐4H‐3,1‐benzothiazine‐2,4‐dithiones (trithioisatoic anhydrides) with N‐substituted benzylamines and trialkyl phosphites

Reactions of 1,2‐dihydro‐4H‐3,1‐benzothiazine‐2,4‐dithiones (trithioisatoic anhydrides) 3 with N‐substi‐tuted benzylamines 9 gave 1,2‐dihydroquinazoline‐4‐thiones 10 , o‐thioureidodithiobenzoic acid 11 , o‐aminothiobenzamides 12 , 2‐amino‐3,1‐benzothiazine‐4‐thiones 13 , or quinazoline‐2,4‐dithiones 14 , depending on the kinds of amine and the reaction solvent. On the other hand, reaction of 3 with trialkyl phosphites afforded dialkyl (1,2‐dihydro‐2‐thioxo‐4H‐3,1‐benzothiazin‐4‐yl)phosphonates 18 .     

Radical-initiated homopolymerization and copolymerization of ethyl α-hydroxymethylacrylate

Ethyl α-hydroxymethylacrylate (EHMA) was synthesized and homopolymerized in bulk and in solution. The poly(EHMA) is readily soluble in alcohol, acetone, tetrahydrofuran, and methylene chloride at room temperature. Intramolecular lactone formation occurred when poly(EHMA) was heated to 180–230°C. The kinetics of EHMA homopolymerization was investigated in ethyl acetate, using α,α′-azobisisobutylonitrile as an initiator. The rate of polymerization R_p was expressed by R_p = k[AIBN]^0.50[EHMA]^1.4 and the overall activation energy was calculated as 71.9 kJ/mol. Kinetic constants for EHMA polymerization were obtained as follows: k_p/k = 0.17L^0.9mol^?0.9s^?0.5; 2fk_d = 1.5 × 10^?5 s^?1. The relative reactivity ratios of EHMA(M₂) copolymerization with styrene (r₁ = 0.472, r₂ = 0.564) in ethyl acetate were obtained. Applying the Q-e scheme led to Q = 0.84 and e = 0.35 for EHMA.     

Grinding-induced equimolar complex formation between thiourea and ethenzamide

We prepared and characterized a grinding-induced equimolar complex of thiourea with ethenzamide. When thiourea and ethenzamide were co-ground at a molar ratio of 3 : 1, new powder X-ray diffraction (PXRD) peaks were observed in addition to PXRD peaks of thiourea crystals. The optimum stoichiometry of the new structure was confirmed as 1 : 1 mol/mol. Effect of grinding time on the thiourea-ethenzamide equimolar complex formation was investigated by using PXRD, differential scanning calorimetry and Fourier transform infrared spectroscopy. The equimolar crystal structure was confirmed by X-ray diffraction measurements of the single crystal which was recrystallized from ethanol. It was found that the intermolecular hydrogen bond formations between thiourea and ethenzamide molecules contributed to the equimolar complex formation. The complex formation was not observed in the cases where benzamide, salicylamide or 3-ethoxybenzamide was co-ground with thiourea. 2-Alcoxyl benzamide structures should be required for the grinding-induced equimolar complex formation with thiourea.     

Preparation and Optical Properties of Gold-Dispersed BaTiO3, PGO (Pb5Ge3O11) and PLT (Pb1-1.5xLaxTiO3) Thin Films by Sol-Gel Process

Gold-dispersed BaTiO₃, PGO and PLT thin films, which will be used for third-order nonlinear optical devices, were prepared by sol-gel process with spin-coating using HAuCl₄4H₂O, Ba(CH₃COO)₂, Ti[O(CH₂)₃CH₃]₄, Pb(CH₃COO)₂3H₂O, Ge[O-n-C₄H₉]₄, La(CH₃COO)₃1.5 H₂O as starting materials. The thin films were heat-treated in air at temperatures ranging from 400 to 800 for 1 h. The nonlinear optical property of these thin films was measured by the degenerate four-wave mixing (DFWM) method using a frequency-doubled Nd: YAG laser with 20 ps pulse duration. Third-order nonlinear susceptibility χ⁽³⁾ of gold-dispersed BaTiO₃, PGO and PLT thin films with 5 vol% of gold were 1.410⁻⁶ esu, 3.510⁻⁷ esu respectively. The large χ⁽³⁾ may be ascribed to the high dielectric constant of the films.     

Site-specific cleavage of glycated human serum albumin in the presence of iron.

Nonenzymatically glycated human serum albumin was incubated with ferric ion at 37 degrees C in 0.2 M phosphate buffer, pH 7.4, up to 30 days. In the incubation mixture, amino acids, tyrosine and phenylalanine, were detected, suggesting site specific cleavage of glycated human serum albumin.