A Source of Systematic Errors in the Determination of Critical Micelle Concentration and Micellization Enthalpy by Graphical Methods in Isothermal Titration Calorimetry.

Isothermal titration calorimetry is frequently employed to determine the critical micelle concentration and the micellization enthalpy of surfactants in terms of geometrical characteristics of the titration curves. Previously we have shown theoretically that even for an infinitesimal injection, the heat per titrant mol depends on the stock solution concentration. In this work, we explore experimentally the influence of the stock solution concentration on the geometrical characteristics of the titration curve and its effect in determining the critical micelle concentration and the micellization enthalpy of surfactants. The systematic study of this phenomenology involves a great number of measurements at different temperatures with several repetitions carried out using a robotic calorimeter. As surfactant hexadecyltrimethylamonium bromide was used. The magnitude and shape of the heat titration depend on the stock solution concentration. As a consequence, the inflexion-point, break-point, and step-height decrease until a limiting value. A qualitative analysis suggests that the limiting value depends only on substance. This work shows that graphical methods could not be suitable for the calculation of the critical micelle concentration and micellization enthalpy because the magnitude and shape of the titration curve depend on the stock solution concentration. Micellar properties should be calculated by the application of theoretical models as in the ligand-binding studies.

Synthesis of hydrogels from biomaterials and their potential application in tissue engineering.

In this study, a series of hydrogels were synthesized from chitosan(s) that was crosslinking with glutaraldehyde at different concentrations. Ascorbic acid in an acidic medium was used to facilitate non-covalent interactions. The chitosan(s) was obtained from shrimp cytoskeleton; while ascorbic acid was extracted from xoconostle juice. The hydrogel reaction was monitored by UV-vis spectroscopy (550 nm) to determine the reaction kinetics and reaction order at 60 °C. The hydrogels structures were characterized by NMR, FT-IR, HR-MS and SEM, while the degree of cross-linking was examined with TGA-DA. The extracellular matrices were obtained as stable hydrogels where reached maximum crosslinking was of 7 %, independent of glutaraldehyde quantity added. The rheological properties showed a behavior of weak gels and a dependence of crosslinking agent concentration on strength at different temperatures. The cytotoxicity assay showed that the gels had no adverse effects on cellular growth for all concentrations of glutaraldehyde.

Analysis of Structural Changes of pH-Thermo-Responsive Nanoparticles in Polymeric Hydrogels.

The pH- and thermo-responsive behavior of polymeric hydrogels MC-co-MA have been studied in detail using dynamic light scattering DLS, scanning electron microscopy SEM, nuclear magnetic resonance (1H NMR) and rheology to evaluate the conformational changes, swelling-shrinkage, stability, the ability to flow and the diffusion process of nanoparticles at several temperatures. Furthermore, polymeric systems functionalized with acrylic acid MC and acrylamide MA were subjected to a titration process with a calcium chloride CaCl2 solution to analyze its effect on the average particle diameter Dz, polymer structure and the intra- and intermolecular interactions in order to provide a responsive polymer network that can be used as a possible nanocarrier for drug delivery with several benefits. The results confirmed that the structural changes in the sensitive hydrogels are highly dependent on the corresponding critical solution temperature CST of the carboxylic (-COOH) and amide (-CONH2) functional groups and the influence of calcium ions Ca2+ on the formation or breaking of hydrogen bonds, as well as the decrease in electrostatic repulsions generated between the polymer chains contributing to a particle agglomeration phenomenon. The temperature leads to a re-arrangement of the polymer chains, affecting the viscoelastic properties of the hydrogels. In addition, the diffusion coefficients D of nanoparticles were evaluated, showing a closeness among with the morphology, shape, size and temperature, resulting in slower diffusions for larger particles size and, conversely, the diffusion in the medium increasing as the polymer size is reduced. Therefore, the hydrogels exhibited a remarkable response to pH and temperature variations in the environment. During this research, the functionality and behavior of the polymeric nanoparticles were observed under different analysis conditions, which revealed notable structural changes and further demonstrated the nanoparticles promising high potential for drug delivery applications. Hence, these results have sparked significant interest in various scientific, industrial and technological fields.

