1H NMR spectroscopic investigation of β-cyclodextrin inclusion compounds with parecoxib

The inclusion complexes of β-CD and parecoxib [PRB] in aqueous solution were investigated using ¹H NMR spectroscopic study revealed the existence of four different equilibria for 1:1 inclusion complexes in which both the aromatic rings of the guest are tightly held by the host cavity. The NMR spectra of the PRB studied in the presence of β-CD are fully assigned and interpreted by means of COSY spectrum for the unambiguous assignment of guest aromatic ring protons. The parallel interpretation of β-CD chemical shift changes and dipolar contacts, with the aid of 2D ROESY, allows the mode of binding to be established for four possible structures of 1:1 PRB-β-CD inclusion complexes.     

1H NMR spectroscopic study of complexation of citalopram with beta-cyclodextrin in aqueous solution

(1)H NMR spectroscopic study of citalopram (CT) in the absence as well as in the presence of beta-cyclodextrin (beta-CD) in aqueous solution revealed the formation of four 1:1 beta-CD-CT inclusion complexes. The stoichiometry of the complexes was determined by the continuous variation (Job) method, which was further confirmed by Scott's method. The binding constants (K(R) and K(R, S)) were calculated using Scott's method. The structures of all the complexes have been proposed as shown in the diagrams. All the CT proton resonances showed splitting in the presence of beta-CD, owing to chiral discrimination by the beta-CD, between the two enantiomers. The chiral discrimination appears to be due to different modes of binding of the R- and S-CT in the complexes involving a CN-containing aromatic ring.     

Cyclodextrin inclusion of four phenylurea herbicides: determination of complex stoichiometries and stability constants using solution 1H NMR spectroscopy

An inclusion complex formation between α- and β-cyclodextrin and four phenylurea analogues, namely metobromuron, monolinuron, monuron and fenuron, is reported. Complex formation was established using solution ¹H NMR spectroscopy. Complex stoichiometries were determined by the method of continuous variation using the chemically induced shifts of both the host and guest protons. An analysis of the spectroscopic data revealed the stoichiometry as 1:1 in all cases while a further analysis of the same data yielded values for the association constant K ranging from 208 to 2749 M^? 1. From the observed chemical shifts it was deduced that in all cases, only the guest aromatic ring enters the host cavities, the substituted urea moiety protruding from the secondary rim in the case of α-cyclodextrin, but from the primary rim in the case of β-cyclodextrin.     

Study on inclusion interaction of piroxicam with beta-cyclodextrin derivatives

The inclusion behavior of piroxicam (PX) with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and carboxymethyl-beta-cyclodextrin (CM-beta-CD) was investigated by using steady-state fluorescence and nuclear magnetic resonance (NMR) technique. The various factors affecting the inclusion process were examined in detail. The remarkable fluorescence emission enhancement upon addition of CDs suggested that cyclodextrins (CDs) were most suitable for inclusion of the uncharged species of PX. The stoichiometry of the PX-CDs inclusion complexes was 1:1, except for beta-CD where a 1:2 inclusion complex was formed. The formation constants showed the strongest inclusion capacity of beta-CD. NMR showed the inclusion mode of PX with CDs.     

Preparation and study on the inclusion complexes of two tanshinone compounds with beta-cyclodextrin

Solid inclusion complexes of two tanshinones (Tans): tanshinone IIA (Tan IIA), tanshinone I (Tan I) with beta-cyclodextrin (beta-CD) were synthesized by coprecipitation method. The solid inclusion complexes were characterized by using several analytical techniques: (1)H NMR spectra, IR spectra and thermal analysis. Stoichiometry of the inclusion complexes of Tans with beta-CD or HP-beta-CD is 1:1 which was investigated in solution. The formation constants of the complexes were determined by UV spectrophotometry. For same kind of CD, the stability was in the order: Tan IIA > Tan I; for same guest, the stability was in the order: HP-beta-CD > beta-CD. The effect of temperature on the inclusion interaction was examined and the thermodynamic parameters of inclusion process, Delta G, Delta H, Delta S were determined as well. The experimental results indicate that the inclusion process was an exothermic and enthalpy-driven process accompanied with a negative entropic contribution. The inclusion interaction between CD and Tans satisfied the law of enthalpy-entropy compensation.     

