1,3-C-H bond activation on a transient gallium(I)/isocyanate adduct.

Reaction of NacNacGa with phenylisocyante generates a transient species amenable to unusual 1,3-C-H bond addition of unactivated sp3 C-H and sp2 C-H bonds of substrates featuring a hard donor atom. This reaction proceeds for pyridine oxide, dimethylsulfoxide, and dimethylacetamide, but not for pyridine, cyclohexanone, and ethyl acetate. C-H activation was also not observed for reactions with triethylphosphine oxide but, interestingly, in the presence of this compound isocyanate undergoes self-coupling on Ga(I) with a regioselectivity that is different when carried out in the absence of Et3PO.

Facile C-H bond activation on a transient gallium imide.

Reaction of NacNacGa with azide N3SiMe3 results in the generation of a transient imide NacNacGa(NSiMe3) that can cleave unactivated sp3 C-H and sp2 C-H bonds of different substrates, affording gallium amides. Pyridine, cyclohexanone, ethyl acetate, DMSO, and triethylphosphine oxide were activated in this process producing corresponding gallium amides. All new compounds were characterised by multinuclear NMR and X-ray diffraction.

An Isolable Gallium-Substituted Nitrilimine and its Reactivity with B-H, Si-H and B-B Bonds.

Reaction of the Ga(I) compound NacNacGa (9) with the diazo compound N2 CHSiMe3 affords the nitrilimine compound NacNacGa(N-NCSiMe3 )(CH2 SiMe3 ) (10). Carrying out this reaction in the presence of pyridine does not lead to C-H activation on the transient alkylidene NacNacGa=CHSiMe3 but generates a metallated diazo species NacNacGa(NHN=CHSiMe3 )(CN2 SiMe3 ) (13) that further rearranges into the isonitrile compound NacNacGa(NHN=CHSiMe3 )(N(NC)SiMe3 ) (15). Reactions of 10 with the silane H3 SiPh and the borane HBcat furnished products of 1,3 addition to the nitrilimine moiety NacNacGa{N(ERn )NCSiMe3 }(CH2 SiMe3 ), whereas reaction with the diborane B2 cat2 gave the product of formal nitrene insertion into the B-B bond. DFT calculations suggest that the interaction of 9 with N2 CHSiMe3 proceeds through intermediate formation of an alkylidene compound that undergoes CH activation with a second molecule of N2 CHSiMe3 . Insertion into the B-B bond likely proceeds through an initial 1,3-addition of the diborane, followed by boryl migration to the former nitrene center.

Sequential Oxidation and C-H Bond Activation at a Gallium(I) Center.

In situ oxidation of the GaI compound NacNacGa by either N2 O or pyridine oxide results in the generation of a labile monomeric oxide, NacNacGa(O), which can easily cleave the C-H bonds of aliphatic and aromatic substrates featuring good donor sites. The products of this reaction are gallium organyl hydroxides. DFT calculations show that these reactions start with the formation of NacNac-Ga(O)(L) adducts, the oxo ligand of which can easily abstract protons from nearby C-H bonds, even for sp2 -hybridized carbon centers. Aliphatic amines do not enter this reaction for kinetic reasons, presumably because of the unfavorable sterics.

Interaction of Multiple Bonds with NacNacGa: Oxidative Cleavage vs Coupling and Cyclization.

The reactivity of the gallium(I) compound NacNacGa (4) to a variety of unsaturated compounds has been studied. Whereas 4 proved surprisingly unreactive toward olefins, ketones, guanidines, and thioureas, it reacts with isocyanates and carbodiimides to furnish the products of coupling of two heterocumulenes. With isothiocyanate, the C═S cleavage occurs, leading to the dimer (NacNacGa)2(µ-S)(µ-CNPh) and the cyclization product NacNacGa(S2C═NPh). These compounds were characterized by multinuclear NMR spectroscopy and X-ray crystal structure analyses. Oxidative addition of S═PPh3 occurs at elevated temperatures and results in the known dimer [NacNacGa(µ-S)]2.

Dysregulation of YAP by ARF Stimulated with Tea-derived Carbon Nanodots.

YAP is a downstream nuclear transcription factor of Hippo pathway which plays an essential role in development, cell growth, organ size and homeostasis. It was previously identified that elevation of YAP in genomics of genetic engineered mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF in prostate cancer. However, the detailed function and trafficking of YAP in cancer cells remains unclear. Using GEM microarray model, we found ARF dysregulates Hippo and Wnt pathways. In particular, ARF knockdown reduced non-nuclear localization of YAP which led to an increase in F-actin. Mechanistically, ARF knockdown suppressed protein turnover of ß-catenin/YAP, and therefore enhanced the activity of AKT and phosphorylation of YAP. Moreover, we found tea-derived carbon dots can interact with ARF in nucleus that may further lead to the non-nuclear localization of YAP. Thus, we reported a novel crosstalk of ARF/ß-catenin dysregulated YAP in Hippo pathway and a new approach to stimulate ARF-mediated signaling to inhibit nuclear YAP using nanomaterials implicating an innovative avenue for treatment of cancer.