A Dual pH‐ and Light‐Responsive Spiropyran‐Based Surfactant: Investigations on Its Switching Behavior and Remote Control over Emulsion Stability

Abstract A cationic surfactant containing a spiropyran unit is prepared exhibiting a dual‐responsive adjustability of its surface‐active characteristics. The switching mechanism of the system relies on the reversible conversion of the non‐ionic spiropyran (SP) to a zwitterionic merocyanine (MC) and can be controlled by adjusting the pH value and via light, resulting in a pH‐dependent photoactivity: While the compound possesses a pronounced difference in surface activity between both forms under acidic conditions, this behavior is suppressed at a neutral pH level. The underlying switching processes are investigated in detail, and a thermodynamic explanation based on a combination of theoretical and experimental results is provided. This complex stimuli‐responsive behavior enables remote‐control of colloidal systems. To demonstrate its applicability, the surfactant is utilized for the pH‐dependent manipulation of oil‐in‐water emulsions.


Table of Contents
In a round-bottom flask, 4-(n-butyl)phenylhydrazine-hydrochloride (  In an oxygen-free atmosphere, 5-Bromosalicylaldehyd   To achieve a bromination, compound 5 (2.0 g, 4.05 mmol) was added along with 1-butyl-3methylimidazolium bromide (2.0 g, 9.1 mmol) in a tapered pear-shaped flask. The mixture was heated to 60°C, whereupon all components molt together. After 2 hours exposure to these conditions, the dark-red mixture was allowed to cool down. The solidified mixture was collected in dichloromethane and extracted with water. The organic phase was dried over Na2SO4, evaporated to dryness and chromatographied over silica gel eluating with a mixture of ethyl acetate/n-hexane = 1:8 to yield compound 6 (1.255 g, 55% yield) as a light-violet oil.      The light intensities are directly measured at the sample position prior to each measurement using a commercial S170C power meter (Thorlabs).

Potentiometric titration of compound 7
The potentiometric titration was conducted in a 80 mL glass beaker as a titration cell with a general-purpose pH probe connected to a Mettler Toledo pH-meter. Prior to each experiment, the pH-meter was thoroughly washed with deionised water and calibrated with standard buffers

Computational details
Density functional theory (DFT) calculations were performed using the Gaussian 16 program. [1] The B3LYP functional [2,3] in combination with the def2-TZVP basis set [4] was used. The D3 empirical dispersion correction with Becke-Johnson (BJ) damping was applied. [5] Solvent (water) effects were accounted for by means of the polarizable continuum model (PCM). [6,7] Surfactant geometries were optimized in the electronic ground state. Normal mode analysis was performed to assess the nature of the optimized geometries, namely zero imaginary frequencies were present for minima and one imaginary frequency for transition states (TS). For the latter, the normal mode corresponding to the imaginary frequency was visually inspected to confirm that this mode corresponds to proper atomic movements (ring-opening or isomerization).
Furthermore, intrinsic reaction coordinate (IRC) calculations [8,9] have been conducted starting from the found TS structures to verify the nature of the reactions and locate reactants and products, which were then fully reoptimized. Preliminary TS searches and IRC calculations were performed with a smaller 6-31G* basis set. [10] The and n-dodecane (8.9 mg mL -1 , Fluka, 98%, used as an internal standard) in toluene as well as another solution with p-toluenesulfonyl chloride (50 mg mL -1 , 5 eq.) in toluene was prepared.
Under ice cooling, 0.25 mL of each of the toluene solutions were pipetted to the aqueous phase.
The heterogenous mixtures were emulsified using the protocol as previously described.

Preparation of (b):
Emulsion (b) was prepared in the same manner as emulsion (a). However, a mixture of 0.25 mL of a diluted solution of p-toluenesulfonyl chloride (10 mg mL -1 , 1 eq.) and 0.25 mL of toluene were mixed with 4.75 mL of the CTAB solution, to which 250 µL of NaOAc (4.0 mg mL -1 ) were added.
The reaction progress in both emulsions (a) and (b) was monitored via pH using a SenTix HW electrode (WTW) and with gas chromatography coupled with mass spectrometry (GC/MS). The latter was performed with a Hewlett Packard HP 6890 series equipped with an Agilent 19091S-43S column with 5% phenylmethylsiloxane, 30 m×250 µm×0.25 µm with 0.8 mL min -1 Helium stream, using a temperature of 70°C for 2 min followed by a temperature ramp with 20°C min -1 for ten minutes and a subsequent constant temperature of 230°C. The gas chromatograph was coupled with a 5973Network mass selective detector (Agilent Technologies). For gas chromatography, after different time points of the reaction, 2 mL of the emulsion was sampled, filled in a glass vial, and a mixture of 1.5 mL dichloromethane and 1 mL brine was added. After vigorous shaking, the emulsion became a stable two-phase system, from which the DCM phase was subjected to GC/MS analysis.

