Photoregulated Sol‐Gel Transition of Novel Azobenzene‐Functionalized Hydroxypropyl Methylcellulose and Its α‐Cyclodextrin Complexes

Summary: Novel azobenzene‐functionalized hydroxypropyl methylcellulose (AZO‐HPMC) polymers and their α‐cyclodextrin (α‐CD) complexes have been prepared. These polymers show interesting sol‐gel transition behavior in aqueous solutions. In the absence of α‐CD, the gelation temperature increases after UV irradiation, while in the presence of α‐CD, the gelation temperature decreases after UV irradiation. The difference in the gelation temperatures between the trans and cis samples of AZO‐HPMC opens a wide operating window for reversible regulation of the sol‐gel transition behavior by photoirradiation.

The UV‐induced cis/trans isomerism of azobenzene‐functionalized hydroxypropyl methylcellulose and its α‐cyclodextrin complexes.     

Cyclodextrins in Polymer Synthesis: Photoinitiated Free‐Radical Polymerization of N‐Isopropylacrylamide in Water Initiated by a Methylated β‐Cyclodextrin/2‐Hydroxy‐2‐methyl‐1‐phenylpropan‐1‐one Host/Guest Complex

Methylated β‐cyclodextrin (Me‐β‐CD) was used to complex a free‐radical photoinitiator, 2‐hydroxy‐2‐methyl‐1‐phenylpropan‐1‐one ( 1 ), yielding the water‐soluble 1 : 1 host/guest complex 1 a . The structure of complex 1 a was verified by means of IR, UV/vis and ¹H NMR spectroscopy. The influence of Me‐β‐CD as the host on the photopolymerization kinetics of N‐isopropylacrylamide was studied. Compared to the photopolymerization carried out under nearly identical conditions but without cyclodextrin, an increase in the polymerization rate was registered in the presence of complex 1 a .     

Ultrasound‐assisted green synthesis of Cu‐based complexes of β‐cyclodextrin and their SOD‐like activity

A novel Cu–Zn β‐cyclodextrin (CuZn/β‐CD) model compound was synthesized under ultrasound irradiation to mimic the functionality of copper zinc superoxide dismutase (CuZnSOD). For comparison, Cu/β‐CD and Zn/β‐CD complexes were also synthesized via a sonochemical approach. The obtained complexes were characterized by FTIR, ICP‐OES, UV–vis and Scanning electron microscopy‐Energy dispersive X‐ray (SEM‐EDX) techniques. The SOD activity of the complexes was evaluated by a pyrogallol autoxidation method. These enzyme‐mimetic materials scavenge ambient free radicals, with the potential to provide significant antioxidant protection (scavenging ability > 70%).     

Layer‐by‐layer Assembled Multilayers of Graphene/Mono‐(6‐amino‐6‐deoxy)‐β‐cyclodextrin for Detection of Dopamine

Graphene/mono‐(6‐amino‐6‐deoxy)‐β‐cyclodextrin multilayer films composed of graphene sheet (GS) and mono‐(6‐amino‐6‐deoxy)‐β‐cyclodextrin (NH₂‐β‐CD) were fabricated easily by two steps. First, negatively charged graphene oxide (GO) and positively charged mono‐(6‐amino‐6‐deoxy)‐β‐cyclodextrin (NH₂‐β‐CD) were layer‐by‐layer (LBL) self‐assembled on glassy carbon electrode (GCE) modified with a layer of poly(diallyldimethylammonium chloride) (PDDA). Then graphene/mono‐(6‐amino‐6‐deoxy)‐β‐cyclodextrin (GS/NH₂‐β‐CD) multilayer films were built up by electrochemical reduction of graphene oxide/mono‐(6‐amino‐6‐deoxy)‐β‐cyclodextrin (GO/NH₂‐β‐CD). Combining the high surface area of GS and the active recognition sites on β‐cyclodextrin (β‐CD), the GS/NH₂‐β‐CD multilayer films show excellent electrochemical sensing performance for the detection of DA with an extraordinary broad linear range from 2.53 to 980.05 µmol·L^?1. This study offers a simple route to the controllable formation of graphene‐based electrochemical sensor for the detection of DA.     

