SAXS, DLS, and MD studies of the <i>R</i>g/<i>R</i>h ratio for swollen and collapsed dendrimers

The radius of gyration, Rg, and the hydrodynamic radius, Rh, are the main experimental parameters that characterize the size of linear and branched macromolecules. In the case of dendrimers in solution, the ratio Rg/Rh, depending on the global conformation, varies from 1 (for a Gaussian soft sphere) to 3/5 (for a hard sphere). However, for high-generation dendrimers, this ratio may be less than the limiting value for a hard sphere. To understand the reasons of the low Rg/Rh value (<0.77), we have studied the second-generation peptide dendrimer containing pH-sensitive histidine amino acid residues (Lys-2His dendrimer) using small-angle x-ray (SAXS) and dynamic light scattering (DLS) experiments, as well as molecular dynamics simulations. The Lys-2His dendrimer takes a swollen conformation at pH = 2 and a collapsed 1 at pH = 7. Our results show that the Rg/Rh ratio for the considered dendrimer decreases from ≈3/5 at pH = 2 to 0.5 at pH = 7. We have found that the very low Rg/Rh value is due to (1) the formation of a dense impenetrable core (i.e., the transformation of the dendrimer from a Gaussian soft sphere into a sphere with a dense core) and (2) the presence of a larger number of solvent molecules in the dendrimer corona than in a typical macromolecule. In addition, in this work, we have directly confirmed in the experiments for the first time, the collapse of the Lys-2His dendrimer with increasing pH.