Molecular recognition and self-assembly special feature: Encapsulation and characterization of proton-bound amine homodimers in a water-soluble, self-assembled supramolecular host

Abstract

Cyclic amines can be encapsulated in a water-soluble self-assembled supramolecular host upon protonation. The hydrogen-bonding ability of the cyclic amines, as well as the reduced degrees of rotational freedom, allows for the formation of proton-bound homodimers inside of the assembly that are otherwise not observable in aqueous solution. The generality of homodimer formation was explored with small N-alkyl aziridines, azetidines, pyrrolidines, and piperidines. Proton-bound homodimer formation is observed for N-alkylaziridines (R = methyl, isopropyl, tert-butyl), N-alkylazetidines (R = isopropyl, tert-butyl), and N-methylpyrrolidine. At high concentration, formation of a proton-bound homotrimer is observed in the case of N-methylaziridine. The homodimers stay intact inside the assembly over a large concentration range, thereby suggesting cooperative encapsulation. Both G3(MP2)B3 and G3B3 calculations of the proton-bound homodimers were used to investigate the enthalpy of the hydrogen bond in the proton-bound homodimers and suggest that the enthalpic gain upon formation of the proton-bound homodimers may drive guest encapsulation.

Fig. 1.

Formation of proton bound homodimers (A) and heterodimers (B).

Fig. 2.

Graphical representation of 1. (Left) A schematic representation of 1 with only 1 ligand shown for clarity. (Right) A space-filling model of 1 as viewed down the 2-fold axis defined by the naphthalene-based ligand.

Fig. 3.

¹H NMR spectrum of 2 equivalents of N-methylpyrrolidine encapsulated in 1 in D₂O. The resonances corresponding to the assembly (*), external N-methylpyrrolidine (○) and encapsulated N-methylpyrrolidine (■) are labeled for clarity.

Fig. 4.

Dilution ¹H NMR experiments of N-methylpyrrolidine and 1. The resonances corresponding to the assembly (*), external N-methylpyrrolidine (○) and encapsulated N-methylpyrrolidine (■) are labeled for clarity. The guest region of the spectra (3 to −3 ppm) has been enlarged 4 times for clarity. The full dilution experiment is shown in Fig. S2.

Fig. 5.

The scope of cyclic amines probed in 1.

Fig. 6.

Scope and results of encapsulation studies in 1.

Fig. 7.

¹H NMR spectra of a solution of 10 with 1 (A), 4 with 1 (B), and an equimolar combination of 4 and 10 with 1 (C).

Fig. 8.

Calculated geometries for [B··H··OH₂]⁺ and [B··H··B]⁺ complexes of 2–14. Atoms are color coded for clarity: carbon (blue), nitrogen (purple), oxygen (red), hydrogen (gray).