Microfluidic-directed assembly of uniform fluorescent supraballs from CdTe nanocrystals-loaded acrylosilane microemulsion

We report herein a facile approach of fabricating fluorescent supraballs from CdTe nanocrystals (NCs)-loaded acrylosilane microemulsion by a simple microfluidic strategy. Initially, core–shell acrylosilane microemulsion with poly(methylmethacrylate-co-butylacrylate-co-vinyltri(isopropoxy)silane) (poly (MMA-co-BA-co-VPS)) as the core and poly(methylmethacrylate-co-butylacrylate-co-vinyltri(isopropoxy)silane-co-acrylamide) (poly(MMA-co-BA-co-VPS-co-AM)) as the shell were synthesized by differential microemulsion polymerization. Subsequently, CdTe NCs were assembled with these acrylosilane microemulsion particles in the presence of N′-(ethylcarbonimidoyl)-N, N-dimethylpropane-1, 3-diaminemonohydrochloride. Eventually, we fabricated uniformly distributed fluorescent supraballs using the as-prepared CdTe-loaded acrylosilane microemulsion as the discontinuous phase, and methylsilicone oil as the continuous phase by means of a microfluidic device. These fluorescent supraballs display unique colors and favorable fluorescence, which might be useful in optoelectronic applications, such as fluorescent switches, light-emitting diode displays, and illuminations.     

Hit identification against peptidyl-prolyl isomerase of Theileria annulata by combined virtual high-throughput screening and molecular dynamics simulation approach

Theileria annulata secretes peptidyl prolyl isomerase enzyme (TaPIN1) to manipulate the host cell oncogenic signaling pathway by disrupting the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) protein level leading to an increased level of c-Jun proto-oncogene. Buparvaquone is a hydroxynaphthoquinone anti-theilerial drug and has been used to treat theileriosis. However, TaPIN1 contains the A53 P mutation that causes drug resistance. In this study, potential TaPIN1 inhibitors were investigated using a library of naphthoquinone derivatives. Comparative models of mutant (m) and wild type (wt) TaPIN1 were predicted and energy minimization was followed by structure validation. A naphthoquinone (hydroxynaphthalene-1,2-dione, hydroxynaphthalene-1,4-dione) and hydroxynaphthalene-2,3-dione library was screened by Schrödinger Glide HTVS, SP and XP docking methodologies and the docked compounds were ranked by the Glide XP scoring function. The two highest ranked docked compounds Compound 1 (4-hydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxynaphthalene-1,2-dione) and Compound 2 (6-acetyl-1,4,5,7,8-pentahydroxynaphthalene-2,3-dione) were used for further molecular dynamics (MD) simulation studies. The MD results showed that ligand Compound 1 was located in the active site of both mTaPIN1 and wtTaPIN1 and could be proposed as a potential inhibitor by acting as a substrate antagonist. However, ligand Compound 2 was displaced away from the binding pocket of wtTaPIN1 but was located near the active site binding pocket of mTaPIN1 suggesting that could be selectively evaluated as a potential inhibitor against the mTaPIN1. Compound 1 and Compound 2 ligands are potential inhibitors but Compound 2 is suggested as a better inhibitor for mTaPIN1. These ligands could also further evaluated as potential inhibitors against human peptidyl prolyl isomerase which causes cancer in humans by using the same mechanism as TaPIN1.     

Optical potential calculations for molecular collisions

The Feshbach optical formalism is applied to elastic, nonreactive atom-diatom scattering on a single potential energy surface. The optical potential depends on GQ, the resolvent of E-QHQ, where Q projects onto open as well as closed channels. A method for generating GQ is developed which goes beyond the free-space approximation by partitioning the radial part of the intermolecular separation into a set of intervals, on each of which the projected interaction QVQ is represented by a constant diagonal form. The resulting GQ is used in calculations on a model collinear system. The calculations are carried out with various approximations on the full nonlocal optical potential equation for Pψ Emphasis is placed on two of these, one of which is characterized by a local homogeneous equation for Pψ, and the other by a local inhomogeneous equation for Pψ.     

