Non-covalent calixarene-amino acid complexes formed by MALDI-MS

Non-covalent inclusion complexes formed between amino acids and derivatized calix[6]arenes are observed in MALDI mass spectrometry. The methyl, ethyl, and propyl ester derivatives of calix[6]arene yielded amino acid complexes, while the smaller calix[4]arene analogs did not. Similarly the underivatized calix[6]arene and calix[4]arene did not produce complexes. Amino acid complexes were observed for nearly all 20 amino acids in time-of-flight (TOF) analysis. In Fourier transform mass spectrometry (FTMS) analysis, however, only the most basic amino acids arginine, histidine, and lysine formed stable adducts. The complexes were abundant under matrix-assisted laser desorption ionization (MALDI) conditions, which suggested favorable interactions between host and guest.     

First total synthesis of A(2) isoprostane

A stereoselective Julia-Lythgoe olefination has allowed the first total synthesis of A(2) isoprostane (1), a recently discovered member of the growing isoprostane family. This elusive compound opens up numerous new avenues for the molecular biology of cyclopentenone prostaglandins, which are endowed of intriguing biological effects such as antitumor, antiinflammatory, and antiviral activities.     

Regio‐ and Enantio‐selective Chemo‐enzymatic C−H‐Lactonization of Decanoic Acid to (S)‐δ‐Decalactone

The conversion of saturated fatty acids to high value chiral hydroxy‐acids and lactones poses a number of synthetic challenges: the activation of unreactive C?H bonds and the need for regio‐ and stereoselectivity. Here the first example of a wild‐type cytochrome P450 monooxygenase (CYP116B46 from Tepidiphilus thermophilus) capable of enantio‐ and regioselective C5 hydroxylation of decanoic acid 1 to (S)‐5‐hydroxydecanoic acid 2 is reported. Subsequent lactonization yields (S)‐δ‐decalactone 3 , a high value fragrance compound, with greater than 90 % ee. Docking studies provide a rationale for the high regio‐ and enantioselectivity of the reaction.     

Effect of anodizing conditions on the cell morphology of anodic films on AA2024-T3 alloy

The effects of applied current density, anodizing time, and electrolyte temperature on the cell and pore morphology of anodic films and the voltage-time response obtained during galvanostatic anodizing of AA2024-T3 alloy in sulphuric acid electrolytes have been studied. Scanning electron microscopy was employed to observe the film morphology. Sponge-like porous structure was promoted by anodizing at relatively low current density and high electrolyte temperature. In contrast, linear porous structure was favoured under the converse conditions. Intermediate conditions resulted in films containing either sequential layers of the 2 morphologies or a morphology incorporating features of the 2 types; such conditions were associated with anodizing voltages in the range 25 to 35 V. The reasons for the morphological differences are proposed to be due to interactions between film growth stresses and stresses arising from oxygen evolution on the development of the alumina cells.     

Effect of Toxic Metal Ions on Photosensitized Singlet Oxygen Generation for Photodegradation of Polyaromatic Hydrocarbon Derivatives and Inactivation of Escherichia coli

Here, we report an experimental study of the effect of toxic metal ions on photosensitized singlet oxygen generation for photodegradation of PAH derivatives, Anthracene‐9,10‐dipropionic acid disodium salt (ADPA) and 1,5‐dihydroxynapthalene (DHN) and photoinactivation of Escherichia coli bacteria by using cationic meso‐tetra(N‐methyl‐4‐pyridyl)porphine tetrachloride (TMPyP) as a singlet oxygen photosensitizer. Three s‐block metals ions, such as Na⁺, K⁺ and Ca²⁺ and five toxic metals such as Cd²⁺, Cu²⁺, Hg²⁺, Zn²⁺ and Pb²⁺ were studied. The s‐block metal ions showed no change in the rate of photodegradation of ADPA or DHN by TMPyP, whereas a dramatic change in the photodegradation of ADPA and DHN was observed in the presence of toxic metals. The maximum photodegradation rate constants of ADPA and DHN were observed for Cd²⁺ ions [(3.91 ± 0.20) × 10^?3 s^?1 and (7.18 ± 0.35) × 10^?4 s^?1, respectively]. Strikingly, the photodegradation of ADPA and DHN was almost completely inhibited in the presence of Hg²⁺ ions and Cu²⁺ ions. A complete inhibition of growth of E. coli was observed upon visible light irradiation of E. coli solutions with TMPyP and toxic metal ions particularly, Cd²⁺, Hg²⁺, Zn²⁺ and Pb²⁺ ions, except for Cu²⁺ ions where a significantly slow inhibition of E. coli's growth was observed.     

