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Nickel catalysis has garnered interest in mainstream organic synthesis for constructing chemical bonds and has been merged with photoredox catalysis and electrocatalysis. Despite its success and increasing adoption by academia and industry, the mechanism by which Ni catalyzes C−C cross-coupling reactions and how the precatalyst is activated remains unclear. An exploration of stabilized dimethylNi II complexes, [(dtbbpy)Ni-(Me) 2 ] (dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine, 1) and [(bpy)-Ni(Me) 2 ] (bpy = 2,2′-bipyridine, 2), as Ni-precatalysts for promoting C sp 2 −C sp 3 cross-coupling revealed that they readily undergo photo-induced Ni−C bond homolysis upon exposure to visible light and are a source of Ni 0 species. Photo-initiation of dimethylNi II complexes 1 and 2 produced active Ni 0 and reactive methyl radicals, which were harnessed to promote methylative and other C sp 2 −C sp 3 cross-coupling reactions.The mechanistic studies conducted to illuminate aspects of the process include a competition reaction, Ni II ArBr-complex synthesis, light-on and lightoff studies, density functional theory (DFT) calculations of the bond dissociation free energies (BDFE), as well as control experiments with a Ni 0 -precursor. We further demonstrated the robustness and utility of dimethylNi II as a Ni 0 -precursor in the latestage installation of methyl, CD 3 , alkyl, and benzyl groups on aryl bromides that have potential value in drug design and optimization. This work sheds light on the activation mechanism of Ni-catalyzed cross-coupling of aryl halides with organozinc reagents when a Ni II -precatalyst is employed and the critical role that visible light plays in the process.

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Limbal stem cell deficiency causes conjunctivalization characterized by the covering of the corneal surface with conjunctival epithelium. However, the driving force for the encroachment of these conjunctival cells is unclear. Conjunctival stem cells are bipotent stem cells that can proliferate and differentiate into conjunctival epithelial cells and goblet cells to maintain regeneration of the conjunctival epithelium. Here, we show a robust proliferative response of conjunctival stem cells and upregulation of Wnt2b and Wnt3a gene expression in the conjunctivae of mice with induced limbal stem cell deficiency. Topical application of the Wnt/β-catenin signaling activator CHIR resulted in increased proliferation of ΔNp63α-positive stem cells in the basal layers of the bulbar and forniceal conjunctivae and enhanced invasion of conjunctival epithelial and goblet cells into the corneal surface. We also found that in cultures of stem cells isolated from the human conjunctiva, Wnt/β-catenin pathway activation improved the expansion of the ΔNp63α/ABCG2 double-positive cell population by promoting the proliferation and preventing the differentiation of these cells. These expanded stem cells formed a stratified epithelium containing goblet cells under airlift culture conditions. Our data reveal that Wnt/β-catenin signaling contributes to the pathological process of limbal stem cell deficiency by promoting the self-renewal of conjunctival stem cells and suggest that these cells are a driving force in corneal conjunctivalization.