Control of redox reactivity of flavin and pterin coenzymes by metal ion coordination and hydrogen bonding

The electron-transfer activities of flavin and pterin coenzymes can be fine-tuned by coordination of metal ions, protonation and hydrogen bonding. Formation of hydrogen bonds with a hydrogen-bond receptor in metal–flavin complexes is made possible depending on the type of coordination bond that can leave the hydrogen-bonding sites. The electron-transfer catalytic functions of flavin and pterin coenzymes are described by showing a number of examples of both thermal and photochemical redox reactions, which proceed by controlling the electron-transfer reactivity of coenzymes with metal ion binding, protonation and hydrogen bonding.     

Steric effect and effect of metal coordination on the reactivity of nitric oxide with cysteine-containing proteins under anaerobic conditions

A comparison is made between the reactivity of nitric oxide (NO) with cysteine, bovine serum albumin (BSA) and metallothionein-1 (MT1) at pH 7 under strictly anaerobic conditions. The rate of reaction of NO with these amino acid/proteins was found to be of the order: cysteine > BSA > MT1, in clear disparity with the size of the reactants. The difference in the reaction rates is attributed to steric effects due to the high molecular size in the case of BSA and to effects of metal coordination proper as well as to steric effects associated with the closed dual shell-like structure resulting from the tight coordination of the thiolate groups with Zn2+ in MT1. The mechanisms of the reaction of NO with cysteine, BSA and MT and its possible implication for the rate of the respective reactions are discussed.     

In-depth insight into metal–alkene bonding interactions

The relative alkene dissociation energies and the structures of Pd(PH₃)₂(η²-CH₂CHX), trans-[Pd(PH₃)₂Cl(η²-CH₂CHX)]⁺, trans-[Pd(PH₃)Cl₂(η²-CH₂CHX)], Cp₂Zr(PH₃)(η²-CH₂CHX) and [Cp₂Zr(CH₃)(η²-CH₂CHX)]⁺ (X = CN, Cl, Br, Me, OMe, NMe₂) were calculated with the B3LYP density functional theory. We examined the correlations between the partial charges of the coordinated alkenes and the relative alkene dissociation energies. Through these correlations, we have been able to see how the alkene(π)-to-metal(d) donation and metal(d)-to-alkene(π*) back-donation interactions affect the relative alkene dissociation energies. We also examined the calculated structures and found that the Zr(IV) and Pd(II) complexes have a rather asymmetric alkene coordination while the Zr(II) and Pd(0) complexes have an approximately symmetric alkene coordination. The effects of the alkene(π)-to-metal(d) donation and metal(d)-to-alkene(π*) back-donation interactions on the structural features have also been discussed.     

An M-H…H-C hydrogen bonding interaction

Study of several X-ray and neutron diffraction crystal structures of aryl phosphine hydride complexes shows that abnormally close CH…HM contacts (1.6–2.1 Å) commonly occur between the arene CH bonds and the hydride. The data suggest that weak CH…HM hydrogen bonds are involved, resembling those we have previously characterized for the NH…HN case. Based on these results, a new mechanism is suggested for cyclometallation.     

Sugar interaction with metal ions. The coordination behavior of neutral galactitol to Ca(II) and lanthanide ions

The crystal structures of CaCl(2).galactitol.4 H(2)O and 2EuCl(3).galactitol.14 H(2)O were determined to compare the coordination behavior of Ca and lanthanide ions. The crystal system of the Ca-galactitol complex, CaCl(2).C(6)H(14)O(6).4 H(2)O, is monoclinic, Cc space group. Each Ca ion is coordinated to eight oxygen atoms, four from two galactitol molecules and four from water molecules. Galactitol provides O-2, -3 to coordinate to one Ca(2+), and O-4, -5 with another Ca(2+), to form a chain structure. The crystal system of the Eu-galactitol complex, 2EuCl(3).C(6)H(14)O(6).14 H(2)O, is triclinic, P1; space group. Each Eu ion is coordinated to nine oxygen atoms, three from an alditol molecule and six from water molecules. Each galactitol provides O-1, -2, -3 to coordinate with one Eu(3+) and O-4, -5, -6 with another Eu(3+). The other water molecules are hydrogen-bonded in the structure. The similar IR spectra of Pr-, Nd-, Sm-, Eu-, Dy-, and Er-galactitol complexes show that those lanthanide ions have the same coordination mode to neutral galactitol. The Raman spectra also confirm the formation of metal ion-carbohydrate complexes.     

Enzymatic activity mastered by altering metal coordination spheres

Metalloenzymes control enzymatic activity by changing the characteristics of the metal centers where catalysis takes place. The conversion between inactive and active states can be tuned by altering the coordination number of the metal site, and in some cases by an associated conformational change. These processes will be illustrated using heme proteins (cytochrome c nitrite reductase, cytochrome c peroxidase and cytochrome cd ₁ nitrite reductase), non-heme proteins (superoxide reductase and [NiFe]-hydrogenase), and copper proteins (nitrite and nitrous oxide reductases) as examples. These examples catalyze electron transfer reactions that include atom transfer, abstraction and insertion.     

