Rotating-frame Overhauser Effect Spectroscopy Research Articles

Supramolecular association of a diguanidine derivative with a porphyrin-cyclodextrin conjugate and its binding to G-Quadruplex DNA

G-quadruplex-selective small molecule binders are synthesized as they find relevance in therapeutic intervention. This article reports a new and novel diguanidine derivative containing benzimidazole moiety. The synthesized compound is characterized using spectroscopic techniques. An inclusion complex of the compound with a porphyrin-tethered β-cyclodextrin where the latter acts as a host molecule. The structure of the complex is optimized by employing a rotating-frame Overhauser effect spectroscopy. Two host molecules encapsulate the diguanidine forming a 1:2 complex, as evidenced by the spectral analysis. The compound and its inclusion complex are analyzed for their binding to duplex and G-quadruplex DNAs viz., kit22, myc22, and telo. The binding constants are derived using fluorescence spectroscopic titrations. The diguanide derivative: porphyrin-cyclodextrin complex shows stronger binding to the quadruplexes than the duplex DNA, with the binding constant values of (8.20 ± 0.51) × 105, (2.40 ± 0.28) × 106, and (8.20 ± 0.10) × 105 M−1 for the interaction with kit22, myc22, and telo, respectively. The complexed form of diguanidine shows a greater affinity for myc22 than the other G-quadruplexes and duplex DNA. Circular dichroism spectra are recorded to further analyze conformational alterations on the binding interaction. The binding characteristics of the ligands against various DNAs are discussed in detail.

Insight into the Molecular Structure, Interaction, and Dynamics of Aqueous Reline Deep Eutectic Solvent: A Nuclear Magnetic Resonance Investigation

Reline, which is composed of choline chloride (ChCl) and urea, is the first and most widely used deep eutectic solvent (DES) described by Abbot and co-workers. Due to the hygroscopic feature, traces of water are unavoidable, which significantly affect the physicochemical properties of reline. At present, the local structure of molecules and the impact from the presence of water are still the most significant questions in this field. Herein, reline and six aqueous dilutions with a controlled amount of water (from 3.2 to 50.0 wt %) were studied mainly by using a combination of nuclear magnetic resonance (NMR) techniques. According to 1D 35Cl NMR, 1D 15N NMR, and 2D 1H-15Cl heteronuclear Overhauser effect spectroscopy, we probed the interactions of urea···Cl- and Ch+···Cl- in pure reline, which gradually dissociated in the presence of water. Moreover, it was revealed that the dissociation rate altered when the water content reached 9.0 wt %, which is ascribed to the higher preference of hydration for Cl- ion compared to other species in the system. Furthermore, selected cross peaks in 1H-1H correlation spectroscopy spectra were analyzed. Accordingly, an enhanced correlation was observed for urea···Ch+ at a lower water fraction within 9.0 wt %. When the water content increased to 24.9 wt %, the water solvation of Ch+ and urea was also observed in COSY spectra. The interaction of H2O···Ch+ got continuously stronger when the water content increased from 24.9 to 50.0 wt %, while H2O···urea got enhanced when the water content reached 33.3 wt % and then diminished gradually from 33.3 to 50.0 wt %. 1H-1H nuclear Overhauser effect spectroscopy and 1H-1H rotating frame Overhauser effect spectroscopy experiments were also conducted for dynamics investigation. The τc value for the species in 9.0 wt % aqueous reline is very close to τccrit of 0.44 ns. For pure reline and the aqueous reline with a water fraction of less than 9.0 wt %, the τc value of the species is longer than 0.44 ns, while for the sample with water of 24.9 wt %, the τc value is much shorter than 0.44 ns. Based on our NMR study, we revealed that with the water amount increasing from 0 to 50.0 wt %, the species involved in the system behaved as the large molecules or molecules in viscous liquids transiting to the medium-sized molecules in nonviscous liquids and finally to small molecules in nonviscous liquids.

Ultra-selective, ultra-clean 1D rotating-frame Overhauser effect spectroscopy.

