Controlling amphiphilic copolymer self-assembly morphologies based on macrocycle/anion recognition and nucleotide-induced payload release

We create polymeric self-assembly morphologies by exploiting the anion binding features of the so-called ‘Texas-sized’ molecular box.


ADP and AMP induced NMR spectrum changes
Nucleotide-induced release experiments

Materials and methods
Compounds 4 S1 and 7 S2 were prepared according to literature procedures. Solvents were either employed as purchased or dried according to procedures described in the literature. 1 H NMR spectra were collected on a Bruker Advance DMX-500 spectrometer using TMS as an internal standard. Low-resolution electrospray ionization mass spectra (LRESI-MS) were obtained on a  The relatively more acidic proton H 7 on the imidazole moiety present in 1 undergoes exchange with the deuterium atoms of D 2 O. As a consequence no signal for this proton is observed in the proton NMR spectrum.

Stoichiometry and association constant determination for the complex formed between 1 and 2
To determine the stoichiometry and association constant corresponding to the interaction between macrocycle 1 and ammonium decanoate 2, 1 H NMR titrations were carried out using solutions that had a constant concentration of 1 (0.500 mM) and varying concentrations of 2. Using a non-linear curve-fitting method, the association constant between guest 2 and receptor 1 was calculated. From a mole ratio plot, evidence for a 1:1 stoichiometry was obtained.
The non-linear curve-fitting was based on the equation: S3

pH-responsiveness of the hostguest interactions
It is well known that the anionic carboxylate group can be converted into the neutral carboxylic group by decreasing the solution pH; thus the carboxylate group of 2 can be changed to their corresponding acid form by adding aqueous HCl to the initial aqueous medium. This leads to disassembly of complex 12. As shown in Figs. S15 and S16, when an aqueous HCl solution was added to a solution of 1 and 2 in D 2 O, the chemical shift values corresponding to protons present in 1 and 2 revert essentially to those of their uncomplexed forms, a result consistent with the interaction between 1 and 2 being essentially reversed. On this basis, we felt it likely that the supramolecular construct made up from 1 and 3 would also show pH-dependent behavior.
Although not a point of emphasis is this submission, support for this contention has been obtained and is given below.
The vesicles and micelles produced from 1 and 3 were used as delivery vehicles. Both sets of structures were expected to be destroyed by decreasing the pH, since this would compete with the key hostguest anion binding interaction. Because the vesicle and micelle forms contain hydrophilic cavities and hydrophobic cores, respectively, it was expected that they could be used  7. ADP and AMP induced NMR spectrum changes

The drug loading percentages
After dialyzing the mixture of DOX (2.00 mg) and micelle solution (10 mL, 42.00 mg of 3 and 17.70 mg of 1), 59.90 mg of a red powder was obtained, thus 0.20 mg DOX was loaded in the micelle solution, and the DOX load percentage is 10 wt%. Similarly, the FITC load percentage is 12 wt%.