# An Amino-Acid-Derived Metal–Organic Framework with Large Pores for Unspecific Enantioseparation

## TL;DR

A new metal-organic framework with large pores is developed to efficiently separate enantiomers of various chiral compounds, including complex pharmaceuticals.

## Contribution

A homochiral MOF with a giant chiral cavity is created for versatile enantioseparation of diverse and bulky substrates.

## Key findings

- The MOF features a 2.2 × 3.1 nm chiral cavity with 42 phenylalanine residues for enantioselective adsorption.
- It enables separation of structurally complex chiral pharmaceuticals and bulky substrates.
- The material can be reused without performance loss and applied in membrane separation processes.

## Abstract

The selective separation
of enantiomers is critical in
pharmaceutical
production, while conventional chiral sorbents always suffer from
the trade-off between selectivity and the substrate scope. Herein,
inspired by a natural unspecific peroxygenase with large protein channels,
we developed a homochiral metal–organic framework (MOF) constructed
from flexible phenylalanine-derived ligands and zinc ions. This MOF
features a giant chiral cavity with a size of 2.2 × 3.1 nm, decorated
with 42 chiral phenylalanine residues, which serves as a solid sorbent
for the highly enantioselective adsorption and separation of diverse
chiral compounds, including aromatic epoxides, β-nitroalcohols,
mandelate derivatives, secondary alcohols, indolin-3-ones, α-methylbenzylamine,
and limonene. Most importantly, benefiting from its large pores, the
MOF demonstrates versatile utility in resolving the enantiomers of
extraordinarily bulky substrates and structurally complex chiral pharmaceuticals,
which can be further processed into a polymer matrix for membrane
separation, enabling an integrated, chromatography-free route from
batch-scale adsorption and separation. This material can be readily
recovered and reused without an apparent loss of performance. Adsorption
experiments and theoretical calculations reveal that the chiral recognition
and separation originate from the distinct binding affinity of enantiomers
within the MOF’s chiral pore environment, presenting a scalable
platform for process-intensified chiral separations.