Duc-Truc Pham

Cooperative binding and stabilization of the medicinal pigment curcumin by diamide linked γ-cyclodextrin dimers: a spectroscopic characterization

Diamide linked γ-cyclodextrin (γ-CD) dimers are used to capture curcumin and suppress its decomposition in water. In this study, succinamide and urea linked γ-CD dimers joined through the C6(A) carbon on each γ-CD are used. The γ-CD dimers, 66γCD(2)su and 66γCD(2)ur, show a remarkable ability to suppress the decomposition of curcumin and extend its half-life from less than 30 min to greater than 16 h. The 1:1 association of curcumin with 66γCD(2)su and 66γCD(2)ur has high stability constants of 8.7 × 10(6) M(-1) and 2.0 × 10(6) M(-1), respectively. In addition, 2D (1)H NOESY NMR results show specific hydrogen interactions in the association of curcumin with 66γCD(2)su and 66γCD(2)ur, consistent with the cooperative binding of curcumin by both γ-CD annuli of 66γCD(2)su and 66γCD(2)ur. The interactions between curcumin in the linked γ-CD dimers and surfactant micelles were studied using fluorescence spectroscopy. While linked γ-CD dimer-bound curcumin has a negligible fluorescence quantum yield, a significant increase in fluorescence intensity (Φ(fl) > 2%) in the presence of micelles suggests that curcumin is delivered to the micelle. The overall results indicate that the diamide linked γ-CD dimers are highly promising systems for curcumin delivery in vivo due to effective curcumin stabilization.

Tailoring Polymeric Hydrogels through Cyclodextrin Host―Guest Complexation

A close correllation between molecular-level interactions and macroscopic characteristics of polymer networks exists. The characteristics of the polymeric hydrogels assembled from β-cyclodextrin (β-CD) and adamantyl (AD) substituted poly(acrylate)s can be tailored through selective host-guest complexation between β-CD and AD substituents and their tethers. Dominantly, steric effects and competitive intra- and intermolecular host-guest complexation are found to control poly(acrylate) isomeric inter-strand linkage in polymer network formation. This understanding of the factors involved in polymeric hydrogel formation points the way towards the construction of increasingly sophisticated biocompatible materials.

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

Summary The employment of cyclodextrin host–guest complexation to construct supramolecular assemblies with an emphasis on polymer networks is reviewed. The main driving force for this supramolecular assembly is host–guest complexation between cyclodextrin hosts and guest groups either of which may be discrete molecular species or substituents on a polymer backbone. The effects of such complexation on properties at the molecular and macroscopic levels are discussed. It is shown that cyclodextrin complexation may be used to design functional polymer materials with tailorable properties, especially for photo-, pH-, thermo- and redox-responsiveness and self-healing.

Host–guest chemistry of linked β-cyclodextrin trimers and adamantyl substituted poly(acrylate)s in aqueous solution

1H NMR spectroscopy, isothermal titration calorimetry and rheological studies show that the β-cyclodextrin (β-CD) groups of two linked β-cyclodextrin trimers, β-CD3bz and β-CDen3bz complex the adamantyl substituents and their tethers in 3.0 ± 0.1% substituted poly(acrylate)s to form intra- and inter-poly(acrylate) strand cross-links in aqueous solution. The structures of the linked-β-cyclodextrin trimers and the length of the tether between the adamantyl substituent and the poly(acrylate) backbone have substantial effects on the complexation constants, K, and the associated thermodynamic parameters. This is partially shown for the complexation by β-CD3bz of the adamantyl substituents as tether length varies from –CONH– (3.45 × 104) through –CONH(CH2)nNHCO– where n = 2 (2.09 × 105), 6 (3.17 × 105) or 12 (7.46 × 104) in 0.13–0.37 wt% substituted poly(acrylate) solutions and the figures in brackets are the K in dm3 mol−1 at 298.2 K. For the same sequence of substituted poly(acrylate)s the variation of viscosity is: 0.03, 3.78, 3.48, and 2.03 Pa s−1 at 500 s−1 shear rate at 298.2 K for 5.0 wt% substituted poly(acrylate) solutions in which the β-CD groups of β-CD3bz and the adamantyl substituents are equimolar at 1.5 × 10−2 mol dm−3. The eight data sets for the β-CD3bz and β-CDen3bz systems are discussed in terms of host–guest interactions between the host β-CD groups and the guest adamantyl substituents of the substituted poly(acrylate)s and are compared with those for the analogous β-CD systems.

The capture and stabilization of curcumin using hydrophobically modified polyacrylate aggregates and hydrogels.

