Hybrid molecular orbitals for reacting systems

A method of describing the interactions between two systems in terms of coupled hybrid molecular orbitals of fragments is discussed and is applied to simple interacting systems to provide information on the processes of bond formation.     

Platinum-catalyzed intramolecular vinylchalcogenation of alkynes with beta-phenylchalcogeno conjugated amides

Platinum-catalyzed intramolecular vinylthiolation and -selenation of internal alkynes with vinylchalcogenides 1 having a carbamoyl group on cis-beta-position of vinyl moiety was developed. The conjugated six-membered lactam framework 2 was constructed in high yields. Density functional theory calculations for alkyne insertion processes suggest seven-membered platinacycle 3 is a kinetically favored intermediate of this catalytic system.     

Design and synthesis of ladder-shaped tetracyclic, heptacyclic, and decacyclic ethers and evaluation of the interaction with transmembrane proteins

Ladder-shaped polyether (LSP) toxins represented by brevetoxins and ciguatoxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and 6/7/6/6/7/6/6/7/6/6 decacyclic systems, based on the convergent method via alpha-cyano ethers. The ALPs possessing the simple iterative structure with different numbers of rings would be useful for structure-activity relationship studies on the molecular length, which is supposed to be important when naturally occurring LSPs elicit their toxicity. Two series of ALPs were prepared to evaluate the hydrophilic or hydrophobic effects of the side chains: (i) both sides were functionalized as diols (A series), and (ii) one side remained as diol and the other side was protected as benzyl ethers (B series). To examine the interaction of these ALPs with TM proteins, dissociation of glycophorin A (GpA) dimers into monomers was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The heptacyclic ether (ALP7B) elicited the most potent activity in the presence of 2% SDS buffer, whereas the decacyclic ether (ALP10A) exhibited an intriguing phenomenon to induce precipitation of GpA in a dose-dependent manner, under the low concentration of SDS (0.03%). ALP10A also induced precipitation of integrin alpha 1beta 1, a TM protein known to form heterodimers in the lipid bilayer membranes. The different activities among the ALPs can be accounted for by the concept of "hydrophobic matching" that is, lengths of the hydrophobic region including the side chains of ALP7B and ALP10A are ca. 25 A, which match the lengths of the hydrophobic region of alpha-helical TM proteins, as well as the hydrophobic thickness of lipid bilayer membranes. The concept of the hydrophobic matching would be a clue to understanding the interaction between LSPs and TM proteins, and also a guiding principle to design ALPs possessing potent affinities with TM proteins.     

Templating route for mesostructured calcium phosphates with carboxylic acid- and amine-type surfactants

Mesostructured calcium phosphates constructed by ionic frameworks were synthesized using carboxylic acid- and amine-type surfactants in mixed solvent systems of ethanol and water. A lamellar mesostructured calcium phosphate was prepared using palmitic acid as an anionic surfactant, as in the case using n-alkylamines. A wormhole-like mesostructured calcium phosphate can be obtained using dicarboxyl N-lauroyl- l-glutamic acid, whose headgroup is larger than that of palmitic acid. Similar mesostructured product was obtained using 4-dodecyldiethylenetriamine with a large headgroup containing two primary amine groups. Interactions of carboxyl and primary amino groups in the surfactant molecules with inorganic species are quite important for the formation of mesostructured calcium phosphates. The Ca/P molar ratio of mesostructured calcium phosphates was strongly affected by the molecular structure of surfactants containing carboxyl and primary amino groups. Ca-rich materials can be obtained using carboxylic acid-type surfactants (Ca/P approximately 1.7) rather than amine-type surfactants (Ca/P approximately 1.0).     

High-resolution NMR spectra of n-alkanes penetrating into carbon fibers and of protons in carbon fibers

We present a simple NMR method for microscopically exploring the local environment in carbon fibers. The method utilizes n-alkanes as probe molecules, where the n-alkanes penetrate carbon fibers of interest. The high-resolution (1)H NMR spectra for a mixture of a carbon fiber and n-alkanes acquired by this method show a shift of the resonance line, which is due to the local structure of the fiber. The utility of this method is discussed on the basis of the (1)H NMR spectra obtained. In addition, the (1)H distribution and the local motion in the structure of the carbon fiber are revealed in view of the (1)H NMR spectra.     

