The essential synergy of MD simulation and NMR in understanding amorphous drug forms
Jamie L Guest1, Esther A E Bourne1, Martin A Screen1
1Department of Chemistry, Durham University, Lower Mountjoy, Stockton Road, Durham, UK. paul.hodgkinson@durham.ac.uk.
Abstract:
Molecular dynamics (MD) simulations and chemical shifts from machine learning are used to predict 15N, 13C and 1H chemical shifts for the amorphous form of the drug irbesartan. The local environments are observed to be highly dynamic well below the glass transition, and averaging over the dynamics is essential to understanding the observed NMR shifts. Predicted linewidths are about 2 ppm narrower than observed experimentally, which is hypothesised to largely result from susceptibility effects. Previously observed differences in the 13C shifts associated with the two tetrazole tautomers can be rationalised in terms of differing conformational dynamics associated with the presence of an intramolecular interaction in one tautomer. 1H shifts associated with hydrogen bonding can also be rationalised in terms of differing average frequencies of transient hydrogen bonding interactions.
More Related Videos
10:10Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study
Published on: August 15, 2016
05:00Author Spotlight: Streamlining Visual Dynamics to Simplify Molecular Dynamics Simulations Using Gromacs
Published on: August 9, 2024
Related Concept Videos
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
¹H NMR: Interpreting Distorted and Overlapping Signals
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are...
Applications Of NMR In Biology
¹H NMR: Complex Splitting
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
Two-Dimensional (2D) NMR: Overview
The first step is the preparation period, during which nucleus A is excited with a radiofrequency pulse....
