Introduction

The solvent, which makes up approx. 90% of the total mass of a reaction solution, plays an important role for a solution based chemical reaction. Solubility, equilibrium position and reaction rate are all affected by solvent1. Solvent selection continues to be one of the most challenging issues for current synthetic chemistry since most of chemical or biochemical reactions on the earth occur in wet environment2. Based on the principle of “like dissolves like”, the single solvent system is the primary choice for chemical synthesis. However, most, if not all, reactions in nature occur in mixed-solvent systems. Up to now, the mixed solvent system has been widely used for many years, especially in the coating industry3. For example, using solvent selection by computer programs, one can now easily predict how to dissolve a given polymer in a mixture of two solvents, neither of which can dissolve the polymer by itself. Though mixed solvents have been used in synthetic chemistry, few investigations have focused on how to select mixed solvents.

Water and ethanol are versatile solvents and the water-ethanol system has been broadly used. For example, mixtures with different fraction of ethanol have been used as alcoholic beverages. Another interesting example is that using 70 percent alcohol is a better disinfectant against the tubercle bacillus than using pure alcohol4. Recently, Zhang et al. developed a mixed-solvent strategy for efficient exfoliation of inorganic graphene analogues (IGAs), e.g., MoS2, WS2 and BN5. In this article, the authors demonstrated how two “poor” solvents, ethanol and water, can be designed to give high solubility to various IGAs.

Messersmith and co-workers demonstrated that dopamine self-polymerization was a powerful approach to apply multifunctional coatings onto various surfaces, including noble metals, metal oxides, ceramics and polymers. These coatings would be served as an adhesion layer to immobilize biological molecules6. Consequently, several PDA-based systems have emerged as powerful tools to address many various challenging surface problems7,8,9,10,11,12. More recently, the monodisperse polydopamine (PDA) spheres have been directly synthesized in a water-alcohol mixed solvent at room temperature. The results revealed that the volume ratio of water to alcohol strongly influenced on the synthesis of the PDA spheres13. Lu and co-workers prepared PDA spheres by use of about 29% ethanol as the solvent14. To our knowledge, there was a lack of a comprehensive principle that applied to select the volume ratio of water to alcohol for PDA synthesis. Inspired by the above results, we therefore designed the experiments to explore the influence of solvent on the synthesis of PDA spheres in the water-ethanol system.

The theory of Hansen solubility parameters (HSP) is a semi-empirical correlation developed to explain dissolution behaviour15. Briefly, HSP formula usually has the symbols δD, δP and δH, which are the dispersive, polar and hydrogen-bonding solubility parameters, respectively and are sometimes replaced by D, P and H, for convenience. The dissolution process is an adaptation between the HSP parameters of solvents and solutes. The HSP distance Ra is used to evaluate the level of adaptation and Ra can be calculated by equation (1).

The smaller the Ra value, the higher the expected solubility. In addition to single-component solvents, HSP theory can be also applied to mixed-solvents, in which each of the three HSP parameters for a solvent mixture is a linear function of composition, calculated by equation (2).

where ϕ is the volume fraction for each composition. Therefore, equation (1) and (2) enable us to predict the solubility of different chemicals in various mixed-solvents, which effectively allows us to design ideal solvent systems.

Before conducting experiments for the synthesis of PDA, Ra values between different solvent mixtures and dopamine were calculated using equation (1) and (2). More details are given in the Supporting Information (see Supplementary Materials online).

Results & discussion

Figure 1 shows the results of experiments performed in the water-ethanol mixed solvents. PDA spheres could not be formed in pure ethanol (Figure 1a), but the PDA spheres could be obtained in the mixed-solvents made with water and ethanol or pure water (Figure 1b and 1c). Monodisperse PDA spheres could be synthesized only at an appropriate ratio of ethanol/water.

Figure 1
figure 1

Synthesis of polydopamine in the water-alcohol mixed solvents.

Photograph and SEM images of polydopamine in (a) pure ethanol, (b) the ethanol-water mixed solvent with the volume ratio of 30% and (c) pure water, respectively.

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To verify the influence of solvent, we conducted the experiments to synthesize PDA in various water-ethanol mixed solvents. Figure 2 shows that the synthesis of PDA is strongly dependent on the volume fraction of ethanol in water. As shown in Figure 2c–f, the well-dispersed PDA spheres were obtained in the mixed solvents with the volume fractions of ethanol from 25% to 40%. We calculated the Ra between dopamine and ethanol/water mixtures using equations (1) and (2) based on the data listed in Table S1. Interestingly, these mixed solvents all have smaller Ra value (Table S2). In contrast, it was difficult to obtain well-dispersed PDA spheres in those mixed solvents with high Ra values. We also investigated the conversion of dopamine in the mixed solvents and found that a smaller Ra value gave a higher conversion (Table S5). Together, it seemed that the well-dispersed products with higher conversions tend to be prepared in the “good” solvents for the reactants.