The active-site metal coordination geometry of cadmium-substituted alcohol dehydrogenase

 The structure of eleven complexes of cadmium-substituted alcohol dehydrogenase with or without coenzyme and with different non-protein cadmium ligands has been estimated by combined quantum chemical and molecular mechanical geometry optimisations. The geometry of the optimised complexes is similar to the crystal structure of cadmium-substituted alcohol dehydrogenase, indicating that the method behaves well. The optimised structures do not differ significantly (except for the metal bond lengths) from those of the corresponding zinc complexes, which shows that cadmium is a good probe of zinc coordination geometries. The electric field gradients at the cadmium nucleus have been calculated quantum chemically at the MP2 level with a large cadmium basis set, and they have been used to interpret experimental data obtained by perturbed angular correlation of γ-rays. The experimental and calculated field gradients (all three eigenvalues) differ by less than 0.35 a.u. (3.4·10²¹ Vm^–2), the average error is 0.11 a.u., and the average relative error in the two largest eigenvalues of the field gradients is 9%. Calculated field gradients of four-coordinate structures agree better with the experimental results than do those of any five-coordinate model. Thus, the results indicate that the catalytic metal ion remains four-coordinate in all examined complexes. Two measurements are best explained by a four-coordinate cadmium ion with Glu-68 as the fourth ligand, indicating that Glu-68 probably coordinates intermittently to the catalytic metal ion in horse liver alcohol dehydrogenase under physiological conditions. Received: 10 January 1997 / Accepted: 24 May 1997     

Formation of peptide nanospheres and nanofibrils by metal coordination

Two amphipathic polypeptides were coordinated to the cis positions of a square planar Pt(II) complex in order to provide the metal center with two noncovalent oligomerization domains. This resulted in the formation of new metal-peptide nanoassemblies which are shown to exist as nanometer-sized spheres and fibrils. Construction of these assemblies was based on the 30-residue polypeptide AQ-Pal14 which was designed for its ability to self-assemble into the common protein oligomerization motif of a noncovalent coiled-coil, and modified to contain a metal-binding 4-pyridylalanine residue at its surface. When AQ-Pal14 was reacted with Pt(en)(NO 3) 2, a new metal-peptide complex was formed in which two AQ-Pal14 peptides were coordinated to a single metal center as determined by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and electrospray ionization mass spectrometry (ESI-MS). When the reaction mixture was analyzed under nondenaturing conditions by high performance size exclusion chromatography (HPSEC), it was found that all species present eluted at the column void volume, indicating the formation of very large metal-peptide assemblies. This was verified by multiangle light scattering (MALS) which showed that the metal-peptide assemblies have a weight-averaged molecular mass and z-average root-mean-square radius of Mw = (7 +/- 4) x 10 (6) g/mol and Rz = 18 +/- 4 nm, respectively. The presence of such nanometer scale assemblies was confirmed by transmission electron microscopy and atomic force microscopy which showed the existence of both spherical and fibrillar nanostructures.     

Principles of bonding and reactivity in transition metal cluster compounds

The bonding in transition metal cluster compounds is examined by partitioning the system into the component parts suggested by expressions for the total energy. The nature of MM (metal-metal) interactions, ML (metal-ligand) interactions and LL (ligand-ligand) interactions are examined, and their effect on the stability and hence structure of the system considered. The processes by which one structure can rearrange into another are discussed. Some consideration is given to the partitioning of a cluster into ML_j fragments, and the interactions between these fragments. Isolobal analogies are discussed in this context. The emphasis of this work is on the general principles behind the structure and reactivity of transition metal cluster compounds, rather than focusing on specific systems.     

3-Ferrocenylamido-5-methylpyrazole: synthesis and metal coordination

The new pyrazole-derived ferrocene ligand 3-ferroceneamido-5-methylpyrazole (3-Fc-AMP, 2) was synthesized from 3-amino-5-methylpyrazole and ferrocenecarboxylic acid. The ligand associates in the solid state into one-dimensional H-bonded polymeric chains and forms N,O-chelating metal complexes of Zn, Cd, Ni and Co, having ML₂ and ML₃ stoichiometries. Their electrochemical properties and the X-ray crystal structures of two Cd and Ni complexes are reported.     

Importance of the +73/294 interaction in Escherichia coli RNase P RNA substrate complexes for cleavage and metal ion coordination

We have studied an interaction, the "73/294-interaction", between residues 294 in M1 RNA (the catalytic subunit of Escherichia coli RNase P) and +73 in the tRNA precursor substrate. The 73/294-interaction is part of the "RCCA-RNase P RNA interaction", which anchors the 3' R(+73)CCA-motif of the substrate to M1 RNA (interacting residues underlined). Considering that in a large fraction of tRNA precursors residue +73 is base-paired to nucleotide -1 immediately 5' of the cleavage site, formation of the 73/294-interaction results in exposure of the cleavage site. We show that the nature/orientation of the 73/294-interaction is important for cleavage site recognition and cleavage efficiency. Our data further suggest that this interaction is part of a metal ion-binding site and that specific chemical groups are likely to act as ligands in binding of Mg(2+) or other divalent cations important for function. We argue that this Mg(2+) is involved in metal ion cooperativity in M1 RNA-mediated cleavage. Moreover, we suggest that the 73/294-interaction operates in concert with displacement of residue -1 in the substrate to ensure efficient and correct cleavage. The possibility that the residue at -1 binds to a specific binding surface/pocket in M1 RNA is discussed. Our data finally rationalize why the preferred residue at position 294 in M1 RNA is U.     

Enhancing effect of phenobarbital sodium on Tyzzer's disease in mice

Tyzzer's disease in mice was aggravated by phenobarbital sodium (PB) given consecutively after bacterial inoculation. In PB-treated mice, mortality rate and severity of liver lesions were higher with more prominent bacterial propagation in hepatocytes as compared with non-treated ones, suggesting that PB had an enhancing effect on metabolic activities of host hepatocytes resulting in increased intracellular growth of bacteria.