Inclusion complexation between baicalein and β-cyclodextrin and the influence of β-cyclodextrin on the binding of baicalein with DNA: a spectroscopic approach

This work deals with the commonly studied cyclic oligosaccharide and gains importance as it is entered on a drug delivering carbohydrate and provides insight into the oligosaccharide complex–biomolecular interaction. The binding of a flavone, baicalein, to β-cyclodextrin and calf thymus DNA is studied. The binding of baicalein to calf thymus DNA in the presence of β-cyclodextrin is analysed using the UV–vis absorption and fluorescence spectroscopy. The mode of binding and structure of the baicalein–β-cyclodextrin complex are reported. The role of the structure and the stoichiometry of the inclusion complex of baicalein–β-cyclodextrin in its influence on DNA binding are analysed.

Highlights

? This paper deals with the binding of a flavone, baicalein to β-cyclodextrin and/or DNA.

? The inclusion complexation between baicalein and β-cyclodextrin is analysed.

? The stoichiometry and the binding strength of the inclusion complex is reported.

? The role of β-cyclodextrin in tuning the binding of baicalein to DNA is emphasized.

? Spectroscopic and docking analysis are used to articulate the results.     

Highly selective recognition of naphthol isomers based on the fluorescence dye-incorporated SH-β-cyclodextrin functionalized gold nanoparticles

In present work, a rhodamine 6G (Rh 6G)-incorporated β-cyclodextrin functionalized gold nanoparticle (Rh 6G-CD-AuNP) based fluorescent assay has been successfully developed for recognizing/detecting the structural isomers, α-naphthol and β-naphthol, in aqueous solution. The β-cyclodextrin functionalized gold nanoparticles (CD-AuNPs) are achieved by conjugating the thiolated β-cyclodextrin (SH-β-CD) with AuNPs via S-Au covalent bonds. Rhodamine 6G (Rh 6G) is chosen as a fluorescent probe in this approach because it can be strongly absorbed on the surface of AuNP by noncovalent interaction. After binding with β-CD cavity, the naphthols enable to act as electron transfer quenchers of Rh 6G, which lead to significant fluorescence quenching of the dye. Because of different association ability of naphthol isomers with the β-CD cavity, the assay can selectively distinguish α-naphthol and β-naphthol with reasonable sensitivity. Detection of naphthols down to 8 nM with a dynamic range of nearly three orders of magnitude (0.01-8 μM) for α-naphthol and 50 nM with two orders of magnitude (0.1-20 μM) for β-naphthol is demonstrated, respectively. The ability of the method for detecting the content of α-naphthol or β-naphthol in the different naphthol mixtures has also been evaluated.     

Binding of 9-aminoacridine to deoxydinucleoside phosphates of defined sequence: Preferences and stereochemistry

The effect of sequence on the binding of 9-aminoacridine to DNA has been investigated by studying its interaction with deoxydinucleoside phosphates of different sequences using proton nuclear magnetic resonance. Quantitative binding information can be obtained by comparison of the proton chemical shift behavior of 9-aminoacridine upon addition of dinucleoside phosphate to various models for the interaction using least-squares computer fitting procedures. The simplest model that fits the data includes (1) dimerization of 9-aminoacridine and (2) a mixture of 1:1 and 2:1 (dinucleoside phosphate/9-aminoacridine) complexes. The computed parameters allow comparison of binding constants and stereochemistry for different sequences. The 1:1 complexes seem to involve interaction of the ring nitrogen with the backbone phosphate and stacking of one or both chromophores on the acridine; preference in binding is observed for alternating (purine-pyrimidine or pyrimidine-purine) over non-alternating (purine-purine) dinucleoside phosphates. The 2:1 complexes involve intercalation of the acridine between two complementary dinucleoside phosphate strands with weak sequence preferences in binding. The stereochemistry of intercalation differs between non-alternating purine-purine sequences and the alternating pyrimidine-purine or purine-pyrimidine sequences in having the 9-aminoacridine stacked with the purines of one strand rather than straddling the purines on opposite strands. The difference in stereochemistry could possibly be a determining factor in frameshift sequence specificity.     

