2D 1H NOESY Research Articles

Modulating the Supramolecular Assembly of α-Cyclodextrin and Anderson-type Polyoxometalate through Covalent Modifications.

A series of unprecedented supramolecular complexes of covalently modified Anderson-type polyoxometalates (POMs) and α-cyclodextrins (α-CDs) have been obtained and characterized in solid state by single-crystal X-ray diffraction, and in aqueous solution using various techniques including 1H DOSY, 2D NOESY 1H NMR, isothermal titration calorimetry (ITC), and electrospray ionization time-of-flight mass spectroscopy (ESI-TOF-MS). It has been demonstrated that the supramolecular assembly process can be modulated by different covalent modification modes of the Anderson POMs, giving rise to a new type of POM/α-CD complexes featuring organic-inorganic pseudo-rotaxane structures, which are in good contrast to those of POM/γ-CD with poly-rotaxane type structures. Moreover, it is delighted to find that these pseudo-rotaxanes of POM/α-CD exhibit stable chirality in aqueous solution, which has not been accomplished in previously reported POM/γ-CD assemblies.

Prediction of Successful Amorphous Solid Dispersion Pairs through Liquid State Nuclear Magnetic Resonance.

Amorphous solid dispersions (ASDs) function in part via a "parachute effect", i.e., polymer-enabled prolonged drug supersaturation, presumably through drug-polymer interactions in the liquid state. We aim to expand the utility of liquid state nuclear magnetic resonance (1HNMR) to streamline polymer selection for ASDs. Our hypothesis is that strong molecular interactions between polymer and drug in 1HNMR anticipate reduced precipitation kinetics in supersaturation studies. For three drug-polymer pairs (i.e., etravirine with each HPMC, HPMCAS-M, and PVP-VA), 1HNMR findings were compared to more common supersaturation studies. Drug-polymer interactions were assessed by saturation transfer difference NMR (STD-NMR) and T1 relaxation time. 2D-1H NOESY experiments were also performed. Supersaturation studies involved precipitation inhibition using the solvent-shift methodology. The results from STD-NMR and T1 relaxation time indicate etravirine bound preferably to HPMCAS-M > HPMC ≫ PVP-VA. STD-NMR and T1 relaxation time yielded insight into which fragments of etravirine structure bind with HPMCAS-M and HPMC. The strong interactions from STD-NMR and T1 relaxation time changes indicated that HPMCAS-M and HPMC, but not PVP-VA, are suitable polymers to maintain etravirine supersaturation and inhibit drug precipitation. 2D-1H NOESY results corroborate the findings of STD-NMR and T1 relaxation time, showing that etravirine interacts preferably to HPMCAS-M than to PVP-VA. Supersaturation studies using solvent-shift technique corroborated our hypothesis as predissolved HPMCAS-M and HPMC, but to a less extent PVP-VA, markedly promoted etravirine supersaturation and inhibited drug precipitation. Supersaturation studies agreed with STD-NMR and T1 relaxation time predictions, as HPMC and HPMCAS-M maintained etravirine in solution for longer time than PVP-VA. The results show promise of 1HNMR to streamline polymer selection in a nondestructive and resource sparing fashion for subsequent ASD development.

Urea Disrupts the AOT Reverse Micelle Structure at Low Temperatures.

Aside from its prominent role in the excretory system, urea is also a known protein denaturant. Here, we characterize urea as it behaves in confined spaces of AOT (sodium bis(2-ethylhexyl) sulfosuccinate) reverse micelles as a model of tight, confined spaces found at the subcellular level. Dynamic light scattering revealed that low temperatures (275 K) caused the smallest of the reverse micelle sizes, w0 = 10, to destabilize and dramatically increase in apparent hydrodynamic diameter. We attribute this to urea embedded into the surfactant interface as confirmed by 2D 1H-NOESY NMR spectroscopy. This increase in size in turn caused the hydrogen exchange between urea and water within the nanosized reverse micelles to increase as measured by 1D EXSY-NMR. A minimal enlarging effect and no increase in hydrogen exchange were observed when aqueous urea was introduced into w0 = 15 or 20 reverse micelles, suggesting that this effect is unique to particularly small-diameter spaces (∼7 nm).

