Biomimetic Chemistry DOI: 10.1002/ange.201001172 Unprecedented Rate Enhancements of Hydrogen-Atom Transfer to a Manganese(V)–Oxo Corrolazine Complex** Katharine A. Prokop, Sam P. de Visser,* and David P. Goldberg* The reactivity of high-valent metal–oxo species is critical to the functioning of a large class of metalloenzymes. In heme enzymes, the identity of the proximal ligand is believed to have an important effect on the generation, stability, and substrate reactivity of these intermediates. For example, the proximal cysteinate ligand in cytochrome P450 (Cyt-P450) has been suggested to increase the oxidizing power of the enzyme toward hydrocarbon (C  H) substrates by enhancing the basicity (i.e. the affinity for H + ) of the [(porph + C)Fe IV (O)] intermediate, thereby increasing the driving force of hydro- gen-atom transfer (HAT). [1] Beyond Cyt-P450, it is of considerable interest to elucidate the factors that control metal–oxo HAT reactions because of the fundamental importance of this chemistry to both biological and synthetic processes. [2] Only recently has limited information become available on the kinetics of HAT reactions for either heme or nonheme iron/manganese–oxo complexes. [3–10] Even fewer of these studies have systematically determined the effects of ancillary ligands on the kinetics of HAT reactions. For example, the influence of axial ligands trans to the oxo group, which is of particular relevance to heme proteins, has only recently been described for discrete iron–oxo complexes. [5, 7, 8] No similar study has yet appeared for analogous manganese–oxo com- plexes. In earlier work, principles of ligand design were used to prepare a porphyrinoid ligand that stabilizes high-valent transition metals. [11, 12] This ligand, which contains a ring- contracted porphyrin nucleus and a 3  charge, provided rare access to a stable manganese(V)–oxo complex, [(TBP 8 Cz)Mn V (O)] (1; TBP 8 Cz = octakis(p-tert-butylphe- nyl)corrolazinato 3 ). [13] Herein, we take advantage of the stability of 1 to determine the influence of axial donors on the kinetics of HAT for a discrete Mn V (O) species. The addition of anionic axial ligands (X  ) to this manganese(V)–oxo complex leads to unprecedented rate enhancements in HAT reactions. Computational studies (density functional theory, DFT) were performed that successfully reproduce the experimental findings, thus providing a comprehensive the- oretical framework in which these unprecedented influences on reactivity can be understood. In a previous study it was shown that mixing 1 with excess 9,10-dihydroanthracene (DHA) at room temperature led to the isosbestic conversion of 1 into 2 (see Scheme 1). [14] The data for this reaction, together with similar reactions involv- ing substituted phenols, were consistent with the mechanism shown in Scheme 1. Complex 1 abstracts a hydrogen atom from the substrate in the rate-determining step, thus leading to a postulated Mn IV (OH) intermediate which is not observed, but is then consumed in a second, fast HAT step to give [(TBP 8 Cz)Mn III ](2). Repetition of the reaction between 1 and DHA in CH 2 Cl 2 at 25 8C in the presence of Bu 4 N + F  ·x H 2 O (TBAF; 1.5 equiv), led to the intriguing result that the reaction was complete in about 1 hour, as compared to the 20 hours needed in the absence of TBAF. The appearance of a UV/Vis spectrum consistent with a fluoride-ligated Mn III complex [2-F] [15] was observed together with the decay of the Mn V (O) species (Figure 1a). No significant UV/Vis change is seen for 1 with Scheme 1. Proposed mechanism of hydrogen-atom abstraction. [*] K. A. Prokop, Prof. D. P. Goldberg Department of Chemistry, Johns Hopkins University Baltimore, MD (USA) Fax: (+ 1) 410-516-8420 E-mail: dpg@jhu.edu Dr. S. P. de Visser Manchester Interdisciplinary Biocentre School of Chemical Engineering and Analytical Science University of Manchester, Manchester (UK) E-mail: sam.devisser@manchester.ac.uk [**] Funding was provided by the NSF (CHE0909587) (D.P.G.) and the Cleio Greer Fellowship (K.A.P.). Financial support for the purchase of the Bruker AutoFlex III MALDI-ToF mass spectrometer was provided by the NSF (CHE-0840463). The National Service of Computational Chemistry Software (NSCCS) is thanked for pro- viding CPU time for the calculations. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201001172. Angewandte Chemie 5217 Angew. Chem. 2010, 122, 5217 –5221  2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim