Preparation and Antibacterial Activity of Thermo-Responsive Nanohydrogels from Qiai Essential Oil and Pluronic F108

Essential oils (EOs) have been used in cosmetics and food due to their antimicrobial and antiviral effects. However, the applications of EOs are compromised because of their poor aqueous solubility and high volatility. Qiai (Artemisia argyi Levl. et Van. var. argyi cv. Qiai) is a traditional Chinese herb and possesses strong antibacterial activity. Herein, we report an innovative formulation of EO as nanohydrogels, which were prepared through co-assembly of Qiai EO (QEO) and Pluronic F108 (PEG-b-PPG-b-PEG, or PF108) in aqueous solution. QEO was efficiently loaded in the PF108 micelles and formed nanohydrogels by heating the QEO/PF108 mixture solution to 37 °C, by the innate thermo-responsive property of PF108. The encapsulation efficiency and loading capacity of QEO reached 80.2% and 6.8%, respectively. QEO nanohydrogels were more stable than the free QEO with respect to volatilization. Sustained QEO release was achieved at body temperature using the QEO nanohydrogels, with the cumulative release rate reaching 95% in 35 h. In vitro antibacterial test indicated that the QEO nanohydrogels showed stronger antimicrobial activity against S. aureus and E. coli than the free QEO due to the enhanced stability and sustained-release characteristics. It has been attested that thermo-responsive QEO nanohydrogels have good potential as antibacterial cosmetics.     

Off-resonance TROSY (R1 rho - R1) for quantitation of fast exchange processes in large proteins

Current solution NMR experiments for characterizing conformational exchange processes in large proteins are limited to exchange rates ca. 500-3000 s-1. A TROSY-based constant relaxation time (R1rho - R1) experiment is designed to extend this capability to measure motion with rates up to 105 s-1 in large macromolecules. The experiment combines off-resonance spin-lock rf fields, which provide access to the faster time-scale dynamics, with TROSY coherence selection, which extends the molecular-weight range available for study. When implemented on the 53-kDa dimeric enzyme triosephosphate isomerase, the experiment yielded substantial gains in signal-to-noise (up to 60%) over current experiments at modest static magnetic fields (14.1 T). The TROSY (R1rho - R1) experiment should therefore be of general utility for investigation of fast conformational exchange events in large proteins.     

Highly sensitive and simple fluorescence staining of proteins in sodium dodecyl sulfate-polyacrylamide-based gels by using hydrophobic tail-mediated enhancement of fluorescein luminescence

Fluorescein has an extremely low luminescence intensity in acidic aqueous media. However, when it was bound to proteins, subsequent increase of luminescence intensity took place. Furthermore, when a hydrophobic tail, such as aliphatic hydrocarbons, was introduced to fluorescein, more dramatic increase of luminescence intensity was observed upon binding to proteins. In the present study, by utilizing this luminescence enhancement, three hydrophobic fluorescein dyes (5-dodecanoyl amino fluorescein, 5-hexadecanoyl amino fluorescein, and 5-octadecanoyl amino fluorescein) were examined as noncovalent fluorescent stains of protein bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Effective incorporation of the dyes to proteins in gels was accomplished either simply by adding dyes at the protein fixation step, or by treating gels with a staining solution after the fixation. The sensitivity of this staining method using the fluorescein derivatives was approximately 1 ng/band for most proteins. For some cases, protein bands containing as low as 0.1 ng were successfully visualized. In addition, the detection sensitivity showed much less protein-to-protein variation than silver staining. This new staining method was also successfully applied to two-dimensional electrophoresis of rat brain proteins. Its overall sensitivity was comparable to that of silver staining.     

One-pot hydrogenation conditions for a sequential process to (+)-monomorine

(+)-Monomorine has been synthesized under mild hydrogenation conditions initiating deprotection followed by intramolecular, sequential reductive amination reactions. The precursors could be prepared concisely using B-alkyl Suzuki cross coupling of a chiral homoallylamine and a vinyl iodide or an iodofuran derivative.     