Capillary electrophoretic separation and computational modeling of inclusion complexes of β‐cyclodextrin and 18‐crown‐6 ether with primaquine and quinocide

The antimalarial drug primaquine (PQ) and its contaminant, the positional isomer quinocide (QC) have been successfully separated using capillary electrophoresis with either β‐cyclodextrin (β‐CD) or 18‐crown‐6 ether (18C6) as chiral mobile phase additive. The interactions of the drugs with cyclodextrins and 18C6 were studied by the semiempirical method (Parametric Model 3) PM3. Theoretical calculations for the inclusion complexes of PQ and QC with α‐CD, β‐CD and 18C6 were performed. Data from the theoretical calculations are correlated and discussed with respect to the electrophoretic migration behavior. More stable complexes are predicted for the PQ–β‐CD and PQ–18C6 complexes. The coelution of PQ and QC when α‐CD was used as buffer additive can be explained by their comparable stabilities of the inclusion complex formed, while significant differences in the complexation stabilities of the drugs with β‐CD is responsible for their separation. The stronger hydrogen bonding in PQ–18C6 system is responsible for the separation between PQ and QC when 18C6 was used as chiral mobile phase additive. Copyright © 2009 John Wiley & Sons, Ltd.     

1H NMR studies of binary and ternary dapsone supramolecular complexes with different drug carriers: EPC liposome,SBE‐β‐CD and β‐CD

Binary and ternary systems composed of dapsone, sulfobutylether‐β‐cyclodextrin (SBE‐β‐CD), β‐CD and egg phosphatidylcholine (EPC) were evaluated using 1D ROESY, saturation transfer difference NMR and diffusion experiments (DOSY) revealing the binary complexes Dap/β‐CD (K_a 1396 l mol^?1), Dap/SBE‐β‐CD (K_a 246 l mol^?1), Dap/EPC (K_a 84 l mol^?1) and the ternary complex Dap/β‐CD/EPC (K_a 18 l mol^?1) in which dapsone is more soluble. Copyright © 2014 John Wiley & Sons, Ltd.     

Structural Studies for Specific Binding Capacity of β‐Cyclodextrin with Ibuprofen

Ibuprofen (Ibu) and β‐cyclodextrin (βCD) and its derivative (hydroxypropyl‐β‐cyclodextrin, HPβCD) complexes spatial geometry information were studyed. Firstly, phase solubility experiment was carried out for S‐(+)‐ibuprofen (SIbu) and cyclodextrins complex. The apparent stability constant (Kc) for 1:1 complexes are 1065 M‐1 (βCD) and 1476 M‐1 (HPβCD) respectively. Secondly, ¹H NMR and two‐dimensional rotating‐frame overhauser effect spectroscopy (2D ROESY) were used for binding study, and confirmed that benzene ring of Ibu is deeply included into the cavity and racemic Ibu (RSIbu) can be discriminated by βCD or HPβCD. Finally, docking model was given by theoretical investigation. The model with ‐4.77 kcal/mol binding energy matches experimental structure.     

Structure and Photochemical Behavior of the Cyclodextrin Inclusion Complexes of the Benzoylthiophene‐Derived Drugs Tiaprofenic Acid (=5‐Benzoyl‐α‐methylthiophene‐2‐acetic Acid) and Suprofen (=α‐Methyl‐4‐(2‐thienylcarbonyl)benzeneacetic Acid)

The effect of β‐cyclodextrin (β‐CD) on the excited‐state reactivity of the two benzoylthiophene derivatives, tiaprofenic acid (TPA; 2 ) and suprofen (SPF; 3 ) in their carboxylate forms is studied. The presence of β‐cyclodextrin does not affect the nature of the photoproduced transients and the photoproducts, but increases the photodegradation quantum yields of both drugs. The efficiency of the photodecarboxylation process is enhanced. This effect is rationalized in the light of the inclusion of 2 and 3 in the β‐CD cavity, affecting the energy of the lowest excited states of the drugs. The structure of the complexes is determined by induced circular dichroism, and molecular‐mechanics and dynamic Monte Carlo calculations. The photoreactivity of the decarboxylated photoproduct 7 of tiaprofenic acid ( 2 ) in presence of β‐CD is also examined.     