Structural transformations of charged spherical surfactant micelles upon solubilization of water-insoluble polymer chains in salt-free aqueous solutions

The structural transformations of charged spherical surfactant micelles of potassium oleate upon solubilization of water-insoluble polymer poly(4-vinylpyridine) were studied in salt-free aqueous solutions by several complementary techniques including SANS with contrast variation, NMR (1H and 2D 1H NOESY) spectroscopy, dynamic light scattering, cryo-TEM, and fluorescence spectroscopy. By SANS it was shown that solubilization of polymer in the micelles results in the formation of complexes with necklace structure, where the mean distance between the micelles bound to polymer (beads) is governed by electrostatic repulsion between them. The polymer penetrates deep into the hydrophobic core of the beads and occupies ca. 60% of their volume. As a result, the average number of surfactant ions in the micelles decreases from 60 till 20. The bound charged micelles impart water solubility to the polymer-surfactant system, and it behaves like a polymer coil in a thermodynamically good solvent.

Micellization of amphiphilic host–guest inclusion complexes of polymers based on β–cyclodextrin trimer and adamantane

The present work aims to study the self–aggregation of amphiphlic miktoarm star polymers synthesized via the inclusion complexation of adamantyl terminated poly(methyl methacrylate) (ADM–PMMA) guest, into β–cyclodextrin grafted polyacrylamide (β–CD–PAM) and β–cyclodextrin trimer (3–β–CD) grafted polyacrylamide (3–β–CD–PAM) star polymer hosts, separately. β–CD and 3–β–CD based hosting star polymers have been synthesized through solution polymerization technique and the guest adamantyl terminated poly(methyl methacrylate) through the technique of atom transfer radical polymerization (ATRP) by using an adamantine–based ATRP initiator. Further, the guest polymer has been incorporated into the host polymer via molecular recognition between adamantyl moiety and β–CD. Construction of β–CD–PAM–b–ADM–PMMA and 3–β–CD–PAM–b–ADM–PMMA miktoarm star polymers has been examined by 1H NMR and 2D 1H NOESY NMR spectra. Their critical micellar concentrations have been estimated by using fluorescence spectroscopy. Further, sizes of the self–aggregates have been anticipated by dynamic light scattering and transmission electron microscopic investigations.

Wholly Visible-Light-Responsive Host-Guest Supramolecular Gels Based on Methoxy Azobenzene and β-Cyclodextrin Dimers.

Much attention has been paid to construct photoresponsive host-guest supramolecular gels; however, red-shifting the responsive wavelength remains a formidable challenge. Here, a wholly visible-light-responsive supramolecular gel was fabricated through the host-guest interaction between a β-cyclodextrin (β-CD) dimer and a tetra-ortho-methoxy-substituted azobenzene (mAzo) dimer (binary gelator) in DMSO/H2O (V/V = 8/2). The minimum gelation concentration of the low-molecular-weight binary gelator was 6 wt % measured via the tube inversion method. The substituted methoxy groups shifted the responsive wavelengths of trans-mAzo and cis-mAzo to the green and blue light regions, respectively. The host-guest interaction between mAzo and β-CD as the driving force for gelation was confirmed using the 1H-NMR and 2D 1H NOESY spectra. The supramolecular gel showed good self-supporting ability with a storage modulus higher than 104 Pa. The release of Rhodamine B loaded in the gel as a model drug could be controlled by green light irradiation. We envisioned the potential applications of the wholly visible-light-responsive supramolecular compounds ranging from biomedical materials to smart materials.

Preparation of hydrophilic polymeric materials with movable cross-linkers and their mechanical property

Hydrophilic polymeric materials with movable cross-linkers were obtained by the bulk copolymerization of a hydrophilic cyclodextrin monomer (γCDAAmMe) and liquid acrylamide monomers. A 2D 1H-NOESY NMR study revealed that the main chains penetrated the CD ring units, which acted as movable cross-linking points. Copolymerization of γCDAAmMe with N,N-dimethyl acrylamide (DMAA) as a small main chain monomer results in hydrophilic movable cross-linked materials (pDMAA-γCDAAmMe (x)). On the other hand, using 4-acryloylmorpholine (ACMO) or N,N-dimethylaminopropyl acrylamide (DMAPAA) as a bulky main chain monomer disfavours the formation of movable cross-links due to steric hindrance between γCDAAmMe and the side chains. In the water content range of approximately 40–80 wt%, the Young's moduli of pDMAA-γCDAAmMe (1)s are similar to those of pDMAA-MBAAm (1). However, the fracture energy of movable cross-linked materials is higher than that of than materials covalently cross-linked with N,N′–methylenebis(acrylamide) (MBAAm). An addition of water enhanced the mobility of the main chain polymers, allowing the movable cross-linking points.