Molecular modelling of the inclusion complexes between β-cyclodextrin and (R)/(S)-methylphenobarbitone and its application to HPLC

Molecular modelling of β-cyclodextrin and optimisation of its potential energy suggests that a favoured conformation is that distorted from a symmetrical torus. The inclusion of water molecules into the torus cavity simulates the increased stability in an aqueous solvent. Complexes of β-cyclodextrin with (R)- and (S)-enantiomers of methylphenobarbitone have been modelled and energetically optimised by the application of molecular mechanics. The simulations suggests that the guest molecules adopt an orientation in which the phenyl ring is projected into the torus cavity, with in each case the plane of the ring parallel to a longer axis of the distorted torus and slightly displaced from the axis through the torus cavity. It is suggested that the asymmetry in the macrocyclic ring contributes to chiral recognition as a result of additional discriminatory binding to the barbiturate ring residue of each enantiomer, which occupy different 3D geometries. The enantiomers form complexes of different minimum potential energies. The resulting difference in complex stability can be related to the behaviour of β-cyclodextrin, as a mobile phase additive in reverse-phase HPLC to effect chiral separation of rac-medthylphenobarbitone during chromatography. © 1994 Wiley-Liss, Inc.     

Supramolecular complex binding to G-quadruplex DNA: Berberine encapsulated by a planar side arm–tethered β-cyclodextrin

G-quadruplex-binders have the plausible potential to act as anticancer agents. Herein, the mode of binding of a synthesized fluorenyl derivative of β-cyclodextrin with a duplex and G-quadrulex DNAs has been investigated. Moreover, the loading of the well-known G-quadruplex binder, berberine, in the β-cyclodextrin derivative using 2-dimensional rotating-frame Overhauser effect spectroscopy is studied. The intensity of proton NMR signals is weakened on the β-cyclodextrin derivative’s interaction with the quadruplexes. Binding constants are reported for each binding of the ligands to calf thymus DNA, kit22, telo24, and myc22 employing fluorescence spectroscopy. A general trend of fluorescence response (quenching) on the β-cyclodextrin derivative to the DNAs is modified when the berberine molecule is loaded in the host structure. Despite berberine binds to the macromolecular target strongly, its host-guest association with the cavity of β-cyclodextrin diminishes the binding strength. A significant difference between the binding strengths of the ligands with duplex and quadruplex structures is observed.

Communicated by Ramaswamy H. Sarma     

The interaction of -cyclodextrin with nucleic acid monomer units

β-Cyclodextrin is examined as a potentially useful probe of nucleic acid structure. From circular dichroism (CD) data the binding constant and the enthalpy and entropy of binding to 5′-AMP are determined. The CD spectrum of the bound complex is calculated. The binding to 5′-dAMP, 3′,5′-cyclic AMP, adenosine and adenine is also examined. No evidence is seen for the involvement of hydrophobic forces. CD data for 5′-UMP, and 5′-CMP in 0.01 M β-cyclodextrin show that the binding is not as specific as previously reported.     

Fluorometric and liquid chromatographic study of the binding of two coumarins to β-cyclodextrin

The fluorescences of warfarin and phenprocoumon are enhanced following complexation with β-cyclodextrin; (+)-(R)- and (?)-(S)-phenprocoumons have different affinities for this cyclodextrin, whereas the corresponding enantiomers of warfarin have similar binding constants. Apparently, hemiketal formation in the case of warfarin minimizes chiral discrimination. This is confirmed using a β-cyclodextrin bonded chromatography column on which the phenprocoumon enantiomers are separated, whereas those of warfarin are not.     