Hydrophobically modified polyacrylates are shown to suppress the degradation of the medicinal pigment curcumin under physiological conditions. In aqueous solution, the 3% octadecyl randomly substituted polyacrylate, PAAC18, forms micelle-like aggregates at a concentration of <1 wt % and a hydrogel at >1 wt %. Under both conditions, PAAC18 shows a remarkable ability to suppress the degradation of curcumin at pH 7.4 and 37 °C such that its degradation half-life is increased by 1600-2000-fold. The suppression of degradation is attributed to hydrophobic interactions between curcumin and the octadecyl substituents of PAAC18 within the micelle-like aggregates and the hydrogel, as indicated by 2D NOESY (1)H NMR spectroscopy. UV-visible absorption titration results are consistent with the interaction of curcumin with five octadecyl substituents on average, which appears to substantially exclude water and greatly decrease the curcumin degradation rate. Dynamic light scattering and zeta potential measurements show the average hydrodynamic diameters of the PAAC18 aggregates to be 0.86-1.15 μm with a negative surface charge. In contrast to the octadecyl substitution, the 3% dodecyl randomly substituted polyacrylate, PAAC12, shows a negligible effect on slowing the degradation of curcumin, consistent with the dodecyl substituents being insufficiently long to capture curcumin in a adequately hydrophobic environment. These observations indicate the potential for PAAC18 to act as a model drug delivery system.

Bridged-cyclodextrin supramolecular hydrogels: host–guest interaction between a cyclodextrin dimer and adamantyl substituted poly(acrylate)s

The formation of a hydrogel constructed from a cyclodextrin dimer (βCD2ur) and adamantyl substituted poly(acrylate) was investigated by 2D NOESY 1H NMR and isothermal titration calorimetry (ITC). The two methods generally demonstrate enhancement of complexation as the length of the hydrophobic tether increases, which is likely to be due to the cooperative effect. An optimal tether length of 6 was found to maximize the complexation between βCD2ur and the polymer. Increasing the tether length to twelve carbons slightly reduces the complexation affinity revealed by ITC experiments. Meanwhile, rheological analysis indicates the maximum degree of crosslinking was achieved by PAAADhn/βCD2ur complexation since the rigid structure of PAAAD restricts the crosslinking based on the host–guest complexation between the cyclodextrin dimer and adamantyl substituent and the competitive binding from the long alkyl tether in PAAADddn reduces the degree of crosslinking.

Dimerisation and complexation of 6-(4′-t-butylphenylamino)naphthalene-2-sulphonate by β-cyclodextrin and linked β-cyclodextrin dimers

This study shows that stereochemical factors largely determine the extent to which 6-(4′-t-butylphenylamino)-naphthalene-2-sulphonate, BNS− and its dimer, (BNS− )2, are complexed by β-cyclodextrin, βCD, and a range of linked βCD dimers. Fluorescence and 1H NMR studies, respectively, show that BNS− and (BNS− )2 form host–guest complexes with βCD of the stoichiometry βCD.BNS− (10− 4 K 1 = 4.67 dm3 mol− 1) and βCD.BNS2 2 − (10− 2 K 2′ = 2.31 dm3 mol− 1), where the complexation constant K 1 = [βCD.BNS− ]/([βCD][BNS− ]) and K 2′ = [βCD. (BNS− )2]/([βCD.BNS− ][BNS− ]) in aqueous phosphate buffer at pH 7.0, I = 0.10 mol dm3 at 298.2 K. (The dimerisation of BNS− is characterised by 10− 2 K d = 2.65 dm3 mol− 1.) For N,N-bis((2AS,3AS)-3A-deoxy-3A-β-cyclodextrin)succinamide, 33βCD2su, N-((2AS,3AS)-3A-deoxy-3A-β-cyclodextrin)-N′-(6A-deoxy-6A-β-cyclodextrin)urea, 36βCD2su, N,N-bis(6A-deoxy-6A-β-cyclodextrin)succinamide, 66βCD2su, N-((2AS,3AS)-3A-deoxy-3A-β-cyclodextrin)-N′-(6A-deoxy-6A-β-cyclodextrin)urea, 36βCD2ur, and N,N-bis(6A-deoxy-6A-β-cyclodextrin)urea, 66βCD2ur, the analogous 10− 4 K 1 = 11.0, 101, 330, 29.6 and 435 dm3 mol− 1 and 10− 2 K 2′ = 2.56, 2.31, 2.59, 1.82 and 1.72 dm3 mol− 1, respectively. A similar variation occurs in K 1 derived by UV–vis methods. The factors causing the variations in K 1 and K 2 are discussed in conjunction with 1H ROESY NMR and molecular modelling studies.

