Degree of N‑Methylation of Nucleosides and Metabolites Controls Binding Affinity to Pristine Silica Surfaces

Biological molecules interact with silica (SiO₂) surfaces with binding affinities that greatly vary depending on their physical–chemical properties. However, the quantitative characterization of biological compounds adsorbed on silica surfaces, especially of compounds involved in fast, reversible interactions, has been challenging, and the driving forces are not well understood. Here, we show how carbon-13 NMR spin relaxation provides quantitative atomic-detail information about the transient molecular binding to pristine silica surfaces, represented by colloidally dispersed silica nanoparticles (SNPs). Based on the quantitative analysis of almost two dozen biological molecules, we find that the addition of N-methyl motifs systematically increases molecular binding affinities to silica in a nearly quantitatively predictable manner. Among the studied compounds are methylated nucleosides, which are common in epigenetic signaling in nucleic acids. The quantitative understanding of N-methylation may open up new ways to detect and separate methylated nucleic acids or even regulate their cellular functions.