Journal of inclusion phenomena

Inclusion complexation between β-cyclodextrin (β-CD),hydroxypropyl-β-cyclodextrin (HP-β-CD), water-solublepolymers (PVP and HPMC) and vinpocetine was studied in aqueous solution and in the solid state.Phase solubility studies were used to evaluate the complexation in aqueous solution at roomtemperature. Stability constants (Kc) of binary and ternary complexes were determined spectrophotometrically. Differential scanning calorimetry (DSC)was used to characterize kneaded, co-evaporated and lyophilised binary and ternary systems.The Kc values obtained were 70.14 M-1 and 35.01 M-1 for vinpocetine-β-CD and vinpocetine-HP-β-CD and increased in a range of 17% to 94%by addition of water-soluble polymers. Some preliminary evidences ofinclusion complexation were obtained from DSC suggesting that co-evaporated and lyophilised binary andternary systems were truly inclusion complexes.

Cyclodextrin (CD) complex stoichiometry and complexation constant with two symmetric curcuminoids and two unsymmetric curcuminoid-like compounds were investigated and compared by two independent methods, the phase-solubility method and ultraviolet-visible absorption spectroscopy (UV–Vis) titration. Two different methods were applied in an effort to increase the apparent intrinsic solubility of the compounds and make the investigation of stoichiometry and complexation constants possible. The intrinsic solubility could be determined for all four compounds in aqueous 10% (v/v) ethanolic solutions. Higher order complexation or solubilization through complex aggregation was observed for the symmetric molecules, while 1:1 complexation was observed for the unsymmetric molecules in the phase-solubility diagram. The UV–Vis investigation showed 1:1 complexation for all compounds, with some indication of higher order complexation for the symmetric molecules. Thus the stoichiometry found with the two methods correlated well for the unsymmetric, but not for the symmetric compounds where the phase-solubility investigations clearly indicated higher order complexation and possible aggregation of complexes. There was also a difference between the 1:1 complexation constants found with the two methods, especially for the compounds with low intrinsic solubility (i.e. the symmetric curcuminoids). However, they agree in the ranking of complexes according to the strength of the association. The 1:2 complexation constant observed with the phase-solubility method was more than 100 times the complexation constant found with the UV–Vis method, which explains why solubility is poorly predicted from the UV–Vis data. This discrepancy may be explained by solubilization by aggregation of complexes or some phenomena other than inclusion complexation.

Two novel alkali cation sandwich complexes have been constructed by reaction of potassium and cesium picrate with double-armed benzo-15-crown-5 ether 1. Crystals of the K+Pic−2(B15C5) and Cs+Pic−2(B15C5) complexes (Mr = 1339.81, 2865.23) are all yellow prisms which belong to the orthorhombic space group Pna2(1) with a = 25.757(5), b = 12.927(3), c = 37.507(8) Å and a = 25.905(7), b = 12.998(3), c = 39.036(10) Å, Z = 8 and 8 respectively. The every K and Cs cation are 11 and 12-coordinate involving ten crown oxygens [K–O, 2.742(3)–3.031(3) Å, Cs–O, 3.029(9)–3.271(7) Å], one crown carbon for K (K–C, 3.533(5) or 3.496(5)), two crown carbons for Cs (Cs–C, 3.658(10), 3.682(10) or 3.665(13), 3.705(14)). Metal cation had no interaction with picrate. Intermolecular C–H–O hydrogen bonds and π–π face-to-face stacking interactions help to consolidate the crystal packing.  

By formylation of calix[4]-1,3-aza-crown in hexamethylenetetramine/trifluoroacetic acid system, the first formylated calix[4]-aza-crown derivative 6 was synthesized in yield of 61%. Reacting compound 6 with salicyloyl hydrazine, 2,4-dinitrophenyl hydrazine, nicotinyl hydrazine or phenyl thiosemicarbazide afforded four novel calix[4]crown hydrazone derivatives 7a–d in yields of 70–90%. By condensating compound 6 with series of bifunctional reagents, the novel mono-bridged biscalix[4]-aza-crown hydrazone derivatives 8a–c were prepared in high yields. The extraction experiments showed that all new compounds were good receptors for metal cations, especially, for soft metal cations. The extraction results suggested that the hydrazone groups produced favorable influences for binding soft cations. The two calix[4]arene units in compounds 8a–c could bind metal cations concurrently.

We have studied the effect of the substituent nature on nitration of 4′-R-dibenzo-18-crown-6 (DB18C6, where R is NO2, CH3CO, or C2H5) in polyphosphoric acid (PPA). We also studied the influence of cations' nature on regioselectivity of nitration. It was found that electron withdrawing substituents direct the incoming NO2-group mainly to the 4″-position of the unsubstituted benzene ring in the reactions with lithium nitrates. If there are two substituents: electron releasing and electron withdrawing in one benzene ring, then the orientation effect of the latest one is stronger. The obtained results once more confirmed the existence of ‘transannular transmission’, which we first of all observed during the acetylation of DB18C6. Based on these observations preparative methods leading to 4′,4″-dinitro-DB18C6, 4′,5″-dinitro-DB18C6, 4′-acetyl-4″-nitro-DB18C6, 4′-acetyl-5″-nitro-DB18C6, 4′-ethyl-5′,5″-dinitro-DB18C6, and 4′-ethyl-5′,4″-dinitro-DB18C6 have been developed.

