Thanks to new water-soluble Ru nanoparticles (NPs) stabilized by sulfonated NHC ligands, we demonstrate that it is possible to monitor the catalyst/substrate interaction using NMR chemical shift perturbations (CSPs), under conditions that closely resemble those applied during the enantiospecific C-H deuteration of l-lysine. Correlating the pH dependence of the interaction of l-lysine with the surface of the RuNPs and its subsequent deuteration, our study underscores the importance of oriented binding to the surface as a critical factor for H/D exchange.