Pluronic P123/DMSO Lyotropic Liquid Crystal for Incorporating Bioactive Substances for Topical Application.

Lyotropic liquid crystals (LLCs) have attracted considerably growing interest in drug delivery applications over the last years. The structure of LLC matrices is complementary to cell membranes and provides an efficient, controlled, and selective release of drugs. In this work, a complex of experimental methods was used to characterize binary LLCs Pluronic P123/DMSO and triple LLC systems Pluronic P123/DMSO/Ibuprofen, which are interesting as transdermal drug delivery systems. Liquid crystalline, thermal, and rheological properties of LLCs were studied. Concentration and temperature areas of the lyomesophase existence were found, and phase transition enthalpies were evaluated. Intermolecular interactions among the components were studied by infrared (IR) spectroscopy. In vitro studies of Ibuprofen (Ibu) release from various LLCs allow differentiation of its release depending on the polymer content. Atomic force microscopy and contact angle methods were used to characterize the surface morphology of the hydrophobic membrane, which was used as a stratum corneum model, and also evaluate the adhesion work of the LLCs. A complex analysis of the results provided by these experimental methods allowed revealing correlations between the phase behavior and rheological characteristics of the LLCs and release kinetics of ibuprofen. The proposed biocompatible systems have considerable potential for a transdermal delivery of bioactive substances.

Determination of Melting Parameters of Cyclodextrins Using Fast Scanning Calorimetry.

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-, ß- 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 ß-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.

2D Monomolecular Nanosheets Based on Thiacalixarene Derivatives: Synthesis, Solid State Self-Assembly and Crystal Polymorphism.

Synthetic organic 2D materials are attracting careful attention of researchers due to their excellent functionality in various applications, including storage batteries, catalysis, thermoelectricity, advanced electronics, superconductors, optoelectronics, etc. In this work, thiacalix[4]arene derivatives functionalized by geranyl fragments at the lower rim in cone and 1,3-alternate conformations, that are capable of controlled self-assembly in a 2D nanostructures were synthesized. X-ray diffraction analysis showed the formation of 2D monomolecular-layer nanosheets from synthesized thiacalix[4]arenes, the distance between which depends on the stereoisomer used. It was established by DSC, FSC, and PXRD methods that the obtained macrocycles are capable of forming different crystalline polymorphs, moreover dimethyl sulphoxide (DMSO) is contributing to the formation of a more stable polymorph for cone stereoisomer. The obtained crystalline 2D materials based on synthesized thiacalix[4]arenes can find application in material science and medicine for the development of modern pharmaceuticals and new generation materials.

Thermally induced cyclization of L -isoleucyl-L -alanine in solid state: Effect of dipeptide structure on reaction temperature and self-assembly.

Thermal treatment of short-chain oligopeptides is able to initiate the process of their self-assembly with the formation of organic nanostructures with unique properties. On the other hand, heating can lead to a chemical reaction with the formation of new substances with specific properties and ability to form structures with different morphology. Therefore, in order to have a desired process, researcher needs to find its temperature range. In the present work, cyclization of L -isoleucyl-L -alanine dipeptide in the solid state upon heating was studied. Kinetic parameters of this reaction were estimated within the approaches of the nonisothermal kinetics. The correlation between side chain structure of dipeptides and temperature of their cyclization in the solid state was found for the first time. This correlation may be used to predict the temperature, at which dipeptide self-assembly changes to chemical reaction. The differences in self-assembly of linear and cyclic dipeptides were demonstrated using atomic force microscopy. The effect of dipeptide concentration in a source solution and an organic solvent used on self-assembly of dipeptides was shown. The new information obtained on the thermal properties and self-assembly of linear and cyclic forms of L -isoleucyl-L -alanine may be useful for the design of new nanomaterials based on oligopeptides, as well as for the synthesis of cyclic oligopeptides.

Role of water in the formation of unusual organogels with cyclo(leucyl-leucyl).

