Formulating Polyethylene Glycol as Supramolecular Emulsifiers for

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Formulating Polyethylene glycol as Supramolecular Emulsifiers for One-Step Double Emulsions Zhen Wang, Jiaqi Song, Shiming Zhang, Xiao-Qi Xu, and Yapei Wang Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.7b02326 • Publication Date (Web): 21 Aug 2017 Downloaded from http://pubs.acs.org on August 21, 2017

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Formulating

Polyethylene

glycol

as

Supramolecular Emulsifiers for One-Step Double Emulsions Zhen Wang, Jiaqi Song, Shiming Zhang, Xiaoqi Xu, and Yapei Wang*

Department of Chemistry, Renmin University of China, Beijing 100872, China

Email: [email protected]

ACS Paragon Plus Environment

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ABSTRACT: One-step double emulsion via only one-step emulsification is leading to an attractive branch of emulsion researches owing to the ease of preparation and reduced surfactant numbers. In addition to controlling oil-water ratio, exploiting emulsifiers with desirable amphiphilicity that can stabilize both the inner and outer water/oil interfaces is crucial to the formation of one-step double emulsions. In particular, new emulsifiers with saving laborious efforts are highly preferred in consideration of low cost and practical applications. In this work, a commonly used homopolymer, polyethylene glycol (PEG), was attempted as emulsifiers to prepare emulsions via one-step emulsification. PEG was generally considered as a hydrophilic polymer and always anchored with a hydrophobic polymer to make the copolymer amphiphilic. In the water-chloroform binary system, PEG itself exhibits amphiphilic performance and tailors the formation of single emulsions or double W/O/W emulsions on the dependence of the oil-water ratio and the PEG concentration. A possible mechanism as explained by dissipative particle dynamics (DPD) simulation was proposed to demonstrate the amphiphilic feature and emulsification capability of PEG. The amphiphilicity of PEG was further tuned by interacting with iodine as a result of the formation of a supramolecular complex, which, in turn, led to the conversion from single emulsions to O/W/O double emulsions. It is believed that this line of research provides inspiration for the preparation of controllable emulsions through supramolecular routes.


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INTRODUCTION Researches on emulsions have never been outdated though this classical field has been developed for several centuries. The past few years have witnessed an explosive innovation of emulsions with different types or formulations for purposed uses in daily life and industrial production.1-8 Of the emulsion family, double emulsions consisting of three separated phases are especially attracting enormous attention in terms of their advantages as soft templates and loading capability of immiscible excipients.9-16 Traditional ways for the preparation of double emulsions contain two-step emulsifications in which at least two distinctive surfactants are involved to stabilize the inner and outer oil/water interfaces. Instead, one-step double emulsions via only one-step emulsification and less use of surfactants are more cost-effective, which also reduce the potential side effect caused by surfactants. To make the one-step double emulsions, changing oil-to-water ratio according to the Ostwald packing theory is one of convenient and straightforward ways.17 Yet emulsion morphologies and types are limited in a specific range with the use of given surfactants. Using particular emulsifiers with appropriate amphiphilicity is an alternative strategy to produce one-step double emulsions with a wider range of morphologies and types.18 Mixed small molecular surfactants with proper hydrophilic and hydrophobic balance have shown great promise for preparing double emulsions in one step. However, the excessive use and difficult removal of surfactants may cause the cytotoxicity issues of emulsion-templated materials for applications in the biological


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areas.19-22 Amphiphilic copolymers are rising as a more attractive class of surfactants on account of high throughput and excellent control over compositions. In addition to self-assembly studies, they have been readily extended as interfacially active materials in emulsion systems.23-30 The precise regulation of polymeric amphiphilicity leads to great benefits of controlling emulsion morphologies and types.31-37 However, the copolymers with elegant topologies and desired amphiphilicity always rely on lengthy laboratory synthesis and purification trials. In this regard, new polymeric emulsifiers with few laborious efforts are extremely preferred for one-step double emulsions in consideration of low cost and practical applications. As one of extensively used polymers, polyethylene glycol (PEG) is usually anchored with hydrophobic polymers to act as amphiphilic materials.38-41 In this work, the intrinsic amphiphilicity of PEG was emphasized in a water-chloroform binary system. It was found that PEG itself could tailor the formation of complex emulsions via a one-step emulsification, with appropriate use of oil-water ratio and PEG concentration. Further association with iodine (I2) forming a supramolecular complex could tune the amphiphilicity of PEG, which induced the phase inversion and changed emulsion types accordingly. As summarized in Scheme 1, single emulsions (O/W, or W/O) were successfully converted to double emulsions (W/O/W, or O/W/O) using PEG or PEG-I2 complex as emulsifiers.