A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy (PT) and photodynamic therapy (PDT) and the largest‐ever mesothelioma PT experience (n = 10). PDT photosensitizers included porfimer sodium (2 mg·kg^?1; 24 h drug‐light interval) or 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a (HPPH) (4 mg·m^?2;48 h) with wavelengths of 630 nm to 60J·cm^?2 and 665 nm to 15‐45J·cm^?2, respectively. With a median age of 69 years, patients were predominantly male (90%) with epithelioid histology (100%) and stage III‐IV disease (100%). PT was delivered to a median of 55.0 CGE/1.8‐2.0 CGE (range 50–75 CGE) adjuvantly (n = 8) or as salvage therapy (n = 2) following extended pleurectomy/decortication (ePD)/PDT. Two‐year local control was 90%, with distant and regional failure rates of 50% and 30%, respectively. All patients received chemotherapy, and four received immunotherapy. Surgical complications included atrial fibrillation (n = 3), pneumonia (n = 2), and deep vein thrombosis (n = 2). Median survival from PT completion was 19.5 months (30.3 months from diagnosis), and 1‐ and 2‐year survival rates were 58% and 29%. No patient experienced CTCAEv4 grade ≥2 acute or late toxicity. Our prolonged survival in very advanced‐stage patients compares favorably to survival for PT without PDT and photon therapy with PDT, suggesting possible spatial or systemic cooperativity and immune effect.     

The Impact of pH on Catalytically Critical Protein Conformational Changes: The Case of the Urease,a Nickel Enzyme

Urease uses a cluster of two Ni^II ions to activate a water molecule for urea hydrolysis. The key to this unsurpassed enzyme is a change in the conformation of a flexible structural motif, the mobile flap, which must be able to move from an open to a closed conformation to stabilize the chelating interaction of urea with the Ni^II cluster. This conformational change brings the imidazole side chain functionality of a critical histidine residue, αHis323, in close proximity to the site that holds the transition state structure of the reaction, facilitating its evolution to the products. Herein, we describe the influence of the solution pH in modulating the conformation of the mobile flap. High-resolution crystal structures of urease inhibited in the presence of N-(n-butyl)phosphoric triamide (NBPTO) at pH 6.5 and pH 7.5 are described and compared to the analogous structure obtained at pH 7.0. The kinetics of urease in the absence and presence of NBPTO are investigated by a calorimetric assay in the pH 6.0–8.0 range. The results indicate that pH modulates the protonation state of αHis323, which was revealed to have pK_a=6.6, and consequently the conformation of the mobile flap. Two additional residues (αAsp224 and αArg339) are shown to be key factors for the conformational change. The role of pH in modulating the catalysis of urea hydrolysis is clarified through the molecular and structural details of the interplay between protein conformation and solution acidity in the paradigmatic case of a metalloenzyme.     

Direct meta-C−H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine-Based Template

The development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine-based selective meta-C−H perfluoroalkenylation of arenes involving several commercially available perfluoroolefins is described. The synthetic versatility of the protocol is demonstrated by an extensive substrate scope including different benzylsulfonyl, alkylarene and phenylacetic acid scaffolds. The generality of this methodology including the meta-C−H perfluoroalkenylation of Ibuprofen, the facile cleavage of the directing group and gram-scale reactions are presented.     

Heterocyclic rearrangements. N,N-diphenylhydrazones,oximes and O-methyloximes of 3-benzoyl-5-phenyl-1,2,4-oxadiazole

The behaviour of (E)- and (Z)-N,N-diphenylhydrazones and O-Methyloximes of 3-benzoyl-5-phenyl-1,2,4-oxadiazole has been studied. When refluxed in benzene, or in dioxane-water (1:1), the (Z)-N,N-diphenylhydrazone 8Z gave the indazole 11 or the substituted semicarbazide 12 , respectively. The O-methyloxime 14Z did not give any rearrangement. A criticism of the oximation reaction of 3-benzoyl-5-phenyl-1,2,4-oxadiazole is also reported.