SANS investigation of water adsorption in tunable cyclodextrin-based polymeric hydrogels.

The focus of this work is on addressing how the adsorption properties of cyclodextrin (CD) based polymeric hydrogels (cyclodextrin nanosponges, CDNS) can be regulated by a precise control of a crucial parameter such as the characteristic pore size of the polymer network. With this aim, Small Angle Neutron Scattering (SANS) experiments are performed on different CDNS polymer formulations, differing by (i) the chemical structure of the cross-linking agent used for the polymerization of CD, which affects the flexibility of the strands between two crosslinking junctions, (ii) the relative molar ratio of cross-linker to monomer, affecting the cross-linking density, and (iii) the dimension of the CD macrocycle, regulating the steric hindrance and number of available reactive sites on the monomer. The analysis of the experimental data in terms of a two-correlation-length model allows one to extract a correlation length ζ that is interpreted as an experimental assessment of the average mesh-size of the cross-linked polymer, confirming the effective nano-size of the cavities formed in the network of CDNS. The hydration-dependence of ζ is modelled by an empirical functional form, that provides as key parameters the swelling rate of the polymeric network and the upper limit for the mesh size of the material. These parameters are useful for the characterization of the dynamic response of the hydrogel to swelling and the maximum mesh size compatible with the chemical structure of the polymer.

Guest-matrix interactions affect the solvation of cyclodextrin-based polymeric hydrogels: a UV Raman scattering study.

The focus of the present work is to shed light on possible modifications of the molecular properties of polysaccharide hydrogels induced by the establishment of specific non-covalent interactions during the loading of a guest compound inside the gel phase. With this aim, a case study of the encapsulation of caffeine (Caf) inside cyclodextrin-based hydrogels, namely, cyclodextrin nanosponges (NS), is systematically investigated here by using UV Raman scattering experiments. The UV Raman spectra of the hydrogels, analysed as a function of temperature, concentration of the guest molecule loaded in the gel phase and pH, prove particularly informative both on the structural rearrangements of the hydrophobic/hydrophilic groups of the polymeric network and on the breaking/formation of specific guest-matrix interactions. Analysis of the temperature dependence of dynamical parameters, i.e., the dephasing time associated with specific vibrational modes of the polymer backbone, enables the proposal of a molecular picture in which the loading of Caf in NS hydrogels tends to favour access of the water solvent to the more hydrophobic portions of the polymer matrix, which is in turn reflected in a marked increase in the solvation of the whole system. The achievements of this work appear of interest with respect to the design of new possible strategies for controlling the diffusion/release of bioactive molecules inside hydrogel networks, besides corroborating the potential of UV Raman scattering experiments to give new molecular insights into complex phenomena affecting hydrogel phases.

Vibrational signatures of the water behaviour upon confinement in nanoporous hydrogels.

The fundamental question of how the reorganization of the hydrogen-bond (HB) network of water is influenced by the combination of nano-confinement and hydrophobic/hydrophilic solvation effects is addressed here using a spectroscopic study of water absorbed in a model, pH-sensitive polysaccharide hydrogel. The effects of temperature, hydration level and pH on the vibrational dynamics associated with the water molecules and the polymer skeleton are disentangled and analysed by a complementary and combined use of UV-Raman scattering and IR spectroscopy. The experimental data give evidence that the solvation effects in the hydrogel matrix are essentially dominated by the hydration of more hydrophobic parts of the polymer network, while the effect of pH on the HB reorganization of confined water molecules is found to be similar to that induced by cooling of the system. A tentative explanation of these results has been provided in terms of interplay between different kinds of interactions, i.e. hydrophobic vs. hydrophilic.

Water and polymer dynamics in a model polysaccharide hydrogel: the role of hydrophobic/hydrophilic balance.

The molecular dynamics of water and a polymer matrix is here explored in a paradigmatic model of a polysaccharide hydrogel, by the combined use of UV Raman scattering and infrared measurements. The case example of cyclodextrin nanosponges (CDNS)/hydrogel is chosen since the simultaneous presence in the structure of the polymer matrix of both hydrophilic and hydrophobic sites mimics the complexity of polysaccharide hydrogels. In this way, the contributions provided by the balance between the hydrophilicity/hydrophobicity and the grade of entanglement of the polymer hydrogel to lead to the formation of the gel phase are separately accounted and evaluated. As main results, we found that the hydrophobic CH groups inserted on the aromatic ring of CDNS experience a more pronounced dynamic perturbation with respect to the carbonyl groups due to the collision between the solvent and vibrating atoms of the polymer. The overall results provide a detailed molecular picture of the swelling phenomena occurring when a chemically cross-linked polymer contacts with water or biological fluids and exploits the potentiality of UV Raman spectroscopy to retrieve dynamic information besides their structural counterpart obtained by the classical analysis of the basic features of vibrational spectra.