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Scheme 1. Schematic illustration of the controllable preparation of double emulsions using PEG or PEG-I2 complex as interfacial emulsifiers.

RESULTS AND DISCUSSION PEG was intended as emulsifier in a water-chloroform binary system to prepare emulsions via one-step emulsification. Insights were firstly provided into the effects of oil-water ratios and PEG concentrations on the formation of emulsions. Two emulsion phase diagrams at different oil-water ratios were summarized in Figure 1. Stable emulsions were obtained without adding other additives in both systems, indicating PEG with specific concentration possesses enough interfacial activity to ensure the formation of emulsions. Notably, the obtained emulsion morphologies are determined by the cooperative effect of the oil-water ratio and PEG concentration. Macroscopic phase separation occurred without addition of PEG that water and oil phases separate immediately once agitation stops. Cloudy phases as indicative of early emulsions were observed at low PEG concentration of 66 mg/mL. The oil phase existing as droplets partially appeared in the water phase at oil-water ratio of 1:3. At


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the same time, water droplets also appeared in the oil phase and their loading amount is obviously more than that of oil droplets in water phase (Figure 1c, f). The formation of both O/W and W/O emulsions in this cloudy state illustrates that PEG should exist in both phases to retain the stable interfacial curvatures. The appearance of more favorable W/O emulsions indicates PEG is likely to be more oleophilic and prefer to form W/O emulsions at low PEG concentration in the water-chloroform binary system. With further increase of PEG concentration in water at the oil-water ratio of 1:3, W/O/W double emulsions were obtained yet they were gradually transformed into O/W emulsions at higher PEG concentrations (Figure 1d, g). The inner water droplets in W/O/W double emulsions have similar size distribution with W/O emulsions prepared at low PEG concentration. In this case, the new added PEG molecules in the water phase tend to serve as hydrophilic interfacial emulsifier to stabilize the external O/W interface. For the system with oil-water ratio of 3:1, the emulsion is always W/O type. The increase of PEG concentration somehow improves the emulsion stability (Figure 1e, h). Phase inversion from O/W to W/O upon the increase of oil-water ratio could be explained by the Ostwald packing theory that the preponderant phase is often preferred as the continuous phase. 22, 35, 42 The size of dispersed water droplets in W/O emulsions prepared at oil-water ratio of 3:1 is smaller than that of dispersed oil droplets in O/W emulsions at oil-water ratio of 1:3. Although PEG can balance the outer O/W interface and inner W/O interface at the same time to enable the formation of W/O/W emulsions, the inherent amphiphilicity of PEG is still not desirable to encapsulate oil droplets in the smaller W/O emulsions prepared at oil-water ratio of


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3:1 due to the limited internal space. For producing O/W/O double emulsions, the enhanced oleophilicity is suggested to precipitate PEG in the water phase and open avenues for loading external oil solvent into water droplets as the new inner phase.

Figure 1. (a, b) Emulsion phase diagrams with PEG as emulsifier at different oil-water ratios: (a) water : oil = 3:1, and (b) oil : water = 3:1. PEG concentrations in water are 0 mg/mL, 66 mg/mL, 132 mg/mL, and 198 mg/mL. PEG concentrations in chloroform are 0 mg/mL, 33 mg/mL, 66 mg/mL, and 132 mg/mL, respectively. (c-e) Bright-field microscopy images and (f-h) fluorescence microscopy images of emulsions marked with dashed circles in the emulsion phase diagrams. (c) Inset: an unstable emulsion with separated oil and water phases. The oil phase is loaded with a probing dye of Nile red. The PEG concentration in water contributes more to determining the emulsion morphologies than the PEG concentration in oil. It is assumed that increasing PEG concentration in water facilitates more PEG molecules to be rearranged and assembled at the oil-water interface. In order to confirm this assumption, dynamic