Enantioselective, chemoenzymatic synthesis, and absolute configuration of the antioxidant (−)-gloeosporiol

The natural antioxidant (−)-gloeosporiol, isolated as a peracetylated derivative from a culture of the fungus Colletotrichum gloeosporioides, has been enantioselectively prepared from 3,4-dihydroxybenzaldehyde by means of a chemoenzymatic synthesis. The key intermediate was obtained by resolution with a lipase from Pseudomonas cepacia. Its stereochemistry, initially assigned as R, according to the Kazlaukas empirical rule for secondary alcohols, was independently confirmed by NMR and chirooptic methods. This, in turn, allowed the assignment of compound (−)-1 as (−)-(2S,3R,4R)-2-(3′,4′dihydroxyphenyl)tetrahydrofuran-3,4-diol.     

Enzymatic resolution of sec-butylamine

Resolution of (±)-sec-butylamine by Candida antarctica lipase provided a very low enantiomeric excess of the residual amine when either ethyl or vinyl butyrate was used as the acylating agent. The enantiomeric excess was increased by using ethyl esters of long chain fatty acids. The rate of the reaction was increased by using methyl t-butyl ether as a solvent. (S)-sec-Butylamine of very high enantiomeric excess was obtained by C. antarctica lipase catalyzed acylation with ethyl decanoate in methyl t-butyl ether.     

Lipase-catalyzed resolution of 5-acetoxy-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene. Application to the synthesis of (+)-(3R,4S)-cis-4-hydroxy-6-deoxyscytalone, a metabolite isolated from Colletotrichum acutatum

(+)-cis-4-Hydroxy-6-deoxyscytalone, a natural product bio-synthesized by Colletotrichum sp., has been prepared and its absolute configuration confirmed as 3R,4S, the key step being a kinetic racemic resolution of a cis-diol easily obtained from commercial 1,2,3,4-tetrahydronaphthalen-1,5-diol. Four lipases and different reaction conditions were tested in order to obtain the best yield and enantiomeric excess. Confirmation of absolute configuration was made by NMR using a single-derivatization low-temperature procedure and MPA as the auxiliary reagent.     

Metal catalyst-free amination of meso-bromoporphyrins: an entry to supramolecular porphyrinoid frameworks

meso-Bromoporphyrins can be conveniently substituted by primary and secondary amines in a metal catalyst-free reaction which gives access to a large variety of meso-N-substituted derivatives. In some cases, considerable acceleration of this amination can be effected under microwave irradiation. The amino anchor on the porphyrin skeleton is useful for constructing novel self-assembling porphyrinoids as demonstrated by a single crystal X-ray analysis as well as stationary absorption and fluorescence spectroscopies.     

Newly Isolated Lactic Acid Bacteria with Probiotic Features for Potential Application in Food Industry

Five newly isolated lactic acid bacteria were identified as Weissella cibaria, Enterococcus faecium, and three different strains of Lactobacillus plantarum by 16S rRNA sequencing. Essential probiotic requirements of these isolates such as tolerance to phenol, low pH, high sodium chloride, and bile salt concentration were checked. Efficiency in adherence to mucin and hydrophobicity of the bacterial cell were also evaluated by in vitro studies. Antimicrobial activities against some pathogens were tried, and the sensitivity of these strains against 25 different antibiotics was also checked. Further studies revealed Weissella and Enterococcus as substantial producers of folic acid. Folate is involved as a cofactor in many metabolic reactions, and it has to be an essential component in the human diet. The folate level in the fermented samples was determined by microbiological assay using Lactobacillus casei NCIM 2364 as indicator strain. The three strains of L. plantarum showed significant inhibitory activity against various fungi that commonly contaminate food stuffs indicating their potential as a biopreservative of food material.     

Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide

By using dimethylformamide to suppress the O-to-N acyl migration, we efficiently synthesized an O-acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys-O-acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH₃CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O-acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O-acyl isopeptides via native chemical ligation, with O-to-N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.     

