Structural, Thermal, and Storage Stability of Rapana Thomasiana Hemocyanin in the Presence of Cholinium-Amino Acid-Based Ionic Liquids.

Novel biocompatible compounds that stabilize proteins in solution are in demand for biomedical and/or biotechnological applications. Here, we evaluated the effect of six ionic liquids, containing mono- or dicholinium [Chol]1or2 cation and anions of charged amino acids such as lysine [Lys], arginine [Arg], aspartic acid [Asp], or glutamic acid [Glu], on the structure, thermal, and storage stability of the Rapana thomasiana hemocyanin (RtH). RtH is a protein with huge biomedicinal potential due to its therapeutic, drug carrier, and adjuvant properties. Overall, the ionic liquids (ILs) induce changes in the secondary structure of RtH. However, the structure near the Cu-active site seems unaltered and the oxygen-binding capacity of the protein is preserved. The ILs showed weak antibacterial activity when tested against three Gram-negative and three Gram-positive bacterial strains. On the contrary, [Chol][Arg] and [Chol][Lys] exhibited high anti-biofilm activity against E. coli 25213 and S. aureus 29213 strains. In addition, the two ILs were able to protect RtH from chemical and microbiological degradation. Maintained or enhanced thermal stability of RtH was observed in the presence of all ILs tested, except for RtH-[Chol]2[Glu].

Enhancement of ibuprofen solubility and skin permeation by conjugation with l-valine alkyl esters.

New ibuprofen derivatives were made via conjugation with l-valine alkyl esters (ValOR), where R was changed from an ethyl to a hexyl group. The ionic structure was confirmed using NMR and FTIR. Specific rotation, solubility in commonly used solvents, thermal properties including phase transitions temperatures, and thermal stability were also determined. The ionic structure with a protonated amine group on an l-valine ester and melting points below 100 °C allowed inclusion of these ibuprofen derivatives into the pharmaceutically active protic ionic liquids. The ibuprofen salt solubility in deionised water and two buffer solutions at pH 5.4 and 7.4 were established and compared with the parent acid solubility. The octanol/water (buffer) partition coefficient, permeation through porcine skin, and accumulation in the skin were also measured. Ibuprofen pairing with l-valine alkyl esters [ValOR][IBU], caused higher solubility and a greater drug molecule absorption through biological membranes. log P was lower for ibuprofen salts than for the acid and it increased with a longer l-valine ester cation alkyl chain. In vitro porcine skin tests showed that ibuprofen salts with a propyl or isopropyl ester in l-valine are particularly relevant for topical application. They provide transport for ibuprofen through the skin at much higher rate than the unmodified acid and a higher permeated ibuprofen concentration, which can improve efficacy. Thus, synthesised ibuprofen derivatives could be used as drug carriers in transdermal systems to provide better drug bioavailability, and they can be also be the source of exogenous l-valine.

The effect of alcohols as vehicles on the percutaneous absorption and skin retention of ibuprofen modified with l-valine alkyl esters.

The effect of various alcohols as vehicles on skin permeability was compared for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with l-valine alkyl esters [ValOR][IBU], in which the alkyl chain R was changed from C1 to C8. In vitro permeation experiments were conducted in a Franz cell with porcine skin. Methanol, ethanol, and isopropanol solutions of 70% (v/v) were chosen as vehicles for penetrants and a buffer solution of pH 5.4 or 7.4 as the acceptor phase. The comparisons of permeation profiles for various [ValOR][IBU] from different alcohols were determined. The cumulative mass, skin accumulation, steady-state flux, diffusion coefficient, and lag time were investigated and compared. It was observed that i-propanol was the best enhancer of skin permeation of both unmodified ibuprofen and its salts with l-valine alkyl esters for both acceptor phases. The permeability of the various carriers increases with increasing chain-length of the alcohol. In most cases, significantly higher cumulative mass was found in the acceptor buffer of pH 7.4. The conjugate of ibuprofen with l-valine propyl ester [ValOPr][IBU] permeated the skin to the highest degree in comparison to unmodified ibuprofen. The accumulation of ibuprofen was higher for all salts in relation to the parent acid applied onto the skin. The greatest amounts of ibuprofen were accumulated in the skin when ibuprofen was used as the ionic pair with l-valine butyl ester, [ValOBu][IBU] in the i-propanol solution and pH 7.4 buffer as the acceptor phase.

Ketoprofen-Based Ionic Liquids: Synthesis and Interactions with Bovine Serum Albumin.