Responsive Polypseudorotaxane Hydrogels Triggered by a Compatible Stimulus of CO2

AbstractRealizing the reversible transformation of the supramolecular hydrogels is essential for their application as smart materials. The reversible sol‐gel transition of the polypseudorotaxane (PPR) hydrogels is achieved through adding a CO2‐switchable guest molecule into the PPR hydrogel of poly(ethylene glycol) (PEG) and α‐cyclodextrins (α‐CDs). Alternating treatments with CO2 and heating drive such reversible transition due to the competitive complexation as evidenced by 2D NOESY 1H NMR and isothermal titration calorimetry as well as X‐ray diffraction. The present work describes a straightforward way to obtain switchable PPR hydrogels triggered by a compatible stimulus of CO2. These stimuli‐responsive PPR hydrogels have potential applications as biomaterials.

The Influence of Fatty Acids on Metoprolol - Human Serum Albumin Interaction in Low Affinity Binding Sites: A Multifactorial NMR Approach.

Metoprolol (MTP) is a cardio-selective β1-blocker used in hypertension, angina pectoris and chronic heart failure therapies. Serum albumin is the most frequently occurring protein in blood plasma. The binding of ligands to human serum albumin (HSA) has an important effect on pharmacokinetics and final clinical effects. The objectives of this study included a detailed analysis of metoprolol - serum albumin interactions in low affinity binding sites, on the surface or within the hydrophobic subdomain of a macromolecule, as well as an analysis of the competition between MTP and fatty acids in binding with protein. The analysis of the drug-albumin interaction was based on the observed chemical shifts in combination with correlation Times (T1 -1 = τ) [1/s], 2D NOESY 1H NMR spectra and association constants Ka [M-1]. For the determination of chemical shifts σ [ppm], relaxation times T1 [s] and for the NOESY experiment, the final concentrations of MTP and albumins (in the presence (HSA) and absence of fatty acids (dHSA)) were 5 x 10-3 M and 2 x 10-5 M - 4.55 x 10-4 M, respectively. In order to calculate the association constants, the final concentrations of MTP and both HSA and dHSA were 2.75 x 10-3 M - 6.25 x 10-2 M and 2.5 x 10-4 M, respectively. For the analysis, the MTP proton resonances of aliphatic H17, aromatic (H2/H6 and H3/H5) and the methoxy group H14 were chosen. Changes in the values of the 1H NMR chemical shift [ppm] are evidence of interaction between MTP, fatted (HSA) and defatted (dHSA) human serum albumin. With an increase of albumin concentration, changes in the chemical shift values were observed for the aromatic protons H2/H6 (Δσ = 0.013 ppm and 0.018 ppm) and H3/H5 (Δσ = 0.015 ppm and 0.019 ppm), the aliphatic proton H17 (Δσ = 0.018 ppm and 0.022 ppm) and the aliphatic protons of the methoxy group H14 (Δσ = 0.019 ppm and 0.022 ppm) for dHSA and HSA, respectively. Greater changes in chemical shifts in the presence of fatty acids (FA) were observed. Changes in the correlation times of MTP aromatic H2/H6 (Δτc = 0.224 1/s and 0.189 1/s) and H3/H5 (Δτc = 0.269 1/s and 0.210 1/s), aliphatic from the methoxy group H14 (Δτc = 0.472 1/s and 0.271 1/s) and aliphatic H17 protons (Δτc = 0.178 1/s and 0.137 1/s) for dHSA and HSA systems, respectively. It confirms the interaction between the drug and albumin are evidence for the dynamics of the process. In the presence of FA the relaxation time of all analyzed MTP proton resonance signals significantly increases (due to the decrease of correlation time). This phenomenon is due to the increase of electron density in the MTP protons' surroundings. Association constants for the MTP-dHSA complex in the low affinity site range between 0.29 x 102 M-1 and 0.47 x 102 M-1. The presence of FA results in a two to three-fold increase of the Ka values of protons from aromatic (H2/H6 and H3/H5), aliphatic H17 and methoxy (H14) groups. In 2D NOESY spectra proton magnetization transfer was observed between cysteine (Cys-34) and aromatic H3/H5 and H2/H6 protons. Cross-peaks were also observed between cysteine and aliphatic protons from the methoxy group. The selective changes in σ [ppm] and τc [1/s] values indicated the unequal participation of chemical groups of MTP in the interaction with HSA and dHSA. The data obtained suggest that the presence of fatty acids increases the accessibility of low affinity sites of serum albumin to MTP, which results in the higher affinity of albumin towards the drug. The results showed that the main binding site of MTP and fatty acid is probably a low affinity site in subdomain IB, where Cys-34 can be located.

