The first halogen-substituted cyclotrigermenes: a unique halogen walk over the three-membered ring skeleton and facial stereoselectivity in the Diels-Alder reaction

Dark red crystals of the halogen-substituted cyclotrigermenes [(tBu3Si)3Ge3X; X = Cl, Br, I] were obtained in good yields by the reaction of [(tBu3Si)3Ge3]+.TTFPB- (TTFPB- = tetrakis(2,3,5,6-tetrafluorophenyl)borate) with potassium halides (KCl, KBr, or KI) in diethyl ether. The crystal structures of the halogen-substituted cyclotrigermenes reveal a cis-bent Ge=Ge double bond, caused by the introduction of the electronegative halogen atom on the sp3 germanium atom of cyclotrigermene. In solution, an intramolecular halogen migration over the three-membered ring skeleton was observed. Facial stereoselectivity in the Diels-Alder reaction of new cyclotrigermenes with 2,3-dimethyl-1,3-butadiene is also reported.     

A concise route to (+)-lactacystin

A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris).     

Separation selectivity of anionic metal complexes of N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid in ion and ion electrokinetic chromatography

The complexes of Fe(III), Co(III), Mn(III), Al(III), Cu(II), Ni(II), Cd(II) and Zn(II) with N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) were separated by ion exchange in different modes: ion chromatography (IC) and ion electrokinetic chromatography (IEKC). In column IC these complexes were separated on an IonPac AS4a anion-exchange column (Dionex, USA). Parameters of the background electrolyte that were examined in IEKC mode include polymer, competing ion concentration and pH. The use of poly(diallyldimethylammonium chloride) (PDADMACl) as a modifier in IEKC provides separation selectivity only slightly different from that observed in IC on the IonPac AS4a column. Optimal separation conditions were found to be: 0.1 mM HBED, 50 mM PDADMAOH, 10 mM Na2 B4 O7, pH adjusted to 10 with acetic acid. The use of an aromatic ligand allowed a 10-fold decrease in detection limits of metal ions in comparison with previously studied EDTA. A separation efficiency up to 400,000 theoretical plates was demonstrated for IEKC.     

Orientation Control of Photo‐Immobilized Antibodies on the Surface of Azobenzene‐Containing Polymers by the Introduction of Functional Groups

In our photo‐induced immobilization technique for an antibody (IgG) using azopolymers, the introduction of COOH and NMe₂ into the azopolymers, which can introduce surface charges, strongly affected the immobilization properties such as the efficiency of immobilization and the activity of the immobilized IgG (i.e., the orientation of the immobilized IgG). The introduction of COOH promoted a more active orientation of the immobilized IgG. The orientation was determined during the adsorption process onto the azopolymer surface in solution before photo‐immobilization, and was maintained during the photo‐immobilization. The surface charge of the azopolymer appears to be an important factor for IgG orientation, which involves electrostatic interactions between its Fab and the azopolymer surface.

     

Mechanism of the decrease in catalytic activity of human cytochrome P450 2C9 polymorphic variants investigated by computational analysis

Cytochrome P450 (CYP) is deeply involved in the metabolism of chemicals including pharmaceuticals. Therefore, polymorphisms of this enzyme have been widely studied to avoid unfavorable side effects of drugs in chemotherapy. In this work, we performed computational analysis of the mechanism of the decrease in enzymatic activity for three typical polymorphisms in CYP 2C9 species: *2, *3, and *5. Based on the equilibrated structure obtained by molecular dynamics simulation, the volume of the binding pocket and the fluctuation of amino residues responsible for substrate holding were compared between the wild type and the three variants. Further docking simulation was carried out to evaluate the appropriateness of the binding pocket to accommodate substrate chemicals. Every polymorphic variant was suggested to be inferior to the wild type in enzymatic ability from the structural viewpoint. F‐G helices were obviously displaced outward in CYP2C9*2. Expansion of the binding pocket, especially the space near F′ helix, was remarkable in CYP2C9*3. Disappearance of the hydrogen bond between K helix and β4 loop was observed in CYP2C9*5. The reduction of catalytic activity of those variants can be explained from the deformation of the binding pocket and the consequent change in binding mode of substrate chemicals. The computational approach is effective for predicting the enzymatic activity of polymorphic variants of CYP. This prediction will be helpful for advanced drug design because calculations forecast unexpected change in drug efficacy for individuals. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Organic functionalization of the surface of silica with arylsilanes. A new method for synthesizing organic-inorganic hybrid materials

Organic functionalization of a silica surface has been realized by employing arylsilanes. Grafting reactions of aryl(3-chloropropyl)dimethylsilanes (aryl = p-anisyl, p-tolyl, phenyl) with silica were carried out in heptane at 80 °C for 24 h. The ²⁹Si and ¹³C CP/MAS spectra of the obtained silica materials clearly showed that the 3-chloropropyldimethylsilyl moieties were cleanly grafted onto silica via a siloxane (Si-O-Si) bond accompanied by the release of the aryl groups. The loading amounts on FSM-type mesoporous silica (TMPS-4) with aryl(3-chloropropyl)dimethylsilanes were comparable to those with 2-propenylsilane and the most commonly used methoxysilane.     

Compressed Corannulene in a Molecular Cage

Self‐assembled coordination cages can be employed as a molecular press, where the bowl‐shaped guest corannulene (C₂₀H₁₀) is significantly flattened upon inclusion within the hydrophobic cavity. This is demonstrated by the pairwise inclusion of corannulene with naphthalene diimide as well as by the dimer inclusion of bromocorannulene inside the box‐like host. The compressed corannulene structures are unambiguously revealed by single‐crystal X‐ray analysis.     

Implementation of pi-pi interactions in molecular dynamics simulation

No explicit pi-pi interaction term has been incorporated in the conventional molecular dynamics (MD) simulation programs in spite of its significant role in the folding of biomolecules and the clustering of organic chemicals. In this article, we propose a technique to emphasize the effect of pi-pi interactions using a function of energy and implement it into an MD simulation program. Several trial calculations show that the pi-pi incorporated program gives improved results consistent with experimental data on atom geometry and has no unfavorable interference with the conventional computational framework. This indicates an importance of the explicit consideration of pi-pi interactions in MD simulation.     

Synthesis and inversion barriers of undeca- and dodeca-substituted saddle shaped porphyrin complexes

Synthesis and barriers to inversion of a series of highly saddle shaped complexes are reported. The ΔG^≠ has decreased by 8 kJ mol⁻¹ at 243 K when the meso phenyl groups are replaced by bulkier 2,6-dichlorophenyl groups, and by 17 kJ mol⁻¹ when one of the peripheral ethyl groups is removed.