Heat‐Induced Supramolecular Organogels Composed of α‐Cyclodextrin and “Jellyfish‐Like” β‐Cyclodextrin–Poly(ε‐caprolactone)

In general, the complexation and gelation behavior between biocompatible poly(ε‐caprolactone) (PCL) derivatives and α‐cyclodextrin (α‐CD) is extensively studied in water, but not in organic solvents. In this article, the complexation and gelation behavior between α‐CD and multi‐arm polymer β‐cyclodextrin‐PCL (β‐CD‐PCL) with a unique “jellyfish‐like” structure are thoroughly investigated in organic solvent N,N‐dimethylformamide and a new heat‐induced organogel is obtained. However, PCL linear polymers cannot form organogels under the same condition. The complexation is characterized by rheological measurements, DSC, XRD, and SEM. The SEM images reveal that the complexes between β‐CD‐PCL and α‐CD present a novel topological helix porous structure which is distinctly different from the lamellar structure formed by PCL linear polymers and α‐CD, suggesting the unique “jellyfish‐like” structure of β‐CD‐PCL is crucial for the formation of the organogels. This research may provide insight into constructing new supramolecular organogels and potential for designing new functional biomaterials. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1598–1606     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

Synthesis of β3‐Peptides and Mixed α/β3‐Peptides by Thioligation

Five β‐peptide thioesters ( 1 – 5 , containing 3, 4, 10 residues) were prepared by manual solid‐phase synthesis and purified by reverse‐phase preparative HPLC. A β‐undecapeptide ( 6 ) and an α‐undecapeptide ( 7 ) with N‐terminal β³‐HCys and Cys residues were prepared by manual and machine synthesis, respectively. Coupling of the thioesters with the cysteine derivatives in the presence of PhSH (Scheme and Fig. 1) in aqueous solution occurred smoothly and quantitatively. Pentadeca‐ and heneicosapeptides ( 8 – 10 ) were isolated, after preparative RP‐HPLC purification, in yields of up to 60%. Thus, the so‐called native chemical ligation works well with β‐peptides, producing larger β³‐ and α/β³‐mixed peptides. Compounds 1 – 10 were characterized by high‐resolution mass spectrometry (HR‐MS) and by CD spectroscopy, including temperature and concentration dependence. β‐Peptide 9 with 21 residues shows an intense negative Cotton effect near 210 nm but no zero‐crossing above 190 nm, (Figs. 2–4), which is characteristic of β‐peptidic 3₁₄‐helical structures. Comparison of the CD spectra of the mixed α/β‐pentadecapeptide ( 10 ) and a helical α‐peptide (Fig. 5) indicate the presence of an α‐peptidic 3.6₁₃ helix.     

固相β-环糊精包结物诱导7-羟基-2-甲氧基-2-甲基色满的不对称合成

研究了室温下间苯二酚和甲基乙烯基酮分别与β-环糊精（ β-CD）形成包结物后的几种不同固相反应,结果表明包结物A（间苯二酚/β-CD）与包结物B（甲基乙烯基酮/β-CD）反应能够很好地得到目的产物,产率及ee值分别为82.8%和78.4%;间苯二酚与包结物B反应仅得到低光学活性产物（ee值为19.5%）;包结物A与甲基乙烯基酮反应却没有得到手性目的产物。以熔点、X-粉末衍射、固相核磁碳谱及ROESY多种方法对所形成的包结物进行了表征,包结物中主客体的比例（1：1）通过¹H NMR (400 MHz)得以确定,文章对固相环加成反应的机制也进行了初步探讨。     

Synthesis and X‐ray Crystal Structures of Zinc Dichloride Complexes Supported by a β‐Diimine Ligand

β‐Diimine zinc dichloride complexes [CH₂{C(Me)NAr}₂]ZnCl₂ [Ar = Mes ( 1 ), Dipp ( 2 )] were obtained from the reactions of ZnCl₂ with the corresponding β‐iminoamines [ArN(H)C(Me)CHC(Me)NAr]. Complexes 1 and 2 were characterized by multinuclear NMR (¹H, ¹³C) and IR spectroscopy, elemental analyses as well as by single‐crystal X‐ray diffraction. The energy differences between the enamine‐imine tautomers of the β‐iminoamines were quantified by quantum chemical calculations.     

