About

Mike Green is a Professor at the Department of Chemistry at the University of California, Irvine. His research focus is not explicitly detailed on the provided page, but he is listed among the faculty members, indicating his role in teaching and research within the department. As a faculty member, he contributes to the academic and scientific community through his expertise and leadership in chemistry. Further specific details about his research interests, background, or key contributions are not available in the provided text.

Research topics

• Organic chemistry
• Chemistry
• Computational chemistry
• Photochemistry
• Stereochemistry
• Thermodynamics
• Crystallography
• Inorganic chemistry

Selected publications

• Computational Design of a Highly Stable Dicopper Catechol Oxidase

  Journal of the American Chemical Society · 2026-02-18 · 1 citations

  article

  Type 3 (T3) Cu proteins play essential roles in binding and activating molecular oxygen (O2) and are prevalent across all domains of life. Despite sharing the same coordination motif, T3 Cu proteins display divergent functions: hemocyanin transports O2, while tyrosinase catalyzes the hydroxylation of monophenols and the subsequent oxidation of diphenols and catechol oxidase oxidizes only diphenols. Here, we report the design and characterization of a di-Cu protein (Cu-HC4) inspired by the active sites of natural T3 Cu proteins to investigate the structural features that facilitate catalytic oxidase activity. Cu-HC4 is roughly 1/5th the size of the commercially available mushroom tyrosinase and shares only around 20% sequence identity with the T3 Cu protein templates. Notably, Cu-HC4 displays high thermostability and exhibits diphenol oxidation activity at ambient and elevated temperatures (≥60 °C). Cu-HC4 also initiates the formation of melanin polymers, mimicking melanin biosynthesis of natural tyrosinases. Mechanistic investigations demonstrate that Cu-HC4 utilizes both Cu centers cooperatively for diphenol oxidation and requires O2 for catalysis like natural Cu oxidases but follows a distinct catalytic pathway compared to those enzymes. Cryo-EM characterization of a tetrameric form of HC4 reveals slight deviations in the relative positions of the active site His residues that may account for differences in reactivity between Cu-HC4 and natural T3 Cu enzymes.

  PublisherDOI

• Importance of the Ferryl Quintet State in Determining the Electronic Properties of P450 Compound I

  Journal of the American Chemical Society · 2025-03-04 · 2 citations

  articleSenior authorCorresponding

  We previously reported a selenolate-ligated P450 compound I intermediate (SeP450-I) to be more reactive toward C–H bonds than its thiolate-ligated counterpart. To gain insight into how the selenolate axial ligand influences the reactivity of compound I, we have investigated the electronic structure of the SeP450-I intermediate using variable temperature Mössbauer (VTM) spectroscopy. The VTM data indicate that electronic spin relaxation rates are significantly slower in SeP450-I than in P450-I. Analyses of these data provide Δ, the energy spacing between the two lowest electronic energy levels in compound I. This spacing is typically determined by the zero-field splitting of the ferryl moiety, D, and the exchange coupling, J, between the iron(IV)oxo unit and the ligand-based radical. However, the systems examined are antiferromagnetically coupled with |J/D| > 1. As a result, Δ ∼ (3/2) J, and measurements of Δ provide J (to within ∼5%). These measurements reveal that the sign and magnitude of J track with the reactivity of compound I toward C–H bonds. Efforts to analyze these and other data highlight the inadequacy of the standard ligand field model that is often used to explain the electronic properties of compound I. Additional analyses combining our data with state energies from a previous theoretical investigation support predictions of a low-lying quintet state within the iron(IV)oxo unit. We discuss these findings in light of computational studies that suggest that access to excited states, particularly those of a high-spin nature, can promote metal-oxo mediated C–H bond cleavage.