In this contribution, we analyze indomethacin–cyclodextrin (IMC–CD) inclusion by means of UV–Vis spectrophotometry and isothermal titration calorimetry (ITC) at 25 °C. Experiments were carried out in water at pH 5 and 7, using β-CD and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The study with UV–Vis was made using a molar relation method analyzing the spectra with Stability Quotients from Absorbance Data (SQUAD) to obtain the inclusion constants. In the case of ITC, the study was performed in aqueous-phosphate buffer at pH 7. The values of ΔG, ΔH, − TΔS were determined for the first time for the inclusion of IMC within β-CD and 2-HP-β-CD. Results for logK1:1 obtained by ITC agree reasonably with those determined by UV–Vis, confirming the formation of a complex of stoichiometric ratio IMC:CD of 1:1. Besides the confirmation of formation of the inclusion complex, inclusion is exothermic, and given the sign of entropy it is suggested that IMC inclusion is driven by release of water molecules from the cavity of CD. With the values of logK1:1 we construct the diagrams of species distribution to compare which CD performs better in including IMC.

In order to investigate the contribution of the hydrophilic parts of guest molecules of aliphatic compounds to the inclusion reaction, the thermodynamic properties of inclusion compounds of cyclodextrin (α-CD) with eight pentane derivatives into the cavity of α-CD in dilute aqueous solutions were measured by micro-calorimeter at 298.15 K. The thermodynamic properties of the inclusion reactions of pentane derivatives into α-CD were compared to the hydrophobicity and polarizability of guest molecules and discussed. The interaction energies of inclusion compounds of α-CD and pentane derivatives were determined by DFT calculation (B3LYP/6-31G (d,p)) in water and compared with the experimental results.

A survey of the literature reveals that the spectroscopic displacement method, in which phenolphthalein is used as a competitive chromophore to determine binding constants of β-cyclodextrin with surfactants was successful in the case of homologous hydrocarbon and fluorocarbon anionic surfactants. We show here that this method can be applied also for homologous alkyltrimethylammonium bromides (with alkyl varying from octyl- to hexadecyl) under the condition that the concentration of the cationic surfactant is distinctly lower than the value of itscritical micelle concentration.

This paper addresses the general question: what are the significant guest properties selected by this host when interacting with guest molecules in the liquid phase, resulting in cocrystallization of the host and guest? In particular, to what extent do π electrons in a guest molecule effect its potential as a guest? Werner clathrates of the host [Ni(NCS)2(4-ViPy)4] with mixtures of tetrahydrofuran (THF) and cyclic hydrocarbons as guests have been synthesised and their structures elucidated. Clathrate (1): [Ni(NCS)2(4-ViPy)4](1.78 THF)(0.22 cyclohexane), crystallizes in the orthorhombic space groupP bcn a=9.976(6),b=20.630(25),c=19.861 (4) Å,V=4087Å3,Z=4,R=0.087 for 1461 reflections; (2): [Ni(NCS)2(4-ViPy)4](1.76 THF)(0.24 cyclohexene),P bcn ,a=9.987(7),b=20.614(4),c=19.898(4)Å,V=4096Å3,Z=4,R=0.084 for 1304 reflections; (3): [Ni(NCS)2(4-ViPy)4](0.48 THF)(0.52 1,3-cyclohexadiene), tetragonalI41/a,a=16.898(3),b=16.898(3),c=26.463(6)Å,V=7556Å3,Z=8,R=0.120 for 1698 reflections; (4): [Ni(NCS)2(4-ViPy)4](0.36 THF)(1.04 1,4-cyclohexadiene),I41/a,a=16.986(4),b=16.986(4),c=25.896(15)Å,V=7472Å3,Z=8,R=0.103 for 2025 reflections; (5): [Ni(NCS)2(4-ViPy)4](0.35 THF)(1.05 benzene),I41/a,a=17.102(10),b=17.102(10),c=25.498(8)Å,V=7458Å3,Z=8,R=0.118 for 2200 reflections; (6): [Ni(NCS)2(4-ViPy)4](3 benzene), triclinicP1,a=10.432(24),b=11.155(9),c=21.581(7)Å, α=78.70(5), β=82.60(7), γ=74.09(13)°,V=2361Å3,Z=2,R=0.078 for 3427 reflections. Host-guest ratios and, for mixtures of guests, guest1/guest2 ratios, were elucidated by density and NMR. We show that the conformational freedom of the substituted pyridines is not the primary reason for the clathrating ability of Werner hosts. All six structures show no host-guest interaction at the level of van der Waals interactions. As non-bonding interactions are not observed between the host and guest, this study shows that the above host's selectivity by enclathration of particular guest molecules cannot be accounted for by solid state structural analysis.