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interfacial tension between chloroform and water was evaluated by a pendant drop method. As shown in Figure 2a, the droplet shape of chloroform which is correlated with the interfacial energy remains unchanged without loading PEG in the water phase. When the chloroform droplet is suspended in PEG aqueous solution, small oil droplets are gradually formed at the oil-water interface and escape into the water phase (Figure 2b). The oil split becomes more serious at higher PEG concentration. The suspended oil droplet tends to be elongated and pulled off from the needle tip (Figure 2c, d). A counterforce against the extraction of PEG from water phase into the chloroform phase is proposed to be responsible for the shaping and splitting of oil droplets. This interfacial evolution as a result of PEG migration inspires us to challenge the common sense that PEG is a kind of water-soluble polymer. In practice, the solubility parameter of PEG is closer to chloroform than water (Table 1), which explains the extraction phenomenon according to solubility parameter close principle.

Figure 2. The interfacial behavior between chloroform solution and PEG aqueous solutions recorded by the pendant drop method. The PEG concentrations in water are (a) 0 mg/mL, (b) 66 mg/mL, (c) 132 mg/mL, and (d) 198 mg/mL, respectively.


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Dissipative particle dynamics (DPD) simulation, which has shown advantages in mesoscopic-scale simulation of oil-water fluid systems,43-47 is used to fully understand the interfacial distribution of PEG and the changes of interfacial curvature in the emulsion system. In order to simplify the atomistic structures of all components, water, oil and PEG molecules are modeled as beads or bead-chains accordingly as stated in the experimental section. A simulation box was set up at a fixed oil-water ratio but changed PEG contents. As shown in Figure 3, geometry optimization and DPD calculation lead to a range of equilibrated morphologies. Apparently, the change of PEG contents has little effect on the emulsion morphologies. PEG molecules are mainly dissolved in the isolated oil phase which is completely surrounded by the water phase. These simulation results agree with the solubility parameters, while they are not in accord with the emulsions phase diagrams (Figure 1) and splitting phenomenon of suspended oil droplets in the pendant drop study (Figure 2b).

Figure 3. Equilibrated morphologies of oil-water systems obtained by DPD simulation with different PEG contents under oil-water ratio of 1:3. The weight concentrations of PEG in water are 10%, 20%, 30%, 50%, 80%, and 100%, respectively. Red, blue and pink beads represent oil, water, and PEG, respectively.


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A new PEG model was proposed to reasonably correlate interfacial behaviors with emulsion phase diagrams and solubility property. As is well known, PEG possesses repeated ether groups which are supposed to interact with water molecules based on hydrogen bonding interaction. In this regard, a supramolecular polymer-water complex termed as PEG-H2O is used to replace free PEG in the water phase. Compared with free PEG in the oil phase (Figure 4a), the PEG-H2O complex is more interfacially active to locate at oil-water interfaces due to the improvement of hydrophilic component (Figure 4b). Likewise, DPD simulation was performed to simulate the interfacial behavior of PEG-H2O in the emulsion system. The PEG-H2O complex is represented by a bead-chain model in which the bonded water beads are attached on the PEG bead-chain backbone as side groups. The effect of PEG-H2O on emulsion formation was investigated by changing the oil-water ratios and the PEG-H2O contents. As shown in Figure 5, in terms of the equilibrated morphologies by DPD simulation, emulsions are successfully formed at each oil-water ratio. The PEG-H2O complexes are rich at the oil-water interface with keeping PEG chain in oil phase and the side water segments in water phase. Specifically, at the oil-water ratio of 1:3, an O/W emulsion was formed at a 10% PEG content (Figure 5a). With more PEG-H2O complexes aggregated at the oil-water interface by increasing the PEG content, the enriched oleophilic moieties induce the local interfacial inversion from the original O/W to a W/O type (Figure 5c, d). This simulated interfacial change demonstrates the PEG molecules can act as hydrophilic and oleophilic emulsifier to stabilize the binary phase interfaces. In addition, it also explains the favorable


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generation of W/O type emulsion at low PEG concentration and appearance of inner water phase in the oil droplets of O/W emulsions which indicates the formation of W/O/W double emulsions (Figure 1a).

Figure 4. (a) Free PEG chains are dissolved in oil phase. (b) Supramolecular PEG-H2O complexes based on hydrogen bonding interaction located at the oil-water interface.

