Non‐Covalently Stabilized Alginate Hydrogels as Functional Cell Scaffold Material

Biopolymers are an attractive class of compounds for being used in biomedical applications as they are widely available from biomass. Their drawback is the lack of mechanical stability and the ability to tune this properly. Covalent chemical cross‐linking is an often used approach but it limits usability due to legislation as well as the need of advanced and specialized knowledge by end users such as clinicians. Here, increased and tunable mechanical properties are achieved of alginate‐based hydrogels with non‐covalent approaches using linear polyethyleneimine (LPEI) as a polyelectrolyte rather than only multivalent metal ions (Ca²⁺). Gel stiffness increases with increasing LPEI content. Gel morphology changes from a thin fibrous mesh for alginate‐Ca²⁺ to thicker fibrous networks when LPEI is introduced. The gels are able to efficiently release encapsulated small molecular dyes and the gels are able to host cells. For the cell encapsulation human skin fibroblasts (HSkF) and human bone marrow‐derived mesenchymal stem cells (hBM‐MSC) are used. HSkF can be successfully incorporated without diminished viability while the matrix components and gel preparation method are not compatible with hBM‐MSC. The newly developed alginate‐based system is regarded as a potential candidate for wound dressing materials.

     

Synthesis of compound X, a non-steroidal constituent of female urine, and congeners

The synthesis of trans-($\text{+}$)- and (?)-3,4-bis [(3-hydroxyphenyl) methyl] dihydro-2-(3H)-furanone ($\text{1}$), a recently discovered constituent of female urine, and some related compounds of biological interest is described.     

Multicomponent synthesis of 2-imidazolines

[reaction: see text] A multicomponent reaction (MCR) between amines, aldehydes, and isocyanides bearing an acidic alpha-proton gives easy access to a diverse range of highly substituted 2-imidazolines. The limitations of the methodology seem to be determined by the reactivity of the isocyanide and by the steric bulk on the in situ generated imine rather than by the presence of additional functional groups on the imine. Less reactive isocyanides, for example p-nitrobenzyl isocyanide 25a, react successfully with amines and aldehydes, using a catalytic amount of silver(I) acetate. Some of the resulting p-nitrophenyl-substituted 2-imidazolines undergo air oxidation to the corresponding imidazoles. Differences in reactivity of the employed isocyanides are explained with use of DFT calculations. Difficult reactions with ketones instead of aldehydes as the oxo-compound in this MCR are promoted by silver(I) acetate as well.     

Influence of Intramolecular Coordination on the Aggregation of Sodium Phenolate Complexes. X-ray Structures of [NaOC(6)H(4)(CH(2)NMe(2))-2](6) and [Na(OC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)(HOC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)](2)

The structural characterization of two new sodium phenolate complexes, containing ortho-amino substituents, enables the influence of intramolecular coordination on the aggregation of sodium phenolate complexes to be determined. Crystals of hexameric [NaOC(6)H(4)(CH(2)NMe(2))-2](6) (1a) are monoclinic, space group P2(1)/c, with a = 11.668(4) ?, b = 18.146(4) ?, c = 14.221(5) ?, beta = 110.76(3) ?, V = 2815.5(16) ?(3), and Z = 2; R = 0.0736 for 2051 reflections with I > 2.0sigma(I). Complex 1a contains a unique Na(6)O(6) core, consisting of two face-fused cubes, with the ortho-amino substituent of each phenolate coordinating to a sodium atom. In addition, two of the phenolate ligands have an eta(2)-arene interaction with an additional sodium atom in the core. Crystals of dimeric [(NaOC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)(HOC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)](2) (2b) are triclinic, space group P&onemacr;, with a = 10.0670(8) ?, b = 10.7121(7) ?, c = 27.131(3) ?, alpha = 92.176(8) degrees, beta = 99.928(8) degrees, gamma = 106.465(6) degrees, V = 2752.1(4) ?(3), and Z = 2; R = 0.0766 for 5329 reflections with I > 2.0sigma(I). Dimeric complex 2b contains two phenolate ligands, which bridge the two sodium atoms, each coordinating with one ortho-amino substituent to a sodium atom, while the second available ortho-amino substituent remains pendant. The coordination sphere of each sodium atom is completed by a (neutral) bidentate O,N-coordinated parent phenol molecule. The second ortho-amino substituent of this neutral phenol is involved in a hydrogen bridge with its acidic hydrogen. On the basis of these two new crystal structures and previously reported solid state structures for sodium phenolate complexes, it is shown that the introduction of first one and then two ortho-amino substituents into the phenolate ligands successively lowers the degree of association of these complexes in the solid state. In this process, the basic Na(2)O(2) building block of the molecular structures remains intact.     

Accurate Modelling of Pore-Scale Films and Layers for Three-Phase Flow Processes in Clastic and Carbonate Rocks with Arbitrary Wettability

Three-phase flow is a key process occurring in subsurface reservoirs, for example, during $\text{ CO }_2$ sequestration and enhanced oil recovery techniques such as water alternating gas (WAG) injection. Predicting three-phase flow processes, for example, the increase in oil recovery during WAG, requires a sound understanding of the fundamental flow physics in water- to oil-wet rocks to derive physically robust flow functions, i.e. relative permeability and capillary pressure. In this study, we use pore-network modelling, a reliable and physically based simulation tool, to predict the flow functions. We have developed a new pore-scale network model for rocks with variable wettability, from water- to oil-wet. It comprises a constrained set of parameters that mimic the wetting state of a reservoir. Unlike other models, it combines three main features: (1) A novel thermodynamic criterion for formation and collapse of oil layers. The new model hence captures wetting film and layer flow of oil adequately, which affects the oil relative permeability at low oil saturation and leads to accurate prediction of residual oil. (2) Multiple displacement chains, where injection of one phase at the inlet triggers a chain of interface displacements throughout the network. This allows for the accurate modelling of the mobilisation of many disconnected phase clusters that arise, in particular, during higher order WAG floods. (3) The model takes realistic 3D pore-networks extracted from pore-space reconstruction methods and CT images as input, preserving both topology and pore shape of the sample. For water-wet systems, we have validated our model with available experimental data from core floods. For oil-wet systems, we validated our network model by comparing 2D network simulations with published data from WAG floods in oil-wet micromodels. This demonstrates the importance of film and layer flow for the continuity of the various phases during subsequent WAG cycles and for the residual oil saturations. A sensitivity analysis has been carried out with the full 3D model to predict three-phase relative permeabilities and residual oil saturations for WAG cycles under various wetting conditions with different flood end-points.     

A flexible six-component reaction to access constrained depsipeptides based on a dihydropyridinone core

Highly functionalized and conformationally constrained depsipeptides based on a dihydropyridin-2-one core are prepared by the combination of a four- and a three-component reaction. The synthesis combines a one-pot Horner-Wadsworth-Emmons/cyclocondensation sequence leading to isonitrile-functionalized DHP-2-ones with an isonitrile-based Passerini multicomponent reaction (MCR). Substituents could be independently varied at six different positions. The two MCRs could also be performed as a one-pot procedure, simplifying the protocol and leading to a new and highly variable six-component process.