Properties of calcium-induced gel beads prepared with alginate and hydrolysates

Calcium-induced alginate gel beads (Alg-Ca) containing alginate hydrolysate, such as the guluronic acid block (GB), was prepared and the drug release profiles were investigated under simulated gastrointestinal conditions. The addition of GB to Alg-Ca altered its rheological properties. A model drug (hydrocortisone) was incorporated at 78% of its theoretical yield within the dried Alg-Ca containing 5% GB and it was gradually released from the beads in JP XIV 1st medium for disintegration test (pH 1.2), while it was rapidly released with disintegration of the gel matrix in JP XIV 2nd medium (pH 6.8). In contrast, for Alg-Ca containing GB and chitosan, disintegration was not observed in these media and the drug release rate was markedly different. These results demonstrate that the release profiles of drugs incorporated into Alg-Ca can be controlled by adding these polysaccharides.     

Theoretical calculation of the steric effects of ortho substituents by the AM1 method

The AM1 calculation was done for ortho-substituted toluenes (o-X-C₆H₄-CH₃) and ortho-substituted tert-butylbenzenes (o-X-C₆H₄-t-Bu). The difference in the calculated heat of formation between o-X-C₆H₄-CH₃ and o-X-C₆H₄-t-Bu was used as a theoretical steric index for ortho-X. The correlation of this theoretical steric index with the empirical steric parameter sets such as our recently defined E_s(AMD) and the Taft–Kutter–Hansch (TKH) E_s was examined. In spite of the simplicity of the model system, the theoretical index was linear with the E_s(AMD) constant with a correlation coefficient of r = 0.972 for 17 substituents of various structures. Including the phenyl group, the correlation with the TKH E_s constant was r = 0.948. The theoretically calculated index was shown to serve as a measure of the ortho steric effect.     

The Electronic Structure of Azuleno[1,2,3-cd]phenalene and Azuleno[5,6,7-cd]phenalene,a Comparison

The photoelectron (PE.) spectra of azuleno[l, 2, 3-cd]phenalene ( 1 ) and azuleno- [5,6,7-cd]phenalene( 2 ) have been recorded. The first five bands of both compounds could be assigned to transitions corresponding to removal of electrons from 4a₂, 6b₁, 5b₁, 3a₂ and 4b_l orbitals. This assignment is based mainly on a comparison between the observed ionization potentials and orbital energies calculated in a HMO and a PPP model. The UV./VIS. polarized absorption spectrum of 1 in the region 10000–45000 cm^?1 has been measured by means of the stretched film technique. The measurements were performed in polyethylene sheets at 77°K. Several bands could be assigned to π* ← π transitions calculated by a PPP-CI method. A comparison between the electronic structures of 1 and 2 is made by means of a simple HMO diagram.     

Phospholipases Induce Melanogenesis in Organ-Cultured Skin

Guinea pig skin becomes more pigmented following exposure to UV rays. This melanization was accompanied by enhanced intensity of tyrosinase-staining and increased number of tyrosinase-positive melanocytes (MEL^ty+), with resultant enhancement of melanin synthesis. To clarify the regulatory mechanism for melanization following UV irradiation, organ-cultured guinea pig skins have been used to examine their melanogenic responses to exogenous stimulation. This organ culture system responded well to UV irradiation, by increasing melanogenic activity. Also, in this system, phospholipases (PL), arachidonic acid, interleukin-1α and melanocytestimulating hormone, but not endothelin-1 or phosphatidylinositol-specific PLC (PI-PLC), stimulated melanogenesis to various extents as indicated by the number of MEL^ty+ and morphological changes. Among them, the PLA₂ and PLD were found to have a potent stimulatory property for melanocytes. They might affect melanocytes directly or indirectly through an effect on keratinocytes. These results suggest that PLA₂ and PLD play a key role in epidermal hyperpigmentation after UV irradiation or inflammation.     

Solvent-free reactions of fullerenes and N-alkylglycines with and without aldehydes under high-speed vibration milling

The solvent-free reactions of fullerenes and N-alkylglycines with and without aldehydes (RCHO) 2a-e under high-speed vibration milling (HSVM) conditions have been investigated. Fulleropyrrolidines 4a-e (C₆₀(CH₂N(CH₃)CHR), R=H (4a), C₆H₅ (4b), p-NO₂-C₆H₄ (4c), p-CH₃O-C₆H₄ (4d), p-(CH₃)₂N-C₆H₄ (4e)) were obtained in moderate yields from reactions of C₆₀ with aldehydes 2a-e and N-methylglycine (Prato reaction). In all these solvent-free reactions, 4a was found to be formed besides 4b-e, indicating that fullerenes can react with N-substituted glycines in the absence of aldehyde to give fulleropyrrolidines. For this novel reaction, a possible reaction mechanism involving an electron transfer process has been proposed. Intrigued by this observation, the dependence of the yield on the reagent ratio for the reaction of C₆₀ with paraformaldehyde and/or N-methylglycine was examined to search the optimal conditions. The reaction of C₇₀ with paraformaldehyde and/or N-methylglycine under HSVM conditions was also studied and was found to give the positional isomers of [70]fulleropyrrolidines.     

