The authors were asked by the Editors of ACS Chemical Biology to write an article titled “Why Nature Chose Selenium” for the occasion of the upcoming bicentennial of the discovery of selenium by the Swedish chemist Jons Jacob Berzelius in 1817 and styled after the famous work of Frank Westheimer on the biological chemistry of phosphate [Westheimer, F. H. (1987) Why Nature Chose Phosphates, Science 235, 1173–1178]. This work gives a history of the important discoveries of the biological processes that selenium participates in, and a point-by-point comparison of the chemistry of selenium with the atom it replaces in biology, sulfur. This analysis shows that redox chemistry is the largest chemical difference between the two chalcogens. This difference is very large for both one-electron and two-electron redox reactions. Much of this difference is due to the inability of selenium to form π bonds of all types. The outer valence electrons of selenium are also more loosely held than those of sulfur. As a result,...

Why Nature Chose Selenium

Structural and functional models related to the nickel hydrogenases

[NiFe] hydrogenases catalyse the reaction H2 2H(+) + 2e(-). Several states of the enzyme have been observed by spectroscopic methods. Among these, the two most oxidized states, called the unready Ni-A and Ni-SU states, have been especially intriguing, because they take a much longer time to activate than the corresponding ready Ni-B and Ni-SI states. It has recently been suggested that the unready states actually contain a (hydro)peroxide bridge between the Ni and Fe ions, in contrast to the hydroxide bridge in the ready states. In this paper, we use quantum refinement (crystallographic refinement, in which the molecular mechanics [MM] calculations, normally employed to supplement the crystallographic data, are replace by more accurate quantum mechanics [QM] calculations), combined QM/MM calculations, and accurate energy estimates to study the nature of a recent oxidised crystal structure of [NiFe] hydrogenase from Desulfovibrio fructosovorans. We show that the structure contains a mixture of several states in the active site. The experimental data is best explained by structures with a hydroxide bridge but with two of the cysteine ligands (one bridging and one terminal) partly oxidised. When the terminal Cys-543 ligand is oxidised, the sulphur occupies an alternative position, observed in several crystal structures. The Glu-25 residue, that forms a hydrogen bond to this sulphur, also changes position. A peroxide ligand may exist as a minor component in the crystal and the suggested structure is supported by the calculations. We suggest that oxidised states are slow-equilibrium mixtures of structures with a peroxide bound and structures with oxidised Cys residues, and that the former can be activated by replacement of the protonated peroxide with a H-2 or CO ligand, as has been observed in electrochemical experiments. (c) 2006 Elsevier B.V. All rights reserved. (Less)

Combined computational and crystallographic study of the oxidised states of [NiFe] hydrogenase

The structural and electronic differences between coordination compounds which model [NiFe] and [NiFeSe] hydrogenase active sites were investigated using quantum chemical methods. A previous study showed that the structural and electronic properties of these model compounds are largely consistent with available experimental data in the case of [NiFe] hydrogenases (L. De Gioia, P. Fantucci, B. Guigliarelli, P. Bertrand, submitted). The extension of this study to models of the NiB, NiSI, NiC, and NiR states of [NiFeSe] hydrogenases show that (i) a hydrogen atom can bridge the two metal centers in the NiC and NiR states of [NiFeSe] hydrogenases and (ii) the structure and electronic features of [NiFeSe] models are in good agreement with available experimental data, except for the NiB model for which the analysis of the spin-density distribution suggests that a bridging oxygen species is still present. In addition, (iii) the similarity between the structural and electronic properties of the [NiFe] and [NiFeSe] models suggests that the activity differences observed between the two kinds of hydrogenases cannot be attributed to the SSe substitution alone, (iv) analysis of frontier orbitals strongly suggests that dihydrogen interacts with the Ni center in the initial step of its activation, and (v) the optimized models of the NiR state of [NiFe] and [NiFeSe] enzymes are characterized by an unusual NiHS bridge and lie about 25 kcal/mol lower in energy when compared to the unbridged structure. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 73: 187–195, 1999

Ab initio investigation of the structural and electronic differences between active‐site models of [NiFe] and [NiFeSe] hydrogenases

Selenium versus sulfur: Reversibility of chemical reactions and resistance to permanent oxidation in proteins and nucleic acids.

The syntheses, structures, and redox properties of isomorphous Ni(I1) thiolato and selenolato complexes of the tridentate ligands bis(2-(hydrochalcogeno)ethyl)methylamines are reported. Reaction of Ni(0Ac)z with bis(2mercaptoethy1)methylamine leads to the formation of a dimeric complex, bis{ [@-2-mercaptoethyl)(2-mercaptoethyl)methylaminato(2-)]nickel(II)}, [Ni(l)]2. This complex contains planar, diamagnetic Ni(I1) centers ligated by a tertiary amine N-donor atom, a terminal thiolate, and two thiolates that bridge to the second Ni center in the dimer. Crystals of [Ni(l)]2 form in orthorhombic space group h a 2 1 with cell dimensions a = 19.695(2) 8, b = 6.042(2) 8, c = 13.463(3) 8, V = 1602(1) A3, and Z = 4. Reaction of Ni(0Ac)p with bis(2-(hydroseleno)ethy1)methylamine results in the formation of a structurally analogous dimeric complex, bis([@-2-(hydroseleno)ethyl)(2-(hydroseleno)ethyl)methylaminato(2-)]nickel(II)}, [Ni(2)]2, where all of the chalcogenolate donors are selenolates. Crystals of [Ni(2)]2 are isomorphous with those of [Ni(l)]z, with a = 20.040(8) 8, b = 6.265(2) 8, c = 13.590(5) 8, and V = 1706(2) A3, One-electron oxidation of either dimeric complex leads to the formation of radical cations, which exhibit EPR spectra consistent with S = l/2 radicals. For [Ni(l)]2+ the g values observed (gx = 2.20, g, = 2.14, g, = 2.02) are essentially identical to those observed for a reduced and catalytically viable redox state of Fe,Ni hydrogenases (gx = 2.20, g, = 2.14, g, = 2.01). The substitution of Sefor S-donors in [Ni(2)]2 does not alter the observed g values much (gx = 2.23, g, = 2.14, g, = 2.05) but leads to the observation of 77Se hyperfine coupling (A, = 129 G) that indicates that the molecular orbital containing the unpaired spin is largely Se in character (54%). Reaction of either dimeric complex with CNleads to the formation of mononuclear trans-dichalcogenolate complexes, [Ni(l)CN]and [Ni(2)CN]-. Exposure of [Ni(l)CN]to 0 2 leads to the quantitative formation of a monosulfinato complex. In contrast, the selenolato complex does not react with 0 2 under the same conditions. The role of selenocysteinate ligation in Fe,Ni,Se hydrogenases is discussed in view of this chemistry.

Ma Pressler

Papers

Chemistry of analogous nickel thiolato and selenolato complexes - implications for the nickel sites in hydrogenases