An ultra-selective 1D NMR experiment - GEMSTONE-ROESY - enables clear, unambiguous assignment of ROE signals in the not uncommon situation that traditional selective methods fail. Its usefulness is demonstrated in the analysis of the natural products cyclosporin and lacto-N-difucohexaose I, providing detailed insight into the structures and conformations of these molecules.

Synthesis and Characterization of Water Soluble Diethylenetriamine‐β‐Cyclodextrin/Ethinylestradiol Inclusion Complex

AbstractEthinylestradiol (EE), is widely used to treat conditions such as breast cancer, prostate cancer and climacteric syndrome. However, due to the low water solubility of EE, the bioavailability of EE is low. Herein, to improve the bioavailability of EE, a hydrosoluble cyclodextrin drug carrier system, diethylenetriamine‐β‐cyclodextrin/ethinylestradiol (DETA‐β‐CD/EE) was prepared. High performance liquid chromatography (HPLC), fourier transform infrared (FTIR), 2D rotating frame overhauser effect spectroscopy (ROESY) spectrum and scanning electron microscope (SEM) were used to characterize the DETA‐β‐CD/EE. HPLC test showed that DETA‐β‐CD was the optimal host molecule, which can improve the solubility of EE to 496 mg L−1. Phase solubility indicated the formation of a soluble inclusion complex with 1 : 1 stoichiometry. In terms of practical application, the solubility and stability of DETA‐β‐CD/EE in blood was proved by dissolution rate studies. Overall, by the encapsulation in polysaccharide DETA‐β‐CD, the water solubility of EE is increased by 100 times. The establishment of hydrosoluble cyclodextrin drug carrier system provides support for the sustained release system or large dose drug delivery.

Major Carotenoids of Meiothermus ruber Are Deinoxanthin Glucoside Esters, Not Meiothermoxanthin Glucoside Esters

Meiothermus ruber DSMZ 1279T was isolated from a hot spring in Kamchatka and was red in color. The major carotenoid present was reported to be 1'-(β-d-glucopyranosyloxy)-3,4,3',4'-tetradehydro-1',2'-dihydro-β,ψ-caroten-2-one after saponification (Burgess et al. J. Nat. Prod. 1999, 62, 859-863). In this study, we purified the major carotenoids in this species without saponification. We then reidentified the major carotenoids present using spectroscopic data, including electronic circular dichroism (ECD), 1H NMR, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), 13C NMR, heteronuclear single-quantum correlation spectroscopy (HSQC), heteronuclear multiple-bond correlation spectroscopy (HMBC), and MS, and enzymatic hydrolysis of fatty acid moieties and found deinoxanthin glucoside iso fatty acid esters. The bound fatty acids present included four iso types, and their composition differed from cellular lipids. Moreover, the previously identified carotenoid glucoside was a saponification artifact of deinoxanthin glucoside esters. Ketomyxocoxanthin glucoside esters and 1'-hydroxytorulene glucoside esters were also present. On the basis of the identification of carotenoids and the whole genome sequence of M.ruber, we propose a carotenoid biosynthetic pathway and note the corresponding genes.

Bis-Thiourea Chiral Sensor for the NMR Enantiodiscrimination of N-Acetyl and N-Trifluoroacetyl Amino Acid Derivatives.

A C2-symmetrical bis-thiourea chiral solvating agent (CSA), TFTDA, for NMR spectroscopy has been obtained by reacting (1R,2R)-1,2-bis(2-hydroxyphenyl)ethylenediamine and 3,5-bis(trifluoromethyl)phenyl isothiocyanate. TFTDA shows remarkable propensity to enantiodiscriminate N-trifluoroacetyl (N-TFA) and N-acetyl (N-Ac) derivatives of amino acids with free carboxyl functions, with the co-presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as the third achiral additive, which is needed for substrate solubilization. TFTDA shows enhanced enantiodiscriminating efficiency in comparison with the corresponding monomeric counterpart, TFTMA, pointing out cooperativity between its two symmetrical entities. A wide range of amino acid derivatives have been efficiently enantiodiscriminated in CDCl3, with high enantioresolution quotients, which guarantee high quality in applications devoted to the quantification of enantiomers. High enantiodiscriminating efficiency is maintained also in diluted 5 mM conditions or in the presence of sub-stoichiometric amounts of CSA (0.3 equiv). The role of phenolic hydroxyls in the DABCO-mediated interaction mechanism between TFTDA and the two enantiomeric substrates has been pointed out by means of diffusion-ordered spectroscopy (DOSY) and rotating frame Overhauser effect spectroscopy (ROESY) experiments. A conformational model for both the CSA and its diastereomeric solvates formed with the two enantiomers of N-acetyl leucine has also been conceived on the basis of ROE data in order to give a chiral discrimination rationale.

Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium.

Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters, suggesting a rich and mostly uncharacterized specialized metabolism. Here, in silico chemical prediction of a non-canonical polyketide synthase cluster has led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of 13C chemical shifts and semiquantitative interpretation of transverse rotating-frame Overhauser effect spectroscopy data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment of the absolute configuration. Janustatins feature a previously unknown pyridodihydropyranone heterocycle and an unusual biological activity consisting of delayed, synchronized cell death at subnanomolar concentrations.

Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.

Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey’s method, 3JHH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 μM).

New polyketides from the liquid culture of Diaporthebreyniae sp. nov. (Diaporthales, Diaporthaceae).

During the course of a study on the biodiversity of endophytes from Cameroon, a fungal strain was isolated. A multigene phylogenetic inference using five DNA loci revealed that this strain represents an undescribed species of Diaporthe, which is introduced here as D.breyniae. Investigation into the chemistry of this fungus led to the isolation of two previously undescribed secondary metabolites for which the trivial names fusaristatins G (7) and H (8) are proposed, together with eleven known compounds. The structures of all of the metabolites were established by using one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) spectroscopic data in combination with High-Resolution ElectroSpray Ionization Mass Spectrometry (HR-ESIMS) data. The absolute configuration of phomopchalasin N (4), which was reported for the first time concurrently to the present publication, was determined by analysis of its Rotating frame Overhauser Effect SpectroscopY (ROESY) spectrum and by comparison of its Electronic Circular Dichroism (ECD) spectrum with that of related compounds. A selection of the isolated secondary metabolites were tested for antimicrobial and cytotoxic activities, and compounds 4 and 7 showed weak antifungal and antibacterial activity. On the other hand, compound 4 showed moderate cytotoxic activity against all tested cancer cell lines with IC50 values in the range of 5.8-45.9 µM. The latter was found to be less toxic than the other isolated cytochalasins (1-3) and gave hints in regards to the structure-activity relationship (SAR) of the studied cytochalasins. Fusaristatin H (8) also exhibited weak cytotoxicity against KB3.1 cell lines with an IC50 value of 30.3 µM. Graphical abstract.

Preparation and Spectroscopic Characterization of Inclusion Complexes of 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin : 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin.

Rifampicin (RFP) solutions, intended to reduce incidence of prosthetic graft infection, were prepared as three-dimensional ground mixtures (3DGMs) using β-cyclodextrin (βCD) and γ-cyclodextrin (γCD) and characterized for their spectroscopic properties and solubility. Phase solubility diagrams revealed that 3DGMs (RFP/βCD and RFP/γCD) produced a complex at 1:1 molar ratio. Pulsed field gradient nuclear magnetic resonance experiments indicated that the diffusion coefficients for RFP/βCD and RFP/γCD were similar to the respective diffusion coefficients for βCD and γCD. Rotating-frame Overhauser effect spectroscopy NMR spectra revealed the existence of a new exchanger peak for RFP/γCD, suggesting an intermolecular interaction different from that of RFP/βCD. Differential scanning calorimetry confirmed the presence of endothermic peak at 191°C indicating the manifestation of RFP in the inclusion complex. Interestingly, molecular interactions from the complexes, RFP/βCD and RFP/γCD, revealed different patterns of inclusion in the 3DGMs. In RFP/βCD, nuclear Overhauser effect spectroscopy NMR spectra indicated cross peaks for the protons of the methyl group of RFP and the protons (H-5 and H-6) in the βCD cavity. The methyl group of RFP interacted with the narrow rim of βCD. With RFP/γCD, cross peaks were due to the protons of the methyl group of RFP and the protons of the cavity of γCD suggesting multiple inclusion patterns. The observed multiple cross peaks affirm the inclusion of RFP into the CD cavity which enhanced its solubility by 1.6-2.0-fold when prepared as 3DGMs as RFP/βCD and RFP/γCD, respectively.