New Carbamates and Ureas: Comparative Ability to Gel Organic Solvents.

Two series of novel amphiphilic compounds were synthesized based on carbamates and ureas structures, using a modification of the synthesis methods reported by bibliography. The compounds were tested for organic solvent removal in a model wastewater. The lipophilic group of all compounds was a hexadecyl chain, while the hydrophilic substituent was changed with the same modifications in both series. The structures were confirmed by FT-IR, NMR, molecular dynamic simulation and HR-MS and their ability to gel organic solvents were compared. The SEM images showed the ureas had a greater ability to gel organic solvents than the carbamates and formed robust supramolecular networks, with surfaces of highly interwoven fibrillar spheres. The carbamates produced corrugated and smooth surfaces. The determination of the minimum gelation concentration demonstrated that a smaller quantity of the ureas (compared to the carbamates, measured as the weight percentage) was required to gel each solvent. This advantage of the ureas was attributed to their additional N-H bond, which is the only structural difference between the two types of compounds, and their structures were corroborated by molecular dynamic simulation. The formation of weak gels was demonstrated by rheological characterization, and they demonstrated to be good candidates for the removal organic solvents.

Synthesis and Antimycobacterial Activity of 2,5-Disubstituted and 1,2,5-Trisubstituted Benzimidazoles.

The appearance of drug-resistant strains of Mycobacterium tuberculosis and the dramatic increase in infection rates worldwide evidences the urgency of developing new and effective compounds for treating tuberculosis. Benzimidazoles represent one possible source of new compounds given that antimycobacterial activity has already been documented for some derivatives, such as those bearing electron-withdrawing groups. The aim of this study was to synthesize two series of benzimidazoles, di- and trisubstituted derivatives, and evaluate their antimycobacterial activity. Accordingly, 5a and 5b were synthesized from hydroxymoyl halides 3a and 3b, and nitro-substituted o-phenylenediamine 4. Compound 11 was synthesized from an aromatic nitro compound, 4-chloro-1,2-phenylenediamine 9, mixed with 3-nitrobenzaldehyde 10, and bentonite clay. Although the synthesis of 11 has already been reported, its antimycobacterial activity is herein examined for the first time. 1,2,5-trisubstituted benzimidazoles 7a, 7b, and 12 were obtained from N-alkylation of 5a, 5b, and 11. All benzimidazole derivatives were characterized by FT-IR, NMR, and HR-MS, and then screened for their in vitro antimycobacterial effect against the M. tuberculosis H37Rv strain. The N-alkylated molecules (7a, 7b, and 12) generated very limited in vitro inhibition of mycobacterial growth. The benzimidazoles (5a, 5b, and 11) showed in vitro potency against mycobacteria, reflected in minimal inhibitory concentration (MIC) values in the range of 6.25-25 µg/mL. Consequently, only the 2,5-disubstituted benzimidazoles were assessed for biological activity on mouse macrophages infected with M. tuberculosis. A good effect was found for the three compounds. The cytotoxicity assay revealed very low toxicity for all the test compounds against the macrophage cell line. According to the docking study, 2,5-disubstituted benzimidazoles exhibit high affinity for an interdomain cleft that plays a key role in the GTP-dependent polymerization of the filamentous temperature-sensitive Z (FtsZ) protein. The ability of different benzimidazoles to impede FtsZ polymerization is reportedly related to their antimycobacterial activity. On the other hand, the 1,2,5-trisubstituted benzimidazoles docked to the N-terminal of the protein, close to the GTP binding domain, and did not show strong binding energies. Overall, 5a, 5b, and 11 proved to be good candidates for in vivo testing to determine their potential for treating tuberculosis.