Spontaneous association of hydrophobized dextran and poly-beta-cyclodextrin into nanoassemblies. Formation and interaction with a hydrophobic drug

New nanoassemblies were instantaneously prepared by mixing two aqueous solutions, one containing a beta-cyclodextrin polymer (pbetaCD), and the other a hydrophobically modified by alkyl chains dextran (MD). The formation mechanism and the inner structure of these nanoassemblies were analysed using surface tension measurements and (1)H NMR spectroscopy. The effect of a hydrophobic guest molecule, such as benzophenone (BZ), on the formation and stability of the nanoassemblies was also evaluated. MD exhibited the typical behaviour of a soluble amphiphilic molecule and adsorbed at the air/water interface. Whereas the injection of native beta-CDs in the solution beneath the adsorbed MD monolayer did not produce any change in the surface tension, that of the pbetaCD resulted in an increase in the surface tension, indicating the desorption of the polymer from the interface. This result accounts for a cooperative effect of beta-CDs linked together in the pbetaCD polymer on dextran desorption. The presence of benzophenone in the system hindered the sequestration of dextran alkyl moieties by beta-CD in the polymer without impeding the formation of associative nanoassemblies of 100-200 nm. (1)H NMR investigations demonstrated that, in the BZ-loaded nanoassemblies, the hydrophobic molecule was mainly located into the cyclodextrin cavities.     

High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-beta-cyclodextrin

Nanosized contrast agents have great potential in magnetic resonance molecular imaging applications for clinical diagnosis. This study proposes new nanoparticles spontaneously formed under mild conditions and composed of a noncovalent adduct between a gadolinium complex, a polymer of beta-cyclodextrin (pbetaCD: MW 1.5 x 10(6) g mol(-1)) and a dextran grafted with alkyl chains (MD). The formation of this supramolecular nanoassembly is based upon a "lock-and-key" recognition process in which the hydrophobic alkyl chains of MD and the adamantyl moieties of macrocyclic Gd(III) chelates are included in the cavities of pbetaCD. The large number of betaCDs contained in the pbetaCD resulted in the formation of 200 nm diameter nanoparticles, each entrapping 1.8 x 10(5) molecules of a low-molecular-weight Gd complex. This system, which exhibits a great relaxivity enhancement (48.4 mM(-1) s(-1), at 20 MHz and 37 degrees C) compared to the Gd(III) chelate itself (5.2 mM(-1) s(-1)), appears to be a promising strategy for the in vivo targeted delivery of Gd(III) complexes. The mechanisms of particle formation, conjugation strategies, and relaxometric characterizations in the field of contrast-enhanced magnetic resonance imaging are discussed.     

Cloud point of poly(N-isopropylacrylamide) synthesized in the presence of cyclodextrin

Polymerization of N-isopropylacrylamide (NIPAAm) was performed in the presence of β-cyclodextrin (β-CD) [or hydroxypropyl-β-cyclodextrin (HOP-β-CD)]. The formation of an inclusion complex between PNIPAAm and β-CD was confirmed by FT-IR, ¹H NMR and 2D-NOESY NMR. It was found that the cloud point (CP) of poly(N-isopropylamide) (PNIPAAm) in the PNIPAAm/β-CD complex in aqueous solution increased up to about 57°C whereas that in the PNIPAAm/β-CD blend is about 33°C. The CP of PNIPAAm in the PNIPAAm/β-CD complex is higher than that in the PNIPAAm/HOP-β-CD inclusion complex. IR and NMR results suggest that PNIPAAm chains are included in CD cavities.     

