The thermodynamics of γ-cyclodextrin hydration was studied using methods of thermal analysis and solution calorimetry. The enthalpy and entropy changes are in a good agreement with two steps of γ‑cyclodextrin hydration isotherm and changes of unit cell volume. The first step of γ-cyclodextrin hydration is more exothermic and has more negative change of entropy while as the second step is less exothermic providing more disorder of water molecules in the hydrate crystal. The kinetic study of γ-cyclodextrin dehydration process revealed the activation energy of this process.

Protic ionic liquids have numerous promising applications as solvents and are more straightforward and less expensive to synthesize than aprotic ionic liquids. This study expands the scarce knowledge on the solvation properties of protic ionic liquids by considering three triethylammonium salts: acetate, trifluoroacetate, and triflate. Additionally, they were characterized by means of TG/DSC analysis and low-temperature DSC in order to determine the liquid range temperature. The limiting activity coefficients of alkanes, alkenes, aromatic hydrocarbons, cycloalkanes, cyclohexene, and thiophene at 298.15 K were measured in these liquids. A higher solubility of hydrocarbons in triethylammonium salts than in many aprotic and several studied protic ionic liquids was observed. The selectivity of triethylammonium triflate for n-hexane/benzene separation is higher than that of sulfolane and N-methyl-2-pyrrolidinone used in industrial extraction processes.

Inclusion compounds of diclofenac sodium, a non-steroidal anti-inflammatory drug, with native α-, β- and γ-cyclodextrins at varying levels of hydration were prepared by co-grinding in a ball mill. Using TG/DSC analysis, powder X-ray diffraction and solid-state IR spectroscopy, it was shown that when equimolar mixtures of native cyclodextrin and diclofenac are milled, complete inclusion of this pharmaceutical ingredient occurs, regardless of cyclodextrin hydration. The absence of water-guest competition in the solid-state inclusion process is explained by high affinity of diclofenac sodium to cyclodextrins. The prepared complexes have a significantly lower thermal stability than the separate native cyclodextrins and diclofenac sodium.

A new polymorph of anhydrous β-cyclodextrin (polymorph III) was obtained and characterized for the first time using powder X-ray diffraction, infrared spectroscopy, and thermal analysis. The solution enthalpy and time of dissolution in water were determined using solution calorimetry for this polymorph and compared with those of the dried commercial form of β-cyclodextrin (polymorph I), its amorphous form, and 2-hydroxypropyl-β-cyclodextrin. The specific heat capacities of polymorphs I and III were determined using differential scanning calorimetry across a wide range of temperatures, providing enthalpy and Gibbs energy values for the polymorphic transition at 298 K. The affinities of polymorph III and 2-hydroxypropyl-β-cyclodextrin for water were characterized by determining their hydration isotherms, which provided values of hydration Gibbs energy. Being energy-rich, the new-found polymorph of β-cyclodextrin has a significantly higher dissolution rate and an increased affinity for water compared with the dried commercial form of β-cyclodextrin. These properties render the new polymorph promising in industrial applications for guest inclusion in aqueous solutions and pastes, and may be a desirable alternative for water-soluble β-cyclodextrin derivatives.

In many industrial applications, preparation of cyclodextrin (CD) inclusion complexes with drugs, food additives, dyes and components of essence oils is performed in solid mixtures, slurries or paste-like systems having lack of water to dissolve cyclodextrin and guest completely. Such systems need a different description than supplied by classical analysis of CD complexation in aqueous solutions. The main feature of solid-state guest inclusion is the phase transition from solid CD to solid inclusion compound. This implies a complex interplay between a size exclusion effect for guest inclusion, a cooperative activation of this process by the third component such as water or organic compound and competition of guest and water for the space inside CD crystal lattice. The present review summarizes the current state of research of guest inclusion by native CDs in solid state and compares the driving forces of this process and its structure-property relationships with those of complexation in aqueous solutions. For an adequate comparison, the latter process was analyzed in thermodynamic activity scale, which allowed to separate hydrophobic effect and such important factors of complex stability as guest molecular shape and “high-energy” water.

Solid-state guest exchange is used as an efficient method to prepare very metastable polymorphs of indomethacin, including the polymorph observed earlier only in a mixture with a polymeric solvent and a new crystalline form of this drug with a negligibly small amount of the included solvent (guest). The used preparation procedure gives less stable inclusion compounds of indomethacin, which require a milder desolvation treatment than inclusion compounds formed in binary host-guest systems, so the metastable forms with a low first melting point can be prepared. For the characterization of indomethacin polymorphs, fast scanning calorimetry was used, along with conventional characterization methods. This method merges multistep polymorphic transitions, making the first melting point much more pronounced, so the different polymorphs become better discriminated.

