Chiral Water-Soluble Molecular Capsules With Amphiphilic Interiors

We present the synthesis of new chiral water-soluble dimeric capsules by the multicomponent Mannich reaction between charged amino acids (glutamic acid or arginine), resorcinarene, and formaldehyde and by subsequent self-assembly. The zwitterionic character of the backbones enables electrostatic interactions between arms and induces self-assembly of dimeric capsules, namely, (L-ArgR)2 and (L-GluR)2, in water with a wide range of pH, as demonstrated by NMR, diffusion coefficient measurement, and circular dichroism. The assembly/disassembly processes are fast on the NMR timescale. This mode of dimerization leaves side chains available for additional interactions and creates chiral cavities of mixed hydrophobic/hydrophilic character. According to this characteristic, capsules do not bind fully nonpolar or fully polar guests but effectively encapsulate a variety of chiral molecules with mixed polar/apolar characters (aliphatic and aromatic aldehydes, epoxides, alcohols, carboxylic acids, amines, and amino acids) with moderate strength. We also demonstrate the formation of heterocapsules (GluR) (ArgR) (homo- and heterochiral) that utilize additional interactions between charged acidic and basic side chains and have better encapsulation properties than those of the homodimers.


Synthesis and compounds characterization
All solvents and chemicals used were purchased from Sigma Aldrich, TCI Europe N. V., Roth, Chem Impex Inc., and Euriso-top, were of reagent grade and were used without further purification.
All reactions were carried out under the atmosphere of the air.
IR spectra were recorded on SHIMADZU IRTracer100 spectrophotometer.
High-resolution mass spectra were recorded on SYNAPT spectrometer.
Optical rotations were recorded on Jasco P-2000 polarymeter.

UV and ECD spectra
, Figure S55. pH-dependent a) ECD and b) UV spectra of L-GluR (C = 3.1 mM concentration calculated per cavitand, water, pH set by NaOH / HCl). Figure S56. a) ECD and b) UV spectra of titration of L-GluR (concentration calculated per cavitand, water, pH = 11.90 pH set by NaOH / HCl).