Vincent L. Pecoraro

A proposal for water oxidation in photosystem II

There has been much speculation concerning the mechanism for water oxidation by Photosystem 11. Based on recent work on the biophysics of Photosystem I1 and our own work on the reactivity of synthetic manganese complexes, we propose a chemically reasonable mechanistic model for the water oxidation function of this enzyme. An essential feature of the model is the nucleophilic attack by calcium-ligated hydroxide on an electrophilic 0x0 group ligated to high-valent manganese to achieve the critical 0-0 bond formation step. We also present a model for S-state advancement as a series of proton-coupled electron transfer steps, which has been proposed previously (Hoganson et. al., Photosynth. Res. 46, 177 (1995); Gilchrist et. al. Proc. Nat. Acad. Sci, USA. 92, 9545 (1995)), but for which we have developed model systems that allow us to probe the thermodynamics in some detail. One of the great unsolved mysteries in bioinorganic chemistry is the mechanism of water oxidation by the oxygen evolving complex (OEC) of Photosystem I1 (PS 11). This reaction is responsible for nearly all of the dioxygen on our planet and conceptually is the reverse reaction of respiration where dioxygen is converted back to water. Plants use an expansive airay of photopigments in Photosystem 11, four manganese ions, calcium and chloride to carry out these reactions. While intensively studied for many years, only now is a picture emerging as to how this fascinating and essential chemistry may result. The scope of this article is far too limited to allow for a detailed summary of previous studies in the field: therefore, interested readers are directed to recent reviews of this topic(ref. 1,2).

Protein Design: Toward Functional Metalloenzymes

1. Overview A 2. Protein Redesign B 2.1. Making Use of Native Proteins: Protein Redesign B 2.2. Protein Redesign Based on Functions C 2.2.1. Redesign of Zinc Finger Structural Sites C 2.2.2. Redesign of Zinc Hydrolytic Centers E 2.2.3. Redesign of Heme Centers J 2.2.4. Redesign of Nonheme Redox Centers M 2.2.5. Artificial Metalloenzymes for Regioand Enantioselective Catalysis AA 2.2.6. Redesigned Protein Assemblies as Nanoreactors AK 2.3. Summary AN 3. De Novo Design AN 3.1. A Minimalist Approach: Designing Proteins from Scratch AN 3.2. Interactions between De Novo Designed Peptides and Metal Ions AN 3.2.1. Heavy Metal Toxicity AO 3.2.2. De Novo Designed Metal Centers Based on β-Structures AT 3.2.3. Metal-Induced Protein Folding AV 3.3. De Novo Designed Functional Metalloproteins: The Grail Quest of Protein Design AX 3.3.1. De Novo Designed Hydrolytic Centers AX 3.3.2. De Novo Designed Electron Transfer Centers BB 3.3.3. Other Catalytic Centers BG 3.4. Summary BN 4. Perspective BO Author Information BO Corresponding Author BO Notes BO Biographies BO Abbreviations BR References BR

Hydrolytic catalysis and structural stabilization in a designed metalloprotein

Metal ions are an important part of many natural proteins, providing structural, catalytic and electron transfer functions. Reproducing these functions in a designed protein is the ultimate challenge to our understanding of them. Here, we present an artificial metallohydrolase, which has been shown by X-ray crystallography to contain two different metal ions – a Zn(II) ion which is important for catalytic activity and a Hg(II) ion which provides structural stability. This metallohydrolase displays catalytic activity that compares well with several characteristic reactions of natural enzymes. It catalyses p-nitrophenyl acetate hydrolysis (pNPA) to within ~100-fold of the efficiency of human carbonic anhydrase (CA)II and is at least 550-fold better than comparable synthetic complexes. Similarly, CO2 hydration occurs with an efficiency within ~500-fold of CAII. While histidine residues in the absence of Zn(II) exhibit pNPA hydrolysis, miniscule apopeptide activity is observed for CO2 hydration. The kinetic and structural analysis of this first de novo designed hydrolytic metalloenzyme uncovers necessary design features for future metalloenzymes containing one or more metals.

