Patricia Liebhäuser

Efficient Biomimetic Hydroxylation Catalysis with a Bis(pyrazolyl)imidazolylmethane Copper Peroxide Complex.

Bis(pyrazolyl)methane ligands are excellent components of model complexes used to investigate the activity of the enzyme tyrosinase. Combining the N donors 3-tert-butylpyrazole and 1-methylimidazole results in a ligand that is capable of stabilising a (μ-η(2) :η(2) )-dicopper(II) core that resembles the active centre of tyrosinase. UV/Vis spectroscopy shows blueshifted UV bands in comparison to other known peroxo complexes, due to donor competition from different ligand substituents. This effect was investigated with the help of theoretical calculations, including DFT and natural transition orbital analysis. The peroxo complex acts as a catalyst capable of hydroxylating a variety of phenols by using oxygen. Catalytic conversion with the non-biological phenolic substrate 8-hydroxyquinoline resulted in remarkable turnover numbers. In stoichiometric reactions, substrate-binding kinetics was observed and the intrinsic hydroxylation constant, kox , was determined for five phenolates. It was found to be the fastest hydroxylation model system determined so far, reaching almost biological activity. Furthermore, Hammett analysis proved the electrophilic character of the reaction. This sheds light on the subtle role of donor strength and its influence on hydroxylation activity.

Decay kinetics of sensitive bioinorganic species in a SuperFocus mixer at ambient conditions

We performed studies on the oxygenation of a copper(I) complex targeting the intrinsic kinetics of this reaction in a continuous flow setup. It is an example reaction for the metal-based activation of dioxygen. For these experiments we used a SuperFocus mixer, a customised micro mixer with fast mixing behaviour. By means of this setup, we were able for the first time to detect the formation and decay of a thermally very sensitive bis(μ-oxo)dicopper species at ambient temperature. Comparing these data to results from a stopped-flow setup we could confirm the performance of the SuperFocus mixer setup. The rate constant for the decay of the bis(μ-oxo)dicopper species was determined to be 0.90 s−1 using the SuperFocus mixer and to be 1.57 s−1 by stopped-flow at slightly different temperatures.

Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster Hydroxylation Catalysis

Tyrosinase model systems pinpoint pathways to translating Natures synthetic abilities for useful synthetic catalysts. Mostly, they use N-donor ligands which mimic the histidine residues coordinating the two copper centres. Copper complexes with bis(pyrazolyl)methanes with pyridinyl or imidazolyl moieties are already reported as excellent tyrosinase models. Substitution of the pyridinyl donor results in the new ligand HC(3-tBuPz)2 (4-CO2 MePy) which stabilises a room-temperature stable μ-η2 :η2 -peroxide dicopper(II) species upon oxygenation. It reveals highly efficient catalytic activity as it hydroxylates 8-hydroxyquinoline in high yields (TONs of up to 20) and much faster than all other model systems (max. conversion within 7.5 min). Stoichiometric reactions with para-substituted sodium phenolates show saturation kinetics which are nearly linear for electron-rich substrates. The resulting Hammett correlation proves the electrophilic aromatic substitution mechanism. Furthermore, density functional theory (DFT) calculations elucidate the influence of the substituent at the pyridinyl donor: the carboxymethyl group adjusts the basicity and nucleophilicity without additional steric demand. This substitution opens up new pathways in reactivity tuning.

On the Way to a Trisanionic {Cu3O2} Core for Oxidase Catalysis: Evidence of an Asymmetric Trinuclear Precursor Stabilized by Perfluoropinacolate Ligands

CuI complexes of the form K[(R3 P)Cu(pinF )], in which (pinF )2- is the bidentate, oxygen-donating ligand perfluoropinacolate, were synthesized and characterized. Low-temperature oxygenation of the K[(R3 P)Cu(pinF )(PR3 )] species resulted in a trisanionic bis(μ3 -oxo) trinuclear copper(II,II,III) core characterized by UV/Vis spectroscopy (λmax [nm] = 330, 535, 630), cryospray-ionization mass spectrometry, and X-band electron paramagnetic resonance spectroscopy (derivative resonance at 3300 G, Δms =2 at 1500 G). The kinetic behavior of the trimeric {Cu3 O2 } species was quantified by stopped-flow spectroscopy and the associated electronic structures were investigated by DFT calculations. An asymmetric {Cu3 O2 } species, As TpinF , which bears a structure similar to multicopper oxidases, forms prior to full formation of the symmetric trinuclear core, Sy TpinF . The trimer catalytically oxidizes para-hydroquinone to benzoquinone (a form of oxidase chemistry).

Designed To React: Terminal Copper Nitrenes and Their Application in Catalytic C−H Aminations

Heteroscorpionate ligands of the bis(pyrazolyl)methane family have been applied in the stabilisation of terminal copper tosyl nitrenes. These species are highly active intermediates in the copper-catalysed direct C-H amination and nitrene transfer. Novel perfluoroalkyl-pyrazolyl- and pyridinyl-containing ligands were synthesized to coordinate to a reactive copper nitrene centre. Four distinct copper tosyl nitrenes were prepared at low temperatures by the reaction with SO2 tBuPhINTs and copper(I) acetonitrile complexes. Their stoichiometric reactivity has been elucidated regarding the imination of phosphines and the aziridination of styrenes. The formation and thermal decay of the copper nitrenes were investigated by UV/Vis spectroscopy of the highly coloured species. Additionally, the compounds were studied by cryo-UHR-ESI mass spectrometry and DFT calculations. In addition, a mild catalytic procedure has been developed where the copper nitrene precursors enable the C-H amination of cyclohexane and toluene and the aziridination of styrenes.