Communication pubs.acs.org/cm
Gating the Trafficking of Molecules across Vesicular Membrane Composed of Dual-Cavity Baskets Shigui Chen,‡ Lu Wang,‡ Shane M. Polen, and Jovica D. Badjić* Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, United States S Supporting Information *
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mphiphilic or bolaamphiphilic molecules assemble into hierarchical nanostructures,1 constituting a variety of functional and soft materials.2 In particular, cone-shaped amphiphiles tend to pack into liposomes/vesicles3 and polymersomes4 with a capacity for storing drug molecules or enzymes in their inner aqueous reservoir.5 The molecular entrapment within such nanosized “bubbles” has permitted the preparation of liposomal formulations capable of (a) controlled delivery of pharmaceuticals,6 (b) transfection of genes,7 (c) detoxification of blood8 and even (d) delivery of dyes to textiles.9 Moreover, the entrapment of enzymes has led to the creation of nanoreactors10,11 in which biological catalysts are protected from undesired environmental influence to facilitate chemical transformations for a prolonged period of time.12 Apparently, the action of doped vesicular material is contingent upon the permeability of amphiphilic membranes13 in addition to relatively slow fusion/rupture of metastable vesicles into other lamellar phases.14 Indeed, one could tune the rate by which polar molecules traverse bipolar membranes15 by varying pH16 or using a chemical input (cholesterol,17 concave hosts,18 CO2,19 peptides,20 carbohydrates,12 etc.). In line with the notion that a passive diffusion of solutes across lipid bilayers21 is a function of the layer’s packing (fluidity),22 thickness23 and polarity24 as well as the size of solutes,25 controlling molecular trafficking to/from vesicles remains to be a challenging task and of a great interest for applications in medicinal chemistry and nanoscience.26 Accordingly, we set to investigate the capacity of large unilamellar vesicles [1]n and [1−2]n (Figure 1),27 composed of bolaamphiphilic baskets 1, to encapsulate biocompatible fluorophore rhodamine B (RhB). In particular, we wondered whether unilamellar membranes of [1]n or [1− 2]n (Figure 1) would be permeable to RhB and if so can we use an external stimulus for tuning in/out trafficking of the dye? We reason that commanding the permeability14,28,29 of vesicles composed of polyvalent bolaamphophiles of type 1, could be of interest for developing novel nanoreactors30 and creating delivery systems for applications in nanomedicine.26,31 D3 symmetric and chiral basket 1 (Figure 1), containing six (S)-alanine residues at its termini, was obtained following an earlier optimized procedure.32,33 With the assistance of both experimental and computational methods, we showed that this bolaamphiphilic host would form large unilamellar vesicles [1]n in water (DH = 230 nm, Figure 1) by placing its hydrophobic framework inside the vesicular monolayer while, concurrently, keeping six carboxylates at the interface with bulk water.27 The critical aggregation concentration corresponding to the formation of [1]n is low (
