Large molecular assembly of amphotericin B formed in ergosterol-containing membrane evidenced by solid-state NMR of intramolecular bridged derivative

Amphotericin B (AmB 1) is known to assemble and form an ion channel across biomembranes. We have recently reported that conformation-restricted derivatives of AmB 2-4 show different ergosterol preferences in ion-channel assays, which suggested that the orientation of the mycosamine strongly affects the sterol selectivity of AmB. The data allowed us to assume that compound 3 showing the highest selectivity would reflect the active conformation of AmB in the channel assembly. In this study, to gain further insight into the active conformation of AmB, we prepared a new intramolecular-bridged derivative 5, where the linker encompassed a hydrophilic glycine moiety. The derivative has almost equivalent ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared with 3 improves significantly, possibly because the increasing hydrophilicity in the linker enhances the penetrability through the fungal cell wall. Conformation of 5 was well converged and very similar to that of 3, thus further supporting the notion that the conformations of these derivatives reproduce the active structure of AmB in the channel complex. Then we used the derivative to probe the mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings and chemical shift anisotropies, we incorporated [1-(13)C,(15)N]glycine into the linker. The results indicate that 5 is mostly immobilized in ergosterol-containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting promotion of AmB aggregation by ergosterol.     

Double Commuting Compressed Shifts and Generalized Interpolation in the Hardy Space over the Bidisk

This paper deals with an operator theory of compressed shifts on the Hardy space over the bidisk. We give commutant lifting type theorems and some interpolation theorems in two variables.     

Heat capacity and phase transition of a five-coordinated antiferromagnet,IODOBIS (N,N-diethyldithiocarbamato) iron (III), in the temperature range from 0.4 TO 300 K

The heat capacity of iodobis (N,N-diethyldithiocarbamato) iron (III) has been measured between 0.4 and 300 K. A phase transition from an antiferromagnetic to a paramagnetic state was found at T_N = (1.937 ± 0.010) K, and a Schottky-type anomaly arising from a zero-field single ion splitting was observed around 12 K. The total magnetic entropy and enthalpy, including the phase transition and the Schottky-type anomaly, are 11.36JK^?1mol^?1 and 134.5 J mol^?1, respectively. The entropy is approximately equal to Rln 4 ( = 11.53 JK^?1mol^?1), confirming that the spin manifold is really a quartet. The entropy and enthalpy due to the phase transition are estimated to be (5.57±0.01)JK^?1mol^?1 and (13.2±0.05)Jmol^?1, respectively. The entropy and enthalpy above t_n are quite large, as in the case of the related compound chlorobis (N,N-diethyldithiocarbamato) iron (III). This fact suggests that the present complex may be considered to have a two-dimensional type of magnetic structure from a thermodynamic point of view. A correlation diagram between the transition entropy and energy is proposed, this being a diagnostic for the determination of the magnetic dimensionality.     

Fe/Cr- and Co/Cr-mediated catalytic asymmetric 2-haloallylations of aldehydes

The first example to couple aldehydes and 3-bromo-2-halopropenes in a catalytic asymmetric manner is reported. The coupling reaction is effected by the use of a chiral sulfonamide-Cr complex (prepared in situ from 1d, CrBr3, Fe(III) or from Co(II), Et3N, and Mn), TMSCl, and 2,6-lutidine. The method reported here is operationally simple and scalable, furnishing 3-halohomoallylic alcohols with a synthetically useful level of enantiomeric excess.     

Dynamical steric effect in the decomposition of methyl chloride on a silicon surface

We report results of a study on the incident energy and the surface-temperature dependence of the steric effects in the dissociative adsorption of CH3Cl on a Si{100} surface. Data presented here show that the initial sticking probability for the Cl-end collision is larger at an incident energy of 120 meV than that in the CH3-end collision. Furthermore, this steric preference is quite sensitive to the kinetic energy and the rotational state of CH3Cl and the surface temperature. This study shows that the nonequilibrium surface trapping plays a key role in the initial step of the decomposition of CH3Cl on Si{100}.     

