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

Abstract

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).

Replacement of the Cobalt Center of Vitamin B12 by Nickel: Nibalamin and Nibyric Acid Prepared from Metal‐Free B12 Ligands Hydrogenobalamin and Hydrogenobyric Acid

“…[18] Ac ommon feature of the valence shell of the low spin states of the transition metal ions Ni II ,C o III ,C o II and Co I is their unoccupied d x 2 Ày 2 orbital, ak ey factor responsible for their strong sigma bonding interactions with the four inner corrin Na toms,l eading to similar radial characteristics of their corrin complexes.Adiffering number of valence shell electrons in Ni II -, Co III -, Co II -a nd Co I -corrins is transduced primarily into characteristically different reactivity of the metal centers in the axial direction, strongly affecting their potential binding sites there.Consequently,Ni II -corrins are to be considered particularly well-suited structural mimics of corresponding isoelectronic Co I -corrins,t he critical intermediates in heterolytic organometallic transitions in B 12dependent enzymes. [28] Crystallographic insights and DFTbased structure calculations also indicate as tructural similarity between Ni II -corrins and the exceptional four-coordinate Co II -corrins.T his result contrasts strikingly with the mutually different structures of the typical five-coordinate Co II -corrins and their Zn II -analogues [5] with similarly sized metal ions [29] that differ by the number of electrons in the valence shell.…”

“…[3] Themethyl group singlet of H 3 C1 at d = 0.81 ppm occurred at 0.47 ppm to higher field, compared to Hby,s uggesting at emporary residence of the heteroaromatic DMB unit of Hbl near to its corrin moiety,aconclusion that was further supported by weak inter-residual correlations in the 1 H, 1 HROESY spectra (see SI, Figure S13). However, the signals of the DMB moiety (HN2 at d = 8.35 ppm, HN4 at d = 7.31 ppm, HCN7 at d = 7.30 ppm) were found at similar chemical shift values to those of the free B 12 nucleotide, [12] effectively incompatible with at ime-averaged positioning of the DMB part close to the corrin chromophore,a sfound for zincobalamin (Znbl) [5] and for typical "base-on" Co III Cbls. [14] TheNi II -corrin nibalamin (Nibl)was prepared by heating adeoxygenated aqueous solution of Hbl and Ni(OAc) 2 for 1h at 90 8 8C(Scheme 2), furnishing Nibl in 77 %yield as ayellow powder.A nu nbuffered aqueous solution of Nibl exhibited aUV/Vis spectrum that is incompatible with coordination by the DMB base and nearly indistinguishable (at > 300 nm) from the spectrum of Niby,and similar to the spectrum of the Ni II -corrin NiCor [6a,c] (see Figure 1).…”

“…The methyl group singlet of H 3 C1 at δ =0.81 ppm occurred at 0.47 ppm to higher field, compared to Hby , suggesting a temporary residence of the heteroaromatic DMB unit of Hbl near to its corrin moiety, a conclusion that was further supported by weak inter‐residual correlations in the 1 H, 1 H ROESY spectra (see SI, Figure S13). However, the signals of the DMB moiety (HN2 at δ =8.35 ppm, HN4 at δ =7.31 ppm, HCN7 at δ =7.30 ppm) were found at similar chemical shift values to those of the free B 12 nucleotide, [12] effectively incompatible with a time‐averaged positioning of the DMB part close to the corrin chromophore, as found for zincobalamin ( Znbl ) [5] and for typical “base‐on” Co III Cbls [14]…”

“…[4] We have recently used Hby for the synthesis of the corresponding zinc-corrin zincobyric acid (Znby)and the Zn analogue of vitamin B 12 zincobalamin (Znbl), of interest as luminescent structural B 12 mimics. [5] Herein, we report on the first nickel-complexes of natural corrin ligands,i ncluding nibalamin (Nibl). We also describe the syntheses of crystalline nibyric acid (Niby), the novel Ni II complex of Hby, [3] and hydrogenobalamin (Hbl), the metalfree complete B 12 ligand (see Scheme 1a nd Scheme 2).…”

“…The availability of Hby has provided an unparalleled opportunity for the effective synthesis of metal‐free and transition metal analogues of the natural cobalt‐corrinoids a previously intractable challenge in bioinorganic and B 12 chemistry [4] . We have recently used Hby for the synthesis of the corresponding zinc‐corrin zincobyric acid ( Znby ) and the Zn analogue of vitamin B 12 zincobalamin ( Znbl ), of interest as luminescent structural B 12 mimics [5] …”