Self-assemblies of γ-CDs with pentablock copolymers PMA-PPO-PEO-PPO-PMA and endcapping via atom transfer radical polymerization of 2-methacryloyloxyethyl phosphorylcholine.

Pentablock copolymers PMA-PPO-PEO-PPO-PMA synthesized via atom transfer radical polymerization (ATRP) were self-assembled with varying amounts of γ-CDs to prepare poly(pseudorotaxanes) (PPRs). When the concentration of γ-CDs was lower, the central PEO segment served as a shell of the micelles and was preferentially bent to pass through the γ-CD cavity to construct double-chain-stranded tight-fit PPRs characterized by a channel-like crystal structure. With an increase in the amount of γ-CDs added, they began to accommodate the poly(methyl acrylate) (PMA) segments dissociated from the core of the micelles. When more γ-CDs were threaded and slipped over the segments, the γ-CDs were randomly distributed along the pentablock copolymer chain to generate single-chain-stranded loose-fit PPRs and showed no characteristic channel-like crystal structure. All the self-assembly processes of the pentablock copolymers resulted in the formation of hydrogels. After endcapping via in situ ATRP of 2-methacryloyloxyethyl phosphorylcholine (MPC), these single-chain-stranded loose-fit PPRs were transformed into conformational identical polyrotaxanes (PRs). The structures of the PPRs and PRs were characterized by means of 1H NMR, GPC, 13C CP/MAS NMR, 2D 1H NOESY NMR, FTIR, WXRD, TGA and DSC analyses.

Synthesis and Characterization of PNIPAm Core Cross‐Linked Star Polymers and Their Functionalization with Cyclodextrin

Poly(N‐isopropylacrylamide) (PNIPAm) core cross‐linked star (CCS) polymers (s‐(PNIPAm)n) are synthesized by arm‐first ATRP method. The related synthesis conditions are investigated and optimized. By varying cross‐linker N,N‐methylenebisacrylamide (BIS) concentration, PNIPAm CCS polymers with about 47, 86, and 211 arms are synthesized. Then, under ATRP condition, the “living” sites at the core of s‐(PNIPAm)n reacting with a monovinyl β‐cyclodextrin (β‐CD) monomer afford β‐CD functionalized s‐(PNIPAm)n (CDF‐SPNIPAm). The structures of the star polymers are characterized. The results indicate that in CDF‐SPNIPAm, the ratio of β‐CD units to PNIPAm arm numbers could be up to 0.6:1. The fluorescence spectra of star polymer/ANS (8‐­anilino‐1‐naphthalenesulfonic acid ammonium salt hydrate) systems prove that the β‐CD moieties of CDF‐SPNIPAm are available for including guest molecules. By using pH‐sensitive adamantyl (Ada)‐terminated poly(4‐vinylpyridine) (Ada‐P4VP) (synthesized by ATRP strategy) as a model guest macromolecule, the host–guest complexation between β‐CD units of CDF‐SPNIPAm and adamantyl groups of Ada‐P4VP is confirmed via 2D NOESY 1H NMR and DLS measurements. The results indicate that the presence of the Ada‐P4VP arms provides temperature‐responsive star polymers with pH sensitivity. Therefore, the β‐CD‐functionalized star PNIPAm could provide host macromolecular platform for constructing novel miktoarm star polymers. image

Thermo-, pH-, and Light-Responsive Supramolecular Complexes Based on a Thermoresponsive Hyperbranched Polymer.

