| dc.description.abstract | Manganese-dependent enzymes that react with dioxygen and its reduced derivatives are ubiquitous in nature, catalyzing pivotal processes such as the light-driven oxidation of water to dioxygen, generation of peroxidized fatty acids, and detoxification of reactive oxygen species such as superoxide and peroxide. Peroxo-, hydroxo-, and oxo-manganese intermediates are often invoked in the mechanisms of a majority of these enzymes. However, detailed understanding of the mechanisms involving Mn-containing enzymes is lacking, warranting further investigations in this area of study. Due to numerous restrictions involved with carrying out such mechanistic studies using the actual proteins of interest, utilization of synthetic bio-inspired model complexes has been a frequent practice. To this end, a series of peroxomanganese(III) complexes with varied steric and electronic properties have been synthesized, and characterized by low-temperature electronic absorption and magnetic circular dichroism (MCD) spectroscopies, as well as complementary density functional theory (DFT) and time-dependent DFT computations. This work resulted in the first report where steric properties of the supporting ligand were shown to play a predominant role in modulating the Mn-peroxo interactions in η2-peroxomanganese(III) intermediates. This study provided intriguing insight into the significance of steric factors of enzymatic active sites in fine-tuning their reactivity properties. Since a majority of peroxomanganese(III) model complexes display impaired thermal stabilities under ambient conditions, designing ligands that minimize their decay pathways is of great interest. This has motivated the design, synthesis, and characterization of such an oxidatively robust supporting ligand, L7BQ (L7BQ = 1,4-di(quinolin-8-yl)-1,4-diazepane), and the characterization of its MnII complex by X-ray diffraction techniques. The corresponding peroxomanganese(III) adduct has been generated and spectroscopically characterized. This adduct exhibits interesting reaction patterns with strong acids and acyl chlorides. Activation of non-prophyrinoid peroxomanganese(III) complexes to generate high-valent oxidants is extremely rare, which makes the reactivity of this new MnIII-O2 adduct highly intriguing. Apart from biological significance, dioxygen activation by MnII centers is of great importance both in environmentally benign synthetic approaches, as well as alternative energy applications such as fuel cells. Several such MnII complexes have been synthesized, and characterized by X-ray diffraction and other techniques. Mechanistic understanding of MnII-mediated dioxygen activation is still in its infancy, although such systems have been successfully utilized in a number of O2-dependent oxidation reactions in generating synthetically desirable organic substrates. We have carried out mechanistic studies of dioxygen activation using electronic absorption, electronic paramagnetic resonance (EPR), and X-ray absorption spectroscopies, in conjugation with mass spectrometric and kinetic analysis. Based on the current evidence, a mechanistic proposal is presented, describing the O2 activation reactivity of these new MnII systems. Intriguingly, the O2 activation reactions of these new MnII complexes yield a single metal product in excellent yields (98%), which has been structurally-characterized as the corresponding MnIII-OH complex. Monomeric hydroxomanganese(III) complexes are relatively rare, and those that can mediate substrate oxidation reactions are even more scarce. In biology, hydroxomanganese(III) adducts are known to mediate crucial proton-coupled electron transfer (PCET) processes, especially during the peroxidation of fatty acids by non-heme Mn-containing enzyme lipoxygenase, and the water oxidation pathway of the oxygen evolving center in photosystem II. In light of these biological examples, we have carried out a thorough kinetic investigation of the PCET reactivity of the monomeric MnIII-OH complex, [MnIII(OH)(dpaq)](OTf), with a series of substituted phenols with variable bond dissociation free energies (BDFEs up to 79 kcal/mol in MeCN), and the weak OH bond substrate TEMPOH (BDFE = 66 kcal/mol in MeCN). [MnIII(OH)(dpaq)](OTf) is the first example of a MnIII-OH adduct that has exhibited saturation kinetics during its PCET reactivity. This kinetic profile implies the presence of an accumulating intermediate during the phenol oxidation reactions. Our data suggest that this intermediate is a H-bonded precursor complex that forms between the oxidant and the substrate prior to the rate-limiting transfer of the hydrogen atom. Stepwise electron and proton transfer processes have been discounted based on our Polanyi analysis of the kinetic data, as well as kinetic isotope studies, among other evidence. Interestingly, the related MnIII-OMe complex, [MnIII(OMe)(dpaq)](OTf), reacts with the same series of phenolic substrates, and does not exhibit the saturation kinetics displayed by the MnIII-OH species. [MnIII(OMe)(dpaq)](OTf) is the only example of a MnIII-OMe complex that mediates PCET with phenolic substrates. Both [MnIII(OH)(dpaq)](OTf) and [MnIII(OMe)(dpaq)](OTf) were found to oxidize TEMPOH to produce TEMPO and the corresponding MnII species as observed by electronic absorption and EPR spectroscopies. Eyring analysis of these reactions has provided insight into the activation parameters dictating these reactions. Furthermore, catalytic dioxygen reduction by [MnIII(OH)(dpaq)](OTf) was also demonstrated, which revealed a turnover number of 1050, with the presence of TEMPOH as the H-atom donor substrate. Extending similar reactivity to other substrates may provide significantly greener, inexpensive oxidation protocols for the dioxygen-dependent generation of desirable synthetic targets. | |
