Proving Nanoscale Chiral Interactions of Cyclodextrins and Propranolol Enantiomers by Means of SERS Measurements Performed on a Solid Plasmonic Substrate

Chiral separation is an important issue for the pharmaceutical industry. Over the years, several separation methods have been developed, mainly based on chromatography. Their working principle is based on the formation of transient diastereoisomers, but the very subtle nanoscale interactions responsible for separation are not always understood. Recently, Raman and surface-enhanced Raman (SERS) spectroscopy have provided promising results in this field. Here we present Raman/SERS experimental data that provide useful information concerning the nanoscale interactions between propranolol enantiomers and α, β, and γ cyclodextrins. Raman spectroscopy was used to prove the formation of host–guest intermolecular complexes having different geometries of interaction. The occurrence of new vibrational bands and a change in the intensities of others are direct proofs of complexes’ formation. These observations were confirmed by DFT calculations. By performing SERS measurements on a new type of plasmonic substrate, we were able to prove the intermolecular interactions responsible for PRNL discrimination. It turned out that the interaction strength between the substrate and the intermolecular complexes is of paramount importance for SERS-based chiral discrimination. This approach could represent a very good starting point for the evaluation of molecular interactions manifesting between other pharmaceutical compounds and different classes of chiral selectors.

Saturation Transfer Difference in Characterization of Glycosaminoglycan-Protein Interactions

Novel methods in nuclear magnetic resonance (NMR) spectroscopy have recently been developed to investigate the binding properties of intermolecular complexes endowed with biomedical functions. Among these methods is the saturation transfer difference (STD), which enables the mapping of specific binding motifs of functional ligands. STD can efficiently uncover the specific and preferential binding sites of these ligands in their intermolecular complexes. This is particularly useful in the case of glycosaminoglycans (GAGs), a group of sulfated polysaccharides that play pivotal roles in various biological and pathological processes. The activity of GAGs is ultimately mediated through molecular interactions with key functional proteins, namely, GAG-binding proteins (GBPs). The quality of the GAG-GBP interactions depends on sulfation patterns, oligosaccharide length, and the composing monosaccharides of GAGs. Through STD NMR, information about the atoms of the GAG ligands involved in the complexes is provided. Here we highlight the latest achievements of the literature using STD NMR on GAG oligosaccharide-GBP complexes. Interestingly, most of the GBPs studied so far by STD NMR belong to one of the three major classes: coagulation factors, growth factors, or chemokine/cytokines. Unveiling the structural requirements of GAG ligands in bindings with their protein partners is a crucial step to understand the biochemical and medical actions of GAGs. This process is also a requirement in GAG-based drug discovery and development.

Probing radical–molecule interactions with a second generation energy decomposition analysis of DFT calculations using absolutely localized molecular orbitals

Proper treatment of intermolecular complexes formed by radicals and closed-shell molecules in energy decomposition analysis of DFT calculations.

MECHANOCHEMICAL MODIFICATION OF TRIKLABENDAZOL TO OBTAIN AN EFFECTIVE DRUG AGAINST FACTIOLESIS

To study the possibility of increasing the solubility of the substance triclabendazole (TCB), we used the technology of mechanochemical modification of TCB using water-soluble polymers, polyvinylpyrrolidone (PVP) and arabinogalactan (AG) from Siberian larch Larix sibirica in particular. After joint machining of TCB with polymers (PVP, AG) in a LE-101 ball mill (made in Hungary), free flowing powder dispersions with an increased solubility (more than 50 times as compared to the original substance TCB) were obtained. This result was explained by the formation of intermolecular complexes of the type of hydrogen bond between the characteristic groups of TCB and polymers, which was confirmed by the data of IR-spectral studies. Tests of intermolecular complexes on spontaneously fasciola-infected sheep have shown high efficiency. As a result of the research, it was found that the complex of TCB: AG composition (1:9), which we named “triclafascid”, possesses a number of positive attributes in comparison with the substance of TCB and provides high fasciolocid and economic efficacy, and safety of use by reducing the therapeutic dose. Inclusion of arabinogalactan, which has hepatoprotective, antimutagenic, mitogenic, gastroprotective properties, in the preparation, made it possible to reduce the toxicity of the preparation proposed for practice. It was shown that residual amounts of TCB and its metabolites were not detected in tissues and organs on the 14th day of the experiment with triclafascid, which indicates the possibility of slaughtering an animal and using meat 14 days after using the drug. The drug has good solubility, bioavailability to helminthes, is non-toxic, and increases antihelminthic and economic efficiency. The obtained results confirmed the previously obtained data on the prospects of an innovative approach to improve the quality indicators of anthelmintic drugs and to obtain effective drugs for veterinary medicine.

Resolving the halogen vs. hydrogen bonding dichotomy in solutions: intermolecular complexes of trihalomethanes with halide and pseudohalide anions

Simultaneous (multivariable) treatments of UV-vis and NMR data yielded formation constants of halogen- and hydrogen-bonded complexes coexisting in solutions.