Chiral bis-Acetal Porphyrazines as Near-infrared Optical Agents for Detection and Treatment of Cancer

We report the preparation of chiral oxygen atom-appended porphyrazines (pzs) as biomedical optical agents that absorb and emit in the near-IR wavelength range. These pzs take the form M[pz(A_4-nB_n)], where “A” and “B” represent moieties appended to the pz’s pyrrole entities, A = (2R,3R) 2,3-dimethyl-2,3-dimethoxy-1,4-diox-2-ene, B = β,β′-di-isopropoxybenzo, M is the incorporated metal ion (M = H₂, Zn), and n = 0, 1, 2 (-cis/-trans) and 3 ( Scheme 1 ). When dissolved in polar media, H₂[pz(trans-A₂B₂)] 5a does not fluoresce and has a negligible quantum yield for singlet oxygen generation (Ф_Δ = 0.074 ± 0.001, methanol), as measured by the photo-oxidation of DMA. However, when sequestered in the nonpolar environment of a liposome, it displays strong NIR emission (λ _max = 705 nm, Ф _f = 0.087) and an extremely high singlet oxygen quantum yield (Ф_Δ→1). Of this series, H₂[pz(trans-A₂B₂)] 5a is attractive as a potential optical probe, showing strongly fluorescent uptake by cells in culture, while 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide measurements of cell viability show no evidence of dark toxicity. This agent does show significant photoinduced toxicity suggesting that pzs such as 5a have promise as “theranostic” optical agents that can be visualized with fluorescence imaging while acting as a sensitizer for photodynamic therapy.

Figure Scheme 1. Open in figure viewer PowerPoint Synthesis of Porphyrazines 3a – 7a , 3b – 7b .     

Determination of Total Phenols in Foods by Boron Doped Diamond Electrode

A robust electrochemical method to measure the total phenol content in food samples is presented. Under optimal condition, BDD electrode showed excellent performance to detect the oxidation of several phenols and does not present the drawback due to electrode fouling. The analytical method used to perform such measurement has been optimized and successfully applied in different food samples. The results obtained were compared with the standard Folin–Ciocalteau method.     

An efficient synthesis of 2-substituted 6-methylpurine bases and nucleosides by Fe- or Pd-catalyzed cross-coupling reactions of 2,6-dichloropurines

Fe-catalyzed cross-coupling reactions of 9-substituted or protected 2,6-dichloropurines with 1 equiv of methylmagnesium chloride gave regioselectively 2-chloro-6-methylpurines in good yields. The same reactions with 3 equiv of methylmagnesium chloride or Pd-catalyzed reactions with trimethylaluminum afforded 2,6-dimethylpurines. The 2-chloro-6-methylpurines underwent another coupling with phenylboronic acid to give 6-methyl-2-phenylpurines. All reactions were perfomed for Bn- and THP-protected purine bases as well as for acyl-protected ribosides and 2-deoxyribosides. After deprotection, free purine bases and nucleosides were obtained.     

N-H insertion reactions of primary ureas: the synthesis of highly substituted imidazolones and imidazoles from diazocarbonyls

Primary ureas have been used as substrates in rhodium-catalyzed N-H insertion reactions with an array of diazocarbonyls. The insertion reaction is efficient and gives excellent selectivity and yields. The products from the insertion reaction with diazoketones cyclize readily in the presence of acid to yield the corresponding imidazolones that can be further derivatized by N-alkylation with alkyl, allyl, and benzyl halides. Alternatively, the imidazolones were treated with phosphorus oxybromide to form the corresponding 2-bromoimidazoles that were further functionalized using a Suzuki coupling reaction.     

