PAMAM dendrimers undergo pH responsive conformational changes without swelling.

Area of Science:

• Computational chemistry
• Materials science
• Nanotechnology

Background:

• Polyamidoamine (PAMAM) dendrimers are highly branched macromolecules with potential applications in drug delivery.
• Understanding their conformational behavior in solution is crucial for optimizing their function.
• Previous studies have suggested pH-dependent structural changes, but atomistic details were lacking.

Purpose of the Study:

• To investigate the pH-dependent conformational changes of a G4-NH(2) PAMAM dendrimer using atomistic molecular dynamics (MD) simulations.
• To compare simulation predictions with experimental data from small angle neutron scattering (SANS).
• To elucidate the structural basis for pH-triggered encapsulation and release of guest molecules.

Main Methods:

• Atomistic molecular dynamics (MD) simulations were performed on a G4-NH(2) PAMAM dendrimer in aqueous solution.
• Explicit water molecules and counterions were included in the simulations.
• The Dreiding III force field, optimized using quantum mechanics, was employed.

Main Results:

• Simulations predicted a minimal change in the radius of gyration (R(g)) of the dendrimer across a pH range of approximately 5 to 10.
• R(g) varied from 21.1 Å at pH ~10 to 22.1 Å at pH ~5, consistent with experimental SANS data (21.4 Å to 21.5 Å).
• Despite minimal R(g) change, a dramatic conformational transformation was observed: a dense core at high pH and a dense shell at low pH due to ion pairing.

Conclusions:

• PAMAM dendrimers exhibit significant pH-induced conformational changes, transitioning from a 'dense core' to a 'dense shell' structure.
• This pH-triggered structural transformation, particularly the formation of a dense shell at low pH, could facilitate the encapsulation and release of guest molecules.
• Dendrimers show promise as tunable drug delivery vehicles, with pH serving as an effective trigger mechanism.