Published on Web Date: June 15, 2010 r2010 American Chemical Society 2020 DOI: 10.1021/jz1006143 | J. Phys. Chem. Lett. 2010, 1, 2020–2024 pubs.acs.org/JPCL Electrostatic Swelling and Conformational Variation Observed in High-Generation Polyelectrolyte Dendrimers Yun Liu, †,‡ Chun-Yu Chen, § Hsin-Lung Chen,* ,§ Kunlun Hong, ) Chwen-Yang Shew, ^ Xin Li, #,3 Li Liu, 3 Yuri B. Melnichenko, # Gregory S. Smith, # Kenneth W. Herwig, # Lionel Porcar,* ,O and Wei-Ren Chen* ,#,[,z † The NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899-6100, ‡ Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716, § Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ) The Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, ^ Department of Chemistry, City University of New York, College of Staten Island, Staten Island, New York 10314, # Neutron Scattering Science Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, 3 Department of Mechanical, Aerospace & Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, O Institut Laue-Langevin, B.P. 156, F-38042 Grenoble CEDEX 9, France, [ Department of Chemical & Biomolecular Engineering, The Universityof Tennessee, Knoxville, Tennessee 37996-2200, and z Joint Institute for Neutron Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 ABSTRACT A combined small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) study was conducted to investigate the structural char- acteristics of aqueous (D 2 O) solution of generation 7 and 8 (G7 & G8) polyamido- amine (PAMAM) dendrimer as a function of molecular protonation. A consequent change in the intramolecular dendrimer conformation was clearly quantified by a detailed data analysis separating intermolecular correlations from the intramole- cular contribution. Our results unambiguously reveal both an increase in the molecular size and a continuous variation of the intramolecular density profile upon increasing molecular protonation. This observation is contrary to current understanding of high-generation polyelectrolyte dendrimers where steric crowd- ing is supposed to stiffen the local motion of dendrimer segments hindering exploration of available intradendrimer free volume and thereby inhibiting elec- trostatic swelling. Our observation is relevant to the elucidation of the general microscopic picture of polyelectrolyte dendrimer structure, as well as the deve- lopment of dendrimer-based packages based on the stimuli-responsive principle. SECTION Macromolecules, Soft Matter P olyamidoamine (PAMAM) dendrimers are man-made spherical-like polyelectrolyte macromolecules with a sophisticated hyperbranched organization. Their struc- tural study is challenging from a theoretical standpoint be- cause of the complexity arising from a single molecule having both polymeric and colloidal characteristics. 1 Moreover, when dissolved in acidified aqueous environments, the binding bet- ween free protons and the constituent amines of PAMAM den- drimer provides a molecular protonation tunable by simply adjusting the pH of the solution. The influence of this addi- tional electrostatic interaction and the prospect of using this charge-stimulated conformational evolution to facilitate and enhance dendrimer applications as hosts for encapsulation of molecules for targeted drug carriers, gene therapy scaffolds, and water decontaminating agents have provided motivation for extensive studies. 1,2 Complemented by molecular dynamics (MD) simulation 3 and theoretical analysis within a framework provided by statis- tical mechanics, small-angle scattering techniques, including neutron (SANS) and X-ray (SAXS), prove to be an effective means to explore the structural evolution of polyelectrolyte dendrimers. 4 A quantitative SANS study of fourth-generation (G4) of PAMAM dendrimer dissolved in D 2 O solutions first revealed that, upon increasing the molecular protonation, the internal structural conformation evolved from a dense- core configuration for the neutral state to a more uniform, outstretched distribution when fully charged. However, only a minor increase of the overall molecular size (less than 4% increase in the radius of gyration R G ) was observed, 5 in con- tradiction to the significant molecular swelling predicted by early computational studies. 3 With an improved force field, recent atomistic MD simulations carried out by Goddard and co-workers confirmed this minor increase in radius of gyration. 6 They have attributed this modest expansion to enhanced counterion association, which was pointed out previously by Received Date: May 12, 2010 Accepted Date: June 9, 2010