1H NMR study on the self-association of quinacridone derivatives in solution

The pi-stacking structures and self-association thermodynamics of N, N'-di(n-alkyl) quinacridone derivatives (n-alkyl QAs) with various substituents on the side aromatic rings and different length of n-alkyl chains are investigated in organic solvents by (1)H NMR spectroscopy. The stacking geometries are built based on both the magnitudes and directions of peak shifts with concentration and solvent polarity. The intermolecular interaction between nitrogen atoms and oxygen atoms dominates the general geometrical preferences of the stacking in which the molecules are face-to-face arranged in a parallel and an antiparallel fashion, respectively. The stacking structures are little affected by the length of the n-alkyl chains but are regulated in an allowed range by the size and properties of the substituents. The association processes of all the n-alkyl QAs are enthalpically favorable at 298 K, while the relative stability of these n-alkyl QAs assemblies is governed mainly by the entropy of the association processes. The introduction of larger substituents and longer n-alkyl chains disfavors the association of the n-alkyl QAs, while the binding of the halogen atoms on the side aromatic rings is favorable to the association. The relative strength of the stacking interaction for the substituted n-alkyl QAs has not obvious correlation with the electron-donating or electron-withdrawing nature of the substituents, while it is well associated to the dispersion energy and repulsive exchange energy. The different entropy-enthalpy compensation of the halogen-substituted n-alkyl QAs from others may suggest different association mechanism for the two types of n-alkyl QAs.     

Theoretical and experimental vibrational study of phenylurea: structure, solvent effect and inclusion process with the beta-cyclodextrin in the solid state

FTIR and Raman vibrational spectroscopic techniques as well as DFT quantum chemical calculation were used for characterizing conformational changes of phenylurea (a herbicide parent molecule) occurring from solid state to aqueous medium. Experimental infrared frequencies were assigned on the base of urea and benzenic derivatives spectroscopic data available in the literature and vibrational normal modes analytical calculation at the fully optimized geometry. Investigation of isotopic and solvent effects has revealed that the structure of phenylurea is particularly sensitive to the electrostatic environment via hydrogen non covalent bonds. The ability of beta-cyclodextrin (beta-CD) to form host-guest inclusion complex with phenylurea in the solid state was also evidenced by significant frequency shifts observed in the 1400-1800 cm(-1) spectral range.     

NMR characterization of the host-guest inclusion complex between beta-cyclodextrin and doxepin

The interaction between doxepin, a member of the tricyclic antidepressant (TCA) class of drugs, with beta-cyclodextrin (beta-CD) was investigated using NMR. Several TCAs have been reported to form a complex with beta-CD having 1:1 stoichiometry. Previous results from UV-visible spectroscopy, fluorescence measurements, and molecular modeling indicated that for imipramine, desipramine, and amitriptyline, the TCA aliphatic tail is included in the cyclodextrin cavity with apparently no interaction of the tricyclic ring. An alternative view of the doxepin-beta-CD complex is presented in this work using analysis of complexation-induced chemical shifts (CICSs), the method of continuous variation (Job's analysis), and analysis of ROESY spectra. The Job's plot derived from the NMR spectral data confirms that the complex formed has 1:1 stoichiometry. The largest changes in the CICS data were observed for the aromatic protons of one of the doxepin rings, with much smaller chemical shift changes observed for the protons of the other aromatic ring and the doxepin tail. Perhaps the most significant evidence for inclusion of the doxepin tricyclic ring is the strong ROESY cross peaks between the doxepin aromatic resonances and the protons located inside the beta-CD cavity. Changes in the doxepin (1)H NMR spectrum and the behavior of ROESY exchange cross peaks suggest that inclusion complex formation decreases the rate of internal motions of doxepin.     

