Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental-Theoretical Study.

Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature (Tg) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations.

Assessing the Novel Mixed Tutton Salts K2Mn0.03Ni0.97(SO4)2(H2O)6 and K2Mn0.18Cu0.82(SO4)2(H2O)6 for Thermochemical Heat Storage Applications: An Experimental-Theoretical Study.

In this paper, novel mixed Tutton salts with the chemical formulas K2Mn0.03Ni0.97(SO4)2(H2O)6 and K2Mn0.18Cu0.82(SO4)2(H2O)6 were synthesized and studied as compounds for thermochemical heat storage potential. The crystallographic structures of single crystals were determined by X-ray diffraction. Additionally, a comprehensive computational study, based on density functional theory (DFT) calculations and Hirshfeld surface analysis, was performed to calculate structural, electronic, and thermodynamic properties of the coordination complexes [MII(H2O)6]2+ (MII = Mn, Ni, and Cu), as well as to investigate intermolecular interactions and voids in the framework. The axial compressions relative to octahedral coordination geometry observed in the crystal structures were correlated and elucidated using DFT investigations regarding Jahn-Teller effects arising from complexes with different spin multiplicities. The spatial distributions of the frontier molecular orbital and spin densities, as well as energy gaps, provided further insights into the stability of these complexes. Thermogravimetry, differential thermal analysis, and differential scanning calorimetry techniques were also applied to identify the thermal stability and physicochemical properties of the mixed crystals. Values of dehydration enthalpy and storage energy density per volume were also estimated. The two mixed sulfate hydrates reported here have low dehydration temperatures and high energy densities. Both have promising thermal properties for residential heat storage systems, superior to the Tutton salts previously reported.

Crystal growth, crystal structure determination, and computational studies of a new mixed (NH4)2Mn1-xZnx(SO4)2(H2O)6 Tutton salt.

Tutton salts have been extensively explored in recent decades due to their attractive physical and chemical properties, which make them potential candidates for thermochemical heat storage systems and optical technologies. In this paper, a series of new mixed Tutton salts with the chemical formula (NH4)2Mn1-xZnx(SO4)2(H2O)6 is reported. Crystals are successfully grown by the solvent slow evaporation method and characterized by powder X-ray diffraction (PXRD) with Rietveld refinement. In particular, the crystal structure of the mixed (NH4)2Mn0.5Zn0.5(SO4)2(H2O)6 crystal is solved through PRXD data using the DICVOL06 algorithm for diffraction pattern indexing and the Le Bail method for lattice parameter and spatial group determination. The structure is refined using the Rietveld method implemented in TOPAS® and reported in the Cambridge Structural Database file number 2104098. Moreover, a computational study using Hirshfeld surface and crystal void analyses is conducted to identify and quantify the intermolecular interactions in the crystal structure as well as to determine the amount of free space in the unit cell. Furthermore, 2D-fingerprint plots are generated to evaluate the main intermolecular contacts that stabilize the crystal lattice. Density functional theory is employed to calculate the structural, thermodynamic, and electronic properties of the coordination [Zn(H2O)6]2+ and [Mn(H2O)6]2+ complexes present in the salts. Molecular orbitals, bond lengths, and the Jahn-Teller effect are also discussed. The findings suggest that in Mn-Zn salts several properties dependent on the electronic structure can be tuned up by modifying the chemical composition.

Theoretical study of keto-enol tautomerism in 7-epi-clusianone by quantum chemical calculations of NMR chemical shifts.

Plants from the Garcinia genus have been used worldwide due to their therapeutic properties. Among the various metabolites isolated from this genus, 7-epi-clusianone, a tetraprenylated benzophenone, stands out for its wide range of identified biological activities. This benzophenone can exist in five tautomeric forms, although the benzene-d6 and chloroform-d3 solution nuclear magnetic resonance (NMR) spectra revealed only two tautomeric forms (B and C) in equilibrium, with concentration ratio depending on the solvent in which the spectrum was obtained. Calculated energy values suggested that tautomeric forms B and E would be prevalent in benzene-d6 solution, in contrast to the experimental data. Considering this conflicting result, we employed the statistical DP4 + method based on 13C and 1H NMR chemical shift calculations, in the gas phase and in benzene-d6 solution, to confirm that the B and C tautomeric forms of 7-epi-clusianone are the most prevalent in the experimental conditions.

Structural, thermal, vibrational, solubility and DFT studies of a tolbutamide co-amorphous drug delivery system for treatment of diabetes.

Among the strategies for bioavailability improvement of poorly soluble drugs, co-amorphous systems have revealed to have a significant impact in the increase of the aqueous solubility of the drug, and at the same time increasing the amorphous state stability and dissolution rate when compared with the neat drug. Tolbutamide (TBM) is an oral hypoglycemic drug largely used in the treatment of type II Mellitus diabetes. TBM is a class II drug according to the Biopharmaceutical Classification System, meaning that it has low solubility and higher permeability. The aim of this study was to synthesize a co-amorphous material of tolbutamide (TBM) with tromethamine (TRIS). Density functional theory (DFT), allowed to study the structural, electronic, and thermodynamic properties, as well as solvation effects. In same theory level, several interactions tests were performed to obtain the most thermodynamically favorable drug-coformer intermolecular interactions. The vibrational spectra (mid infrared and Raman spectroscopy) are in accordance with the theoretical studies, showing that the main molecular interactions are due to the carbonyl, sulfonyl, and amide groups of TMB and the alcohol and amine groups of TRIS. X-ray powder diffraction was used to study the physical stability in dry condition at 25 °C of the co-amorphous system, indicating that the material remained in an amorphous state up to 90 days. Differential scanning calorimetry and thermogravimetric results showed a high increase of the Tg when compared with the amorphous neat drug, from 4.3 °C to 83.7 °C, which generally translated into good physical stability. Solubility studies demonstrated an increase in the solubility of TBM by 2.5 fold when compared with its crystalline counterpart.

