Enantioselective outer-sphere complexation of lanthanide(III) tris (pyridine-2,6-dicarboxylate) chelates with vitamin B 12 derivatives. An NMR and CD study

Abstract

The binding of three corrinoids, cyanocobalarnin (vitamin B 12, CNCbl), aquacobalamin (vitamin B 12a, H 2OCbl +) and dicyanocobinamide ((CN) 2Cbi), collectively denoted by Q, to the Δ- and Λ-enantiomer of Ln(DPA) 3 3− complexes (Ln=lanthanide, DPA=2,6-pyridine dicarboxylate) in aqueous solution at room temperature is investigated by NMR and Circular Dichroism (CD) spectroscopy. Tb(DPA) 3 3− induces shifts of the 1H-NMR resonances of Q. A formula, describing the dipolar interaction between the proton spin and the paramagnetic moment of the lanthanide complex, is fitted to the lanthanide induced shifts, yielding the position of Tb(DPA) 3 3− and the orientation of its magnetic axis with respect to the corrinoid. The magnitude of the shifts provide the value of K avg, an average of the association constants of the two diastereomeric complexes {Δ-Tb(DPA) 3 3−Q) and {Λ-Tb(DPA) 3 3−Q}. We find K avg=4±0.5 (B 12) and 0.8±0.2 M −1 ((CN) 2Cbi). The value for H 2OCbl + depends strongly on the solution’s ionic strength I: K avg=(7±1)×10 1, 22±5 and 16±7 M −1 at I=0.007, 0.12 and 0.22 M, respectively. The addition of the corrinoids to a (racemic) solution of Nd(DPA) 3 3−, induces CD in the electronic Nd(III) transitions in the 700–800 nm region (ICD). This Pfeiffer effect is attributed to an excess of Λ-Nd(DPA) 3 3− in the enantioselective, outer-sphere association with the corrinoids. From the magnitude of the ICD as a function of [Q], in conjunction with the (indirectly) determined CD effect of Λ-Nd(DPA) 3 3−, values are determined for K Δ− K Λ. We find K Δ− K Λ=−24±2 M −1 for H 2OCbl + at pH 6.7 and I=0.12 M and −12±2 M −1 at I=0.22 M; −4.4±0.5 M −1 for CNCbl and −0.9±0.3 M −1 for (CN) 2Cbi. Adopting the view that in the lanthanide series Ln(DPA) 3 3− chelates are isostructural, the results of the NMR and CD experiments are combined to estimate the enantioselectivity in the binding E b, defined as ( K Δ− K Λ)/2 K avg. We find E b=−0.5±0.2 for H 2OCbl +, −0.7±0.2 for CNCbl and −0.7±0.3 for (CN) 2Cbi. On the basis of the NMR data, a molecular structure is proposed for the two diastereomeric {Ln(DPA) 3 3−Q} complexes. The bonding involves hydrogen bonds between the amide proton on the a and g side chain of the corrinoid and the carboxylate oxygen of two DPA ligands.