Structure and dynamics of perfluoroalkane/beta-cyclodextrin inclusion compounds as studied by solid-state 19F MAS and 1H -->19F CP/MAS NMR spectroscopy

The molecular structure and dynamics of novel inclusion compounds (ICs) consisting of n-perfluoroalkane (PFA) guests and beta-cyclodextrin (beta-CD) host (PFA/beta-CD) have been investigated using 19F magic angle spinning (MAS) and 1H-->19F cross polarization (CP)/MAS NMR spectroscopy with the aid of thermal analyses, FT-IR spectroscopy, and X-ray diffraction method. The ICs of C9F20/beta-CD and C20F42/beta-CD were successfully obtained as precipitates from mixtures of respective PFAs and saturated aqueous solution of beta-CD. The wide-angle X-ray diffraction (WAXD) revealed that C9F20/beta-CD forms a channel-type crystallite, while C20F42/beta-CD is nearly amorphous at room temperature. The structural orders in both ICs increase at elevated temperatures. The 19F NMR signals obtained by the direct polarization (DP) method for PFA/beta-CD are resonated at higher frequencies than those for original PFA. This can be ascribed to the lower dielectric environment of the beta-CD cavity. Above 80 degrees C, 1H-->19F CP/MAS NMR technique revealed that C9F20 molecules undergo vigorous molecular motion and partly come out of the beta-CD channel. However, the guests hardly degrade or evaporate unless the host is pyrolytically decomposed above ca. 300 degrees C. The spin-lattice relaxation times in the laboratory frame for 19F (T1F) are almost identical for all the fluorines in PFA/beta-CD at each temperature, while significantly different values were observed for fluorines in neat PFA. This indicates that effective intramolecular spin diffusion occurs within a PFA molecule included in beta-CD.     

Fluorometric study of the inclusion interaction of beta-cyclodextrin derivatives with tetraphenylporphyrin and its analytical application

The effects of native beta-cyclodextrin (beta-CD) and four kinds of alkylated beta-cyclodextrin (beta-CDs), i.e. heptakis (2,6-di-O-isobutyl-beta-cyclodextrin) (I), heptakis (2,6-di-O-octyl-beta-cyclodextrin) (II), heptakis (2,6-di-O-dodecyl-beta-cyclodextrin) (III), and heptakis (2,6-di-O-hexadecyl-beta-cyclodextrin) (IV), on the fluorescence behaviors of tetraphenylporphyrin (TPP) are investigated. An obvious fluorescence enhancement is observed from TPP by using alkylated derivatives compared to that obtained in beta-CD aqueous or in water. A 114-N fluorescence emission intensity enhancement is found for the complex with 2,6-di-O-octyl-beta-cyclodextrin relative to the free analyte. The exact stoichiometric ratios and the formation constants of the inclusion complexes have been examined by application of curve fitting method. The linear calibration plots between fluorescence intensity and TPP concentration are determined in the 1.14 x 10(-8)-5.06 x 10(-6) mol l(-1) range.     

1H NMR study on the inclusion of bicyclo[3.3.1]nonanes in cyclodextrins

- and -cyclodextrins were found to form 1:1 inclusion complexes with 2,6- and 2,9-substituted bicyclo[3.3.1]nonanes. The binding constants and the structure of the complexes were estimated from titration studies and 2D ROESY experiments.     

Synthesis and1H NMR study of some organotin derivatives of diethanolamines

A number of organotin derivatives of diethanolamines (stannocanes) R₂Sn(OCH₂CH₂)₂NR', O(SiMe₂CH₂)₂Sn(OCH₂CH₂)₂NR', and Sn[(OCH₂CH₂)₂NR']₂ (R = Ph,cyclo-Hex; R' = H, Me, Ph) were synthesized and studied by¹H NMR spectroscopy. The effect of steric factors on the ability of molecules of stannocanes to form associates in solutions is discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp.714–718, April, 1994.     

