1H NMR spectroscopy as a probe of intermolecular interactions in ?-cyclodextrin inclusion compounds (original) (raw)
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Cyclodextrin Inclusion Complexes Probed by NMR Techniques
2012
Cyclodextrins (CDs) are cyclic oligomers of glucopyranose units that play an important role as a host in inclusion complexes, where non-covalent interactions are involved. They have been extensively studied in supramolecular chemistry. Because of its biocompatibility, relatively non-toxicity and relatively low price, CDs have been widely employed for encapsulation of several substances, being used in food, cosmetic and pharmaceutical industries. Nuclear Magnetic Resonance spectroscopy (NMR) is one of the most useful techniques to study interactions of cyclodextrins with guest compounds. It is relatively easy to apply, the experiments are fast and it is the only technique that provides information on the right orientation of the guest molecule inside the cavity and also on other important parameters related to the physico-chemical characteristics of the inclusion complexes. In this review, it will be discussed the study of inclusion complexes between drugs and cyclodextrins by differ...
Bulletin of the Chemical Society of Japan, 2012
The binding constants (K a 's) for the complexation of ¡and ¢-cyclodextrins (¡-and ¢-CDs) with some hydrophilic organic solvents such as methanol, dimethyl sulfoxide, acetone, etc., were successfully determined in D 2 O by following changes in the 1 H NMR chemical shift of the C(3)H signal of CD, using the C(1)H signal as an internal reference. The K a value obtained for a ¢-CDmethanol complex was 0.088 mol ¹1 dm 3 at 298 K, which is, as we know, the smallest among K a 's measured thus far for CD complexes. The same method was also applied to the determination of K a 's for the complexation of ¡-CD with ethylene glycol and some related compounds. It was revealed that these molecules were certainly included within the cavity of ¡-CD, though the K a values are fairly small.
1999
Abstract. The interaction in solution between 2,4-dichlorophenoxyacetic acid with α- and β-cyclodextrins was evaluated by phase solubility studies. Association constants were calculated by this technique. The stoichiometries were 1: 2 and 1: 1 for the α- and β-cyclodextrin complexes, respectively. In order to corroborate the complexation and the knowledge of structural aspects of the host: guest interaction, proton nuclear magnetic resonance (1H-NMR) spectroscopy was employed. The application of the continuous variation technique corroborated the calculated complex stoi-chiometries by solubility assays. Complementary NOE studies were applied in order to corroborate the proposed complex structures. Key words: solubility, 1H-NMR, stoichiometry, cyclodextrins 1.
1H NMR study of inclusion compounds of phenylurea derivatives in β-cyclodextrin
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2005
Proton nuclear magnetic resonance spectroscopy ( 1 H NMR), which has become an important tool for the study "in situ" of -cyclodextrin (-CD) complexes, was used to study and structurally characterize the inclusion complexes formed between -CD and isoproturon, fenuron, monuron and diuron. The high variation of the chemical shifts from the proton located inside the cavity (H-3, H-5 and H-6) coupled with the non variation of the one located outer sphere of the -CD (H-1, H-2 and H-4) provided clear evidence of the inclusion phenomena. Twodimensional rotating frame Overhauser effect spectroscopy (ROESY) experiments were carried out to further support the proposed inclusion mode.
Beilstein journal of organic chemistry, 2017
Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1/β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule.
SN Applied Sciences, 2022
Forming complexes with β-cyclodextrin can enhance stability, dissolution rate, solubility, and bioavailability of an active pharmaceutical ingredient. In this study, the inclusion behavior between β-cyclodextrin (β-CD) and diphenhydramine, clonidine, and tolperisone in DMSO-d6 was investigated using NMR spectroscopy. 1H, 13C, COSY, HMQC, and ROESY data were applied to determine the structure of inclusion complexes, and molecular docking analysis was engaged to identify the most favorable host–guest interactions in the inclusion complexes. Complexation of β-CD with diphenhydramine, clonidine, and tolperisone is accompanied by the insertion of a molecular fragment of the guest molecule, one molecule of diphenhydramine and tolperisone, and two molecules of clonidine, into the inner sphere of one host molecule. The reported study provides useful information for the potential application of the complexation of β-CD with diphenhydramine, clonidine, and tolperisone. This may be a good stra...
NMR studies of complex formation between natural cyclodextrins and benzene
Research Square (Research Square), 2023
Inclusion complexes of benzene (Bz) with cyclodextrins (CD) have been investigated so far using non-NMR techniques resulting in con icting data. Here, the rst application of NMR spectroscopy in combination with rigorous statistical analysis of the results has allowed us to determine accurately the stoichiometry of complexes and their association constants. Titration measurements have been performed by 1 H NMR spectroscopy in D 2 O at a magnetic eld B 0 of 14.1 T. αCD and γCD host molecules form weak 1 : 1 complexes with Bz. In contrast, Bz and βCD build 1 : 1 and 2 : 1 complexes coexisting in solution with large binding constants. Binding of second benzene molecule is strongly cooperative.
NMR spectroscopy of inclusion complex of sodium diclofenac with β-cyclodextrin in aqueous solution
Biospectroscopy, 1997
The interaction between diclofenac (sodium salt of 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid) and b-cyclodextrin in aqueous solution has been investigated by 1 H-NMR spectroscopic technique. The technique is based on the shielding of the b-cyclodextrin and drug protons. The spectra showed upfield shifts of the b-cyclodextrin protons in the presence of diclofenac, and the diclofenac protons also shifted upfield in the presence of b-cyclodextrin. The changes in chemical shifts of suitable guest-host protons are consistent with the formation of an inclusion complex diclofenac/ b-cyclodextrin. Presented in part at the European Conference of the Spec-is present in water, so it can be considered as a troscopy of Biomolecules, ECSBM'95, Villeneuve d'Ascq, 3-8 hydrophobic cavity. The inner cavity diameters of September 1995, France.
Bioorganic & Medicinal Chemistry, 2007
The aim of this paper is to describe the inclusion properties and the factors affecting the complexation selectivity and stabilization of catechin (CA) into β-cyclodextrin (β-CD) and two of its derivatives, namely Heptakis 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) and 2 hydroxypropyl-β-cyclodextrin (HP-β-CD). Analysis of the proton shift change using the continuous variation method confirm the formation of a 1:1 stoichiometric complex for catechin and the different CDs in aqueous medium. The formations constant obtained by diffusion-ordered spectroscopy (DOSY) techniques indicated the following trend upon complex formation: β-CD > HP-β-CD > DM-β-CD. The detailed spatial configuration is proposed based on 2D NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data. The models confirm that when CA-β-CD is formed, the catechol moiety in the complex is oriented toward the primary rim; however when CD is derivatized to HP-β-CD and DM-β-CD this ring is oriented toward the secondary rim.The inclusion properties of catechin into native and modified β-cyclodextrin have been evaluated using NMR and molecular modeling techniques.