Interaction of anti-inflammatory drug naproxen with essential amino acids: Quantitative thermodynamic insights

A combination of ultrasensitive isothermal titration calorimetry and uv–visible spectroscopy has been employed to unravel interaction of anti-inflammatory drug naproxen with five essential amino acids L-arginine, L-lysine, L-phenylalanine, L-valine and L-tryptophan. The nature of interaction in each case has been examined based on standard molar enthalpy of interaction $\left({\Delta H}_m^o\right)$ and changes in the spectral properties. The values and sign of ${\Delta H}_m^o$ have been related with the nature of interacting groups and solvent reorganization as a result of drug-amino acid association. Exothermic standard molar enthalpy of interaction of naproxen with L-arginine indicated significant of polar interactions, and endothermic heat effects with all other amino acids suggested dominance of hydrophobic effect and desolvation penalty in the association process. The overall value of enthalpy of interaction for all the studied amino acids is less than 2 $\mathrm{kJ}{\mathrm{mol}}^{-1}$ suggesting that these interactions are not very strong. The uv–visible results provided support to ITC results in obtaining mechanistic insights into the nature of interactions. The results derive significance from the fact that sometimes anti-inflammatory drug naproxen may be administrated along with supplements of essential amino acids. In case there is a strong drug-amino acids interaction, efficacy of each one may be affected.