  PublisherDOI

• <i>In Crystallo</i> O ₂ Cleavage at a Preorganized Triiron Cluster

  Journal of the American Chemical Society · 2024-12-24 · 5 citations

  articleOpen access

  In Nature, the four-electron reduction of O2 is catalyzed at preorganized multimetallic active sites. These complex active sites often feature low-coordinate, redox-active metal centers precisely positioned to facilitate rapid O2 activation processes that obviate the generation of toxic, partially reduced oxygen species. Very few biomimetic constructs simultaneously recapitulate the complexity and reactivity of these biological cofactors. Herein, we report solid-state O2 activation at a triiron(II) active site templated by phosphinimide ligands. Insight into the structure of the O2 reduction intermediates was obtained via in crystallo O2 dosing experiments in conjunction with spectroscopic, structural, magnetic, and computational studies. These data support the in situ formation of an Fe2IIIFeIV-dioxo intermediate upon exposure to O2 that participates in oxygen atom and hydrogen atom transfer reactivity with exogenous substrates to furnish a stable FeIIFe2III-oxo species. Combined, these studies provide an extraordinary level of detail into the dynamics of bond-forming and -breaking processes operative at complex multimetallic active sites.

  PublisherOA PDFDOI

• In Crystallo O2 Cleavage at a Preorganized Triiron Cluster

  ChemRxiv · 2024-09-27

  preprint

  In Nature, the four-electron reduction of O2 is catalyzed at preorganized multimetallic active sites. These complex active sites often feature low-coordinate, redox-active metal centers precisely positioned to facilitate rapid O2 activation processes that obviate the generation of toxic, partially-reduced oxygen species. Very few biomimetic constructs simultaneously recapitu-late the complexity and reactivity of these biological cofactors. Herein, we report solid-state O2 activation at a triiron(II) active site templated by phosphinimide ligands. Insight into the structure of the O2 reduction intermediates was obtained via in crystallo O2 dosing experiments in conjunction with spectroscopic, structural, magnetic, and computational studies. These data support the in situ formation of an Fe2IIIFeIV-dioxo intermediate upon O2 exposure that participates in oxygen atom and hydrogen atom transfer reactivity with exogenous substrates to furnish a stable FeIIFe2III-oxo species. Combined, these stud-ies provide an extraordinary level of detail into the dynamics of bond forming and breaking processes operative at complex multimetallic active sites.

  PublisherDOI

• ¹⁷O Electron Nuclear Double Resonance Analysis of Compound I: Inverse Correlation between Oxygen Spin Population and Electron Donation

  Journal of the American Chemical Society · 2022-10-14 · 14 citations

  articleSenior authorCorresponding

  Although the activation of inert C–H bonds by metal-oxo complexes has been widely studied, important questions remain, particularly regarding the role of oxygen spin population (i.e., unpaired electrons on the oxo ligand) in facilitating C–H bond cleavage. In order to shed light on this issue, we have utilized 17O electron nuclear double resonance spectroscopy to measure the oxygen spin populations of three compound I intermediates in heme enzymes with different reactivities toward C–H bonds: chloroperoxidase, cytochrome P450, and a selenolate (selenocysteinyl)-ligated cytochrome P450. The experimental data suggest an inverse correlation between oxygen spin population and electron donation from the axial ligand. We have explored the implications of this result using a Hückel-type molecular orbital model and constrained density functional theory calculations. These investigations have allowed us to examine the relationship between oxygen spin population, oxygen charge, electron donation from the axial ligand, and reactivity.

  PublisherDOI

• Role of Serine Coordination in the Structural and Functional Protection of the Nitrogenase P-Cluster

