Control of the Helical Chirality of Enantiopure Sulfinyl (Z)‐Azobenzene‐Based Photoswitches

A new class of enantiopure ortho,ortho‐disubstituted azobenzene photoswitches has been synthesized from (S)‐2‐(p‐tolylsulfinyl)benzoquinone and arylhydrazines. The sulfoxide acts as a unidirectional controller of the helical chirality that arises in the Z isomer after photoisomerization. Highly congested E‐azobenzenes 5 c showed two atropisomeric diastereoconformers in the solid state that converged upon irradiation into a unique Z isomer with defined helicity (M), as evident in the X‐ray structure. The chiroptical properties of this three‐state enantiopure switch can be externally tuned both photochemically and/or thermally. Theoretical CD spectra calculated by using time‐dependent DFT methods support the existence of two atropoisomeric E isomers and only one Z isomer with (M) helicity. Complementary to the classical azobenzene‐based switches, the photoswiching event is promoted under green/blue light and do not occur under UV irradiation.     

Cellulose Hydrolysis by Cellobiohydrolase Cel7A Shows Mixed Hyperbolic Product Inhibition

In order to establish which are the contribution of linear (total), hyperbolic (partial) or parabolic inhibitions by cellobiose, and also a special case of substrate inhibition, the kinetics of cellobiohydrolase Cel7A obtained from Trichoderma reesei was investigated. Values of kinetic parameters were estimated employing integrated forms of Michaelis–Menten equations through the use of non-linear regression, and criteria for selecting inhibition models are discussed. With cellobiose added at the beginning of the reaction, it was found that cellulose hydrolysis follows a kinetic model, which takes into account a mixed hyperbolic inhibition, by cellobiose with the following parameter values: K _m 5.0 mM, K _ic 0.029 mM, K _iu 1.1 mM, k _cat 3.6 h⁻¹ and k _cat′ 0.2 h⁻¹. Cellulose hydrolysis without initial cellobiose added also follows the same inhibition model with similar values (4.7, 0.029 and 1.5 mM and 3.2 and 0.2 h⁻¹, respectively). According to Akaike information criterion, more complex models that take into account substrate and parabolic inhibitions do not increase the modulation performance of cellulose hydrolysis.     

Unprecedented μ-1,2-bis(monodentate) coordination mode of croconate dianion (C5O5): Synthesis and crystal structures of manganese- and copper-based coordination polymers

Two new coordination polymers {[Mn₂(BPP)₂(C₅O₅)₂(OH₂)₄]·3H₂O}_n (1) and {[Cu₄(BPP)₄(C₅O₅)₄]·8H₂O}_n (2) [BPP = 1,3-bis(4-pyridyl)propane and C₅O₅²⁻ = croconate anion] were synthesized and characterized by thermal analysis, vibrational spectroscopy (Raman and infrared) and single crystal X-ray diffraction analysis. Compound 1 was obtained under solvothermal conditions and 2 by the diffusion method. Structure determination by single crystal X-ray diffraction analysis revealed that compound 1 presents two-dimensional polymeric nature due to the bridging coordination mode of both BPP ligand and croconate anion. In this case, the croconate anion acts in the unprecedented μ-1,2-bis(monodentate) coordination mode, forming interpenetrated grids of 6³ topology. On the other hand, compound 2 is a three-dimensional 4-connected uninodal net of (4²·8⁴) topology, due to the presence of the flexible BPP ligand that bridges two Cu(II) sites connecting perpendicular one-dimensional polymeric chains, formed by croconate anions coordinated to the metal centers in a bis-bidentate coordination mode.     