Министерство науки и высшего образования Российской Федерации Российское химическое общество им.Д.И.Менделеева Секция по химической термодинамике и термохимии Научного совета РАН по физической химии Сибирское Отделение Российской Академии Наук Институт неорганической химии им.А.В.Николаева СО РАН

В работе изучено влияние размера макроцикла нативных циклодекстринов и их гидратации на инкапсуляцию ритонавира в условиях механического перемалывания. Разработан способ оценки степени включения ритонавира циклодекстринами, используя кристаллизацию несвязанного «гостя» в продуктах перемалывания при обработке парами воды. Установлено, что ритонавир практически полностью связывается безводными α-, β- и γ-циклодекстринами с образованием соединений включения. Для гидратов циклодекстринов соотношение структура-свойство для связывания ритонавира в зависимости от размера макроцикла «хозяина» является нелинейным. Ритонавир полностью связывается насыщенным гидратом β-циклодекстрина и промежуточными гидратом γ-циклодекстрина. Степень включения ритонавира насыщенными гидратами α-циклодекстрина и особенно γ-циклодекстрина невелика, что обусловлено конкуренцией этого гостя с водой.

The interaction of phosphorus-containing epoxy trifunctional monomer – triglycidyl phosphate (TGPhT), with europium (III) nitrate hexahydrate is studied. A dissolution of europium salt added into TGPhT is occurred due to the interaction of the cation with phosphoryl groups and oxygen atoms of the epoxy ring, that is accompanied by the opening reaction and led to the formation of a polymer. The interaction of triepoxide with salt is investigated by FTIR-spectroscopy and differential scanning calorimetry (DSC). The thermal stability of the samples is determined by combined method of thermogravimetry and differential scanning calorimetry (TG/DSC), coupled with a quadrupole mass spectrometry to identify the gaseous products evolved during the thermal analysis of the samples. The kinetic parameters of the curing reaction are computed by using Thermokinetics software. The interaction of TGPhT with europium nitrate is suggested to occur through opening of epoxy rings in the presence of europium ions via the mechanism of cationic polymerization. The cured epoxy polymer exhibits luminescent properties.

We study how the size of the macrocycle of native cyclodextrins and their hydration influence the inclusion of ritonavir under mechanical grinding conditions. A procedure is proposed to estimate the degree of inclusion of ritonavir by cyclodextrins using the crystallization of the unincluded guest in the grinding products at the water vapor treatment. Ritonavir is almost completely included by anhydrous α-, β-, and γ-cyclodextrins, resulting in the formation of inclusion compounds. The structure–property relationship between ritonavir inclusion in cyclodextrin hydrates and the size of the host macrocycle is nonlinear. Ritonavir is completely included by saturated β-cyclodextrin hydrate and intermediate γ-cyclodextrin hydrates. The degree of ritonavir inclusion by saturated hydrates of α-cyclodextrin and particularly of γ-cyclodextrin is small due to the competition of this guest with water.

The hydration was found to reduce an efficiency of drug encapsulation by native cyclodextrins (CDs) when water is added above a certain threshold level. The hydration water competes with indomethacin for solid-phase inclusion in gamma-cyclodextrin (gamma CD) and beta-cyclodextrin (beta CD) with an increase of water contents to the saturation level. No compe ting effect was observed for alpha-cyclodextrin (alpha CD) with this drug. The hydration effect for indomethacin correlates with the influence of hydration water on inclusion of volatile organic guests by native CDs. For these guests and gamma CD, the competing hydration effect was estimated also by determination of vapor sorption isotherms and was found higher than that for beta CD but in most cases lower than such effect for alpha CD. The inclusion affinity and capacity of dried gamma CD for water and organic guests were determined and a significant size exclusio n effect was observed, which contributes to the water-guest competition. The ratio between competing and activation roles of water for the studied three native cyclodextrins correlates with the parameters of their unit cells in hydrates and in dried state.

The solid-phase exchange of ethanol in γ-cyclodextrin inclusion compounds has afforded binding of volatile organic compounds not forming inclusion compounds with dry γ-cyclodextrin or its hydrates. The obtained results can be used in the development of efficient filters to remove aromatic compounds from air.

