INTRODUCTION 28 Originally proposed by Paul Flory,1 dendritic polymers are a class of macromolecules consisting 29 of highly branched polymer units. Within this class are dendrons, dendrimers, and 30 hyperbranched polymers.1 Dendrimers can be precisely synthesized with high order and 31 monodispersion, with well defined branching units emanating from a central core.1 The number 32 of these branching iterations is termed the Generation of the dendrimer and determines its size, 33 structure, and function. Hyperbranched polymers, in contrast, possess less well-defined branched 34 interiors, resulting in a higher polydispersity at a much lower production cost. Due to their 35 unique physicochemical properties, there are a wide variety of current and potential applications 36 of dendrimers ranging from environment to energy and biomedicine. For example, hydroxyl37 terminated PAMAM dendrimers have been shown to remove contaminants such as humic acids2 38 and metal ions3,4 from drinking water or contaminated soils. Dendrimers can be used in light39 harvesting applications for superior transduction efficiency in diodes and other photonic 40 devices.5,6 The surface functionality of PAMAM dendrimers has been altered to include long41 lifetime ibuprofen release in vivo7 and conjugation with partially anionic folate-conjugates has 42 been explored for the delivery of anti-arthritic drugs.8 The ability of dendrimers to encapsulate 43 small organic molecules has also been studied in terms of dendrimer generation9 as well as the 44 shape of a guest molecule,10 demonstrating a wide array of hosting capabilities of dendrimers in 45 aqueous solution. 2 Given their hosting capabilities, we have previously proposed 46 PAMAM polymers as oil 47 dispersants,11 and showed that cationic PAMAM dendrimers are capable of hosting both 48 polyaromatic and linear hydrocarbons in water.11 Conventionally, lipid-like oil dispersants have 49 been in use since at least the 1960s12 and also during the large scale Deepwater Horizon disaster 50 of 2010. However, concerns over the potential toxicity of conventional oil dispersants have been 51 recently raised.13–15 There is a renewed and pressing desire for effective yet biocompatible 52 dispersing agents. Our previous work has shown, however, that highly cationic amine-terminated 53 poly(amidoamine) (PAMAM) dendrimers cause acute toxicity in amoebas at a high 54 concentration.16 Similarly, several other studies have also shown that highly cationic PAMAM 55 dendrimers cause significant charge-induced toxicity in vitro17–20 and rapid blood clotting in 56 vivo.21 It has been suggested that the electrostatic interaction between highly cationic PAMAM 57 and negatively charged cell membrane results in pore formation to trigger cytotoxicity. 58 Therefore, efforts are increasingly being focused on altering dendrimer terminal charges in order 59 to reduce the toxicity or improve the efficacy of dendrimer agents.22,23 60 Many studies have been conducted on the size, structure, and dynamics of dendrimers 61 depending on dendrimer generation24,25 and environmental conditions such as solution pH and 62 ionic strength.24–28 It has been shown that PAMAM dendrimers adopt globular-like structures 63 with the repeating monomers loosely packed in the interior and the surface groups protruding, 64 forming hydrogen bonds with water. Simulations revealed dynamically forming pores in the 65 interior that can bind various guest molecules.24,29 Solution pH and ionic strength can also affect 66 dendrimer structure by changing the dendrimer protonation states and screening of electrostatic 67 interactions, respectively.26,27,30 It is not understood, however, how surface modifications of 3 dendrimers, a common strategy in dendrimer design and synthesis, 68 might affect their size, 69 structure, dynamics, and subsequent functionality. 70 Here, we investigate the effects of varying the surface charge and functionality on 71 dendrimers’ ability to serve as effective oil dispersants. Specifically, we examine cationic amine72 terminated (G4-NH2), neutral hydroxyl-terminated (G4-OH), and anionic succinamic acid73 terminated (G4-SA) PAMAM dendrimers (Fig. 1A). Synergistic experiments and molecular 74 dynamics simulations are performed to probe the interactions, limitations, mechanisms, and 75 differences between cationic, anionic, and neutrally charged PAMAM dendrimers with linear, 76 polyaromatic, and hybrid hydrocarbons as well as the combination thereof. These various 77 combinations of hydrocarbon are studied in order to gain a more fundamental understanding of 78 dendrimer oil dispersant interactions with the various hydrocarbon components of crude oil as 79 well as illuminate any potential synergistic dispersion effects of hydrocarbon mixtures. The 80 advantages of model hydrocarbons over whole crude oil include the real-time tracking and 81 accurate quantification for mechanistic studies of the structure-function relationship. Additional 82 studies of dendrimer dispersion efficacy and toxicity with crude oil have been done in a separate 83 work. The implications of this study reach beyond oil dispersion to other biomedical and 84 environmental applications including drug delivery and water purification, noting the differences 85 in dendrimer interactions with aliphatic and aromatic hydrophobic molecules as well as 86 potentially unanticipated effects of altering dendrimer surface functionality. We find that marked 87 differences in hosting capacity for hydrocarbons arise from changes in both the structure and 88 dynamics of the dendrimers with varying terminal functionality.
