Synthesis, structure determination, and spectroscopic/computational characterization of a series of Fe(II)-thiolate model complexes: implications for Fe-S bonding in superoxide reductases.
A combined synthetic/spectroscopic/computational approach has been employed to prepare and characterize a series of Fe(II)-thiolate complexes that model the square-pyramidal [Fe(II)(N(His))(4)(S(Cys))] structure of the reduced active site of superoxide reductases (SORs), a class of enzymes that detoxify superoxide in air-sensitive organisms. The high-spin (S = 2) Fe(II) complexes [(Me(4)cyclam)Fe(SC(6)H(4)-p-OMe)]OTf (2) and [FeL]PF(6) (3) (where Me(4)cyclam = 1,4,8,11-tetramethylcyclam and L is the pentadentate monoanion of 1-thioethyl-4,8,11-trimethylcyclam) were synthesized and subjected to structural, magnetic, and electrochemical characterization. X-ray crystallographic studies confirm that 2 and 3 possess an N(4)S donor set similar to that found for the SOR active site and reveal molecular geometries intermediate between square pyramidal and trigonal bipyramidal for both complexes. Electronic absorption, magnetic circular dichroism (MCD), and variable-temperature variable-field MCD (VTVH-MCD) spectroscopies were utilized, in conjunction with density functional theory (DFT) and semiemperical INDO/S-CI calculations, to probe the ground and excited states of complexes 2 and 3, as well as the previously reported Fe(II) SOR model [(L(8)py(2))Fe(SC(6)H(4)-p-Me)]BF(4) (1) (where L(8)py(2) is a tetradentate pyridyl-appended diazacyclooctane macrocycle). These studies allow for a detailed interpretation of the S-->Fe(II) charge transfer transitions observed in the absorption and MCD spectra of complexes 1-3 and provide significant insights into the nature of Fe(II)-S bonding in complexes with axial thiolate ligation. Of the three models investigated, complex 3 exhibits an absorption spectrum that is particularly similar to the one reported for the reduced SOR enzyme (SOR(red)), suggesting that this model accurately mimics key elements of the electronic structure of the enzyme active site; namely, highly covalent Fe-S pi- and sigma-interactions. These spectral similarities are shown to arise from the fact that 3 contains an alkyl thiolate tethered to the equatorial cyclam ring, resulting in a thiolate orientation that is very similar to the one adopted by the Cys residue in the SOR(red) active site. Possible implications of our results with respect to the electronic structure and reactivity of SOR(red) are discussed.
Fiedler
Adam T
AT
University of Wisconsin-Eau Claire, Department of Chemistry, 105 Garfield Avenue, Eau Claire, WI 54702, USA.
Halfen
Heather L
HL
Halfen
Jason A
JA
Brunold
Thomas C
TC
D001665:Binding Sites; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D005296:Ferrous Compounds / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism
D005296:Ferrous Compounds; D008024:Ligands; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase