Abstract
It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1–S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.
Highlights
Because of the cooperation of the catalytic centre and the second coordination sphere, a native metalloenzyme can achieve biological transformations with remarkable efficiency and enantioselectivity under mild conditions in vivo[1,2]
We reported the construction of metallohydrolase mimics and superoxide dismutase mimics with CD domains[5,33,34,35,36,37,38,39]
Because of the relationship between coordination geometry and catalytic ability, we were interested in probing the coordination geometries of the copper(II) centre by using electron paramagnetic resonance (EPR) spectroscopy, which were performed at 100 K in a frozen solution of water and dimethylsulfoxide (DMSO)
Summary
Because of the cooperation of the catalytic centre and the second coordination sphere, a native metalloenzyme can achieve biological transformations with remarkable efficiency and enantioselectivity under mild conditions in vivo[1,2]. The chiral nature of the CD cavity, the cooperative effects of CDs with coordinated metal ion, has been somewhat underestimated. A number of studies have reported the use of unmodified or modified CD monomers without metal ions for the enantioselective deacylation of chiral esters[26,27,28,29,30,31,32]. Interactions with coordinated metal ions have rarely been reported, and the cooperative mechanism remains unclear. Chiral t-butyloxycarbonyl (Boc)-protected aromatic amino acid esters S1-S3 were chosen as substrates (Fig. 1) These substrates, which contain amino acid moieties, are biologically relevant than the previously used substrates and allowed us to evaluate the interactions of chiral CD cavities with naturally occurring substances. Electrospray ionization mass spectrometry (ESI-MS), an inhibition assay, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations were performed to gain deeper insights into the underlying mechanism
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