Resolution of 5- and 6-Membered P-Heterocycles: Racemic and Optically Active Platinum(II)-3-Phospholene Complexes

Abstract

Methods were developed for the resolution of several five- and six-membered phosphorus heterocycles (1c-e, 2, 4). It was investigated if the optical activity is preserved during the 1a→2→3→4 reaction sequence. Racemic and optically active 1b-e 3-phospholene 1-oxides were converted to the corresponding platinum-complexes (10b-e), which are potential catalysts.     

One-Pot Vinylation of Secondary Phosphine Chalcogenides with Vinyl Sulfoxides

A facile, one-pot vinylation of secondary phosphine chalcogenides with alkyl(or aryl) vinyl sulfoxides has been elaborated. The vinylation comprises the nucleophilic addition of secondary phosphine chalcogenides to the vinyl sulfoxides (～50 mol% KOH, dioxane, 25–40°C, 1 h) followed by the elimination of sulfenic acids from the adducts (additional equivalent of KOH, 60–70°C, 1.5–2.0 h), the yields of target tertiary vinyl phosphine chalcogenides reaching 92%.     

2,6,9-Trioxabicyclo[3.3.1]nona-3,7-dienes and 2,4,6,8-Tetraoxaadamantanes: Novel Chiral Spacer Units in Macrocyclic Polyethers

The unusual chiral heterocyclic systems, trioxabicyclo[3.3.1]nona-3,7-dienes ("bridged bisdioxines"), are incorporated as novel spacer molecules into macrocyclic polyether ring systems of various sizes (8, 9 as well as 11-15) by cyclocondensation reaction of the bisacid chloride 4b or bisesters 6,7 and 10, with several ethylene glycols. The 2:2 macrocycles 12-14 are obtained in approximately 50:50 mixtures of diastereomers. These conclusions are mainly based on HPLC data presented in Table I as well as X-ray analyses of (1R,5R)-8c (space group Pbca, a =10.163(3) Å, b =18.999(4) Å, c =36.187(10) Å, V =6987(3) ų , Z =8, d _calc =1.218 g cm^{m 3}, 6974 reflections, R =0.0553), meso/rac-11 (space group P1 ¥ , a =10.472(5) Å, b=16.390(5) Å, c =17.211(5) Å, f =98.69(2)°, g =93.04(2)°, n =98.52(2)°, V =2879.3(18) Å 3 , Z =2, d _calc =1.173 g cm m 3 , 11,162 reflections, R =0.0945) and meso-12 (space group P2₁/c, a =9.927(2), b =18.166(3), c =17.820(3) Å, g =96.590(10)°, V =3192.3(10) Å 3 , Z =4, D _c =1.109 g cm^{m 3}, 3490 reflections, R =0.0646). The 1:1 macrocycles 8b,c are also formed by intramolecular transesterification of the open-chain bisesters 7b,c and their formation is favored by the use of metal ions as templates. The bridged bisdioxine moieties in 8b and 12 are converted into the corresponding chiral tetraoxaadamantane spacers to afford macrocycles 16 and 17. Preliminary metal ion complexation studies with selected species (8c, 11-14) were also performed.     

Studies on the Structure and Properties of Membrane Phospholipase A1 Inclusion Bodies Formed at Low Growth Temperatures Using GFP Fusion Strategy

The effect of cultivation temperatures (37, 26, and 18 °C) on the conformational quality of Yersinia pseudotuberculosis phospholipase A₁ (PldA) in inclusion bodies (IBs) was studied using green fluorescent protein (GFP) as a folding reporter. GFP was fused to the C-terminus of PldA to form the PldA-GFP chimeric protein. It was found that the maximum level of fluorescence and expression of the chimeric protein is observed in cells grown at 18 °C, while at 37 °C no formation of fluorescently active forms of PldA-GFP occurs. The size, stability in denaturant solutions, and enzymatic and biological activity of PldA-GFP IBs expressed at 18 °C, as well as the secondary structure and arrangement of protein molecules inside the IBs, were studied. Solubilization of the chimeric protein from IBs in urea and SDS is accompanied by its denaturation. The obtained data show the structural heterogeneity of PldA-GFP IBs. It can be assumed that compactly packed, properly folded, proteolytic resistant, and structurally less organized, susceptible to proteolysis polypeptides can coexist in PldA-GFP IBs. The use of GFP as a fusion partner improves the conformational quality of PldA, but negatively affects its enzymatic activity. The PldA-GFP IBs are not toxic to eukaryotic cells and have the property to penetrate neuroblastoma cells. Data presented in the work show that the GFP-marker can be useful not only as target protein folding indicator, but also as a tool for studying the molecular organization of IBs, their morphology, and localization in E. coli, as well as for visualization of IBs interactions with eukaryotic cells.     

