Synthesis and Characterization of a Model Complex for Flavodiiron NO Reductases That Stabilizes a Diiron Mononitrosyl Complex

Overview

Journal J Inorg Biochem

Specialty Biochemistry

Date 2022 Jan 25

PMID 35074551

Authors

Hai T Dong

Yu Zong

Abigail J Bracken

Michael O Lengel

Jeff W Kampf

Debangsu Sil

Carsten Krebs

Nicolai Lehnert

Affiliations

Soon will be listed here.

Abstract

Flavodiiron NO reductases (FNORs) are important enzymes in microbial pathogenesis, as they equip microbes with resistance to the human immune defense agent nitric oxide (NO). DFT calculations predict that a network of second coordination sphere (SCS) hydrogen bonds is critical for the key NN coupling step in the NO reduction reaction catalyzed by FNORs. In this study, we report the synthesis of a model complex of FNORs with pendant hydrogen bond donors. For this purpose, the ligand H[BPMP] (= 2,6-bis[[bis(2-pyridylmethyl)amino]methyl]-4-methylphenol) was modified with two amide groups in the SCS. Reaction of the precursor complex [Fe(BPMP(NHCOBu))(OAc)](OTf) (1) (OTf = triflate anion) with NO in the presence of base led to the surprising isolation of a diiron mononitrosyl complex, [Fe(BPMP(NHCOBu)(NCOBu))(OAc)(NO)](OTf) (2) and a triiron decomposition product, [Fe(BPMP(NHCOBu))(OAc)(μ-O)(ONO)](OTf) (3), which were both structurally characterized. Complex 2 models the corresponding mononitrosyl adduct in FNORs. This result points towards a strategy that can be used to stabilize mononitrosyl diiron complexes, using the SCS.

Citing Articles

Synthesis and Structural Characterization of a Non-Heme Iron Hyponitrite Complex.

Lengel M, Dong H, Lehnert N Angew Chem Int Ed Engl. 2024; 63(49):e202409700.

PMID: 39254923 PMC: 11586694. DOI: 10.1002/anie.202409700.

References

MacMicking J, Xie Q, Nathan C . Nitric oxide and macrophage function. Annu Rev Immunol. 1997; 15:323-50. DOI: 10.1146/annurev.immunol.15.1.323. View

Sarti P, Fiori P, Forte E, Rappelli P, Teixeira M, Mastronicola D . Trichomonas vaginalis degrades nitric oxide and expresses a flavorubredoxin-like protein: a new pathogenic mechanism?. Cell Mol Life Sci. 2004; 61(5):618-623. PMC: 11146037. DOI: 10.1007/s00018-003-3413-8. View

Frazao C, Silva G, Gomes C, Matias P, Coelho R, Sieker L . Structure of a dioxygen reduction enzyme from Desulfovibrio gigas. Nat Struct Biol. 2000; 7(11):1041-5. DOI: 10.1038/80961. View

Jana M, White C, Pal N, Demeshko S, Cordes Nee Kupper C, Meyer F . Functional Models for the Mono- and Dinitrosyl Intermediates of FNORs: Semireduction versus Superreduction of NO. J Am Chem Soc. 2020; 142(14):6600-6616. DOI: 10.1021/jacs.9b13795. View

Wink D, Mitchell J . Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med. 1998; 25(4-5):434-56. DOI: 10.1016/s0891-5849(98)00092-6. View

Pal N, Jana M, Majumdar A . Reduction of NO by diiron complexes in relation to flavodiiron nitric oxide reductases. Chem Commun (Camb). 2021; 57(70):8682-8698. DOI: 10.1039/d1cc03149j. View

Dong H, White C, Zhang B, Krebs C, Lehnert N . Non-Heme Diiron Model Complexes Can Mediate Direct NO Reduction: Mechanistic Insight into Flavodiiron NO Reductases. J Am Chem Soc. 2018; 140(41):13429-13440. DOI: 10.1021/jacs.8b08567. View

Gomes C, Giuffre A, Forte E, Vicente J, Saraiva L, Brunori M . A novel type of nitric-oxide reductase. Escherichia coli flavorubredoxin. J Biol Chem. 2002; 277(28):25273-6. DOI: 10.1074/jbc.M203886200. View

Zheng S, Berto T, Dahl E, Hoffman M, Speelman A, Lehnert N . The functional model complex [Fe2(BPMP)(OPr)(NO)2](BPh4)2 provides insight into the mechanism of flavodiiron NO reductases. J Am Chem Soc. 2013; 135(13):4902-5. DOI: 10.1021/ja309782m. View

10.