Determination of lignans in Schisandra chinensis using micellar electrokinetic capillary chromatography

Micellar electrokinetic capillary chromatography (MEKC) has been developed as a promising method for the determination of lignans in plant samples. The separation conditions have been optimized with respect to the different parameters including sodium dodecyl sulfate (SDS) and acetonitrile concentration, pH of the background electrolyte, separation voltage, and capillary temperature. The background electrolyte consisting of 40 mM SDS and 35% acetonitrile in 10 mM tetraborate buffer (pH 9.3) was found to be the most suitable electrolyte for this analysis. The applied voltage of 28 kV (positive polarity) and the capillary temperature 25 degrees C gave the best separation of lignans. The interday reproducibility of the peak areas and the migration times was below 2.0%. The results of MEKC analyses were compared with those obtained by capillary electrochromatography (CEC) and reversed-phase high-performance liquid chromatography (RP-HPLC). The possibilities of using this method for the determination of lignans in drug and in serum samples were also tested.     

Synthesen von Aminolumazinen

Syntheses of Aminolumazines 6-aminolumazien 2 (1-(6-amino-2,4,7-trioxo-1,2,3,4,7,8-hexahydropteridin-8-yl)-1-deoxy-D -ribitol), a degradation product of russupteridine-yellow I ( 1 ) has been prepared from l-deoxy-l-(2,4,7-trioxo-1,2,3,4,7,8-hexahydeopteridin-8-yl)-D -ribitol ( 5 ) via the azo compound 6 and its reduction with Sn/HCOOH. Condensation of 5-amono-6-(D-ribitylamino)uracil ( 8 ) with parabanic acid ( 9 ) has led to ta synthesis of russupteridine-yellow IV ( 4 ); l-deoxy-l-(2,6,8-trioxo-2,4,5,6,7,8-hexahydro-lH-imidazolo[4,5-g]pteridin-4-yl-D -ribitol), albeit in low yield.     

Protein-poly(silicic) acid interactions at the air/solution interface

The structure of the interface generated by a spread layer of beta-casein on an aqueous colloidal poly(silicic) acid subphase is described. The results are compared with data for the protein alone spread at the air/water interface and the silicate solution. Films develop at the air-solution interface and a strong pH dependence of the interaction causing this is demonstrated. Reflectometry with X-rays and neutrons was used to probe the interaction as a function of subphase pH and film compression. Film thickness, tau/A, scattering length density, rho/A(-2), water volume fraction, phi(w), and surface coverage, Gamma/mg m(-2), were used to quantify the interfacial structure. Where possible, the X-ray and neutron data sets were co-refined enabling phi(w) to be evaluated without assumption regarding the protein density. At pH 5-7, strong protein-silicate interaction occurred, the interface comprising three regions: a discrete protein upper layer on top of a 15 +/- 2 A layer of silicated material followed by a diffuse layer that extended into the subphase.     

Voltammetry of osmium-modified DNA at a mercury film electrode: application in detecting DNA hybridization

Mercury film electrodes (MFE) have recently been used in nucleic acid electrochemical analysis as alternatives to the classical mercury drop ones. DNA modified with osmium tetroxide, 2,2'-bipyridine (Os,bipy) can be detected with a high sensitivity at mercury electrodes via measurements of a catalytic osmium signal. In this paper we show that mercury film on a glassy carbon electrode can be used in voltammetric analysis of Os,bipy-modified DNA. Application of the MFE as a detection electrode in double-surface electrochemical DNA hybridization assay involving osmium labeling of target DNA is demonstrated.     

Asymptotic behavior of a nonisothermal viscous Cahn-Hilliard equation with inertial term

We consider a differential model describing nonisothermal fast phase separation processes taking place in a three-dimensional bounded domain. This model consists of a viscous Cahn-Hilliard equation characterized by the presence of an inertial term χtt, χ being the order parameter, which is linearly coupled with an evolution equation for the (relative) temperature ?. The latter can be of hyperbolic type if the Cattaneo-Maxwell heat conduction law is assumed. The state variables and the chemical potential are subject to the homogeneous Neumann boundary conditions. We first provide conditions which ensure the well-posedness of the initial and boundary value problem. Then, we prove that the corresponding dynamical system is dissipative and possesses a global attractor. Moreover, assuming that the nonlinear potential is real analytic, we establish that each trajectory converges to a single steady state by using a suitable version of the ?ojasiewicz-Simon inequality. We also obtain an estimate of the decay rate to equilibrium.