Exceptional Photochemical Stability of the Co–C Bond of Alkynyl Cobalamins, Potential Antivitamins B₁₂ and Core Elements of B₁₂-Based Biological Vectors

Abstract

Alkynylcorrinoids are a class of organometallic B12 derivatives, recently rediscovered for use as antivitamins B12 and as core components of B12-based biological vectors. They feature exceptional photochemical and thermal stability of their characteristic extra-short Co–C bond. We describe here the synthesis and structure of 3-hydroxypropynylcobalamin (HOPryCbl) and photochemical experiments with HOPryCbl, as well as of the related alkynylcobalamins: phenylethynylcobalamin and difluoro-phenylethynylcobalamin. Ultrafast spectroscopic studies of the excited state dynamics and mechanism for ground state recovery demonstrate that the Co–C bond of alkynylcobalamins is stable, with the Co–N bond and ring deformations mediating internal conversion and ground state recovery within 100 ps. These studies provide insights required for the rational design of photostable or photolabile B12-based cellular vectors.

A Series of Mono- and Bis-Alkynyl Co(III) Complexes Supported by a Tetra-imine Macrocyclic Ligand (TIM)

“…Whereas the precedent of M(TIM)-based alkynyl complexes is lacking to the best of our knowledge, there are a number of . 43 A mono-phenylacetylide complex of Co IV (cz) (cz = corrolazine) was prepared from the reaction of Co III (cz) with phenyl acetylene in the presence of Et 3 N. 44 The reaction of aquocobalamin chloride (Co(III)) with RCCI (R = Phand HOCH 2 -) in the presence of triethylammonium formate under an inert atmosphere furnished the corresponding acetylide cobalamins, 45,46 where a Co(II) species generated from the reduction by formate was postulated as the key intermediate. In contrast, a reduction free synthesis of acetylide cobalamins was accomplished via a Hagihara coupling reaction (Cu(I)/base catalyzed).…”

Visualizing ultrafast chemical dynamics with X-rays

“…Measurements with parallel and perpendicular polarizations for the optical and X-ray pulses permit the assignment of the excited state structural changes to axial and equatorial motions. Comparisons with simulated difference spectra demonstrate that the excited state has an extended Co-N axial bond but the Co-C bond is locked at the ground state bond length, providing direct experimental insight into the mechanism for the photostability of this compound (13,14).…”

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

“… 8 − 10 The unique Co–C bond of organometallic Cbls also provides space for chemical manipulation of both their thermal and photochemical reactivity. 13 , 22 − 24 Strong Co–C bonds and their photochemical stability are exploited in a range of alkynyl cobalamins 23 , 25 , 26 designed as potential antivitamins B 12 . 27 …”

“…Cobalamins (Cbls, Figure ) comprise a unique class of cyclic tetrapyrroles with a cobalt ion bonded to a corrin ring, a lower dimethyl­benzimidazole ligand (DMB) covalently tethered to the corrin ring, and a variable upper axial ligand. − The lower axial DMB ligand can be replaced with histidine in some enzymes or by water in a protonated base-off configuration at low pH and is decoordinated without replacement in some proteins. − B 12 -dependent enzymes exploit the distinct reactive pathways of two organometallic Cbls: 5′-deoxyadenosyl­cobalamin (coenzyme B 12 or AdoCbl) and methyl­cobalamin (MeCbl). − These Cbls are also light sensitive and undergo photoinduced homolysis of their Co–C bond. − The unique Co–C bond of organometallic Cbls also provides space for chemical manipulation of both their thermal and photochemical reactivity. ,− Strong Co–C bonds and their photochemical stability are exploited in a range of alkynyl cobalamins ,, designed as potential antivitamins B 12 …”

“…Here we report broadband transient absorption and steady state fluorescence measurements for three photostable cobalamins, CNCbl, 3-hydroxypropynyl­cobalamin (HOPryCbl), and 2­[4,6-difluorophenyl]­ethynylcobalamin (F 2 PhEtyCbl) . The results are compared with steady state fluorescence measurements on the zinc corrin Znbl .…”