The key role of water in the formation of cyclo(leucyl-leucyl) organogels was demonstrated. The conditions required for preparation of previously unknown gels with aliphatic hydrocarbons at room temperature were determined. Cyclo(leucyl-leucyl) self-assembles to form different structures depending on the medium used. The molecular organization of gels was studied by the methods of microscopy, spectroscopy and X-ray powder diffractometry. The organogel of cyclo(leucyl-leucyl) can reversibly change volume during the heating/cooling cycle. We showed the possibility of practical application of cyclo(leucyl-leucyl) for water purification. The results obtained give a new insight into the mechanism of gelation with cyclo(dipeptide)-based low-molecular-weight gelators and may be useful for the preparation of new physical gels.

Smart control of guest inclusion by α-cyclodextrin using its hydration history.

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.

Smart Molecular Recognition: From Key-to-Lock Principle to Memory-Based Selectivity.

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.

Size exclusion effect in binary inclusion compounds of α-cyclodextrin.

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.

On the Solvation Behavior of Graphene Oxide in Ethylene Glycol/Water Mixtures.

The self-association and solvation pattern of graphene oxide (GO) in water, ethylene glycol (EG), and their mixtures were analyzed by means of UV/Vis spectrophotometry. A careful analysis of the absorbance dependencies vs. the GO concentration shows that self-association of the GO sheets in EG occurs at higher concentration compared to that in water. It was established that depending on the mixed solvent composition, two different types of the GO solvates are formed. The results of quantum chemical calculations allow one to suggest that in the water-rich compositions, the GO oxygen-containing groups are in direct contact with water molecules while in the glycol-rich media the EG molecules fully substitute water in the GO's first solvation layer.

Thermally Induced Self-Assembly and Cyclization of l-Leucyl-l-Leucine in Solid State.

Thermal treatment of oligopeptides is one of the methods for synthesis of organic nanostructures. However, heating may lead not only to self-assembly of the initial molecules, but also to chemical reactions resulting in the formation of new unexpected nanostructures or change in the properties of the existing ones. In the present work, the reaction of cyclization of dipeptide l-leucyl-l-leucine in solid state under heating was studied. The change in morphology of dipeptide thin film and formation of nanostructures after heating was visualized using atomic force microscopy. This method also was used for demonstration of differences in self-assembly of linear and cyclic dipeptides. The chemical structure of reaction product was characterized by NMR spectrometry, FTIR spectroscopy and GC-MS analysis. Kinetic parameters of cyclization were estimated within the approaches of the nonisothermal kinetics ("model-free" kinetics and linear regression methods for detection of topochemical equation). The results of present work are useful for explanation the changes in the properties of nanostructures based on short-chain oligopeptides, notably leucyl-leucine, after thermal treatment, as well as for the synthesis of cyclic oligopeptides.

Non-zeolitic properties of the dipeptide l-leucyl-l-leucine as a result of the specific nanostructure formation.

The non-zeolitic behavior of l-leucyl-l-leucine and its self-organization in solid state and from solutions with the formation of different nanostructures are reported. This dipeptide forms porous crystals, but does not exhibit molecular sieve effects typical of classical zeolites and biozeolites. The specific sorption properties of l-leucyl-l-leucine result from a change in its crystal packing from channel-type to layered-type, when binding strong proton acceptors or proton donors of molecular size greater than 18-20 cm3 mol-1. The high sorption capacity of l-leucyl-l-leucine toward dichloromethane results from the self-organization of the dipeptide, by forming nanofibers or web-like structures. The low thermal stability of clathrates of the dipeptide containing large guest molecules and the selectivity of l-leucyl-l-leucine toward alcohols over nitriles can be used to separate organic mixtures such as methanol/n-butanol and methanol/acetonitrile.

Thermodynamics of dissolution and infrared-spectroscopy of solid dispersions of phenacetin.