The development of ionic liquids based on active pharmaceutical ingredients (API-ILs) is a possible solution to some of the problems of solid and/or hydrophobic drugs such as low solubility and bioavailability, polymorphism and an alternative route of administration could be suggested as compared to the classical drug. Here, we report for the first time the synthesis and detailed characterization of a series of ILs containing a cation amino acid esters and anion ketoprofen (KETO-ILs). The affinity and the binding mode of the KETO-ILs to bovine serum albumin (BSA) were assessed using fluorescence spectroscopy. All compounds bind in a distance not longer than 6.14 nm to the BSA fluorophores. The estimated binding constants (KA) are in order of 105 L mol-1, which is indicative of strong drug or IL-BSA interactions. With respect to the ketoprofen-BSA system, a stronger affinity of the ILs containing l-LeuOEt, l-ValOBu, and l-ValOEt cation towards BSA is clearly seen. Fourier transformed infrared spectroscopy experiments have shown that all studied compounds induced a rearrangement of the protein molecule upon binding, which is consistent with the suggested static mechanism of BSA fluorescence quenching and formation of complexes between BSA and the drugs. All tested compounds were safe for macrophages.

The Relationship between the Structure and Properties of Amino Acid Ionic Liquids.

Ionic liquids based on different l-amino acids (glycine, l-valine, l-leucine, l-isoleucine, l-histidine, l-methionine, l-tyrosine, l-tryptophan, l-arginine, and l-threonine) and different cations (tetrabutylammonium (TBA), tributylmethylammonium (tBMA), didecyldimethylammonium (DDA), (2-hydroxyethyl)trimethylammonium (choline) (Chol), alkyl(C12-C14) dimethylbenzylammonium (benzalkonium) (BA), dodecyltrimethylammonium (DDTMA), hexadecyltrimethylammonium (HDTMA), octadecyltrimethylammonium (ODTMA) and 1-ethyl-3-methylimidazolium (EMIM)) have been synthesized and characterized by NMR and FTIR. Viscosity, specific rotation, surface activity, thermal stability (TG), and phase transformations (DSC) have been determined and compared with available data. Furthermore, benzalkonium, didecyldimethylammonium, dodecyltrimethylammonium, hexadecyltrimethylammonium, and octadecyltrimethylammonium amino acid ionic liquids have been shown to exhibit surface activity. The dissolution of cellulose in amino acid ionic liquids (AAILs) composed of various cations was also investigated. Cellulose was only dissolved in EMIM salts of amino acids. In particular, the influence of the cation type on selected physicochemical and spectroscopic properties were discussed. The article is a mini review on amino acid ionic liquids.

Advances in Rosin-Based Chemicals: The Latest Recipes, Applications and Future Trends.

A comprehensive review of the publications about rosin-based chemicals has been compiled. Rosin, or colophony, is a natural, abundant, cheap and non-toxic raw material which can be easily modified to obtain numerous useful products, which makes it an excellent subject of innovative research, attracting growing interest in recent years. The last extensive review in this research area was published in 2008, so the current article contains the most promising, repeatable achievements in synthesis of rosin-derived chemicals, published in scientific literature from 2008 to 2018. The first part of the review includes low/medium molecule weight compounds: Especially intermediates, resins, monomers, curing agents, surfactants, medications and biocides. The second part is about macromolecules: mainly elastomers, polymers for biomedical applications, coatings, adhesives, surfactants, sorbents, organosilicons and polysaccharides. In conclusion, a critical evaluation of the publications in terms of data completeness has been carried out with an indication of the most promising directions of rosin-based chemicals development.

Rapana thomasiana hemocyanin modified with ionic liquids with enhanced anti breast cancer activity.

This is the first study on the surface modification of a hemocyanin from marine snail Rapana thomasiana (RtH) with series of imidazolium-based amino acid ionic liquids [emim][AA]. We monitored the induced by [emim][AA] conformational changes in RtH molecule and evaluated the effect of these ionic liquids (ILs) on the protein thermal stability. The cytotoxicity of all obtained RtH-[emim][AA] complexes was assessed toward breast cancer cells (MCF-7) and murine fibroblasts (3T3). As a whole, even small amounts of the tested ILs altered the secondary structure of RtH. The thermal denaturation of RtH in presence of [emim][AA] displayed multi-component transitions, which were shifted toward lower temperatures in comparison to those estimated for the native RtH. The profiles of the RtH-IL calorimetric curves show a clear dependence on the structure of the added salts. In addition, all RtH-[emim][AA] complexes exhibited an enhanced antiprofilerative activity of toward MCF-7 cells in comparison to that of the native RtH. The best results are observed for RtH-[emim][Leu], RtH-[emim][Trp] or RtH-[emim][Ile], which applied in concentration of 700 µg/mL inhibited the MCF-7 cell viability (for 24h) by 66, 63 and 53%, respectively. In addition, these IL-RtH complexes were less cytotoxic to 3T3 cells, i.e. they exhibited some cell specificity.

Spectroscopic studies of amino acid ionic liquid-supported Schiff bases.

Amino acid ionic liquid-supported Schiff bases, derivatives of salicylaldehyde and various amino acids (L-threonine, L-valine, L-leucine, L-isoleucine and L-histidine) have been investigated by means of various spectroscopic techniques (NMR, UV-Vis, IR, MS) and deuterium isotope effects on ¹³C-NMR chemical shifts. The results have shown that in all studied amino acid ionic liquid-supported Schiff bases (except the L-histidine derivative) a proton transfer equilibrium exists and the presence of the COO⁻ group stabilizes the proton transferred NH-form.