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Computer Simulation Studies on the pH-Responsive Self-assembly of Amphiphilic Carboxy-Terminated Polyester Dendrimers in Aqueous Solution Chunyang Yu, Li Ma, Ke Li, Shanlong Li, Yannan Liu, Lifen Liu, Yongfeng Zhou, and Deyue Yan Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.6b03480 • Publication Date (Web): 21 Dec 2016 Downloaded from http://pubs.acs.org on December 23, 2016
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Computer Simulation Studies on the pH-Responsive Self-assembly of Amphiphilic Carboxy-Terminated Polyester Dendrimers in Aqueous Solution Chunyang Yua, Li Maa, Ke Lia, Shanlong Lia, Yannan Liua, Lifen Liub*, Yongfeng Zhoua*and Deyue Yana a
School of Chemistry & Chemical Engineering, State Key Laboratory of Metal Matrix
Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, China, 200240. b
Center for Membrane and Water Science and Technology, Ocean College, Zhejiang University
of Technology, Hangzhou, China, 310014. KEYWORDS: computer simulation, dissipative particle dynamics, pH-responsive self-assembly, amphiphilic dendritic polymer
ABSTRACT: This paper investigates the pH-responsive self-assembly of an amphiphilic carboxyl-terminated polyester dendrimer, H20-COOH, in aqueous solution by using dissipative particle dynamics method. The electrostatic interactions were described by introducing the explicit interaction between smeared charges on ionized polymer beads and the counterions. The results show that the self-assemblies could change from unimolecular micelles, microphaseseparated small micelles, wormlike micelles, sheet-like micelles, small vesicles, to large vesicles with the decrease of the degree of ionization (α) of carboxylic acid groups. In addition, the
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detailed self-assembly mechanisms as well as the molecular packing models have also been disclosed for each self-assembly stages. Interestingly, the wormlike micelles are found to change from linear to branched when α decreases from 0.182 to 0.109. The current work might serve as a comprehensive understanding on the effect of carboxylic acid groups on the self-assembly behaviors of dendritic polymers.
1. INTRODUCTION In recent years, the self-assembly of amphiphilic dendritic polymers in solution has been sparked great interest and has been widely used in constructing supramolecular structures, such as tubes, micelles, vesicles, fibers, etc.1-4 The constructed structures have shown many potential applications such as gene transfection,5 protein delivery and purification,6-7 encapsulating and releasing agents for drug delivery,8-10 bioimaging and diagnosis,11 bio-mineralization,12-13 and tissue engineering,14-15 etc. In order to extend applications, it is usually required that the polymer aggregates should have an ability to respond to the external stimuli. Currently, there are a large amount of reports on the studies of stimuli-responsive dendritic polymers and their self-assemblies,16-27 mainly including pH,16-22 temperature,23 light,24 redox or chemical changes,25 or the combination of two or more of them.26-27 Among all the stimuli, the changing pH of solution is one of the most common and easy handled method, so it has been widely used to construct stimuli-responsive dendritic polymers. For example, to realize the pH-responsive self-assembly, Zhou and Yan introduced the hydrophilic maleic anhydride group (-COOH) onto the hydrophobic hyperbranched poly(3-ethyl3-oxetanemethanol) (HBPO), and the obtained pH-responsive hyperbranched polymers of HBPO-COOH existed as unimolecular micelles at high pH and then aggregated into multimolecular micelles from 10 to 500 nm with the decrease of pH.16 Similarly, they introduced
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the hydrophilic succinic anhydride (-COOH) onto the aliphatic polyester dendrimer Boltorn H20, and then obtained a new amphiphilic pH-responsive polymers H20-COOH.17 The polymers can self-assemble into vesicles in aqueous solution and the vesicle size can be controlled from 200 nm to 10µm by adjusting the pH of the solution. Jiang and coworkers synthesized hyperbranched poly(methyl acrylate)-block-poly(acrylic acid)s by introducing pH-responsive acrylic acid group onto hyperbranched poly(methyl acrylate).18 The copolymer could spontaneously form spherical micelles in solution and the size of spherical particles could increase from 8.18 to 19.18 nm with the increase of pH from 3.0 to 12.0. Kim and coworkers linked double hydrophilic poly(ethylene oxide)-hyperbranched-polyglycerol
copolymer
with
the
hydrophobic
anticancer
agent
doxorubicin through pH-sensitive hydrazone bonds.19 Then pH-responsive controlled release of doxorubicin was realized by regulating the pH of the solution. Zhu and coworkers also conjugated hyperbranched polyacylhydrazone (HPAH) with the anticancer drug doxorubicin (DOX) through the reversible acylhydrazone bond.21 Their research showed that HPAH-DOX could self-assemble into micelles with an average diameter of 20 nm, which were stable under physiological (pH=7.4) but cleavable after endocytosis (pH=5~6). Evidently, the construction of pH-responsive dendritic polymers and its self-assemblies in aqueous solution are extremely important and meaningful for developing functional materials. However, despite these experimental progress, there are still many problems such as the microscopic mechanism and the dynamic process of the self-assembly of pH-responsive dendritic polymers have not been fully disclosed due to the limitation of the experimental measurements. Naturally, we hope to deal with these problems with the aid of computer simulation technique, which has already been proved as a powerful tool to disclose the details of the self-assembly process.
