Chromium -nucleotide complexes

Exchange-inert complexes of Co(III) with nucleotides that have proven to be extremely useful as chirality probes because the different coordination isomers are stable and can be prepared and separated In addition, these nucleotides can be used as dead-end inhibitors of enzyme-catalyzed reactions and, since Co(III) is diamagnetic, a number of spectroscopic protocols can be utilized. See Exchange-Inert Complexes Chromium-Nucleotide Complexes Metal Ion-Nucleotide Interactions... 

Armbruster DA, Rudolph FB. 1976. Rat liver pyruvate carboxylase Inhibition by chromium nucleotide complexes. J Biol Chem 251 320-323. 

A metal-nucleotide complex that exhibits low rates of ligand exchange as a result of substituting higher oxidation state metal ions with ionic radii nearly equal to the naturally bound metal ion. Such compounds can be prepared with chromium(III), cobalt(III), and rhodi-um(III) in place of magnesium or calcium ion. Because these exchange-inert complexes can be resolved into their various optically active isomers, they have proven to be powerful mechanistic probes, particularly for kinases, NTPases, and nucleotidyl transferases. In the case of Cr(III) coordination complexes with the two phosphates of ATP or ADP, the second phosphate becomes chiral, and the screw sense must be specified to describe the three-dimensional configuration of atoms. 

Chromium(III) is oxophilic and can occupy sites in nucleotide complexes similar to those bound by Mg. Since Cr -nucleotide complexes are relatively inert, however, they do not support the phosphoryl transfer chemistry catalyzed by Mg in polymerases or other nucleotide-dependent enzymes. Thus, Cr -nucleotide complexes have been used to study structure and mechanism, particularly in polymerases. As one example, a co-crystal of DNA polymerase /3 with Cr -dTTP substrate shows Cr occupying one site in the two metal binding active site as a replacement of Mgii 44 structure, Cr binds to the /3,7-phosphate oxygens of the 5 -dTTP substrate. 

Applications of RPC include separation of metalloproteins, such as. metallothionein isoforms and superoxide dismutase [7]. The majority of applications use ion-pair reagents like trifluoroacetic acid or tetraalky-lammonium hydroxides in the mobile phase to increase the retention of ionic compounds, for example, selenoamino acids [20], trivalent and hexavalent chromium [21], or Pt-nucleotide complexes [22]. 

The carcinogenicity and mutagenicity of chromium(VI) are well established.The toxicity is usually considered in terms of the uptake/reduction modeP since chromium(VI) readily passes into the cell, via anion channels, and once within the cell it is eventually reduced by cellular components to chromium(III) species. Figure 6 illustrates the likely fate of chromate within a mammalian cell. As can be appreciated from Figure 6 it is complexes trapped within the cell that are the agents responsible for the toxic effects of chromate. The systems which reduce the chromiumfvi) are as yet unknown, as are the final products of the reaction. However, microsomes are capable of reducing chromium(VI) as are various nucleotides and even fulvic acids.In these cases chromium(V) species of considerable stability have been observed using EPR spectroscopy. Within the cell reduction by a sulfide is the most probable reaction. 

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