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.