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Research in the Stack group focuses on the mechanism of dioxygen activation and the subsequent oxidative reactivity with primarily copper complexes ligated by imidazoles or histamines. Specifically, the group is interested in substrate hydroxylations and full dioxygen reduction. The remarkable specificity and energy efficiency of metalloenzymes provide the inspiration for the work. Trapping and characterizing immediate species, primarily at low temperatures, provide key mechanistic insights especially through substrate reactivity along with spectroscopic and metrical correlation to DFT calculations. Our objective is to move these efficient enzymatic mechanisms into small synthetic complexes, not only to reproduce biological reactivity, but more importantly to move the oxidative mechanism beyond that possible in the protein matrix.

Daniel Stack was born, raised and attended college in Portland Oregon. He received his B.A. from Reed College in 1982 (Phi Beta Kappa), working with Professor Tom Dunne on weak nickel-pyrazine complexes. In Boston, he pursued his doctoral study in synthetic inorganic chemistry at Harvard University (Ph.D., 1988) with Professor R. H. Holm, investigating site-differentiated synthetic analogues of biological Fe4S4 cubanes. As an NSF Postdoctoral Fellow with Professor K. N. Raymond at the University of California at Berkeley, he worked on synthesizing new, higher iron affinity ligands similar to enterobactin, a bacterial iron sequestering agent. He started his independent career in 1991 at Stanford University primarily working on oxidation catalysis and dioxygen activation, and was promoted to an Associate Professor in 1998. His contributions to undergraduate education have been recognized at the University level on several occasions, including the Dinkelspiel Award for Outstanding Contribution to Undergraduate Education in 2003.

Areas of current focus include:

Copper Dioxygen Chemistry
Our current interests focus on stabilizing species formed in the reaction of dioxygen with Cu(I) complexes formed with biologically relevant imidazole or histamine ligation. Many multi-copper enzymes ligated in this manner are capable of impressive hydroxylation reactions, including oxidative depolymerization of cellulose, methane oxidation, and energy-efficient reduction of dioxygen to water. Oxygenation of such complexes at extreme solution temperatures (-125°C) yield transient Cu(III) containing complexes. As Cu(III) is currently uncharacterized in any biological enzyme, developing connections between the synthetic and biological realms is a major focus.

Surface Immobilization of Catalysts in Mesoporous Materials
In redox active biological metal sites, the ligation environment is coupled tightly to the functional chemistry. Yet, the metal sites are also site-isolated, creating species that may only have a transient existence in a homogeneous solution. Site isolation of synthetic complexes can be achieved synthetically by supporting the metal complex on a solid matrix. Movement of these complexes into silica based materials or onto electroactive carbon electrodes represent a new direction for the group in the development of bio-inspired metal-based catalysts.

Academic Appointments

Honors & Awards

  • Dinkelspiel Award for Outstanding Contribution to Undergraduate Education, Stanford University (2003)
  • Hoefer Teaching Award, Stanford University (1997)
  • Bing Foundation Teaching Award, Stanford University (1995-98)
  • Shell Foundation New Faculty Award, Shell Foundation (1993-95)
  • Harvard Danforth Distinguished Teaching Award, Harvard University (1983, 1984)

Professional Education

  • NSF Postdoctoral Fellow, University of California at Berkeley, Inorganic Chemistry (1988)
  • PhD, Harvard University, Inorganic Chemistry (1988)
  • BA, Reed College, Chemistry (1982)

Contact

Additional Info

  • Mail Code: 5080

Links

2023-24 Courses

Stanford Advisees

All Publications

  • Simplest Monodentate Imidazole Stabilization of the oxy-Tyrosinase Cu2 O2 Core: Phenolate Hydroxylation through a Cu(III) Intermediate. Angewandte Chemie (International ed. in English) Chiang, L., Keown, W., Citek, C., Wasinger, E. C., Stack, T. D. 2016; 55 (35): 10453-10457

    Abstract

    Tyrosinases are ubiquitous binuclear copper enzymes that oxygenate to Cu(II) 2 O2 cores bonded by three histidine Nτ-imidazoles per Cu center. Synthetic monodentate imidazole-bonded Cu(II) 2 O2 species self-assemble in a near quantitative manner at -125 °C, but Nπ-ligation has been required. Herein, we disclose the syntheses and reactivity of three Nτ-imidazole bonded Cu(II) 2 O2 species at solution temperatures of -145 °C, which was achieved using a eutectic mixture of THF and 2-MeTHF. The addition of anionic phenolates affords a Cu(III) 2 O2 species, where the bonded phenolates hydroxylate to catecholates in high yields. Similar Cu(III) 2 O2 intermediates are not observed using Nπ-bonded Cu(II) 2 O2 species, hinting that Nτ-imidazole ligation, conserved in all characterized Ty, has functional advantage beyond active-site flexibility. Substrate accessibility to the oxygenated Cu2 O2 core and stabilization of a high oxidation state of the copper centers are suggested from these minimalistic models.