Hamuramicin C, a Cytotoxic Bicyclic Macrolide Isolated from a Wasp Gut Bacterium.

A new bicyclic macrolide, hamuramicin C (1), was isolated from Streptomyces sp. MBP16, a gut bacterial strain of the wasp Vespa crabro flavofasciata. Its 22-membered macrocyclic lactone structure was determined by NMR and mass spectrometry. The relative configurations of hamuramicin C (1) were assigned by J-based configuration analysis utilizing 1H rotating frame Overhauser effect spectroscopy and heteronuclear long-range coupling NMR spectroscopy. Genomic and bioinformatic analyses of the bacterial strain enabled identification of the type-I polyketide synthase pathway, which employs a trans-acyltransferase system. The absolute configurations of 1 were proposed based on the analysis of the sequences of ketoreductases in the modular gene cluster. Moreover, hamuramicin C (1) demonstrated significant inhibitory activity against diverse human cancer cell lines (HCT116, A549, SNU-638, SK-HEP-1, and MDA-MB-231).

Differential interaction of Fluorescein-β-cyclodextrin conjugate to quadruplex kit22 DNA: Inclusion of Berberine and modulation of binding

Clinical applicability of G-quadruplexes as anticancer drugs is an area of current interest. Identification of supramolecular systems for selective targeting G-quartets is particularly intriguing. In this work, the DNA binder Berberine is encapsulated inside the molecular cavity of the synthesised host structure, Fluoresecein-β-cyclodextrin conjugate. The host: guest complex is characterized and the mode of binding is optimized using two dimensional rotating-frame Overhauser effect spectroscopy. The conjugate is examined for its binding to quadruplex DNAs viz., kit22, myc22, telo24 and the duplex calf-thymus DNA before and after Berberine encapsulation. UV–vis and fluorescence spectroscopic methods were employed to determine the strength of binding of the complex with the DNAs. The binding strength and the stoichiometry of the host: guest complex are 1.9 × 106 mol−1 dm3 and 1:1, respectively. A quenching of fluorescence of the quadruplex kit22 and duplex ctDNA is observed on binding to the Fluorescein-β-cyclodextrin conjugate. The quadruplexes of myc22 and telo24 display an enhanced fluorescence on binding to the modified cyclodextrin. The Stern-Volmer quenching constants are 1.4 × 106 mol−1 dm3 and 3.8 × 105 mol−1 dm3 for binding to kit22 and ctDNA respectively. kit22 shows a different emission profile on interacting with the Berberine encapsulated conjugate, whereas all the other quadruplexes and duplex exhibit similar emission profiles. The results indicate a variation in the binding mode and strength of the ligand-quadruplexes and depend on the conformation of the quadruplexes. Communicated by Ramaswamy H. Sarma

Molecular encapsulation by eosin yellow-β-cyclodextrin conjugate: Differential binding to quadruplex and duplex DNA

G-Quadruplexes exist in cells and are involved in several cancer-related processes. Thus, G-quadruplex binding is an effective way of aiming at cancer cells. In this paper, the binding of a new β-cyclodextrin conjugate, eosin yellow-CD, with quadruplex DNAs viz., kit22, myc22, telo24 and duplex calf-thymus DNA, is studied by UV–vis and fluorescence spectroscopic methods. Berberine, a known G-quadruplex binder, is loaded in the modified cyclodextrin. The binding constant of the host: guest complex is 1.9 × 106 mol−1 dm3. The proximity of the protons of the conjugate and Berberine with those of the internal cavity of β-cyclodextrin in the conjugate is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy. The conjugate displays a quenching of fluorescence selectively to the quadruplex kit22 and telo24 that contrasts the spectral characteristics of the ligand-bound complexes of myc22 and ctDNA. The Stern-Volmer quenching constants are 1.08 × 106 mol−1 dm3 and 1.6 × 106 mol−1 dm3, respectively for binding to kit22 and telo24. The duplex ctDNA exhibits an enhanced fluorescence in the absence and the presence of Berberine complex, whereas the quadrulex DNAs exhibit dissimilar emission profiles when the eosin yellow-CD encapsulates Berberine. We report the differences in the binding constants and the mode of binding of free- and Berberine-loaded eosin yellow-CD to the duplex and quadruplex DNAs.

