A guide to small-molecule structure assignment through computation of (¹H and ¹³C) NMR chemical shifts.
Nat Protoc
; 9(3): 643-60, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24556787
This protocol is intended to provide chemists who discover or make new organic compounds with a valuable tool for validating the structural assignments of those new chemical entities. Experimental ¹H and/or ¹³C NMR spectral data and its proper interpretation for the compound of interest is required as a starting point. The approach involves the following steps: (i) using molecular mechanics calculations (with, e.g., MacroModel) to generate a library of conformers; (ii) using density functional theory (DFT) calculations (with, e.g., Gaussian 09) to determine optimal geometry, free energies and chemical shifts for each conformer; (iii) determining Boltzmann-weighted proton and carbon chemical shifts; and (iv) comparing the computed chemical shifts for two or more candidate structures with experimental data to determine the best fit. For a typical structure assignment of a small organic molecule (e.g., fewer than â¼10 non-H atoms or up to â¼180 a.m.u. and â¼20 conformers), this protocol can be completed in â¼2 h of active effort over a 2-d period; for more complex molecules (e.g., fewer than â¼30 non-H atoms or up to â¼500 a.m.u. and â¼50 conformers), the protocol requires â¼3-6 h of active effort over a 2-week period. To demonstrate the method, we have chosen the analysis of the cis- versus the trans-diastereoisomers of 3-methylcyclohexanol (1-cis versus 1-trans). The protocol is written in a manner that makes the computation of chemical shifts tractable for chemists who may otherwise have only rudimentary computational experience.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Orgánicos
/
Bibliotecas de Moléculas Pequeñas
/
Conformación Molecular
Idioma:
En
Revista:
Nat Protoc
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido