Vesicle Formed by Amphiphilc Cucurbit[6]uril:  Versatile, Noncovalent Modification of the Vesicle Surface, and Multivalent Binding of Sugar-Decorated Vesicles to Lectin

Abstract

We report a novel vesicle formed by an amphiphilic CB[6] derivative, the surface of which can be easily modified via host-guest interactions by taking advantage of molecular cavities, readily accessible at the vesicle surface, and their strong affinity toward polyamines. Amphiphilic CB[6] derivative 1 synthesized by reaction between (allyloxy)12CB[6] and 2-[2-(2-methoxyethoxy)ethoxy]ethanethiol affords a vesicle that has been characterized by TEM, light scattering, and fluorescent dye entrapment experiments. Treatment of vesicle 1 with FITC (fluorescein isothiocyanate)-spermine conjugate ligand 2, in which spermine serves as a binding motif to CB[6] and FITC as a fluorescent tag, produced a surface-modified vesicle, which can be easily visualized by a confocal microscope. This result provides us with a new noncovalent, modular approach to the modification of vesicle surfaces. By treating the vesicle derived from the amphiphilic CB[6] with a tag-attached polyamine, we can easily decorate the surface of the vesicle with the tag. Sugar-decorated vesicles were prepared by this noncovalent method, and their interactions with concanavalin A (ConA) were studied. The binding constant of the vesicle decorated with mannose-spermidine conjugate 3 to ConA was measured to be approximately 3 x 104 M-1, which is almost 3 orders of magnitude higher than that of free ligand 3 to ConA (K = approximately 50 M-1). On the other hand, the binding constant of the vesicle coated with galactose-spermidine conjugate 4 to ConA was too small to be measured. These results illustrate the specific and multivalent interactions between the mannose-decorated vesicle and ConA. The ability for facile surface modification suggests many practical applications, including its use in targeted drug delivery and immunization.

Synthesis and X-ray Structure of the Inclusion Complex of Dodecamethylcucurbit[6]uril with 1,4-Dihydroxybenzene

“…The TLC analysis showed three well separated spots with a ratio of 3(s1):1(s2):1(s3), which corresponded to the normal cucurbit [5,6,7]urils (Q [5], Q [6], Q [7], Figure 1). The typical guest probe tests showed that the substituted s3 cucurbit[n]uril(s) were not SQ [7], but rather SQ [6], because no included 1-adamantaneamine (ad) resonance signals were observed in the 1 H-NMR spectrum of the s3-ad system [23], while the 1 H-NMR spectra exhibited two sets of signals for the bound (indicated by wedges) and unbound protons of the HCl salt of 2,2'-bispyridine (bpy·1HCl) which suggested that the s3 was definitely SQ [6]s [24].…”

“…The chemistry of cucurbit[n]uril (Q[n]s) has expanded dramatically with the discovery of cucurbituril(Q [6]) and its homologues (Q [5], Q [7], Q [8], and Q [10]) [1][2][3]. Recently, the direct functionalization of CB[n] [4][5][6] and introduction of building blocks for the preparation of Q[n] derivatives [7][8][9] and analogues [10][11] providing CB[n]s with solubility in both organic and aqueous solution has further expanded the range of the research and applications, which have been summarized in related reviews [12][13][14][15][16][17][18][19].…”

“…Recently, the direct functionalization of CB[n] [4][5][6] and introduction of building blocks for the preparation of Q[n] derivatives [7][8][9] and analogues [10][11] providing CB[n]s with solubility in both organic and aqueous solution has further expanded the range of the research and applications, which have been summarized in related reviews [12][13][14][15][16][17][18][19]. More recently, we have found that the solubilities of substituted cucurbit[n]urils (SQ[n]s) are dependent upon the kind, position and number of substituent groups on the substituted cucurbit[n]urils Q[n]s [20].…”

“…In this work, a similar approach to substituted cucurbituril synthesis is reported (Scheme 1), whereby one mole equivalent of monomethylglycoluril (1) was added to four mole equivalent of dimethylglycoluril (2) in 12 M HCl with the addition of formaldehyde to produce a mixture of methyl-substituted cucurbit[n=5,6]urils (Me-SQ [5,6]). From this mixture a very rare dodecamethycucurbit [6]uril (DDMeQ [6] shown in Scheme 2) can be obtained in moderate yield (compared to the yield of 0.2% in the literature method [22]). The crystal structure of DDMeQ [6] has been characterized for the first time as the inclusion host-guest complex of dodecamethycucurbit [6]uril (DDMeQ [6], host) and 1,4-dihydroxybenzene (DHOBEN, guest).…”

“…From this mixture a very rare dodecamethycucurbit [6]uril (DDMeQ [6] shown in Scheme 2) can be obtained in moderate yield (compared to the yield of 0.2% in the literature method [22]). The crystal structure of DDMeQ [6] has been characterized for the first time as the inclusion host-guest complex of dodecamethycucurbit [6]uril (DDMeQ [6], host) and 1,4-dihydroxybenzene (DHOBEN, guest).…”