    View details for DOI 10.1002/anie.201605159

    View details for PubMedID 27440390

  • Direct Copper(III) Formation from O2 and Copper(I) with Histamine Ligation. Journal of the American Chemical Society Gary, J. B., Citek, C., Brown, T. A., Zare, R. N., Wasinger, E. C., Stack, T. D. 2016; 138 (31): 9986-9995

    Abstract

    Histamine chelation of copper(I) by a terminal histidine residue in copper hydroxylating enzymes activates dioxygen to form unknown oxidants, generally assumed as copper(II) species. The direct formation of copper(III)-containing products from the oxygenation of histamine-ligated copper(I) complexes is demonstrated here, indicating that copper(III) is a viable oxidation state in such products from both kinetic and thermodynamic perspectives. At low temperatures, both trinuclear Cu(II)2Cu(III)O2 and dinuclear Cu(III)2O2 predominate, with the distribution dependent on the histamine ligand structure and oxygenation conditions. Kinetics studies suggest the bifurcation point to these two products is an unobserved peroxide-level dimer intermediate. The hydrogen atom reactivity difference between the trinuclear and binuclear complexes at parity of histamine ligand is striking. This behavior is best attributed to the accessibility of the bridging oxide ligands to exogenous substrates rather than a difference in oxidizing abilities of the clusters.

    View details for DOI 10.1021/jacs.6b05538

    View details for PubMedID 27467215

  • Manganese(II)/Picolinic Acid Catalyst System for Epoxidation of Olefins ORGANIC LETTERS Moretti, R. A., Du Bois, J., Stack, T. D. 2016; 18 (11): 2528-2531

    Abstract

    An in situ generated catalyst system based on Mn(CF3SO3)2, picolinic acid, and peracetic acid converts an extensive scope of olefins to their epoxides at 0 °C in <5 min, with remarkable oxidant efficiency and no evidence of radical behavior. Competition experiments indicate an electrophilic active oxidant, proposed to be a high-valent Mn = O species. Ligand exploration suggests a general ligand sphere motif contributes to effective oxidation. The method is underscored by its simplicity and use of inexpensive reagents to quickly access high value-added products.

    View details for DOI 10.1021/acs.orglett.6b00518

    View details for Web of Science ID 000377319000003

    View details for PubMedID 27191036

  • Metal complex assembly controlled by surface ligand distribution on mesoporous silica: Quantification using refractive index matching and impact on catalysis JOURNAL OF CATALYSIS Smith, B. J., Gallegos, P. A., Butsch, K., Stack, T. D. 2016; 335: 197-203

    View details for DOI 10.1016/j.jcat.2015.11.008

    View details for Web of Science ID 000371098200019

  • Catalytic Phenol Hydroxylation with Dioxygen: Extension of the Tyrosinase Mechanism beyond the Protein Matrix ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Hoffmann, A., Citek, C., Binder, S., Goos, A., Ruebhausen, M., Troeppner, O., Ivanovic-Burmazovic, I., Wasinger, E. C., Stack, T. D., Herres-Pawlis, S. 2013; 52 (20): 5398-5401

    View details for DOI 10.1002/anie.201301249

    View details for Web of Science ID 000318370200039

    View details for PubMedID 23609983

  • Self-assembly of the oxy-tyrosinase core and the fundamental components of phenolic hydroxylation NATURE CHEMISTRY Citek, C., Lyons, C. T., Wasinger, E. C., Stack, T. D. 2012; 4 (4): 317-322

