Theoretical Evaluation of the Nanocarrier Properties of Two Families of Functionalized Dendrimers AURELIO EVANGELISTA-LARA, PATRICIA GUADARRAMA Instituto de Investigaciones en Materiales, Universidad Nacional Auto´noma de Me´xico, Apartado Postal 70-360, CU, Coyoaca´n, Me´xico DF 04510, Me´xico Received 29 September 2004; accepted 2 December 2005 Published online 22 February 2005 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/qua.20517 ABSTRACT: Two families of dendrimers, denamide (oxy-amide) and denurea (oxy-urea), of second and third generation were designed as possible nanocarriers for high-spectral parasiticide drugs of the family of macrocyclic lactones. Their geometric description was carried out by Connolly’s algorithm, obtaining molecular volumes and sizes of cavities. According to these calculations, about 50% of the total dendrimeric molecular volume in both families corresponds to cavities that are able to shelter guest drugs, forming complexes in ratios higher than 1:1. The molecular shape suffers more notorious changes, going through higher dendrimeric generations; therefore, third-generation dendrimers with two carbon atoms in their fractal patterns are more spherical than second-generation dendrimers with six carbon atoms in their fractal patterns. The experimentally studied host– guest system formed by PAMAM and ibuprofen (analgesic drug) was taken as a reference in the present study. Molecular dynamics and mechanics calculations were able to reproduce some experimental observations. Nevertheless, the interaction energies of some of the 1:1 complexes were calculated at the density functional theory (DFT) level. Comparing the fractal patterns of the denamide and denurea families with polyamidoamine dendrimers (PAMAM), the observed order of efficiency, in terms of favorable interactions with guest molecules, is as follows: denamide  PAMAM  denurea. The differences in functionalization are responsible for such behavior. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem 103: 460 – 470, 2005 Key words: nanocarriers; dendrimers; molecular mechanics; molecular dynamics; density functional theory Introduction D endrimeric molecules, especially perfect monodisperse dendrimers, have been con- sidered interesting candidates, like artificial models of natural proteins, in spite of their globular struc- tures as they reach higher generations. Besides the spherical conformations, another resemblance be- tween dendrimers and natural proteins is the pos- sibility of having internal cavities. In proteins, the cavities already exist, and they are actually related to their stabilization by the close packing of their amino acid side chains; however, in the case of dendrimers, these cavities can be created to a cer- Correspondence to: P. Guadarrama; e-mail: patriciagua@ correo.unam.mx International Journal of Quantum Chemistry, Vol 103, 460 – 470 (2005) © 2005 Wiley Periodicals, Inc.