However, the equilibrated morphology presents a disordered structure as the PEG-H2O content is further increased to 100% (Figure 5e). It is noteworthy that the number of oil and free water beads is dramatically reduced in a given simulation box if the PEG content reaches a high level. Due to this limitation, such a simulated box is difficult to represent the real status within the emulsions loaded with a high PEG content. In the practical emulsion system, the emulsion morphology was turned to O/W type once again at PEG concentration higher than that for W/O/W type. It is assumed that free water molecules become less because more water is consumed into PEG-H2O complex at high PEG concentration. As such, water is not enough for the formation of inner water droplets in W/O/W emulsions. On the other hand, denser


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PEG-H2O is assumed to assemble at oil-water interface at higher PEG concentration which may hinder external water molecules to enter into the oil phase. When the oil-water ratio is changed as 3:1, water is always in oil form W/O interfaces no matter how high the PEG content is, fully agreeing with the emulsion phase diagram in Figure 1b.

Figure 5. Equilibrated morphologies of oil-water systems obtained by DPD simulation with the increase of PEG-H2O contents at different oil-water ratios: (a-e) oil: water = 1:3, and (f-j) oil : water = 3:1. The weight concentrations of PEG in water are 10%, 20%, 30%, 50%, 80%, and 100%, respectively. Red, blue, yellow-green and pink beads refer to oil, free water, combined water and PEG, respectively. Temperature-dependent 1H-NMR measurements were performed in D2O to confirm the contribution of hydrogen bonding interaction to improve the hydrophilicity of PEG. The change of chemical shifts against the increase of temperature is summarized in Figure 6a. With the temperature increasing from 5oC to 45oC, the proton signal at 3.4 ppm referring to the repeating CH2 groups of PEG moves downfield gradually to 3.8 ppm. The evolution of chemical shifts is attributed to the loss of bonded water molecules on PEG chains, accounting for the change of


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PEG amphiphilicity with temperature. The characteristic peaks of PEG in CDCl3 showed almost no change against the increase of temperature, indicating that the solvation of PEG by chloroform is not sensitive to temperature. PEG under different temperatures was used to act as emulsifiers in the emulsion systems. Stable emulsion could be prepared at 5oC. When the temperature was increased to 45oC, macroscopic phase separation occurred due to the insufficient amphiphilicity as a result of the dissociation of hydrogen bonding interaction between PEG and water molecules (Figure 6b).

Figure 6. (a) Temperature-dependent 1H-NMR spectra of PEG dissolved in D2O. Inset: Temperature-dependent 1H-NMR spectra of PEG dissolved in CDCl3. (b) Optical images of emulsions prepared under different temperatures. Oil-water ratio is 1:3 and PEG concentration in water is 198 mg/mL. Another oil-water binary system was also exploited to confirm the above assumption about the distinct interfacial activity of PEG in the water and oil phases. As an alternative oil to chloroform, n-hexane has a remarkably different solubility parameter with PEG, suggesting PEG has limited solubility in n-hexane (Table 1).


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Under this circumstance, PEG is supposed to only act as a hydrophilic emulsifier in the formation of emulsions. The emulsion morphologies prepared under different oil-water ratios and PEG concentrations in water were summarized in Figure 7. When the oil-water ratio is fixed at 1:3, the oil-insoluble PEG chains are located at O/W interface as expected, leading to the formation of O/W emulsions. Different from the water-chloroform binary system, the emulsion type is always O/W without the influence by PEG concentration in water, whereas no W/O/W type emulsion and phase inversion are observed. It is because that PEG is almost insoluble in n-hexane, and thus the inner W/O interface in W/O/W emulsion is unable to exist stably. The emulsion behavior could be also predicted and proved in the case of binary system with n-hexane-water ratio of 3:1. Macroscopic phase separation took place including a top layer phase only consisting of n-hexane and a bottom layer phase formulated by O/W emulsion. These supplementary studies support that only the appropriate cooperation of interfacial organization of PEG at O/W and W/O interfaces can induce the formation of double emulsions via one-step emulsification.


