Artificial metalloenzymes derived from bovine β-lactoglobulin for the asymmetric transfer hydrogenation of an aryl ketone – synthesis, characterization and catalytic activity†
A series of diimines derived from saturated and unsaturated fatty acids and including a dipyridylamine (dpa) or a bispyridylmethane (bpm) scaffold as a chelating moiety were synthesized and characterized spectroscopically. Complexation by [LM(μ-Cl)Cl]2 (M = Ru, L = p-cymene; M = Rh, L = Cp*) afforded the monocationic, mononuclear complexes of general formula [LM(N^N)Cl]Cl with N^N being the diimine ligand. Unsurprisingly, these new complexes catalysed the transfer hydrogenation of an activated aromatic ketone, namely 2,2,2-trifluoroacetophenone (TFACP), in water at neutral pH and mild temperature in the presence of formate as a hydrogen donor. The catalytic activity of the complexes expressed as TOF was shown to depend not only on the metal (Ru or Rh) but also on the chelating entity (dpa or bpm) and the length and nature of the lipidic chain tethered to it. Incorporation of the complexes within bovine β-lactoglobulin (βLG) as the protein host was studied by circular dichroism and fluorescence spectroscopy and again noticeable differences were observed between the saturated and unsaturated fatty acid derivatives. Eventually, the ability of the protein hybrids to catalyse the transfer hydrogenation of TFACP was demonstrated. Good-to-quantitative conversions in the corresponding alcohol were reached within 72 h with the rhodium(III) hybrids and the best enantioselectivities (up to 32% ee for the (R)-enantiomer) were measured with the Rh(III) cofactors derived from palmitic and stearic acids once incorporated into the isoform A of βLG.