Structural and electronic effects resulting from metal-flavin ligation.

Clarke, Michael J.; Dowling, Michael G.; Garafalo, Alfred R.; Brennan, Tim

doi:10.1016/s0021-9258(19)85723-x

Cited by 32 publications

(3 citation statements)

References 62 publications

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“…Flavin bending was also observed in a ruthenium-flavin complex and used as one of the criteria to support the notion that coordinated flavin was partially reduced and that the ruthenium-flavin complex was best described as a delocalized system of flavinsemiquinone coordinated to ruthenium(III). 15 Applying the same argument to explain the nonplanarity of tmaz in 1 leads to assigned formal oxidation states of Mo(V) and (tmazH • ) radical. Interestingly, the Mo(V) oxidation state is consistent with XPS data.…”

Section: Discussionmentioning

confidence: 95%

Molybdenum−Pterin Chemistry. 2. Reinvestigation of Molybdenum(IV) Coordination by Flavin Gives Evidence for Partial Pteridine Reduction

1999

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The coordination of alloxazine and pterins to molybdenum(IV) is demonstrated in this study. The synthesis of MoOCl 3 (pteridineH), where pteridineH is the protonated form of 1,3,7,8-tetramethylalloxazine (tmaz), 2-pivaloyl-6,7-dimethylpterin (piv-dmp), and 6,7-dimethylpterin (dmp), proceeds readily starting from Mo(IV)Cl 4 (acetonitrile) 2 and the pteridine ligand in chloroform or methanol. X-ray crystal structures of MoOCl 3 (tmazH) (1) and MoOCl 3 -(piv-dmpH) (2) show that Mo chelates each pteridine at the carbonyl oxygen and pyrazine nitrogen and that the pteridine ligand is protonated at the other nitrogen in the pyrazine ring. A third X-ray structure for MoOCl 3 (H 3dmp) (4) is included in this work since its determination permits the comparison of metrical parameters for the oxidized and reduced forms of a pterin in identical molybdenum coordination environments. The major difference observed in the structures of 2 as compared to 4 is the Mo-N5 bond length which is significantly shorter in compound 4 containing the reduced form of the pterin. Pteridine protonation is facilitated by molybdenum(IV) coordination due to partial reduction of the pteridine ring through electronic delocalization from Mo to the pteridine ligand. Electronic spectroscopy monitoring the solution reactivity of 1, 2, and MoOCl 3 (dmpH) (3) provides evidence to support this idea. Solution conditions favoring deprotonation of the complexes 1-3 promote pteridine dissociation and complex decomposition.

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Section: Discussionmentioning

confidence: 95%

Molybdenum−Pterin Chemistry. 2. Reinvestigation of Molybdenum(IV) Coordination by Flavin Gives Evidence for Partial Pteridine Reduction

1999

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“…Crystallographic studies on metalloflavin models showed that the N 4 and O 5 atoms of the isoalloxazine ring are the primary sites for metal coordination ( , ). Metal binding to the flavin ring produces steric and electronic effects that induce very important modifications in both absorption and RR spectra ( , ). We found no equivalence in the corresponding spectra of the EH 2 -metal ion complexes.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Glutathione Reductase with Heavy Metal: The Binding of Hg(II) or Cd(II) to the Reduced Enzyme Affects Both the Redox Dithiol Pair and the Flavin

Picaud

Desbois

2006

Biochemistry

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To determine the inhibition mechanism of yeast glutathione reductase (GR) by heavy metal, we have compared the electronic absorption and resonance Raman (RR) spectra of the enzyme in its oxidized (Eox) and two-electron reduced (EH2) forms, in the absence and the presence of Hg(II) or Cd(II). The spectral data clearly show a redox dependence of the metal binding. The metal ions do not affect the absorption and RR spectra of Eox. On the contrary, the EH2 spectra, generated by addition of NADPH, are strongly modified by the presence of heavy metal. The absorption changes of EH2 are metal-dependent. On the one hand, the main flavin band observed at 450 nm for EH2 is red-shifted at 455 nm for the EH2-Hg(II) complex and at 451 nm for the EH2-Cd(II) complex. On the other hand, the characteristic charge-transfer (CT) band at 540 nm is quenched upon metal binding to EH2. In NADPH excess, a new CT band is observed at 610 nm for the EH2-Hg(II)-NADPH complex and at 590 nm for EH2-Cd(II)-NADPH. The RR spectra of the EH2-metal complexes are not sensitive to the NADPH concentration. With reference to the RR spectra of EH2 in which the frequencies of bands II and III were observed at 1582 and 1547 cm-1, respectively, those of the EH2-metal complexes are detected at 1577 and 1542 cm-1, indicating an increased flavin bending upon metal coordination to EH2. From the frequency shifts of band III, a concomitant weakening of the H-bonding state of the N5 atom is also deduced. Taking into account the different chemical properties of Hg(II) and Cd(II), the coordination number of the bound metal ion was deduced to be different in GR. A mechanism of the GR inhibition is proposed. It proceeds primarily by a specific binding of the metal to the redox thiol/thiolate pair and the catalytic histidine of EH2. The bound metal ion then acts on the bending of the isoalloxazine ring of FAD as well as on the hydrophobicity of its microenvironment.

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“…Ruthenium(II) complexes of flavins, pterins and alloxazines have been synthesised and studied from an electrochemical point of view. [22][23][24] Whilst an adduct between [cis-Ru(2,2′bipy) 2 ] 2+ and folic acid has been reported, 23 a limited analysis of the product led to the conclusion that folic acid had chelated to the metal through the O4 and N5 in a motif analogous to flavin coordination. Such binding would produce a single pair of enantiomers (identical by NMR spectroscopy).…”

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confidence: 99%

Folates are potential ligands for ruthenium compounds in vivo

et al. 2014

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Under physiologically relevant conditions, cis-bis(2,2'-bipyridine)dichlororuthenium(II), [cis-Ru(2,2'-bipy)2Cl2] was observed to bind to folic acid via replacement of the two chloride ligands. This binding was shown to be pH dependent and afforded diastereomers, the structures of which were determined by 1- and 2D NMR spectroscopic techniques. We propose that when studying the cytotoxicity of labile ruthenium complexes in cells, folate coordination should be considered.

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Structural and electronic effects resulting from metal-flavin ligation.

Cited by 32 publications

References 62 publications

Molybdenum−Pterin Chemistry. 2. Reinvestigation of Molybdenum(IV) Coordination by Flavin Gives Evidence for Partial Pteridine Reduction

Molybdenum−Pterin Chemistry. 2. Reinvestigation of Molybdenum(IV) Coordination by Flavin Gives Evidence for Partial Pteridine Reduction

Interaction of Glutathione Reductase with Heavy Metal: The Binding of Hg(II) or Cd(II) to the Reduced Enzyme Affects Both the Redox Dithiol Pair and the Flavin

Folates are potential ligands for ruthenium compounds in vivo

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