Flavin metal chelates

ESR and ENDOR spectral data on flavin-metal chelates in which the metal has a magnetic moment (e.g. Zn, Cd, Cd) have shown that the hyperfine couplings on the flavin are comparable to those of the anionic flavin semiquinone (as is the... 

The o-character of flavin-metal contacts is more easily accepted a priori, since kinetic stability of metal-N,0-ligation need not be apprehended. Metal chelates (bidentate or polydentate structures) may, however, exhibit enough thermodynamic advantages to preclude dissociation and thereby, electron transfer. Flavin, however, is established being a... 

Three types of flavin metal chelates have been distinguished according to Figure 4 (25). 

Blocking can also be achieved by metal 4a,5-chelation (70). The biological relevance of direct flavin-metal interaction is, however, still questionable. The chelates MeFl are dark red with an additional absorption band of still unknown character in the near infrared (70). 

The metal chelating ability of flavins has been extensively investigated predominately in Hemmerich s laboratory While the oxidized and reduced (hydroquinone) forms of flavin are poor chelating ligands to divalent metal ions in aqueous solution, the flavin semiquinone forms chelates of considerable stability. This is readily demonstrated by the increase in semiquinone formation on the addition of metal ions to a half-reduced flavin solution which occurs by shifting the equilibrium away from semiquinone dismutation ... 

The stability constant for the lumiflavin semiquinone Zn chelate in aqueous solution was found to be 2xlfr M , with the Cd chelate having about equal stability Aprotic solvents such as DMF serve to increase the stability constants relative to H2O about 10-fold. In all systems tested, the stoichiometry of the flavin semiquinone-metal complex is 1 1. 

Ehrenberg, A. Flavin radical-metal chelates. In Vitamins and hormones, Vol. 28 (Harris, R. S., Munson, P. L., Diezfalusy, E. eds.) pp. 489-503, New York, London, Academic Press 1970... 

The presence of metal ions in many flavoproteins suggested a direct association of metal ions and flavins. Although oxidized flavins do not readily bind most metal ions, they form red complexes with Ag+ and Cu+ with a loss of a proton from N-3.278 Flavin semiquinone radicals also form strong red complexes with many metals.264 If the complexed metal ion can exist in more than one oxidation state, electron transfer between the flavin and a substrate could take place through the metal atom. However, chelation by flavins in nature has not been observed. Metalloflavoproteins probably function by having the metal centers close enough to the... 

C(6)H causes steric hindrance of metal coordination in all flavin redox states to further prevent unfavorably high chelate stability. 

Valuable spectroscopic studies on the dithiolene chelated to Mo in various enzymes have been enhanced by the knowledge of the structure from X-ray diffraction. Plagued by interference of prosthetic groups—heme, flavin, iron-sulfur clusters—the majority of information has been gleaned from the DMSO reductase system. The spectroscopic tools of X-ray absorption spectroscopy (XAS), electronic ultraviolet/visible (UV/vis) spectroscopy, resonance Raman (RR), MCD, and various electron paramagnetic resonance techniques [EPR, electron spin echo envelope modulation (ESEEM), and electron nuclear double resonance (ENDOR)] have been particularly effective probes of the metal site. Of these, only MCD and RR have detected features attributable to the dithiolene unit. Selected results from a variety of studies are presented below, chosen because their focus is the Mo-dithiolene unit and organized according to method rather than to enzyme or type of active site. 

Many synthetic dyes such as porphyrins, acridine, thlonlne and flavin dyes have been used in photosensltlzatlon of electron transfer reactions. In the past few years several promising organometalllc compounds have been prepared as substitutes for the natural labile chlorophyll. These organometalllcs Include a variety of metals, chelated to bipyridine or porphyrin ligands ( ). The photophysical properties of these sensitizers and their potential use in artificial photosynthetic devices have been extensively reviewed ( 7, ). In particular, sensitizers such as... 

It was discovered in 1958 that anaerobically grown yeast contains a form of lactate dehydrogenase which is different from the d- and L-lac-tate cytochrome c reductases of aerobic yeast (306, 319). The enzyme has been partially purified (320, 321), and shown to contain flavin (320-322). Gel filtration studies have suggested a molecular weight of about 100,000 (320, 321). Preparations of the enzyme oxidize several d-2-hydroxyacids to the respective keto acids in a reversible manner (320). For the forward reaction, ferricyanide, 2,6-dichloroindophenol, menadione, and methylene blue have been used as electron acceptors, and for the reverse reaction leucomethyl viologen and FMNHa are effective electron donors (320). A number of L-2-hydroxyacids and 2-keto acids have been shown to be competitive inhibitors. Oxalate, cyanide, o-phenanthro-line, and EDTA are also potent inhibitors (320, 321, 323, 324). The inhibition by metal chelators develops slowly and is reversed by addition of Zn, Co, Mn +, or Fe + (320, 323-326). Substrates prevent the inhibition by chelators at concentrations considerably lower than their respective Km values (327). It has been suggested that EDTA inactivation involves the removal of a metal, most probably Zn +, from the substrate binding site of the enzyme (325, 326, 328, 329). However, others have... 

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