Manipulating interactions between functional colloidal particles and polyethylene surfaces using interfacial engineering

Polymer-hybridized liposomes (PHLs) of saturated lecithin were formed by association of poly(asparagines) grafted with alkyl chains (PAsn-g-Cn). The thermal, physical, and surface properties of the polymer-hybridized liposomes were examined with varying polymer concentration, alkyl chain length (C(8), C(12), C(18), C(22)), and degree of substitution (DS) in the polymer. The inclusion of the polymer raised the membrane fluidity of liposomes. By the incorporation of small amount of polymer, the membrane rigidity of liposomes dropped sharply and then increased close to the original level as the polymer concentrations increased in the cases of PAsn-g-C(18) and PAsn-g-C(22). Also, the membrane rigidity and stability of PHLs increased with alkyl chain length at the same polymer concentration. The surface charge of PHL associated with PAsn-g-C(22) was changed by DS of alkyl chains. The polymer bearing long alkyl chains (C(12), C(18), C(22)) formed PHLs well at low polymer concentration and the number of disk-shaped polymer-lipid mixed micelles increased with polymer concentration. The anchored polymers induced shifts in gel-to-liquid crystal transition temperature (Tc) of the vesicles and Tc varied with polymer concentration, alkyl chain length, and DS of the polymer.     

基于星型杂臂环糊精聚合物的纳米胶束: 构筑及包合特性

通过胺化反应和原子转移自由基聚合(ATRP),合成了以β-环糊精为“核”,以1条聚乙二醇和2~4条聚N-异丙基丙烯酰胺为“臂”的双亲水性星型杂臂聚合物(MPEG-CD-PNIPAMx)。通过1H NMR,13C NMR和凝胶渗透色谱/多角度激光光散射联用(SEC/MALLS)对其结构进行了表征。对1H NMR峰面积积分计算得聚N-异丙基丙烯酰胺“臂”数为2~4。通过紫外-可见分光光度计测得该星型大分子的较低溶液临界温度(LCST)为37℃。MPEG-CD-PNIPAMx在其水溶液温度达到LCST以上时呈现两亲性,并通过疏水相互作用自组装成以聚N-异丙基丙烯酰胺为“核”,以β-环糊精及聚乙二醇为“壳”的纳米级胶束粒子。通过MPEG-CD-PNIPAMx及其胶束粒子在芘溶液中的荧光光谱,发现胶束粒子对疏水性客体小分子的包合可发生在处于壳层的β-环糊精的疏水性空腔和胶束粒子的疏水性内核。     

Self-assembly of Aβ-based peptide amphiphiles with double hydrophobic chains

Two peptide-amphiphiles (PAs), 2C(12)-Lys-Aβ(12-17) and C(12)-Aβ(11-17)-C(12), were constructed with two alkyl chains attached to a key fragment of amyloid β-peptide (Aβ(11-17)) at different positions. The two alkyl chains of 2C(12)-Lys-Aβ(12-17) were attached to the same terminus of Aβ(12-17), while the two alkyl chains of C(12)-Aβ(11-17)-C(12) were separately attached to each terminus of Aβ(11-17). The self-assembly behavior of both the PAs in aqueous solutions was studied at 25 °C and at pHs 3.0, 4.5, 8.5, and 11.0, focusing on the effects of the attached positions of hydrophobic chains to Aβ(11-17) and the net charge quantity of the Aβ(11-17) headgroup. Cryogenic transmission electron microscopy and atomic force microscopy show that 2C(12)-Lys-Aβ(12-17) self-assembles into long stable fibrils over the entire pH range, while C(12)-Aβ(11-17)-C(12) forms short twisted ribbons and lamellae by adjusting pHs. The above fibrils, ribbons, and lamellae are generated by the lateral association of nanofibrils. Circular dichroism spectroscopy suggests the formation of β-sheet structure with twist and disorder to different extents in the aggregates of both the PAs. Some of the C(12)-Aβ(11-17)-C(12) molecules adopt turn conformation with the weakly charged peptide sequence, and the Fourier transform infrared spectroscopy indicates that the turn content increases with the pH increase. This work provides additional basis for the manipulations of the PA's nanostructures and will lead to the development of tunable nanostructure materials.     