In this work enthalpies of dissolution in water of polyethylene glycols (PEGs) having an average molecular weight of 1000 and 1400, Pluronic-F127, phenacetin as well as the composites prepared from them were measured using solution calorimetry at 298.15 K. Intermolecular interaction energies of polymer-phenacetin were calculated on the basis of an additive scheme. It was shown that for mixtures with high content of polymer (>90 wt%) Pluronic-F127 has the highest solubilizing effect, while for mixtures with (4-6):1 polymer: phenacetin ratio the best solubilizing agent is PEG-1400. Infrared-spectra showed a decrease of the number of self-associated molecules of phenacetin with increasing of polymer content in the composites. The obtained results enabled us to identify the features of intermolecular interactions of polymers with a model hydrophobic drug and may be used for optimizing the conditions for preparing solid dispersions based on hydrophilic polymers.

Interaction of L-alanyl-L-valine and L-valyl-L-alanine with organic vapors: thermal stability of clathrates, sorption capacity and the change in the morphology of dipeptide films.

The strong effect of the amino acid sequence in L-alanyl-L-valine and L-valyl-L-alanine on their sorption properties toward organic compounds and water, and the thermal stability of the inclusion compounds of these dipeptides have been found. Generally, L-valyl-L-alanine has a greater sorption capacity for the studied compounds, but the thermal stability of the L-alanyl-L-valine clathrates is higher. Unusual selectivity of L-valyl-L-alanine for vapors of few chloroalkanes was observed. The correlation between the change in the surface morphology of thin film of dipeptides and stoichiometry of their clathrates with organic compounds was found. This discovery may be used to predict the influence of vapors on the morphology of films of short-chain oligopeptides.

Unusually high efficiency of ß-cyclodextrin clathrate preparation by water-free solid-phase guest exchange.

An effective preparation procedure is offered for ß-cyclodextrin (bCD) clathrates with volatile guests of moderate hydrophilicity, which otherwise require a finely tuned optimization of the bCD/water/guest ratio. The proposed procedure includes guest exchange in a water-free bCD matrix. As a result, more stable clathrates with a higher inclusion capacity can be prepared than by direct saturation of dried or hydrated bCD. To find an optimal preparation method, the structure-property relationships were studied for four different ways of bCD clathrate formation with guests of varying molecular structure. The study was much simplified by used procedures excluding direct contact of guest and water liquids with bCD. Besides, in clathrate preparation experiments, the thermodynamic activities of water and guest were varied independently, which makes explicit the role of water in this process. Hydration of bCD reduces its inclusion threshold for hydrophobic guests by their activity (relative vapor pressure), giving favorable hydration effect for their inclusion. Besides, water competes with hydrophilic guests for binding sites in bCD at high water activities. Together with bCD dehydration by excess of hydrophilic guests, these observations give a complete thermodynamic picture, which may be fruitful for elaboration of guest encapsulation techniques by cyclodextrins.

Analysis of guest binary mixtures by tert-butylcalix[6]arene using host memory of previously bound guests.

A new principle of quantitative and qualitative analysis of binary organic mixtures is offered, which is based on an ability of calixarene receptor for specific polymorphic transitions related to the composition of the analyzed guest mixture. The ability of tert-butylcalix[6]arene to remember selectively some guests bound from headspace both of pure liquids and their binary mixtures is used. The image of guest mixture remains written in metastable polymorphs of host after partial or complete guest elimination from clathrates. The memory was read using differential scanning calorimetry as the enthalpy of exothermic polymorphic transition of host collapse. This enthalpy monotonously changes with the variation of guests' ratio in mixture, unlike the enthalpies of endothermic pseudopolymorphic transitions of guest release. So, the composition of volatile binary mixture can be estimated using only one receptor and only one its parameter even in absence of preferential binding from a binary mixture of guests. This is an example of a genuine molecular recognition.

Unusually high selectivity of guest exchange in tert-butylthiacalix[4]arene clathrate producing more thermostable inclusion and memory of guest.