Binding of a chromen-4-one Schiff’s base with bovine serum albumin: capping with β-cyclodextrin influences the binding

This work deals with the synthesis of 6-methyl-3-[(4′-methylphenyl)imino]methyl-4H-chromen-4-one (MMPIMC), its binding to β-cyclodextrin, and the influence of the cyclodextrin complexation on the compound’s binding to bovine serum albumin (BSA). The 1:2 stoichiometry for the complexation of MMPIMC with β-cyclodextrin is determined with the binding constant of 1.90 × 10⁴ M^?2. The structure of host–guest complex plays a role in protein binding of MMPIMC. One- and two-dimensional NMR spectra are used to determine the mode of binding of the guest to β-cyclodextrin cavity and the structure of the inclusion complex is proposed. The binding of MMPIMC with BSA in the absence and the presence of β-cyclodextrin is studied. The binding strengths of MMPIMC–BSA (1.73 × 10⁵ M^?1) and β-cyclodextrin-complexed MMPIMC–BSA (9.0 × 10⁴ M^?1) show difference in magnitude. The Förster Resonance Energy Transfer efficiency and the proximity of the donor and acceptor molecules, are modulated by β-cyclodextrin. Molecular modeling is used to optimize the sites and mode of binding of MMPIMC with bovine serum albumin.     

Interaction of a flavone loaded on surface-modified dextran-spooled superparamagnetic nanoparticles with β-cyclodextrin and DNA

Flavones are biologically active compounds obtained mainly from plant sources. Pharmaceutically important compounds can be delivered to the physiological target by loading them in carriers like cyclodextrins and magnetic nanoparticles. Herein, the binding of 6-methoxyflavone to β-cyclodextrin and DNA is studied using UV–visible absorption and fluorescence spectroscopy. The loading of 6-methoxyflavone onto a magnetic nanoparticles is employed. β-cyclodextrin encapsulates the 6-methoxyflavone to form an inclusion complex. β-cyclodextrin also used to draw forth 6-methoxyflavone loaded onto a magnetic nanoparticles. The morphology, magnetic property and the crystallite size of the nanoparticles are studied using scanning electron microscopy, vibrating sample magnetometry and X-ray diffraction techniques, respectively. The binding of the drug-loaded magnetic nanoparticles to DNA shows that the compound is accessible to DNA and available mostly on the surface of the nanoparticles despite a modified dextan polymer supposedly encapsulates the flavone.     

Study on the interaction between the inclusion complex of hematoxylin with β-cyclodextrin and DNA

Ultraviolet-visible (UV-vis) spectra, fluorescence spectra, electrochemistry, and the thermodynamic method were used to discuss the interaction mode between the inclusion complex of hematoxylin with β-cyclodextrin and herring sperm DNA. On the condition of physiological pH, the result showed that hematoxylin and β-cyclodextrin formed an inclusion complex with binding ratio n(hematoxylin):n(β-cyclodextrin) = 1:1. The interaction mode between β-cyclodextrin-hematoxylin and DNA was a mixed binding, which contained intercalation and electrostatic mode. The binding ratio between β-cyclodextrin-hematoxylin and DNA was n(β-cyclodextrin -hematoxylin):n(DNA) = 2:1, binding constant was K(?)(298.15K) = 5.29 × 10? L·mol?1, and entropy worked as driven force in this action.     

Circular dichroism study of 2'-5' dinucleoside monophosphates modified with N-2-acetylaminofluorene.

The conformational properties of four 2′ – 5′ dinucleoside monophosphates modified with $\text{N}$-2-acetylaminofluorene have been studied by circular dichroism spectroscopy. Covalent binding of this chemical carcinogen at the C₈ position of guanosine in the 2′ – 5′ dinucleoside monophosphates induces striking changes in their circular dichroic spectra depending on their base sequence and composition. The changes in CD spectra, redshift of the extrema and change of their polarity, not observed in the spectra of corresponding 3′ – 5′ derivatives modified with $\text{N}$-2-acetylaminofluorene are correlated with the difference in the configuration of 2′ – 5′ and 3′ – 5′ dinucleoside monophosphates and discussed in respect to the intramolecular stacking interactions.     

Molecular mechanics studies of dinucleoside methylphosphonates: influence of methylphosphonate and its chirality on the phosphodiester conformation.

