NMR and MD as two methods of monitoring the self-association of small molecules in aqueous solutions for biological application

Small molecules, whether natural (as secondary metabolites) or synthetic (as many drugs), play an important role in regulating biological processes. Due to their low molecular weight (< 900 Da) and size of about 1 nm, they can bind to and be probes of biological macromolecules such as proteins and nucleic acids. However, since most of the molecules were found to have hydrophobic properties, from low to very high levels, and their physicochemical properties depend on their solubility in water, two problems of How their aggregation (self-association) in aqueous solutions can be monitored and How the aggregation can affect their biological properties, including the interaction with the macromolecules have been tried to be addressed. Form various in-vitro and computational methods, nuclear magnetic resonance (NMR) spectroscopy and molecular dynamic (MD) simulations can be used. For the former method, 1H NMR spectra of a small molecule in ascending concentrations (in mM or M, depending on the power of the NMR spectrometer) and dissolved in a constant ratio of solvents (usually H2O:DMSO) are recorded so that the chemical shift variations as a function of the concentration represent the affinity of the small molecules for self-association. For the latter one, several molecules are placed in a solvated simulation box and their behavior is monitored during the simulation time. Using NMR and MD, we showed that curcumin and quercetin are two small molecules with remarkable affinity for self-association, while rosmarinic acid has a much lower affinity.

Keywords:

Small molecule , Self-association , NMR , MD , Curcumin , Quercetin