Synthesis, Characterization, and Spectroscopic Studies of 2,6-Dimethylpyridyl-Linked Cu(I)-CNC Complexes: The Electronic Influence of Aryl Wingtips on Copper Centers.

Six new Cu(I) complexes containing pincer ligands of the type 2,6-bis(3-alkyl/arylimidazol-2-ylidene) methylpyridine I(R/R'Ar) CN̂C, where R = trifluoroethyl (TFE) and R' = 4-CF3, 4-NO2, 4-CN, 4-H, and 4-CH3, have been synthesized. These complexes, namely, [Cu(I(TFE)CN̂C)]PF6, 1-TFE; [Cu(ICF3Ar CN̂C]PF6, 2-CF3; [Cu(INO2Ar CN̂C)]PF6, 3-NO2; [Cu(ICNAr CN̂C]PF6, 4-CN; [Cu(IHAr CN̂C)]2(PF6)2, 5-H; and [Cu(ICH3Ar CN̂C)]2(PF6)2, 6-CH3, were fully characterized by 1H, 13C, and HMBC NMR spectroscopy, elemental analysis, electrochemical studies, and single-crystal X-ray crystallography. The crystallographic data revealed different structures and copper nuclearities for the complexes bearing aryl wingtips with electron-withdrawing (2-CF3, 3-NO2, and 4-CN) and electron-donating (5-H and 6-CH3) substituents. The solution-phase conductivity measurements in acetonitrile revealed a mix-electrolyte behavior for these complexes, supporting the presence of both mono- and binuclear forms of each complex. The fast monomer-dimer equilibrium of the Cu-CNC complexes at room temperature is reflected in their simple 1H NMR spectra in acetonitrile. However, both mono- and binuclear forms were identifiable in 1H diffusion-ordered spectroscopy (DOSY) at low temperatures. The dynamic behavior of these complexes in solution was further examined by variable-temperature 1H NMR (VT 1H NMR) experiments, and the relevant thermodynamic parameters were determined. The process was also probed by one-dimensional rotating-frame Overhauser enhancement spectroscopy (1D ROESY) experiments to elucidate the coexisting species in solution. The 2,6-dimethylpyridyl-linked Cu-CNC complexes also presented a quasi-reversible Cu(II)/Cu(I) couple in cyclic voltammetry studies, wherein a clear influence of the aryl wingtips on the E1/2 values was observed. Furthermore, the percent buried volumes (% Vbur) of the complexes were calculated, showing a similar steric hindrance around copper in all complexes. These findings support the importance of electronic effects, induced by the aryl wingtips, on the preferred coordination geometry, copper nuclearity, and redox properties of the Cu-CNC complexes.

pH Changes That Induce an Axial Ligand Effect on Nonheme Iron(IV) Oxo Complexes with an Appended Aminopropyl Functionality.

Nonheme iron enzymes often utilize a high-valent iron(IV) oxo species for the biosynthesis of natural products, but their high reactivity often precludes structural and functional studies of these complexes. In this work, a combined experimental and computational study is presented on a biomimetic nonheme iron(IV) oxo complex bearing an aminopyridine macrocyclic ligand and its reactivity toward olefin epoxidation upon changes in the identity and coordination ability of the axial ligand. Herein, we show a dramatic effect of the pH on the oxygen-atom-transfer (OAT) reaction with substrates. In particular, these changes have occurred because of protonation of the axial-bound pendant amine group, where its coordination to iron is replaced by a solvent molecule or anionic ligand. This axial ligand effect influences the catalysis, and we observe enhanced cyclooctene epoxidation yields and turnover numbers in the presence of the unbound protonated pendant amine group. Density functional theory studies were performed to support the experiments and highlight that replacement of the pendant amine with a neutral or anionic ligand dramatically lowers the rate-determining barriers of cyclooctene epoxidation. The computational work further establishes that the change in OAT is due to electrostatic interactions of the pendant amine cation that favorably affect the barrier heights.

Computational studies of DNA base repair mechanisms by nonheme iron dioxygenases: selective epoxidation and hydroxylation pathways.

DNA base repair mechanisms of alkylated DNA bases is an important reaction in chemical biology and particularly in the human body. It is typically catalyzed by an α-ketoglutarate-dependent nonheme iron dioxygenase named the AlkB repair enzyme. In this work we report a detailed computational study into the structure and reactivity of AlkB repair enzymes with alkylated DNA bases. In particular, we investigate the aliphatic hydroxylation and C[double bond, length as m-dash]C epoxidation mechanisms of alkylated DNA bases by a high-valent iron(iv)-oxo intermediate. Our computational studies use quantum mechanics/molecular mechanics methods on full enzymatic structures as well as cluster models on active site systems. The work shows that the iron(iv)-oxo species is rapidly formed after dioxygen binding to an iron(ii) center and passes a bicyclic ring structure as intermediate. Subsequent cluster models explore the mechanism of substrate hydroxylation and epoxidation of alkylated DNA bases. The work shows low energy barriers for substrate activation and consequently energetically feasible pathways are predicted. Overall, the work shows that a high-valent iron(iv)-oxo species can efficiently dealkylate alkylated DNA bases and return them into their original form.

C-X (X = N, O) Cross-Coupling Reactions Catalyzed by Copper-Pincer Bis(N-Heterocyclic Carbene) Complexes.

Over the last two decades, N-heterocyclic carbene (NHC)-copper catalysts have received considerable attention in organic synthesis. Despite the popularity of copper complexes containing monodentate NHC ligands and recent development of poly(NHC) platforms, their application in C-C and C-heteroatom cross-coupling reactions has been limited. Recently, we reported an air-assisted Sonogashira-type cross-coupling catalyzed by well-defined cationic copper-pincer bis(NHC) complexes. Herein, we report the application of these complexes in Ullmann-type C-X (X = N, O) coupling of azoles and phenols with aryl halides in a relatively short reaction time. In contrast to other well-defined copper(I) catalysts that require an inert atmosphere for an efficient C-X coupling, the employed Cu(I)-pincer bis(NHC) complexes provide good to excellent yields in air. The air-assisted reactivity, unlike that in the Sonogashira reaction, is also affected by the base employed and the reaction time. With Cs2CO3 and K2CO3, the oxygen-generated catalyst is more reactive than the catalyst formed under argon in a short reaction time (12 h). However, the difference in reactivity is compromised after a 24 h reaction with K2CO3. The efficient pincer Cu-NHC/O2/Cs2CO3 system provides great to excellent cross-coupling yields for electronically diverse aryl iodides and imidazole derivatives. The catalyst scope is controlled by a balance between nucleophilicity, coordinating ability, and the steric hindrance of aryl halides and N-/O-nucleophiles.