Effect of Solvent and pH on the Structure of PAMAM Dendrimers

We report various structural and conformational properties of generations 4, 5, and 6 PAMAM (polyamidoamine) dendrimer [EDA (ethylenediamine) core)] at various protonation levels through extensive molecular dynamics (MD) simulations in explicit solvent. The presence of solvent leads to swelling of the dendrimer (by 33% for G5 compared to the case of no solvent). We find that decreasing the solution from high pH (∼10, no protonation) to neutral (∼7, only primary amines protonated) to low pH (∼4, tertiary amines also protonated) changes the radius of gyration of G5 from 21 to 22 to 25 Å, respectively. We also report such other structural quantities as radial density, distribution of terminal groups, solvent accessible surface area and volume, shape, and structure factors (to compare with SAXS and SANS experiments) at various pH conditions. We find significant back-folding of the outer subgenerations in the interior of the molecules at all levels of pH, contrary to original expectations and some SANS experiments but in agreement with other SANS experiments. We find significant water penetration inside the dendrimer, with ∼3 water/tertiary amine for high pH and ∼6 water/tertiary amine for low pH (all for G5). This indicates that the interior of the dendrimer is quite open with internal cavities available for accommodating guest molecules, suggesting using PAMAM dendrimer for guest−host applications. This estimate of internal waters suggests that sufficient water is available to facilitate metal ion binding