Comparison of Nonheme Manganese- and Iron-Containing Flavone Synthase Mimics

Abstract

Heme and nonheme-type flavone synthase enzymes, FS I and FS II are responsible for the synthesis of flavones, which play an important role in various biological processes, and have a wide range of biomedicinal properties including antitumor, antimalarial, and antioxidant activities. To get more insight into the mechanism of this curious enzyme reaction, nonheme structural and functional models were carried out by the use of mononuclear iron, [FeII(CDA-BPA*)]2+ (6) [CDA-BPA = N,N,N’,N’-tetrakis-(2-pyridylmethyl)-cyclohexanediamine], [FeII(CDA-BQA*)]2+ (5) [CDA-BQA = N,N,N’,N’-tetrakis-(2-quinolilmethyl)-cyclohexanediamine], [FeII(Bn-TPEN)(CH3CN)]2+ (3) [Bn-TPEN = N-benzyl-N,N’,N’-tris(2-pyridylmethyl)-1,2- diaminoethane], [FeIV(O)(Bn-TPEN)]2+ (9), and manganese, [MnII(N4Py*)(CH3CN)]2+ (2) [N4Py* = N,N-bis(2-pyridylmethyl)-1,2-di(2-pyridyl)ethylamine)], [MnII(Bn-TPEN)(CH3CN)]2+ (4) complexes as catalysts, where the possible reactive intermediates, high-valent FeIV(O) and MnIV(O) are known and well characterised. The results of the catalytic and stoichiometric reactions showed that the ligand framework and the nature of the metal cofactor significantly influenced the reactivity of the catalyst and its intermediate. Comparing the reactions of [FeIV(O)(Bn-TPEN)]2+ (9) and [MnIV(O)(Bn-TPEN)]2+ (10) towards flavanone under the same conditions, a 3.5-fold difference in reaction rate was observed in favor of iron, and this value is three orders of magnitude higher than was observed for the previously published [FeIV(O)(N2Py2Q*)]2+ [N,N-bis(2-quinolylmethyl)-1,2-di(2-pyridyl)ethylamine] species.

Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

“…The catalytic mechanism of FNS I/FNS II is a radical reaction mediated by non‐heme iron or heme iron (Figure S19) [25] . The catalysis of CfoJ is an FMN‐dependent reaction, which is obviously different from that of FNSs.…”

“…The catalytic mechanism of FNS I/FNS II is a radical reaction mediated by non-heme iron or heme iron (Figure S19). [25] The catalysis of CfoJ is an FMN-dependent reaction, which is obviously different from that of FNSs. In order to investigate the catalytic mechanism of CfoJ, the 3D structure was predicted using Alphfold2.…”

Metal Stereogenicity in Asymmetric Transition Metal Catalysis

“…The efficiency of complex M54 in asymmetric catalysis was depicted by the group in the enantioselective oxidation of 4-methoxythioanisole ( 79 ) to its chiral sulfoxide ( R )- 80 in high yield with 98% ee. The complex was later also applied to an asymmetric hydroxylation of ethylbenzene and other stoichiometric oxidation reactions. − …”