I. N. Topchieva

Novel Derivatives of Cyclodextrins, Modified with Poly(ethylene Oxide) and Their Complexation Properties

A new family of bouquet-like molecules based on cyclodextrins is described. These compounds were obtained by polymerization of ethylene oxide. This reaction was initiated by primary and secondary hydroxyl groups of cyclodextrins, which constitute an organizing core. Analysis of structure and composition of conjugates based on alpha-CD and beta-CD was performed using the data of MALDI-MS, GC-MS, and 13C-NMR spectra. Glass transition behavior of the conjugates shows that the above compounds are amorphous. Complexation properties of the conjugates are described with respect to sodium 4-nitrophenolate and calcium acetylhomotaurinate, which are used as guest molecules. Binding interaction between cyclodextrins or their conjugates and sodium 4-nitrophenolate was studied using differential absorption spectra. Association constants Ka between CD hosts and calcium acetylhomotaurinate composed of two equal anionic moieties were studied using 1H-NMR spectroscopy. The values of binding constant for beta-CD were found to increase by more than 2 orders of magnitude than that of the corresponding system based on alpha-CD. alpha-CD was shown to form the inclusion complex with one anionic moiety, whereas beta-CD produces a ternary complex with two anionic moieties of CAHT. For PEO derivatives of CDs, Ka decreases as compared with that of parent CD for both guests. These conjugates may be used as potent drug-delivery systems.

Stability of α-chymotrypsin conjugated with poly (ethylene glycols) and proxanols at high temperature and in watercosolvent mixtures

α-Chymotrypsin has been modified with poly(ethylene glycols) and proxanols, block-copolymers of poly(propylene oxide) and poly(ethylene oxide). These conjugates were several-fold more thermostable and showed high catalytic activity at elevated concentrations of water-miscible organic cosolvents (alcohols and dimethyl sulfoxide) which caused inactivation of free (non-modified) α-chymotrypsin.

Noncovalent columnar structures based on β-cyclodextrin

A new method for the synthesis of associates of cyclodextrins (CDs) of the columnar type consisting of the precipitation of CDs from aqueous solutions into acetone at lowered temperatures is developed. It is shown that columnar structures exist in both a crystalline state and in aqueous solutions. Hydrodynamic radii and molecular masses of noncovalent columnar structures (NCSs) in aqueous solutions are determined by the dynamic and static light scattering methods. The degree of association of noncovalent columnar polymers is ∼40. It is revealed the NCS associates based on β-CD are stable and their hydrodynamic radius Rh is equal to 100 ± 10 nm. The kinetics of interactions of initial β-CD and NCS with poly(propylene oxide) (PPO) is studied. The pattern of kinetic curves of Rh growth upon interaction between NCS and PPO indicates that the aggregation of the particles of polymer inclusion complex proceeds in the regime of reaction-limited cluster-cluster aggregation. Kinetic curves describing the interaction processes between β-cyclodextrin and PPO are characterized by the presence of induction period t0. At t > t0, Rh ∞ t0.56 which is typical for the diffusion-limited cluster-cluster aggregation. Schemes of the formation of polymer inclusion complexes between initial β-CD or NCS and poly(propylene oxide) are proposed. Comparison of kinetic data on the complexation of β-CD in solution in the form of associates of two types with PPO demonstrates that columnar forms of associates are reactive species acting as macroreceptors.

The detection of cyclodextrin self- association by titration with dyes

A simple procedure is proposed for the detection of association of cyclodextrins (CDs) and their derivatives in aqueous solutions by analyzing the curves of titration of these substances with dyes. Dissociation constants of cyclodextrin-dye complexes and concentrations of sites involved in the complexation are determined by the nonlinear regression analysis. The processes of CD association were characterized using deviations of the function of CD saturation with ligands from a simple scheme CD + ligand ⇆ complex. Two association mechanisms were disclosed: cooperative association (for α-CD and dihydroxypropyl-β-CD) and step association (for β-CD, dimethyl-β-CD, hydroxypropyl-β-CD, and γ-CD). In the case of stepwise-associating compounds, association constants for head groups of cyclodextrins are found to vary from 3 × 103 to 8 × 103 M−1. The titration data on CD association are confirmed by studying solutions of the above compounds using dynamic light scattering.

Non-covalent columnar cyclodextrin-based structures

Examples of the formation of ordered ensembles of α-, β-, and γ-cyclodextrins (CDs) molecules with a columnar packing of macrocycles are reported. These ensembles are formed by (1) the supramolecular dissociation of polymer inclusion complexes under the action of organic solvents that are selective with respect to a polymer guest and (2) the fixation of columnar CD aggregates self-organized in aqueous solutions at high temperatures upon the precipitation from water into organic solvents. Specific features of the organization of cyclodextrins in the thus-synthesized structures are studied by X-ray diffraction. Preliminarily oriented polymer inclusion complexes based on corresponding CDs are used as a model with the columnar arrangement of macrocycles.

