The hybrid bidentate 1‐(2‐pyridyl)benzotriazole (pyb) ligand was introduced into 3d transition metal catalysis. Specifically, [CuII(OTf)2(pyb)2]⋅2 CH3CN (1) enables the synthesis of a wide range of propargylamines by the A3 coupling reaction at room temperature in the absence of additives. Experimental and high‐level theoretical calculations suggest that the bridging N atom of the ligand imposes exclusive trans coordination at Cu and allows ligand rotation, while the N atom of the pyridine group modulates charge distribution and flux, and thus orchestrates structural and electronic precatalyst control permitting alkyne binding with simultaneous activation of the C−H bond via a transient CuI species.

A dimeric Cu(II) complex [Cu(II) 2 L 2 (μ 2 -Cl)Cl] (1) built from an asymmetric tridentate ligand (2-(((2aminocyclohexyl)imino)methyl)-4,6-di-tert-butylphenol) and weakly coordinating anions has been synthesized and structurally characterized. In dichloromethane solution, 1 exists in a monomeric [Cu(II)LCl] (1′) (85%)−dimeric (1) (15%) equilibrium, and cyclic voltammetry (CV) and electron paramagnetic resonance (EPR) studies indicate structural stability and redox retention. Addition of phenylacetylene to the CH 2 Cl 2 solution populates 1′ and leads to the formation of a transient radical species. Theoretical studies support this notion and show that the radical initiates an alkyne C−H bond activation process via a fourmembered ring (Cu(II)−O•••H−C alkyne ) intermediate. This unusual C−H activation method is applicable for the efficient synthesis of propargylamines, without additives, within 16 h, at low loadings and in noncoordinating solvents including late-stage functionalization of important bioactive molecules. Single-crystal X-ray diffraction studies, postcatalysis, confirmed the framework's stability and showed that the metal center preserves its oxidation state. The scope and limitations of this unconventional protocol are discussed.

We disclose a synthetic route that providess an unprecedented library of C1 salan ligands endowed with (N-H) backbones, previously limited to N-methylated backbones. Efforts to identify a generic complexation protocol...

We report the rational design of a tunable Cu(II) chelating scaffold, 2-(((2-((pyridin-2-ylmethyl)amino)ethyl)amino)methyl)phenol, Salpyran. This tetradentate (3N,1O) ligand is predicated to have suitable permeation, has an extremely high affinity for Cu compared to clioquniol (pCu 7.4 = 10.65 vs 5.91), and exhibits excellent selectivity for Cu(II) over Zn(II) in aqueous media. Solid and solution studies corroborate the formation of a stable [Cu(II)(3N,1O)] + monocationic species at physiological pH values (7.4). Its action as an antioxidant was tested in ascorbate, tau, and human prion protein assays, which reveal that Salpyran prevents the formation of reactive oxygen species from the binary Cu(II)/ H 2 O 2 system, demonstrating its potential use as a therapeutic small molecule metal chelator. for example, Aβ has a picomolar affinity for Cu(II) binding via 49 histidine binding. 27,28 Cu(II) imbalances exist in AD affected 50 brains, and Cu(II) can be found either upregulated or 51 downregulated depending on the locality of the tissue. 6,29 52 Due to its redox potential when bound to Aβ, Cu(II) 53 contributes to the generation of reactive oxygen species 54 (ROS), leading to oxidative neuronal damage. 30−32 55 In the past decade, there has been an increasing interest in 56 designing Cu-specific small molecule metal chelators 57 (SMMCs) aiming to reduce Cu(II)-Aβ induced oxidative 58 stress and the resulting pathogenic consequen-59 ces. 6,15,[34][35][36][37][38][39][16][17][18][19][20][21][22]33 Chelation therapy aims to disrupt 60 potential toxic interactions of metal ions and biomolecules 61 by targeting specific metal ions and promoting redistribution 62 or excretion. When designing a Cu-specific SMMC, both the 63 thermodynamic properties of the metal chelate and the 64 pharmacological properties of the ligand must be considered. 65 The key criteria for Cu(II) targeting AD therapeutic are 66 denticity, metal/ligand stoichiometry, and the coordination 67 environment and geometry of the complex at physiological pH 68 values. Ideally, the given ligand would coordinate to Cu(II) in 69 a 1:1 stoichiometry, as ligands of this type exhibit a higher 70 copper affinity than similar 1:2 complexes due to the