Unveiling the relevance of the redox character of nitroaromatic and nitroheteroaromatic compounds as potential medicines

This review discusses the state of the art, challenges, and perspectives in recent applications of nitroaromatics and nitroheteroaromatics, which are redox-bio-activated drugs or leads, in Medicinal Chemistry. It deals mainly with the electrochemical approach toward the electron transfer-based molecular mechanisms of drug action, drug design, estimation and measurement of redox potentials, correlation of physicochemical and pharmacological data, and electrochemical studies of the main representatives of nitro-containing prodrugs, along with approaches to combat their toxicity issues, aiming at a better therapeutic profile. Electrochemical investigation plays essential roles, being strategic in the design and discovery of potential medicines.     

Novel betulin derivatives inhibit IFN-γ and modulates COX-2 expression

Abstract

Betulin (BE) is a pentacyclic triterpenes, obtained from natural sources and with several biological activities described, such as anti-tumoral and anti-inflammatory activities. The BE esterification at hydroxyl group (C-3 and C-28) resulted in five new ester derivatives with different numbers of carbons or halogens (chlorine and fluorine). Among these BE derivatives, two (2a e 2c) were able to significantly decrease IFN-g (*p?=?0.0391; **p?=?0.0156) and 2c modulated the expression of COX-2 better than Dexamethasone (DEXA). Regarding to cytotoxic assay, the best results were obtained for BE without modifications, with emphasis on tumoral cell lines Raji and MCF-7. The derivatives 2a and 2c showed immunomodulation activity (for the cytokines IFN-g). The presence of chorine in BE seems to be important for the ability of modulate COX-2 expression, since the ester chloride derivative 2c at 100?μM is more powerful inhibitor of COX-2 than DEXA.     

High pressure: a tool to improve the enzymatic production of glycosides

Naringinase, an enzyme complex that expresses α -l-rhamnosidase and β -d-glucosidase activities in native state, can be used to deglycosylate natural glycosides. The selective inactivation of one of these activities will allow the biosynthesis of different bioactive compounds in a simple, effective and cheap way. In this work, pressure and temperature were the tools used to selectively inactivate the activities expressed by naringinase. The main goal was the identification of pressure–temperature conditions to acquire conditions for the maximization of enzymatic hydrolysis of substrates with different numbers of glycosidic residues. α -l-Rhamnosidase was 32-fold more resistant against inactivation at 250 MPa than at atmospheric pressure. The best pressure condition to reduce β -d-glucosidase inactivation at 75°C was 173 MPa, while in the case of α -l-rhamnosidase inactivation at 85°C, it was above 250 MPa. Moreover, a selective inactivation of β -d-glucosidase activity of naringinase was attained, allowing an easy and cheap method with which to produce prunin and other expensive glycosides. The present work highlights the effect of high pressure on enzyme protection against thermal inactivation, demonstrating its potential as a powerful tool in biosynthesis.     

Thermodynamics of the xenon + methyl chloride system

The total vapour pressure of the xenon + methyl chloride system has been measured as a function of composition at 175.44 and 182.32 K. The resulting data have been used to evaluate the excess Gibbs functions G^E at the same temperatures. The excess enthalpy and excess molar volume have also been measured at 182.32 K. The system shows large positive deviations from Raoult's law but negative volumes on mixing. These results are compared with theoretical predictions of a recent molecular theory and of standard engineering methods. The calculations show the superiority of the molecular theory over more empirical procedures such as those based on the Redlich-Kwong equation of state or the regular-solution model.     

Liquid—vapor equilibrium in the system H2Ar at temperatures from 83 to 141 K and pressures to 52 MPa

Calado, J.C.G. and Streett, W.B., 1979. Liquid—vapor equilibrium in the system H₂Ar at temperatures from 83 to 141 K and pressures to 52 MPa. Fluid Phase Equilibria, 2: 275–282.Experimental measurements of liquid—vapor phase equilibria in the system H₂Ar are reported for thirteen temperatures in the range 83.09 to 141.42 K, and pressures to 52 MPa. The mixture critical line and the pressure—temperature trace of the three-phase line solid—liquid—gas have been located. These lines intersect at T = 84.0 K and P = 52.5 MPa to form an upper critical end point. The pressure—temperature trace of the three-phase line has a temperature minimum at T ? 82.5 K, P ? 20 MPa.     

Pelseneeriol-1 and -2: new furanosesquiterpene alcohols from porostome nudibranch Doriopsilla pelseneeri

The paper reports the first chemical study of the porostome nudibranch Doriopsilla pelseneeri collected off the Portuguese coast (Atlantic Ocean). Two new furanosesquiterpene alcohols, pelseneeriol-1 (1) and pelseneeriol-2 (2), have been isolated together with known compounds, 15-acetoxy-ent-pallescensin-A (5), and dendocarbin-A (6), from the mantle of the nudibranch, whereas euryfuran (3) and drimane ester mixture 4 were identified in the extract of the internal glands. The structures of 1 and 2 have been determined by extensive spectroscopic studies as well as by comparison with literature model compounds. In order to assess the relative stereochemistry of 1 and 2, full NMR assignment of related sponge metabolite microcionin-2 (8) and of co-occurring sesquiterpenes 9-11, that have been re-isolated from the Mediterranean sponge Fasciospongia cavernosa, has been also conducted. In particular, the relative stereochemistry of tricyclic sesquiterpene microcionin-1 (9) has now been rigorously assigned by detailed analysis of NOE difference experiments.     

Shape Effects in the Partial Molar Volume of Tetraethylphosphonium and Ammonium Iodides in Six Nonaqueous Solvents

Densities of dilute solutions of the electrolytes tetraethylphosphonium iodide and tetraethylammonium iodide in the nonaqueous solvents methanol, ethanol, 1-propanol, 1-butanol, acetonitrile, and 2-propanone were measured at 25^°C. Using published values for the Debye-Hückel limiting slopes A _V, apparent molar volume data were fitted to the Pitzer equation yielding infinite-dilution partial molar volumes and deviation parameters B _V. It is found that the variation in the van der Waals volume of the cationic central atoms is about one half the experimental volume change in 2-propanone solutions, but twice that value in the other five solvents. This finding is interpreted in terms of openness of solute structure and solvent penetration. Parameter B _V for each salt is shown to be solvent dependent. An interesting approximate linear variation between A _V and B _V parameters is suggested by the data. This empirical relationship would entail correlation of short- and long-range interionic interactions in solution.     

Molecular dynamics simulations of monoclinic calcium apatites: A universal equation of state

Molecular dynamics simulations of monoclinic (P2₁/b) hydroxy- and chlorapatite were undertaken in the range 498 K < T < 1298 K, and for pressures up to 7.5 GPa. The all-atom Born–Huggins–Mayer force field, that had been previously used to successfully describe the room temperature isotherms of both compounds, was also used in this work. The isothermal sets of p–V data generated by simulation were each fitted to the three-parameter form of the isothermal Parsafar and Mason equation of state (EoS) with an accuracy better than 0.07%. Taking the temperature dependence of the coefficients into account, it was found that the MD data are satisfactorily reproduced by the universal EoS. The isothermal compressibility coefficient dependence with pressure can be described by a linear relation.