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Figure 7. Bright-field microscopy images and fluorescence microscopy images of emulsions prepared with the use of n-hexane as oil phase under different oil-water ratios: (a-f) water : oil = 3:1, and (g-l) oil : water = 3:1; and different PEG concentrations in water: (a, d, g, j) 66 mg/mL, (b, e, h, k) 132 mg/mL, and (c, f, i, l) 198 mg/mL, respectively. (g, h, i) Insets: stable emulsions (a-c), and unstable emulsions with separated oil phase and water phase containing O/W emulsions (g-i). PEG can tailor the formation of one-step W/O/W double emulsions but not O/W/O double emulsions. As stated above, PEG existing as PEG-H2O complex should have an appropriate hydrophile-lipophile balance for W/O/W. In the water-chloroform binary system, more oil-favorable emulsifiers are expected to offer more opportunities for preparing O/W/O double emulsions. Therefore, improving amphiphilicity to be more oleophilic may broaden the interfacial activities of PEG, especially for one-step O/W/O double emulsions. It has been demonstrated that iodine


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(I2) can be associated with the oxygen atoms of PEG forming another supramolecular complex.48-50 Water molecules are difficult to bond on the PEG chains once the binding sites are occupied by I2 molecules (Figure 8a), leading to enhanced liphophilicity. Titration studies as monitored by UV-Vis spectroscopy and 1H NMR spectroscopy confirmed the supramolecular interaction between PEG and iodine. As shown in Figure 8b, iodine dissolved in chloroform has a maximum absorption band at 512 nm. Upon addition of PEG, two new absorptions at 293 nm and 363 nm, referring to the formation of PEG-I2 complex, are gradually increased along with the weakened adsorption at 512 nm. Such a supramolecular interaction is attributed to a coordination-like bonding association, in which iodine offers an unoccupied orbital and the oxygen atom of PEG offers a lone pair of electrons. In the NMR study, the proton signal of PEG at 3.65 ppm gradually downshifts with stepwise addition of iodine, as a result of the lowered electron density of oxygen atoms when they are bound with iodine.

Figure 8. (a) Schematic of the supramolecular interaction between PEG and I2. (b, c) Titration studies to confirm the supramolecular interaction between PEG and I2 by UV-Vis spectroscopy (b), and 1H NMR spectroscopy (c).


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To identify if the I2 bonding can change the hydrophile-lipophile balance as well as amphiphilcity of PEG, the interfacial tension between chloroform and water in the presence or absence of I2 was recorded. As compared in Figure 9, PEG-I2 can remarkably lower the interfacial tension more than that of PEG at a given PEG concentration. It is notable that PEG-I2 is relatively more active than neat PEG at the oil/water interface because of the well modified amphiphilicity. The improved amphiphilicity thereby facilitates more PEG-I2 supramolecular complex to be assembled at oil-water interface, which thus enhances the stability of prepared emulsions and also opens ways for changing the emulsion types. When PEG-I2 was used as emulsifier to prepare emulsions at the oil-water ratio of 1:3, the originally separated two phases at low PEG concentration were stabilized into emulsions (Figure 10c, f) and the O/W emulsions at high PEG concentration were partially transformed into W/O/W emulsions (Figure 10d, g). At the oil-water ratio of 3:1, like the cases using neat PEG as emulsifiers, stable W/O emulsions were not formed at low PEG concentration. However, at high PEG concentrations, O/W/O double emulsions, instead of W/O single emulsions, were successfully achieved after the one-step emulsification. This phenomenon has been predicted above that the enhancement of oleophilicity may cause the precipitation of PEG-I2 complex in the disperse phase of W/O emulsions. As a result, external oil solvents are simultaneously loaded into it, leading to the formation of inner oil phase in the W/O droplets (Figure 10e, h).


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Figure 9. The record of interfacial tension over time between aqueous solution and chloroform solutions containing different concentrations of PEG or PEG-I2. L, M, and H refer to low, medium, and high concentration, respectively.

Figure 10. (a, b) Emulsion phase diagrams with PEG-I2 as emulsifier at different oil-water ratios: (a) water : oil = 3:1, and (b) oil : water = 3:1. PEG concentrations in water are 0 mg/mL, 66 mg/mL, 132 mg/mL, and 198 mg/mL. PEG concentrations in chloroform are 0 mg/mL, 33 mg/mL, 66 mg/mL, and 132 mg/mL, respectively. (c-e) Bright-field microscopy images and (f-h) fluorescence microscopy images of emulsions marked with dashed circles in the emulsion phase diagrams.