Costa型长链烷基钴化合物的合成、表征及其与β-环糊精的作用

烷基钴Costa型化合物是一种以N,N‘－双（2,3－丁二酮－2－亚胺－3肟）丙二胺为平面配体[简称（DO）（DOH)pn]的有机钴化合物,与烷基钴肟和Schiff碱类烷基钴辅酶B12模型化合物比较,它有较好的水溶性,更接近生物体系,因而是一类重要的模型化合物^[1],近来,模拟辅酶B12在与酶相似的疏水环境中的结构和性质的全酶模型已成为研究的热点。     

Hydrophobic Derivatives of Dextran Polysaccharide: Characterization and Properties

This study reports the synthesis and characterization of hydrophobic derivatives of dextran in which long alkyl chains substituted a proportion of the hydroxyl groups. These derivatives were characterized by ¹³C and ¹H NMR and infrared spectroscopy. Information about hydrophobic associations in aqueous solutions was obtained by fluorescence spectroscopy in the presence of pyrene and nabumetone probes. These results, in addition to the swelling‐index data of derivatives, showed that there are perspectives of using them as a starting point for models of drug delivery.     

Structural study of the inclusion compounds of thymol, carvacrol and eugenol in β-cyclodextrin by X-ray crystallography

The crystal structures of the inclusion compounds of thymol, carvacrol and eugenol, (components of essential oils of vegetable origin) in β-cyclodextrin have been determined. Thymol/β-CD crystallizes in the space group P1 containing two host molecules in its asymmetric unit whereas both carvacrol/β-CD and eugenol/β-CD complexes crystallize in the space group C2. In all three complexes two host molecules form head-to-head dimers their guest/host stoichiometry being: 1/2 (carvacrol/β-CD), 2/2 (thymol/β-CD) and 3/2 (eugenol/β-CD). In the cases of the thymol/β-CD and the carvacrol/β-CD complexes the β-CD dimers are arranged according to the channel packing mode. The accommodation of the geometrical isomer guests is performed solely by their hydrophobic groups revealing the leading role of the hydrophobic driving forces in the complexation process whereas the position of their hydroxyl group affects the stoichiometry of the formed dimeric complexes. In the case of the eugenol/β-CD dimeric complex one guest molecule is found lying between the β-CD groups in a sandwich fashion whereas the other two symmetry related guests protrude outwards the narrower rim of the hosts with only their hydrophobic allyl-chain located inside the hosts’ cavities. This arrangement prohibits the formation of a channel and the observed crystal packing is that of a Tetrad mode.     

β-环糊精与十四烷基硫酸钠和全氟辛酸钠等摩尔混合体系的相互作用

通过¹H NMR和¹⁹F NMR相结合的方法研究了十四烷基硫酸钠(C₁₄H₂₉SO₄Na, STS)和全氟辛酸钠(C₇F₁₅COONa, SPFO)等摩尔混合体系与β-环糊精(β-CD)的相互作用. 实验发现, 尽管STS的临界胶束浓度(cmc)明显小于SPFO, 即在水溶液中STS的疏水性要强于SPFO, 但是β-CD仍首先选择性包结SPFO形成1∶1包结物, 然后随β-CD浓度增加主要生成STS的1∶1包结物, 最后STS的2∶1 (β-CD/STS)包结物和SPFO的2∶1 (β-CD/SPFO)包结物同时生成. 结合我们以前的工作, 本文表明, 随着碳氢表面活性剂烷基硫酸钠的链长(8～12)进一步增加到14, β-CD对氟表面活性剂SPFO的选择性进一步减弱. 也就是说, 由于β-CD的空腔和碳氟链更加匹配以及碳氟链的刚性使得β-CD/SPFO包结物的形成始终更为有利, 但这两类表面活性剂疏水性的差别对于这种选择性的程度会产生一定影响.     

