Deep Inside Cucurbiturils: Physical Properties and Volumes of their Inner Cavity Determine the Hydrophobic Driving Force for Host–Guest Complexation
TL;DR: Mecozzi et al. as discussed by the authors showed that the inner cavity cavity of cucurbit[n]urils (CBn) is the most significant cavity for binding hydrophobic residues, which is confined by the planes through the oxygen carbonyls.
Abstract: Cucurbit[n]urils (CBn) bind guest molecules through a combination of electrostatic interactions with the carbonyl rims and hydrophobic interactions with the inner cavity. Investigations with solvatochromic probes in CB7 reveal that the polarity of the cavity resembles that of alcohols (e.g., n-octanol), while its polarizability (P=0.12) and apparent refractive index (nD=1.10±0.12) are extremely low, close to the gas phase. The calculated molecular quadrupole moments of CBs are extremely large (Θzz=−120 to −340 Buckingham). A survey of reported binding constants of neutral guests and hydrophobic residues that form 1 : 1 inclusion complexes with CB6, reveals a preferential inclusion of C3–C5 residues in its cavity. The largest guests which show non-negligible binding contain 7 heavy atoms (excluding hydrogen). For CB7, the strongest binding is observed for guests with adamantyl (10 heavy atoms) and ferrocenyl groups (11 heavy atoms), while the largest guests known to be complexed are carborane and the adduct of two pyridine derivatives (12 heavy atoms). The evaluation of different volumes shows that the most meaningful cavity, namely that responsible for binding of hydrophobic residues, is confined by the planes through the oxygen carbonyls. The volume of this inner cavity follows the formula V/A3=68+62(n−5)+12.5(n−5)2, affording representative cavity volumes of 68 A3 for CB5, 142 A3 for CB6, 242 A3 for CB7, and 367 A3 for CB8. The volume of the 2 bond dipole regions is comparably smaller, amounting, for example, to 2×35 A3 for CB6. The analysis of packing coefficients for representative sets of known guests with clearly defined hydrophobic binding motifs reveals average values of 47 % for CB5, 58 % for CB6, 52 % for CB7, and 53 % for CB8, which are well in line with the preferred packing (“55 % solution”, see S. Mecozzi, J. Rebek, Chem. Eur. J.1998, 4, 1016–1022) in related supramolecular host–guest assemblies. The driving force for binding of hydrophobic guests and residues by CBs is interpreted in terms of the unimportance of dispersion interactions (owing to the low polarizability of their cavity) and the dominance of classical and nonclassical hydrophobic effects related to the removal of very-high-energy water molecules (2 for CB5, 4 for CB6, 8 for CB7, and 12 for CB8) from the cavity.
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1,254 citations
TL;DR: The fundamental properties of CBn homologues and their cyclic derivatives are discussed with a focus on their synthesis and their applications in catalysis.
Abstract: In the wide area of supramolecular chemistry, cucurbit[n]urils (CBn) present themselves as a young family of molecular containers, able to form stable complexes with various guests, including drug molecules, amino acids and peptides, saccharides, dyes, hydrocarbons, perfluorinated hydrocarbons, and even high molecular weight guests such as proteins (e.g., human insulin). Since the discovery of the first CBn, CB6, the field has seen tremendous growth with respect to the synthesis of new homologues and derivatives, the discovery of record binding affinities of guest molecules in their hydrophobic cavity, and associated applications ranging from sensing to drug delivery. In this review, we discuss in detail the fundamental properties of CBn homologues and their cyclic derivatives with a focus on their synthesis and their applications in catalysis.
960 citations
TL;DR: Fluorescent Dyes and Their Supramolecular Host/Guest Complexes with Macrocycles in Aqueous Solution and how these complexes interact with each other and with solvent-free substrates is studied.
Abstract: Fluorescent Dyes and Their Supramolecular Host/Guest Complexes with Macrocycles in Aqueous Solution Roy N. Dsouza, Uwe Pischel,* and Werner M. Nau* School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany Centro de Investigaci on en Química Sostenible (CIQSO) and Departamento de Ingeniería Química, Química Física y Química Org anica, Universidad de Huelva, Campus de El Carmen s/n, E-21071 Huelva, Spain
897 citations
TL;DR: Cucurbit[n]urils have become key units in various self-organizing and stimulus-controlled assemblies, as well as in advanced materials and drug carriers.
Abstract: This review highlights the past six year advances in the blossoming field of cucurbit[n]uril chemistry. Because of their exceptional recognition properties in aqueous medium, these pumpkin-shaped macrocycles have been generating some tremendous interest in the supramolecular community. They have also become key units in various self-organizing and stimulus-controlled assemblies, as well as in advanced materials and drug carriers. The scope of this review is limited to the main family of cucurbit[n]urils (n = 5, 6, 7, 8, 10). The reader will find an overview of their preparation, their physicochemical and biological properties, as well as their recognition abilities towards various organic and inorganic guests. Detailed thermodynamic and kinetic considerations, as well as multiple applications including supramolecular catalysis are also discussed.
792 citations
TL;DR: Artificial catalysts and biomacromolecule hybrid catalysts which constitute good models towards the development of truly competitive artificial enzymes are presented.
Abstract: The design of artificial catalysts able to compete with the catalytic proficiency of enzymes is an intense subject of research. Non-covalent interactions are thought to be involved in several properties of enzymatic catalysis, notably (i) the confinement of the substrates and the active site within a catalytic pocket, (ii) the creation of a hydrophobic pocket in water, (iii) self-replication properties and (iv) allosteric properties. The origins of the enhanced rates and high catalytic selectivities associated with these properties are still a matter of debate. Stabilisation of the transition state and favourable conformations of the active site and the product(s) are probably part of the answer. We present here artificial catalysts and biomacromolecule hybrid catalysts which constitute good models towards the development of truly competitive artificial enzymes.
663 citations
References
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TL;DR: In this paper, the authors derived a modified 1/τ0=2.880×10−9n2/n2-1(gl/gu) ∫ edlnν, which should be valid for broad molecular bands when the transition is strongly allowed.
Abstract: The equations usually given relating fluorescence lifetime to absorption intensity are strictly applicable only to atomic systems, whose transitions are sharp lines. This paper gives the derivation of a modified formula 1/τ0=2.880×10−9n2〈νf−3〉Av−1(gl/gu) ∫ edlnν, which should be valid for broad molecular bands when the transition is strongly allowed.Lifetimes calculated by this formula have been compared with measured lifetimes for a number of organic molecules in solution. In most cases the values agree within experimental error, indicating that the formula is valid for such systems. The limitations of the formula and the results expected for weak or forbidden transitions are also discussed.
2,203 citations
TL;DR: 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.
Abstract: 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.
2,074 citations
1,976 citations
TL;DR: This Account is a compilation of recent literature covering the syntheses of the homologues and derivatives, and their supramolecular chemistry of cucurbituril, a synthetic receptor.
Abstract: The supramolecular chemistry of cucurbituril, a synthetic receptor, is fascinating because of the remarkable guest binding behavior of the host. Studies in the field, however, have met with limitations, since the only species known was the hexameric macrocyclic compound, cucurbit[6]uril. Recently we synthesized its homologues, cucurbit[n]uril (n = 5, 7, 8), and derivatives. These new members of the cucurbituril family have expanded the scope further, and interest in them has grown enormously. This Account is a compilation of recent literature covering the syntheses of the homologues and derivatives, and their supramolecular chemistry.
1,544 citations