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For the water-hexane binary system, the enhanced oleophilicity of PEG negligibly affects the emulsion types on account of the poor solubility of PEG in n-hexane. As shown in Figure 11, when the oil-water ratio is fixed at 1:3, the O/W emulsions are always formed independent on PEG concentrations in water. The O/W emulsions are still predominant for the cases with oil-water ratio of 3:1. Yet the size of dispersed emulsion droplets is increased with the increase of PEG concentration and coalescence into bigger droplets is observed at even higher PEG concentration, suggesting the decreased stability of emulsions. Notably, PEG is neither insoluble in water nor oil phase once it bonded with I2 molecules. When the high PEG concentration is used, there exist plenty of precipitated substances at the oil-water interface. These precipitates as a form of PEG-I2 aggregation behave like Pickering particles to be restrained at the interface. This control study, once again, confirms the importance of the formation and distribution of supramolecular emulsifiers, either PEG-H2O complex or PEG-I2 complex, in the two phases for the formation of double emulsions.


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Figure 11. Bright-field microscopy images and fluorescence microscopy images of emulsions prepared with the use of n-hexane as oil phase under different oil-water ratios: (a-f) water : oil = 3:1, and (g-l) oil : water = 3:1; and different PEG-I2 concentrations in water: (a, d, g, j) 66 mg/mL, (b, e, h, k) 132 mg/mL, and (c, f, i, l) 198 mg/mL.

CONCLUSION As a proof-of-concept demonstration, we presented a generally applicable strategy for preparing one-step double emulsions using PEG-based supramolecular emulsifiers. This supramolecular route avoids complicated synthesis for emulsifiers with appropriate amphiphilicity. The possible mechanism that PEG-based supramolecular complex has excellent interfacial activity was proposed and confirmed by DPD simulation. Water or iodine acts as critical actuator to tune the amphiphilicity of PEG, which enables the phase inversion and the formation of emulsions with different types. This line of research provides new inspirations for building controllable emulsions by


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using polymeric emulsifiers with supramolecular amphiphilicity regulation. It is envisioned that the concept of tuning amphiphilicity for preparing the complex emulsions could be extended to other common polymers. It is also believed that such an emulsion-templated supramolecular chemistry will offer a platform for exploiting functional materials with special topologies.

EXPERIMENTAL SECTION Materials and Instruments. Polyethylene glycol (PEG, average Mn ≈ 6000) and iodine (I2) and n-hexane were purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd.. Chloroform was provided by Beijing Chemical Works. Water (H2O) was purchased from Hangzhou Wahaha Group Co., Ltd.. A high-speed shearing emulsifier (Fluko FA25) was used to mix oil phase with water phase to prepare emulsions. The morphologies of obtained emulsions were observed and recorded by a fluorescence microscope (Zeiss Axio Scope A1). A digital camera (Olympus, E-PM1) was used to acquire optical pictures of the emulsions. The interfacial behavior between oil phase and water phase was recorded on an optical contact-angle measuring device (KRÜSS Drop Shape Analyzer DSA30). The interfacial tension was measured by the same instrument via a pendant drop method. Ultraviolet-visible (UV-Vis) spectra measurements were carried on a UV-Vis spectrophotometer (Hitachi UH-4150). 1H-NMR spectra were recorded on a Bruker 600 MHz spectrometer in CDCl3 or D2O. Preparation of Emulsions with PEG as Emulsifier. Taking the emulsion (water-oil ratio=3:1) as an example, it was prepared by emulsifying a mixture containing PEG


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aqueous solution (1.2 mL, 66 mg/mL) and PEG chloroform solution (0.4 mL, 33 mg/mL) with a high-speed shearing emulsifier (10000 rpm, 1 min). The emulsion phase diagram was built by changing concentration of PEG in aqueous solution as 0 mg/mL, 66 mg/mL, 132 mg/mL, and 198 mg/mL and in chloroform solution as 0 mg/mL, 33 mg/mL, 66 mg/mL, and 132 mg/mL, respectively. Emulsions with water-oil ratio of 1:3 were prepared according to the same procedure as stated above, while the oil-water mixture was composed of 0.4 mL aqueous solution and 1.2 mL chloroform solution. Emulsions with the use of n-hexane as oil phase were prepared by emulsifying the mixtures containing PEG aqueous solution (1.2 mL) and n-hexane solution (0.4 mL) for water-oil ratio of 3:1, and PEG aqueous solution (0.4 mL) and n-hexane solution (1.2 mL) for water-oil ratio of 1:3. PEG concentration in water was varied as 66 mg/mL, 132 mg/mL, and 198 mg/mL. Nile red was dissolved in n-hexane as an oil phase probe. Preparation of Emulsions with PEG-I2 as Emulsifier. The emulsions and phase diagrams with PEG-I2 as emulsifiers were obtained by using the same method as those using PEG as emulsifiers. Instead of the PEG chloroform solution, the oil phase of chloroform solution was loaded with PEG-I2 containing iodine with a fixed concentration (10 mM). For the water-hexane binary system, the oil phase was I2 n-hexane solution (10 mM) with Nile red as an oil probing dye. Characterization of PEG-I2 Supramolecular Interaction by UV-Vis Spectroscopy Studies. UV-Vis spectroscopy was used to identify the formation of PEG-I2 supramolecular complex. A PEG chloroform solution (0.025 mL, 2.0 M) was mixed


