Addressing the Glycine Rich Loop of Protein Kinases by a Multi Facetted Interaction Network Inhibition of Pka and a Pkb Mimic

Protein kinases continue to be hot targets in drug discovery research, as they are involved in many essential cellular processes and their deregulation can lead to a variety of diseases. A series of 32 enantiomerically pure inhibitors was synthesized and tested towards protein kinase A PKA and protein kinase B mimic PKAB3 PKA triple mutant . The ligands bind to the hinge region, ribose pocket, and glycine rich loop at the ATP site. Biological assays showed high potency against PKA, with Ki values in the low nanomolar range. The investigation demonstrates the significance of targeting the often neglected glycine rich loop for gaining high binding potency. X ray co crystal structures revealed a multi facetted network of ligand loop interactions for the tightest binders, involving orthogonal dipolar contacts, sulfur and other dispersive contacts, amide amp; 960; stacking, and H bonding to organofluorine, besides efficient water replacement. The network was analyzed in a computational approac

Photocatalytic Aqueous CO2 Reduction to CO and CH4 Sensitized by Ullazine Supramolecular Polymers

There has been rapid progress on the chemistry of supramolecular scaffolds that harness sunlight for aqueous photocatalytic production of hydrogen. However, great efforts are still needed to develop similar photosynthetic systems for the great challenge of CO2reduction especially if they avoid the use of nonabundant metals. This work investigates the synthesis of supramolecular polymers capable of sensitizing catalysts that require more negative potentials than proton reduction. The monomers are chromophore amphiphiles based on a diareno-fused ullazine core that undergo supramolecular polymerization in water to create entangled nanoscale fibers. Under 450 nm visible light these fibers sensitize a dinuclear cobalt catalyst for CO2photoreduction to generate carbon monoxide and methane using a sacrificial electron donor. The supramolecular photocatalytic system can generate amounts of CH4comparable to those obtained with a precious metal-based [Ru(phen)3](PF6)2sensitizer and, in contrast to Ru-based catalysts, retains photocatalytic activity in all aqueous media over 6 days. The present study demonstrates the potential of tailored supramolecular polymers as renewable energy and sustainability materials

Antiaromatic Covalent Organic Frameworks Based on Dibenzopentalenes

Despite their inherent instability, 4n amp; 960; systems have recently received significant attention due to their unique optical and electronic properties. In dibenzopentalene DBP , benzanellation stabilizes the highly antiaromatic pentalene core, without compromising its amphoteric redox behavior or small HOMO LUMO energy gap. However, incorporating such molecules in organic devices as discrete small molecules or amorphous polymers can limit the performance e.g., due to solubility in the battery electrolyte solution or low internal surface area . Covalent organic frameworks COFs , on the contrary, are highly ordered, porous, and crystalline materials that can provide a platform to align molecules with specific properties in a well defined, ordered environment. We synthesized the first antiaromatic framework materials and obtained a series of three highly crystalline and porous COFs based on DBP. Potential applications of such antiaromatic bulk materials were explored COF films show a conductivity of 4 10 8 S cm 1 upon doping and exhibit photoconductivity upon irradiation with visible light. Application as positive electrode materials in Li organic batteries demonstrates a significant enhancement of performance when the antiaromaticity of the DBP unit in the COF is exploited in its redox activity with a discharge capacity of 26 mA h g 1 at a potential of 3.9 V vs. Li Li . This work showcases antiaromaticity as a new design principle for functional framework material

Comparing the Halogen Bond to the Hydrogen Bond by Solid-State NMR Spectroscopy: Anion Coordinated Dimers from 2- and 3-Iodoethynylpyridine Salts

Halogen bonding is an increasingly important tool in crystal engineering, and measuring its influence on the local chemical and electronic environment is necessary to fully understand this interaction. Here, we present a systematic crystallographic and solid-state NMR study of self-complementary halogen-bonded frameworks built from the halide salts (HCl, HBr, HI, HI3) of 2-iodoethynylpyridine and 3-iodoethynylpyridine. A series of single crystal X-ray structures reveals the formation of discrete charged dimers in the solid state, directed by simultaneous X-H-N+hydrogen bonds and C-IX-halogen bonds (X=Cl, Br, I). Each compound was studied using multinuclear solid-state magnetic resonance spectroscopy, observing1H to investigate the hydrogen bonds and13C,35Cl, and79/81Br to investigate the halogen bonds. A natural localized molecular orbital analysis was employed to help interpret the experimental results.1HSSNMR spectroscopy reveals a decrease in the chemical shift of the proton participating in the hydrogen bond as the halogen increases in size, whereas the13CSSNMR reveals an increased13C chemical shift of the C-I carbon for C-IX-relative to C-IN halogen bonds. Additionally,35Cl and79/81Br SSNMR, along with computational results, have allowed us to compare the C-IX-halogen bond involving each halide in terms of NMR observables. Due to the isostructural nature of these compounds, they are ideal cases for experimentally assessing the impact of different halogen bond acceptors on the solid-state NMR response

Supramolecular macrocycles reversibly assembled by Te…O chalcogen bonding

Organic molecules with heavy main-group elements frequently form supramolecular links to electron-rich centres. One particular case of such interactions is halogen bonding. Most studies of this phenomenon have been concerned with either dimers or infinitely extended structures (polymers and lattices) but well-defined cyclic structures remain elusive. Here we present oligomeric aggregates of heterocycles that are linked by chalcogen-centered interactions and behave as genuine macrocyclic species. The molecules of 3-methyl-5-phenyl-1,2-tellurazole 2-oxide assemble a variety of supramolecular aggregates that includes cyclic tetramers and hexamers, as well as a helical polymer. In all these aggregates, the building blocks are connected by Te(…)O–N bridges. Nuclear magnetic resonance spectroscopic experiments demonstrate that the two types of annular aggregates are persistent in solution. These self-assembled structures form coordination complexes with transition-metal ions, act as fullerene receptors and host small molecules in a crystal

Photosensitized oxidative addition to gold(i) enables alkynylative cyclization of o-alkylnylphenols with iodoalkynes

International audienceThe well-established oxidative addition-reductive elimination pathway is the most followed one in transition metal catalyzed cross coupling reactions. While readily occurring with a series of transition metals, it does not take place with gold(I) complexes which have shown some reluctance to undergo oxidative addition unless special sets of ligands on gold(I), reagents or reaction conditions are used. A new possibility to overcome this hurdle has been devised. Upon visible light irradiation, an iridium photocatalyst triggers via triplet sensitization the oxidative addition of an al-kynyliodide onto a vinylgold(I) intermediate to deliver Csp 2-Csp coupling products after reductive elimination. Mechanistic and modeling studies support that an energy transfer takes place and not a redox pathway. This novel mode of activation in gold homogenous catalysis was applied in several dual catalytic processes. Alkynylbenzofuran derivatives were obtained from o-alkynylphenols and iodoalkynes in the presence of catalytic gold(I) and iridium(III) complexes under blue LED irradiation. Over the last two decades, homogeneous gold catalysis has been extensively used to efficiently and selectively promote a variety of cyclization processes. 1-3 The typical casting involves bifunctional substrates bearing an unsaturation prompt to electrophilic activation and a judiciously positioned internal nucleophile. A protodemetalation of the organogold intermediates to afford hydrofunctional-ized products generally terminates the catalytic cycles. 4 Pursuing the step economy principle and also aiming at higher level of molecular complexity, some in situ post-functionalization reactions of the organogold 5 intermediate have been devised such as electrophilic halogenation or cross-coupling reactions. Although palladium catalyzed cross coupling from an organogold(I) intermediate has bee