The Effect of Fluoro Substitution upon the β‐Hairpin Fold of a β‐Tetrapeptide in Methanol

The importance of β‐peptides lies in their ability to mimic the conformational behavior of α‐peptides, even with a much shorter chain length, and in their resistance to proteases. To investigate the effect of substitution of β‐peptides on their dominant fold, we have carried out a molecular‐dynamics (MD) simulation study of two tetrapeptides, Ac‐(2R,3S)‐β^2,3hVal(αMe)‐(2S)‐β²hPhe‐(R)‐β³hLys‐(2R,3S)‐β^2,3‐Ala(αMe)‐NH₂, differing in the substitution at the C_α of Phe2 (pepF with F, and pepH with H). Three simulations, unrestrained (UNRES), using ³J‐coupling biasing with local elevation in combination with either instantaneous (INS) or time‐averaging (AVE) NOE distance restraining, were carried out for each peptide. In the unrestrained simulations, we find three (pepF) and two (pepH) NOE distance bound violations of maximally 0.22 nm that involve the terminal residues. The restrained simulations match both the NOE distance bounds and ³J‐values derived from experiment. The fluorinated peptide shows a slightly larger conformational variability than the non‐fluorinated one.     

Preparation and characterization of poly(ethylene oxide)‐loaded hydroxypropyl‐β‐cyclodextrin nanofibers

Hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) is a modified β‐cyclodextrin (β‐CD) derivative, which is toxicologically harmless to mammals and other animals. HP‐β‐CD is electrospun from an aqueous solution by blending with a non‐toxic, biocompatible, synthetic polymer poly(ethylene oxide) (PEO). Aqueous solutions containing different HP‐β‐CD/PEO blends (50:50–80:20) with variable concentrations (4 wt%–12 wt%) were used. Scanning electron microscope was used to investigate the morphology of the fibers, and Fourier transform infrared spectroscopy analysis confirmed the presence of HP‐β‐CD in the fiber. Uniform nanofibers with an average diameter of 264, 244, and 236 nm were obtained from 8 wt% solution of 50:50, 60:40, and 70:30 HP‐β‐CD/PEO, respectively. The average diameter of the fiber was decreased with increasing of HP‐β‐CD/PEO ratio. However, a higher proportion of HP‐β‐CD in the spinning solution increased beads in the fibers. The polymer concentration had no significant effect on the fiber diameter. The most uniform fibers with the narrowest diameter distribution were obtained from the 8 wt% of 50:50 solution. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative ROESY analysis of computational models: structural studies of citalopram and β‐cyclodextrin complexes by 1H‐NMR and computational methods

Complexation of racemic citalopram with β‐cyclodextrin (β‐CD) in aqueous medium was investigated to determine atom‐accurate structure of the inclusion complexes. ¹H‐NMR chemical shift change data of β‐CD cavity protons in the presence of citalopram confirmed the formation of 1 : 1 inclusion complexes. ROESY spectrum confirmed the presence of aromatic ring in the β‐CD cavity but whether one of the two or both rings was not clear. Molecular mechanics and molecular dynamic calculations showed the entry of fluoro‐ring from wider side of β‐CD cavity as the most favored mode of inclusion. Minimum energy computational models were analyzed for their accuracy in atomic coordinates by comparison of calculated and experimental intermolecular ROESY peak intensities, which were not found in agreement. Several least energy computational models were refined and analyzed till calculated and experimental intensities were compatible. The results demonstrate that computational models of CD complexes need to be analyzed for atom‐accuracy and quantitative ROESY analysis is a promising method. Moreover, the study also validates that the quantitative use of ROESY is feasible even with longer mixing times if peak intensity ratios instead of absolute intensities are used. Copyright © 2015 John Wiley & Sons, Ltd.     

Crystal Structures of β‐Cyclodextrin Inclusion Complexes with 7‐Hydroxycoumarin and 4‐Hydroxycoumarin and Substituent Effects on Inclusion Geometry

Two inclusion complexes of β‐cyclodextrin‐7‐hydroxycoumarin ( 1 ) and β‐cyclodextrin‐4‐hydroxycoumarin ( 2 ) were prepared and their crystal structures were investigated by single crystal X‐ray crystallography under cryogenic condition. Both structures consist of stacks of face‐to‐face cyclodextrin dimers arranged in brickwork‐like pattern along the crystallographic a‐axis. For complex 1 , each of the two dimeric β‐cyclodextrins includes one 7‐hydroxycoumarin molecule that penetrates deeply into the cyclodextrin dimer and locates its lactonering at the center of the dimer cavity. For complex 2 , each cyclodextrin dimer accommodates three 4‐hydroxycoumarin molecules. One of them is sandwiched between two units of the cyclodextrin dimer, the other two are shallowly included in the cavities of the dimeric cyclodextrins respectively and protrude their lactone rings from the primary end of the cyclodextrin. The substituent effects of guest molecules on inclusion geometry of various coumarin molecules in β‐cyclodextrin were examined.     

