Interactions of tetrakis(4-N-methylpyridyl)porphyrin with cyclodextrins and disodium phthalate in aqueous solution

In pH 7.3 buffers, the interactions of a cationic porphyrin, tetrakis(4-N-methylpyridyl)porphyrin (TMPyP), with cyclodextrins (CDs) and disodium phthalate (DSP) have been examined by means of absorption, fluorescence, and induced circular dichroism spectroscopy. α-CD, β-CD, and γ-CD form a 1:1 inclusion complex with a TMPyP monomer, which dimerizes in solution without CD. TMPyP also forms a 1:1 organic cation–organic anion complex with DSP. The 1:1 TMPyP–DSP complex forms a ternary CD–TMPyP–DSP inclusion complex with α-, β-, and γ-CD, in which a DSP molecule is not incorporated into the CD cavity. From the fluorescence intensity change, the␣equilibrium constants have been evaluated for the formation of the inclusion complexes and the organic cation–anion complexes.     

Interactions of xanthine and its derivatives with cyclodextrins in aqueous solutions

Using calorimetry, ¹H NMR, UV spectroscopy, and solubility methods, the interactions of natural and hydroxypropylated 6h-, β-, and γ-cyclodextrins with xanthine and its methylated derivatives (theophylline, theobromine, and caffeine) were studied in aqueous solutions at 298.15 K. Cyclodextrins revealed low complexation ability toward xanthine and its methylated derivatives. Hydroxypropyl-γ-cyclodextrin with the largest internal cavity is the most effective solubilizing agent for this type of compounds. The calculated thermodynamic parameters are discussed in terms of structural effects of cyclodextrins and purine alkaloids on the character of their intermolecular interactions in aqueous medium.     

Hydration and dynamic behavior of cyclodextrins in aqueous solution

The hydration state and dynamics of plain and chemically modified cyclodextrins (CDs) in aqueous solution were investigated by using dielectric relaxation measurements at 25 degrees C over a wide frequency range up to 20 GHz, which is the relaxation frequency of pure liquid water molecules. The obtained dielectric relaxation spectra were decomposed into two major and one minor relaxation modes with relaxation times of approximately 8.3, 20-25, and 1000-2500 ps, respectively, depending on the CD species. The two major modes, fast and medium, were attributed to a rotational relaxation process of water molecules belonging to the bulk (free) state and an exchange of water molecules hydrated to CDs owing to hydrogen bond formation. The hydration numbers of the CDs strongly depend on the number of hydroxy (OH) groups controlled by chemical modification such as methylation. Increasing the number of methoxy or 2-hydroxypropoxy groups increases the hydration number of CD molecules, and results in higher solubilities of the chemically modified CDs than those of the plain CDs. The minor, slow mode was assigned to overall rotational relaxation for CDs with finite permanent dipole moments, which also depends on the number of OH groups.     

Tetrakis(4-pyridyl)porphyrin supramolecular complexes with cyclodextrins in aqueous solution

The formation of inclusion complexes of hydroxypropyl-beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin with 5,10,15,20-tetrakis(4-pyridyl)porphyrin (TpyP) has been studied in aqueous buffer solution (phosphate buffer pH = 7 and I = 0.01 M) to give a structural and spectroscopic characterization of a new class of potential sensitizers for photodynamic therapy. The interaction was investigated by a combination of UV/Vis absorption, fluorescence anisotropy, time-resolved fluorescence and circular dichroism. The experimental results point to the presence of the pigment in water in a monomeric complexed form. The fluorescence anisotropy measurements suggest that TpyP forms 1:1 complexes with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, while 1:2 complexes are obtained with heptakis(2,6-di-O-methyl)-beta-cyclodextrin.     

