Experimental and molecular dynamics simulation study of the sublimation energetics of cyclopentadienyltricarbonylmanganese (Cymantrene)

The standard molar enthalpy of sublimation of monoclinic cyclopentadienyltricarbonylmanganese, Mn(eta (5)-C 5H 5)(CO) 3, at 298.15 K, was determined as Delta sub H m (o)[Mn(eta (5)-C 5H 5)(CO) 3] = 75.97 +/- 0.37 kJ x mol (-1) from Knudsen effusion and Calvet-drop microcalorimetry measurements, thus considerably improving the very large inaccuracy (>10 kJ x mol (-1)) of the published data. The obtained value was used to assess the extension of the OPLS-based all-atom force field we previously developed for iron metallocenes to manganese organometallic compounds. The modified force field was able to reproduce the volumetric properties (density and unit-cell volume) of crystalline Mn(eta (5)-C 5H 5)(CO) 3 with a deviation of 0.6% and the experimentally determined enthalpy of sublimation with an accuracy of 1 kJ x mol (-1). The interaction (epsilon) and atomic-diameter (sigma) parameters of the Lennard-Jones (12-6) potential function used to calculate dispersion contributions within the framework of the force field were found to be transferable from iron to manganese.     

Chemical Characterization and Bioactivity of Commercial Essential Oils and Hydrolates Obtained from Portuguese Forest Logging and Thinning

Essential oils (EOs) and hydrolates (Hds) are natural sources of biologically active ingredients with broad applications in the cosmetic industry. In this study, nationally produced (mainland Portugal and Azores archipelago) EOs (11) and Hds (7) obtained from forest logging and thinning of Eucalyptus globulus, Pinus pinaster, Pinus pinea and Cryptomeria japonica, were chemically evaluated, and their bioactivity and sensorial properties were assessed. EOs and Hd volatiles (HdVs) were analyzed by GC-FID and GC-MS. 1,8-Cineole was dominant in E. globulus EOs and HdVs, and α- and β-pinene in P. pinaster EOs. Limonene and α-pinene led in P. pinea and C. japonica EOs, respectively. P. pinaster and C. japonica HVs were dominated by α-terpineol and terpinen-4-ol, respectively. The antioxidant activity was determined by DPPH, ORAC and ROS. C. japonica EO showed the highest antioxidant activity, whereas one of the E. globulus EOs showed the lowest. Antimicrobial activity results revealed different levels of efficacy for Eucalyptus and Pinus EOs while C. japonica EO showed no antimicrobial activity against the selected strains. The perception and applicability of emulsions with 0.5% of EOs were evaluated through an in vivo sensory study. C. japonica emulsion, which has a fresh and earthy odour, was chosen as the most pleasant fragrance (60%), followed by P. pinea emulsion (53%). In summary, some of the studied EOs and Hds showed antioxidant and antimicrobial activities and they are possible candidates to address the consumers demand for more sustainable and responsibly sourced ingredients.     

Molecular Hybridization Strategy on the Design,Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141–156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC₅₀ values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.     

Surfactant design for the 1,1,1,2-tetrafluoroethane-water interface: ab initio calculations and in situ high-pressure tensiometry

In situ high-pressure tensiometry and ab initio calculations were used to rationally design surfactants for the 1,1,1,2-tetrafluoroethane-water (HFA134a|W) interface. Nonbonded pair interaction (binding) energies (E(b)) of the complexes between HFA134a and candidate surfactant tails were used to quantify the HFA-philicity of selected moieties. The interaction between HFA134a and an ether-based tail was shown to be predominantly electrostatic in nature and much more favorable than that between HFA134a and a methyl-based fragment. The interfacial activity of (i) amphiphiles typically found in FDA-approved pressurized metered-dose inhaler (pMDI) formulations, (ii) a series of nonionic surfactants with methylene-based tails, and (iii) a series of nonionic surfactants with ether-based tails was investigated at the HFA134a|W interface using in situ tensiometry. This is the first time that the tension of the surfactant-modified HFA134a|W interface has been reported in the literature. The ether-based surfactants were shown to be very interfacially active, with tension decreasing by as much as 27 mN.m(-)(1). However, the methyl-based surfactants, including those from FDA-approved formulations, did not exhibit high activity at the HFA134a|W interface. These results are in direct agreement with the E(b) calculations. Significant differences in interfacial activity are noted for surfactants at the 2H,3H-perfluoropentane (HPFP)|water and HFA134a|W interfaces. Care should be taken, therefore, when results from the mimicking solvent (HPFP) are extrapolated to HFA134a-based systems. The results shown here are of relevance in the selection of surfactants capable of forming and stabilizing reverse aqueous aggregates in HFA-based pMDIs, which are promising formulations for the systemic delivery of biomolecules to and through the lungs.     

