DFT analysis of co-alkyl and co-adenosyl vibrational modes in B12-cofactors

Abstract

Density functional theory (DFT)-based normal mode calculations have been carried out on models for B12-cofactors to assign reported isotope-edited resonance Raman spectra, which isolate vibrations of the organo-Co group. Interpretation is straightforward for alkyl-Co derivatives, which display prominent Co-C stretching vibrational bands. DFT correctly reproduces Co-C distances and frequencies for the methyl and ethyl derivatives. However, spectra are complex for adenosyl derivatives, due to mixing of Co-C stretching with a ribose deformation coordinate and to activation of modes involving Co-C-C bending and Co-adenosyl torsion. Despite this complexity, the computed spectra provide a satisfactory re-assignment of the experimental data. Reported trends in adenosyl-cobalamin spectra upon binding to the methylmalonyl CoA mutase enzyme, as well as on subsequent binding of substrates and inhibitors, provide support for an activation mechanism involving substrate-induced deformation of the adenosyl ligand.

Figure 1

Molecular structure of B₁₂ cofactors (left panel) where R = Me for MeCbl and R = Ado for AdoCbl (R₁ = CH₂CONH₂, R₂ = CH₂CH₂CONH₂, R₃ = (CH₂)₂CONHCH₂CH(CH₃)OPO₃) Right panel: structural model of B₁₂ cofactors employed in the present work, B–[Co^IIIcorrin]-R⁺ (B = DBI or Im, R = Me, Et, iso-Prop, or Ado).

Figure 2

Simulated nonresonance Raman spectra, in the low-frequency region, for the indicated Im–[Co^IIIcorrin]–R⁺ models (R = Me, Et, iso-Prop, and Ado). A uniform scaling factor (0.86) was applied to B3LYP force constants for all shown models.

Figure 3

Comparison of computed isotope difference spectra for Im–[Co^IIIcorrin]–R⁺ (R = Me and Et) with experimental spectra (ref 18) for MeCbl and EtCbl. Computed spectra are based on refined B3LYP force constants applying multiple scaling factors. The alignment of experimental spectra to one common scale might be slightly affected by electronic manipulation of digitalized data.

Figure 4

Comparison of computed isotope difference spectra for Im–[Co^IIIcorrin]–Ado⁺, with experimental spectra (ref for AdoCbl). Computed spectra are based on refined B3LYP force constants applying multiple scaling factors and empirical enhancement of Raman intensities for δ and τ modes (see text for details). The alignment of experimental spectra to one common scale might slightly be affected by electronic manipulation of digitalized data.

Figure 5

Schematic eigenvectors for the four isotope-sensitive Co–Ado modes identified in Figure 4.