Electroenzymatic synthesis of chiral alcohols in an aqueous–organic two-phase system

The reduction of acetophenone to (R)-phenylethanol catalysed by the alcohol dehydrogenase from Lactobacillus brevis in combination with electrochemical regeneration of NADPH mediated by a rhodium complex is reported. The reaction in buffer solution was optimised with regard to high productivity (up to 14 gL⁻¹d⁻¹) and enantioselectivity (>99.9%). Enzyme stability under the reaction conditions was increased either by addition of bovine serum albumin as a sacrificial protein or by immobilisation, leading to full conversion and enzyme ttn’s of up to 75,000. To improve the utilisation of cofactor and mediator as well as to broaden the substrate spectrum to more hydrophobic substrates, we introduced an organic phase of methyl tert-butyl ether. This is the first reported two-phase approach for electrochemical cofactor regeneration, which yielded mediator and cofactor ttn’s twice as high as in the one-phase approach. Furthermore, a concentrated product solution of 180 mM enantiopure (R)-phenylethanol was obtained, facilitating product work-up.     

Dialkyl quinone-2,3-dicarboxylates in the Nenitzescu reaction

Diethyl naphthoquinone-2,3-dicarboxylate reacts with different enamines to give 5-oxo-1,5-dihydro-benzo[g]indole-3,4,9b-tricarboxylate derivatives by migration of one ethoxycarbonyl group. These new products aromatize to planar indoles by elimination of one ethoxycarbonylgroup. With an N,N-dimethyl-enamine cyclization yields a 5-oxo-4,5-dihydro-cyclopenta[a]naphthalene-3,3a,4-tricarboxylate as well as a naphthyl-malonic acid derivative by migration of an ethoxycarbonylgroup.     

Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems

Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.     

Synthetic approach to cis and trans-decalins via Diels—Alder reaction and ring-closing metathesis as key steps: further extension to dioxapropellane derivative by ring-closing metathesis

9,10-Substituted cis and trans-decalins were synthesized by a simple route using the Diels-Alder reaction and ring-closing metathesis (RCM) as key steps. Later, the cis-decalin system has been extended to 3,8-dioxa[8.4.4]propellane derivative by RCM sequence as a key step.     

Introduction of N,N'-disulfonylhydrazines as new sulfonylating reagents for highly efficient synthesis of (E)-β-iodovinyl arenesulfones under mild conditions

N,N'-Disulfonylhydrazines have been proven to be the most reactive precursors of the sulfonyl radicals among all types of sulfonyl substituted hydrazines as early as half a century ago. However, the sulfonyl radicals generated from these compounds have not been used in organic synthesis except the simple self-dimerization synthesis of disulfones controlled by the “solvent-cage-effects”. In this article, N,N′-disulfonylhydrazines were introduced as new sulfonylating reagents and their combinations with NIS were disclosed as new iodosulfonylating reagents of alkynes. Finally, a highly efficient method for the synthesis of (E)-β-iodovinyl arenesulfones was developed by mixing an alkyne, a N,N′-disulfonyl-hydrazine and NIS in aqueous THF at room temperature for 5 min.     

Metal exchange in cadmium porphyrins with spatially shielded coordination centers

Shielding of coordination centers in metalloporphyrins (MPs, M = Cd) through covering it with a covalently bonded “lid” or by an endocyclic N-substituent results in retardation of metal exchange reaction (Cd/Zn or Cd/Cu) by up to 10 times. A decrease in the metal exchange rate was observed in spite of the fact that the shielding gave rise to a pronounced distortion of the predominately planar structure of aromatic ligands in the MP structure in the studied objects, which was confirmed by electronic and fluorescence spectroscopy as well as by ¹H NMR spectroscopy. It was found that 2,8,12,18-tetramethyl-3,7,13,17-tetrabutyl-10,20-di-ortho-methoxyphenylporphin exists as a mixture of cis- and trans-atropisomers with a ratio of 1: 2.     

Identification,Cloning and Biochemical Characterization of Pseudomonas putida A (ATCC 12633) Monooxygenase Enzyme necessary for the Metabolism of Tetradecyltrimethylammonium Bromide