Pectin from leaves of birch (Betula pendula Roth.): Results of NMR experiments and hypothesis of the RG-I structure

We report that in birch leaf pectin, rhamnogalacturonan-I (RG-I) and galacturonan (HG) were found as separate polymers rather than domains of a complex macromolecule. RG-I and HG were separated by anion-exchange and size-exclusion chromatography and studied by using NMR spectroscopy. NMR spectra showed that methyl-esterified D-galactosyluronic acid residues were located only in HG. Oligosaccharides of similar structure to the backbone, but without terminal reducing residues in the NMR spectra, were found in RG-I. We hypothesize, these oligosaccharides and RG-I backbone can be covalently bound due to its co-eluted of from DEAE-cellulose and Sepharose CL-4B. This result differs from the classical RG-I model, which assumes that all Rhap and GalpA residues are located only in the RG-I backbone. In the heteronuclear multiple bond correlation (HMBC) and rotating frame Overhauser effect spectroscopy (ROESY) spectra, the correlation peaks confirming the substitution of 2,4-rhamnose residues at O-4 by only single D-galactose residues were identified.

Remotely controllable supramolecular rotor mounted inside a porphyrinic cage

Remotely controllable supramolecular rotor mounted inside a porphyrinic cage

Tetrahydrocurcumin encapsulation in cyclodextrins for water solubility improvement: Synthesis, characterization and antifungal activity as a new biofungicide

The solubility of the scarcely water-soluble molecule tetrahydrocurcumin (THC), a promising curcumin derivative to be used as biopesticide, was enhanced through the formation of inclusion complexes with different cyclodextrins (CDs). Randomly methylated β-cyclodextrin (MeβCD) gave the best results among the different CDs whose size, substituent or structure was changing. Differential scanning calorimetry as well as 1H- and 2D-Nuclear Magnetic Resonance (NMR) proved the inclusion of THC in MeβCD. Rotating-frame Overhauser effect spectroscopy NMR especially illustrated specific interactions of aromatic protons of THC and protons located inside the CD cavity. The complex formation between THC and MeβCD was studied using the Higuchi and Connor method, giving an association constant of 591 M−1. THC-loaded MeβCD did not show any growth inhibition of the target fungus Fusarium graminearum. However, THC-loaded MeβCD polymers exhibited 25% inhibition of the fungal growth, thus making them promising material for solvent-free, aqueous and bio-based fungicide formulations.

Five Tetramic Acid Derivatives Isolated from the Iranian Fungus Colpomaquercinum CCTU A372.

Submerged mycelial cultures of the ascomycete Colpoma quercinum CCTU A372 were found to produce five previously undescribed tetramic acids, for which we propose the trivial names colposetins A–C (1–3) and colpomenoic acids A and B (4 and 5), along with the known compounds penicillide (6) and monodictyphenone (7). The planar structures of 1–5 were determined by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) and extensive 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Their absolute configurations were determined by the combination of electronic circular dischroism (ECD) analysis, J-based configurational analysis, and a rotating-frame Overhauser effect spectroscopy (ROESY) experiment. Colposetin B displayed weak antimicrobial activity against Bacillus subtilis and Mucor hiemalis (MIC 67 µg/mL).

The Total Solubility of the Co-Solubilized PAHs with Similar Structures Indicated by NMR Chemical Shift.