1H and 13C NMR study of dihydro derivatives of methylphenobarbital

Sodium borohydride reduction of methylphenobarbital leads to the formation of two different dihydroderivatives, reduced either in position 4 or position 6. The structures of the derivatives have been determined through analysis of the ¹H and ¹³C NMR spectra of phenobarbital, methylphenobarbital and their derivatives. Detailed interpretation of the spectra and the resulting spectral parameters indicate conformations where the hydroxyl groups are axial and trans to the ethyl group. In these configurations the phenyl ring becomes equatorial. The results also allow an unambiguous assignment of the resonances of the phenyl carbons 2′(6′) and 3′(5′) of phenobarbital and the carbonyl carbons 4 and 6 of methylphenobarbital, differing interpretations having been previously advanced in the literature.     

Interaction of pyromellitic diimide derivatives with beta-cyclodextrin and anthracene-appended beta-cyclodextrin: rim binding vs inclusion complexation

Complex formation of pyromellitic diimide derivatives with beta-cyclodextrin and anthracene-appended beta-cyclodextrin was studied with use of induced circular dichroism and 1H NMR spectroscopies. It is revealed that pyromellitic diimides form rim-binding type complexes with beta-CD and in these complexes the pyromellitic diimides lie just outside of the narrow rim of the CD. With anthracene-appended beta-CD the pyromellitic diimides form true inclusion complexes. Implications of the formation of rim-binding type complexes are also discussed.     

1H NMR study of the inclusion of Costa-type organocobalt(III) complexes in cyclodextrins

The inclusion behavior between Costa-type complexes and cyclodextrins (CDs) was studied by 1H NMR in aqueous solution. The results indicated that 1:1 inclusion complex was formed, in which the alkyl group of the guest was included in the cavity of CDs. The stability constants of the inclusion complexes were determined by the quantitative 1H NMR method. The effects on stability constants were discussed when various host and guest compounds were used.     

1H and 13C NMR investigations of inclusion complexes between β-cyclodextrin and naphthalenediamines/phenol derivatives

Three inclusion complexes between β-CD and 1,5-naphthalenediamine, 1,8-naphthalenediamine, ethyl p-hydroxylbenzoate are synthesized and identified via ¹H and ¹³C NMR spectra, respectively. The possible conformations of the inclusion complexes are depicted.     

NMR studies on solid cyclohexaamylose inclusion compounds

Orthorhombic inclusion compounds of cyclohexaamylose with methanol,n-propanol, acetic acid and water as guest molecules were studied using¹³C and²H NMR techniques.¹³C chemical shifts were correlated with structural data, whereas²H NMR lineshapes were used to derive information on guest molecule motions.Issued as NRCC No. 25568. Presented in part at the 2nd International Symposium on Clathrate Compounds and Molecular Inclusion Phenomena, Parma, Italy, 30 Aug.–3 Sept. 1982     

The 1H NMR spectra of some norbornene derivatives,a LIS study

The ¹H NMR spectra of 2-exo-hydroxymethyl-3-endo-methylnorbornene and the corresponding 2-endo-3-exo isomer have been completely assigned with the aid of lanthanide reagents. This enabled a full analysis of the unusual spectrum of 2-exo-hydroxy-methyl-3-endo-methylnorbornene to be undertaken, confirming the proposed structure. The ΔEu values for 2-exo-hydroxymethyl-3-endo-methylnorbornene and the 2-endo-3-exo-isomer have been used to test the effect of rotational averaging on the calculated pseudo contact shifts. Good agreement is obtained for a dynamic model in which the Eu atom exchanges between two sites on the oxygen atom of the OH bond, and in which the rotational equilibrium about the CH? CH₂OH bond is explicitly considered.