# Determination of Enantiomeric Excess in Confined Aprotic Solvent

## TL;DR

This paper introduces a new nanopore-based method for quickly and cheaply measuring the stereochemical purity of compounds, which is important for drug production.

## Contribution

A novel nanopore-based platform using ion-current rectification for rapid enantiomeric excess determination is introduced.

## Key findings

- The nanopore method distinguishes enantiomers through changes in ion-current rectification.
- The platform successfully determined enantiomeric excess for multiple compounds in minutes.
- The method uses low-cost equipment and minimal sample volumes.

## Abstract

The validation of the stereochemical purity of synthesized
compounds
is a requisite for the fine-chemical industry, particularly in the
production of enantiopure drug compounds. However, most methodologies
employed in the determination of enantiopurity require carefully chosen
chiral GC or HPLC columns, increasing associated cost, analysis time,
and complexity. Herein, we present a nanopore-based technology for
the determination of enantiopurity, exploiting changes in ion-current
rectification of quartz nanopipettes containing an aprotic organic
electrolyte. Changes in solvent ordering at the quartz surface upon
enantiomerically preferential adsorption give rise to distinguishable
current-voltage responses. The applicability of our simple and cost-effective
platform is demonstrated through the determination of the enantiomeric
excess of commercially available (R)- and (S)-enantiomers of 4-methoxy-α-methylbenzylamine and
duloxetine hydrochloride, as well as the product of a decarboxylative
asymmetric allylic alkylation. Ion-current rectification (ICR)-based
enantiomeric excess determination is completed within minutes, using
negligible sample volumes and with simple low-cost electrical instrumentation.