Structural determination of hexadecanoic lysophosphatidylcholine regioisomers by fast atom bombardment tandem mass spectrometry

The structural determination of sn-1 and sn-2 hexadecanoic lysophosphatidylcholine (LPC) regioisomers was carried out using fast atom bombardment tandem mass spectrometry (FAB-MS/MS). The collision-induced dissociation (CID) of protonated and sodiated molecules produced diverse product ions due mainly to charge remote fragmentations. Based on the information obtained from the CID spectra of protonated and sodiated molecules, sn-1 and sn-2 hexadecanoic LPC isomers could be discriminated. Especially, the abundance ratio of the diagnostic ion pair [m/z 224/226] in the CID spectra of [M + H](+) ions was shown to be greatly different. Moreover, the CID-MS/MS spectra of sodium-adducted molecules for hexadecanoic LPC isomers showed characteristic product ions such as [M + Na - 103](+), [M + Na - 85](+), and [M + Na - 59](+), by which their regio-specificity can be differentiated.     

Reactions of N-silylphosphoranimines with alcohols: synthesis and structure of cyclotriphosphazenes with nongeminal methyl and phenyl substituents

The reactions of Me(3)SiN=P(OR")RR'(R" = Ph, CH(2)CF(3); R, R' = Me, Ph) with alcohols were investigated. With nonequivalent amounts of CF(3)CH(2)OH, the reactions produced high yields of the cyclic phosphazene (Me(2)PN)(3) and both the cis and trans isomers of nongeminally substituted [(Ph)(Me)PN](3). The isomers of this new cyclic phosphazene were separated by column chromatography and characterized by NMR and IR spectroscopy, elemental analysis, and X-ray crystallography. Crystals of the cis isomer 6a have a monoclinic crystal system, while the trans isomer 6b has a triclinic crystal system with two different molecules in an asymmetric unit. The bond lengths and bond angles are very similar to those of the simpler cyclic trimers (Me(2)PN)(3) and (Ph(2)PN)(3.) A likely pathway for the formation of these compounds is discussed.     

Syntheses of 1beta-methylcarbapenems bearing 5-methyl-4-hydroxypyrrolidinone

A new series of 1beta-methylcarbapenems 1a-d bearing 5-methyl-4-mercaptopyrrolidinone rings has been prepared and evaluated for in vitro antibacterial activity and pharmacokinetic parameters. Most compounds showed excellent antibacterial activity and high stability to dehydropeptidase-1. We have synthesized optically active 5-methyl-4-hydroxypyrrolidinones from enantiomerically pure aziridine esters.     

Azinoiminophosphorane mediated synthesis of 5H, 7H‐1,2,4‐triazolo[1,5‐c][1,3]benzoxazepin‐7‐ones and 6H,8H‐1,2,4‐triazolo‐[1,5‐c][1,3]oxazepin‐6‐ones

The aza‐Wittig reactions of benzophenone‐, acetophenone‐ and benzaldehyde l‐[(triphenylphosphoranyl‐idene)amino]ethylidenehydrazones (4) with phthalic anhydride, 2,3‐dimethylmaleic anhydride and 7‐oxabi‐cyclo[2,2,l]hept‐5‐ene‐2,3‐dicarboxylic anhydride ( 5a ) provide a new route to 5H,7H‐1,2,4‐triazolo[1,5‐c]‐[1,3]benzoxazepin‐7‐ones 8a‐c or 6H,8H‐1,2,4‐triazolo[1,5‐c][1,3]oxazepin‐6‐ones 8d‐h via the thermal reaction of the expected azinoimine lactones 6 .     

Chiral Brønsted acid-catalyzed Friedel–Crafts reaction of 3-indolylsulfamidates with indoles: Synthesis of enantioenriched bisindolylmethane sulfamates

A Brønsted acid-catalyzed asymmetric Friedel–Crafts alkylation of 3-indolylsulfamidates with indoles has been established toward the efficient synthesis of biologically important bisindolylarylmethane derivatives containing the phenylsulfamate group. The reaction using chiral BINOL-derived phosphoric acid as the catalyst was tolerant to a diverse range of 3-indolylsulfamates and indoles, and provided for the first time bisindolylarylmethane sulfamate derivatives in good yields and with moderate to high enantioselectivities (up to 89% yield, 94:6 er). Moreover, some of these novel compounds were evaluated for their biological activities and confirmed to show bioactivity for preventing peripheral nerve degeneration.     

Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy

The total synthesis of (+)‐neooxazolomycin was achieved from the amino‐acid d ‐serine. The efficiency of this approach is derived from the use of principles of memory of chirality and dynamic kinetic resolution in the intramolecular aldol reaction of a serine derivative to build the densely functionalized lactam framework and to install three contiguous stereocenters. The key intermediate was readily elaborated to the target natural product.