Mechanisms controlling the cellular accumulation of copper bis(thiosemicarbazonato) complexes

Copper (Cu) bis(thiosemicarbazonato) metal complexes [Cu(II)(btsc)s] have unique tumor-imaging and treatment properties and more recently have revealed potent neuroprotective actions in animal and cell models of neurodegeneration. However, despite the continued development of Cu(II)(btsc)s as potential therapeutics or diagnostic agents, little is known of the mechanisms involved in cell uptake, subcellular trafficking, and efflux of this family of compounds. Because of their high lipophilicity, it has been assumed that cellular accumulation is through passive diffusion, although this has not been analyzed in detail. The role of efflux pathways in cell homeostasis of the complexes is also largely unknown. In the present study, we investigated the cellular accumulation of the Cu(II)(btsc) complexes Cu(II)(gtsm) and Cu(II)(atsm) in human neuronal (M17) and glial (U87MG) cell lines under a range of conditions. Collectively, the data strongly suggested that Cu(II)(gtsm) and Cu(II)(atsm) may be taken into these cells by combined passive and facilitated (protein-carrier-mediated) mechanisms. This was supported by strong temperature-dependent changes to the uptake of the complexes and the influence of the cell surface protein on Cu accumulation. We found no evidence to support a role for copper-transporter 1 in accumulation of the compounds. Importantly, our findings also demonstrated that Cu from both Cu(II)(gtsm) and Cu(II)(atsm) was rapidly effluxed from the cells through active mechanisms. Whether this was in the form of released ionic Cu or as an intact metal complex is not known. However, this finding highlighted the difficulty of trying to determine the uptake mechanism of metal complexes when efflux is occurring concomitantly. These findings are the first detailed exploration of the cellular accumulation mechanisms of Cu(II)(btsc)s. The study delineates strategies to investigate the uptake and efflux mechanisms of metal complexes in cells, while highlighting specific difficulties and challenges that need to be considered before drawing definitive conclusions.     

Stereoselective synthesis of (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanols targeted to the C1 domain of protein kinase C

Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. By using the X-ray crystal structure of the PKCδ C1b domain combined with molecular modeling, we discovered (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanol as a novel C1 domain ligand. The stereoselective synthesis of this tricyclic γ-amino alcohol was based on two successive Diels-Alder reactions to construct the six continuous stereocenters of the key intermediate.     

Ab initio quantum dynamical study of photoinduced ring opening in furan

The nonadiabatic photoinduced ring opening occurring in the two lowest excited singlet states of furan is investigated theoretically, using wave-packet propagation techniques. The underlying multidimensional potential energy surfaces (PESs) are obtained from ab initio computations, using the equation-of-motion coupled cluster method restricted to single and double excitations (EOM-CCSD), reported in earlier recent work [E. V. Gromov, A. B. Trofimov, F. Gatti, and H. Ko?ppel, J. Chem. Phys. 133, 164309 (2010)]. Up to five nuclear degrees of freedom are considered in the quantum dynamical treatment. Four of them represent in-plane motion for which the electronic states in question (correlating with the valence (1)B(2)(V) and Rydberg (1)A(2)(3s) states at the C(2v) ground-state molecular configuration) have different symmetries, A(') and A('), respectively. The fifth mode, representing out-of-plane bending of the oxygen atom against the carbon-atom plane, leads to an interaction of these states, as is crucial for the photoreaction. The nonadiabatic coupling and conical intersection cause an electronic population transfer on the order of ～10 fs. Its main features, and that of the wave-packet motion, are interpreted in terms of properties of the PES. The lifetime due to the ring-opening process has been estimated to be around 2 ps. The dependence of this estimate on the nuclear degrees of freedom retained in the computations is discussed.     

Structural and mechanical properties of "peelable" organoaqueous dispersions with partially hydrolyzed poly(vinyl acetate)-borate networks: applications to cleaning painted surfaces

