Ruthenium(II)-catalyzed hydrogenation of carbon dioxide to formic acid. Theoretical study of real catalyst, ligand effects, and solvation effects

Ruthenium-catalyzed hydrogenation of carbon dioxide to formic acid was theoretically investigated with DFT and MP4(SDQ) methods, where a real catalyst, cis-Ru(H)2(PMe3)3, was employed in calculations and compared with a model catalyst, cis-Ru(H)2(PH3)3. Significant differences between the real and model systems are observed in CO2 insertion into the Ru(II)-H bond, isomerization of a ruthenium(II) eta1-formate intermediate, and metathesis of the eta1-formate intermediate with a dihydrogen molecule. All these reactions more easily occur in the real system than in the model system. The differences are interpreted in terms that PMe3 is more donating than PH3 and the trans-influence of PMe3 is stronger than that of PH3. The rate-determining step is the CO2 insertion into the Ru(II)-H bond. Its deltaG(o++) value is 16.8 (6.8) kcal/mol, where the value without parentheses is calculated with the MP4(SDQ) method and that in parentheses is calculated with the DFT method. Because this insertion is considerably endothermic, the coordination of the dihydrogen molecule with the ruthenium(II)-eta1-formate intermediate must necessarily occur to suppress the deinsertion. This means that the reaction rate increases with increase in the pressure of dihydrogen molecule, which is consistent with the experimental results. Solvent effects were investigated with the DPCM method. The activation barrier and reaction energy of the CO2 insertion reaction moderately decrease in the order gas phase > n-heptane > THF, while the activation barrier of the metathesis considerably increases in the order gas phase < n-heptane < THF. Thus, a polar solvent should be used because the insertion reaction is the rate-determining step.     

Novel type of heterogenized CuCl2 catalytic systems for oxidative carbonylation of methanol

A novel type of heterogenized CuCl₂ catalysts was designed for the oxidative carbonylation of methanol to dimethyl carbonate (DMC) taking account of the plausible reaction mechanism and intermediates. To prevent severe corrosion of the reaction equipment materials due to Cl^– while keeping the catalytic activity of the homogeneous CuCl₂ catalyst, we adopted, as supports (or ligands) of CuCl₂, four polymers, bearing a 2,2-bipyridine (bpy) or pyridine (py) unit, namely, poly(2,2-bipyridine-5,5-diyl) (Pbpy), poly(pyridine-2,5-diyl) (Ppy), poly(N,N-bisphenylene-2,2-bipyridine-4,4-dicarboxylic amide) (Bpya), and poly(4-methyl-4-vinyl-2,2-bipyridine) (Pvbpy), together with one chelate compound, 8-quinolinol. The catalytic activity, stability of heterogenized CuCl₂ and their corrosivities to stainless steels were examined in the liquid-phase reaction of the oxidative carbonylation of methanol. These polymer-supported catalysts showed considerable catalytic activity and stability for the DMC synthesis. In particular, the Pbpy-CuCl₂ and Ppy-CuCl₂ catalysts exhibited high DMC yields and selectivity comparable to those of the homogeneous CuCl₂ catalyst. This high activity appears to be associated with the presence of the -conjugated system in the polymers, which affect the redox reactions of Cu involved in the catalytic reaction. All of the polymer-supported CuCl₂ catalysts could be easily recycled after filtration, and the initial catalytic activity was maintained after three times of use. The corrosive characters of the catalysts were closely related to CuCl₂ leaching from the supports, which reflects the ability of supports to coordinate Cu. These experimental results suggest that both the electronic structure and the coordination ability of the polymer supports are key factors for the development of an effective catalytic system.     

Electrical conducting and magnetic properties of (ethylenedithiotetrathiafulvalenothioquinone-1,3-diselenolemethide)2.FeBr4 (GaBr4) crystals with two different interlayer arrangements of donor molecules

Two donor molecules newly synthesized, dimethylthio- and ethylenedithio-tetrathiafulvalenothioquinone-1,3-diselenolemethides (1 and 2), were used to prepare their charge-transfer (CT) salts with a magnetic FeBr(4)(-) counteranion. For 1, a low electrical conducting 1:1 salt (1.FeBr(4)) was obtained, in which molecules of 1 are tightly dimerized in a one-dimensional (1D) stacking column. On the other hand, 2 gave a 2:1 salt (2(2).FeBr(4)) as two different kinds of plate crystals (I and II). Both I and II possess similar stacking structures of molecules of 2 in each 1D column with a half-cut pipelike structure along the c axis. However, for I, the stacking columns are aligned in the same direction along the a and b axes, while for II they are in the same direction along the a axis, but in the reverse direction along the b axis, resulting in the difference in the relative arrangement of molecules of 2 and FeBr(4)(-) ions between the two crystals. The room-temperature electrical conductivities of the single crystals of I and II were 13.6 and 12.7 S cm(-)(1), respectively. The electrical conducting behavior in I was metallic above 170 K but changed to be semiconducting with a very small activation energy of 7.0 meV in the temperature range 4-170 K. In contrast, II showed the semiconducting behavior in the whole temperature range 77-285 K. The corresponding nonmagnetic GaBr(4)(-) salts with almost the same crystal structure as I and II showed definitively different electrical conducting properties in the metal to semiconductor transition temperature in I as well as in the magnitude of activation energy in the semiconducting region of I and II. The interaction between the d spins of FeBr(4)(-) ions was weak and antiferromagnetic in both I and II, but the magnitude of the spin interaction was unexpectedly larger compared with that in the FeBr(4)(-) salt of the corresponding sulfur derivative of 2 with closer contact between the neighboring FeBr(4)(-) ions. These electrical conducting and magnetic results suggest a significant interaction between the conducting pi electrons and the d spins of FeBr(4)(-) ions located near the columns or layers.     

