Uril Family Research Articles

Toxicology and drug delivery by cucurbit[n]uril type molecular containers.

BackgroundMany drug delivery systems are based on the ability of certain macrocyclic compounds – such as cyclodextrins (CDs) – to act as molecular containers for pharmaceutical agents in water. Indeed β-CD and its derivatives have been widely used in the formulation of hydrophobic pharmaceuticals despite their poor abilities to act as a molecular container (e.g., weak binding (Ka<104 M−1) and their challenges toward chemical functionalization. Cucurbit[n]urils (CB[n]) are a class of molecular containers that bind to a variety of cationic and neutral species with high affinity (Ka>104 M−1) and therefore show great promise as a drug delivery system.MethodologyIn this study we investigated the toxicology, uptake, and bioactivity of two cucurbit[n]urils (CB[5] and CB[7]) and three CB[n]-type containers (Pentamer 1, methyl hexamer 2, and phenyl hexamer 3). All five containers demonstrated high cell tolerance at concentrations of up to 1 mM in cell lines originating from kidney, liver or blood tissue using assays for metabolic activity and cytotoxicity. Furthermore, the CB[7] molecular container was efficiently internalized by macrophages indicating their potential for the intracellular delivery of drugs. Bioactivity assays showed that the first-line tuberculosis drug, ethambutol, was as efficient in treating mycobacteria infected macrophages when loaded into CB[7] as when given in the unbound form. This result suggests that CB[7]-bound drug molecules can be released from the container to find their intracellular target.ConclusionOur study reveals very low toxicity of five members of the cucurbit[n]uril family of nanocontainers. It demonstrates the uptake of containers by cells and intracellular release of container-loaded drugs. These results provide initial proof-of-concept towards the use of CB[n] molecular containers as an advanced drug delivery system.

Effects of the number and placement of positive charges on viologen–cucurbit[n]uril interactions

Recent developments in the synthesis and applications of the cucurbit[n]uril family of synthetic hosts has led to an increasing interest in the detailed studies of their interactions with a wide variety of guests. This paper describes a quantitative study of the effects of the number and placement of positive charges on the binding of viologen guests to cucurbit[7]uril and cucurbit[8]uril. A series of viologen derivatives with one to four charges was characterised by isothermal titration calorimetry, 1H NMR spectroscopy and mass spectrometry to determine the stoichiometry, affinity and mode of binding. These data show that stoichiometry can be controlled by the placement of charge, and that affinity can be increased by the addition of positive charges. This study should serve as a guide for the design of supramolecular structures built from viologens and cucurbit[n]urils.

A thermodynamic analysis of the mechanism of formation of homologs of the cucurbit[n]uril family

A mechanism of the formation of cyclic cavitand CB[n] macromolecules based on the aggregation in solution of monomeric hydrate derivatives of glycoluril and formaldehyde was suggested. A quasi-chemical description of the formation of macrorings led us to conclude that the formation of the population of a definite CB[n] homolog was controlled by the solution composition. For this reason, homologs were formed in closed systems sequentially, first higher and then lower homologs, and the stable CB[6] macroring formed at the last stage of the process. Nucleation theory was used to describe the sequential formation of homolog solid phases. The use of open systems allows stationary conditions to be created for the formation of individual homologs by maintaining a constant solution composition.

Refolding Foldamers: Triazene-Arylene Oligomers That Change Shape with Chemical Stimuli

We describe the preparation of five triazene-arylene oligomers (3, 4, 7, 8, and 11) and investigations of their folding properties in aqueous solution. These oligomers contain four 2-fold rotors and populate a conformational ensemble comprising at least 10 states. Extensive 1D and 2D NMR studies as well as X-ray crystallography establish that the presence of three members of the cucurbit[n]uril family (CB[n]), CB[10], CB[7], and CB[8], results in the selective population of the (a,a,a,a)-, (a,s,s,a)-, and (a,a,a,s)-conformers. As a result of the high affinity and highly selective binding properties of the CB[n] family, it is possible to fold a single foldamer strand (3) into the CB[8].(a,a,a,s)-3 conformer by the addition of CB[8], then unfold and refold it into the CB[7].(a,s,s,a)-3.CB[7] conformer by addition of CB[7] and 3,5-dimethylaminoadamantane (17), then unfold and refold it again into the CB[10].(a,a,a,a)-3 conformer by addition of CB[10].CB[5] and aminoadamantane (18). The transformation of CB[8].(a,a,a,s)-3 into CB[7].(a,s,s,a)-3.CB[7] proceeds through the intermediacy of CB [8].(a,a,s,a)-3.CB[7], which enhances the rate of dissociation of strand 3 from CB[8].

The Cucurbit[n]uril Family

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Cucurbit[n]uril Family

In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed "cucurbituril" by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants--the pumpkin. In the intervening years, the fundamental binding properties of CB[6]-high affinity, highly selective, and constrictive binding interactions--have been delineated by the pioneering work of the research groups of Mock, Kim, and Buschmann, and has led to their applications in waste-water remediation, as artificial enzymes, and as molecular switches. More recently, the cucurbit[n]uril family has grown to include homologues (CB[5]-CB[10]), derivatives, congeners, and analogues whose sizes span and exceed the range available with the alpha-, beta-, and gamma-cyclodextrins. Their shapes, solubility, and chemical functionality may now be tailored by synthetic chemistry to play a central role in molecular recognition, self-assembly, and nanotechnology. This Review focuses on the synthesis, recognition properties, and applications of these unique macrocycles.

Acyclic Congener of Cucurbituril: Synthesis and Recognition Properties.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Acyclic congener of cucurbituril: synthesis and recognition properties.

The cucurbit[n]uril (CB[n]) family of macrocycles occupies a prominent role in molecular recognition and self-assembly studies despite the current inability to access specific cucurbit[n]uril homologues, derivatives, and analogues by straightforward tailor-made synthetic procedures. In this paper, we explore an approach that circumvents the challenges posed by the tailor-made synthesis of macrocyclic CB[n] by preparing 1, which functions as an acyclic CB[6] congener. The o-xylylene connections to the glycoluril rings preorganize 1 into the (a,a,a,a)-1 conformation required for binding and reduce its tendency to undergo self-association. We surveyed the binding properties of 1 toward 16 amines (K(a) <or= 1.52 x 10(4) M(-)(1)) and diol, diacid, guanidinium, and pyridinium species in pD 7.4 phosphate-buffered D(2)O. We find that the recognition properties of 1 parallel those of CB[6], binding tightly to alkaneammonium species in water and exhibiting length-dependent selectivity and competitive binding with alkali metals present in solution. Compound 1 binds hexanediammonium ion only 180-fold less tightly than CB[6]. The modular synthesis of 1 suggests synthetic methods toward the preparation of acyclic CB[n] congeners with complex functional groups on the edges of their aromatic rings and cavity volumes similar to CB[7] and CB[8]. In combination, these results suggest that acyclic CB[n] congeners hold promise in molecular recognition and self-assembly studies that complements that of macrocyclic CB[n].