Complexation of triptolide and its succinate derivative with cyclodextrins: affinity capillary electrophoresis, isothermal titration calorimetry and 1H NMR studies

The complexation of the triptolide PG490 and its succinate derivative PG490-88Na with various cyclodextrins was studied using three complementary techniques: affinity capillary electrophoresis (ACE), isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). The apparent binding constants of the complexes formed between the drugs and 8 CDs (α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD, HP-γ-CD, CM-β-CD and amino-β-CD) were determined by ACE through linear Scott's plots. The apparent and averaged binding constants of the complexes formed between PG490-88 and β-CD, γ-CD, HP-α-CD, HP-β-CD or HP-γ-CD are contained in the narrow range 135-167 M(-1). For the anionic CM-β-CD and cationic amino-β-CD, these constants are 38 and 278 M(-1), respectively, which is in accordance with electrostatic repulsions or attractions with the succinate moiety. ITC and NMR investigations for the binding constants determinations were performed for 2 CDs allowing high complexation: HP-β-CD and amino-β-CD. The three techniques provided similar results. ITC and NMR, in contrast to ACE, allowed to study the complexes formed between the neutral compound PG490 and neutral cyclodextrins. A more advanced characterization of the PG 490-88Na/amino-β-CD complex, which displays the highest apparent binding constant, was undertaken using NMR spectroscopy. The 1:1 stoichiometry of the complex was established by (1)H NMR 1D and selective 1D TOCSY experiments using the continuous variation method. Moreover, the 1D and 2D ROESY experiments revealed the inclusion of the isopropyl moiety of the triptolide derivative in the hydrophobic CD cavity. Altogether, the data provide strong evidences that the two triptolide compounds can be efficiently complexed with CD.     

Circular dichroism and fluorescence spectroscopy studies of the effect of cyclodextrins on the thermal stability of chicken egg white lysozyme in aqueous solution

Circular dichroism spectroscopy revealed that the thermal stability of chicken egg white lysozyme in an aqueous buffer solution is significantly lowered by the addition of 6-O-α-d-glucosyl-β-cyclodextrin (G1-β-CD), whereas it is raised by the addition of methyl α-d-glucopyranoside. The α- and γ-cyclodextrin also lowered the thermal stability, although the effects were less prominent than that of G1-β-CD. Fluorescence spectroscopy suggested that cyclodextrins include the side chains of tryptophan residues within their internal cavities to lower the thermal stability of lysozyme. The fluorescence intensity of a sample, re-cooled to 25 °C after thermal denaturation at 75 °C in the presence of G1-β-CD, was stronger than that observed for native lysozyme. The fact that the fluorescence intensity of the re-cooling sample was stronger than that of the native one indicates that G1-β-CD persists in binding to the side chains of tryptophan residues of the re-cooled lysozyme.     

Graphene quantum dots/β-cyclodextrin nanocomposites: A novel electrochemical chiral interface for tryptophan isomer recognition

Graphene quantum dots (GQDs) were prepared by pyrolysis of citric acid, and then incorporated into β-cyclodextrin (β-CD) via H-bonds between the oxygen-containing groups on GQDs and the hydroxyl groups on β-CD. The nanocomposites of GQDs and β-CD (GQDs/β-CD) were negatively charged due to the ionization of carboxyl groups of GQDs, and therefore they could be effectively electrodeposited onto a glassy carbon electrode (GCE). The electrodeposited GQDs/β-CD were optically active due to the introduction of β-CDs with well-defined hydrophobic central cavities, and it was employed as an electrochemical chiral interface for enantiorecognition of tryptophan (Trp) isomers.     

Solid-state NMR and wide-angle X-ray diffraction study of hydrofluoroether/β-cyclodextrin inclusion complex