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In fact, nowadays, the solution properties of the charged polymers have been widely investigated by computer simulation. The computational methods mainly include Monte Carlo (MC), molecular dynamics (MD), self-consistent field theory (SCFT) and dissipative particle dynamics (DPD). Generally, MC and all-atom MD (AAMD) simulations were always employed to investigate the conformation and dynamical behaviors of charged polymers in solution. For example, Kłos and Sommer studied the properties of weak dendritic polyelectrolytes of generation G=5 with flexible spacers of various lengths and explicit counterions in an athermal solvent using MC simulations.28-29 Wu and coworkers investigated the local dynamics of polyelectrolyte dendrimers dissolved in deuterium oxide and its dependence on molecular charge through AAMD simulations.30 The coarse-grained molecular dynamics (CGMD), SCFT and DPD were often used to investigate the self-assembly behaviors of charged polymers in solution. For example, Karatasos reported the self-organization of charged dendrimer molecules upon the variation of the strength of the electrostatic interactions in solutions by using united atom MD simulations.31 In addition, the same method was also used by them to examine a symmetric binary mixture of terminally charged trifunctional-core/difunctional-branched dendrimers of the third and the fourth generation in explicit solvent solution.32 Yang and coworkers explored the self-assembly of polyelectrolyte copolymers by using SCFT complemented with the Poisson– Boltzmann equation.33 Compared with CGMD and SCFT method, the advantage of DPD method lies in that it can investigate the self-assembly behavior at a larger time scale and spatial scale. Especially by introducing the electrostatic interaction into DPD method, it has provided a promising tool for investigating the self-assembly behaviors of charged polymers in aqueous solution.34-48 For example, Yamamoto and Hyodo studied the mesoscopic structure of the perfluorinated sulfonic acid membrane Nafion containing water.34 Ibergay and coworkers
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investigated the bulk electrolytes and polyelectrolyte brushes.35 Procházka and co-workers explored the pH-dependent self-assembly of a diblock copolymer, P2VP−PEO in aqueous media.36 They also studied the associative behavior of aqueous mixtures of diblock copolymers containing one neutral water-soluble block and one either positively or negatively charged polyelectrolyte block by employing the same method.37-38 Moreover, Mao et al. explored the specifics of micellization in solution of anionic and cationic surfactants and their mixtures by using DPD simulations.39 Evidently, the distinct progress has been made in computer simulations of the self-assembly of charged polymers in solution. However, most of the reports are mainly focused on the selfassembly of linear block copolymers (for example, diblock copolymer with one neutral block and one polyelectrolyte block) in solution. As we know, the molecular structures and properties of dendritic polymers are significantly different from those of linear polymers. In addition, it has been proved that dendritic polymers have demonstrated unique self-assembly behaviors when compared with the linear polymers, for example the diverse morphologies and structures, special properties, characteristic self-assembly mechanism and facile functionalization process.1,2 So, how can the charges influence the self-assembly behavior of dendritic polymers? Are there some unique characteristics when compared it with that of the linear polymers? To address these questions, herein, the pH-responsive self-assembly process of a carboxylterminated dendritic polymer H20-COOH in aqueous solution17 was investigated by using the DPD simulations. The aim of the present work was to fully disclose the self-assembly behaviors of H20-COOH in different pH solutions, including the self-assembly mechanisms and the dynamic self-assembly processes. The results show that H20-COOHs under low concentration can self-assemble into unimolecular micelles, microphase-separated small micelles, wormlike
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micelles, sheet-like micelles, small vesicles and large vesicle with the decrease of pH (the degree of ionization (α) of carboxylic acid groups). In other words, the pH-responsive self-assembly of dendritic polymers in solution has richer morphologies than that of the diblock copolymers. In addition, the microphase-separation behaviors of H20-COOH molecules into sphere, cone-shape, truncated cone-shape, cylindrical geometry, or trapezoidal shape in these supramolecular aggregates have also been fully disclosed. The article is organized as follows. Section 2 contains the description of DPD and AAMD simulation methods. The self-assembled mechanism and the aggregation processes of the dendritic molecules are described in Section 3. Finally, conclusions and outlooks are given in Section 4. 2. SIMULATION DETAILS 2.1 DPD Model and Simulations The DPD method employed in the present work is a particle-based, mesoscale simulation technique. It was first introduced by Hoogerbrugge and Koelman in 199249 and improved by Español and Warren.50 In the method, one DPD bead represents a group of atoms, and the motion of all beads in the system obeys Newton’s equations of motion. In DPD method, the force on bead i is consisted of conservative force , dissipative force ()
, random force , bond force , and electrostatic force . ()
()
( )
( )
( ) = (r ) + (r ) + (r ) + (r ) + (r ) ()
()
()
( )
( )
(1)
The conservative force, dissipative force and random force are given by: v Fij( C ) = −α ij ω C ( rij ) e ij ,
(2)
v v v Fij( D) = −γω D ( rij ) vij ⋅ eij eij ,
(3)
v Fij( R ) = σω R ( rij ) ξ ij ∆ t −1/ 2 e ij ,
(4)
(
)
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v v v v v v v v where r ij = r i − r j , rij = r ij , e ij = r ij / rij , ri and r j are the positions of bead i and bead j, v v v v v respectively. v ij = v i − v j , vi and v j are the velocities of bead i and bead j, respectively. αij is a
constant that describes the maximum repulsion between two interacting beads. γ and σ are the amplitudes of dissipative and random forces, respectively. ωC, ωD and ωR are three weight functions for the conservative, dissipative, and random forces, respectively. For the conservative force, we choose ωijC(rij)=1-rij/Rc for rij
