In this feature article, we discuss selected recent aspects of metal boryl (M-BR2) chemistry pertaining, in particular, to the role of late and post-transition metal boryl complexes in various catalytic processes. The exceptionally strong sigma-donor properties of boryl ligands and their related nucleophilic behaviour are highlighted.

A simple but effective copper-catalyzed borylation of aryl halides, including electron-rich and sterically hindered aryl bromides, with alkoxy diboron reagents occurs under mild conditions (see scheme). Preliminary DFT studies of the mechanism suggest that sigma-bond metathesis between a copper-boryl intermediate and the aryl halide generates the aryl boronate product.

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.

SummaryGut microbiota can influence the aging process and may modulate aging‐related changes in cognitive function. Trimethylamine‐N‐oxide (TMAO), a metabolite of intestinal flora, has been shown to be closely associated with cardiovascular disease and other diseases. However, the relationship between TMAO and aging, especially brain aging, has not been fully elucidated. To explore the relationship between TMAO and brain aging, we analysed the plasma levels of TMAO in both humans and mice and administered exogenous TMAO to 24‐week‐old senescence‐accelerated prone mouse strain 8 (SAMP8) and age‐matched senescence‐accelerated mouse resistant 1 (SAMR1) mice for 16 weeks. We found that the plasma levels of TMAO increased in both the elderly and the aged mice. Compared with SAMR1‐control mice, SAMP8‐control mice exhibited a brain aging phenotype characterized by more senescent cells in the hippocampal CA3 region and cognitive dysfunction. Surprisingly, TMAO treatment increased the number of senescent cells, which were primarily neurons, and enhanced the mitochondrial impairments and superoxide production. Moreover, we observed that TMAO treatment increased synaptic damage and reduced the expression levels of synaptic plasticity‐related proteins by inhibiting the mTOR signalling pathway, which induces and aggravates aging‐related cognitive dysfunction in SAMR1 and SAMP8 mice, respectively. Our findings suggested that TMAO could induce brain aging and age‐related cognitive dysfunction in SAMR1 mice and aggravate the cerebral aging process of SAMP8 mice, which might provide new insight into the effects of intestinal microbiota on the brain aging process and help to delay senescence by regulating intestinal flora metabolites.

The detailed mechanisms for the borylation of R,β-unsaturated carbonyl compounds, acrolein and methylacrylate, catalyzed by phosphine copper(I) boryl complexes were studied with the aid of density functional theory calculations. The results show that the catalyzed borylation occurs through CdC insertion into Cu-B to give a β-borylalkyl C-bound Cu(I) enolate intermediate. In the borylation of acrolein, the C-bound Cu(I) enolate undergoes a keto-to-enol isomerization to give an O-bound enolate intermediate followed by a σ-bond metathesis with a diboron reagent. In the borylation of methylacrylate, a keto-toenol isomerization does not occur due to the inertness of the ester group. Alcoholysis or hydrolysis is necessary to convert the C-bound Cu(I) enolate intermediate efficiently to the borylation product and Cu(I) alkoxide that can easily undergo σ-bond metathesis with a diboron reagent. The different borylation reaction mechanisms of acrolein and methylacrylate are closely related to the relative thermodynamic and kinetic stability of the C-and O-enolate intermediates involved in the reactions of the two different classes of substrates. The insertion reactions of ethene, formaldehyde, acrolein (2-propenal, CH 2 dCHsCHO), and methylacrylate (CH 2 dCHsCO 2 Me) into a Cu-B bond were compared. It was found that the insertion barriers correlate very well with the orbital energies of the LUMOs calculated for the four substrates, supporting the notion that the insertion mainly involves a nucleophilic attack of the Cu-B σ bond at the coordinated unsaturated substrate molecule. Although formaldehyde is more active than ethene in the insertion reaction, the reactivity of the CdC bond is greater than that of the CdO bond in R,β-unsaturated aldehyde and ester. In addition, the thermodynamics and kinetics of interconversions between O-and C-bound enolates of Cu, B, and Si have been investigated.

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DFT calculations have been carried out to study the insertion reactions of alkenes into the Cu-B bond in (NHC)Cu(boryl) complexes (NHC ) N-heterocyclic carbene). The nature of the insertion reactions and the relevant regiochemistry have been examined along with β-hydride eliminations, which are followed by reinsertion of the alkene into the Cu-H bond. Hyperconjugation (i.e., π bonding) between the Cu-C σ bond and the "empty" p z orbital on boron has been identified as the cause of the unexpectedly small Cu-C-B angle found experimentally by X-ray diffraction in R-borylalkyl Cu(I) complexes.