Effect of pH on Eosin Y/PAMAM interactions studied from absorption spectroscopy and molecular dynamics simulations

Absorption spectroscopy experiments were carried out to examine the 1: 1 supramolecular interaction between Eosin Y (EOS) and low generation G0-G3 poly(amido amine) (PAMAM) dendrimers at neutral and basic media, aimed at gaining insight about the role of pH and dendrimer generation on EOS-PAMAM binding. Our results revealed that EOS complexation is favored under neutral pH conditions, and that the supramolecular interaction strengthens as the dendrimer generation increases. Further molecular-level information regarding EOS-PAMAM systems was obtained from Molecular Dynamics (MD) simulations, Non-Covalent Interaction (NCI) analysis and MM/PBSA binding free energy calculations, which were carried out to examine the role of the generation, charge, and protonation state of PAMAM on the structure, conformation, and preferable interactions with EOS at neutral and basic pH conditions. Theoretical predictions were in high agreement with experimental results, showing that neutral pH allows a faster, deeper, and more stable complexation of the dye within dendrimer cavities, and that higher generation dendrimers induce a larger affinity towards EOS. According to MD results, the binding mode of the dye favors the interaction of the xanthene moiety within internal dendrimer cavities through the establishment of attractive van der Waals contacts. On the other hand, the carboxylate moiety interacts with the outermost dendrimer branches and remains exposed towards the solvent in G0-G2 PAMAM. These results support the validity of using MD simulations as auxiliary tools to deal with supramolecular complexation phenomena involving PAMAM dendrimers as host molecules.