The first evidence of native cyclodextrins fusion was registered using fast scanning calorimetry (FSC) with heating rates up to 40,000 K s−1. The endothermal effects, detected at low heating rates, correspond to the decomposition processes. Upon the increase of the heating rate the onset of these effects shifts to higher temperatures, reaching a limiting value at high heating rates. The limiting temperatures were identified as the melting points of α-, β- and γ-cyclodextrins, as the decomposition processes are suppressed at high heating rates. For γ-cyclodextrin the fusion enthalpy was measured. The activation energies of thermal decomposition of cyclodextrins were determined by dependence of the observed thermal effects on heating rates from 4 K min−1 in conventional differential scanning calorimetry to 40,000 K s−1 in FSC. The lower thermal stability and activation energy of decomposition of β-cyclodextrin than for the other two cyclodextrins were found, which may be explained by preliminary phase transition and chemical reaction without mass loss. The obtained values of fusion parameters of cyclodextrins are needed in theoretical models widely used for prediction of solubility and solution rates and in preparation of cyclodextrin inclusion compounds involving heating.

The limited applications of α-cyclodextrin (αCD) require elaboration of effective preparation procedures for inclusion compounds of this native macrocyclic host. The solid-phase guest exchange in anhydrous inclusion compounds with organic guests was used in the present work to activate the inclusion properties of αCD without the presence of water. The initial inclusion compounds and the products of this exchange process were characterized using thermogravimetry combined with mass spectrometry of evolved vapors (TG/MS) and powder X-ray diffraction. Solid-phase guest exchange in inclusion compounds of αCD enables encapsulation of organic guests in the higher amounts than can be achieved with a saturated hydrate of α-cyclodextrin under the same conditions. The developed guest exchange procedure does not demand optimization of components ratio and preparation conditions. The solid-phase guest exchange in one of the studied ternary systems produces an amorphous inclusion compound, which heating gives a true amorphous αCD without any traces of its crystalline phase. This is a first evidence of α-cyclodextrin amorphization without its complete dissolution, that can be used in practical applications where an amorphous state of this host is needed having a higher inclusion capacity than its crystalline forms.

The formation and decomposition of inclusion compounds with a solid-solid phase transition may be very selective to the guest molecular structure. This selectivity may function in essentially different ways than defined by the classical concept of molecular recognition, which implies the preferential binding of complementary molecules. Solid inclusion compounds may take part as an initial or/and final state in several processes of different types summarized in this review, which selectivity is boosted by cooperativity of participating molecular crystals. Some of these processes resemble switching electronic devices and can be called smart giving practically absolute molecular recognition.

Hydration history was found to control the inclusion capacity of α-cyclodextrin (aCD) for volatile organic guests, so that its level may be switched from zero to the stoichiometric value and back by the variation of aCD hydration/dehydration order and direction. Such variation of the inclusion capacity is caused by the balance of two water roles: the activation of guest inclusion and guest/water competition. These observed concurrent roles and the cooperativity of guest inclusion and hydration make possible the smart tuning of the guest inclusion by the subtle change of preparation procedure. Depending on the hydration history, aCD was shown to form hydrates with the same water contents but different packing types and different kinetics of dehydration, which correlates with their different inclusion capacities for organic guests. This correlation reveals how the "high-energy" and "low-energy" water works in the guest inclusion by aCD, which may be relevant for other cyclodextrins and hydrophilic receptors of biomimetic and biological natures. The results can help to rationalize the technologies of producing various inclusion compounds of cyclodextrins.

The size exclusion of guests by α-cyclodextrin (aCD) in binary host-guest systems was observed to be a key structure-property relationship for the choice of this host as a receptor. For this, vapor sorption isotherms of water and volatile organic compounds were determined using dry aCD, which show an inclusion threshold by sorbate activity corresponding to a phase transition of guest (or water) inclusion. These phase transitions were also characterized using X-ray powder diffractograms. The analysis of these data shows that interaction of aCD with water does not differ much from that with organic compounds that can be included by aCD without water and therefore are water-mimicking as such. The inclusion and hydration Gibbs energies and composition of the saturated host-guest clathrates were determined from sorption isotherms. The Gibbs energies of guest inclusion by solid aCD and its hydration characterize the guest-host and water-host affinity in the solid state. The correlation of the obtained inclusion parameters with that of guest size indicate the ban on the inclusion of volatile hydrophilic organic compounds with more than three carbon atoms and smaller molecules without hydrophilic groups. These data may be used for estimation of the relative ability of more hydrophobic guests to replace water and organic solvents in solid aCD. The observed inclusion of water and small hydrophilic molecules by solid aCD with phase transition gives an alternative insight into the role of water in activating the inclusion of more hydrophobic guests. Furthermore, the results show the extent to which aCD may be preferable in applications using water or other solvents.