Khatua S, Majumdar A . Flavodiiron nitric oxide reductases: Recent developments in the mechanistic study and model chemistry for the catalytic reduction of NO. J Inorg Biochem. 2014; 142:145-53. DOI: 10.1016/j.jinorgbio.2014.09.018. View

11.

Berto T, Hoffman M, Murata Y, Landenberger K, Ercan Alp E, Zhao J . Structural and electronic characterization of non-heme Fe(II)-nitrosyls as biomimetic models of the Fe(B) center of bacterial nitric oxide reductase. J Am Chem Soc. 2011; 133(42):16714-7. DOI: 10.1021/ja111693f. View

12.

Dong H, Speelman A, Kozemchak C, Sil D, Krebs C, Lehnert N . The Fe (NO) Diamond Core: A Unique Structural Motif In Non-Heme Iron-NO Chemistry. Angew Chem Int Ed Engl. 2019; 58(49):17695-17699. PMC: 6878145. DOI: 10.1002/anie.201911968. View

13.

Missall T, Lodge J, McEwen J . Mechanisms of resistance to oxidative and nitrosative stress: implications for fungal survival in mammalian hosts. Eukaryot Cell. 2004; 3(4):835-46. PMC: 500878. DOI: 10.1128/EC.3.4.835-846.2004. View

14.

Comba P, Gahan L, Mereacre V, Hanson G, Powell A, Schenk G . Spectroscopic characterization of the active Fe(III)Fe(III) and Fe(III)Fe(II) forms of a purple acid phosphatase model system. Inorg Chem. 2012; 51(22):12195-209. DOI: 10.1021/ic301347t. View

15.

Silaghi-Dumitrescu R, Kurtz Jr D, Ljungdahl L, Lanzilotta W . X-ray crystal structures of Moorella thermoacetica FprA. Novel diiron site structure and mechanistic insights into a scavenging nitric oxide reductase. Biochemistry. 2005; 44(17):6492-501. DOI: 10.1021/bi0473049. View

16.

Stuehr D, Gross S, Sakuma I, Levi R, Nathan C . Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med. 1989; 169(3):1011-20. PMC: 2189276. DOI: 10.1084/jem.169.3.1011. View

17.

Jiang Y, Hayashi T, Matsumura H, Do L, Majumdar A, Lippard S . Light-induced N₂O production from a non-heme iron-nitrosyl dimer. J Am Chem Soc. 2014; 136(36):12524-7. PMC: 4160282. DOI: 10.1021/ja504343t. View

18.

Lehnert N, Kim E, Dong H, Harland J, Hunt A, Manickas E . The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity. Chem Rev. 2021; 121(24):14682-14905. DOI: 10.1021/acs.chemrev.1c00253. View

19.

Jana M, Pal N, White C, Kupper C, Meyer F, Lehnert N . Functional Mononitrosyl Diiron(II) Complex Mediates the Reduction of NO to NO with Relevance for Flavodiiron NO Reductases. J Am Chem Soc. 2017; 139(41):14380-14383. DOI: 10.1021/jacs.7b08855. View

20.

Mills P, Rowley G, Spiro S, Hinton J, Richardson D . A combination of cytochrome c nitrite reductase (NrfA) and flavorubredoxin (NorV) protects Salmonella enterica serovar Typhimurium against killing by NO in anoxic environments. Microbiology (Reading). 2008; 154(Pt 4):1218-1228. DOI: 10.1099/mic.0.2007/014290-0. View