In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC₅₀ (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC₅₀ (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots’ crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.     

Titanium‐Catalyzed Hydroalumination of Conjugated Dienes: Access to Fulvene‐Derived Allylaluminium Reagents and Their Diastereoselective Reactions with Carbonyl Compounds

The described titanium‐catalyzed hydroalumination of conjugated dienes opens up a new way to allylaluminium reagents. The reaction is carried out by using diisobutylaluminium hydride (DIBAL‐H) and a catalytic amount of [Cp₂TiCl₂] (Cp=cyclopentadienyl). When applied to mono‐ and disubstitued pentafulvenes, this reaction proceeds in a highly endocyclic manner. The formed allylaluminium compounds react regio‐ and stereoselectively with both aldehydes and ketones to afford homoallylic alcohols that are suitable synthons for functionalized cyclopentanones. An extension of this methodology to simple dienes was also investigated. In the proposed mechanism, the initially formed bimetallic species (Ti/Al) are involved in the two possible catalytic cycles with a direct hydroalumination or/and a hydrotitanation followed by a titanium to aluminium transmetallation.     

Versatile post-functionalisation strategy for the formation of modular organic–inorganic polyoxometalate hybrids

Hybrid structures incorporating different organic and inorganic constituents are emerging as a very promising class of materials since they synergistically combine the complementary and diverse properties of the individual components. Hybrid materials based on polyoxometalate clusters (POMs) are particularly interesting due to their versatile catalytic, redox, electronic, and magnetic properties, yet the controlled incorporation of different clusters into a hybrid structure is challenging and has been scarcely reported. Herein we propose a novel and general strategy for combining multiple types of metal-oxo clusters in a single hybrid molecule. Two novel hybrid POM structures (HPOMs) bis-functionalised with dipentaerythritol (R–POM₁–R; R = (OCH₂)₃CCH₂OCH₂C(CH₂OH)) were synthesised as building-blocks for the formation of heterometallic hybrid triads (POM₂–R–POM₁–R–POM₂). Such a modular approach resulted in the formation of four novel heterometallic hybrids combing the Lindqvist {V₆}, Anderson–Evans {XMo₆} (X = Cr or Al) and trisubstituted Wells–Dawson {P₂V₃W₁₅} POM structures. Their formation was confirmed by multinuclear Nuclear Magnetic Resonance (NMR), infrared (IR) and UV-Vis spectroscopy, as well as Mass Spectrometry, Diffusion Ordered Spectroscopy (DOSY) and elemental analysis. The thermal stability of the hybrids was also examined by Thermogravimetric Analysis (TGA), which showed that the HPOM triads exhibit higher thermal stability than comparable hybrid structures containing only one type of POM. The one-pot synthesis of these novel compounds was achieved in high yields in aqueous and organic media under simple reflux conditions, without the need of any additives, and could be translated to create other hybrid materials based on a variety of metal-oxo cluster building-blocks.

A versatile modular approach has been developed for incorporating different metal-oxo nanoclusters with characteristic structures into a single hybrid molecule by covalently linking them with polyol ligands.     

Cooperativity as quantification and optimization paradigm for nuclear receptor modulators

Nuclear Receptors (NRs) are highly relevant drug targets, for which small molecule modulation goes beyond a simple ligand/receptor interaction. NR–ligands modulate Protein–Protein Interactions (PPIs) with coregulator proteins. Here we bring forward a cooperativity mechanism for small molecule modulation of NR PPIs, using the Peroxisome Proliferator Activated Receptor γ (PPARγ), which describes NR–ligands as allosteric molecular glues. The cooperativity framework uses a thermodynamic model based on three-body binding events, to dissect and quantify reciprocal effects of NR–coregulator binding (K^I_D) and NR–ligand binding (K^II_D), jointly recapitulated in the cooperativity factor (α) for each specific ternary ligand·NR·coregulator complex formation. These fundamental thermodynamic parameters allow for a conceptually new way of thinking about structure–activity-relationships for NR–ligands and can steer NR modulator discovery and optimization via a completely novel approach.

A cooperativity framework describes the formation of nuclear receptor ternary complexes and deconvolutes ligand and cofactor binding into intrinsic affinities and a cooperativity factor, providing a conceptually new understanding of NR modulation.     

Perfect state transfer on weighted graphs of the Johnson scheme

Letters in Mathematical Physics - We characterize quantum perfect state transfer on real-weighted graphs of the Johnson scheme $${\mathcal {J}}(n,k)$$ , which represent spin networks with...     

Dual-fibre stretcher and coma as tools for independent 2nd and 3rd order tunable dispersion compensation in a fibre-based ‘scan-free’ time domain optical coherence tomography system

Dispersion compensation up to the third order is experimentally demonstrated by using a dual-fibre stretcher combined with the coma of an imaging lens, in a fibre-based scan-free time domain optical coherence tomography system, leading to an axial resolution of less than 3 μm.     

A Facile Synthesis of Trifluoroacetaldehyde by Electroreduction Of Cf3Br In Dimethylformamide

Trifluoroacetaldehyde, isolated as CF₃CH(OCOCH₃)₂, is obtained in high yield by electroreduction of CF₃Br in DMF, using an undivided cell and a sacrificial aluminium anode.     

Cucurbituril‐mediated immobilization of fluorescent proteins on supramolecular biomaterials

The reversible introduction of functionality at material surfaces is of interest for the development of functional biomaterials. In particular, the use of supramolecular immobilization strategies facilitates mild reaction and processing conditions, as compared to other covalent analogues. Here, the engineering of multicomponent supramolecular materials, beyond the use of a single supramolecular entity is proposed. Cucurbit[8]uril (Q8) mediated host–guest chemistry is combined with hydrogen bonding supramolecular 2‐ureido‐4‐pyrimidinone (UPy)‐based materials. The modular incorporation of a UPy‐additive that presents one guest to incorporate into the Q8 host allows for selective supramolecular functionalization at the water–polymer material interface. Supramolecular ternary complex formation at the material surface was studied by X‐ray photoelectron spectroscopy, which as a result of large overlap in atomic composition of the different components showed minor changes is surface composition upon complex formation. Surface MALDI‐ToF MS measurements revealed useful insights in the formation of complexes. Protein immobilization was monitored using both fluorescence spectroscopy and quartz crystal microbalance with dissipation monitoring, which successfully demonstrated ternary complex formation. Although proteins could selectively be immobilized onto the surfaces, control of the system's stability remains a challenge as a result of the dynamicity of the host–guest assembly. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3607–3616