Antimicrobial Imidazolium Ionic Liquids for the Development of Minimal Invasive Calcium Phosphate-Based Bionanocomposites.

Biofilm formation is one of the main obstacles that occur during in vivo implantation, which compromises the implant functionality and patients' health. This is the inspiration for the development of novel implant materials that contain broad-spectrum antimicrobial activity, including antibacterial and antifungal, and enable the local release of antimicrobial agents. Here, multifunctional calcium phosphate-ionic liquid (IL) materials, possessing antimicrobial and repair/regeneration features plus injectability, are proposed as implants in minimally invasive surgery. This approach was based on the loading of 1-alkyl-3-alkylimidazolium chloride ionic liquids (ILs) (C nMImCl ( n = 4, 10, 16) and (C10)2MImCl) during the in situ sol-gel synthesis of calcium phosphates (CaP) and study of their effects on CaP crystallization and biological properties. Physical, morphological, and biological investigations were performed to evaluate the bionanocomposites' properties. The IL N-alkyl chain length influenced the crystallization of CaP and, consequently, the biological properties, which afforded bionanocomposites (when loaded with C16MImCl or (C10)2MImCl) that, (i) inhibit both in vitro bacterial and fungal growth; (ii) reduce the in vitro inflammatory response; (iii) induce osteogenic differentiation in the basal medium of human mesenchymal stem cells; and (iv) are injectable. This will enable the design of multifunctional injectable implants with antimicrobial, anti-inflammatory, and regenerative properties to be used in minimally invasive surgery of bone and maxillofacial defects.

Molecular spherical nucleic acids.

Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.

Bifunctional fluorescent benzimidazo[1,2-α]quinolines for Candida spp. biofilm detection and biocidal activity.

Biofilms provide an ideal environment for protecting the microbial cells from damage caused by humoral and cellular immune system components, promoting resistance, infections and increasing mortality and morbidity of patients in health facilities. In an attempt to provide an innovative solution for preventing contamination in hospital environments, this study evaluated nine structural complementary fluorescent benzimidazo[1,2-α]quinolines as bifunctional agents that both detect and have biocidal activity against yeast biofilms on stainless steel surfaces. The benzimidazoles' staining capability was determined by a fluorescence microscopy study and spraying the substance on yeast biofilm contaminated stainless steel surfaces. Furthermore, their in vitro human leukocyte cytotoxicity was evaluated with trypan blue and their biocidal activity was determined as the minimum inhibitory concentration against Candida tropicalis, C. albicans and C. parapsilosis strains. Moreover, scanning electron micrographs were recorded to study the biocidal activity. This resulted in the identification of 7, which presents all the desired characteristics (such as solubility) and capabilities (staining and biocide activity against all tested biofilm forming yeast strains) at the same time. As such, benzimidazole 7 has the potential to guarantee the use of disinfected medical and surgical instruments in clinical and surgical procedures, consequently, contributing to an increased safety for patients.

Multitask Imidazolium Salt Additives for Innovative Poly(l-lactide) Biomaterials: Morphology Control, Candida spp. Biofilm Inhibition, Human Mesenchymal Stem Cell Biocompatibility, and Skin Tolerance.

Candida species have great ability to colonize and form biofilms on medical devices, causing infections in human hosts. In this study, poly(l-lactide) films with different imidazolium salt (1-n-hexadecyl-3-methylimidazolium chloride (C16MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS)) contents were prepared, using the solvent casting process. Poly(l-lactide)-imidazolium salt films were obtained with different surface morphologies (spherical and directional), and the presence of the imidazolium salt in the surface was confirmed. These films with different concentrations of the imidazolium salts C16MImCl and C16MImMeS presented antibiofilm activity against isolates of Candida tropicalis, Candida parapsilosis, and Candida albicans. The minor antibiofilm concentration assay enabled one to determine that an increasing imidazolium salt content promoted, in general, an increase in the inhibition percentage of biofilm formation. Scanning electron microscopy micrographs confirmed the effective prevention of biofilm formation on the imidazolium salt containing biomaterials. Lower concentrations of the imidazolium salts showed no cytotoxicity, and the poly(l-lactide)-imidazolium salt films presented good cell adhesion and proliferation percentages with human mesenchymal stem cells. Furthermore, no acute microscopic lesions were identified in the histopathological evaluation after contact between the films and pig ear skin. In combination with the good morphological, physicochemical, and mechanical properties, these poly(l-lactide)-based materials with imidazolium salt additives can be considered as promising biomaterials for use in the manufacturing of medical devices.

The role of ether-functionalized ionic liquids in the sol-gel process: effects on the initial alkoxide hydrolysis steps.

The ether-functionalized imidazolium ionic liquids (IL) applied in the silica sol-gel process demonstrated a defined coordination potential. These IL display the capacity to control the system organization from the reactions' first moments through a dynamic system-assembling ability, being the sum of ionic and physical interactions, i.e. Coulomb forces, H-bonding and London forces. The initial hydrolysis steps of tetraethyl orthosilicate (TEOS) in the presence of these IL were followed by Fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS), both in time-resolved experiments, in an attempt to correlate the structuring and the bonding dynamics of these systems.

Disclosure of the imidazolium cation coordination and stabilization mode in ionic liquid stabilized gold(0) nanoparticles.

A surface-enhanced Raman spectroscopy (SERS) study of imidazolium ionic liquid stabilized gold(0) nanoparticles (GNPs) furnished previously unknown knowledge about the coordination and stabilization mode of the imidazolium cation. GNPs were prepared by hydrazine reduction of a chloroauric acid solution in 1-triethylene glycol monomethyl ether-3-methylimidazolium methanesulfonate 2 as ether-functionalized room-temperature ionic liquid (RTIL). UV-vis spectroscopy showed the presence of GNP aggregates as absorptions extended to the NIR region. A parallel coordination mode for the imidazolium cation of RTIL 2 on the GNP surface was observed by SERS, which occurred without the simultaneous coordination of the 1-triethylene glycol monomethyl ether-functionality. Instead of this, the ether-functionality was directed away from the GNP surface and acted as steric barrier between the GNPs/GNP aggregates, thus preventing further aggregation. These new insights suggest that the imidazolium cation is responsible for electrosteric stabilization.

In situ formation of allyl ketones via Hiyama-Nozaki reactions followed by a chromium-mediated Oppenauer oxidation.

In Hiyama-Nozaki reactions of allylchromium with aldehydes the expected products are homoallylalcohols. However, oxidation products derived from these, predominantly allyl ketones, can be common side products. This can be explained by an Oppenauer-(Meerwein-Ponndorf-Verley)-type mechanism (OMPV-reaction). The amount of oxidation is strongly dependent on the substitution pattern of the reaction partners and the reaction conditions. An appropriate choice of these can lead to preferential formation of ketones instead of the alcohols. In addition to its synthetic usefulness, the oxidation-reduction equilibrium is of the utmost importance for the design of enantioselective Hiyama-Nozaki reactions because it is also a potential racemization pathway.