(724c) Molecular Dynamics Investigations of Dendrimer–Aromatic Hydrocarbon Interactions

Dendrimers are a class of branched macromolecules with generational growth that have been explored for applications in fields including water purification, drug delivery and light harvesting. Dendrimers offer desirable properties, such as precise control of the size, shape, and chemical functionality of the molecule. Some proposed applications involve dendrimer interactions with aromatic and hydrophobic hydrocarbons, or molecules containing moieties with these properties. A detailed description of the interactions between dendrimers and aromatic hydrocarbons can assist researchers in selecting and tuning dendrimer properties for specific applications.

We used all-atom molecular dynamics (MD) simulations to investigate the interactions between dendrimers and hydrocarbons. All of our studies focused on polyamidoamine (PAMAM) dendrimers. All-atom MD simulations with explicit water were used to investigate the mechanistic details of association of model aromatic hydrocarbon guest molecules, naphthalene (NPH), and its derivatives, with 3^rd – 6^th generation (G3–G6) dendrimers. We performed extensive simulations of aromatic hydrocarbon–dendrimer interactions, totaling several microseconds of simulation time for 70,000+ atom systems.  

We find that the mechanism of NPH association with the dendrimers is similar for G3–G6 dendrimers. In all dendrimer generations, NPH associates at a distance from the dendrimer center that is accessible to the water solvent. However, we observe dendrimer branches form local pocket-like structures around NPH molecules associated with the dendrimers. These pockets provide a local environment around NPH that is protected from water. Of particular note, we find that NPH molecules associated closer to the dendrimer center are not necessarily more protected from the water environment. We also studied the effect of increasing the NPH concentration. We found no clear saturation point, but instead observe a transition to NPH molecules aggregating together on the dendrimers. In order to better understand the driving forces of NPH association with dendrimers, we studied the association of increasingly hydrophilic model compounds. To retain similar guest size and chemistry to NPH, we performed simulations with model compounds that were created by adding two and four hydroxyl groups to NPH. We also report differences in the saturation and aggregation behavior of the increasingly hydrophilic guest molecules.

Our results provide a detailed mechanism of NPH association with dendrimers. In addition, they show the effect of hydrophobicity on NPH association with dendrimers. We highlight the importance of considering both dendrimer-guest and guest-guest interactions when designing dendrimers for host–guest applications. Insights from our results can be used when designing dendrimers for specific applications.