Trans and cis effects of axial fluoroalkyl ligands in vitamin B12 analogues: relationship between alkyl- and fluoroalkyl-cobalamins.
CF2HCbl, CF3Cbl , and CF3CH2Cbl have been synthesized and characterized in solution by (1)H NMR and UV-vis spectroscopy, and their X-ray crystal structures have been determined using synchrotron radiation. The structure of CF3CH2Cbl is reported for the first time, whereas those of CF2HCbl and CF3Cbl are re-examined to obtain more precise structural data. Comparison of the structural data obtained with the alkylcobalamin analogues, MeCbl and EtCbl, indicates that the Co-C and Co-NB3 bond lengths are shorter in the fluoroalkylcobalamins. The structural data of the fluoroalkylcobalamins previously reported in the literature had been conflicting in this regard. Thus, a much less dramatic shortening of the two axial bonds was found for CF3Cbl, whereas in the case of CF2HCbl, the Co-NB3 bond length is shorter than in MeCbl. Direct comparison of the structures of CF3CH2Cbl and EtCbl indicates a large distortion of the axial fragment in the former case that can be attributed to steric effects. A number of previously reported correlations of the effect of the β-ligand on the structure and properties of cobalamins are re-examined in light of the present results. Particular emphasis is placed on the axial fragment. This analysis substantially confirms and, with the new data reported here, adjusts and expands the data set for correlations between trans and cis influences of the β-ligand of cobalamins and their structure (Co-X and Co-NB3 distances and corrin fold angle) and properties (UV-vis spectra, NMR spectra, and pK(base-off)).
Department of Chemical and Pharmaceutical Sciences, University of Trieste , 34127 Trieste, Italy.
Lucio
L
Randaccio
Giovanna
G
Brancatelli
Nicola
N
Demitri
Renata
R
Dreos
Neal
N
Hickey
Patrizia
P
Siega
Silvano
S
Geremia
D000478:Alkylation; D018360:Crystallography, X-Ray; D054879:Halogenation; D007536:Isomerism; D008958:Models, Molecular; D014805:Vitamin B 12 / Q000031:analogs & derivatives*; D014803:Vitamin B Complex / Q000737:chemistry*
D014803:Vitamin B Complex; D014805:Vitamin B 12