Multicomponent assembly of cavitand-based polyacylhydrazone nanocapsules

Abstract

The thermodynamically controlled syntheses of different di-, tetra-, and hexacavitand polyacylhydrazone nanocapsules are reported. [2+4]-, [4+8]-, and [6+12]-nanocapsules assemble upon reacting a tetraformyl cavitand with two equivalents of isophthalic dihydrazide, or terephthalic dihydrazide in the presence of trifluoroacetic acid, whereby the building blocks are linked together through 8, 16, or 24 newly formed acylhydrazone bonds. Futhermore, the reaction of the tetraformylcavitands with different trigonal planar trihydrazides, simultaneously leads to the formation of [2+4]- and [6+8]-nanocapsules in varying ratios that depend on the cavitand to trihydrazide ratio and the nature of the cavitand and trihydrazide building blocks. The product ratios are rationalized with the different conformational strain of the acylhydrazone linkages in these nanocapsules. Diffusion NMR experiments with the hexacavitand polyacylhydrazone nanocapsules yield solvodynamic radii that range from 1.6 to 2.5 nm, consistent with estimates from force field calculations, and support, that these capsules have solvent filled, spherical interiors, the sizes of which approaches those of smaller proteins.