Hyperbranched polyethylenimine terminated with isobutyramide groups (HPEI-IBAm) was mixed with 4-(phenylazo)benzoic acid (PABA) to form supramolecular complexes through the neutralization reaction between the amino groups of HPEI-IBAm and the carboxylic acid group of PABA, which was verified by 1H and 2D NOESY 1H NMR spectroscopy. The obtained supramolecular complexes with a molar ratio of PABA to HPEI-IBAm of ≤8 were soluble in water and exhibited thermoresponsive properties. Their cloud point temperature (Tcp) was sensitive to PABA content, and PABA molecules were exchanged between HPEI-IBAm hosts. The topology of the polymer affected the change in Tcp of the complexes. At pH ∼7, increasing the PABA content decreased Tcp, whereas it caused Tcp to increase at pH ∼9. Reversible trans-to-cis photoisomerization of azobenzene units in the complexes occurred following irradiation with UV or visible light. At pH ∼7, trans-to-cis isomerization of azobenzene units increased Tcp, whereas the opposite occurred at pH ∼9.

Synthesis, characterization and structure optimization of a series of thiazolidinone derivatives as Entamoeba histolytica inhibitors

A series of thiazolidinone derivatives were synthesized by sodium acetate assisted cyclization of 1-isobutyl-3-phenylthiourea with chloroacetic acid followed by the piperidine facilitated substitution of the resulting thiazolidinone with different substituted aldehydes. The ethene and imine double bonds adopt (Z,Z) configuration as indicated by 1H–1H COSY and 2D-NOESY 1H NMR and further confirmed by the crystal structure studies. The in vitro antiamoebic activity of these compounds was evaluated against HM1:IMSS strain of Entamoeba histolytica. Eight compounds exhibited promising activity with IC50 values (0.11–0.172 μM) lower than the standard drug metronidazole (IC50 1.64 μM). In vitro cytotoxicity results revealed low cytotoxic up to the concentration of 25 μM.

Aggregation and Host–Guest Interactions in Dansyl-Substituted Poly(acrylate)s in the Presence of β-Cyclodextrin and a β-Cyclodextrin Dimer in Aqueous Solution: A UV–Vis, Fluorescence, 1H NMR, and Rheological Study

A UV–vis, steady-state, and time-resolved fluorescence 2D 1H NOESY NMR spectroscopic and rheological study of new poly(acrylate)s 3% randomly substituted with either N-(2-aminoethyl)-, N-(6-aminohexyl)-, or N-(12-aminododecyl)-5-dansyl-sulfonamide to give the substituted polymers PAADSen, PAADShn, and PAADSddn, respectively, is reported. Their dansyl substituent aggregation and complexation by β-cyclodextrin, βCD, and its covalently linked dimer N,N′-bis(6A-deoxy-6A-β-cyclodextrin)urea, 66βCD2ur, is also reported. The βCD complexation of the dansyl substituents is characterized by apparent complexation constants, K = 89, 105, and 55 dm3 mol–1 for PAADSen, PAADShn, and PAADSddn, respectively, and the analogous complexations by 66βCD2ur are characterized by K = 3.04 × 103, 3.42 × 104, and 2.42 × 105 dm3 mol–1 at pH 7.0 in aqueous 0.10 mol dm–3 NaCl at 298.2 K. Under the same conditions the dansyl substituent shows three fluorescence decay constants assigned to the aggregated (τ1 = 2.2, 2.5, and 3.2 ns), sin...

Selective supramolecular bindings for stepwise signal output

The design and construction of functional supramolecular systems capable of digital information processing is very important. In this work, we synthesized two fluorescent guest compounds (OVN and MVN) for supramolecular bindings at different sites with cucurbit[7]uril (CB7) and α-cyclodextrin (α-CD). The selective host–guest formation was employed to control the systems’ fluorescent signal for different-mode performances. The structural characterizations were conducted by 1H NMR, HRMS, and 2D NOESY 1H NMR spectroscopy. Specifically, the selective supramolecular bindings of CB7 and α-CD will cause a stepwise variation of the fluorescent signal output in OVN guest system. This signal can also be stepwise reset by introduction of different competing substances. On the other hand, supramolecular bindings can only lead to a binary signal change in MVN guest system.