Targeted destabilization of the emulsion droplets used as microreactors
For this purpose, the two emulsions (a) and (b) were prepared in analogy to the previous section.

Supplementary spectra characterizing the target compound and its intermediates
In this section, a supplementary NMR and ESI-MS spectra are provided for the characterization of the compounds 1 -7.

Photophysical investigations
This section provides an overview about supplementary details of the photophysical characterization of compound 7. These were performed using LED lamps, whose emission characteristics are displayed in Figure S 25.

Kinetic Investigations
Here supplementary discussions about the isomerization kinetics of compound 7, both, under pH-neutral and acidic conditions are provided. The respective data is presented in Figure S   In a next step, the absorption intensities as concluded from Figure Table S 1. The data reveal rapid conversions with reaction half-lives of approx.
6 min for the thermodynamic relaxation of the SP to the MC form as well as half-lives ranging from 1 to 16 min for the photochemically induced transfer from MC to SP depending on the wavelength (I = 1 mW cm -2 ) used for irradiation.  To investigate the kinetic behavior of the relaxation reaction in more detail, the relaxation (after switching into the SP form) was investigated in dependence of the temperature. Figure

Determination of the pH-dependent behavior of the surfactant
In this section, the characterization of surfactant 7 regarding its protonation behavior in aqueous solution, depending on its switching state, is discussed. Accordingly, the titration curve reveals a protonation of the molecule in its thermally relaxed form at a pH value of 4.5, being indicative for the protonation of MC to MCH + , while the absence of an inflection point in the titration curve of the molecule after irradiation with blue hints towards the fact that SP form does not undergo a protonation reaction in the monitored pH range. Figure   S31 shows a set of the respective UV/Vis absorption spectra under different pH values.

Micellization behavior of the surfactant
Here, supplementary insights into the micellization behavior of the surfactant are provided.  To obtain an improved insight into possible self-assembly processes, the molar extinction coefficient ε is plotted against the absorption wavelength. In a solution, in which the molecules do not show an intermolecular interaction, ε is supposed to be independent of the concentration.
In the spectra shown here, however, a decrease of characteristic molar extinction coefficients is obvious for concentrations > 0.8 mM. In solutions with concentrations higher than this (conc. > CMC of the system), self-assembly processes occur. Since these processes are accompanied by a re-arrangement of the delocalized π-system of the molecule, namely by its conversion from the MC to the SP form, species absorbing at the wavelengths characteristic for MC disappear from the solution. This is reflected by decreased ε.
Explanations on the supplementary video V1: Diluting a surfactant solution with a high concentration (containing a mixture of MC and micellized SP molecules) to a lower concentration changes the intensity of the red color.
Interestingly, a slightly red-colored solution intensifies during the dilution process. This can be explained by the fact that during the addition of water, remaining SP molecules forming micelles of are now expelled into the bulk solution to form molecules in the MC form therein (corresponding to an equilibrium shift of aggregated SP molecules due to dilution). The thermal relaxation switches over time all single SP molecules back to the MC state and the red intense color appears again over the time. The observations from Video S1 can, therefore, fairly be explained.

Theoretical considerations
Having discussed the thermodynamic details of compound 7 based on quantum-chemical calculations ( Figure Figure S34). In particular, open forms I and II differ by rotation of oxygencontaining ring around the adjacent CC bond, whereas closed forms III and IV differ in spatial arrangement of the additional proton and the nearby methyl group with respect to the ring system as shown in Figure S35. We note that here protonation is assumed to occur on oxygen for the open form and on nitrogen of spiropyran for the closed form. The SPH + form is ~ +70 kJ mol -1 higher in Gibbs free energy than the MCH + form. Protonation of SP on oxygen resulted in ring-opening during geometry optimization, in agreement with an earlier computational report for another spiropyran derivative. [11]  Thus, MCH + is much more stable than SP at acidic conditions. Finally, we note that spiropyrans were reported to undergo a spontaneous ring-opening upon protonation. [11] 6. Emulsification experiments Here, the emulsification experiments are discussed in more detail. Figure S 36 shows light micrographs of emulsions, which are displayed in Figure 6 in the main part of the manuscript.  Figure 5 in the manuscript. During 6 to 8 h, the emulsions possess a reasonable stability. After one day, however, the integrity of the acidic sample is severely affected. The scalebars are 100 µm.
Based on the pH value and the GC/MS conversion, the reaction progress can be monitored.  As a comparison experiment to the one shown in Figure 7 in the manuscript, an emulsion was prepared, which merely contains toluene sulfonyl chloride (emulsion (b), see section 1.6.4 in the SI). As this compound rapidly hydrolyses, the emulsion can be destabilized already after two hours. As a matter of the hydrolysis reaction, the emulsion quickly acidifies. (b) Image of an emulsion, which has been irradiated for 9 min with UV light, sampled after 2 h. Due to the rapid pH decrease as a result of the quick hydrolysis reaction, the surfactantstabilized emulsion can be destabilized with UV light.