Engineering a Surfactant Trap via Postassembly Modification of an Imine Cage

Abstract

Imine self-assembly stands as a potent strategy for the preparation of molecular organic cages. However, challenges persist, such as water insolubility and limited recognition properties due to constraints in the application of specific components during the self-assembly process. In this study, we addressed these limitations by initially employing a locking strategy, followed by a postassembly modification. This sequential approach enables precise control over both the solubility and host-guest properties of an imine-based cage. The resulting structure demonstrates water solubility and exhibits an exceptional capacity to selectively interact with anionic surfactants, inducing their precipitation. Remarkably, each cage precipitates 24 equiv of anionic surfactants even at concentrations much lower than the surfactant's critical micelle concentration (CMC), ensuring their complete removal. Molecular simulations elucidate how anionic surfactants specifically interact with the cage to facilitate aggregation below the surfactant CMC and induce precipitation as a micellar cross-linker. This innovative class of cages paves the way for the advancement of materials tailored for environmental remediation.

Figure 1

Schematic illustration of the synthetic approach to develop a molecular cage capable of precipitating anionic surfactants.

Figure 2

Synthesis and characterization of molecular cage A₄B₄. (a) Preparation of the molecular cage. (b) ¹H NMR of A₄B₄ in DMSO (blue) and D₂O (pink), showing one set of signals from the aromatic panel, where the broadening of the signals in water due to slow rotation can be observed. (c) Comparison of the solubility of A₄B₄ in both acidic water and PBS buffer.

Figure 3

Synthesis and characterization of p-A₄B₄. (a) Preparation of the molecular cage. (b) HPLC chromatogram obtained for purified p-A₄B₄. The conditions of the analysis went from 95% of water to 95% of acetonitrile, both with 0.1% of TFA, in 40 min. (c) Predicted (purple profile) and obtained (red lines) MS spectra for p-A₄B₄. Spectrum shows m/z for C₂₁₆H₃₁₁N₂₈O₁₂ [M+7TFA]⁵⁺.

Figure 4

Interaction of p-A₄B₄ with SDS. (a) ¹H NMR spectra for the titration of SDS (1 mM) with cage p-A₄B₄ (from 0 to 0.04 equivalents) in D₂O, where the complete disappearance of the surfactant signal is observed. (b) Linear fit for the titration, where the equivalents of p-A₄B₄ are represented vs the surfactant’s methyl group integral. (c) Photo of the NMR tubes showing the precipitate formed after the addition of 0.04 equiv of p-A₄B₄ to the solution of SDS (1 mM).

Figure 5

¹H NMR spectra (300 MHz, 298 K) for the titration of p-A₄B₄ and three different surfactants (1 mM) with p-A₄B₄ in D₂O. (a) 16C, (b) 6C, and (c) oleate. (d) Representation of the data obtained from the titration of the former surfactants, showing the decrease in the signal corresponding to the terminal methyl group of each one. The represented data were the result of three different titrations for each surfactant. (e) Structures of the surfactants that did not show interaction with p-A₄B₄: the neutral n-dodecyl-β-d-maltoside (left) and the positively charged CTAB (right).

Figure 6

MD simulations of p-A₄B₄ and the surfactants. (a) Number of surfactants in the vicinity of p-A₄B₄ as a function of time. SDS* represents the gradual introduction of SDS into the cell to emulate the dilution conditions. (b) The relative frequency or proportion of charged (ionic, left) and neutral (aliphatic, right) groups of surfactant molecules interacting with inner, outer, or cationic regions of p-A₄B₄. Surfactant interactions with p-A₄B₄ are defined if any atoms between the two groups are within 3.0 Å. Surfactants that are not in the vicinity of p-A₄B₄ are labeled “free”. The inset shows the decomposition of regions defined for p-A₄B₄, with the inner, outer, and cationic regions highlighted in purple, orange, and green, respectively. (c) Representative simulation snapshot of SDS interacting with p-A₄B₄. The anionic headgroup is shown in red, while the aliphatic group is shown in blue. (d) Fraction of surfactant molecules assigned to the largest aggregate for simulations with multiple p-A₄B₄ units. Insets show p-A₄B₄ molecules and their attached surfactants.