Angewandte
Chemie
situated slightly out of the plane of the four corrin nitrogen
atoms and is shifted by 0.031(1) ꢀ towards the a-DMB ligand,
two structural features similar to those of vitamin B12 (5). The
orientation of the phenyl group (in the crystal) is in “north–
south”, and the plane of the phenyl group has a twist of
15.36(10)8 relative to the DMB ligand. The angle of the triple
bond to the aromatic carbon is almost linear (C1L-C2L-
C3L = 179.2(4)8) whereas the Co-C1L-C2L angle (172.1(3)8)
sum of the covalent radii of an sp C (r= 0.69 ꢀ) and the
CoIII ion (see Figure 2). The length of the Co Cb bond of 4-
À
ethylphenyl cobalamin (1.98 ꢀ)[10] roughly matches the sum
of the covalent radii of an sp2 C (r= 0.73 ꢀ) and of the CoIII
ion, whereas in vinylcobalamin it is considerably shorter (by
about 0.08 ꢀ).[22] The structural data may thus suggest
À
a higher effective bond order of the Co Cb bonds to the
unsaturated carbon of ethynylcobalamin 3 (and of vinyl-
cobalamin). A similar situation would also hold for 5[16]
(Figure 2).
À
is slightly bent. The triple bond C1L C2L is longer
(1.209(5) ꢀ) than in organic alkynes (mean value of
1.18 ꢀ[17,18]). The bond C2L C3L (from the alkyne to the
The acetylide ligand of 2-phenylethynylcobalamin (3)
exerts a thermodynamic trans effect that is roughly similar to
that of the cyano group in 5. A similar observation was made
with ethynylcobalamin[11] and ethynylaquocobinamide.[23] The
trans effect of alkynyl groups falls outside of the range known
for alkyl and aryl groups in corresponding organocobala-
mins.[13] Thus, protonation of the DMB moiety of 3 is
insignificant even at pH 1.6, indicating a tightly cobalt-
bound DMB base. However, proteolytic detachment of the
phenylethynyl moiety occurred readily at this pH (t1/2 of about
15 min at room temperature), furnishing aquocobalamin (6)
and phenylacetylene (Supporting Information, Figures S6 and
S8). In the pH range from pH 2 to pH 5 the rate of
decomposition of 3 at room temperature decreased linearly
with the proton concentration, and 3 was extrapolated to be
effectively rather stable at pH 7 and room temperature (t1/2 ca.
350 days; Supporting Information, Figure S7). In contrast to
the acidolytic removal of the organometallic ligand of 3
observed here, ethynylcobalamin was reported to decompose
in acidic aqueous solution to acetylcobalamin by an acid-
induced addition of water to the ethynyl group.[11] In both
cases, the organometallic group presumably undergoes pro-
tonation at one of the sp-hybridized carbon atoms with
intermediate formation of a stabilized, metal-coordinated
vinyl cation. By this path, ethynylcobalamin is indicated to be
protonated at the terminal carbon, whereas 2-phenylethynyl-
cobalamin (3) appears to be protonated at the directly cobalt-
bound carbon.
À
phenyl group) has a length of 1.444(5) ꢀ, and is in the typical
range of sp2–sp bonds (mean value of 1.43 ꢀ[17]).
Not unexpectedly, the alkyne group of 3 is bound with
À
a short Co Csp bond (1.861(3) ꢀ), which is slightly shorter
than that reported for a model alkynyl CoIII complex.[19] The
À
length of the Co Cb bond in 3 also falls below the range found
in all other known organometallic B12 derivatives.[14,15]
À
Similarly, the trans-axial Co Na bond of 3 (2.084(2) ꢀ) is
also shorter than in other organometallic B12 derivatives
(Figure 2). The correlated shortening (or lengthening) of the
two axial bonds is a qualitative feature of organocorrinoids
and has been described as the inverse “structural” trans
effect.[14,15]
As expected, 2-phenylethynylcobalamin (3) displayed
À
a high intrinsic resistance to thermolytic cleavage of its Co
C bond: a deoxygenated solution of 3 in dry DMSO could be
heated to 1008C for 5 days without significant decomposition
(see the Supporting Information for details). An oxygen-
saturated solution of 3 in [D6]DMSO decomposed slowly at
1008C (t1/2 > 72 h), giving 6 and other Co-corrins (Supporting
Information, Figures S11 and S12). At 1208C 3 eventually
decomposed in [D6]DMSO (with a half-life of about 30 h) to
a mixture of Co-corrins and some phenylacetylene. The
decomposition products formed at this temperature were
Figure 2. Lengths of axial bonds in selected organometallic B12 deriva-
À
tives (see text). The Cb Co bond lengths of organocobalamins
correlate with the s character of the Co-bound carbon; that is, Csp
À
À
À
Co <Csp2 Co <Csp3 Co. However, the organometallic bonds of the
ethynylcobalamin 3, of vinylcobalamin, and of vitamin B12 (5) are
shorter than expected on the basis of the sum of the corresponding
radii of covalent single bonds of C and of an (octahedral) CoIII center
(see marks “x” on the dotted line).[20] Ado=5’-deoxyadenosyl.
À
largely indicative of the cleavage of the Co C bond.
In further contrast to other organocobalamins, an aerated
aqueous solution of 3 did not undergo significant spectral
changes when exposed to daylight for 75 h (Supporting
Information, Figure S15). However, this observation is con-
sistent with early findings with ethynylcobalamin,[13] and it is
in line with the remarkable photostability of vitamin B12
(5).[24]
À
As shown in Figure 2, the lengths of the Co C bonds of
model organocobalamins correlate qualitatively with the
hybridization of the directly bound carbon atom.[18] In fact,
À
the length of the Co Cb bonds in coenzyme B12 (1), methyl-
cobalamin (2),[14,15] and ethylcobalamin[21] roughly matches
the sum of the covalent radii of an sp3 C (r= 0.76 ꢀ) and of
a low-spin CoIII ion (r= 1.26 ꢀ).[20] However, in 3 the Co Cb
To explore the potential use of Cob-2-phenylethynylcoba-
lamin (3) in studies with mammals, binding of 3 to the
À
bond (1.861 ꢀ) is strikingly shorter by about 0.09 ꢀ than the
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!
Ruetz, Markus
