Theoretical evaluation of poly(amidoamine) dendrimers with different peripheral groups as a purinethol drug delivery system in aqueous medium.

In this work, density functional theory calculations were used to study the association of PUR with amine- and acetyl-terminated PAMAM dendrimers considering implicit solvent effect at neutral and low pH conditions. Frontier molecular orbitals' analysis indicates that the electronic properties of dendrimers are extremely sensitive to the presence of PUR molecule at both neutral and low pH conditions. Encapsulation of PUR molecule into the both amine- and acetyl-terminated PAMAM dendrimers leads to a Gibbs free energy of (ΔG) - 20.25 kcal.mol-1 at physiological pH. The corresponding ΔG values reduce to the - 1.45 and - 0.91 kcal.mol-1 at low pH, indicating that the drug molecule is released easily at low pH. The calculated recovery times for amine- (3.87 ×102 and 3.87 ×102, at neutral and low pH, respectively) and acetyl-terminated (5.34 ×1010 and 1.81 ×10-1, at neutral and low pH, respectively) dendrimers suggest that acetylation can improve the release pattern of drug molecule.