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Part~I. XAS structural investigations of the nickel site in Thiocapsa roseopersicina hydrogenase. Part~II. Models of iron binding by the anthracycline drugs
Abstract
In order to examine the redox role of the Ni center in hydrogenases, the XAS spectra of redox poised samples of Thiocapsa roseopersicina hydrogenase were examined. The Ni K-edge energy remains remarkably constant during the reductive activation of the enzyme, which demonstrates that no significant change in the electron density of the Ni site occurs. Analysis of the EXAFS spectra obtained from scattering atoms in the first coordination sphere of Ni in all five states of the enzyme are consistent with a Ni site composed of 3 $\pm$ 1 N(O)-donors at 2.00 $\pm$ 0.06 A and 2 $\pm$ 1 S-donors at 2.23 $\pm$ 0.03 A. No evidence is found in the XAS data to support a redox role for Ni in hydrogenase. The active form of the enzyme is light sensitive and is converted to a photoproduct that exhibits a unique EPR signal. This conversion has been studied using EPR and x-ray absorption (XAS) spectroscopic studies. Recent studies using $\sp1$H-ENDOR spectra revealed the presence of two sets of protons that interact with the EPR active center in Ni-C. Upon irradiation and conversion of the EPR signal to Ni-L one proton set is no longer observed. Upon annealing and regeneration of Ni-C, the feature associated with this proton set is again observed. XAS data do not reveal any changes in the XANES region or in the first shell coordination geometry around the Ni, which raises the possibility that Ni is not the hydrogen binding site. The iron complexes of anthracycline drugs have been implicated as the form of these drugs that is involved in mediating their anticancer activity and/or their cardiotoxicity. Due to their complex structure several binding sites are possible. Models have been developed using Quinizarin (Qz), which models the chromophore of the drugs. Resonance Raman spectroscopy indicates that the iron is binding at the phenolate oxygens present on both the drugs and the Qz molecule. These conclusions are supported by the crystal structures of two of the Fe model systems, (Fe(salen)) $\sb2$Qz and (Hpip$\sp+\rbrack\sb2\{$ (Fe(nta)) $\sb2$Qz$\}.$
Subject Area
Inorganic chemistry|Biochemistry|Chemistry
Recommended Citation
Whitehead, Joyce Patricia, "Part~I. XAS structural investigations of the nickel site in Thiocapsa roseopersicina hydrogenase. Part~II. Models of iron binding by the anthracycline drugs" (1993). Doctoral Dissertations Available from Proquest. AAI9329681.
https://scholarworks.umass.edu/dissertations/AAI9329681