Peptide Metal–Organic Frameworks for Enantioselective Separation of Chiral Drugs

Abstract

We report the use of a chiral Cu(II) 3D metal-organic framework (MOF) based on the tripeptide Gly-l-His-Gly (GHG) for the enantioselective separation of metamphetamine and ephedrine. Monte Carlo simulations suggest that chiral recognition is linked to preferential binding of one of the enantiomers as a result of either stronger or additional H-bonds with the framework that lead to energetically more stable diastereomeric adducts. Solid-phase extraction of a racemic mixture by using Cu(GHG) as the extractive phase permits isolating >50% of the (+)-ephedrine enantiomer as target compound in only 4 min. To our knowledge, this represents the first example of a MOF capable of separating chiral polar drugs.

Biologically derived metal organic frameworks

“…[231] Martí-Gastaldo et al reported a chiral Cu II 3-dimensional bio-MOF based on Gly-L-His-Gly (GHG) for the enantioselective separation of methamphetamine and ephedrine. [232] While both compounds are well known as recreational drugs, they are also components used in the preparation of therapeutics such as bronchodilators and respiratory stimulants. [232] Cu(GHG) is constructed through an interconnecting four-fold helicoidal Cupeptide-Cu chains via a µ2-carboxylate bridging C-terminal Gly, with porosity forming via interconnected 1-dimensional empty channels.…”

“…[232] While both compounds are well known as recreational drugs, they are also components used in the preparation of therapeutics such as bronchodilators and respiratory stimulants. [232] Cu(GHG) is constructed through an interconnecting four-fold helicoidal Cupeptide-Cu chains via a µ2-carboxylate bridging C-terminal Gly, with porosity forming via interconnected 1-dimensional empty channels. [232] Post-synthetic modification of the peptide allows a variety of functional groups (carboxylate, amide, amino and imidazole) to be added to the surface of the pore with the groups pointing into the channel.…”

“…[232] Cu(GHG) is constructed through an interconnecting four-fold helicoidal Cupeptide-Cu chains via a µ2-carboxylate bridging C-terminal Gly, with porosity forming via interconnected 1-dimensional empty channels. [232] Post-synthetic modification of the peptide allows a variety of functional groups (carboxylate, amide, amino and imidazole) to be added to the surface of the pore with the groups pointing into the channel. The Cu(GHG) crystals display a sponge-like behaviour with a reversible crystalline-to-amorphous transformation after activation.…”

“…Initial studies to recognize the selectivity were performed by soaking the bio-MOF in racemic mixtures of methamphetamine and ephedrine, resulting in a 30 ± 3 % and 37 ± 3 % adsorption of (+)-methamphetamine and (+)-ephedrine, respectively. [232] These results are attributed to the preferential interaction of the (+)-enantiomers in the chiral pocket of the bio-MOF that aid in hydrogen bond formation with the His side chain. [232] The authors further demonstrated the applicability of their work by packing 50 mg of…”

“…[232] These results are attributed to the preferential interaction of the (+)-enantiomers in the chiral pocket of the bio-MOF that aid in hydrogen bond formation with the His side chain. [232] The authors further demonstrated the applicability of their work by packing 50 mg of…”