ROESY Spectral Data Research Articles

GKK1032C, a new alkaloid compound from the endophytic fungus Penicillium sp. CPCC 400817 with activity against methicillin-resistant S. aureus.

Five alkaloid compounds (1-5), including one new compound, GKK1032C (1), and four known compounds, pyrrospirones E (2) and F (3), and GKK1032B (4) and A2 (5) were isolated from the culture of endophytic fungus Penicillium sp. CPCC 400817. The planar structures of all compounds were elucidated by NMR and MS spectra. The relative configuration of new compound GKK1032C (1) was deduced from the vicinal J-values and ROESY spectral data. Compound 1 exhibited potent antibacterial activity against methicillin-resistant Staphylococcus aureus with an MIC value of 1.6 μg ml-1.

Molecular recognition of flunarizine dihydrochloride and \u03b2-cyclodextrin inclusion complex by NMR and computational approaches

BackgroundFlunarizine dihydrochloride (FLN) is used in the prophylactic treatment of migraine, vertigo, occlusive peripheral vascular disease and epilepsy. Cyclodextrins (CDs) are chiral, truncated cone shaped macrocycles known for their inner hydrophobic and outer hydrophilic site. They form complexes with hydrophobic drug molecules and enhance the solubility and bioavailability of such compounds by enhancing drug permeability through mucosal tissues. NMR spectroscopy and computational docking have been recognized as an important tool for the interaction study of CDs-drug inclusion complexes in solution state.ResultsThe structural assignments of FLN and β-CD protons were determined by 1H NMR and 2D 1H-1H COSY NMR spectroscopy. 1H NMR spectroscopic studies of FLN, β-CD and their mixtures confirmed the formation of β-CD-FLN inclusion complex in solution. 1H NMR titration data for β-CD-FLN inclusion complex showed 1:1 stoichiometry, an association constant of Ka = 157 M−1 and change in Gibbs free energy of ∆G = − 12.65 kJ mol−1. The binding constant of the β-CD inclusion complex with two nearly similar structures, FLN and cetirizine dihydrochloride, were compared. Two-dimensional 1H-1H ROESY spectral data and molecular docking studies showed the modes of penetration of the aromatic rings from the wider rim side into the β-CD cavity. The possible geometrical structures of the β-CD-FLN inclusion complex have been proposed in which aromatic rings protrude close to the narrower rim of the β-CD truncated cone.ConclusionNMR spectroscopic studies of FLN, β-CD and FLN:β-CD mixtures confirmed the formation of 1:1 inclusion complex in solution at room temperature. Two-dimensional 1H-1H ROESY together with molecular docking study confirmed that the F-substituted aromatic ring of FLN penetrates into β-CD truncated cone and the tail of aromatic rings were proximal to narrower rim of β-CD. The splitting of aromatic signals of FLN in the presence of β-CD suggests chiral differentiation of the guest FLN by β-CD.

Complexation of sodium picosulphate with beta cyclodextrin: NMR spectroscopic study in solution

Sodium Picosulphate (SPL) is a synthetic drug, widely used for thorough evacuation of the bowel, usually for patients who are preparing to undergo a colonoscopy. Cyclodextrins (CDs) are chiral, truncated cone shaped, cyclic oligosaccharides that can encapsulate a variety of drug molecules into inclusion complexes, thereby increasing their stability and solubility. 1H NMR spectroscopic studies showed the inclusion complexation between β-CD and SPL, based on the upfield shift changes in the β-CD cavity protons (H-3′ and H-5′) and downfield shift changes in the guest (SPL) protons. The structure of inclusion complexes was determined by 2D ROESY spectral data. The 1:1 stoichiometry and overall association constant (Ka) were determined by using Scott’s plot method to be 450 M−1.

Structure determination of fexofenadine-α-cyclodextrin complex by quantitative 2D ROESY analysis and molecular mechanics studies

Complexation of fexofenadine with α-cyclodextrin in aqueous medium was studied. The stoichiometry of the resulting inclusion complex was determined by (1) H NMR titration data. 2D ROESY data provided the evidence of formation of the complex by entry of the phenyl ring into the α-cyclodextrin cavity probably from wider opening. Determination of relative peak intensities of intermolecular cross-peaks for the most stable complexes obtained by molecular mechanics (MM2) studies and from 2D ROESY spectral data confirmed the presence of only one complex in solution that has been fully characterized.

NMR investigation on the interaction of β-cyclodextrin and ampicillin

The penetration of ampicillin molecule into the β-cyclodextrin cavity in aqueous solution is studied by 1 H NMR, 2D COSY and ROESY spectroscopy. Obtained data suggest that the phenyl moiety of ampicillin is included inside the hydrophobic cavity of β-cyclodextrin molecule in the solution, and the mode and depth of this inclusion is confirmed on the basis of 2D ROESY spectral data.

