Oxidation of disulfides with Selectfluor™: concise syntheses of thiosulfonates and sulfonyl fluorides

The reaction of aromatic or benzylic disulfides with 2.5 equiv of Selectfluor™ in acetonitrile/water (10:1) at room temperature efficiently produced the corresponding thiosulfonates. On the other hand, the reaction of disulfides with 6.5 equiv of Selectfluor™ in refluxing acetonitrile/water (10:1) provided sulfonyl fluoride in high yields.     

In silico design, synthesis and evaluation of 3'-O-benzylated analogs of salacinol, a potent α-glucosidase inhibitor isolated from an Ayurvedic traditional medicine "Salacia"

With the aid of an in silico method, α-glucosidase inhibitors with far more potent activities than salacinol (1), a potent natural α-glucosidase inhibitor isolated from an Ayurvedic traditional medicine Salacia reticulata, have been developed.     

How lipid unsaturation, peroxyl radical partitioning, and chromanol lipophilic tail affect the antioxidant activity of α-tocopherol: direct visualization via high-throughput fluorescence studies conducted with fluorogenic α-tocopherol analogues

The preparation of two highly sensitive fluorogenic α-tocopherol (TOH) analogues which undergo >30-fold fluorescence intensity enhancement upon reaction with peroxyl radicals is reported. The probes consist of a chromanol moiety coupled to the meso position of a BODIPY fluorophore, where the use of a methylene linker (BODIPY-2,2,5,7,8-pentamethyl-6-hydroxy-chroman adduct, H(2)B-PMHC) vs an ester linker (meso-methanoyl BODIPY-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid, H(2)B-TOH) enables tuning their reactivity toward H-atom abstraction by peroxyl radicals. The development of a high-throughput fluorescence assay for monitoring kinetics of peroxyl radical reactions in liposomes is subsequently described where the evolution of the fluorescence intensity over time provides a rapid, facile method to conduct competitive kinetic studies in the presence of TOH and its analogues. A quantitative treatment is formulated for the temporal evolution of the intensity in terms of relative rate constants of H-atom abstraction (k(inh)) from the various tocopherol analogues. Combined, the new probes, the fluorescence assay, and the data analysis provide a new method to obtain, in a rapid, parallel format, relative antioxidant activities in phospholipid membranes. The method is exemplified with four chromanol-based antioxidant compounds differing in their aliphatic tails (TOH, PMHC, H(2)B-PMHC, and H(2)B-TOH). Studies were conducted in six different liposome solutions prepared from poly- and mono-unsaturated and saturated (fluid vs gel phase) lipids in the presence of either hydrophilic or lipophilic peroxyl radicals. A number of key insights into the chemistry of the TOH antioxidants in lipid membranes are provided: (1) The relative antioxidant activities of chromanols in homogeneous solution, arising from their inherent chemical reactivity, readily translate to the microheterogeneous environment at the water/lipid interface; thus similar values for k(inh)(H(2)B-PMHC)/k(inh)(H(2)B-TOH) in the range of 2-3 are recorded both in homogeneous solution and in liposome suspensions with hydrophilic or lipophilic peroxyl radicals. (2) The relative antioxidant activity between tocopherol analogues with the same inherent chemical reactivity but bearing short (PMHC) or long (TOH) aliphatic tails, k(inh)(PMHC)/k(inh)(TOH), is ~8 in the presence of hydrophilic peroxyl radicals, regardless of the nature of the lipid membrane into which they are embedded. (3) Antioxidants embedded in saturated lipids do not efficiently scavenge hydrophilic peroxyl radicals; under these conditions wastage reactions among peroxyl radicals become important, and this translates into larger times for antioxidant consumption. (4) Lipophilic peroxyl radicals show reduced discrimination between antioxidants bearing long and short aliphatic tails, with k(inh)(PMHC)/k(inh)(TOH) in the range of 3-4 for most lipid membranes. (5) Lipophilic peroxyl radicals are scavenged with the same efficiency by all four antioxidants studied, regardless of the nature of their aliphatic tail or the lipid membrane into which they are embedded. These data underpin the key role the lipid environment plays in modulating the rate of reaction of antioxidants characterized by similar inherent chemical reactivity (arising from a conserved chromanol moiety) but differing in their membrane mobility (structural differences in the lipophilic tail). Altogether, a novel, facile method of study, new insights, and a quantitative understanding on the critical role of lipid diversity in modulating antioxidant activity in the lipid milieu are reported.     

