Poor aqueous solubility of low molecular weight drug substances hampers their development as pharmacological agents. Here, we have examined the effects of arginine on the solubility of organic compounds, coumarin, caffeine and benzyl alcohol, in aqueous solution. Arginine increased the solubility of aromatic coumarin, but not non-aromatic caffeine, concentration dependently, suggesting the favourable interaction of arginine with the aromatic structure. Consistent with this, arginine also increased the solubility of aromatic benzyl alcohol. Guanidine hydrochloride, urea and salting-in salts increased both coumarin and caffeine solubilities, while salting-out salts decreased them. These results suggest the specific interaction of arginine with aromatic groups, leading to increased solubility of coumarin. However, the effect of 1 M arginine on coumarin solubility was at most ∼2-fold, which may limit its applications as a solubility enhancing agent.

Aromatic carbon nanomaterials, such as carbon nanotubes and graphene, undergo protein adsorption in the early stages of their uptake into biological systems, which determines their bioavailability and cytotoxicity. Although a mechanistic understanding of protein–nanomaterial interactions is essential for realizing safe and controlled in vivo applications of nanomaterials, it remains challenging to predict arbitrary protein–nanomaterial interactions. This study introduces an index, “aromaphilicity (aromatic-loving nature) index”, for 20 proteinogenic amino acids. This index reflects the affinity of the amino acid side chains for the aromatic carbon surfaces, which was quantified by molecular dynamics simulations. This index is significantly correlated with the experimental data (R² = 0.789) and successfully utilized as a versatile tool for predicting the affinity hot spots of the proteins for the aromatic carbon nanomaterials. This approach advances the understanding of the mechanism of protein–nanomaterial interactions and improves prediction of the biological impacts of nanomaterials.