  Journal of the American Chemical Society · 2022-11-29 · 8 citations

  articleOpen access

  Nitrogenase catalyzes the multielectron reduction of dinitrogen to ammonia. Electron transfer in the catalytic protein (MoFeP) proceeds through a unique [8Fe-7S] cluster (P-cluster) to the active site (FeMoco). In the reduced, all-ferrous (PN) state, the P-cluster is coordinated by six cysteine residues. Upon two-electron oxidation to the P2+ state, the P-cluster undergoes conformational changes in which a highly conserved oxygen-based residue (a Ser or a Tyr) and a backbone amide additionally ligate the cluster. Previous studies of Azotobacter vinelandii (Av) MoFeP revealed that when the oxygen-based residue, βSer188, was mutated to a noncoordinating residue, Ala, the P-cluster became redox-labile and reversibly lost two of its eight Fe centers. Surprisingly, the Av strain with a MoFeP variant that lacked the serine ligand (Av βSer188Ala MoFeP) displayed the same diazotrophic growth and in vitro enzyme turnover rates as wild-type Av MoFeP, calling into question the necessity of this conserved ligand for nitrogenase function. Based on these observations, we hypothesized that βSer188 plays a role in protecting the P-cluster under nonideal conditions. Here, we investigated the protective role of βSer188 both in vivo and in vitro by characterizing the ability of Av βSer188Ala cells to grow under suboptimal conditions (high oxidative stress or Fe limitation) and by determining the tendency of βSer188Ala MoFeP to be mismetallated in vitro. Our results demonstrate that βSer188 (1) increases Av cell survival upon exposure to oxidative stress in the form of hydrogen peroxide, (2) is necessary for efficient Av diazotrophic growth under Fe-limiting conditions, and (3) may protect the P-cluster from metal exchange in vitro. Taken together, our findings suggest a structural adaptation of nitrogenase to protect the P-cluster via Ser ligation, which is a previously unidentified functional role of the Ser residue in redox proteins and adds to the expanding functional roles of non-Cys ligands to FeS clusters.

  PublisherOA PDFDOI

• CCDC 2082983: Experimental Crystal Structure Determination

  The Cambridge Structural Database · 2021-09-16

  datasetOpen access
  PublisherDOI

• Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis

  Chemistry - A European Journal · 2021-08-23 · 13 citations

  articleOpen access

  Diazophosphonates, readily prepared from α-ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3-dipolar cycloaddition reactions to alkynes to give N-H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties into the diazo 1,3-dipole. The electron-withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]-sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product. Overall, the diazophosphonate acts as a surrogate for the much less stable diazoalkane in cycloadditions, with the phosphoryl group playing a vital, but traceless, role. The cycloaddition proceeds more readily with alkynes bearing electron-withdrawing groups, and is regiospecific with asymmetrical alkynes. The potential of diazophosphonates for use in bioorthogonal cycloadditions is demonstrated by their facile addition to strained alkynes.

  PublisherOA PDFDOI

• Semiempirical method for examining asynchronicity in metal–oxido-mediated C–H bond activation

  Proceedings of the National Academy of Sciences · 2021 · 61 citations

  • Chemistry
  • Stereochemistry
  • Photochemistry

  in their second-order rate constants that tracked with the acidity of the C-H bonds. Mechanisms that included either synchronous PCET or rate-limiting PT, followed by ET, did not explain our results, which led to a proposed PCET mechanism with asynchronous transition states that are dominated by PT. To support this premise, we report a semiempirical free energy analysis that can predict the relative contributions of PT and ET for a given set of substrates. These findings underscore why the basicity of M-oxido units needs to be considered in C-H functionalization.

  PublisherOA PDFDOI

• NRVS investigation of ascorbate peroxidase compound II: Observation of Iron(IV)oxo stretching

  Journal of Inorganic Biochemistry · 2021-07-24 · 3 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM055365

  NIH · $3.7M · 2013

• Thermodynamic, Electronic, Structural, and Kinetic Characterizations of Cytochrome P450 Compounds I & II

  NIH · $3.0M · 2012–2029

• CAREER: Experimental and Theoretical Studies of Thiolate-Heme Enzymes

  NSF · $728k · 2004–2010

Frequent coauthors

• Rachel K. Behan

  Pennsylvania State University

  25 shared

• Courtney M. Krest

  22 shared

• David P. Goldberg

  18 shared

• Pierre Moënne‐Loccoz

  Oregon Health & Science University

  16 shared

• F. Namuswe

  14 shared

• G.D. Kasper

  14 shared

• Carsten Krebs

  Pennsylvania State University

  14 shared

• A. S. Borovik

  14 shared