Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and Its Enantiomeric,Epimeric, and N‐Demethylated Analogues

Lysocin E, a macrocyclic peptide, exhibits potent antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA) through a novel mechanism. The first total synthesis of lysocin E was achieved by applying a full solid‐phase strategy. The developed approach also provides rapid access to the enantiomeric, epimeric, and N‐demethylated analogues of lysocin E. Significantly, the antibacterial activity of the unnatural enantiomer was comparable to that of the natural isomer, suggesting the absence of chiral recognition in its mode of action.     

Ultrasound‐assisted extraction method for the simultaneous determination of emerging contaminants in freshwater sediments

Sediments are the fate of several emerging organic contaminants, such as pharmaceuticals, personal care products and hormones, and therefore an important subject in environmental monitoring studies. In the present work, a simple and sensitive method was developed, validated and applied for the simultaneous extraction of atenolol, caffeine, carbamazepine, diclofenac, ibuprofen, naproxen, propranolol, triclosan, estrone, 17‐β‐estradiol and 17‐α‐ethinylestradiol using ultrasound‐assisted extraction from freshwater sediment samples followed by solid‐phase extraction clean‐up and liquid chromatography with tandem mass spectrometry detection. The solvent type and extraction pH were evaluated to obtain the highest recoveries of the compounds. The best method shows absolute recoveries between 54.0 and 94.4% at 50 ng/g concentration. The method exhibits good precision with relative standard deviation ranging from 1.0–16%. The detection and quantification limits ranged from 0.006–0.067 and 0.016–0.336 ng/g, respectively. The developed method was successfully applied to freshwater sediment samples collected from different sites in Jundiaí River basin of São Paulo State, Brazil. The compounds atenolol, caffeine, propranolol and triclosan were detected in all the sampling sites with concentrations of 13.8, 41.0, 28.5 and 176 ng/g, respectively.     

Conserved Tyr223(5.58) plays different roles in the activation and G-protein interaction of rhodopsin

Rhodopsin, a seven transmembrane helix (TM) receptor, binds its ligand 11-cis-retinal via a protonated Schiff base. Coupling to the G-protein transducin (G(t)) occurs after light-induced cis/trans-retinal isomerization, which leads through photoproducts into a sequence of metarhodopsin (Meta) states: Meta I ? Meta IIa ? Meta IIb ? Meta IIbH(+). The structural changes behind this three-step activation scheme are mediated by microswitch domains consisting of conserved amino acids. Here we focus on Tyr223(5.58) as part of the Y(5.58)X(7)K(R)(5.66) motif. Mutation to Ala, Phe, or Glu results in specific impairments of G(t)-activation measured by intrinsic G(t) fluorescence. UV-vis/FTIR spectroscopy of rhodopsin and its complex with a C-terminal G(t)α peptide allows the assignment of these deficiencies to specific steps in the activation path. Effects of mutation occur already in Meta I but do not directly influence deprotonation of the Schiff base during formation of Meta IIa. Absence of the whole phenol ring (Y223A) allows the activating motion of TM6 in Meta IIb but impairs the coupling to G(t). When only the hydroxyl group is lacking (Y223F), Meta IIb does not accumulate, but the activity toward G(t) remains substantial. From the FTIR features of Meta IIbH(+) we conclude that proton uptake to Glu134(3.49) is mandatory for Tyr223(5.58) to engage in the interaction with the key player Arg135(3.50) predicted by X-ray analysis. This polar interaction is partially recovered in Y223E, explaining its relatively high activity. Only the phenol side chain of tyrosine provides all characteristics for accumulation of the active state and G-protein activation.     

Automatic twin vessel recrystallizer. Effective purification of acetaminophen by successive automatic recrystallization and absolute determination of purity by DSC

