Research in Bioinorganic & Bio-inspired Chemistry
Oxidation-reduction reactions, in which electrons (and, in some cases, atoms) are transferred between two or more molecules, are central to biological and industrial processes. While biological systems often catalyze these processes with nontoxic, abundant transition metals, such as iron, copper, and manganese, many industrial processes employ toxic and/or expensive metals. One of the major goals of my research is to understand how Nature uses transition metals to perform oxidation-reduction reactions and apply this knowledge to design new, environmentally-friendly transition metal catalysts. To address this goal, my group uses spectroscopic and computational techniques to determine the relationship between electronic structure (distribution of electrons) and reactivity for transition metal compounds involved in these reactions.
Manganese is employed by a variety of enzymes to catalyze reactions both vital to life and of fundamental interest. These enzymes include manganese superoxide dismutase, which detoxifies free radicals in humans, and photosystem II, which splits water to protons, electrons, and dioxygen in plants. The reactions of a variety of manganese-dependent enzymes are shown in the scheme below.
In spite of their diverse functions, most manganese enzymes employ a common set of intermediates. For example manganese(III)-hydroxo adducts have been proposed as intermediates in the enzymes manganese superoxide dismutase and manganese lipoxygenase. Manganese-oxo species have been invoked as intermediates in manganese ribonucleotide reductase and photosystem II. Manganese-oxo intermediates are also of interest for their presumed role in synthetic oxidation catalysts. Both manganese(III)-hydroxo and manganese-oxo species function primarily in proton-coupled electron transfer (PCET) reactions with substrates. In these reactions, a proton and electron are transferred from substrate to the Mn-OH or Mn=O unit. Mechanistic studies typically imply these PCET reactions to occur by concerted proton-electron transfer (CPET), where the proton and electron transfer in the same kinetic step.
One of the central aims of our research is to determine how we can manipulate the coordination environment of a metal center to control reactivity. To achieve this aim, we synthesized a variety of metal complexes where we have systematically perturbed the microenvironment of the metal. We then use kinetic, spectroscopic, and computational methods to correlate changes in reactivity to particular perturbations in geometric and electronic structure.
The enzyme Mn lipoxygenase eschews high-valent manganese intermediates and utilizes a mid-valent MnIII-hydroxo species to abstract a hydrogen atom from a weak C-H bond. Although this intriguing chemistry has been known for some time, models of Mn lipoxygenase capable of C-H bond oxidation are fairly rare. In an effort to better understand this chemistry, my lab has investigated the physical properties and reactivity of MnIII-hydroxo complexes supported by an amide-containing pentadentate ligand, dpaq, and its derivatives. The [MnIII(OH)(dpaq)]+ complex (see below) is capable of oxidizing substrates with C-H and O-H bonds with bond dissociation energies less than ca. 78 kcal/mol.
Top: Reaction between [MnIII(OH)(dpaq)]+ and TEMPOH. Bottom left: Electronic absorption spectra of a solution of 1.25 mM [MnIII(OH)(dpaq)]+
before (red) and after (blue) the addition of 60 eq. TEMPOH. The inset shows the decay of the feature at 770 nm as a function of time.
Bottom right: Plot of observed rate constants as a function of TEMPOH concentration at −35 °C.
(Image from Mayfield, Grotemeyer, and Jackson, Chem. Commun., 2020, 56, 9238-9255.)
We have been able to enhance the reactivity of the MnIII-hydroxo unit by modulating the properties of the dpaq ligand. By appending functional groups para to the amide donor, we can control the MnIII/II reduction potential and the rate of reaction with TEMPOH (shown as log(k2) below). This work reveals that electron-deficient MnIII centers display faster CPET reactions. Current work is aimed at incorporating additional design elements to further tune the reactivity MnIII-hydroxo adducts.
Left: Schematic structure of [MnIII(OH)(dpaq5R)]+ complexes with substituents para to the amide nitrogen.
Right: Dependence of the reaction rate for TEMPOH oxidation by the [MnIII(OH)(dpaq5R)]+ complexes as a function of
the MnIII/II cathodic peak potential, Ep,c, (top), and the MnIII/II peak potentials as a function of the σ parameter (bottom).
(Image from Mayfield, Grotemeyer, and Jackson, Chem. Commun., 2020, 56, 9238-9255.)
Manganese(IV)-oxo centers are proposed to effect CPET and oxygenation reactions in the catalytic cycles of biological and synthetic manganese systems. Although there are now quite a few examples of synthetic manganese(IV)-oxo centers that are reactive towards C-H bonds, there is still debate regarding why some MnIV-oxo species are capable of attacking strong C-H bonds while others react quite sluggishly with weak C-H bonds. The Jackson lab uses systematic ligand modifications to better understand ligand contributions to reactivity in MnIV-oxo complexes. Our lab also develops correlations between experimental parameters obtained from Mn X-ray measurements (i.e., X-ray absorption) and EPR spectroscopy to specific geometric and electronic properties. Such spectro-structural correlations can prove useful in understanding the properties of transient intermediates formed in enzymes or synthetic catalytic systems.
One of the major challenges in comparing the reactivity of MnIV-oxo complexes has been the diverse supporting ligand scaffolds and various experimental conditions (i.e., solvent and temperature) employed. To understand the influence of ligand perturbations on reactivity, we generated a series of MnIV-oxo complexes based on perturbations of the N4py ligand (see below).
Molecular structures of MnIV-oxo complexes with systematically perturbed equatorial ligand fields.
The Jackson lab and the lab of Prof. W. Nam (Ewha Womans University, South Korea) had independently reported the [MnIV(O)(N4py)]2+ complex in 2013, with the work from our lab focusing on detailed spectroscopic and kinetic analysis. For example, the enhanced reactivity of [MnIV(O)(N4py)]2+ was attributed to a low-lying 4E excited state that offers a low-energy pathway for CPET reactions. We experimentally identified this 4E excited state using magnetic circular dichroism spectroscopy. We have since employed multireference CASSCF calculations to learn more about bonding in this excited state. These computations support the involvement of the 4E state in CPET reactions.
To complement our spectroscopic and computational studies, we are generating new MnIV-oxo complexes using N4py derivatives. These studies allow us to correlate particular changes in the ligand field to modifications in chemical reactivity. For example, this work established that equatorial ligand perturbations can have a dramatic influence on the rates of CPET and oxygen-atom transfer reactions. These studies have been enabled by a collaboration with Prof. E. Nordlander (Lund University, Sweden), who has supplied our lab with some of the N4py derivatives.