The synergism/inhibition level, solubilization sites and the total solubility (St) of co-solubilization systems of phenanthrene, anthracene and pyrene in Tween 80 and sodium dodecyl sulfate (SDS) are studied by 1H-NMR, 2D nuclear overhauser effect spectroscopy (NOESY) and rotating frame overhauser effect spectroscopy (ROESY). In Tween 80, inhibition for phenanthrene, anthracene and pyrene is observed in most binary and ternary systems. However, in SDS, synergism is predominant. After analysis, we find that the different synergism or inhibition situation between Tween 80 and SDS is related to the different types of surfactants used and the resulting different co-solubilization mechanisms. In addition, we also find that three polycyclic aromatic hydrocarbons (PAHs) have similar solubilization sites in both Tween 80 and SDS, which are almost unchanged in co-solubilization systems. Due to the similar solubilization sites, the chemical shift changes of surfactant and PAH protons follow the same pattern in all solubilization systems, and the order of chemical shift changes is consistent with the order of changes in the St of PAHs. In this case, it is feasible to evaluate St of PAHs by chemical shift. In both Tween 80 and SDS solutions, the ternary solubilization system has relatively high St rankings. Therefore, in practical applications, a good overall solubilization effect can be expected.

G-Quadruplex binding of cavity-containing anthraquinonesulfonyl-β-cyclodextrin conjugate. Effect of encapsulation of ethidium bromide and berberine

An anthraquinonesulfonyl derivative of β-cyclodextrin is prepared and characterized employing spectroscopic techniques. The binding interactions of the compound with ethidium bromide, berberine, calf-thymus DNA, quadruplex DNAs viz., kit22, telo24, and myc22 are investigated by ultraviolet-visible, and fluorescence spectroscopic methods. Anthraquinonesulfonyl-β-cyclodextrin conjugate acts as a host molecule and enhances ethidium bromide and berberine fluorescence due to their encapsulation in cyclodextrin’s cavity. The binding constant values are 9.0 × 105 mol−1 dm3 and 5.7 × 104 mol−1 dm3 for the formation of host: guest complexes of the β-CD derivative with ethidium bromide and berberine respectively. The proximity of the protons of ethidium bromide and berberine protons with those of the internal cavity of β-CD in the anthraquinonesulfonyl-β-CD conjugate is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy. The conjugate displays a quenching of fluorescence selectively to the quadruplexes kit22 and telo24 that is contrast to the spectral behavior with duplex DNA. ctDNA and myc22 exhibit different absorption and emission profiles with ethidium bromide on encapsulation by β-CD. The encapsulation of berberine leads to a fluorescence enhancement on binding to ctDNA, telo24, and myc22 with binding constants of 5.6 × 105, 3.3 × 105 mol−1 dm3, and 1.5 × 105 mol−1 dm3 respectively. In contrast, kit22 leads to fluorescence quenching on berberine encapsulated-anthraquinonesulfonyl-β-cyclodextrin conjugate with a Stern-Volmer constant of 3.3 × 105 mol−1 dm3. Communicated by Ramaswamy H. Sarma

Molecular encapsulation of berberine and ethidium bromide in anthraquinonecarboxamido-β-cyclodextrin conjugate: supramolecular association with DNA duplex and G-quadruplexes

G-quadruplex DNA in recognized as a potential target for anti-cancer drugs. In this work, an anthraquinonecarboxamido derivative of β-cyclodextrin (AQCC) is synthesized as a novel DNA binder that further can deliver an additional molecule at the target, carrying it in the cavity of modified cyclodextrin. The binding of AQCC with ethidium bromide (EtBr), berberine (Ber), duplex calf-thymus DNA (CT-DNA), quadruplexes (G4) viz., kit22, myc22, and telo24 are studied. The compound acts as a host molecule for the encapsulation of DNA binders viz., EtBr, Ber and enhances their fluorescence due to the encapsulation in its AQCC’s cyclodextrin cavity. The binding constant of the host: guest complex of EtBr and Ber with AQCC’s cavity are 6.4 × 105 and 3.3 × 106 mol−1 dm3, respectively. The proximity of the protons of the guest and host molecules is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY). The conjugate displays a quenching of fluorescence selectively on the association with CT-DNA and quadruplex kit22 that is contrast to the spectral behavior with quadruplex myc22 and telo24. CT-DNA exhibits dissimilar fluorescence spectra in free- and EtBr-bound forms. In addition, kit22 exhibit dissimilar emission profile when AQCC encapsulates Ber. Therefore, the Ber-loaded complexes and the AQCC molecule bind to different G-quadruplexes with different binding strengths. In addition, the effect of Ber in binding to the target DNAs is pronounces since the Ber molecule has more affinity to bind to quadruplexes than the duplex.