The preparation and structural characterization of a family of viscoelastic dispersions of borate cross-linked, 80% hydrolyzed poly(vinyl acetate) (80PVAc) in aqueous-organic liquids are presented. Correlations between mechanical properties (from rheological measurements) and the degree and nature of cross-linking (from (11)B NMR spectroscopy) are reported, and the results are used to assess their potential as low-impact cleaning agents for the surfaces of paintings. Because the dispersions can be prepared at room temperature by simple procedures from readily available materials and can contain up to 50% (w/w) of an organic liquid, they offer important advantages over previously described cleaning agents that are based on fully hydrolyzed PVAc (i.e., poly(vinyl alcohol). The mechanical properties of the various aqueous-organic dispersions, as determined quantitatively by rheological investigations and qualitatively by their ease of removal from a solid surface (i.e., the so-called "peel-off" ability) have been tuned systematically by varying the amount of organic liquid, its structure, and the concentrations of borax and 80PVAc. The (11)B NMR studies demonstrate that the concentration of borate ions actively participating in cross-linking increases significantly with the amount of organic liquid in the mixture. The degree of cross-linking remains constant when the 80PVAc and borax concentrations are varied, as long as their ratios are kept constant. Some of the 80PVAc-borax dispersions have been tested successfully as cleaning agents on the surface of a 16th-17th century oil-on-wood painting by Lodovico Cardi, "Il Cigoli", that was covered by a brown patina and on the surface of a Renaissance wall painting by Vecchietta in Santa Maria della Scala, Siena, Italy, that had a degraded polyacrylate coating from a previous conservation treatment.     

Pharmacophore-driven identification of PPARγ agonists from natural sources

In a search for more effective and safe anti-diabetic compounds, we developed a pharmacophore model based on partial agonists of PPARγ. The model was used for the virtual screening of the Chinese Natural Product Database (CNPD), a library of plant-derived natural products primarily used in folk medicine. From the resulting hits, we selected methyl oleanonate, a compound found, among others, in Pistacia lentiscus var. Chia oleoresin (Chios mastic gum). The acid of methyl oleanonate, oleanonic acid, was identified as a PPARγ agonist through bioassay-guided chromatographic fractionations of Chios mastic gum fractions, whereas some other sub-fractions exhibited also biological activity towards PPARγ. The results from the present work are two-fold: on the one hand we demonstrate that the pharmacophore model we developed is able to select novel ligand scaffolds that act as PPARγ agonists; while at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery.     

Human plasma protein adsorption onto dextranized surfaces: a two-dimensional electrophoresis and mass spectrometry study

Protein adsorption is fundamental to thrombosis and to the design of biocompatible materials. We report a two-dimensional electrophoresis and mass spectrometry study to characterize multiple human plasma proteins adsorbed onto four different types of model surfaces: silicon oxide, dextranized silicon, polyurethane and dextranized polyurethane. Dextran was grafted onto the surfaces of silicon and polyurethane to mimic the blood-contacting endothelial cell glycocalyx surface. Surface topography and hydrophobicity/hydrophilicity were determined and analyzed using atomic force microscopy and water contact angle measurements, respectively. Using two-dimensional electrophoresis, we show that, relative to the unmodified surfaces, dextranization significantly inhibits the adsorption of several human plasma proteins including IGHG1 protein, fibrinogen, haptoglobin, Apo A-IV, Apo A-I, immunoglobulin, serum retinal-binding protein and truncated serum albumin. We further demonstrate the selectivity of plasma protein adsorbed onto the different functionalized surfaces and the potential to control and manipulate proteins adsorption on the surfaces of medical devices, implants and microfluidic devices. This result shows that adsorption experiments using a single protein or a binary mixture of proteins are consistent with competitive protein adsorption studies. In summary, these studies indicate that coating blood-contacting biomedical applications with dextran is an effective route to reduce thrombo-inflammatory responses and to surface-direct biological activities.     

Influence of the relative humidity on aminosilane molecular grafting properties

Functional coatings with amino groups are used in a wide range of biochemistry-related applications. A technological platform that takes advantage of the affinity between amino-functionalized coatings and biomolecules is the DNA microarray methodology. Reliability and reproducibility of the microarray data strongly depend on the quality of the substrate; therefore, a proper awareness of how the storage conditions affect the amino-functionalized coatings is necessary. In this work we have studied the influence of different relative humidity levels on amino-methyl-silane coatings prepared via sol–gel methodology. Drops of a buffer solution containing a luminescent dye have been deposited (or spotted) on the coating; the dye molecules react with the amino-groups and leave circular luminescent marks (spots) on the substrate surface. Shape and luminescence of the spots, as well as background signals, have been monitored using a microarray laser scanner. With the proposed protocol we have measured the changes of these variables due to different storage conditions. FT-IR measurements have been performed to investigate the related chemistry changes.