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with an I2 chloroform solution (0.1 mL, 2.0 mM). A certain amount of chloroform (3.875 mL) was subsequently added to maintain the total volume as 4.0 mL. After adequate mixing, the solution was characterized by the UV-Vis spectrophotometer to record its UV-Vis absorption spectrum. With keeping the total volume as 4.0 mL, other mixed solutions upon changing the volume of PEG chloroform solution (2.0 M) as 0 mL, 0.075 mL, 0.125 mL, 0.175 mL, 0.225 mL, 0.275 mL, 0.325 mL, 0.375 mL, 0.425 mL, and 0.475 mL, respectively, were also prepared for UV-Vis absorption measurements. Characterization of PEG-I2 Supramolecular Interaction by 1H-NMR Studies. 1

H-NMR study was also used to verify the supramolecular interaction between PEG

and iodine. The iodine CDCl3 solution (20 µL, 2.5 mM) was mixed into a PEG CDCl3 solution (400 µL, 200 mM). A certain amount of CDCl3 (380 µL) was added to maintain the total volume as 800 µL. The 1H-NMR spectrum of such a mixed solution was characterized on the NMR spectrometer. With keeping the total volume as 800 µL, other mixtures upon changing the volume of iodine CDCl3 solution (2.5 mM) as 0 µL, 80 µL, 140 µL, 200 µL, 260 µL, 320 µL, 380 µL, respectively, were also prepared for 1

H-NMR studies.

Characterization of Oil-Water Interfacial Behaviour and Measurement of Oil-Water Interfacial Tension. The optical contact-angle measuring apparatus was used to record the oil-water interfacial behaviour via a pendant drop method. Typically, a drop of chloroform solution was suspended into the PEG aqueous solution (66 mg/mL). The real-time change of interfacial shape was captured by a


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charge-coupled-device (CCD) camera. A series of images were obtained by changing the concentration of PEG in water as 0 mg/mL, 132 mg/mL, and 198 mg/mL. For measurement of oil-water interfacial tension, the same instrument and method were used. Differently, a drop of PEG chloroform solution (33 mg/mL) was suspended into the aqueous solution. The interfacial profiles were captured in real time by using CCD camera. The values of interfacial tension were evaluated by fitting the interfacial profiles with software. A series of interfacial tensions were obtained by changing the concentration of PEG in chloroform solution as 0 mg/mL, 66 mg/mL, and 132 mg/mL, and replacing the PEG chloroform solution with chloroform solution containing PEG-I2 supramolecular complex. Dissipative Particle Dynamics Simulation. Dissipative particle dynamics (DPD) simulation was employed to demonstrate the contribution of emulsifier to the formation of emulsions at molecular level. The emulsion system is composed of water, oil, and PEG. PEG is relatively oil-soluble and difficult to stabilize the oil-water interface by itself. However, PEG can behave like amphiphilic substance to induce the formation complex emulsions after it interacts with water molecules based on hydrogen bonding interaction. It is expected that DPD simulation may provide insights into the interfacial behavior of pure PEG and PEG with H2O (PEG-H2O) in the process of emulsification. The first step for running DPD simulation is to build proper mesomolecule models of water, oil, PEG, and PEG-H2O complex by coarse-graining superfluous atomistic models. Considering the basic requirements of DPD simulation and the components