Blue myoglobin reconstituted with an iron porphycene shows extremely high oxygen affinity

Myoglobin will be a good scaffold for engineering a function into proteins. To modulate the physiological function of myoglobin, almost all approaches have been demonstrated by site-directed mutagenesis, however, there are few studies which show a significant improvement in the function. In contrast, we focused on the replacement of heme in the protein with an artificial prosthetic group. Recently, we prepared a novel myoglobin reconstituted with an iron porphycene as a structural isomer of mesoheme. The bluish colored reconstituted myoglobin is relatively stable and the deoxymyoglobin reversibly binds ligands. Interestingly, the O2 affinity of the reconstituted myoglobin, 1.1 x 109 M-1, is a significant 1,400-fold higher than that of the native myoglobin. Furthermore, the unfavorable autoxidation kinetics show 7-fold decrease in rate for the reconstituted myoglobin relative to the native myoglobin, indicating the stable oxy-form against autoxidation. The net results come from the slow dissociation of the O2 ligand in the reconstituted myoglobin, koff = 0.11 s-1, because of the formation of strong hydrogen bond between His64 and negatively charged dioxygen. The present study indicates that the replacement of native heme with an artificially created prosthetic group will give us a unique function into a hemoprotein.     

Two New Spermidine Alkaloids from Chisocheton weinlandii

The investigation of the MeOH extract of the leaves of Chisocheton weinlandii Harms (Meliaceae) revealed two new open‐chain spermidine alkaloids, chisitine 1 ( 1 ) and chisitine 2 ( 2 ). Their structures were elucidated by NMR spectroscopy, tandem‐mass spectrometry, and independant syntheses (Scheme 3). Detailed MS/MS fragmentation pathways are discussed for both compounds based on H/D exchange and ¹⁸O‐labeling experiments (Schemes 1 and 2).     

Cation recognition on a fullerene-based macrocycle

Heterocyclic orifices in cage-opened fullerene derivatives are regarded as potential ligands toward metals or ions, being reminiscent of truncated fullerenes as a hypothetical class of macrocycles with spherical π-conjugation. Among a number of cage-opened examples reported thus far, the coordination ability and dynamic behavior in solution still remained unclear due to difficulties in structural determination with multiple coordination sites on the macrocycles. Herein, we present the detailed solution dynamics of a cage-opened C₆₀ derivative bearing a diketo bis(hemiketal) moiety in the presence of alkali metal ions. The NMR spectroscopy disclosed the coordination behavior which is identified as a two-step process with a 1 : 2 stoichiometry. Upon coordination to the Li⁺ ion, the macrocycle largely varies its properties, i.e., increased absorption coefficients in the visible region due to weakly-allowed charge transfer transitions as well as the inner potential field from neutral to positive by the charge delocalization along with the spherical π-surface. The Li⁺-complexes formed in situ underwent unprecedented selective dehydroxyhydrogenation under high-pressure conditions. These findings would facilitate further studies on fullerene-based macrocycles as metal sensors, bulky ligands in organic reactions, and ion carriers in batteries and biosystems.

A fullerene-based Lewis-basic macrocyclic ligand underwent complexation with alkali-metal ions in 1 : 1 and 1 : 2 fashions, resulting in considerable perturbation to absorption properties as well as the potential surface inside the cage.     

Molecular mechanics (MM3) calculations on lithium amide compounds

The MM3 force field has been extended to deal with the lithium amide molecules that are widely used as efficient catalysts for stereoselective asymmetric synthesis. The MM3 force field parameters have been determined on the basis of the ab initio MP2/6-31G* and/or DFT (B3LYP/6-31G*, B3-PW91/6-31G*) geometry optimization calculations. To evaluate the electronic interactions specific to the lithium amides derived from the diamine molecules properly, the Lewis bonding potential term for the interaction between the lithium atom and the nonbonded adjacent electronegative atom such as nitrogen was introduced into the MM3 force field. The bond dipoles were evaluated correctly from the electronic charges on the atoms calculated by fitting to the electrostatic potential at points selected. The MM3 results on the molecular structures, conformational energies, and vibrational spectra show good agreement with those from the quantum mechanical calculations.     

Influence of amino acid side chain packing on Fe-methionine coordination in thermostable cytochrome C

Paramagnetic NMR and optical studies of the oxidized forms of mesophile Pseudomonas aeruginosa cytochrome c(551) and its quintuple mutant (F7A/V13M/F34Y/E43Y/V78I), and thermophile Hydrogenobacter thermophilus cytochrome c(552) demonstrated that the amino acid side chain packings in the protein interior influence the coordination bond between the heme iron and the axial methionine in the proteins. The strength of heme axial coordinations was found to correlate with the overall protein thermostability.