Molecular mechanics studies are performed on single stranded as well as base paired forms of dinucleoside methylphosphonates comprising different base sequences for both the S- and R-isomers of methylphosphonate (MP). S-MP produces noticeable distortions in the geometry, locally at the phosphate center, and this enables the stereochemical feasibility of compact g- g- phosphodiester. Besides, it tends to perturb the conformations around the P-O3' and glycosyl bonds, causing minor variations in stacking interactions. In single stranded dinucleosides, the gain in adjacent base stacking interaction energies seems to be sufficient to overcome the barrier to P-O3' bond rotation arising due to S-MP...sugar interaction, and this results in transition to a compact phosphodiester (BI-type) from an initial extended phosphodiester (BII-type) conformation. Such a thing seems rather difficult in base pair constrained duplexes. Dinucleosides with R-MP behave analogous to normal phosphate duplexes as the methyl group is away from the sugar. It is found that dinucleoside methylphosphonates are energetically less favoured than the corresponding dinucleoside phosphates mainly due to the depletion of contributions from electrostatic attractive interactions involving the base and sugar with the methylphosphonate consequent to the nonionic nature of the latter. Neither S-MP nor R-MP seem to significantly alter the stereochemistry of duplex structure.     

Synthesis,structure, and evaluation of a β-cyclodextrin-artificial carbohydrate conjugate for use as a doxorubicin-carrying molecule

This paper describes the synthesis of a β-cyclodextrin (β-CyD) derivative conjugated with a C,C-glucopyranoside containing a benzene unit. Its doxorubicin-inclusion ability and structure are also discussed. SPR analysis revealed that the β-CyD conjugate had a high inclusion association value of 3.8 × 10⁶ M⁻¹ for immobilized doxorubicin. NMR structural analysis suggested that its high doxorubicin-inclusion ability was due to the formation of the inclusion complex as a result of the π–π stacking interaction between the benzene ring of the conjugate and the A ring of doxorubicin.     

Impact of β-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters1

To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of β-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of β-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, β-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, β-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine–glycine conjugation, β-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by ?75% and ?44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with β-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. β-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% β-cyclodextrin and 19-times with 1% cholestyramine compared to control. β-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of β-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol excretion is most likely the primary mechanism responsible for the lipid-lowering action of β-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.     

The role of encapsulation by β-cyclodextrin in the interaction of raloxifene with macromolecular targets: a study by spectroscopy and molecular modeling

We report the binding of the drug raloxifene with Calf thymus DNA (ctDNA) and bovine serum albumin (BSA) in the presence and absence of β-cyclodextrin (β-CD) and explain the influence of β-cyclodextrin on the binding of the drug to macromolecules. UV-Vis absorption, fluorescence, proton nuclear magnetic resonance and two-dimensional rotating-frame nuclear overhauser effect spectroscopic techniques are used to study the stoichiometry and the binding strength of the complexes. Molecular modeling is used in combination with other techniques to propose the structure of the inclusion complex and the interaction with ctDNA. The Stern–Volmer quenching constants of the interaction of raloxifene with ctDNA in aqueous and in β-CD solution are compared. The competition for binding of ctDNA with raloxifene and Methylene Blue is studied. The apparent binding constant and the number of binding sites for the binding of raloxifene with BSA in aqueous solution are significantly different from those in the presence of β-CD. The influence of β-CD on the binding of the small molecules with biological macromolecules is discussed. We infer that the binding strengths between raloxifene and macromolecules, viz., ctDNA and BSA are influenced by the β-CD encapsulation. These results may suggest new ways to tune the drug binding to biomacromolecules by encapsulating specific moieties of drugs.     