Concise and stereoselective synthesis of 2,5- and 2,4-disubstituted thiazole amino acid subunits for synthesizing thiazole-containing peptides

A concise, highly stereoselective synthesis of 2,4- and 2,5-disubstituted thiazole amino acids was developed. These are important building blocks for various biologically active thiazole-containing natural peptides and their regioisomeric analogues. The fundamental reactions are diastereoselective addition of (4- or 5-bromothiazol-2-yl)lithium to N-tert-butanesulfinyl imine with subsequent Pd-catalyzed phenoxycarbonylation.     

q-Dependence of the giant bond-stretching phonon anomaly in the stripe compound La1.48Nd0.4Sr0.12CuO4 measured by IXS

Inelastic X-ray scattering (IXS) was used to study the Cu-O bond-stretching vibrations in the static stripe phase compound La_1.48Nd_0.4Sr_0.12CuO₄. It was found that the intrinsic width in Q-space of the previously reported huge anomalous phonon softening and broadening is approximately 0.08 r.l.u. HWHM. A detailed comparison was also made to inelastic neutron scattering (INS) studies, which indicate a two-peak lineshape (with superimposed broad and narrow peaks) in the vicinity of the anomaly. The high resolution IXS data show that the narrow peak is mostly an artifact of the poor transverse Q-resolution of INS. Otherwise, the agreement between the INS and IXS was excellent.     

Chiral amines as reagents for HPLC-MS enantioseparation of chiral carboxylic acids

Mass spectrometry (MS) has become a popular analytical technique because of its high sensitivity and specificity. Therefore, the use of a chiral derivatization reagent for the MS detection seems to be efficient for the enantiomeric separation of racemates. However, the number of chiral reagents for the liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis is very limited. The applicability of commercially available chiral amines as the derivatization reagents for the enantiomeric separation of chiral carboxylic acids is reported in this paper by using non-steroidal anti-inflammatory drugs (NSAIDs), i.e. ibuprofen, flurbiprofen, and loxoprofen. The efficiency of the chiral reagents was evaluated in terms of tagging easiness, separation by reversed-phase chromatography, and detection sensitivity by electrospray ionization (ESI)-MS/MS. Among the tested eight chiral amines, i.e. (R)-(+)-4-(3-aminopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-APy), (S)-(+)-1-(2-pyrrolidinylmethyl)-pyrrolidine (PMP), L-prolinamide, (3R)-(-)-1-benzyl-3-aminopyrrolidine, (S)-(+)-1-cyclohexyl-ethylamine, (3R)-(+)-3-(trifluoroacetamido)-pyrrolidine (TFAP), (R)-(-)-1-aminoindan (AI), and (S)-(+)-tetrahydrofurfuryl-amine, DBD-APy, PMP, AI, and TFAP could be used as the chiral reagents for the enantiomeric separation of the NSAIDs. The Rs values and the detection limits of the derivatives were in the range of 1.29-3.85 and 0.57-0.96 fmol, respectively. These four reagents were applied for the determination of the NSAIDs in rat plasma.     

Sm atomic dynamics in a charge density wave compound SmNiC2

¹⁴⁹Sm nuclear resonant inelastic scattering was carried out in a charge density wave compound SmNiC₂. We have investigated temperature dependences of the Sm partial phonon density of states and recoil-free fraction at the Sm site and the average sound velocity estimated from the Sm partial density of states. The Sm partial density of states exhibits temperature dependence, suggesting that the phonon modes between 20 and 25 meV may correlate with the charge density wave. Temperature dependence of the recoil-free fraction is difficult to prove the correlation with either the charge density wave or ferromagnetic ordering. The average sound velocity obtained by the Sm partial phonon density of states exhibits temperature dependence, agreeing qualitatively with very recent elastic constant measurements.     

B(0)-B(0) mixing in unquenched lattice QCD

We present an unquenched lattice calculation for the B(0)-B(0) transition amplitude. The calculation, carried out at an inverse lattice spacing 1/a=2.22(4) GeV, incorporates two flavors of dynamical quarks described by the O(a)-improved Wilson fermion action and heavy quarks described by nonrelativistic QCD. Particular attention is paid to the uncertainty that arises from the chiral extrapolation, especially the effect of pion loops, for light quarks, which we find could be sizable for the leptonic decay constant, whereas it is small for the B parameters. We obtain f(B(d))=191(10)(+12-22) MeV, f(B(s))/f(B(d))=1.13(3)(+13-2), B(B(d))(m(b))=0.836(27)(+56-62), B(B(s))/B(B(d))=1.017(16)(+56-17), and xi=1.14(3)(+13-2), where the first error is statistical, and the second is systematic, including uncertainties due to chiral extrapolation, finite lattice spacing, heavy quark expansion, and perturbative operator matching.     

Mott gap excitations in twin-free YBa2Cu3O7-delta (Tc=93 K) studied by resonant inelastic x-ray scattering

Mott gap excitations in the optimally doped high-T(c) superconductor YBa(2)Cu(3)O(7-delta) (T(c)=93 K) have been studied by the resonant inelastic x-ray scattering method. Anisotropic spectra in the ab plane are observed in a twin-free crystal. The excitation from the one-dimensional CuO chain is enhanced at 2 eV near the zone boundary of the b* direction, while the excitation from the CuO2 plane is broad at 1.5-4 eV and almost independent of the momentum transfer. Theoretical calculations based on the one-dimensional and two-dimensional Hubbard model reproduces the observed spectra when different values of the on-site Coulomb energy are assumed. The Mott gap of the CuO chain site is found to be much smaller than that of the CuO2 plane site.