Complete resonance assignment of a pharmaceutical drug at natural isotopic abundance from DNP-Enhanced solid-state NMR.
Solid State Nucl Magn Reson
; 119: 101794, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35462269
ABSTRACT
Solid-state dynamic nuclear polarization enhanced magic angle spinning (DNP-MAS) NMR measurements coupled with density functional theory (DFT) calculations enable the full resonance assignment of a complex pharmaceutical drug molecule without the need for isotopic enrichment. DNP dramatically enhances the NMR signals, thereby making possible previously intractable two-dimensional correlation NMR spectra at natural abundance. Using inputs from DFT calculations, herein we describe a significant improvement to the structure elucidation process for complex organic molecules. Further, we demonstrate that a series of two-dimensional correlation experiments, including 15N-13C TEDOR, 13C-13C INADEQUATE/SARCOSY, 19F-13C HETCOR, and 1H-13C HETCOR, can be obtained at natural isotopic abundance within reasonable experiment times, thus enabling a complete resonance assignment of sitagliptin, a pharmaceutical used for the treatment of type 2 diabetes.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
Limite:
Humans
Idioma:
En
Revista:
Solid State Nucl Magn Reson
Assunto da revista:
DIAGNOSTICO POR IMAGEM
/
MEDICINA NUCLEAR
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Emirados Árabes Unidos