N-hydroxyguanidines as new heme ligands: UV-visible, EPR, and resonance Raman studies of the interaction of various compounds bearing a C=NOH function with microperoxidase-8

Citation
D. Lefevre-groboillot et al., N-hydroxyguanidines as new heme ligands: UV-visible, EPR, and resonance Raman studies of the interaction of various compounds bearing a C=NOH function with microperoxidase-8, BIOCHEM, 40(33), 2001, pp. 9909-9917
Citations number
53
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY
ISSN journal
00062960 → ACNP
Volume
40
Issue
33
Year of publication
2001
Pages
9909 - 9917
Database
ISI
SICI code
0006-2960(20010821)40:33<9909:NANHLU>2.0.ZU;2-4
Abstract
Interaction between microperoxidase-8 (MP8), a water-soluble hemeprotein mo del, and a wide range of N-aryl and N-alkyl N ' -hydroxyguanidines and rela ted compounds has been investigated using UV-visible, EPR, and resonance Ra man spectroscopies. All the N-hydroxyguanidines studied bind to the ferric form of MPS with formation of stable low-spin iron(IH) complexes characteri zed by absorption maxima at 405, 535, and 560 nm. The complex obtained with N-(4-methoxyphenyl) N ' -hydroxyguanidine exhibits EPR g-values at 2.55, 2 .26, and 1.86. The resonance Raman (RR) spectrum of this complex is also in agreement with an hexacoordinated low-spin iron(III) structure. The dissoc iation constants (K-s) of the MP8 complexes with mono- and disubstituted N- hydroxyguanidines vary between 15 and 160 muM at pH 7.4. Amidoximes also fo rm low-spin iron(HI) complexes of MP8, although with much larger dissociati on constants. Under the same conditions, ketoximes, aldoximes, methoxyguani dines, and guanidines completely fail to form such complexes with MP8. The K-s values of the MP8-N-hydroxyguanidine complexes decrease as the pH of th e solution is increased, and the affinity of the N-hydroxyguanidines toward MP8 increases with the pK(a) of these ligands. Altogether these results sh ow that compounds involving a -C(NHR)=NOH moiety act as good ligands of MP8 -Fe(III) with an affinity that depends on the electron-richness of this moi ety. The analysis of the EPR spectrum of the MP8-N-hydroxyguanidine complex es according to Taylor's equations shows a strong axial distortion of the i ron, typical of those observed for hexacoordinated heme-Fe(III) complexes w ith at least one pi donor axial ligand (HO-, RO-, or RS-). These data stron gly suggest that N-hydroxyguanidines bind to MP8 iron via their oxygen atom after deprotonation or weakening of their O-H bond. It thus seems that N-h ydroxyguanidines could constitute a new class of strong ligands for hemepro teins and iron(III)-porphyrins.