Paramagnetic spectroscopy of vanadyl complexes and its applications to biological systems

The ability to determine the ligand environment around vanadium(IV), usually as the vanadyl ion (VO 2 + ), has become crucial to the understanding of many biological systems. In addition to those systems in which vanadium naturally occurs, the vanadyl ion has found favor as a spectroscopic probe in place of spectroscopically silent cations, EPR, ESEEM, and ENDOR spectroscopies are the tools of choice for examining these paramagnetic systems. A variety of model complex studies allow good comparisons to be made to known vanadium environments. The complimentary nature of the strengths and weaknesses of these techniques can combine to give an accurate picture of the metal ligation in a number of cases herein.

The development of chiral metallacrowns into anion recognition agents and porous materials

Abstract Chiral metallacrowns can be prepared by the reaction of resolved amino hydroxamic acids with divalent metal ions. The 15-metallacrown-5 structure is achieved by the reaction of α-amino hydroxamic acids (e.g. l -alanine hydroxamic acid, l -phenylalanine hydroxamic acid and l -tyrosine hydroxamic acid) with Cu(II) and a Ln(III) ion. If a resolved ligand is used, the structure obtained contains all sidechain functional groups on the same face of the metallamacrocycle. The metallacrowns made with l -phenylalanine hydroxamic acid and l -tyrosine hydroxamic acid dimerize in the solid state, forming cavities that selectively recognize anions. If one uses resolved β-aminohydroxamic acids (which have fused 5 and 6 membered chelate rings), chiral 12-MC-4 complexes can be realized. The resultant structure with β-phenylalanine hydroxamic acid and Cu(II) is remarkably similar in size and shape to Cu(II) tetraphenylporphyrin. These chiral units can be linked via Cu(II) paddle wheel dimers and nitrate to form microporous layered solids. Because the of the modular synthesis strategy, grams of solid with defined chiral centers can be prepared in excellent yield.

Manganese Redox Enzymes and Model Systems: Properties, Structures, and Reactivity

Publisher Summary This chapter discusses properties, structures, and reactivity of manganese redox enzymes and model systems. Manganese is one of several first-row transition elements that are employed by biological systems to assist in varied metabolic and structural roles. Manganese is used to give structural support to proteins and is a cofactor in chemical transformations that include hydrolytic and redox reactions. Perhaps the best-known function, and the one of great importance to aerobic life, is in the oxygen-evolving complex, which oxidizes water to dioxygen during photosynthesis. The discussions of data gathering on enzyme systems and model chemistry, both structural and functional, presented in this chapter provides a foundation for exploring current and as yet undiscovered manganese enzymes. The biological applications of manganese are numerous and quite varied. The manganese-containing redox enzymes are unique. Most of these deal with dioxygen metabolism in one form or another.

Assembly of Near‐Infrared Luminescent Lanthanide Host(Host–Guest) Complexes With a Metallacrown Sandwich Motif

