Daylight-driven rechargeable antibacterial and antiviral nanofibrous membranes for bioprotective applications.

Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Most present personal protective equipment used to prevent EID transmission and infections is typically devoid of antimicrobial activity. We report on green bioprotective nanofibrous membranes (RNMs) with rechargeable antibacterial and antiviral activities that can effectively produce biocidal reactive oxygen species (ROS) solely driven by the daylight. The premise of the design is that the photoactive RNMs can store the biocidal activity under light irradiation and readily release ROS under dim light or dark conditions, making the biocidal function "always online." The resulting RNMs exhibit integrated properties of fast ROS production, ease of activity storing, long-term durability, robust breathability, interception of fine particles (>99%), and high bactericidal (>99.9999%) and virucidal (>99.999%) efficacy, which enabled to serve as a scalable biocidal layer for protective equipment by providing contact killing against pathogens either in aerosol or in liquid forms. The successful synthesis of these fascinating materials may provide new insights into the development of protection materials in a sustainable, self-recharging, and structurally adaptive form

Synthesis of pyrrolizines by intramolecular capture of 1,4-dipolar intermediates in reactions of enamines with dimethyl acetylenedicarboxylate

Solvent polarity and reaction temperature strongly influence the reactions of dimethyl acetylenedicar-boxylate (DMAD) with 1-pyrrolidinyl enamines of acyclic and cyclic ketones. Whereas DMAD and 1-[1-phenyl-2-(phenylthio)ethenyl]pyrrolidine (3) give only a mixture of the isomeric 1,3-butadienes (5) in apolar solvents, in methanol the main product is the pyrrolizine 7, together with 5. Again in methanol, DMAD reacts at 0-5° with 8, 9 and 10 to give exclusively 1:1 adducts, the pyrrolizines 11,12 and 13, respectively, whereas at −50° 8 and 9 give 1:2 (enamine : DMAD) adducts, the pyrrolizines 14 and 15, respectively; a single crystal X-ray analysis of 14 gave the structure of the 1:2 adducts. In the same solvent methyl propiolate and 8 give only the linear Michael adduct 17. The enamine-ketone 18 reacts with DMAD in propylene carbonate at 0–5° to give, via (2 + 2)-cycloaddition and ring expansion, 19, and the linear Michael adduct 20. The mechanism of (2 + 2)-cycloaddition and pyrrolizine formation is discussed in terms of a common tied-ion pair intermediate formed in the first, rate-determining step, followed by a second solvent-dependent step

From 2,3-Diazabicyclo[2.2.2]oct-2-ene to Fluorazophore-L, a membrane-bound fluorescent probe for antioxidants

The aim of this work was to synthesize and to establish a new fluorescent membrane probe for antioxidants by exploiting the exceptional properties of the long-lived fluorophore 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) alias Fluorazophore-P. The first step was to find an appropriate synthetic route towards a lipophilic derivative of Fluorazophore-P, namely Fluorazophore-L, that should enable an efficient and facile incorporation into model membrane systems. The water-soluble hydroxy-substituted Fluorazophore-H was chosen as a key compound and served as a versatile precursor for various members of the Fluorazophore-family, including Fluorazophore-L. For example, substantial contributions in the synthesis of fluorazophore-labeled peptides to monitor the length-dependence of end-to-end collision rates of polypeptides were done within this work: "A Fluorescence Based Method for Direct Measurement of Submicrosecond Intramolecular Contact Formation in Biopolymers: An Exploratory Study with Polypeptides", R. R. Hudgins, F. Huang, G. Gramlich, W. M. Nau, J. Am. Chem. Soc. 2002, 124, 556-564. (Appendix) In this context, the search for a mild and selective method to substitute a harsh hydrolysis step, led to a study about a photo-cleavable Fluorazophore: "A Photoactivable Fluorophore Based on Thiadiazolidinedione as Caging Group", G. Gramlich, W. M. Nau, Org. Let. 1999, 1, 603-605. (Appendix) Fluorazophore-L (Fluoazophore-L) was designed as a head-labeled palmitic acid derivative. Experiments in homogeneous solution confirmed that Fluoazophore-L preserves its photophysical properties, namely the long-lived fluorescence and the essentially diffusion-controlled reactivity towards α-tocopherol (α-Toc). Its capability to serve as a membrane probe was assessed by air/water monolayer experiments (surface pressure-area isotherms) and preliminary spectroscopic measurements. It could be shown that Fluoazophore-L partitions into monolayers of 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC) and that even pure Fluoazophore-L forms stable monolayers at the air-water interface thus presents a highly amphiphilic molecule: "A Long-Lived Amphiphilic Fluorescent Probe studied in POPC Air-Water Monolayer and Solution Bilayer Systems", G. Gramlich, J. Zhang, M. Winterhalter, W. M. Nau, Chem. Phys. Lipids 2001, 113, 1-9 (Appendix). The first assignment of Fluoazophore-L in model membranes was a study of its interaction with the water-soluble antioxidant vitamin C, thus examining interfacial reactivity. Singlet-excited Fluoazophore-L was used as a mimic for highly reactive lipid alkoxyl and peroxyl radicals. This work revealed an unexpected inversion of the pHdependent activity pattern, which could be ascribed to an interesting surface effect: "Increased Antioxidant Reactivity of Vitamin C at low pH in Model Membranes", G. Gramlich, J. Zhang, W. M. Nau, J. Am. Chem. Soc. 2002, 124, 11252-11253 (Appendix). Finally, the intrafacial reactivity of α-Toc in liposomes and micelles could be probed by means of Fluoazophore-L. In micelles and in membrane structures a more demanding quenching kinetics than in usual organic solvents arises. In the case of small micelles Poissonian statistics has to be applied while in liposomes a two dimensional diffusion rate limits the maximum reactivity. In this study, the "immobile" probe/quencher pair Fluoazophore-L/α-Toc was used for the first time and the validity of different quenching models was discussed. The resulting diffusion rate constants for α-Toc provide important benchmark values for antioxidant research: "Diffusion of α-Tocopherol in Membrane Models: Probing the Kinetics of Vitamin E Antioxidant Action by Fluorescence in Real Time", G. Gramlich, J. Zhang, W. M. Nau, J. Am. Chem. Soc. 2004, 126, 5482-5492 (Appendix). A global fitting routine was developed to allow appropriate data processing of fluorescence quenching in membrane models. This fitting procedure was also successfully employed in the simultaneous fitting of steady-state and time-resolved fluorescence quenching by host-guest complexation with cyclodextrins. "A Joint Structural, Kinetic, and Thermodynamic Investigation of Substituent Effects on Host- Guest Complexation of Bicyclic Azoalkanes by β-Cyclodextrin", X. Zhang, G. Gramlich, X. Wang, W. M. Nau, J. Am. Chem. Soc. 2002, 124, 254-263 (Appendix). For the quenching models used, it is essential to ensure that reaction between singletexcited fluorazophores and hydrogen donors as antioxidants occurs only by hydrogen transfer and upon contact of probe and quencher. To clarify this process experiments using spectroscopic methods were contributed to a detailed theoretical study of reaction pathways: "Fluorescence Quenching by Sequential Hydrogen, Electron, and Proton Transfer in the Proximity of a Conical Intersection", A. Sinicropi, R. Pogni, R. Basosi, M. A. Robb, G. Gramlich, W. M. Nau, M. Olivucci, Angew. Chem., Int. Ed. 2001, 40, 4185-4189 (Appendix). In summary, the result of this study was the design and synthesis of the new fluorescent membrane probe Fluorazophore-L that combines the unusual properties of DBO with a complete incorporation into model membranes. The properties of the new probe were assessed in monolayer and by fluorescence lifetime experiments. Its potency was proven by the interaction with natural antioxidants located in the proximity of membrane mimetic systems. These quenching experiments allowed a new insight into the processes involving antioxidants in microheterogeneous environments, especially an unusual inversion of the well-known reactivity pattern of ascorbic acid and the observation of the lateral diffusion of α-tocopherol along the surface of supramolecular assemblies