    Abstract

    The enzyme tyrosinase contains two Cu(I) centres, trigonally coordinated by imidazole nitrogens of six conserved histidine residues. The enzyme activates O(2) to form a µ-η(2):η(2)-peroxo-dicopper(II) core, which hydroxylates tyrosine to a catechol in the first committed step of melanin biosynthesis. Here, we report a family of synthetic peroxo complexes, with spectroscopic and chemical features consistent with those of oxygenated tyrosinase, formed through the self-assembly of monodentate imidazole ligands, Cu(I) and O(2) at -125 °C. An extensively studied complex reproduces the enzymatic electrophilic oxidation of exogenous phenolic substrates to catechols in good stoichiometric yields. The self-assembly and subsequent reactivity support the intrinsic stability of the Cu(2)O(2) core with imidazole ligation, in the absence of a polypeptide framework, and the innate capacity to effect hydroxylation of phenolic substrates. These observations suggest that a foundational role of the protein matrix is to facilitate expression of properties native to the core by bearing the entropic costs of assembly and precluding undesired oxidative degradation pathways.

    View details for DOI 10.1038/nchem.1284

    View details for Web of Science ID 000301983400019

    View details for PubMedID 22437718

  • Tyrosinase reactivity in a model complex: An alternative hydroxylation mechanism SCIENCE Mirica, L. M., Vance, M., Rudd, D. J., Hedman, B., Hodgson, K. O., Solomon, E. I., Stack, T. D. 2005; 308 (5730): 1890-1892

    Abstract

    The binuclear copper enzyme tyrosinase activates O2 to form a mu-eta2:eta2-peroxodicopper(II) complex, which oxidizes phenols to catechols. Here, a synthetic mu-eta2:eta2-peroxodicopper(II) complex, with an absorption spectrum similar to that of the enzymatic active oxidant, is reported to rapidly hydroxylate phenolates at -80 degrees C. Upon phenolate addition at extreme temperature in solution (-120 degrees C), a reactive intermediate consistent with a bis-mu-oxodicopper(III)-phenolate complex, with the O-O bond fully cleaved, is observed experimentally. The subsequent hydroxylation step has the hallmarks of an electrophilic aromatic substitution mechanism, similar to tyrosinase. Overall, the evidence for sequential O-O bond cleavage and C-O bond formation in this synthetic complex suggests an alternative intimate mechanism to the concerted or late stage O-O bond scission generally accepted for the phenol hydroxylation reaction performed by tyrosinase.

    View details for DOI 10.1126/science.1112081

    View details for Web of Science ID 000230120000034

    View details for PubMedID 15976297

  • Structure and spectroscopy of copper-dioxygen complexes CHEMICAL REVIEWS Mirica, L. M., Ottenwaelder, X., Stack, T. D. 2004; 104 (2): 1013-1045

    View details for DOI 10.1021/cr020632z

    View details for Web of Science ID 000188934400022

    View details for PubMedID 14871148

  • Efficient epoxidation of electron-deficient olefins with a cationic manganese complex JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Murphy, A., Dubois, G., Stack, T. D. 2003; 125 (18): 5250-5251

    Abstract

    The complex [MnII(R,R-mcp)(CF3SO3)2] is an efficient and practical catalyst for the epoxidation of electron-deficient olefins. This catalyst is capable of epoxidizing olefins with as little as 0.1 mol % catalyst in under 5 min using 1.2 equiv of peracetic acid as the terminal oxidant. A wide scope of substrates are epoxidized including terminal, tertiary, cis and trans internal, enones, and methacrylates with >85% isolated yields.

    View details for DOI 10.1021/ja0299962r

    View details for Web of Science ID 000182682700002

    View details for PubMedID 12720417

  • C-H bond activation by a ferric methoxide complex: Modeling the rate-determining step in the mechanism of lipoxygenase JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Goldsmith, C. R., Jonas, R. T., Stack, T. D. 2002; 124 (1): 83-96

