Ternary Inclusion Complexes Research Articles

Physicochemical investigation of the effects of water-soluble polymers on vinpocetine complexation with beta-cyclodextrin and its sulfobutyl ether derivative in solution and solid state.

The studies reported in this work aimed to elucidate the inclusion complex formation of vinpocetine (VP), a poorly water-soluble base type drug, with beta-cyclodextrin (betaCD) and its sulfobutyl ether derivative (sulfobutyl ether beta-cyclodextrin (SBEbetaCD)), with or without water-soluble polymers (PVP and HPMC), by thoroughly investigating their interactions in solution and solid state. Phase solubility studies were carried out to evaluate the solubilizing power of both cyclodextrins (CDs), in association with water-soluble polymers, towards VP and to determine the apparent stability constants (Kc) of the complexes. SBEbetaCD showed higher solubilizing efficacy toward VP than the parent betaCD due to its greater solubility and complexing abilities, what was reflected in higher Kc values. Improvement in Kc values for ternary complexes clearly proves the benefit on the addition of water-soluble polymers to promote higher complexation efficiency. VP-CDs (1:1) binary and ternary systems were prepared by physical mixing, kneading, co-evaporation, and lyophilization methods. In the solid state, drug-carrier interactions were studied by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier-transform infrared spectroscopy. The results of these analysis suggested the formation of new solid phases, some of them in amorphous state, allowing to the conclusion of strong evidences of binary and ternary inclusion complex formation between VP, CD and water-soluble polymers, particularly for co-evaporated and lyophilized binary and ternary products.

Evidence of Ternary Inclusion Complexes Formation Using Factorial Design and Determination of Their Formation Constant

Evidence of the interaction among the [PbAc]+ and[PbEDTA]-2 with the β-cyclodextrin (β-CD)is shown, using a 24 factorial design. The factors used werethe [Pb(II)], [β-CD], [Ac-] and [EDTA] concentrationsat pH = 6.2. The statistical results indicate that the changes inchemical response for these species are associated to theinteraction among these factors. Spectrophotometric andelectrochemical studies were undertaken to assess the interactions.The equilibrium constants for inclusion complexes were determinedFor β-CD-[PbAc]+ and β-CD-[PbEDTA]-2.

Effect of small organic molecules on room temperature phosphorescence properties of naphthol ternary inclusion complexes in β-cyclodextrin

The influence of nine small organic molecules on the phosphorescence properties of β-cyclodextrin (β-CD)/1-naphthol/1,2-dibromoethane (DBE) and β-CD/2-naphthol/DBE ternary inclusion complexes are examined by means of room temperature phosphorescence (RTP) measurements. It was demonstrated that the rigidity of β-CD/naphthol inclusion complex, RTP intensity and lifetime could be enhanced when different small organic molecules (less than 1% v/v) were added respectively; the analytical characters of two kinds of naphthols in host–guest stabilized-RTP were improved. The linear range of 1-naphthol become broad in the presence of n-propanol, methanol, ethanol or 2-propanol and its detection limit was reduced from 4×10 −6 to 7.5×10 −8 mol l −1 in the presence of 0.6% (v/v) methanol. Likewise, for 2-naphthol, the detection limit was reduced from 2.0×10 −6 to 2.8×10 −7 mol l −1 and to 8.1×10 −7 mol l −1 after 0.5% (v/v) glycol and 0.2% (v/v) 2-propanol being added, respectively.

Inclusion Complexes of Cyclodextrins with Methylene Blue and α-Naphthol Orange and Temperature Dependence of the Inclusion Complexation in Aqueous Solutions

Abstract Methylene Blue (MB) has been found to form a complex with α-Naphthol Orange (αNO) in aqueous solution. From a simulation concerning the fluorescence quenching of MB by αNO, an equilibrium constant for the formation of the 1 : 1 MB–αNO complex has been estimated to be 79900 mol-1 dm3. Upon the addition of γ-CD to MB solution containing αNO, the absorption of the MB monomer band is enhanced in intensity without an appearance of the MB dimer band, indicating the formation of a ternary γ-CD–MB–αNO inclusion complex. To determine a stoichiometry of the ternary inclusion complex, a continuous variation method using the fluorescence intensities has been performed under the condition that the sum of the initial concentrations of γ-CD and αNO has been kept constant. The result of the continuous variation method indicates the formation of a 2 : 1 : 1 γ-CD–MB–αNO inclusion complex. The equilibrium constant for the formation of the γ-CD–MB–αNO inclusion complex from γ-CD and the 1 : 1 MB–αNO complex has been evaluated to be 1.86 × 109 mol-2 dm6 from a simulation concerning the absorbance change. From the temperature dependence of the equilibrium constants, ΔH and ΔS values have been evaluated for the γ-CD–MB–αNO and γ-CD–MB–Acid Orange 7 systems. The ΔH and ΔS values for the formation of the γ-CD–MB–αNO inclusion complex have been positive in sign, in contrast to those for the formation of the MB–αNO and γ-CD–αNO complexes.