A comparative study of inclusion complexes of flunarizine with alpha (α-CD) and beta-cyclodextrin (β-CD)

A detailed NMR (1H, COSY, and ROESY) spectroscopic study of complexation of Flunarazine (FL) with α- and β-CD was carried out. 1H NMR titration studies confirmed the formation of FL/α-CD and FL/β-CD complexes as evidenced by chemical shift variations of the proton resonances of both the CDs and FL. The stoichiometry of the complexes was determined to be 1:2 (FL/α-CD) and 1:1 (FL/β-CD) and overall binding constants were also calculated. It was confirmed with the help of ROESY spectral data that only one of the F-substituted aromatic ring and phenyl ring penetrate the α-CD cavity while both F-substituted aromatic rings as well as phenyl ring penetrates the β-CD cavity during complexation. The binding modes of FL/CD cavity interactions derived from ROESY experimental data show that the resulting complex of FL with β-CD possesses better induced fit interaction as compared to α-CD, which is responsible for the enhanced molecular stability with β-CD in comparison to α-CD. The mode of penetration of guest into the CD cavity and structures of the complexes has been established.

Solution structure of loperamide and β-cyclodextrin inclusion complexes using NMR spectroscopy

Loperamide (LPR) is a synthetic, poorly water soluble, peripherally acting opiate agonist drug used for the treatment of diarrhea. Major challenges in formulating this drug for clinical applications include solubility enhancement and improved stability in biological systems. Cyclodextrins (CDs) are chiral, truncated cone shaped; cyclic oligosaccharides that can encapsulate a variety of poorly water soluble drug molecules into inclusion complexes, thereby increasing their stability and solubility. 1H NMR spectroscopic studies showed the inclusion complexation between β-CD and LPR, based on the upfield shift changes in the β-CD cavity protons (H-3′ and H-5′) and downfield shift changes in the guest (LPR) protons. 2D COSY spectral data was used for assignment of β-CD as well as LPR protons and 2D ROESY spectral data to know the inclusion of LPR inside the β-CD cavity. The 1: 1 stoichiometry and overall association constant (K a) were determined by using Scott’s plot method to be 68·805 M−1. 2D ROESY spectral data suggest that the inclusion of aromatic rings of LPR in β-CD cavity can be from narrower as well as the wider rim side and the six possible 1: 1 LPR: β-CD inclusion complexes have been proposed. Thus, we anticipate that complexation of LPR with β-CD would increase its solubility and stability in biological system.

Complexation study of midazolam hydrochloride with β‐cyclodextrin: NMR spectroscopic study in solution

(1)H NMR spectroscopic study of midazolam hydrochloride (MDL), beta-cyclodextrin (beta-CD) and their mixtures confirmed the formation of beta-CD-MDL inclusion complex in aqueous solution. The stoichiometry of the complexes was determined by Scott's method to be 1:1, and the association constant (K(a)) was calculated to be 108 M(-1). It was confirmed on the basis of 2D ROESY spectral data that only a fluorine-substituted aromatic ring acted as guest in complexation. Most of the aromatic signals of MDL exhibited induced shift changes as well as splitting, in the presence of beta-CD, indicating chiral differentiation of MDL by beta-CD.

Complexation between Venlafaxine Hydrochloride and β -Cyclodextrin:Structural Study by Nuclear Magnetic Resonance Spectroscopy

A detailed spectroscopic study (<TEX>$^1H$</TEX> NMR, COSY, ROESY) of complexation of venlafaxine hydrochloride (VEN) with <TEX>$\beta$</TEX>-cyclodextrin (<TEX>$\beta$</TEX>--CD) was carried out in solution. The stoichiometry of the complex was determined to be 1 : 1 and penetration of aromatic ring into <TEX>$\beta$</TEX>-Cyclodextrin cavity was confirmed from primary rim side, with the help of ROESY spectral data. The structure of the venlafaxine hydrochloride-<TEX>$\beta$</TEX>-CD complex has been proposed. The association constant was determined to be 234 <TEX>$M^{-1}$</TEX>.

Complexation of Fluvastatin Sodium with β-Cyclodextrin: NMR Spectroscopic Study in Solution

1H NMR spectroscopic study of fluvastatin sodium (FLU), β-Cyclodextrin (β-CD) and their mixtures confirmed the formation of FLU/β-CD inclusion complex in solution. The stoichiometry of the complex was determined to be 1:1 and the overall binding constant (Ks) was calculated to be 340 M−1. Two dimensional COSY, ROESY and DEPTO experiments were performed for the unambiguous assignment of aromatic proton resonances and it was found that two isomeric forms of FLU are present in solution. It was confirmed with the help of ROESY spectral data that only F-substituted aromatic ring penetrates the β-CD cavity and there is chiral differentiation by the β-CD as one of the isomer binds more strongly, which is indicated by the intensity of correlation peaks. The mode of penetration of the guest into the β-CD cavity was also established and structure of the complex has been proposed.

A new germacranolide from Carpesium cernuum

As a part of our interest in biologically active germacranolides from the genusCarpesium (Compositae), we have investigated the constituents ofCarpesium cernuum. This paper reports the isolation and structural elucidation of a new germacranolide, cernolide A (Compound 1), from the herb. The structure of Compound 1 was determined as 2α,3β-dihydroxy-9-angeloxygermacra-4-en-6,12-olide on the basis of spectral evidence. The skeleton of Compound 1 was elucidation by IR, MS,1H and13CNMR, COSY, HMQC and HMBC experiments. The stereochemistry of Compound 1 was deduced by ROESY spectral data. Finally, the procedures of extraction and isolation were described in detail.