Aggregation of Inclusion Complexes Formed by Noncovalent Columnar Structures Based on α- and γ-Cyclodextrins and Poly(alkylene glycols)

Kinetic analysis of the aggregation of complexes formed by columnar types of α- and γ-cyclodextrins (α-CDcol and γ-CDcol) and poly(alkylene glycols) is performed by the dynamic light scattering method. For comparison, analogous studies were conducted for systems containing initial α- and γ-cyclodextrins (α-CD and γ-CD). Upon the aggregation of systems containing α-CD, the number of nuclei with critical sizes slowly increases at the initial part of kinetic curve throughout the solution bulk; when some limiting concentration and sizes of formed aggregates are achieved, the system is transformed into the gel-like state. The aggregation of γ-CDcol-poly(ethylene glycol) system proceeds into two stages. At the first fast stage, aggregates are formed by particles representing single-strand inclusion complexes composed of one γ-CDcol molecule and two units of ethylene oxide. At the second, much slower stage, aggregates are formed by two-strand complexes composed of one γ-CDcol molecule and four units of ethylene oxide. It follows from the comparison of aggregative properties of γ-CDcol-poly(ethylene glycol) and γ-CDcol-poly(propylene glycol) systems that the rate of aggregation is much higher in the second case.

On the Possibility of Chemical Modification of Polyethylene Glycol in Melt

SummaryThe reactions between polyethylene glycol of molecular weights 1000–15000 and benzoyl bromide, acetic anhydride and dinitrofluorobenzene in melt have been studied. The advantage of chemical modification in melt, in comparison with that in solution, has been shown.

Supramolecular Dissociation of Polymeric Inclusion Complexes Containing Cyclodextrins as a Method of Preparing New Columnar Structures

Polymeric inclusion complexes formed from cyclodextrins (CDs) and linear polymers are molecular necklaces (MNs), structures in which dozens of CD molecules are tightly thread onto a polymer chain [1]. These systems clearly exemplify the significance of the geometric match between the size of the CD cavity and the cross section of the polymer. For example, α -CD forms complexes with poly(ethylene oxide) (PEO) but not with poly(propylene oxide) (PPO); β -CD forms complexes with PPO but not with PEO; and γ -CD interacts either with one PPO molecule or with two PEO molecules [2]. In crystals of MNs, CD molecules are arranged in channels, forming a columnar structure. The question arises as to whether this structure will survive after removal of the thread polymer. Similar structures are of interest as new crystalline CD modifications with a common extended channel and, hence, exhibiting new properties. The resolution of the problem calls for a method of removing the polymer from the MN cavity that would leave the type of crystal lattice unaltered. In this paper, we describe a new property of MNs, namely, their ability to dissociate under the action of an organic solvent, selective to the thread polymer but inert to the macrocycle, to produce a new ordered CD form, a columnar CD structure (CD column ). The synthesis of complexes and their properties are described elsewhere [3‐5]. Previously, we studied the formation, composition, and structure of MNs based on α -, β - , and γ -CDs. These MNs are precipitated on mixing water solutions of a CD and a poly(alkylene oxide) (PAO) complementary in size to the CD. The complexes contain one macrocyclic molecule per two monomeric units of PAO (except the γ -CD‐PEO, which contains a double amount of the polymer). As a third component, MNs also include water, which is involved in the formation of intermolecular hydrogen bonds between hydroxyls of neighboring CD molecules. Therefore, we obtained the complexes α - CD‐PEO, γ -CD‐PEO, and β -CD‐PPO, composed of macrocycles threaded on polymer chains and characterized by a lack of covalent bonds between cyclic and thread molecules. To selectively extract the polymers from MNs, we used both polar (acetone, THF) and nonpolar (chloroform, carbon tetrachloride, benzene, tert -butylbenzene, Tetralin) organic solvents inert to CDs. A solvent was added to a MN powder, stirred for several hours, and then the organic phase was separated. For all three types of complexes, the corresponding polymer was identified in the solution within several hours. The polymer content of the β -CD‐PPO-3500 complexes was quantitatively assessed by IR spectroscopy [6].

Receptor properties of nanoporous structures based on β-cyclodextrin

A columnar modification of β-cyclodextrin (β-CDcol) has been synthesized using self-assembly and self-organization processes. It is shown that the obtained macrocycle assemblies in the solid state are highly ordered structures with through cylindrical pores with an average diameter of ∼0.7 nm and a length of about 60 nm. These structures can be of interest as a new type of macroreceptors for the inclusion of molecules with diameters not exceeding 0.7 nm belonging to various chemical classes. The abilities of the common cage structure of β-CD and the β-CDcol modification to bind low-molecular-weight volatile organic compounds have been compared. The dependence of the composition, structure, and thermal stability of the inclusion complexes on the ligand nature and geometry is analyzed. The absence of any specificity in the adsorption of ligands on β-CDcol and the possibility of using this structure as a stable nanocontainter for the storage of volatile compounds is demonstrated.

Iron-containing nanoparticles based on the 2-hydroxypropyl-β-cyclodextrin in aqueous solutions

The water-soluble hybrid nanoparticles based on high-substituted 2-hydroxypropyl-β-cyclodextrin were formed in situ during the reduction of iron(+2) salts by hypophosphite ion in alkaline medium. These nanoparticles are high sensitive to temperature and ultrasonication. It was established that the temperature and ultrasonication time of exposure increase leads to the successive dissociation of the nanoparticles.