Die Hydrogenobyrsäure‐Struktur enthüllt den Corrin‐Liganden als entatisches Zustandsmodul zur Steigerung der Katalyseaktivität von B₁₂‐Cofaktoren

Abstract

Die B 12 -Cofaktoren erzeugen eine natürliche Neugier bezüglichd er ursprünglichen Selektion und Evolution ihres Corrin-Liganden. Bisher entzogs ich dieser wichtige na-türlicheM akrocyclus überraschenderweise einer detaillierten Untersuchung, sodass seine spezifischeR olle bei der Prädisposition des eingebauten Cobalt-Ions zur organometallischen Katalyse ungeklärt blieb.H ier berichten wir über die Hydrogenobyrsäure (Hby), den cobaltfreien Corrin-Liganden von Vitamin B 12 ,der über eine neuartig programmierte Biosynthese hergestellt wurde.D etaillierte Einblicke in die Rçntgen-Einkristall-und Lçsungs-Strukturen der Hby zeigten einen verzerrt helikalen Hohlraum, der das Bindungsmuster fürCobalt-Ionen in B 12 redefiniert. Der Corrin-Ligand koordiniert Cobalt-Ionen in unsymmetrischen entatischen Zuständen, was B 12 -Cofaktoren füra nspruchsvolle chemische Übergänge aktiviert. Die Verfügbarkeit von Hby erçffnet auch neue Syntheserouten für Übergangsmetallanaloga von Vitamin B 12 .

Zinc Substitution of Cobalt in Vitamin B12: Zincobyric acid and Zincobalamin as Luminescent Structural B12‐Mimics

“…Acomparison of the crystal structures of Znby and Hby [3] (Figure 4a nd Supporting Information, Table S4) indicates am inor increase only in the radial size of the coordination hole on Zn-binding. Thea verage lengths of the N1-N3 and N2-N4 diagonals in Hby (d = 3.82 )a nd in Znby (d = 3.84 )are similar.…”

“…The biological use of cobalt as the specific transition metal center in natural B 12 -cofactors and the interaction between cobalt and the corrin ligand raise intriguing questions concerning the origins of its natural selection. [1] Engineered B 12 -biosynthesis [2] has opened up ap reparative route to hydrogenobyric acid (Hby), [3] the metal-free corrin ligand of vitamin B 12 ,p roviding an excellent opportunity for the synthesis of transition-metal analogues of the natural cobaltcorrinoids. [4] Zn II -analogues of natural corrinoids have hardly been explored [4b] but are attractive,asZn-and low-spin Co IIcenters exhibit similar structural properties in small complexes and in metalloproteins.…”

“…[4a, 6] Indeed, in the Eschenmoser [7] and Woodward labs [8] a5 ,15-nor-zincobyrinate was an intermediate of the B 12 -synthesis.U V/Visspectroscopically characterized samples of zincobalamin (Znbl)a nd zincobyric acid (Znby), the Zn-analogues of vitamin B 12 (CNCbl)and cobyric acid (Cby)(Scheme 1), were first reported by Koppenhagen and Pfiffner. [9] Herein, we delineate an effective synthesis of Znby and of Znbl,s tarting from crystalline Hby, [3] describe the pertinent spectroscopic and structural properties of these luminescent B 12 -derivatives and report ak inetic study of the binding of Zn II -ions to Hby.Znby was prepared at room temperature in 83 %yield from Hby [3] and Zn II acetate (see Scheme 2and the Supporting Information). Zn II -ions bound to Hby readily under these conditions (Supporting Information, Figure S4), and over 20 times faster than Co II -ions.…”

Hypothesis: entaticversusecstatic states in metalloproteins

“…The joint groups of Watter and Kräutler reported the biosynthesis of the cobalt-free B 12 corrin and concluded from its X-ray structure that ''the corrin ligand coordinates cobalt ions in de-symmetrized 'entatic' states''. 5 This assignment actually presents a head-on collision with the original entatic-state hypothesis which mandatorily required the presence of a protein (or a similarly large structure with a flattened energy landscape). The entatic cobalamin is actually a present-day mark of an increasing trend that developed over the last two decades in which ever more non-protein, free coordination compounds were stickered as entatic-state complexes.…”

“…Note that entasis has been a framework to describe the chemistry of radical-forming Co(II)balamin systems but only for the metal site and only for the situation before the homogeneous Co-C bond splitting. 5 Likewise, entasis in the active site of Fusarium spp. galactose oxidase was ascribed solely to the Cu(II) site and not to the Cu-coordinating tyrosine radical.…”