1H NMR spectroscopy as a probe of intermolecular interactions in ?-cyclodextrin inclusion compounds (original) (raw)
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.
Structure and spectroscopic properties of cyclodextrin inclusion complexes
Journal of Inclusion Phenomena and Molecular Recognition in Chemistry, 1996
We compare spectroscopic properties of higher order complexes of organic guests (e.g. naphthalene, phenols, indole, C60-fullerene ) with cyclodextrins (CDx) to results of molecular modeling investigations. Naphthalene 1:2 complexes with a-CDx show high spectral resolution and peculiar triplet properties. Molecular simulations and calculation of the experimentally measured induced circular dichroism (ICD) provide detailed structural information.
The Journal of Physical Chemistry B, 2013
The structural characterization and dynamic properties of solid state inclusion complexes (ICs) 23 formed between β-cyclodextrin (β-CD; host) and perfluorooctanoic acid (PFOA; guest) were investigated using C NMR spectroscopy. The 1:1 and 2:1 host/guest solid state complexes 25 were prepared using a modified dissolution method to obtain complexes with high phase purity. 26 These complexes were further characterized using differential scanning calorimetry (DSC), FT-27 IR spectroscopy, PXRD, 19 F direct polarization (DP) and 13 C cross polarization (CP) with magic-28 angle spinning (MAS) NMR spectroscopy. The 19 F→ 13 C CP results provided unequivocal 29 support for the formation of well-defined inclusion compounds. The phase purity of the 30 complexes formed between β-CD and PFOA were assessed using the 19 F DP NMR technique 31 at variable temperature (VT) and MAS at 20 kHz. The complexes were found to be of high 32 phase purity when prepared in accordance with the modified dissolution method. The motional 33 dynamics of the guest in the solid complexes were assessed using T 1 /T 2 /T 1ρ relaxation NMR 34 methods at ambient and variable temperatures. The relaxation data revealed reliable and 35 variable guest dynamics for the 1:1 vs. 2:1 complexes at the variable temperatures investigated. 36 The motional dynamics of the guest molecules involve an ensemble of axial motions of the 37 whole chain and 120° rotational jumps of the methyl (CF 3) group at the termini of the 38 perfluorocarbon chain. The axial and rotational dynamics of the guest in the 1:1 and 2:1 39 complexes differ in distribution and magnitude in accordance with the binding geometry of the 40 guest within the host.
Inclusion complexing by water-soluble ?-cyclodextrin polymers
Journal of Inclusion Phenomena, 1984
Cross-linked fl-cyclodextrin with a molecular weight of less than 10000 has good solubility in water, and it is a better inclusion complexing agent than the parent fl-cyclodextrin. By including lipophilic guest molecules into the apolar cyclodextrin cavity, their apparent lipophilicity is reduced because the outer surface of the molecular 'wrapping' (the crosslinked fl-CD) is highly hydrophilic. The relative stability of the inclusion complexes can be rapidly determined by reversed-phase thin-layer chromatography. The reversed-phase TLC behaviour of 25 triphenylmethane derivatives and analogues were studied in the presence of fl-cyclodextrin polymers containing neutral and carboxyl groups. Increasing the molecular weight results in an increased complex-forming capacity. The carboxyl group modifies the accessibility of the CD cavity which in turn results in increased or decreased complex stability, depending on the guest molecule. The presence of organic solvents diminishes the stability of the CD complexes: