Determining the Absolute Configuration of Small Molecules by Diffusion NMR Experiments

Author(s)

Gomes Cabral, Tadeu Luiz ; Dal Poggetto, Guilherme ; Brussolo da Silva, Joo Pedro ; Nilsson, Mathias ; Tormena, Claudio F.

• Document type: Journal article
• Source: LANCET GASTROENTEROLOGY & HEPATOLOGY; v. 10, n. 2, p. 6-pg., 2025-02-01.

Abstract

Enantiomers are ubiquitous in many areas of science, such as pharmaceuticals, agriculture, and food. Nuclear magnetic resonance (NMR) alone is not able to differentiate enantiomers as their spectra are identical. However, these can be distinguished using chiral auxiliaries (such as chiral complexing agents) that form diastereomeric complexes, but absolute identification is still troublesome, usually requiring a chemical reaction with a chiral derivatizing agent. Here, we propose a new method that uses a hybrid mixture of solvating agents in a simple comparison of diffusion NMR experiments, which can discriminate enantiomers in both frequency and diffusion domains, dubbed CHIMERA (CHIral Micelle Enantiomer Resolving Agent). The new method was assessed for twenty-three small chiral molecules using a combination of BINOL and (-)-DMEB, a chiral surfactant, and initial results indicate that absolute configuration can be obtained from a simple experiment. (AU)

• FAPESP's process: 21/05081-5 - Chiral micelles for matrix-assisted DOSY
• Grantee: Tadeu Luiz Gomes Cabral
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/10246-0 - Nuclear magnetic resonance spectroscopy: from pulse sequences to structural assignments
• Grantee: Claudio Francisco Tormena
• Support Opportunities: Research Projects - Thematic Grants