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of emulsion system, a coarse-graining approach based on water molecules was selected and five molecules of water were grouped as one bead. This approach has been used generally in DPD simulation and produced many ideal results. The volume of one water molecule is about 30 Å3. Correspondingly, the volume of one bead is determined to be (5×30) = 150 Å3. Under the condition that the bead density is set to 3 (ρ = 3), this length unit is calculated as (3×150)1/3 = 7.66 Å, and the radius of one bead is 7.66/2 = 3.83 Å. Likewise, the mass of one bead is calculated as (5×18) = 90 amu. In addition, one bead is also defined to represent one chloroform molecule, or seven ethylene oxide units. As shown in Scheme 2, the group of five water molecules is represented by one blue bead (W), and one chloroform molecule by one red bead (O). PEG molecule is modeled with a bead-chain containing twenty pink beads (P1). In particular, the water molecules interacting with PEG are represented by yellow-green beads (P2), and PEG-H2O is modeled with a bead-chain containing twenty pink beads (P1) as main chain and twelve yellow-green beads (P2) as side chains.

Scheme 2. Schematic representation of the coarse-graining model for water, oil, PEG, and PEG-H2O. Subsequently, the interaction parameters α between all beads above need to be set up to parameterize the bead-spring mesoscale model of DPD simulation. Generally, the interaction parameters can be obtained in two steps: the determination of the


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Flory-Huggins interaction parameters χ, and the conversion of them to DPD interaction parameters. Here the Flory-Huggins interaction parameters are calculated from the solubility parameters which can be found in chemical handbooks and given in the table below: Table 1. Solubility Parameter δ of Solvents and Polymer materials

δD

δP

δH

δ

water

15.551

16.051

42.351

47.8

chloroform

17.851

3.151

5.751

18.9

n-hexane

14.951

051

051

14.9

PEG

17.3±252

3.0±152

9.4±0.352

19.9±2.252

Then, according to eq 1, χij = Vbead(δi-δj)2/RT

(1)

where Vbead is the molar volume of beads, δi and δj are the solubility parameters of bead i and j, R denotes the gas constant, and T is the absolute temperature, the Flory-Huggins parameters can be obtained as follows: Table 2. Flory-Huggins Parameters χij between Beads O

W

P1

P2 (W)

O

0

-

-

-

W

30.45

0

-

-

P1

0.37

24.08

0

-

P2 (W)

30.45

0

24.08

0

For polymer system with the bead density as 3, the interaction parameters between


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different DPD beads is linearly related to the Flory-Huggins parameters as shown in eq 2, αij = αii + 3.27χij

(2)

It is worth noting that when five water molecules were grouped into one bead, the interaction parameters between the same beads αii should equal 131.5 according to the previous study.53 Therefore, the interaction parameters for the DPD calculation are derived as follows: Table 3. Interaction Parameters αij between Beads O

W

P1

P2 (W)

O

131.5

-

-

-

W

231.08

131.5

-

-

P1

132.72

210.25

131.5

-

P2 (W)

231.08

131.5

210.25

131.5

The DPD simulation is performed on the DPD module of Mesocite Tools in Material Studio 8.0. The simulation box size was set to 100 × 100 × 100 Å, and the bead density was selected to be 3 as general setup. The emulsions in simulation were prepared in three steps. Firstly, water beads, oil beads and PEG bead-chains are filled in a simulation box; secondly, the structures are equilibrated via geometry optimization and followed with DPD calculation. For the emulsions with PEG as emulsifier, the oil-water ratio was fixed as 1:3 and the weight concentration of PEG in water was changed as 10%, 20%, 30%, 50%, 80%, and 100% to explore the effect of emulsifier concentration on the formation of emulsions. In the preparation of


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emulsions with PEG-H2O as emulsifier, the ratios between PEG beads and all water beads including free water beads and combined water beads were maintained and oil-water ratio was changed as 1:3 or 3:1 to correspond to the experimental emulsion phase diagrams. Lastly, all systems were optimized for 5000 steps by the smart minimizer algorithm. In addition, the dissipative (γ) and random (σ) forces parameters are set to 4.5 and 3, and the simulation runs for 20000 steps with a time step of 0.05.


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AUTHOR INFORMATION Corresponding Author Email: [email protected]. Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT This work was financially supported by the National Natural Science Foundation of China (21674127, 51373197, and 21422407). We are grateful to Mr. Zehuan Huang and Mr. Yang Jiao from Tsinghua University for their helpful discussion on the supramolecular chemistry. We also thank Ms. Jiarui Lu and Professor Wenzhen Lai from Renmin University of China for experimental assistance.

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Formulating Polyethylene Glycol as Supramolecular Emulsifiers for

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