Enhanced stability of electrohydrodynamic jets through gas ionization

Theoretical predictions of the nonaxisymmetric instability growth rate of an electrohydrodynamic jet based on the measured total current overestimate experimental values. We show that this apparent discrepancy is the result of gas ionization in the surrounding gas and its effect on the surface charge density of the jet. As a result of gas ionization, a sudden drop in the instability growth rate occurs below a critical electrode separation, yielding highly stable jets that can be used for nano- to microscale printing.     

Facile synthesis of phosphorylated azides in ionic liquids and their use in the preparation of 1,2,3‐triazoles

The facile general synthetic route to azidoalkylphosphonates by the nucleophilic substitution reaction in a series of bromoalkylphosphonates was elaborated, using 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([bmim][PF₆]) as a recyclable reaction medium. These azidoalkylphosphonates were used as intermediates for copper(I)‐catalyzed regioselective 1,3‐dipolar cycloaddition with a variety of alkynes to afford 4‐substituted (1H‐1,2,3‐triazol‐1‐yl)alkylphosphonates as potential drug candidates. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:293–300, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20420     

Axisymmetric Fractional Diffusion with Mass Absorption in a Circle under Time-Harmonic Impact

The axisymmetric time-fractional diffusion equation with mass absorption is studied in a circle under the time-harmonic Dirichlet boundary condition. The Caputo derivative of the order 0<α≤2 is used. The investigated equation can be considered as the time-fractional generalization of the bioheat equation and the Klein–Gordon equation. Different formulations of the problem for integer values of the time-derivatives α=1 and α=2 are also discussed. The integral transform technique is employed. The outcomes of numerical calculations are illustrated graphically for different values of the parameters.     

Hesperetin—Between the Ability to Diminish Mono- and Polymicrobial Biofilms and Toxicity

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it’s inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin (<50% inhibition with MIC 4 mg/mL). Establishment of polymicrobial C. albicans-S. aureus biofilm was significantly inhibited with the lowest examined hesperetin concentration (1 mg/mL) in crystal violet and CFU assays. Hesperetin toxicity was examined towards MRC-5 fibroblasts (IC₅₀ 0.340 mg/mL) and in brine shrimp lethality assay (LC₅₀ > 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations.     

Additive and Emergent Catalytic Properties of Dimeric Unnatural Amino Acid Derivatives: Aldol and Conjugate Additions

Different densely substituted L- and D-proline esters were prepared by asymmetric (3+2) cycloaddition reactions catalyzed by conveniently selected EhuPhos chiral ligands. The γ-nitro-2-alkoxycarbonyl pyrrolidines thus obtained in either their endo or exo forms were functionalized and coupled to yield the corresponding γ-dipeptides. The catalytic properties of these latter dimers were examined using aldol and conjugate additions as case studies. When aldol reactions were analyzed, an additive behavior in terms of stereocontrol was observed on going from the monomers to the dimers. In contrast, in the case of the conjugate additions between ketones and nitroalkenes, the monomers did not catalyze this reaction, whereas the different γ-dipeptides promoted the formation of the corresponding Michael adducts. Therefore, in this latter case emergent catalytic properties were observed for these novel γ-dipeptides based on unnatural proline derivatives. Under certain conditions stoichiometric amounts of ketone, acid and nitroalkene), formation of N-acyloxy-2-oxooctahydro-1H-indoles was observed.