Stereoselective Synthesis of (Z)-β-Enamido Triflates and Fluorosulfonates from N-Fluoroalkylated Triazoles

N-Fluoroalkylated 1,2,3-triazoles in the presence of triflic acid or fluorosulfonic acid underwent a cascade reaction consisting of triazole protonation, ring opening, nitrogen elimination, sulfonate addition, HF elimination, and hydrolysis to furnish novel trifluoromethanesulfonyloxy- or fluorosulfonyloxy-substituted enamides, respectively, in a highly stereoselective fashion. The vinyl triflates underwent cross-coupling reactions to a variety of substituted enamides and serve as sources of the aminovinyl cations. In reactions with triflic acid, electron-rich triazoles afforded 2-fluoroalkylated oxazoles.     

Identification of two Ag‐2,2′:6′,2″‐terpyridine surface species on Ag nanoparticle surfaces by excitation wavelength dependence of SERS spectra and factor analysis: evidence for chemical mechanism contribution to SERS of Ag(0)–tpy

Measurement and interpretation of the excitation wavelength dependence of surface‐enhanced Raman scattering (SERS) spectra of molecules chemisorbed on plasmonic, e.g. Ag nanoparticle (NP) surfaces, are of principal importance for revealing the charge transfer (CT) mechanism contribution to the overall SERS enhancement. SERS spectra, their excitation wavelength dependence in the 445–780‐nm range and factor analysis (FA) were used for the identification of two Ag‐2,2′:6′,2″‐terpyridine (tpy) surface species, denoted Ag⁺–tpy and Ag(0)–tpy, on Ag NPs in systems with unmodified and/or purposefully modified Ag NPs originating from hydroxylamine hydrochloride‐reduced hydrosols. Ag⁺–tpy is a spectral analogue of [Ag(tpy)]⁺ complex cation, and its SERS shows virtually no excitation wavelength dependence. By contrast, SERS of Ag(0)–tpy surface complex generated upon chloride‐induced compact aggregate formation and/or in strongly reducing ambient shows a pronounced excitation wavelength dependence attributed to a CT resonance (the chemical mechanism) contribution to the overall SERS enhancement. Both the resonance (λ_exc = 532 nm) and off‐resonance (λ_exc = 780 nm) pure‐component spectra of Ag(0)–tpy obtained by FA are largely similar to surface‐enhanced resonance Raman scattering (λ_exc = 532 nm in resonance with singlet metal to ligand CT (¹ MLCT) transition) and SERS (λ_exc = 780 nm) spectra of [Fe(tpy)₂]²⁺ complex dication. Copyright © 2014 John Wiley & Sons, Ltd.     

SERS microRaman spectral probing of adsorbate‐containing,liquid‐overlayed nanosponge Ag aggregates assembled from fractal aggregates

Adsorbate‐containing, nanosponge Ag aggregates overlayed by a thin (~1.5 mm) liquid layer are reported as a new type of sample for Surface‐enhanced Raman scattering (SERS) microRaman spectral measurements and adsorbate (analyte) detection. Macroscopic Ag aggregates (of about 1.5 × 1.0 × 0.025 mm size) with the nanosponge internal morphology (revealed by Scanning electron microscopy (SEM)) were prepared by 3D assembling of fused fractal aggregates (D = 1.84 ± 0.04) formed in Ag nanoparticle hydrosol/HCl/adsorbate systems with 2,2’‐bipyridine (bpy) and/or a cationic free‐base tetrakis(2‐methyl‐4‐pyridiniumyl) porphine (H₂TMPyP) as the testing adsorbates. For SERS microRaman measurements, the macroscopic aggregate was overlayed by a thin (~1.5 mm) layer of the residual liquid. Preparation procedure, nanoscale imaging, and SERS spectral probing including the determination of the detection limits of the adsorbates revealed the following advantages of the adsorbate‐containing, liquid‐overlayed 3D nanosponge aggregate as a sample for SERS microRaman spectral measurements: (1) localization of adsorbate (analyte) into hot spots and, simultaneously, prevention of the analyte decomposition during the spectral measurement (carried out without an immersion objective), (2) fast and simple sample preparation, and (3) minimization of sample volume and an efficient concentration of hot spots into the focus of the laser beam. The advantages of the nanosponge Ag aggregates are further demonstrated by the 40 fmol limit of detection of bpy as Ag(0)‐bpy surface complex, as well as by preservation of the native structure of the cationic free‐base porphyrin H₂TMPyP. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of novel dithiocarbamates and xanthates using dialkyl azodicarboxylates: SN bond formation

A one?pot three?component route for the synthesis of a novel category of dithiocarbamates or xanthates is developed by a reaction of in-situ generated dithiocarbamic acids or xanthates with dialkyl azodicarboxylates under mild and catalyst-free conditions. The reaction is characterized by a wide scope, high efficiency and straightforward isolation protocol. The synthetic utility of the dithiocarbamates and xanthates was demonstrated on the preparation of symmetrical and unsymmetrical thioureas, isothiocyanates, and thiocarbamates.     