The SAAP force field. A simple approach to a new all-atom protein force field by using single amino acid potential (SAAP) functions in various solvents

A simple strategy to compose a new all-atom protein force field (named as the SAAP force field), which utilizes the single amino acid potential (SAAP) functions obtained in various solvents by ab initio molecular orbital calculation applying the isodensity polarizable continuum model (IPCM), is presented. We considered that the total energy function of a protein force field (E(TOTAL)) is divided into three components; a single amino acid potential term (E(SAAP)), an interamino acid nonbonded interaction term (E(INTER)), and a miscellaneous term (E(OTHERS)), which is ignored (or considered to be constant) at the current version of the force field. The E(INTER) term consists of electrostatic interactions (E(ES')) and van der Waals interactions (E(LJ')). Despite simplicity, the SAAP force field implicitly involves the correlation among individual terms of the Lifson's potential function within a single amino acid unit and can treat solvent effects unambiguously by choosing the SAAP function in an appropriate solvent and the dielectric constant (D) of medium. Application of the SAAP force field to the Monte Carlo simulation of For-Ala(2)-NH(2) in vacuo reasonably reproduced the results of the extensive conformational search by ab initio molecular orbital calculation. In addition, the preliminary Monte Carlo simulations for For-Gly(10)-NH(2) and For-Ala(10)-NH(2) showed reversible transitions from the extended to the pseudosecondary structures in water (D = 78.39) as well as in ether (D = 4.335). The result suggested that the new approach is efficient for fast modeling of protein structures in various environments. Decomposition analysis of the total energy function (E(TOTAL)) by using the SAAP force field suggested that conformational propensities of single amino acids (i.e., the E(SAAP) term) may play definitive roles on the topologies of protein secondary structures.     

Enantioselective cyclization of alkene radical cations

[reaction: see text] Enantiomerically enriched beta-(diphenylphosphatoxy)nitroalkanes undergo radical ionic fragmentation, induced by tributyltin hydride and AIBN in benzene at reflux, to give alkene radical cations in contact radical ion pairs. These contact ion pairs are trapped intramolecularly by amines to give pyrrolidines and piperidines with significant enantioselectivity ( approximately 60% ee), indicative of cyclization competing effectively with equilibration within the ion pairs. Use of an intramolecular N-propargylamine as a nucleophile provides an enantiomerically enriched pyrrolizidine skeleton via a tandem polar/radical crossover sequence.     

Asymmetric reaction. XV. Structure and relative configuration of a reductive dimerization product of ethyl phenylglyoxylate,diethyl diphenyltartrate

The hydrogenation of ethyl phenylglyoxylate catalyzed by bis(dimethylglyoximato)cobalt(II)-quinine gave a novel reductive dimerization product, diethyl diphenyltartrate, with a slight optical activity. The crystals obtained from its benzene-hexane solution were investigated by X-ray diffraction method. The crystal is triclinic, space group p1, a = 10.078(3), b = 10.283(2), c = 9.781(3) Å, α = 109.80(2), β = 102.35(3), γ = 78.50(2)°, Z = 2, V = 922.7 ų, Dc = 1.29 g cm^?3,μ = 7.46 cm^?1 for Cu Kα. The structure was solved by the direct method, and refined by a block-diagonal least-squares procedure: R = 0.059 for 2568 reflections with | Fo | >3σ(| Fo | ). The relative configuration around the two chiral carbons indicated that the molecule is in the threo-form, and the Newman projection showed that the molecule has the staggered conformation. There were two relatively strong intramolecular hydrogen bonds between the two hydroxyl groups and the two carbonyl oxygen atoms of ethoxycarbonyl groups.     

Millimeter-wave spectrum of DCCCHO in the ground vibrational state

About 140 a- and b-type millimeter-wave transitions of propynal-d₁, DCCCHO, were measured in the ground vibrational state. The accurate rotational and centrifugal distortion constants were determined from the observed frequencies including the previous microwave measurements. Seven microwave transitions observed by infrared-microwave double resonance were also included in the analysis. The determined constants are A = 66778.016(12), B = 4463.8489(7), C = 4177.7950(7), Δ_J = 0.0015919(5), Δ_JK = −0.139214(13), Δ_K = 9.4328(18), δ_J = 0.0002885(4), δ_K = 0.03069(4), H_JK = −0.817(13) × 10⁻⁶, H_KJ = −9.62(4) × 10⁻⁶, H_K = 0.00255(8), h_J = 0.0047(3) × 10⁻⁶, in MHz.