Aggregation of Hydrophobic Substituents of Poly(acrylate)s and Their Competitive Complexation by β- and γ-Cyclodextrins and Their Linked Dimers in Aqueous Solution

Competition between the aggregation of the octadecyl substituents of 3% randomly substituted poly(acrylate), PAAC18, and of the dodecyl substituents of the PAAC12 analogue, and their complexation by β-cyclodextrin, βCD, the linked dimers, N,N′-bis(6A-deoxy-6A-β-cyclodextrin)urea, 66βCD2ur, and N,N′-bis(6A-deoxy-6A-β-cyclodextrin)succinamide, 66βCD2su, and γ-cyclodextrin, γCD, and the analogous dimers 66γCD2ur and 66γCD2su have been studied in aqueous solution. The zero-shear viscosities of 3.3 wt % aqueous solutions of PAAC18, decreases in the presence of βCD, 66βCD2ur, 66βCD2su and γCD, is little changed in the presence of 66γCD2ur, and increases in the presence of 66γCD2su. In contrast, the zero-shear viscosities of aqueous solutions of PAAC12 increase in the presence of βCD, γCD, and their dimers but they are much less than those of the corresponding PAAC18 solutions. These macroscopic variations are due to host–guest complexation of the octadecyl and dodecyl substituents by βCD, γCD, and their dimers (as shown by 2D 1H NOESY NMR spectroscopy) competing with aggregation of the octadecyl and dodecyl substituents where differences in substituent length and cyclodextrin annular size are dominant factors.

Meta-Substituted benzamide oligomers that complex mono-, di- and tricarboxylates: folding-induced selectivity and chirality

meta-Substituted arylamide trimer, pentamer and heptamer have been prepared from simple benzene-1,3-diamine, benzene-1,3-dicarboxylic acid, and 3-aminobenzoic acid units. 2D NOESY (1)H NMR experiments reveal that these flexible oligomers form folded conformations to complex di- and tricarboxylate anions of varying sizes and shapes in DMSO of high polarity, which is driven by multiple intermolecular N-H···O=C and C-H···O=C hydrogen-bonds between the amide and aromatic hydrogens of the oligomers and the carboxylate oxygens of the anions. Generally, tricarboxylate anions display an increased binding affinity compared with the dicarboxylate anions and the complexes formed by 1,3-benzenedicarboxylate anion are more stable than those formed by 1,2- or 1,4-benzenedicarboxylate anions. Circular dichroism experiments show that chiral glutamic acid dianion can induce the oligomers to produce chiral bias, leading to the formation of chiral supramolecular complexes.

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.

Cooperative molecular recognition of dyes by two bis(β-cyclodextrin)s with aromatic, sulfur-containing, diamine tethers

The molecular binding behavior of two bis(β-cyclodextrin (CD))s, that is, 4,4′-diaminodiphenylsulfone-bridged bis(β-CD) 2 and 4,4′-diaminodiphenyldisulfide-bridged bis(β-CD) 3 with some representative organic dyes, i.e., acridine red (AR), neutral red (NR), ammonium 8-anilino-1-naphthalenesulfonate (ANS), sodium 2-(p-toluidinyl)naphthalenesulfonate (TNS), rhodamine B (RhB), and brilliant green (BG), has been investigated at 25 °C in phosphate buffer (pH 7.20) by ultraviolet, fluorescence and 2D NMR spectroscopy. The fluorescence of ANS, TNS, AR, and NR are enhanced, whereas that of RhB is quenched, by inclusion complexation with both host compounds. The results obtained show bridged bis(β-CD)s 2 and 3 with dye guests give higher complex stability constants (KS) than those of the native β-CD 1, through cooperative binding of two hydrophobic CD cavities with one guest. In addition, the KS values of all guests with host 3 are much larger than those with 2 except for NR as guest. The 2D 1H NOESY spectrum of host 3 and RhB was acquired to confirm the cooperative binding mode. The molecular binding ability of dyes by hosts 1–3 are discussed from the viewpoint of the size and shape-fitting relationship between host and guest.

ChemInform Abstract: Electro-organic Reactions. Part 51. Reactivity and Stereochemical Pathways for Cathodically Generated Radical-Anions of α,β-Unsaturated Ketones in Aqueous Media.

The cathodic reduction of α,β-unsaturated ketones in aqueous electrolyte gives efficient C–C coupling with the high stereoselectivity associated with similar reactions in aprotic media. The key features of these reactions are consistent with those expected from the likely mechanism involving water-templated coupling of radical-anions. As a further consequence the stereochemistry of the major products (cyclopentanols and linear hydrodimers) has been unambiguously assigned using X-ray crystallography and 2D NOESY 1H NMR experiments.