1 research outputs found
Compound Aggregation in Drug Discovery: Implementing a Practical NMR Assay for Medicinal Chemists
The
pharmaceutical industry has recognized that many drug-like
molecules can self-aggregate in aqueous media and have physicochemical
properties that skew experimental results and decisions. Herein, we
introduce the use of a simple NMR strategy for detecting the formation
of aggregates using dilution experiments that can be performed on
equipment prevalent in most synthetic chemistry departments. We show
that <sup>1</sup>H NMR resonances are sensitive to large molecular-size
entities and to smaller multimers and mixtures of species. Practical
details are provided for sample preparation and for determining the
concentrations of single molecule, aggregate entities, and precipitate.
The critical concentrations above which aggregation begins can be
found and were corroborated by comparisons with light scattering techniques.
Disaggregation can also be monitored using detergents. This NMR assay
should serve as a practical and readily available tool for medicinal
chemists to better characterize how their compounds behave in aqueous
media and influence drug design decisions