An inclusion complex (IC) composed of a hydrofluoroether (HFE) guest and a β-cyclodextrin (β-CD) host was newly prepared, and the crystalline structure and the thermal stability of the IC were examined using several analytical methods, including wide-angle X-ray diffraction (WAXD), solid-state NMR, thermogravimetric analysis (TGA), TG–mass spectrometry (TG–MS), and quantum chemical calculation. The WAXD patterns and elemental analysis identified that the IC of an HFE/β-CD form of a channel-type structure, in which one HFE molecule is included in a common cavity of two β-CD molecules. TGA and TG–MS analysis indicated that the HFE molecules included in β-CD are hardly evaporated or degraded up to the decomposition temperature of the β-CD host. Solid-state ¹³C NMR indicated that the β-CD ring structure was deformed by including an HFE molecule in it, and that the ¹⁹F NMR signals of the HFE guest were significantly shifted to higher frequencies by the inclusion due to the dielectric media effect in the cavity of β-CD. Moreover, the ¹⁹F NMR signals of HFE included in IC were further shifted after annealing at 150 °C, which reflected structural changes in HFE/β-CD IC caused at elevated temperatures. The WAXD patterns also confirmed that the packing structure along the crystalline b-direction of HFE/β-CDs, which penetrates the cavities of β-CDs, was compressed by annealing and transformed to a more stable structure.     

Relaxation phenomena of polyethyleneimine molecules within saturated homogeneous and heterogeneous layers adsorbed at a silica/water interface

Surface area exclusion chromatography was used to investigate the adsorption characteristics of the highly branched polyethyleneimine (PEI) molecule and of a related molecule resulting from the grafting of PEI with C12 to C22 alkyl chains. The interfacial relaxation and surface affinity of the two polymers was determined in homogeneous and heterogeneous layers. The presence of hydrophobic moieties within the branched morphology of the grafted PEI molecule was found to modify the adsorption histogram as compared to bare PEI and to lead to greater interfacial stability. The relaxation of the bare and grafted macromolecules proved to be of equal extent but to develop at different rates within homogeneous layers. In heterogeneous layers composed of the two polymers, the slower relaxation of the grafted macromolecules decreased the rate of relaxation of the bare molecules, while the faster relaxation of the bare molecules strongly increased the rate and extent of the relaxation of the grafted macromolecules. The same technique was then used to determine the mode of establishment of the layers. The polymer coating profiles on successive glass fiber filters of the chromatography column were found to depend on the sequence of injection of the two polymers. Simultaneous and sequential adsorption processes were analyzed on the basis of the random sequential adsorption of macromolecules.     

Zn<Superscript>2+</Superscript> cation triggers self-assembly of cyclen into a stable metallogel

A novel type of ligands contained 1,4,7,10-tetrazacyclododecane and functionalized by two azobenzene moieties grafted with two alkyl chains was designed and synthesized. The ligands with long alkyl chains can form metallogels in the presence of Zn²⁺ cations. The formation of metallogel was followed by NMR and electronic spectral detection. The morphology of the xerogels is varied with the equivalent of Zn²⁺ cations and the concentration of the gel. Spectral and structural analysis indicated that the driving forces of the gel formation were attributed to intermolecular hydrophobic interactions between alkyl chains and π-π interaction between azobenzenes.     

Antibacterial modification of cellulose fibers by grafting β-cyclodextrin and inclusion with ciprofloxacin

Antibacterial-modified cellulose fiber was prepared by covalently bonding β-cyclodextrin (β-CD) with cellulose fiber via citric acid (CA) as crosslinking agent, followed by the inclusion of ciprofloxacin hydrochloride (CipHCl) as antibiotic. Effects of reaction time, temperature, concentration of β-cyclodextrin citrate (CA-β-CD) and pH on the grafting reaction were investigated, and the grafting ratio of β-CD onto cellulose fibers was 9.7 % at optimal conditions; the loading and releasing behaviors of CipHCl into/from β-CD grafted cellulose fibers were also revealed, the load amount of CipHCl into grafted cellulose fibers increased remarkably, and the release of CipHCl from the grafted cellulose fibers was prolonged. The microstructure, phase and thermal stability of modified cellulose fibers were characterized by FT-IR, ¹³C CPMAS NMR, X-ray diffraction and TGA. Considerably longer bacterial activity against E. coli and S. aureus was observed for grafted fibers loading CipHCl compared to virgin ones. Optical and mechanical properties of the paper sheets decreased generally with more antibacterial-modified fibers added.     