Conformations and complexation abilities of chemically modified cyclodextrins in aqueous solution

Circular dichroism spectral and fluorescence decay methods have been employed to determine the conformations of mono[6-(p-tolylseleno)-6-deoxy]-β-CD(1), mono(6-anilino-6-deoxy) −β -CD (2) and mono[6-(L-tryptophan)-6-deoxy]−β -CD (3) in phosphate buffer solution (pH 7.2, 0.1 mol dm⁻³) at 298.15 K. The results indicate that compounds 2 and 3 formed self-inclusion complexes in aqueous buffer solution, while the substituent of compound 1 was not included into cyclodextrin cavity at all. Furthermore, the complex stability constant (logK _s) and Gibbs free en-ergy change (−ΔAG °) of these three cylcodextrin derivatives with several cycloalkanols have been determined by circular dichroism spectral titration in phosphate buffer solution at 298.15 K. It is found that the location of the substituent affects the stability of host-guest complex in aqueous solution.     

Diffusion properties of cyclodextrins in aqueous solution at 25°C

Diffusion, density, and viscosity data are collected for the systems -cyclodextrin and -cyclodextrin in water. Frictional coefficients were computed with the help of literature activity data and a qualitative discussion of their concentration dependence was attempted.     

Complexation of cyclodextrins with nicotinamide and N-(hydroxymethyl)nicotinamide in aqueous solution

Complex formation of α- and β-cyclodextrins with biologically active nicotinamide and Nhydroxymethylnicotinamide (nicodine) was studied by calorimetry and ¹H NMR spectroscopy. Cyclodextrins showed a weak complexing ability toward nicotinamide and nicodine: 1: 1 enthalpy-stabilized host-guest complexes were formed in aqueous solution at 298.15 K. Nicotinamide and nicodine molecules appeared inside the macrocycle cavity of cyclodextrins, but interaction between their polar side-chain groups with the outer surface of cyclodextrins cannot be ruled out. Thermodynamic parameters of the complexation process were calculated, and a mechanism was proposed for the observed interaction. The results were compared with those obtained previously for the complexation of cyclodextrins with nicotinic acid.     

Phase solubility analysis in studying the interaction of nifedipine with selected cyclodextrins in aqueous solution

The solubilizing potential and complexing tendencies of six cyclodextrins (CyD) with nifedipine in aqueous solution were evaluated using phase solubility methods. Solubility curves of nifedipine with -CyD, 2-hydroxypropyl--CyD (2HP--CyD) and 2-hydroxypropyl--cyclodextrin (2HP--CyD) were classified as type A_L, while for heptakis (2,6-dimethyl)--CyD (DIMEB), randomly methylated--CyD (RAMEB) and -CyD, A_p type phase behaviour was observed. Stability constants, calculated from phase solubility diagrams, decreased in the order: DIMEB > RAMEB > -CyD > 21HP--CyD > -CyD > 2HP--CyD.     

Volume change on complex formation between anions and cyclodextrins in aqueous solution

Partial molal volume changes during complex formation between SCN^–, I^–, and ClO₄ ^– -and -cyclodextrin have been determined by two independent methods of measurements; one based on density measurement and subsequent calculation of apparent molal volumes, the other on differentiating the association constants with respect to pressure. Results from the two methods are in good agreement.Negative volume changes were observed for complex formation between the anions and -cyclodextrin while zero or slightly positive values were observed for complex formation with -cyclodextrin. The result is consistent with the idea that the anions do not become dehydrated as they form complexes with cyclodextrins.     

Substrate binding to cyclodextrins in aqueous solution: A multicomponent self-diffusion study

It is demonstrated that substrate binding to α- and β-cyclodextrins (CD) in solution can conveniently and directly be monitored from multicomponent self-diffusion data on these solutions, using the Fourier Transform NMR pulsed-gradient spin-echo technique. Included are aromatics and a series of alcohols ranging from methanol to octanol. Experimentally it was found thatn-alcohols associate more strongly with α-CD than with β-CD. As the bulkiness of the alcohol increased, binding to β-CD was enhanced while the reverse effect was observed in the case of α-CD. For both cyclodextrins it was found thatn-alcohol complexation in the homologous series was attributable to an increment in standard free energy of complexation of ～ ?3.0 kJ/mol for each ?CH₂? group, suggesting that the binding mechanism is of a hydrophobic nature.     