The Molecular Structure and Crystal Organization Of Rac -terfenadine/β-cyclodextrin/tartaric Acid Multicomponent Inclusion Complex

The crystalline ternary inclusion complex terfenadine/ g -cyclodextrin/tartaric acid (TFN/ g CD/TA, 2:4:1) has been prepared from a aqueous solution (terfenadine, TFN, rac - f -[4-(1,1-dimethylethyl)phenyl]-4-(hydroxy-diphenylmethyl)-1-piperidine-butanol). The solubility of the multicomponent system in water is remarkably different from that of the single components. The crystal structure shows that the TFN guest adopts an extended conformation and that the diphenyl end of the molecule is docked in the cavity formed by the association of two independent g CD molecules through hydrogen bonds connecting their wide rims. The structure of the dimer is deformed with respect to uncomplexed g CDs, due to the shape of the guest. The two aromatic rings interact differently with the macrocycles forming the dimer, one being included perpendicular in the central cavity of one g CD, the other laying parallel to the interface between the two rims. The t-Bu- end of the guest is included in the cavity of a g CD belonging to a different dimer, entering from the side of the narrow rim. The central part of the guest is surrounded by water molecules and tartaric acid, which creates a hydrophilic microenvironment in the interstices among dimers. The enhanced solubility of the multicomponent system could be related to the hydrogen bonds between the tartaric acid and the oxygens belonging to the wide rims. The overall structural arrangement of the g CD units is driven by the shape of the TFN guest which needs a hydrophobic environment at both ends. The lipophilic interactions between TFN and g CD cavities are responsible for the relevant perturbation in the regularity of the packing of the hosts.

Inclusion Complexes of Cyclodextrins with Methylene Blue and Acid Orange 7 in Aqueous Solutions

Abstract Upon the addition of Acid Orange 7 (AO7) to aqueous Methylene Blue (MB) solution buffered at pH 5.0, the absorption spectrum of MB is reduced in intensity, accompanied by a red shift of the absorption peak, indicating the formation of a complex between MB and AO7. From a simulation concerning the fluorescence intensity change of MB, the equilibrium constant for the formation of the 1 : 1 MB-AO7 complex has been estimated to be 66300 mol-1 dm3. γ-Cyclodextrin (γ-CD) forms a 1 : 2 and a 1 : 1 inclusion complex with MB and AO7, respectively. From the absorbance changes, equilibrium constants for the formation of the 1 : 2 γ-CD-MB and 1 : 1 γ-CD-AO7 inclusion complexes have been evaluated to be 2.95×107 mol-2 dm6 and 11000±300 mol-1 dm3, respectively. When γ-CD is added to MB solution containing AO7, the absorption band of MB is enhanced in intensity without an appearance of the MB dimer band, in contrast to MB solution without AO7. This finding indicates the formation of a ternary γ-CD-MB-AO7 inclusion complex. To determine the stoichiometry of the ternary inclusion complex, a continuous variation method using the absorption and fluorescence intensities has been performed under the conditions that the sum of the initial concentrations of γ-CD and AO7 has been kept constant. Both the results indicate the formation of a 2 : 1 : 1 γ-CD-MB-AO7 inclusion complex. The equilibrium constant for the formation of the ternary inclusion complex from γ-CD and the 1 : 1 MB-AO7 inclusion complex has been evaluated to be 3.40×1010 mol-2 dm6 from the fluorescence intensity change.

