Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Recent advances in C-H hydroxylation using Cu, H2O2 and directing groups   (121451)

Isaac Garcia-Bosch 1
  1. Carnegie Mellon University, Pittsburgh, PA, United States

Cu-dependent metalloenzymes catalyze a wide array of oxidative transformations using O2 under mild conditions (i.e. room temperature, atmospheric pressure).1 Lytic polysaccharide monooxygenases enzymes (LPMOs) promote the C-H hydroxylation and subsequent cleavage of the polysaccharide chains found in natural materials such as cellulose or chitin. Recent reports on the reactivity of LPMOs suggest that, instead of O2, these Cu-dependent metalloenzymes might utilize H2O2 as oxidant.2 In 2015, our research lab reported that the catalytic hydroxylation of strong C-H bonds (e.g. cyclohexane) using Cu and H2O2 proceeded via formation of non-selective Fenton-like oxidants (hydroxyl and hydroperoxyl radicals).3 To achieve regioselectivity, LPMOs bind the organic substrate before exposing the Cu center to the oxidant, a reaction that leads to the formation of highly organized ternary complex prior to substrate hydroxylation (i.e. metal-substrate-oxidant). In this talk, we will present our recent findings on the utilization of Cu, H2O2, and directing groups to promote regioselective C-H hydroxylation.4-7

  1. (1) Solomon, E. I.; Heppner, D. E.; Johnston, E. M.; Ginsbach, J. W.; Cirera, J.; Qayyum, M.; Kieber-Emmons, M. T.; Kjaergaard, C. H.; Hadt, R. G.; Tian, L. Copper Active Sites in Biology. Chem. Rev. 2014, 114 (7), 3659-3853.
  2. (2) Bissaro, B.; Røhr, Å. K.; Müller, G.; Chylenski, P.; Skaugen, M.; Forsberg, Z.; Horn, S. J.; Vaaje-Kolstad, G.; Eijsink, V. G. H. Oxidative cleavage of polysaccharides by monocopper enzymes depends on H2O2. Nature Chemical Biology 2017, 13, 1123.
  3. (3) Garcia-Bosch, I.; Siegler, M. A. Copper-Catalyzed Oxidation of Alkanes with H2O2 under a Fenton-like Regime. Angew. Chem., Int. Ed. 2016, 55 (41), 12873-12876