This study presents the first report of the purification and characterization of a monooxygenase enzyme from Pseudomonas putida A (ATCC 12633) that is responsible for the oxidation of physiologically relevant quaternary ammonium compounds, the tetradecyltrimethylammonium bromide. The degradation of tetradecyltrimethylammonium bromide by P. putida A (ATCC 12633) is initiated by N-dealkylation and catalysed by tetradecyltrimethylammonium monooxygenase (TTABMO), resulting in the formation of tetradecylalkanal and trimethylamine. Based on sequence analysis, the gene for TTABMO (ttbmo) corresponded to an ORF named PP2033 in the genome of P. putida KT2440. Mutation in ttabmo blocked the utilization of tetradecyltrimethylammonium bromide by Pseudomonas putida A (ATCC 12633) as carbon and nitrogen sources. The enzyme can be highly overexpressed in P. putida Δttabmo-T7 in active form and purified as a hexahistidine fusion protein. Like the native enzyme, the his-TTABMO was found to be a monomer with molecular mass of 40 kDa, the isoelectric point 7.3, that catalyses the breakdown of tetradecyltrimethylammonium bromide and utilized NADPH and FAD as cofactor. The biochemical properties and the analysis of the respective protein sequence revealed that TTABMO represents a typical flavoprotein monooxygenase, which is member of a flavoprotein family that is distinct from Baeyer–Villiger monooxygenases.     

Diffusion des additifs du polyethylene—II: Influence de la structure du polyethylene

In the previous paper, the length (L) of the diffusing molecule was compared with h (as defined by Klein) in a sample of polyethylene. It is interesting to study the variation of h with the crystallinity of the polymer sample, for molecules with lengths less than, greater than or equal to h. The value of h depends upon the density of the polymer; it is possible to define conditions such that the diffusing molecule migrates as a gas or as a long molecule. The polymer crystallinity influences the solubility of the additive but this solubility is affected also by the average molecular weight of the polymer.     

Structural screening by multiple reaction monitoring as a new approach for tandem mass spectrometry: presented for the determination of pyrrolizidine alkaloids in plants

In tandem mass spectrometry the multiple reaction monitoring (MRM) mode is normally used for targeted analysis but this mode also has the potential to screen for structural similarities of analytes. On the basis of the fact that in general similar molecular structures result in similar fragments or losses of neutrals, this approach was used for pyrrolizidine alkaloid (PA) screening but could also be easily adapted to screen for other compound classes. PA are plant toxins of which several hundred individual compounds have been identified. Our MRM screening approach uses the structural relation and similar core structure of all PA which results in a common and thus predictable mass spectrometric fragmentation behaviour. On this basis a method was developed which screens for PA structures by MRM transitions and allows the detection of each individual PA down to a low microgram per kilogram concentration range. The approach was applied to investigate plants from the families of Asteraceae (several species of Senecio and Eupatorium), Boraginaceae (Echium, Cynoglossum, Borago and Anchusa officinalis as well as Heliotropium europaeum) and Fabaceae (Crotalaria incana) for a complete qualitative and quantitative PA characterisation. All analytes that were detected as possible PA by MRM screening were further investigated by recording product ion spectra. Analytes which exhibited a typical PA fragmentation pattern were either confirmed as PA or otherwise deleted as false positive signals (false positive rate was below 10 %). Sum formulas of confirmed PA were determined by additional measurements applying high resolution mass spectrometry. In that way 121 unknown PA were identified and for the first time complete PA profiles of different PA plants were delivered.     

Practical synthesis of blepharismone,a mating inducing pheromone of Blepharisma japonicum

Both enantiomers of blepharismone, a mating inducing pheromone produced by type II cells of Blepharisma japonicum, were synthesized via the Stille cross-coupling reaction of [4-(tert-butyl-dimethyl-silanyloxy)-2-trimethylstannanyl-phenyl]-carbamic acid tert-butyl ester with an acid chloride derived from (S)- and (R)-malic acid as a key reaction. The mating inducing activity of synthetic (S)-blepharismone was as effective as that of the natural one. The enantiomer (R)-blepharismone showed no mating inducing activity.     

General synthetic strategies towards N-alkyl sulfoximine building blocks for medicinal chemistry and the use of dimethylsulfoximine as a versatile precursor

The sulfoximine group has great potential as a substituent in drug discovery, as evidenced by two new clinical candidates, and can be viewed as an isosteric alternative to the commonly used sulfone. Our aim was to improve the accessibility of this group by synthesising a diverse range of S-alkyl and N-alkyl sulfoximine building blocks with procedures that are applicable on a practical scale (>10 g). In particular, synthesis of the less well exploited N-alkyl sulfoximines and the use of dimethylsulfoximine as a versatile, commercially available precursor is discussed.