Properties of TiO2-polyacrylic acid dispersions with potential for molecular recognition

Titanium dioxide (TiO₂)/polyacrylic acid (PAA) (TiO₂/PAA) particles were formed by mixing PAA and an acidic solution of TiO₂ nanoparticles in dimethylformamide (DMF) followed by heat treatment. TEM and particle analysis showed that the resulting particles had a narrow size distribution. The colloid was very stable and aggregation was not observed over a wide pH range (3–9) or at high salt concentration. The residual carboxylic acid of PAA could be modified via EDC/NHS activation to form an amide bond with a protein. An antibody was attached to the hybrid nanoparticle and specific binding to antigen was monitored by surface plasmon resonance. The results suggest that TiO₂/PAA nanoparticles are candidates as the base component of a photocatalytic system with potential for substrate selectivity.     

Self-assembled amphotericin B is probably surrounded by ergosterol: bimolecular interactions as evidenced by solid-state NMR and CD spectra

Amphotericin B (AmB) is thought to exert its pharmacological effects by forming a barrel-stave assembly with ergosterol in fungal membranes. To examine the interaction between AmB and ergosterol (Erg) or cholesterol (Cho), (13)C- and (19)F-labelled covalent conjugates were prepared as reported previously (N. Matsumori et al. Chem. Biol. 2004, 11, 673-679). The CD spectra of the conjugates in a membrane-bound form suggested that the distance between the heptaene moieties of the ergosterol conjugates AmB-C(2)-(6-F)Erg 2 and AmB-C(2)-Erg 3 is similar to that of AmB in ergosterol-containing membranes, but significantly larger than that of AmB in nonsterol or cholesterol-containing membranes. These observations suggest that, as is the case with ergosterol-containing membranes, the conjugated sterol moiety prevents the close contact between the heptaene moieties within the membrane that would reduce channel conductivity of the AmB assemblies. To further investigate this bimolecular interaction, we recorded the solid-state NMR spectra of conjugates 2 and AmB-C(2)-(6-F)Cho 4, which are composed of uniformly (13)C-labelled AmB and 6-fluorinated ergosterol or cholesterol; the conjugates were expected to facilitate the estimation of distances between the fluorine and carbon atoms. By using rotor-synchronous double resonance (rotational echo double resonance of X cluster; RDX) experiments, we deduced the distance between the fluorine atom and its nearest carbon atom in the heptaene moiety of 2 to be less than 8.6 A. This indicates that the B ring of ergosterol comes close to the AmB polyene moiety. A conformational search of the AmB-ergosterol conjugate by using distance constraints derived from the RDX results suggested that ergosterol molecules possibly surround the AmB assembly, which is in contrast with the conventional image in which ergosterol is inserted into AmB molecules.     

Palladium-catalyzed selenoacylation of allenes leading to the regioselective formation of functionalized allyl selenides

Palladium-catalyzed regio- and stereoselective selenoacylation of allenes with selenol esters proceeded to produce functionalized allyl selenides with the acyl moiety at the inner carbon and the SePh group at the terminal carbon in high yields. A mechanism accounting for the observed regio- and stereoselectivities is proposed based on the results of DFT calculations.     

Conformation and location of membrane-bound salinomycin-sodium complex deduced from NMR in isotropic bicelles

An ionophore antibiotic salinomycin was studied in a membrane environment consisting of isotropic bicelles, a better model for biological membranes than micelles, and its conformation and topological orientation in bicelles was determined. 2D NMR measurements and restrained conformational search revealed that salinomycin-sodium salt in bicelles adopts an open conformation in which the orientation of the E-ring is significantly different from that in crystal and solution structures. This conformational alteration breaks an intramolecular hydrogen bond between 28-OH and 1-O, dislocates the ether oxygen of the E-ring from a coordinated position to the sodium ion observed in the crystal, and consequently weakens the complexation between salinomycin and the sodium ion. Paramagnetic relaxation experiments using doxyl-phospholipids reveal that salinomycin is embedded shallowly in bicelles, with both terminals being closer to the water interface and the olefin portion facing the bicelle interior. Measurements of intermolecular NOEs between salinomycin and phospholipids further supported this orientation. Weaker complexation with sodium ion and positional preference in the membrane polar region may facilitate the catch-and-release of metal ions at the polar/nonpolar interface of bilayers. On the basis of these findings, a model for salinomycin-assisted transport of metal ions across biological membranes is proposed.     

N-carbonylation of lithium azaenolates of amides, formamides, ureas, and carbamates with carbon monoxide mediated by selenium

N-Carbonylation of less nucleophilic nitrogen compounds was achieved by the reaction of the lithium azaenolates with carbon monoxide and selenium. This reaction proceeds in the cases of amides, formamides, ureas, and carbamates, leading to the formation of the corresponding carbamoselenoates in good to high yields after trapping with BuI.