Bioactivity and molecular properties of Phenoxyacetic Acids Derived from Eugenol and Guaiacol compared to the herbicide 2,4-D.

Herbicides are agrochemicals applied in the control of weeds. With the frequent and repetitive use of these substances, serious problems have been reported. Compounds of natural origin and their derivatives are attractive options to obtain new compounds with herbicidal properties. By aiming to develop compounds with potentiated herbicidal activity, phenoxyacetic acids were synthesized from eugenol and guaiacol. The synthesized compounds were characterized and the herbicidal potential of phenoxyacetic acids and precursors was evaluated through bioassays regarding the germination and initial development of Lactuca sativa and Sorghum bicolor seedlings, with the induction of DNA damage. The induction of changes in the mitotic cycle of meristematic cells of roots of L. sativa was also analyzed. At the concentration of 3 mmol L-1, phenols and their respective phenoxyacetic acids presented phytotoxic and cytotoxic activities in L. sativa and S. bicolor. Eugenol and guaiacol also presented genotoxic action in L. sativa. The toxic effect of eugenoxyacetic acid was more pronounced in L. sativa than in S. bicolor, similar to the commercial 2,4-D herbicide. Molecular properties of the phenols and their derivatives phenoxyacetic acids were compared with the ones obtained for the herbicide 2,4-D, where it was found a correlation between their molecular properties and bioactivity.

Adsorption of the herbicides diquat and difenzoquat on polyurethane foam: Kinetic, equilibrium and computational studies.

This work reports a study about the adsorption of the herbicides diquat and difenzoquat from aqueous medium employing polyurethane foam (PUF) as the adsorbent and sodium dodecylsulfate (SDS) as the counter ion. The adsorption efficiency was shown to be dependent on the concentration of SDS in solution, since the formation of an ion-associate between cationic herbicides (diquat and difenzoquat) and anionic dodecylsulfate is a fundamental step of the process. A computational study was carried out to identify the possible structure of the ion-associates that are formed in solution. They are probably formed by three units of dodecylsulfate bound to one unit of diquat, and two units of dodecylsulfate bound to one unit of difenzoquat. The results obtained also showed that 95% of both herbicides present in 45mL of a solution containing 5.5mgL-1 could be retained by 300mg of PUF. The experimental data were well adjusted to the Freundlich isotherm (r2 ≥ 0.95) and to the pseudo-second-order kinetic equation. Also, the application of Morris-Weber and Reichenberg equations indicated that an intraparticle diffusion process is active in the control of adsorption kinetics.

Natural polyprenylated benzophenone: keto-enol tautomerism from density functional calculations and the AIM theory.

The quantum theory of atoms in molecules (QTAIM) and density functional theory (DFT) calculations were employed to investigate the structure and tautomeric equilibrium of epiclusianone, a polyisoprenylated benzophenone with interesting biological activities. Two different exchange-correlation functionals were employed, namely ωB97x-D and M06-2x, including implicit solvent models (benzene and DMSO). Our results for the thermodynamic properties show that the isomer in which the H atom is bonded to the oxygen away from the benzene ring is the most stable tautomer form of the epiclusianone, thus confirming previous charge density analysis from X-ray diffraction data (Martins et al. J Braz Chem Soc 18(8):1515-1523, 22).

Modeling, kinetic, and equilibrium characterization of paraquat adsorption onto polyurethane foam using the ion-pairing technique.

We studied the adsorption of paraquat onto polyurethane foam (PUF) when it was in a medium containing sodium dodecylsulfate (SDS). The adsorption efficiency was dependent on the concentration of SDS in solution, because the formation of an ion-associate between the cationic paraquat and the dodecylsulfate anion was found to be a fundamental step in the process. A computational study was carried out to identify the possible structure of the ion-associate in aqueous medium. The obtained data demonstrated that the structure is probably formed from four units of dodecylsulfate bonded to one paraquat moiety. The results showed that 94% of the paraquat present in 45 mL of a solution containing 3.90 × 10(-5) mol L(-1) could be retained by 300 mg of PUF, resulting in the removal of 2.20 mg of paraquat. The experimental data were reasonably adjusted to the Freundlich isotherm and to the pseudo-second-order kinetic model. Also, the application of Morris-Weber and Reichenberg models indicated that both film-diffusion and intraparticle-diffusion processes were active during the control of the adsorption kinetics.

Synthesis of rubrolide analogues as new inhibitors of the photosynthetic electron transport chain.

Many natural products have been used as a model for the development of new drugs and agrochemicals. Following this strategy 11 rubrolide analogues, bearing electron-withdrawing and -donating groups at both benzene rings, were prepared starting from commercially available mucobromic acid. The ability of all compounds to inhibit the photosynthetic electron transport chain in the chloroplast was investigated. The rubrolide analogues were effective in interfering with the light-driven ferricyanide reduction by isolated chloroplasts. The IC(50) values of the most active derivatives are in fact only 1 order of magnitude higher than those of commercial herbicides sharing the same mode of action, such as Diuron (0.27 µM). QSAR studies indicate that the most efficient compounds are those having higher ability to accept electrons, either by a reduction process or by an electrophilic reaction mechanism. The results obtained suggest that the rubrolide analogues represent promising candidates for the development of new active principles targeting photosynthesis to be used as herbicides.