New properties, earlier unknown for calixarenes, were found for tert-butylthiacalix[4]arene (1) clathrate with 1,2-dichloroethane (DCE). Guest exchange in 1·1.90DCE for vapors of some organic compounds gives clathrates, which are more thermostable at 34-59 °C than those prepared by direct saturation of guest-free 1 with pure guests. Besides, guest exchange may produce clathrates that cannot be formed by direct saturation in binary host-guest systems. Some compounds, like water, toluene, and trichloroethylene, expel DCE from its clathrate with 1 but are not included above the trace level. Residual contents of DCE in clathrate may be controlled by variation of water and 1·1.90DCE ratio in the studied system. Host 1 can remember methanol after its elimination from the guest exchange product. This memory can be read as an exoeffect by differential scanning calorimetry. Only methanol and only after guest exchange is remembered giving an example of a genuine molecular recognition.

Interaction of L-leucyl-L-leucyl-L-leucine thin film with water and organic vapors: receptor properties and related morphology.

The ability of highly ordered tripeptide structures to keep or change their morphology in contact with organic vapors was studied. A thin film of tripeptide L-leucyl-L-leucyl-L-leucine (LLL) was prepared having microcrystals and nanocrystals on its surface, which are stable upon vacuum drying but become objects of selective morphology change after a contact with vapors of organic solvents. Fine separate LLL crystals and their agglomerates of submicron and larger dimensions were observed by atomic force microscopy and scanning electron microscopy. After saturation with guest vapors, these crystals can remain intact or change their morphology with the increase in size or complete destruction depending on the guest molecular structure. The crystals completely lose their shape after the binding of pyridine vapors. The other studied guests produce much smaller transformations or have no effect on crystal morphology despite being sorbed by solid LLL, which was shown using quartz crystal microbalance sensor. The observed size-exclusion effect for guest sorption by LLL was found to be broken by the same guests that can change the initial crystal shape. This helps to explain the morphology changes of LLL crystals after the guest sorption and release.

Specific vapor sorption properties of phosphorus-containing dendrimers.

Specific combination of guest sorption properties was observed for phosphorus-containing dendrimers, which distinguish them from ordinary polymers and clathrate-forming hosts. The sorption capacity for 30 volatile guests, binding reversibility, guest desorption kinetics and guest exchange, glass transition behavior and ability to be plasticized with guest were studied for phosphorus dendrimers of different generations (G(1)-G(4) and G(9)) using quartz crystal microbalance sensor, FTIR microspectroscopy, atomic force microscopy, simultaneous thermogravimetry and differential scanning calorimetry combined with mass-spectrometry of evolved vapors. The dendrimers were found to have a different selectivity for different homological series of guests, high glass transition points without plasticization with guest even at high temperatures and saturation levels, moderate guest-binding irreversibility and ability both for effective guest exchange and independent guest sorption. These properties constitute an advantage of the studied dendrimers as receptor materials in various applications.

Metastable tert-butylcalix[6]arene with unusually large tunable free volume for non-threshold enclathration of volatiles.

A metastable material with tunable free volume of molecular size, vapor sorption properties of a porous sorbent and variable thermal stability was prepared from tert-butylcalix[6]arene.

Molecular recognition of organic vapors by adamantylcalix[4]arene in QCM sensor using partial binding reversibility.

The parameters of stability, guest binding reversibility, and Gibbs energy of guest inclusion were determined for clathrates of adamantylcalix[4]arene (1). These data provide a new insight into the structure-property relationships in vapor sensor applications of clathrate-forming hosts. A thin layer of 1, used in the quartz microbalance (QCM) sensor, demonstrates a selectivity for organic vapors, which depends on the regeneration technique after the guest binding. Complete regeneration of 1 on the sensor surface was reached through the exchange of bound guest with ethanol vapor, which forms an unstable clathrate with 1. The efficiency of the used regeneration technique was proved by comparing the QCM data with the isotherms of guest vapor sorption by guest-free host 1 and with the data of simultaneous thermogravimetry and differential scanning calorimetry for the saturated clathrates of 1. In sensor, the extent of host regeneration without guest exchange depends on the guest molecular structure. This extent, or guest-binding reversibility parameter, being determined in a combination with the sensor responses of completely regenerated 1 to guest vapors, increases the recognition capability of single sensor device. Using this technique, 13 of 15 studied guests were discriminated. The structural hints on the suitable sensor properties of 1 were found in the determined X-ray monocrystal data for clathrate of this host with toluene.