Electrochemical study of the cyclodextrin encapsulation of a macrocyclic nickel complex

The influence of cyclodextrin complexation on the electrochemistry of a macrocyclic Ni(II) complex has been studied. Both β-CD and γ-CD form 1:1 inclusion complexes with the Ni(II) complex. The interaction of the Ni(II) complex with γ-CD is stronger than with β-CD. The formation constant values show that the reduced form of the nickel complex (Ni(I)) is bound more strongly into the cavity of β-CD and γ-CD when compared to the oxidized form (Ni(II)). The Ni(II) complex experiences a less polar microenvironment which results in a positive shift in the peak potential. When the size and hydrophobicity of the supporting electrolyte molecules (NaClO 4, TMA +, TEA + and TBA +) are increased, the interaction between the CD and Ni(II) complex decreases due to the inclusion of the supporting electrolyte molecule into the cavity of γ-CD. The formation constants calculated in the presence of different supporting electrolytes decrease with the increase in the size of the supporting electrolyte. Inclusion of both the supporting electrolyte and the Ni(II) complex into the cavity of γ-CD (ternary inclusion complex) is observed. β-CD forms a weak complex with Ni(II) when NaClO 4 is used as supporting electrolyte and the complexation was not observed when TBA + is used as supporting electrolyte. The inclusion of a butyl chain of the TBA + molecule into the cavity of β-CD hinders the entry of the Ni(II) complex into the cavity of β-CD.

Study of bimolecular processes in ternary cyclodextrin complexes in the solid state by diffuse reflectance laser flash photolysis

The photochemistry of binary inclusion complexes of nitroveratrole (NV) and p-dinitrobenzene (DNB) with β-cyclodextrin (β-CD) and of ternary inclusion complexes of NV or DNB and L-phenylethylamine (PhEA) with β-CD has been examined in the solid state by diffuse reflectance laser flash photolysis. The binary NV/β-CD complex shows a transient absorption signal assigned to the triplet excited state of NV. The binary DNB/β-CD complex shows a transient signal assigned to the protonated anion of DNB formed via hydrogen abstraction from the β-CD cavity. Laser excitation of the ternary complexes generates the corresponding radical ion pairs via photoinduced electron transfer from the amine to the nitroaromatic triplet state. Comparison with previously described conventional laser flash photolysis studies in solution shows that the investigation of solid ternary CD inclusion complexes by diffuse reflectance laser flash photolysis is valuable in the case of bimolecular photoreactions that are difficult to study in solution due to the existence of other competitive processes.

Study of room-temperature phosphorescence of 1-bromonaphthalene in sodium dodecylbenzene sulfonate and β-cyclodextrin solution

Intense room-temperature phosphorescence (RTP) of 1-bromo-naphthalene (1-BrN) was studied in aerated aqueous solutions containing sodium dodecylbenzene sulfonate (SDBS) and β-cyclodextrin (β-CD). It has been found that considerably enhanced RTP arises from the formation of the 1:1:1/SDBS:1-BrN:β-CD ternary inclusion complex in premicellar solutions. The spectral and structural analyses of molecules indicate that the phenyl ring of SDBS is included in the apolar cavity of β-CD and the polar head group and a part of hydrocarbon chain located outside the cavity. Surface tension of the solutions demonstrates that the presence of micelles results in serious phosphorescence quenching.

Inclusion of azulene and alcohol by .beta.-cyclodextrin in aqueous solution.

β-Cyclodextrin (β-CD) has been found to form a ternary inclusion complex with alcohol and azulene, with a stoichiometry of 2:2:1. By means of a fluorescence method, equilibrium constants for the formation of the ternary inclusion complex have been evaluated for alcohols from ethanol to 1-pentanol. Induced circular dichroism studies suggest that in the ternary inclusion complex azulene slightly extrudes from the β-CD cavity compared with a 1:1 inclusion complex between β-CD and azulene

Molecular motions and the structure of?-cyclodextrin inclusion complexes with ferrocene, [3]-ferrocenophane-1,3-dione and ruthenocene

Spin-lattice relaxation time measurements in laboratory and rotating frames as well as proton second moment analysis have been used to investigate molecular motions in β-cyclodextrin (CD) and its solid inclusion complexes with the title organometallic compounds. Different dynamical processes have been identified in the host lattice along with high mobility of the ferrocene and ruthenocene guest molecules. The Arrhenius parameters of all motions were obtained. The assumption based on the second moment measurements was made about the axial structure of the ferrocene complex and the equatorial one of the ruthenocene complex at low temperatures. The bridged ferrocenophane molecule was shown to be rigid on the NMR time scale. The ternary inclusion complex of β-CD with ruthenocene and iodine was also studied and no evidence of redox reactions was observed.