Simultaneous assay of four stereoisomers of diltiazem hydrochloride. Application to in vitro chiral inversion studies

Summary The simultaneous stereospecific assay of four stereoisomers of diltiazem hydrochloride in bulk drug and aqueous solution was developed using HPLC on a Chiralcel OF column. The four isomers were quantitated with good precision by the internal standard method. The chiral inversion of (+)-cis-diltiazem hydrochloride in vitro, stability of its (2S, 3S) configuration in the solid and aqueous states was examined by HPLC. Chiral inversion of (+)-cis-diltiazem hydrochloride was not observed in the solid state, and its (2S, 3S) configuration was stable to heat, humidity and light. Chiral inversion of (+)-cis-diltiazem hydrochloride (2S, 3S) was observed in aqueous solution under UV, but not in aqueous solution stored at 80°C for 5h nor under visible light for 10 h. The (+)-cis-diltiazem hydrochloride (2S, 3S) epimerized to (+)-trans-diltiazem hydrochloride (2R, 3S) with a half-life of 5h in aqueous solution under UV but the reverse chiral inversion of (+)-trans-diltiazem hydrochloride (2R, 3S) to (+)-cis-diltiazem hydrochloride (2S, 3S) was not observed.     

Preparation of zein microspheres conjugated with antitumor drugs available for selective cancer chemotherapy and development of a simple colorimetric determination of drugs in microspheres

Zein microspheres conjugated with antitumor drugs (mitomycinc (MMC), daunomycin hydrochloride (DM), peplomycin sulfate (PEP] were prepared by using a dimethyl sulfoxide (DMSO)-H2O system. MMC with low solubility in H2O was easily entrapped by the standard procedure, whereas some modifications were required for moderately and highly soluble drugs such as DM and PEP. Colorimetric determination of the drugs in microspheres was easily achieved by use of the phenol-sulfuric acid method for drugs with sugar moieties in their molecules, such as DM and PEP, while a simple treatment of the microspheres with concentrated sulfuric acid was applied in the case of drugs having a chromophore in their molecules, such as DM and MMC.     

A synthesis of 2-substituted 2-aminoethanol derivatives having inhibitory activity against protein kinase C.

A series of 2-aminoethanol derivatives was synthesized and their inhibitory activities against protein kinase C were investigated. Among these compounds, 2-endo-hexadecylamino-5-norbornene-2- exo-methanol (4h) and 2-endo-hexadecylamino-5-norbornene-2,3-exo-dimethanol (4i) inhibited protein kinase C at the IC50 values of 2 x 10(-5) and 1 x 10(-5) M, respectively, but not protein kinase A at a concentration of 1 x 10(-3) M. The structure-activity relationships are discussed.     

Quantification of 5-fluoro-2'-deoxyuridine in plasma by gas chromatography and negative-ion chemical ionization mass spectrometry.

A sensitive and specific method using gas chromatography and negative-ion chemical ionization mass spectrometry is described for the determination of 5-fluoro-2'-deoxyuridine (FdUrd) in plasma. The method is based on the formation of the pentafluoropropionyl derivative of FdUrd and of its stable isotope as internal standard after sample clean-up by solid-phase extraction and purification by high-performance liquid chromatography. Quantification in plasma was possible down to 300 pg/ml. The method was applied to the analysis of plasma levels of FdUrd in mice and dogs.     

Asymmetric 1,4-addition of alkenylzirconium reagents to α,β-unsaturated ketones catalyzed by chiral rhodium complexes

Highly enantioselective 1,4-addition of alkenylzirconocene chlorides to α,β-enones was found to be catalyzed by a chiral rhodium complex generated from [Rh(cod)(MeCN)₂]BF₄ and (S)-BINAP. The reaction can be applied to either cyclic or acyclic enones and the optical yield was up to 99% ee. The reaction mechanism would involve the transmetalation between the alkenylzirconocene chloride and the rhodium complex to give the alkenylrhodium species as a key intermediate.     

Basic evaluation of highly sensitive thyroid stimulating hormone immunoradiometric assay kits

Usefulness of three kinds of TSH kits by immunoradiometric assay (IRMA) was evaluated. They were able to measure low levels (less than 0.1 microIU/ml) in serum thyroid stimulating hormone (TSH) with incubation of short time (4 hours). In particular, RIABEAD II kit had a highly specific affinity for TSH and the normal range (+/- 2 S.D.) using it showed from 0.20 to 3.50 microIU/ml in 150 normal subjects. In patients with hyperthyroidism and in patients with hypothyroidism, the values of TSH were lower and higher than those of normal subjects, respectively. Another kits showed similar results. These results indicate that these TSH-IRMA kits are useful to evaluate serum TSH levels exactly.