Reversible Formation of Alkyl Radicals at [Fe4S4] Clusters and Its Implications for Selectivity in Radical SAM Enzymes.
J Am Chem Soc
; 142(33): 14240-14248, 2020 08 19.
Article
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| MEDLINE
| ID: mdl-32696642
ABSTRACT
All kingdoms of life use the transient 5'-deoxyadenosyl radical (5'-dAdoâ¢) to initiate a wide range of difficult chemical reactions. Because of its high reactivity, the 5'-dAdo⢠must be generated in a controlled manner to abstract a specific H atom and avoid unproductive reactions. In radical S-adenosylmethionine (SAM) enzymes, the 5'-dAdo⢠is formed upon reduction of SAM by an [Fe4S4] cluster. An organometallic precursor featuring an Fe-C bond between the [Fe4S4] cluster and the 5'-dAdo group was recently characterized and shown to be competent for substrate radical generation, presumably via Fe-C bond homolysis. Such reactivity is without precedent for Fe-S clusters. Here, we show that synthetic [Fe4S4]-alkyl clusters undergo Fe-C bond homolysis when the alkylated Fe site has a suitable coordination number, thereby providing support for the intermediacy of organometallic species in radical SAM enzymes. Addition of pyridine donors to [(IMes)3Fe4S4-R]+ clusters (R = alkyl or benzyl; IMes = 1,3-dimesitylimidazol-2-ylidene) generates Râ¢, ultimately forming R-R coupled hydrocarbons. This process is facile at room temperature and allows for the generation of highly reactive radicals including primary carbon radicals. Mechanistic studies, including use of the 5-hexenyl radical clock, demonstrate that Fe-C bond homolysis occurs reversibly. Using these experimental insights and kinetic simulations, we evaluate the circumstances in which an organometallic intermediate can direct the 5'-dAdo⢠toward productive H-atom abstraction. Our findings demonstrate that reversible homolysis of even weak M-C bonds is a feasible protective mechanism for the 5'-dAdo⢠that can allow selective X-H bond activation in both radical SAM and adenosylcobalamin enzymes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
S-Adenosilmetionina
/
Sulfuros
/
Hierro
/
Proteínas Hierro-Azufre
Idioma:
En
Revista:
J Am Chem Soc
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos