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Synthesis and self-assembly processes of monofunctionalized cucurbit[7]uril.

ABSTRACT: We present a building-block approach toward functionalized CB[7] derivatives by the condensation of methylene-bridged glycoluril hexamer 1 and glycoluril bis(cyclic ethers) 2 and 12. The CB[7] derivatives Me2CB[7] and CyCB[7] are highly soluble in water (264 mM and 181 mM, respectively). As a result of the high intrinsic solubility of Me2CB[7], it is able to solubilize the insoluble benzimidazole drug albendazole. The reaction of hexamer 1 with glycoluril derivative 12, which bears a primary alkyl chloride group, gives CB[7] derivative 18 in 16% isolated yield. Compound 18 reacts with NaN3 to yield azide-substituted CB[7] 19 in 81% yield, which subsequently undergoes click reaction with propargylammonium chloride (21) to yield CB[7] derivative 20 in 95% yield, which bears a covalently attached triazolyl ammonium group along its equator. The results of NMR spectroscopy ((1)H, variable-temperature, and DOSY) and electrospray mass spectrometry establish that 20 undergoes self-assembly to form a cyclic tetrameric assembly (204) in aqueous solution. CB[7] derivatives bearing reactive functional groups (e.g., N3, Cl) are now available for incorporation into more complex functional systems.

SUBMITTER: Vinciguerra B

PROVIDER: S-EPMC3510339 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Synthesis and self-assembly processes of monofunctionalized cucurbit[7]uril.

Vinciguerra Brittany B Cao Liping L Cannon Joe R JR Zavalij Peter Y PY Fenselau Catherine C Isaacs Lyle L

Journal of the American Chemical Society 20120730 31

We present a building-block approach toward functionalized CB[7] derivatives by the condensation of methylene-bridged glycoluril hexamer 1 and glycoluril bis(cyclic ethers) 2 and 12. The CB[7] derivatives Me2CB[7] and CyCB[7] are highly soluble in water (264 mM and 181 mM, respectively). As a result of the high intrinsic solubility of Me2CB[7], it is able to solubilize the insoluble benzimidazole drug albendazole. The reaction of hexamer 1 with glycoluril derivative 12, which bears a primary alk ...[more]

PMID: 22799491

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Project description:Mesoporous silica nanoparticles (MSNs) are promising solid supports for controlled anticancer drug delivery. Herein, we report biocompatible layer-by-layer (LbL) coated MSNs (LbL-MSNs) that are designed and crafted to release encapsulated anticancer drugs, e.g., doxorubicin hydrochloride (DOX), by changing the pH or by adding competitive agents. The LbL coating process comprises bis-aminated poly(glycerol methacrylate)s (BA-PGOHMAs) and cucurbit[7]uril (CB[7]), where CB[7] serves as a molecular bridge holding two different bis-aminated polymeric layers together by means of host-guest interactions. This integrated nanosystem is tuned to respond under specific acidic conditions or by adding adamantaneamine hydrochloride (AH), attributed to the competitive binding of hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSN hybrids possess excellent biostability, negligible premature drug leakage at pH 7.4, and exceptional stimuli-responsive drug release performance. The pore sizes of the MSNs and bis-aminated compounds (different carbon numbers) of BA-PGOHMAs have been optimized to provide effective integrated nanosystems for the loading and release of DOX. Significantly, the operating pH for the controlled release of DOX matches the acidifying endosomal compartments of HeLa cancer cells, suggesting that these hybrid nanosystems are good candidates for autonomous anticancer drug nanocarriers actuated by intracellular pH changes without any invasive external stimuli. The successful cellular uptake and release of cargo, e.g., propidium iodide (PI), in human breast cancer cell line MDA-231 from PI-loaded LbL-MSNs have been confirmed by confocal laser scanning microscopy (CLSM), while the cytotoxicities of DOX-loaded LbL-MSNs have been quantified by the Cell Counting Kit-8 (CCK-8) viability assay against HeLa cell lines and fibroblast L929 cell lines. The uptake of DOX-loaded LbL-MSNs by macrophages can be efficiently reduced by adding biocompatible hydrophilic poly(ethylene glycol) or CB[7] without destroying the capping. In vivo tumor-growth inhibition experiments with BALB/c nude mice demonstrated a highly efficient tumor-growth inhibition rate of DOX-loaded LbL-MSNs, suggesting that the novel type of LbL-MSN materials hold great potentials in anticancer drug delivery.

Project description:Living systems utilize sophisticated biochemical regulators and various signal transduction mechanisms to program bio-molecular assemblies and their associated functions. Creating synthetic assemblies that can replicate the functional and signal-responsive properties of these regulators, while also interfacing with biomolecules, holds significant interest within the realms of supramolecular chemistry and chemical biology. This pursuit not only aids in understanding the fundamental design principles of life but also introduces novel capabilities that contribute to the advancements in medical and therapeutic research. In this study, we present a cucurbit[7]uril (CB[7]) host-guest system designed to regulate the dynamics and functions of microtubules (MTs) in living cells. To establish communication between MTs and CB[7] and to reversibly control MT function through host-guest recognition, we synthesized a two-faced docetaxel-p-xylenediamine (Xyl-DTX) derivative. While Xyl-DTX effectively stabilized polymerized MTs, inducing MT bundling and reducing dynamics in GFP-α-tubulin expressing cells, we observed a significant reduction in its MT-targeted activity upon threading with CB[7]. Leveraging the reversible nature of the host-guest complexation, we strategically reactivated the MT stabilizing effect by programming the guest displacement reaction from the CB[7]·Xyl-DTX complex using a suitable chemical signal, namely a high-affinity guest. This host-guest switch was further integrated into various guest activation networks, enabling 'user-defined' regulatory control over MT function. For instance, we demonstrated programmable control over MT function through an optical signal by interfacing it with a photochemical guest activation network. Finally, we showcased the versatility of this supramolecular system in nanotechnology-based therapeutic approaches, where a self-assembled nanoparticle system was employed to trigger the MT-targeted therapeutic effect from the CB[7]·Xyl-DTX complex.

Dataset Information

Synthesis and self-assembly processes of monofunctionalized cucurbit[7]uril.

Publications

Synthesis and self-assembly processes of monofunctionalized cucurbit[7]uril.

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