Facile Fabrication of Robust Organic Counterion‐Induced Vesicles: Reversible Thermal Behavior for Optical Temperature Sensor and Synergistic Catalyst upon Removal of Amine

Abstract

A general concept of organic counterion‐directed molecular strategy for thepreparation of robust vesicles is developed. Functional amphiphilic ammonium salts (L1‐L3) bearing readily available oligo‐ethyleneglycol‐based ligand 1 and single‐tailed fatty amines self‐assemble into vesicles with controllable sizes in aqueous media. The organic counterion‐induced vesicles (OCIVs) are characterized by dynamic light scattering, transmission electron microscopy, and acid triggered release of hydrophilic drug (DOX·HCl). The introduction of organic counterion not only plays an important role in vesicle construction, but also endows the material with greatly practical values. By virtue of alkynyl groups attached on the organic ligand, the OCIVs can be easily cross‐linked via thiol‐ene reaction to generate a robust material. Importantly, the cross‐linked OCIVs exploit reversible temperature‐dependant size change, which can be repeated over 10 times without appreciable size fluctuating. Based on the unique property, a robust luminescence temperature sensor with a useful detection range of 35–70 °C is developed. Besides, removing the amines buried in the polymerized OCIVs under acidic condition, the resulting carboxylic acid‐functionalized material is found to have unusual efficiency as “nanozyme” for acetal hydrolysis, which exhibits over 20‐fold rate acceleration compared with that catalyzed by 1 or benzoic acid.

Biogenic (R)‐(+)‐Lipoic Acid Only Constructed Cross‐Linked Vesicles with Synergistic Anticancer Potency

“…The macrocyclic polyamine was selected to form SA with lipoic acid considering mainly its adjustable nitrogen atoms, which facilitate the optimization of the areas between hydrophobic and hydrophilic parts of the resulting SA to achieve the construction of expected nanovesicles. [6a,b] As shown in Figure a–c, the transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements exhibited that the SA‐bearing different macrocyclic polyamines can all self‐assemble into spherical nanoparticles above their critical aggregation concentrations (CACs; Figure S1, Supporting Information). However, the well‐established Phloxine B leakage assay indicated that only SA‐bearing macrocyclic polyamines with three and four nitrogen atoms self‐assembled into lipoic acid vesicles (LAVs), while the sample with two nitrogen atoms gave rise to a micelle‐like structure (Figure S2, Supporting Information).…”

“…The synthesis of the cross‐linked lipoic acid vesicles was exemplified with the vesicles constructed by the SA containing three nitrogen atoms (Scheme 7), and the synthetic details could be found in the “Experimental Section.” The 1 H NMR measurement verified the successful preparation of the cLAVs with the broadened proton signals after ring‐opening disulfide exchange polymerization (Figure S3a,b, Supporting Information) and the disappeared macrocyclic polyamine signals after removal of polyamine (Figure S3c, Supporting Information). The gel permeation chromatography (GPC) analysis demonstrated that the number‐average molecular weight of cLAVs reached up to 26 370 g mol −1 (Figure S4, Supporting Information), over 120 times higher than that of LA (M.W.…”

“…Typical Preparation of the Nanoparticles Formed by Lipoic Acid and Macrocyclic Polyamine with the Aid of the Counterion‐Directed Molecular Strategy :[6a] ( R )‐(+)‐Lipoic acid (82.4 mg, 0.4 mmol) and the corresponding macrocyclic polyamine (piperazine: 17.2 mg, 0.2 mmol, 1,4,7‐triazacyclononane: 17.2 mg, 0.13 mmol, or cyclen: 17.3 mg, 0.1 mmol) was added into 1 mL of dimethyl sulfoxide (DMSO) at room temperature under shaking to form SA via the acid–base neutralization. The above transparent solution of SA (50 µL) was then added dropwise into 5.0 mL of deionized water under vortex.…”

“…Phloxine B Leakage Assay :15 The structure of the LAVs was validated by well‐established Phloxine B leakage assay, where Phloxine B was trapped inside the large vesicles at a high concentration that gave significant self‐quenching; after the addition of Titron X‐100 aqueous solution (1%) to lyse the vesicles, all entrapped contents would be released and lead to a sharp increase of fluorescence at 575 nm. Briefly, the SA (50 µL, 0.2 m in DMSO) formed by LA and macrocyclic polyamine was added into 5.0 mL of aqueous solution of Phloxine B (0.5 mg mL −1 ) under vortex in the dark.…”

“…We report here the first drug carrier with the strong synergistic anticancer ability constructed totally by biogenic compounds with the aid of the counterion‐directed molecular strategy . As shown in Scheme a, the biogenic lipoic acid and macrocyclic polyamines form superamphiphile (SA) via the acid–base neutralization, which self‐assemble further into vesicles in water by adjusting the nitrogen atoms of macrocyclic polyamines.…”