Combining Raman and infrared spectroscopy as a powerful tool for the structural elucidation of cyclodextrin-based polymeric hydrogels.

A detailed experimental and theoretical vibrational analysis of hydrogels of ß-cyclodextrin nanosponges (ß-CDNS), obtained by polymerization of ß-cyclodextrin (ß-CD) with the cross-linking agent ethylenediaminetetraacetic acid (EDTA), is reported here. Thorough structural characterization is achieved by exploiting the complementary selection rules of FTIR-ATR and Raman spectroscopies and by supporting the spectral assignments by DFT calculations of the spectral profiles. The combined analysis of the FTIR-ATR spectra of the polymers hydrated with H2O and D2O allowed us to isolate the HOH bending of water molecules not involved in symmetrical, tetrahedral environments. The analysis of the HOH bending mode was carried out as a function of temperature, showing the existence of a supercooled state of the water molecules. The highest level of cooperativity of the hydrogen bond scheme was reached at a value of the ß-CD/EDTA molar ratio n = 6. Finally, the connectivity pattern of "uncoupled" water molecules bound to the nanosponge backbone was found to be weakened by increasing T. The temperature above which the population of non-tetracoordinated water molecules becomes predominant turned out to be independent of the parameter n.

Probing the molecular connectivity of water confined in polymer hydrogels.

The molecular connectivity and the extent of hydrogen-bond patterns of water molecules confined in the polymer hydrogels, namely, cyclodextrin nanosponge hydrogels, are here investigated by using vibrational spectroscopy experiments. The proposed spectroscopic method exploits the combined analysis of the vibrational spectra of polymers hydrated with water and deuterated water, which allows us to separate and selectively investigate the temperature-evolution of the HOH bending mode of engaged water molecules and of the vibrational modes assigned to specific chemical groups of the polymer matrix involved in the physical interactions with water. As main results, we find a strong experimental evidence of a liquid-like behaviour of water molecules confined in the nano-cavities of hydrogel and we observe a characteristic destructuring effect on the hydrogen-bonds network of confined water induced by thermal motion. More interestingly, the extent of this temperature-disruptive effect is found to be selectively triggered by the cross-linking degree of the hydrogel matrix. These results give a more clear picture of the molecular mechanism of water confinement in the pores of nanosponge hydrogel and open the possibility to exploit the spectroscopic method here proposed as investigating tools for water-retaining soft materials.

UV-vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-beta-cyclodextrin inclusion complex.

In this work, the usefulness of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) as a tool to form an inclusion complex with 9-fluorenonic derivative (AG11) has been investigated, in pure water, by UV absorption. Phase-solubility diagrams allowed the determination of the association constant between AG11 and HP-beta-CyD. At the same time, solid binary systems between AG11 and HP-beta-CyD have been prepared in 1:1 stoichiometry by co-precipitation method. In order to confirm the complexation, FTIR spectroscopy in ATR geometry measurements have been performed and the results have been compared with the free compounds and the corresponding physical mixture in the same molar ratio. The nature of the interactions between AG11 and HP-beta-CyD has been elucidated also by applying mathematical procedures such as deconvolution and curve fitting. Improvement of the aqueous solubility is expected to improve the bioavailability of the drug in oral administration.

UV-vis and FTIR-ATR spectroscopic techniques to study the inclusion complexes of genistein with beta-cyclodextrins.