Effect of cyclodextrins on the physicochemical properties of chlorophyll a in aqueous solution

The interactions between chlorophyll a and two beta-cyclodextrins, that have the same cavity size but different substituents, were studied in aqueous solutions. These supramolecular host-guest complexes were examined by a combination of UV/vis absorption, circular dichroism, NMR, and steady-state and time-resolved fluorescence measurements. The results indicate that all cyclodextrins solubilize the pigment mainly in monomeric form in water. The pigment forms 1:1 complexes with the heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin and 1:2 complexes with the hydroxypropyl-beta-cyclodextrin. In such complexes the methyl groups of the cyclodextrin inner cavity are involved in the interaction with the pigment as evidenced by NMR measurements. We also measured the luminescence of singlet oxygen photosensitized by chlorophyll a in the inclusion complexes.     

Complexation of cyclodextrins with flavines in aqueous solutions

Data on the binding mode and thermodynamics of complex formation for various cyclodextrins (CDs) with flavines are summarized. It is shown that the governing factors of complexation are the size, degree of hydration, and hydrophobicity of the guest molecule. It is found that the presence of small hydrophobic substituents in a flavine’s structure increases their affinity toward cyclodextrin cavities, raising the stability of a complex. In contrast, the presence of bulky and polar side groups in a flavine’s structure prevents its inclusion in a macrocyclic cavity and weakens complexation. The size of a CD cavity plays a minor role in the interaction between CDs and flavines, since the inclusion of a guest molecule is only partial.     

Complex formation of large-ring cyclodextrins with iodine in aqueous solution as revealed by isothermal titration calorimetry

Complex formation of large cyclodextrins(CDs) having DP 21–32 with iodine in aqueous KI solution was studied by isothermal titration calorimetry. The curves obtained for the titration of the CDs with iodine cannot be analyzed by a model based on a single set of identical sites, but, rather, by a model assuming 1 : 2 complex formation with identical interacting sites. For the two identical interacting sites, the binding constants K₁ and K₂ (K₁ < K₂), defined relative to the progress of saturation, lie in the range 0.7 to 7.3×10³ M^–1 and 3.0 to 62.6×10³ M^–1, respectively. The values of ΔH₂ and T ΔS₂ lie in the range –34.9 to –136.4 kJ·mol^–1 and –15.5 to –112.8 kJ·mol^–1, respectively. The largest values of –T ΔS₂ obtained for a CD of DP 26 can, in part, be attributed to a large decrease in conformational flexibility of the CD which occurs during complex formation.     

Interaction of heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin with cholesterol in aqueous solution

The interaction of cholesterol with heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin (TOM-beta-CyD) was investigated in water using solubility method. It was found that TOM-beta-CyD forms two kinds of soluble complexes, with molar ratios of 1:1 and 1:2 (cholesterol:TOM-beta-CyD). The thermodynamic parameters for 1:1 and 1:2 complex formation of cholesterol with TOM-beta-CyD were: DeltaG0(1:1)=-11.0 kJ/mol at 25 degrees C (K1:1=7.70 x 10 M(-1)); DeltaH0(1:1)=-1.28 kJ/mol; TDeltaS0(1:1)=9.48 kJ/mol; DeltaG0(1:2)=-27.8 kJ/mol at 25 degrees C (K1:2)=7.55 x 10(4) M(-1)); DeltaH0(1:2)=-0.57 kJ/mol; TDeltaS0(1:1)=27.3 kJ/mol. The formation of the 1:2 complex occurred much more easily than that of the 1:1 complex. The driving force for 1:1 and 1:2 complex formation was suggested to be exclusively hydrophobic interaction. Based on the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structures of the 1:2 complex were estimated. In addition, the interaction of TOM-beta-CyD with cholesterol was compared with that of heptakis (2,6-di-O-methyl)-beta-CyD (DOM-beta-CyD). The interaction of TOM-beta-CyD is more hydrophobic than that of DOM-beta-CyD, and the life time of the complexed TOM-beta-CyD is sufficiently long to give separated signals, at the NMR time scale, which differs from that of complexed DOM-beta-CyD.     