Synthesis and structure of lanthanide complexes with large-bite diphosphine dioxide ligands

Three large-bite diphosphine dioxide ligands were reacted with lanthanide salts to yield either molecular or polymeric complexes. The two flexible ligands gave bischelate complexes of general formulae [Ln(dppfO₂)₂Cl_x(NO₃)_2−x][FeCl₄] and [Ln(dppdO₂)₂(NO₃)₂]NO₃, where dppfO₂ and dppdO₂ are bis(diphenylphosphoryl)ferrocene and bis(diphenylphosphoryl)diphenyl ether, respectively. Reactions of the rigid bis(diphenylphosphoryl)benzene (dppbO₂) with lanthanide salts yielded linear coordination polymers of a 1:1.5 metal-to-ligand stoichiometry. The compounds were studied by single crystal X-ray diffraction, IR spectroscopy, mass spectrometry, and TG/DSC techniques.     

Synthesis of HPMA Copolymers Containing Doxorubicin Bound via a Hydrazone Linkage. Effect of Spacer on Drug Release and in vitro Cytotoxicity

The aim of this study was the synthesis, physico‐chemical characterization and preliminary evaluation of biological activity of novel polymer drugs based on conjugates of anti‐cancer drug doxorubicin (Dox) with water‐soluble polymer drug carriers based on N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymers. In the conjugates, Dox is attached to the polymer via a pH‐sensitive linkage susceptible to hydrolysis at pH ≈ 5–6, thus enabling intracellular Dox release. Seven Dox‐containing polymer conjugates differing in the length and structure of the single‐amino‐acid or oligopeptide spacer were synthesized (Gly, β‐Ala, 6‐aminohexanoyl, 4‐aminobenzoyl, GlyGly, GlyLeuGly, Gly‐DL ‐PheLeuGly) and the relationship between the spacer structure and the rate of in vitro Dox release was studied at various pH. The rate of Dox release at pH 5 (close to lysosomal pH) ranged from 70 to 96% of total Dox/48 h, depending on the spacer structure and being the highest for the conjugate containing the 6‐aminohexanoyl spacer. The rate of Dox release from most conjugates incubated at pH 7.4 (blood pH) was more than 10 times slower, ca. 4–10% of total Dox/48 h. Molecular weight of the polymer (25 000–115 000 g/mol) did not significantly influence the rate. The presence of lysosomal enzyme cathepsin B in incubation media increased the rate of Dox release from the conjugates with oligopeptide GlyLeuGly and Gly‐DL ‐PheLeuGly spacers by 15–30%, whereas the release from conjugates with other spacers remained unchanged. Cytotoxicity of all hydrazone conjugates for mouse EL‐4 T cell lymphoma cells was much higher and close to that of free Dox (IC₅₀ ≈ 0.1–0.34 μg Dox/mL), in contrast to cytotoxicity of similar classic conjugates bearing Dox attached via an amide bond (IC₅₀ ≈ 19 μg Dox/mL).     

N-(2-hydroxypropyl) methacrylamide copolymers containing pendant saccharide moieties: Synthesis and bioadhesive properties

A new route for the synthesis of bioadhesive water soluble polymeric drug carriers has been developed. Novel monomers, namely, N-methacryloylglycylglycylgalactosamine (MA-Gly-Gly-GalN) [ 8 ], MA -Gly-Gly-FucN [ 9 ], MA -Gly-Gly-GlcN [ 10 ], and MA-Gly-Gly-ManN [ 11 ], and copolymers [ 12–16 ] based on N-(2-hydroxypropyl) methacrylamide (HPMA) containing different content of pendant saccharide moieties (galactosamine, fucosylamine, glucosamine, or mannosamine), were synthesized. Copolymerization parameters for the copolymerization of HPMA [M₁] and MA-Gly-Gly-GalN [M₂] have been determined (r₁ = 0.82, r₂ = 0.38). Bioadhesion studies with everted sacs of guinesa pig small intestine and colon in vitro demonstrated that HPMA copolymers containing side-chains terminated in fucosylamine bind selectively to the colonic tissue. The extent of binding was dependent on the fucosylamine content of copolymers.