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

Abstract

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.

Ultrafast Excited State Dynamics and Fluorescence from Vitamin B12 and Organometallic [Co]–C≡C–R Cobalamins

“… 29 , 33 , 34 The structure is less pronounced in the αβ-band of so-called “atypical” cobalamins, including the biologically active coenzymes AdoCbl and MeCbl (see Figure S1 ). The absorption spectrum of the zinc analogue zincobalamin (Znbl), 35 also plotted in Figure 2 , is similar to the typical cobalamins, although blue-shifted by ca. 24 nm (800 cm –1 ).…”

“…This hypothesis is further supported by comparison of spectra of the metal free hydrogenobyric acid (Hby) and zinc-substituted zincobyric acid (Znby). 35 , 36 …”

“…Fluorescence from the ππ* state of the corrin ring has been reported for metal-free corrins. 36 − 38 The fluorescence spectra of metal-free corrins 36 , 38 and Zn corrins 35 exhibit varied vibrational structure, providing the strongest evidence to date for a vibrational assignment of the αβ-band absorption of “typical” cobalamins. 34 , 39 The data on the metal free corrins are complicated, however, as their strong emission in the visible features considerable temperature dependence.…”

“…34 , 39 The data on the metal free corrins are complicated, however, as their strong emission in the visible features considerable temperature dependence. 36 , 38 The zinc corrins also exhibit strong fluorescence spectra with a clear vibrational progression, 35 although the rapid decrease in intensity at longer wavelengths suggests that the entire width of the αβ-band in the absorption spectrum cannot be attributed to a vibrational progression in a single electronic state (see below).…”

Resonance Raman Optical Activity Spectroscopy in Probing Structural Changes Invisible to Circular Dichroism Spectroscopy: A Study on Truncated Vitamin B12 Derivatives

“…These methods supported by a theoretical approach guarantee insight into the complex nature and electronic or vibrational properties of corrinoids. As it turned out, there is a range of factors influencing the electronic character of the corrin chromophore e.g., (1) type of the central metal ion [ 33 , 34 ]; (2) type of axial ligands attached to the metal ion [ 35 , 36 , 37 ]; (3) oxidation state of the cobalt center [ 27 , 38 ]; (4) character of substituents attached to the corrin ring or presence/absence of the nucleotide loop [ 18 , 39 ]. Also, electronic circular dichroism spectroscopy (ECD) has proven to be a sensitive method for the detection of a substitution at the central cobalt ion or functionalization of the corrinoid ring [ 37 , 40 ].…”