Sequestration of naphthenic acids from aqueous solution using β-cyclodextrin-based polyurethanes

The sorption characteristics of naphthenic acids (NAs) in their anion form with β-cyclodextrin (β-CD) based polyurethanes, as sorbents, from aqueous solutions that simulate the conditions of oil sands process water (OSPW) are presented. The copolymer sorbents were synthesized at various β-CD:diisocyanate monomer mole ratios (e.g., 1:1, 1:2, and 1:3) with diisocyanates of variable molecular size and degree of unsaturation. The equilibrium sorption properties of the copolymer sorbents were characterized using sorption isotherms in aqueous solution at pH 9.00 with electrospray ionization mass spectrometry to monitor the equilibrium unbound fraction of anionic NAs in the aqueous phase. The copolymer sorbents were characterized in the solid state using (13)C CP-MAS NMR spectroscopy, IR spectroscopy and elemental analysis. The sorption results of the copolymer sorbents with anion forms of NAs in solution were compared with a commercially available carbonaceous standard: granular activated carbon (GAC). The monolayer sorption capacities of the sorbents (Q(m)) were obtained from either the Langmuir or the Sips isotherm model used to characterize the sorption characteristics of each copolymer sorbent. The estimated sorption capacity for GAC was 142 mg NAs per g sorbent whereas the polymeric materials ranged from 0-75 mg NAs per g sorbent over the experimental conditions investigated. In general, significant differences in the sorption capacities between GAC and the copolymer sorbents were related to the differences in the accessible surface areas and pore structure characteristics of the sorbents. The Sips parameter (K(eq)) for GAC and the copolymer materials reveal differences in the relative binding affinity of NAs to the sorbent framework in accordance with the synthetic ratios and the value of Q(m). The diisocyanate linker plays a secondary role in the sorption mechanism, whereas the β-CD macrocycle in the copolymer framework is the main sorption site for NAs because of the formation of inclusion complexes with β-CD.     

Thermal stability of solid dispersions of naphthalene derivatives with β-cyclodextrin and β-cyclodextrin polymers

The thermal stabilities of some naphthalene derivatives (1-naphthyl acetate, 2-acetylnaphthalene, 1-naphthol) in β-cyclodextrin (β-CD) inclusion complexes and in β-CD-containing polymeric systems (Polyβ-CD) have been studied using thermal and thermogravimetric analyses and infrared spectroscopy. In β-CD systems, the stability of the 1-naphthyl acetate complex is lower than that of the 2-acetylnaphthalene complex, and both are more stable than the corresponding physical mixtures. For Polyβ-CD systems, the solid dispersions result much more stable than the corresponding β-CD ones, both at room temperature and at 60 °C. In the case of Polyβ-CD, besides the inclusion within CD cavities, the interaction of the guest with the crosslinking network confers an additional stability against volatilization. In contrast, an analogous crosslinked polymer prepared using sucrose instead of β-CD does not retain noticeable amounts of the naphthalene derivatives.     

Redox-responsive Inclusion Complexation between β-Cyclodextrin and Ferrocene-functionalized Poly(N-isopropylacrylamide) and its Effect on the Solution Properties of this Polymer

Ferrocene-functionalized polymers (poly(NIPAM/FCN)) and their β-CD (β-Cyclodextrin) complex have been prepared. The inclusion complexation between them was investigated by several techniques, including ¹H NMR spectra, cyclic voltammetry, UV–vis spectra and dynamic light scattering measurements. The results showed that β-CD could interact with the reduced ferrocene side groups and hardly affect the oxidized form. Thus a redox-responsive inclusion complexation system based on β-CD and poly(NIPAM/FCN) was obtained. In addition, the effect of this inclusion complexation on the solution properties of this polymer was also investigated. LCST (lower critical solution temperature) increased and the viscosity decreased upon addition of β-CD into the reduced polymer solution due to the disruption of the hydrophobic interaction between the ferrocene side groups by the inclusion complexation. Yet LCST and viscosity of the oxidized polymer solution changed slightly, which resulted from the weak interaction exerted by β-CD.