Femtosecond Transient Absorption Spectroscopy of the Medicinal Agent Curcumin in Diamide Linked γ‑Cyclodextrin Dimers

Curcumin is a biologically active polyphenol and a yellow pigment extracted from turmeric. Our previous study has shown effective encapsulation of curcumin using diamide linked γ-cyclodextrin dimers, namely 66γCD2su and 66γCD2ur, through cooperative 1:1 host-guest complexation. In this study, the excited-state dynamics of curcumin complexed with either 66γCD2su or 66γCD2ur in water are investigated using femtosecond transient absorption spectroscopy. Both 66γCD2su-curcumin and 66γCD2ur-curcumin complexes in water show only an excited-state absorption (ESA) band at 530 nm without any stimulated emission (SE) signals, indicating non-radiative decays as the major relaxation pathways. The ESA dynamics of 66γCD2su-curcumin are similar to those of 66γCD2ur-curcumin, consisting of a rapid growth component and three decay components. The growth component, which has a time constant of 0.25-0.41 ps, is assigned to solvent reorganization. The relatively fast decay components with time constants of 9.3-21.8 ps show significant deuterium isotope effect, consistent with the presence of excited-state intramolecular hydrogen atom transfer (ESIHT) of curcumin. The small-amplitude and slow decay components may be attributed to the dynamics of complexed curcumin and molecular motions due to flexibility of 66γCD2su and 66γCD2ur. In addition, transient absorption anisotropy measurements reveal slow rotational motions of 66γCD2su-curcumin and 66γCD2ur-curcumin complexes. The overall results show that complexation in 66γCD2su and 66γCD2ur has pronounced effects on the photophysics of curcumin.

Complexation of Crystal Violet, Pyronine B, and Rhodamine B by Linked β-Cyclodextrin Trimers

The host-guest complexation by β-cyclodextrin (βCD), 1,3,5-N,N,N-tris-(6A-deoxy-6A-β-cyclodextrin)-benzene (βCD3bz), and 1,3,5-N,N,N-tris(6A-(2-aminoethyl)amino-6A-deoxy-6A-β-cyclodextrin)-benzene (βCDen3bz) of cationic crystal violet (CV+) and pyronine B (PB+) and zwitterionic rhodamine B (RB) in aqueous phosphate buffer at pH 7.0 and I = 0.10 mol dm–3 has been studied by UV-Vis and 1H NMR spectroscopy. The complexation constants 10–3K1 (298.2 K) are 4.68, 86.3, and 7.08 dm3 mol–1 for the 1 : 1 host-guest complexes: βCD.CV+, βCD3bz.CV+, βCDen3bz.CV+, respectively, and those for the analogous PB+ and RB complexes have also been determined. The associated ΔHo and TΔSo for all nine complexes coincide with an entropy-enthalpy compensation plot for the formation of a wide range of βCD and modified βCD host-guest complexes reported in the literature. Crystal violet also forms (βCD)2.CV+, (βCD3bz)2.CV+ and (βCDen3bz)2.CV+ complexes characterised by 10–2K2 (298.2 K) = 2.14, 4.57, and 3.86 dm3 mol–1 and analogous (βCD)2.PB+, (βCDen3bz)2.PB+ and (βCDen3bz)2.RB complexes also form, but the (βCD3bz)2.PB+, (βCD)2.RB, and (βCD3bz)2.RB complexes were not detected. The effects of the structures of the hosts and guests on the complexation processes are discussed.

Supramolecular Chemistry of Pyronines B and Y, β-Cyclodextrin and Linked β-Cyclodextrin Dimers

The complexation of cationic pyronine B (PB+) and pyronine Y (PY+) by β-cyclodextrin (βCD) and two linked βCD dimers, N,N′-bis((2AS,3AS)-3A-deoxy-β-cyclodextrin-3A-yl)succinamide, 33βCD2suc, and N,N′-bis(6A-deoxy-β-cyclodextrin-6A-yl)succinamide, 66βCD2suc, in aqueous solution has been studied by UV-vis, fluorescence, and 1H NMR spectroscopy. The complexation constants for the 1:1 complexes: βCD.PB+, 33βCD2suc.PB+, 66βCD2suc.PB+, and the analogous PY+ complexes are reported as are the dimerization constants for PB+ and PY+. The modes of complexation, dimerization, and fluorescence quenching are discussed.