I describe an interchangeable twin vessel (J, N) automatic glass recrystallizer that eliminates the time-consuming recovery and recycling of crystals for repeated recrystallization. The sample goes in the dissolution vessel J containing a magnetic stir-bar K; J is clamped to the upper joint H of recrystallizer body D. Empty crystallization vessel N is clamped to the lower joint M. Pure solvent is delivered to the dissolution vessel and the crystallization vessel via the head of the condenser A. Crystallization vessel is heated (P). The dissolution reservoir is stirred and heated by the solvent vapor (F). Continuous outflow of filtrate E out of J keeps N at a stable boiling temperature. This results in efficient dissolution, evaporation and separation of pure crystals Q. Pure solvent in the dissolution reservoir is recovered by suction. Empty dissolution and crystallization vessels are detached. Stirrer magnet is transferred to the crystallization vessel and the role of the vessels are then reversed. Evacuating mother liquor out of the upper twin vessel, the apparatus unit is ready for the next automatic recrystallization by refilling twin vessels with pure solvent. We show successive automatic recrystallization of acetaminophen from diethyl ether obtaining acetaminophen of higher melting temperatures than USP and JP reference standards by 8× automatic recrystallization, 96% yield at each stage. Also, I demonstrate a novel approach to the determination of absolute purity by combining the successive automatic recrystallization with differential scanning calorimetry (DSC) measurement requiring no reference standards. This involves the measurement of the criterial melting temperature T₀ corresponding to the 100% pure material and quantitative ΔT in DSC based on the van’t Hoff law of melting point depression. The purity of six commercial acetaminophen samples and reference standards and an eight times recrystallized product evaluated were 98.8 mol%, 97.9 mol%, 99.1 mol%, 98.3 mol%, 98.4 mol%, 98.5 mol% and 99.3 mol% respectively.     

Oxo-tethered ruthenium(II) complex as a bifunctional catalyst for asymmetric transfer hydrogenation and H2 hydrogenation

Newly developed oxo-tethered Ru amido complexes (R,R)-1 and their HCl adducts (R,R)-2 exhibited excellent catalytic performance for both asymmetric transfer hydrogenation and the hydrogenation of ketonic substrates under neutral conditions without any cocatalysts to give chiral secondary alcohols with high levels of enantioselectivity.     

On homotopy groups of quandle spaces and the quandle homotopy invariant of links

For a quandle X, the quandle space BX is defined, modifying the rack space of Fenn, Rourke and Sanderson (1995) [13], and the quandle homotopy invariant of links is defined in Z[π₂(BX)], modifying the rack homotopy invariant of Fenn, Rourke and Sanderson (1995) [13]. It is known that the cocycle invariants introduced in Carter et al. (2005) [3], Carter et al. (2003) [5], Carter et al. (2001) [6] can be derived from the quandle homotopy invariant.In this paper, we show that, for a finite quandle X, π₂(BX) is finitely generated, and that, for a connected finite quandle X, π₂(BX) is finite. It follows that the space spanned by cocycle invariants for a finite quandle is finitely generated. Further, we calculate π₂(BX) for some concrete quandles. From the calculation, all cocycle invariants for those quandles are concretely presented. Moreover, we show formulas of the quandle homotopy invariant for connected sum of knots and for the mirror image of links.     

Efficient and stable panchromatic squaraine dyes for dye-sensitized solar cells

A new series of stable, unsymmetrical squaraine near-IR sensitizers (JK-216 and JK-217), which are assembled using both thiophenyl pyrrolyl and indolium groups, exhibit a panchromatic light harvesting up to 780 nm. The JK-216 based cell exhibited a record efficiency of 6.29% for near-IR DSSCs. In addition, the JK-217 device showed an excellent stability under a light soaking test at 60 °C for 1000 h.     

Soluble magnesium and titanium catalyst components for ethylene polymerization

The catalyst system comprised of a heptane solution of magnesiumoctoate-H₂O-Tetrabutoxytitanium/diethylaluminumchloride was highly active for ethylene polymerization at a high temperature. High productivity for the catalyst system at a low temperature was achieved by the aging of the catalyst components. The effect of different orders of addition of the catalyst components on productivity was investigated to assume the role of each components in the formation of active species.     

Conduction band structure of solid n-alkanes studied by electron-transmission spectra

Transmission of low-energy electrons (0–15 eV) through 10–100 Å flms of n-alkanes has been studied. The peak positions in the electron-transmission spectra were suggested to give approximate energies of the rising parts of high density-of-state conduction bands.     

Probability distribution of metric measure spaces

In this paper we are going to generalize Gromov's mm-Reconstruction theorem (cf. [Metric Structures for Riemannian and Non-Riemannian Spaces, Birkhäuser, Basel, 1999] ) to a probability measures on the spaces of mm-spaces. And for this purpose, we give alternative proof of mm-Reconstruction theorem.