IrIII and RuII Complexes Containing Triazole‐Pyridine Ligands: Luminescence Enhancement upon Substitution with β‐Cyclodextrin

Novel 2‐(1‐substituted‐1H‐1,2,3‐triazol‐4‐yl)pyridine (pytl) ligands have been prepared by “click chemistry” and used in the preparation of heteroleptic complexes of Ru and Ir with bipyridine (bpy) and phenylpyridine (ppy) ligands, respectively, resulting in [Ru(bpy)₂(pytl‐R)]Cl₂ and [Ir(ppy)₂(pytl‐R)]Cl (R=methyl, adamantane (ada), β‐cyclodextrin (βCD)). The two diastereoisomers of the Ir complex with the appended β‐cyclodextrin, [Ir(ppy)₂(pytl‐βCD)]Cl, were separated. The [Ru(bpy)₂(pytl‐R)]Cl₂ (R=Me, ada or βCD) complexes have lower lifetimes and quantum yields than other polypyridine complexes. In contrast, the cyclometalated Ir complexes display rather long lifetimes and very high emission quantum yields. The emission quantum yield and lifetime (Φ=0.23, τ=1000 ns) of [Ir(ppy)₂(pytl‐ada)]Cl are surprisingly enhanced in [Ir(ppy)₂(pytl‐βCD)]Cl (Φ=0.54, τ=2800 ns). This behavior is unprecedented for a metal complex and is most likely due to its increased rigidity and protection from water molecules as well as from dioxygen quenching, because of the hydrophobic cavity of the βCD covalently attached to pytl. The emissive excited state is localized on these cyclometalating ligands, as underlined by the shift to the blue (450 nm) upon substitution with two electron‐withdrawing fluorine substituents on the phenyl unit. The significant differences between the quantum yields of the two separate diastereoisomers of [Ir(ppy)₂(pytl‐βCD)]Cl (0.49 vs. 0.70) are attributed to different interactions of the chiral cyclodextrin substituent with the Δ and Λ isomers of the metal complex.     

Mass spectrometric investigations of α‐ and β‐cyclodextrin complexes with ortho‐, meta‐ and para‐coumaric acids by negative mode electrospray ionization

The mass spectrometric characterization of aqueous solutions of α‐ and β‐cyclodextrins (CDs) and o‐, m‐ and p‐coumaric acids (CAs) by negative ion electrospray ionization (ESI) indicates that the [CD+CA]^? ions were sourced from the inclusion complex present in solution and from the anion attached to CD molecules formed in the spray processes. The anion adducts formed in the spray process contribute significantly to the signal intensity of an ionized inclusion complex thus overestimating the calculated stability constant (K) of solution‐phase complexes by one to two orders of magnitude. The relative intensities of anion adducts in mass spectra depend on the concentration ratio of the anion and the CD in spray droplets, while the relative intensity of the ionized inclusion complex depends on CD and CA concentrations in solutions and the value of K. Ion Mobility Spectrometry Mass Spectrometry [IMS‐MS] measurements show that the collision cross‐section (Ω) values of the [CD+CA]^? or [(CD)₂₊CA]^2? and [CD+CA] complex ions are 5–6% larger than or equal to CD^? or [CD], respectively. Therefore, in the gas phase the anion adducts [CD+CA^?] on cyclodextrin molecules possess the same conformations as the ionized inclusion complexes [CD+CA]^?. Copyright © 2008 John Wiley & Sons, Ltd.     

Significant Phenomena Observed in the Molecule‐Ion Adduct System of Sodium Arsenite with α‐Cyclodextrin

The data of ¹H nuclear magnetic resonance and molar conductivity prove that there is a molecule‐ion interaction between α‐cyclodextrin (α‐CD) and sodium arsenite (SA), and the interaction site is different from that between β‐CD and SA. The packing mode of α‐CD molecules after adduct with SA is changed from cage to channel type. Several experimental phenomena from thermogravimetric analyses and gas chromatography coupled to time‐of‐flight mass spectrometry measurements reveal that the presence of SA has led to a large change of thermal decomposition behavior of α‐CD, and vice versa. The current work reveals the particularity of the interaction between SA and α‐CD, which would provide new insight into the understanding of molecule‐ion interactions.