The effect of beta-cyclodextrin (beta-CyD), (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) and methyl-beta-cyclodextrin (Me-beta-CyD) complexation on the UV absorption of genistein (Gen) was studied in pure water. A phase solubility study was performed, according to the method reported by Higuchi and Connors, to evaluate the changes of isoflavone in the complexation state and the obtained diagrams suggested that it forms complexes with a stoichiometry of 1:1. Then, the solid complexes of genistein with these macrocycles in 1:1 molar ratio were prepared by the co-precipitation method and characterized by FTIR absorption spectroscopy in ATR geometry. The host-guest interactions have been evidenced by monitoring, in the FTIR-ATR spectra, the changes in some guest molecule bands relative to those observed in the spectra of the 1:1 physical mixtures and complexes. In particular, for the high-frequency O-H stretching band, a quantitative vibrational assignment of the observed sub-bands has been made. From the results, the inclusion phenomena have been discussed.

Elastic neutron scattering study of water dynamics in ion-exchanged type-A zeolites.

With the aim to investigate, by means of elastic neutron scattering, the effects produced by the cation substitution on the dynamics of water in zeolites, we measured, using a neutron backscattering spectrometer, the temperature dependence of mean-square atomic displacements [u2] derived from window integrated quasielastic spectra of fully and partially hydrated Na-A and Mg50-A zeolites. The results, collected in the 20-273 K temperature range, reveal that, at low temperature, the [u2] shows a harmonic trend independent of hydration and cation substitution, and, at higher temperatures, the onset of a non-Gaussian dynamics of the elastic intensity. This latter takes place at T approximately 200 K and approximately 150 K for fully and partially hydrated samples, respectively. This behavior has been interpreted in terms of reorientational jumps of H atoms described by two-site processes within an asymmetric double-minimum potential. In spite of its simplicity, the model seems to reproduce the rearrangement of the hydrogen bond network of zeolitic water. The fit results indicate a reduced proton mobility by diminishing the water content and by the induced Na+-->Mg2+ ion exchange, in agreement with previous incoherent quasielastic neutron scattering results at higher temperatures.

A FT-IR absorption analysis of vibrational properties of water encaged in NaA zeolites: evidence of a "structure maker" role of zeolitic surface.

We performed, in the O-H stretching region, Fourier-transform Infrared (FT-IR) Absorption measurements for investigating the vibrational dynamics on water confined in NaA zeolite, vs. temperature and for different hydration percentages. The spectral substructure of the O-H stretching band is explained postulating the existence of three major components centred at approximately 3290 cm(-1) (omega(1)), approximately 3470 cm(-1) (omega(2)), approximately 3590 cm(-1) (omega(3)), with different dynamical properties traced over the full T-range investigated.

FT-IR spectroscopy: a powerful tool in pharmacology.

In the present work we report a Fourier Transform Infrared (FT-IR) analysis performed on rat encephalon samples in the CH-OH vibrational stretching region (2400-3800) cm(-1), in order to reveal the presence of a very diffuse commercial benzodiazepine: VALIUM. The comparison between the spectral features of normal brain and the ones of samples with administrated substance has unambiguously showed that the CH stretching region seems not to suffer from any change for the pharmacological treatment, instead the OH band is strongly modified probably due to the presence of a new spectral contribution characteristic of diazepam molecule.

Physico-chemical characterization of an amphiphilic cyclodextrin/genistein complex.

Specific recognition of cell-targeting systems as host-carriers modified with receptor targeting groups, is a major ambition in the application of supramolecular science to medicine and life science. Genistein (Gen), an isoflavone belonging to the class of phytoestrogens, is of great interest because it has been considered as potential remedy for many kinds of disease. In this work, genistein in aqueous medium and in the presence of an host nanocarrier as amphiphilic cyclodextrin (CyD) modified in the upper rim with oligoethylene hydroxyl groups [(2-oligo(ethyleneoxide)-6-hexylthio)-beta-CyD, SC6OH] at 1:1 molar ratio, has been firstly investigated by UV-vis measurements coupled with circular dichroism data, in order to characterize the drug/macrocycle binding affinity through the formation of the complex. Furthermore, FTIR-ATR technique has been used to detect the complex formation in solid phase and to characterize the functional groups responsible of the solid Gen/SC6OH complex stability. The infrared absorbance spectra of the complex, collected in a wide range of wavenumber and around the physiological temperature, have been analysed and compared with the spectra of the pure compounds and their physical mixture. By monitoring the most significant changes in the shape and position of the absorbance bands of the Gen functional groups, we showed that the formation and/or modification of polar bonds play the main role in the interaction of the drug with the amphiphilic CyD. From the results, Gen is shown to be entangled in SC6OH nanoaggregates, establishing hydrogen bonding with the hydrophilic PEG chains.