    Abstract

    Lipoxygenases are mononuclear non-heme iron enzymes that regio- and stereospecifcally convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active ferric hydroxide species to give a ferrous water species and an organic radical. Reported here are the synthesis and characterization of a ferric model complex, [Fe(III)(PY5)(OMe)](OTf)(2), that reacts with organic substrates in a manner similar to the proposed enzymatic mechanism. The ligand PY5 (2,6-bis(bis(2-pyridyl)methoxymethane)pyridine) was developed to simulate the histidine-dominated coordination sphere of mammalian lipoxygenases. The overall monoanionic coordination provided by the endogenous ligands of lipoxygenase confers a strong Lewis acidic character to the active ferric site with an accordingly positive reduction potential. Incorporation of ferrous iron into PY5 and subsequent oxidation yields a stable ferric methoxide species that structurally and chemically resembles the proposed enzymatic ferric hydroxide species. Reactivity with a number of hydrocarbons possessing weak C-H bonds, including a derivative of the enzymatic substrate linoleic acid, scales best with the substrates' bond dissociation energies, rather than pK(a)'s, suggesting a hydrogen atom abstraction mechanism. Thermodynamic analysis of [Fe(III)(PY5)(OMe)](OTf)(2) and the ferrous end-product [Fe(II)(PY5)(MeOH)](OTf)(2) estimates the strength of the O-H bond in the metal bound methanol in the latter to be 83.5 +/- 2.0 kcal mol(-1). The attenuation of this bond relative to free methanol is largely due to the high reduction potential of the ferric site, suggesting that the analogously high reduction potential of the ferric site in LO is what allows the enzyme to perform its unique oxidation chemistry. Comparison of [Fe(III)(PY5)(OMe)](OTf)(2) to other coordination complexes capable of hydrogen atom abstraction shows that, although a strong correlation exists between the thermodynamic driving force of reaction and the rate of reaction, other factors appear to further modulate the reactivity.

    View details for DOI 10.1021/ja016451g

    View details for Web of Science ID 000173217900022

    View details for PubMedID 11772065

  • Aryl C-H activation by Cu-II to form an organometallic Aryl-Cu-III species: A novel twist on copper disproportionation ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Ribas, X., JACKSON, D. A., Donnadieu, B., Mahia, J., Parella, T., Xifra, R., Hedman, B., Hodgson, K. O., Llobet, A., Stack, T. D. 2002; 41 (16): 2991-2994

    View details for Web of Science ID 000177597700023

    View details for PubMedID 12203435

  • Stereospecificity and self-selectivity in the generation of a chiral molecular tetrahedron by metal-assisted self-assembly ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Enemark, E. J., Stack, T. D. 1998; 37 (7): 932-935

    View details for Web of Science ID 000073339000013

  • Catalytic galactose oxidase models: Biomimetic Cu(II)-phenoxyl-radical reactivity SCIENCE Wang, Y. D., Dubois, J. L., Hedman, B., Hodgson, K. O., Stack, T. D. 1998; 279 (5350): 537-540

    Abstract

    Biomimetic functional models of the mononuclear copper enzyme galactose oxidase are presented that catalytically oxidize benzylic and allylic alcohols to aldehydes with O2 under mild conditions. The mechanistic fidelity between the models and the natural system is pronounced. Modest structural mimicry proves sufficient to transfer an unusual ligand-based radical mechanism, previously unprecedented outside the protein matrix, to a simple chemical system.

    View details for Web of Science ID 000071616000038

    View details for PubMedID 9438841

  • Irreversible reduction of dioxygen by simple peralkylated diamine-copper(I) complexes: Characterization and thermal stability of a [Cu-2(mu-O)(2)](2+) core JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Mahadevan, V., Hou, Z. G., Cole, A. P., Root, D. E., Lal, T. K., SOLOMON, E. I., Stack, T. D. 1997; 119 (49): 11996-11997

    View details for Web of Science ID A1997YK70800036

  • C-H bond activation by a ferric methoxide complex: A model for the rate-determining step in the mechanism of lipoxygenase JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Jonas, R. T., Stack, T. D. 1997; 119 (36): 8566-8567

    View details for Web of Science ID A1997XV70000022

  • Trinuclear intermediate in the copper-mediated reduction of O-2: Four electrons from three coppers SCIENCE Cole, A. P., Root, D. E., Mukherjee, P., SOLOMON, E. I., Stack, T. D. 1996; 273 (5283): 1848-1850

    Abstract

    The reaction of metal complexes with dioxygen (O2) generally proceeds in 1:1, 21, or 41 (metal:O2) stoichiometry. A discrete, structurally characterized 31 product is presented. This mixed-valence trinuclear copper cluster, which contains copper in the highly oxidized trivalent oxidation state, exhibits O2 bond scission and intriguing structural, spectroscopic, and redox properties. The relevance of this synthetic complex to the reduction of O2 at the trinuclear active sites of multicopper oxidases is discussed.

    View details for Web of Science ID A1996VJ71300041

    View details for PubMedID 8791587