Conformational analysis of the dinucleotides 5'-methylphospho-N6-dimethyladenylyl-uridine (mpm62A-U) and 5'methylphospho-uridylyl-N6-dimethyladenosine (mpU-m62A) and of the trinucleotide U-m62A-U. A nuclear magnetic resonance and circular dichroic study

NMR and CD studies were carried out on the dinucleotides 5'-methylphospho-N6-dimethyladenylyl-uridine (mpm62-U) and 5'-methylphospho-uridylyl-N6-dimethyladenosine (mpU-m62A) and on the trinucleotide U-m62A-U. A detailed comparison is given of the conformational features of mpm62A-U and mpU-m62A with the corresponding 5'-nonphosphorylated dinucleotides m62A-U and U-m62A, respectively. The behaviour of the trinucleotide U-m62A-U is compared with the properties of the constituent dinucleotides U-m62A and mpm62A-U. Chemical-shift and CD data were used to determine the amount of stacking interactions. For each compound NMR spectra were recorded at two or three sample concentrations in order to separate intermolecular and intramolecular base-base interactions. The coupling constants of the ribose ring are interpreted in terms of the N/S equilibrium, and population distributions along the backbone angles beta, gamma and epsilon are presented. The combined data indicate a strong similarity between mpm62A-U and m62A-U both in degree and in mode of stacking. In contrast, the existence of different types of stacking interactions in mpU-m62A and U-m62A is suggested in order to explain the NMR and CD data. It is concluded that dinucleoside bisphosphates serve better as a model for the behaviour of trinucleotides than dinucleoside monophosphates. The trinucleotide U-m62A-U adopts a regular single-stranded stacked RNA structure with preference for N-type ribose and gamma+ and beta t backbone torsion angles. The difference in behaviour between the U-m62A- part of U-m62A-U and the dimer U-m62A is seen as a typical example of conformational transmission.     

β-环糊精对甾体微生物羟化反应的影响

考察了β-环糊精(β-cyclodextrin, CD)对雄甾-4-烯-3,17-二酮(androst-4-ene-3,17-diorle,AD)在水中的溶解度及微生物对其11а羟化反应的影响,结果表明β-环糊精能显著提高底物AD在发酵培养基中的溶解度,增溶效果优于有机溶剂.在底物投料浓度0.2%(w/v)时,与4%无...     

A highly sensitive probe detecting low pH area of HeLa cells based on rhodamine B modified β-cyclodextrins

Two kinds of rhodamine modified β-cyclodextrins (R-1 and R-2), which are coupled up ethylene diamine (EDA) and tetraethylene pentamine (TEPA) between Rh B and β-cyclodextrin, respectively, have been synthesized. R-1 and 2 work as a new fluorogenic probe for monitoring pH of Hela cells, and MTT of assay R-1, R-2, and rhodamine B indicate that less a cytotoxicity of those R-1 and R-2 than that of rhodamine B, where R-1 has much less one than that of R-2. The fluorogenetic probe capability of R-2 was recognized in an area of acidic area in living cell, which is lysosome.     

Methyl β-cyclodextrin reduces accumulation of reactive oxygen species and cell death in yeast

Stabilized F-actin structures have been shown to be detrimental to both mammalian and yeast cells. In yeast, stabilization of actin caused by addition of jasplakinolide, by point mutations in the act1 gene, or by deletion of certain genes that regulate F-actin leads to cell death with hallmarks of apoptosis. In particular, there is an elevation in the levels of reactive oxygen species, and we have shown the importance of the Ras/cAMP pathway for this effect. Here we show that in yeast cells deleted for end3, which functions to regulate actin organization during endocytosis, treatment of cells with methyl β-cyclodextrin reduces levels of reactive oxygen species and inhibits cell death progression. Methyl β-cyclodextrin is widely used to disrupt lipid rafts that contain cholesterol. The mechanism through which the rescue is achieved was investigated and we demonstrate that methyl β-cyclodextrin reduces accumulation of Ras2 at the plasma membrane in Δend3 cells. We use FRAP and live cell imaging to determine the possible mechanism through which methyl β-cyclodextrin functions to elicit this effect on Ras2 localization. Finally, we demonstrate that addition of methyl β-cyclodextrin to wild-type cells can act to protect cells from acute oxidative stress caused by addition of hydrogen peroxide.