Figure 2
figure 2

SEM images of PDA obtained in various ethanol/water mixtures.

The volume fractions of ethanol are (a) 0%, (b) 20%, (c) 25, (d) 30%, (e) 35%, (f) 40%, (g) 50%, (h) 70% and (i) 100%, respectively. The scale bars are 500 nm.

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It was worth mentioning that the concentration of ammonia had a dramatic effect on controlling the size of PDA spheres, but no effect on the morphology and yield of PDA sphere (Figure 3), consistent with previous reports14.

Figure 3
figure 3

SEM images of PDA spheres with different diameters prepared at different concentration of ammonia, (a) 0.1, (b) 0.17, (c) 0.2, (d) 0.28 and (e) 0.35 mL (28–30%).

The volume fractions of ethanol are all 30%.

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This alcohol-water system was not only limited to ethanol, other alcohols such as methanol or 2-propanol with smaller Ra were both proven to be efficient solvent systems. The Ra values between dopamine and methanol (or 2-propanol)/water mixtures are listed in Table S3 and S4. As predicted, the well-dispersed PDA spheres were obtained in 10% or 20% of methanol or 40% 2-propanol with smaller Ra (Figure 4). Based on the analysis of the data, it was found that in all the three mixed solvent system the solvents with the smallest Ra gave the highest percent conversion of dopamine (ρ), as shown in Tables S5–S7. It should be pointed that the ρ was calculated via the weight ratio of PDA to DA and the morphology was ignored. Under optimum experiment conditions the ρ in methanol, ethanol and 2-propanol-water system with smallest Ra was 50.57%, 40.25% and 37.18%, respectively (Table S8). The yield of PDA spheres in methanol-water mixed solvent could even reach more than 50%, indicating that the organic component of the mixed solvents is the main influence factor for the conversion of dopamine when using different solvents. Figure S1 and Figure S2 show the SEM images of PDA prepared in different methanol/water and 2-propanol/water mixtures. The PDA products tended to be assembled together in the solvents with higher Ra.

Figure 4
figure 4

SEM images of PDA obtained in (a), (b) methanol/water and (c), (d) 2-propanol/water mixtures.

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The theory of chemical equilibrium may facilitate the understanding of this concept. The concentrations of the reactants or products do not affect the equilibrium constant, but does affect the equilibrium position16. For example, a decrease in concentration of the products causes the equilibrium to shift to the side of product. In other words, if the solvent can dissolve the reactants better than the products, the equilibrium will also tend to generate products. Apparently, the solubility of solvent is very important for chemical synthesis.

In summary, we demonstrated that the PDA spheres could be more easily obtained in the weakly alkaline alcohol-water mixed solvents with smaller Ra. Although the synthesis of PDA spheres in alcohol-water mixed solvents has been reported earlier13,14, the present report is the first example of the application of HSP theory for the prediction of the PDA synthesis in alcohol-water mixed solvents. This empirical formula might be useful to predict other reaction media in chemical synthesis. Further, with the aid of computers, more complex solvents with smaller Ra for reactants can be designed for synthesis. We expect to extend the selection of mixed solvents to other synthesis in inorganic, organic and biologic chemistry.

Methods

Materials

Dopamine hydrochloride (DA) was purchased from Acros Organics (New Jersey, USA). Ammonia aqueous solution, methanol, ethanol and 2-propanol were obtained from J&K Scientific Ltd (Shanghai, China). Other chemical reagents were of analytical grade and were obtained commercially. All the solutions were prepared with Milli-Q purified water (Millipore, ≥18.2 MΩ cm).

Preparation of PDA nano-spheres

The synthesis of PDA spheres was carried out in a water-alcohol mixed solvent. The alcohol (methanol, ethanol, or 2-propanol) was mixed with water and the volume of the mixed solvent was fixed at 40.0 mL. Ammonia aqueous solution (NH4OH, 0.20 mL, 28–30%) was added to the alcohol/water mixtures under mild stirring at room temperature for 30 min. Finally, dopamine hydrochloride was directly added to the mixed solution. The color of this solution immediately turned to pale brown and gradually changed to dark brown. The reaction was allowed to proceed for 30 h according to the literature14. The product was centrifuged and washed with water and anhydrous ethanol for three times. The product was dried in vacuum overnight at 60°C was used to calculate the conversion of dopamine.

Characterization

Field-emission SEM (Hitachi S4800) was used study the morphology of the products.