StudyontheMultifunctionalDinitrosylIronComplexesContainingRedox-ActivatedNitricOxide,IronandReducingThiolateLigand

• Main Authors: Lu, Tsai-Te, 魯才德
• Other Authors: Liaw, Wen-Feng
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/22908860681460878816

博士 === 國立清華大學 === 化學系 === 98 === Despite of the identification of dinitrosyl iron complexes (DNICs) featuring the EPR signal at g = 2.03 forty-five years ago, the de novo synthesis of DNICs in biological system remains elusive. Compared to the nitrosylation of complexes [Fe(SR)4]2–/1– (R = Ph, Et, tBu) leading to the formation of DNIC [(RS)2Fe(NO)2]– (2) via the intermediate mononitrosyl iron complexes (MNIC) [Fe(NO)(SR)3]– (1), binding of nitric oxide to complex [(SEt)2Fe(μ-S)2Fe(SEt)2]2– yields DNIC 2-Et through a concerted reaction pathway. Acting as the endogenous NO-carrier, the release of distinct redox-interrelated forms of NO ([NO]+, •NO and [NO]–) from DNIC [(NO)2Fe(C12H8N)2]– (2-Car) modulated by the incoming ligands (S2CNMe2)2, (PyPepS)2 and P(C6H3-3-SiMe3-2-SH)3) supports the N-/S-nitrosation, heme-nitrosylation and nitroxyl-related vascular relaxation triggered by DNICs. In contrast to the conversion of DNIC 2-tBu into anionic Roussin’s red ester (RRE) [Fe(μ-StBu)(NO)2]2– (8-tBu) in CH3CN and into neutral RRE [Fe(μ-StBu)(NO)2]2 (3-tBu) in CH2Cl2, respectively, the dynamic equilibrium between DNIC 2-tBu and neutral RRE 3-tBu observed in CH3OH illustrates the aspect of how the hydrophobic/hydrophilic protein environment regulates the transformation of DNICs in the biological system. In combination with the typical EPR signal at g = 2.03 of {Fe(NO)2}9 DNICs and 1.997 of {Fe(NO)2}9-{Fe(NO)2}10 anionic RREs, the pre-edge energy derived from 1s→3d transition in a distorted Td environment of the Fe center of DNICs within the range of 7113.3-7113.8 eV could be utilized to probed the formation of the monomeric {Fe(NO)2}9/{Fe(NO)2}10 DNICs, {Fe(NO)2}9-{Fe(NO)2}10 anionic RREs and {Fe(NO)2}9-{Fe(NO)2}9 RREs containing thiolate/sulfide bridging ligands in biological systems. Transformation of DNICs into [2Fe-2S] clusters facilitated by HSCPh3 or Me2S3 via the reassembling process ([(NO)2Fe(SEt)2]– (2-Et)/ [(NO)2Fe(μ-SEt)2Fe(NO)2]– (8-Et)→ [(NO)2Fe(μ-SEt)(μ-S)Fe(NO)2]– (9-Et)→ [(NO)2Fe(μ-S)2Fe(NO)2]2– (10)→ [(SEt)2Fe(μ-S)2Fe(SEt)2]2–) was consistent with the repair of DNICs back to the ferredoxin [2Fe-2S] cluster by cysteine desulfurase (IscS) and L-cysteine in vitro with no need of the addition of iron or any other protein components in E. coli. The distinct spectroscopic feature of S K-edge spectra displayed by monomeric DNICs 2-Et/2-Ph, dimeric/dinuclear DNICs 3-Et/8-Et/9-Et/10 and [2Fe-2S] clusters could be used to probe the transformation of DNICs into [2Fe-2S]. On the basis of the pre-edge energy in the Fe K-edge spectra and the pre-edge energy in combination with the 1s(S)����*(C-S bond) transition energy in the S K-edge spectra, the electronic structure of DNICs is best described as {FeIII(NO–)2}9. Furthermore, the nature of the SOMO of DNIC 2-Ph and the LUMO of RRE 3-Et characterized by S K-edge XAS is the Fe-S antibonding orbital. This rationalizes the ligand-exchange reaction observed in the reaction of DNIC 2-Ph and [SEt]– yielding DNIC 2-Et, the bridged-thiolate cleavage reaction upon addition of [SEt]– to RRE 3-Et leading to the formation of DNIC 2-Et and conversion of complex 2-Et into complex 9-Et via reduction of HSCPh3/Me2S3 by the pendant thiolate of complex 2-Et. In addition to acting as the endogenous NO-carrier and redox-activating nitric oxide to donate distinct redox-interrelated forms of nitric oxide, DNICs serve as not only the thiolate/electron carrier activating the incorporation of sulfide to assemble [Fe(��-S)2Fe] core but also the Fe carrier/source in the biosynthesis of [2Fe-2S] and [4Fe-4S] iron-sulfur clusters