Protease Production by Different Thermophilic Fungi

A comparative study was carried out to evaluate protease production in solid-state fermentation (SSF) and submerged fermentation (SmF) by nine different thermophilic fungi – Thermoascus aurantiacus Miehe, Thermomyces lanuginosus, T. lanuginosus TO.03, Aspergillus flavus 1.2, Aspergillus sp. 13.33, Aspergillus sp. 13.34, Aspergillus sp. 13.35, Rhizomucor pusillus 13.36 and Rhizomucor sp. 13.37 – using substrates containing proteins to induce enzyme secretion. Soybean extract (soybean milk), soybean flour, milk powder, rice, and wheat bran were tested. The most satisfactory results were obtained when using wheat bran in SSF. The fungi that stood out in SSF were T. lanuginosus, T. lanuginosus TO.03, Aspergillus sp. 13.34, Aspergillus sp. 13.35, and Rhizomucor sp. 13.37, and those in SmF were T. aurantiacus, T. lanuginosus TO.03, and 13.37. In both fermentation systems, A. flavus 1.2 and R. pusillus 13.36 presented the lowest levels of proteolytic activity.     

Computational study on the bond dissociation enthalpies in the enolic and ketonic forms of beta-diketones: their influence on metal-ligand bond enthalpies

A computational study on the thermodynamic properties of 13 beta-diketones is presented. The B3LYP//6-311+G(2d,2p)//B3LYP/6-31G(d) theoretical approach was employed to compute the O-H and C-H bond dissociation enthalpies and enthalpy of tautomerization and to estimate standard gas-phase enthalpies of formation for the radicals and for the parent molecules. The gas-phase enthalpies of formation for the neutral molecules are in excellent agreement with available experimental data, supporting the estimates made for the radicals. The latter are very important for the clarification of the thermochemistry of many beta-diketonato metal complexes previously reported in the literature. Importantly, when substituents R = -CHR' are attached to the beta-diketone's scaffold, C-H homolytic bond cleavage is always favored with respect to O-H bond scission.     

Experimental and theoretical electron density study of estrone

The electron density and the electrostatic potential (ESP) distributions of estrone have been determined using X-ray diffraction analysis and compared with theoretical calculations in the solid and gas phases. X-ray diffraction measurements are performed with a Rigaku Rapid rotating anode diffractometer at 20 K. The electron density in the estrone crystal has been described with the multipole model, which allowed extensive topological analysis and calculation of the ESP. From DFT calculations in the solid state a theoretical X-ray diffraction data set has been produced and treated in the same way as the experimental data. Two sets of single molecule DFT calculations were performed: (a) An electron density distribution was obtained via a single-point calculation with a large basis set at the experimental geometry and subsequently analyzed according to the quantum theory of atoms in molecules (AIM) to obtain the bond and most atomic properties, and (b) another electron density distribution was obtained with a smaller basis set, but at a geometry optimized using the same basis set for the analysis of atomic energies. An interesting locally stabilizing hydrogen-hydrogen bond path linking H(1) and H(11B) is found which represents the first characterization of such bonding in a steroid molecule. AIM delocalization indices were shown to be well correlated to the experimental electron density at the bond critical points through an exponential relationship. The aromaticity of ring A, chemical bonding, the O(1)...O(2) distance necessary for estrogenic activity, and the electrostatic potential features are also discussed.     

Effects of the attractive interactions in the thermodynamic, dynamic, and structural anomalies of a two length scale potential

Using molecular dynamic simulations, we study a system of particles interacting through a continuous core-softened potentials consisting of a hard core, a shoulder at closest distances, and an attractive well at further distance. We obtain the pressure-temperature phase diagram of this system for various depths of the tunable attractive well. Since this is a two length scale potential, density, diffusion, and structural anomalies are expected. We show that the effect of increasing the attractive interaction between the molecules is to shrink the region in pressure in which the density and the diffusion anomalies are present. If the attractive forces are too strong, particle will be predominantly in one of the two length scales and no density of diffusion anomaly is observed. The structural anomalous region is present for all the cases.     

Thermal characterization of hydrotalcite used in the transesterification of soybean oil

Hydrotalcite was synthesised by co-precipitation method, calcined and characterized by XRD, BET, IR and TG/DTA/DTG analyses and tested as solid base catalyst in the transesterification of soybean oil with methanol, achieving a methyl ester content of 99.5%. The thermal decomposition of hydrotalcite calcined occurred in four mass loss steps at 28, 105, 203 and 400 °C. The hydrotalcite was recovered and through a simple evaluation by TG/DTA/DTG techniques it was found that at 500 °C is the temperature, where the organic matter should be eliminated from the catalyst. This study shows the importance of thermal analysis in the evaluation of the recovery temperature of hydrotalcite.