Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Phd by thesis

The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pKa, intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, 18F has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in po...

Applications of Fluorine in Medicinal Chemistry

The photoisomerization of azobenzene has been known for almost 75 years but only recently has this process been widely applied to biological systems. The central challenge of how to productively couple the isomerization process to a large functional change in a biomolecule has been met in a number of instances and it appears that effective photocontrol of a large variety of biomolecules may be possible. This critical review summarizes key properties of azobenzene that enable its use as a photoswitch in biological systems and describes strategies for using azobenzene photoswitches to drive functional changes in peptides, proteins, nucleic acids, lipids, and carbohydrates (192 references).

Azobenzene photoswitches for biomolecules.

Thiol-ene “click” reactions and recent applications in polymer and materials synthesis

A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions.

/pdf/functional-atlas-of-the-integrin-adhesome-3zgod6tuts.pdf

Functional atlas of the integrin adhesome

Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly

Coating of surfaces by RGD peptides is well-known. Herein we describe the possibility to switch cell adhesion properties by changing the distance and orientation of the RGD peptides to the surface. A set of RGD peptides of the type cyclo(-RGDfK-) was synthesized containing the photoswitchable 4-[(4-aminophenyl)azo]benzocarbonyl central unit as spacer between the acrylamide anchor and the RGD peptide. PMMA (poly methyl methacrylate) surfaces were coated with these peptides. Control of adhesion stimulation by irradiation with 366 or 450 nm light could be achieved.

/pdf/photoswitched-cell-adhesion-on-surfaces-with-rgd-peptides-1llsbo7cp4.pdf

Photoswitched cell adhesion on surfaces with RGD peptides.

One key point for improving osseous integration of implants is to render them osteopromotive by specifically favoring the adhesion of osteoblasts. Mimicking the physiological adhesion process of osteoblasts to the extracellular matrix improves cell adhesion in vitro and results in improved and earlier osseous integration of implants in vivo. Our approach involves coating titanium implants with a tailor-made cyclic-RGD peptide, thus allowing them to bind to specific integrin receptors on the cell surface through multimeric phosphonates. The advantages of this very stable, new type of anchoring for practical application are presented.

Titanium implant materials with improved biocompatibility through coating with phosphonate-anchored cyclic RGD peptides.

A new 2-oxazoline monomer with a Boc protected amino function, 2-[N-Boc-5-aminopentyl]-2-oxazoline; (Boc-AmOx), was synthesized from commercially available compounds. With an initiator salt system (N-methyl-2-methyl-2-oxazolinium triflate; MeOxOTf), the monomer could be converted via living cationic ring-opening polymerization to well-defined homopolymers with narrow molar mass distributions and targeted polymer chain length. After a quantitative deprotection, poly(2-oxazoline)s with pendant amino functions were obtained. In order to vary the polymer functional group density and solubility of the polymer, copolymerization with different monomer ratios of Boc-AmOx and 2-ethyl-2-oxazoline (EtOx) was performed. Exsitu NMR spectroscopy studies verified the randomness of the cationic copolymerization. The accessibility of the pendant amino side functions was confirmed in polymer analog thiourea formation with different isothiocyanates, such as benzyl isothiocyanate (BzNCS), or a fluorescence dye, tetramethyl rhodamine isothiocyanate (TRITC). A cross-linking reaction with a bifunctional isothiocyanate (Ph(NCS) 2 ) resulted in poly(2-oxazoline) hydrogels.

First poly(2-oxazoline)s with pendant amino groups

Stretched gels made of cross-linked poly(acrylonitrile) swollen in DMSO are introduced as freely scalable and widely applicable alignment media for the measurement of anisotropic NMR parameters such as residual dipolar couplings. The production process using accelerated electrons for cross-linking is described, NMR signals originating from the alignment medium are characterized, as well as methods for their suppression, and RDC measurements are demonstrated for a number of example molecules.

Jörg Auernheimer

Papers

Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly

Photoswitched cell adhesion on surfaces with RGD peptides.

Titanium implant materials with improved biocompatibility through coating with phosphonate-anchored cyclic RGD peptides.

First poly(2-oxazoline)s with pendant amino groups

Stretched poly(acrylonitrile) as a scalable alignment medium for DMSO.