Optical devices and biomedical imaging probes increasingly utilize the long lifetimes and narrow linewidths of luminescent lanthanide (Ln) ions. Near-infrared (NIR) emitting Ln ions draw particular interest because of the transparency of biological tissue in this spectral range and applications in telecommunications. Ln ions are typically sensitized through ligand absorptions by the antenna effect because the low extinction coefficients of the Laporte-forbidden f–f transitions preclude direct excitation. The major hindrance in realizing efficient Ln ion luminescence in the NIR region is non-radiative quenching by high energy X H (X = C, N, O) vibrations in the ligand. Vibrational quenching has limited luminescence lifetimes to less than 6 ms in protic solvents. While careful ligand design can exclude N H and O H oscillators, C H bonds are difficult to eliminate from organic substrates without relying on synthetically cumbersome deuterated or fluorinated ligands. Herein we present a self-assembly approach to realizing long-lived Ln luminescence in the NIR region by utilizing the unique metallacrown (MC) topology to eliminate high energy X H oscillators from within 6.7 of the lanthanide ion. We report the synthesis, solution stability, and remarkable luminescence properties of a unique host(host–guest) complex in which a Ln[12-MC4]2 3+ sandwich complex is a guest encapsulated by a [24-MC8] host (Ln-1, Figure 1). MCs are inorganic analogues of crown ethers. Much of the interest in MCs has focused on the exceptional solid-state architectures, magnetic properties, and molecular recognition capabilities that arise from their metal-rich topologies. Ln MCs have been prepared that display singlemolecule magnetism and selectively encapsulate anions in monomeric cavitands or dimeric compartments. Chiral Ln[15-MC-5] complexes can serve as building blocks for mesoporous solids, resolved helices, and noncentrosymmetric solids that display second-harmonic generation. To date, Ln MCs have been prepared only with ring metals that contain partially filled d orbitals, which could provide a quenching pathway for luminescence. For this work, the Zn ion was judiciously chosen as the ring metal because its d electronic configuration precludes quenching through a d–d transition. To the best of our knowledge, no Ln MCs with Zn ring metals have been reported. Picoline hydroxamic acid (picHA) was selected as the ligand because it contains no N H or O H oscillators when bound in a Ln MC. The reaction between picHA, sodium hydroxide, zinc(II) triflate, and terbium(III) nitrate in methanol provided the complex formulated as Tb[12-MCZnII,N,picHA-4]2 [24MCZnII, N,picHA-8]·(pyridine)8·(triflate)3 (Tb-1, Figure 1) upon crystallization from the reaction solution with added pyridine. Single crystal X-ray crystallographic analysis shows two concave [12-MCZnII, N, picHA-4] units that sandwich an eightcoordinate Tb central metal. This sandwich complex (Figure 2A, B) is encapsulated in the cavity of a [24-MCZnII, N,picHA8] unit (Figure 2C). The Tb[12-MC-4]2 [24-MC-8] comFigure 1. X-ray crystal structure of Tb-1 shown a) perpendicular to the C4 axis, b) down the C4 axis, and c) highlighting the MC macrocycle. Color scheme: bronze= [12-MC-4], purple= [24-MC-8], green= Tb. Pyridine ligands are displayed as thin purple lines.

Recent advances in the understanding of the biological chemistry of manganese

Developments in manganese biochemistry have centered on the discovery of new manganese enzymes, X-ray analysis of binuclear manganese enzymes, and the discovery of new spectroscopic signatures for the oxygen-evolving complex. Despite these gains, many questions regarding the structure, composition and redox state of the oxygen-evolving complex remain unanswered.

Structural characterization of [VO(salicylhydroximate)(CH3OH)]3: Applications to the biological chemistry of vanadium(V)