New insight into the discrimination between omeprazole enantiomers by cyclodextrins in aqueous solution

We report results regarding the use of ¹H-NMR spectroscopy in the study of the conformational behaviour and optical activity of omeprazole. Changes in the chemical shifts of chosen atoms reveal that the conformational behaviour of omeprazole is temperature and pH sensitive. Separation and identification of omeprazole enantiomers in the presence of natural and derivative cyclodextrins, such as β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) are achieved using ¹H-NMR spectroscopy, with information from molecular dynamics simulation. This work shows that βCD includes preferentially R-(–)-omeprazole, acting as a chiral selector. This discrimination of omeprazole enantiomers by cyclodextrins allows development of pharmaceutical formulations with a better bioavailability profile.     

Interactions of native and modified cyclodextrins with some B-vitamins

Interactions of native and modified α- and β-cyclodextrins with nicotinic acid, pyridoxine and pyridoxal were studied by isothermal titration calorimetry, solution calorimetry, and ¹H NMR spectroscopy at 298.15 K and pH 6.8. Weak 1:1 complex formation was found only between α-cyclodextrin and nicotinic acid. The stability constant and corresponding thermodynamic parameters of complex formation (Δ_c G, Δ_c H and Δ_c S) were calculated using the calorimetric data. The ¹H NMR data indicate the shallow insertion of the carboxylic group of the nicotinic acid molecule into α-CD cavity. For all other compounds the weak interactions, not accompanied by complex formation, were characterized by the enthalpic virial coefficients calculated on the basis of McMillan-Mayer approach. The obtained thermodynamic parameters were analyzed in the terms of influence of the solutes’ structure on the selectivity of intermolecular host-guest interactions.     

Study on the aggregation and electrochemical properties of Rose Bengal in aqueous solution of cyclodextrins

The interactions of Rose Bengal (RB) with alpha-cyclodextrin (alpha-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), heptakis(2,3,6-tri-O-methyll)-beta-cyclodextrin (TM-beta-CD) were studied in aqueous solutions of 0.1 M KClO(4) and 0.1 M LiClO(4) by vis absorption, fluorescence spectroscopy as well as electrochemical measurements at 298 K. The spectrophometric results indicate that RB is included in all beta- and gamma-CDs forming complexes with a stoichiometry 1:1 whose stability is slightly higher in KClO(4) than in LiClO(4) solutions. The complex stability constants determined for salt-containing CD solutions are lower than those for water solutions. The complexation of RB with beta- and gamma-CD and the differences between the complexes obtained in the presence of the two salts were confirmed by an electrochemical study.     

Inclusion complexes of spin-labeled indoles with cyclodextrins in aqueous solutions

Guest-host complexes of β- and γ-cyclodextrins (CDs) with two spin-labeled indole derivatives having the same molecular weights but different structures were studied by EPR spectroscopy in aqueous solutions and semiempirical quantum-chemical calculations of these systems were carried out. In the presence of CD the polarity of the NO group environment decreases and the rotational correlation time (τ) of guest molecules increases. Both indole derivatives form 1 : 1 complexes with γ-CD, the binding constants of the complexes being different more than twice. Simulation of EPR spectra made it possible to determine the indole ring orientation relative to the plane of the host molecule (at angles in the range 30–60°) and the rotational diffusion coefficients of the complexes, which corresponded to the hydrodynamic volume of one γ-CD molecule. In contrast to the complexes with γ-CD the rotational correlation times, τ, of the complexes with β-CD correspond to a hydrodynamic volume which much exceeds the volume of a single β-CD molecule. The complexes with β-CD are also characterized by more hydrophobic environment for guest molecules and absence of spin exchange with Ni²⁺ ions in the aqueous solution. There results are consistent with a dimeric structure of β-CD in the complex and with the orientation of the long axis of the guest molecule along the dimer axis. The energies and geometric parameters were calculated for all complexes by the PM3 method with a conventional set of parameters. The optimized energetically stable structures of the 1 : 1 complexes with γ-CD and of the 1 : 2 complexes with β-CD are consistent with experimental data. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1139–1147, May, 2005.