Crystallization and preliminary X-ray diffraction analysis of levansucrase (LsdA) from Gluconacetobacter diazotrophicus SRT4

The endophytic bacterium Gluconacetobacter diazotrophicus SRT4 secretes a constitutively expressed levansucrase (LsdA; EC 2.4.1.10), which converts sucrose to fructo-oligosaccharides and levan. Fully active LsdA was purified to high homogeneity by non-denaturing reversed-phase HPLC and was crystallized at room temperature by the hanging-drop vapour-diffusion method using ammonium sulfate and ethanol as precipitants. The crystals are extremely sensitive, but native data have been collected to 2.5 A under cryogenic conditions using synchrotron radiation. LsdA crystals belong to the orthorhombic space group P22(1)2(1) or P2(1)2(1)2, with unit-cell parameters a = 53.80, b = 119.39, c = 215.10 A

The Vinylogous Wolff Rearrangement Catalyzed with RhII Complexes

Decomposition of β,γ-unsaturated diazoketones has been investigated in the presence of Rh2(OAc)4 catalyst. These reactions produce exclusively the products of the vinylogous Wolff rearrangement with higher yields than CuII catalysts. Chiral catalysts such as tetrakis [methyl (S)-5-oxopyrrolidine-2-carboxylate]dirhodium(II) and CuI bis(oxazoline) complexes, which are effective catalysts for the inter and/or intramolecular cyclopropanations reactions, catalyze the vinylogous Wolff rearrangement to produce the expected products with low levels of enantioselectivity

Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation

Synthetic methods that enable the macrocyclisation of peptides facilitate the development of effective therapeutic and diagnostic tools. Herein we report a peptide cyclisation strategy based on intramolecular interception of visible-light-mediated cysteine desulfurisation. This method allows cyclisation of unprotected peptides in an aqueous solution via the installation of a hydrocarbon linkage. We explore the limits of this chemistry using a range of model peptides of increasing length and complexity, including peptides of biological/therapeutic relevance. The method is applied to replace the native disulfide of the peptide hormone, oxytocin, with a proteolytically/redox-stable hydrocarbon, and internal macrocyclisation of an MCL-1-binding peptide

On The Mechanism Of The Aza-morita-baylis-hillman Reaction: Esi-ms Interception Of A Unique New Intermediate.

Solutions of aza-Morita-Baylis-Hillman (aza-MBH) reactions were directly monitored by ESI(+)-MS(/MS) spectrometry to obtain information on their mechanism. A unique bis-sulfonamide intermediate was intercepted and characterized and, based on this novel species, a mechanism that rationalizes the uniqueness of aza-MBH reactions is proposed.476593-