The biological chemistry of vanadium has garnered increased attention due to the recent isolation of vanadium enzymes capable of nitrogenase [l] and bromoperoxidase [2,3] activities. The latter enzymes, isolated from marine algae, contain a mononuclear V(V) active site [4] that does not appear to require redox chemistry in the catalytic mechanism. It is well established that bacteria and algae often produce low molecular weight chelating agents (siderophores) which will sequester metal ions and facilitate the transport of these nutrients into the cell [5]. The two major classes of siderophores are based on catecholate and hydroxamate metal ligands [6]. Because vanadium bromoperoxidase is isolated from algae and bacteria, we felt that it would be interesting to examine the coordination chemistry of vanadium with hydroxamate ligands that might form the basis of vanadium sequestering agents for these organisms. In the process of our studies, we have isolated an intriguing trinuclear cluster composed of V03+ and salicylhydroxamic acid and report herein the structure and solution chemistry of this molecule. [VO(salicylhydroximate)(CHsOH)] a (1) can be prepared in 70% yield by the room temperature reaction of one equivalent of VO(acetylacetonate)z or VCla with salicylhydroxamic acid and three equivalents of NaOCHs or NaOH in methanol. Air acts as the oxidant to form deep blue solutions of 1. Slow evaporation of a methanol solution gave deep blue blocks which were suitable for X-ray crystallographic analysis. Crystallographic data for 1: monoclinic, space group P2Jc, a = 11.006(3), b = 15.722(7), c = 2 1.240(6) A; fi = 111.40(2)‘; v = 3422(2) A3, Z = 4; l(Mo Kor) =0.7107 A; crystal dimensions 0.42 X 0.49 X 0.52 mm3; p = 8.19 cm-l. The intensities of 4504 reflections were measured at room temperature (0 G26 < 453 on a P2r diffractometer using MO Ka radiation. The structure was solved using the SHELX-86 program. All nonhydrogen atoms were refined using anisotropic thermal parameters. Hydrogen atoms were located, but not refined, and placed at fixed distances (0.95 A) from bonded carbon atoms. All calculations were carried out using the SHELX-86 program. For Fig. 1. An ORTEP diagram of 1 with thermal ellipsoids at 30% probability. Selected mean bond lengths (A) and angles (“) for chemically equivalent bonds with range in parentheses: V=O, 1.59 (1.582-1.602); V-O,, 1.85 (1.8421.861); v-o,, 2.08 (2.061-2.096); V-O,., 2.12 (2.0902.143); V-On, 1.86 (1.858-1.868); V-N, 2.02 (2.0142.030); On-N, 1.37 (1.362-1.376); Cn-N, 1.33 (1.3181.339); Cn-0, 1.26 (1.260-1.275); V-V, 4.66 (4.6524.671); O=V-0,, 91 (88.1-92.7); O=V-O,, 108 (107.5108.6); O=V-On, 94 (93.8-94.7); O=V-N, 98 (97.098.1); O=V-0,, 165 (163.1-166.7); V-N-On, 120 (119.5-120.6); N-0,-V, 120 (119.4-120.2).

Catalytic oxidation of 3,5-Di-tert-butylcatechol by a series of mononuclear manganese complexes: synthesis, structure, and kinetic investigation.

The manganese compounds [Mn(bpia)(OAc)(OCH 3 )](PF 6 ) (1), [Mn(bipa)(OAc)(OCH 3 )](PF 6 ) (2), [Mn(bpia)(Cl) 2 ](ClO 4 ) (3), [Mn(bipa)(Cl) 2 ](ClO 4 ) (4), [Mn(Hmimppa)(Cl) 2 ].CH 3 OH (5), and [Mn(mimppa)(TCC)].2CHCl 3 (6) (bpia= bis-(picolyl)(N-methylimidazole-2-yl)amine; bipa = bis(N-methylimidazole-2-yl)(picolyl)amine; Hmimppa = ((1-meth-ylimidazole-2-yl)methyl)((2-pyridyl)methyl)(2-hydroxyphenyl)amine; TCC = tetrachlorocatechol) were synthesized and characterized by various techniques such as X-ray crystallography, mass spectrometry, IR, EPR, and UV/vis spectroscopy, cyclic voltammetry, and elemental analysis. 1 and 2 crystallize in the triclinic space group P1 (No. 2), 4 and 6 crystallize in the monoclinic space group P2 1 /n (No. 14), and 5 crystallizes in the orthorhombic space group Pna2 1 . Complexes 1-4 are structurally related to the proposed active site of the manganese-dependent extradiol-cleaving catechol dioxygenase exhibiting an N 4 O 2 donor set (1 and 2) or N 4 Cl 2 donor set (3 and 4). Cyclic voltammetric data show that the substitution of oxygen donor atoms with chloride causes a shift of redox potentials to more positive values. These compounds show high catalytic activity regarding the oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone exhibiting saturation kinetics at high substrate concentrations. The turnover numbers k c a t = (86 ′ 7) h - 1 (1), k c a t = (101 ′ 4) h - 1 (2), k c a t = (230 ′ 4) h - 1 (3), and k c a t = (130 ′ 4) h - 1 (4) were determined from the double reciprocal Lineweaver-Burk plot. Compounds 5 and 6 can be regarded as structural and electronic Mn analogues for substituted forms of Fe-containing intradiol-cleaving catechol dioxygenases. To our knowledge 5 is the first mononuclear Mn(II) compound featuring an N 3 OCl 2 donor set.