The B12 cofactors instill a natural curiosity regarding the primordial selection and evolution of their corrin ligand. Surprisingly, this important natural macrocycle has evaded molecular scrutiny, and its specific role in predisposing the incarcerated cobalt ion for organometallic catalysis has remained obscure. Herein, we report the biosynthesis of the cobalt‐free B12 corrin moiety, hydrogenobyric acid (Hby), a compound crafted through pathway redesign. Detailed insights from single‐crystal X‐ray and solution structures of Hby have revealed a distorted helical cavity, redefining the pattern for binding cobalt ions. Consequently, the corrin ligand coordinates cobalt ions in desymmetrized “entatic” states, thereby promoting the activation of B12‐cofactors for their challenging chemical transitions. The availability of Hby also provides a route to the synthesis of transition metal analogues of B12.

Replacing the central cobalt ion of vitamin B12 by other metals has been a long‐held aspiration within the B12‐field. Herein, we describe the synthesis from hydrogenobyric acid of zincobyric acid (Znby) and zincobalamin (Znbl), the Zn‐analogues of the natural cobalt‐corrins cobyric acid and vitamin B12, respectively. The solution structures of Znby and Znbl were studied by NMR‐spectroscopy. Single crystals of Znby were produced, providing the first X‐ray crystallographic structure of a zinc corrin. The structures of Znby and of computationally generated Znbl were found to resemble the corresponding CoII‐corrins, making such Zn‐corrins potentially useful for investigations of B12‐dependent processes. The singlet excited state of Znby had a short life‐time, limited by rapid intersystem crossing to the triplet state. Znby allowed the unprecedented observation of a corrin triplet (ET=190 kJ mol−1) and was found to be an excellent photo‐sensitizer for 1O2 (ΦΔ=0.70).

Vitamin B is made by only certain prokaryotes yet is required by a number of eukaryotes such as mammals, fish, birds, worms, and Protista, including algae. There is still much to learn about how this nutrient is trafficked across the domains of life. Herein, we describe ways to make a number of different corrin analogs with fluorescent groups attached to the main tetrapyrrole-derived ring. A further range of analogs were also constructed by attaching similar fluorescent groups to the ribose ring of cobalamin, thereby generating a range of complete and incomplete corrinoids to follow uptake in bacteria, worms, and plants. By using these fluorescent derivatives we were able to demonstrate that Mycobacterium tuberculosis is able to acquire both cobyric acid and cobalamin analogs, that Caenorhabditis elegans takes up only the complete corrinoid, and that seedlings of higher plants such as Lepidium sativum are also able to transport B.

Replacing the central cobalt ion of vitamin B 12 by other metals has been al ong-held aspiration within the B 12field. Herein, we describe the synthesis from hydrogenobyric acid of zincobyric acid (Znby)a nd zincobalamin (Znbl), the Zn-analogues of the natural cobalt-corrins cobyric acid and vitamin B 12 ,r espectively.T he solution structures of Znby and Znbl were studied by NMR-spectroscopy. Single crystals of Znby were produced, providing the first X-ray crystallographic structure of az inc corrin. The structures of Znby and of computationally generated Znbl were found to resemble the corresponding Co II -corrins,m aking such Zn-corrins potentially useful for investigations of B 12 -dependent processes.The singlet excited state of Znby had as hort life-time,l imited by rapid intersystem crossing to the triplet state. Znby allowed the unprecedented observation of ac orrin triplet (E T = 190 kJ mol À1 )and was found to be an excellent photo-sensitizerThe 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. [5] Fischli and Eschenmoser reported the synthesis and characterization of the first Zn-corrin (ZnCor), when exploring the synthesis and chemistry of corrins in model studies towards the total synthesis of vitamin B 12 . [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 Scheme 1. Formulae of metal-free, cobalt-and zinc-corrinoids. Left: General formula of the cobalamins vitamin B 12 (R = CN, CNCbl), coenzyme B 12 (R = 5'-deoxyadenosyl, AdoCbl), cob(II)alamin (R = e À , Cbl II )C enter:F ormulae of hydrogenobyric acid (Hby), Co II -cobyric acid (Cby II )and zincobyrate (Znby), where the axial solvent ligands for both the Zn II and Co II have been omitted. Right:formula of zincobalamin (Znbl)i nits "base-on"f orm.

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 .