The title compound 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione was obtained by reaction of thymine with 3-nitrobenzylbromide in the presence of cesium carbonate. Characterization of the product was achieved by NMR spectroscopy and its stability was probed in basic condition using UV-Visible analysis. Furthermore, the molecular structure was confirmed by X-ray diffraction analysis. The compound crystallizes in orthorhombic Pna21 space group with unit cell parameters a = 14.9594 (15) Å, b = 25.711 (3) Å, c = 4.5004 (4) Å, V = 1731.0 (3) Å3 and Z = 4. The crystal packing of the title compound is stabilized by intermolecular hydrogen bond, π···π and C−H···π stacking interactions. The intermolecular interactions were furthermore analyzed through the mapping of different Hirshfeld surfaces. The two-dimensional fingerprint revealed that the most important contributions to these surfaces come from O···H (37.1%), H···H (24%) and H···C/C···H (22.6%) interactions. The interaction energies stabilizing the crystal packing were calculated and were presented graphically as framework energy diagrams. Finally, the energy-framework analysis reveals that π···π and C−H···π interactions energies are mainly dispersive and are the most important forces in the crystal.

The hydrolysis of 2-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide (2) during crystallization under humidity (85 %) conditions, lead to N-(2-(N-methylsulfamoyl)phenyl)formamide as second step hydrolysis product, identified in the proposed degradation mechanism. Crystal of N-(2-(N-methylsulfamoyl)phenyl)formamide C8H10N2O3S (4), was obtained and characterized. The molecular structure determination was carried out with MoKα X-ray and data measured at 100 K. The compound 4 crystallizes in triclinic P͞1 space group with unit cell parameters a = 4.8465(4) Å, b = 8.1942(9) Å, c = 11.8686(13) Å, α = 77.080(4)°, β = 82.069(4)°, γ = 80.648(4)°, V = 450.76 (8) Å3 and Z = 2. The crystal structure is stabilized by intramolecular N-H···O and intermolecular C-H···O and N-H···O hydrogen bonds that extended as infinite 1D chain along [100]. Stabilization is also ensured by oxygen-π stacking interaction between the aromatic ring and oxygen of the sulfonamide group. The analysis of intermolecular interactions through the mapping of dnorm and shape-index revel that the most significant contributions to the Hirshfeld surface 40.6 and 33.9% are from H···H and O···H contacts, respectively.

There is a growing interest in the use of natural compounds to tackle inflammatory diseases and cancers. However, most of them face the bioavailability and solubility challenges to reaching cellular compartments and exert their potential biological effects. Polyphenols belong to that class of molecules, and numerous efforts have been made to improve and overcome these problems. Curcumin is widely studied for its antioxidant and anti-inflammatory properties as well as its use as an anticancer agent. However, its poor solubility and bioavailability are often a source of concern with disappointing or unexpected results in cellular models or in vivo, which limits the clinical use of curcumin as such. Beside nanoparticles and liposomes, cyclodextrins are one of the best candidates to improve the solubility of these molecules. We have used lysine and cyclodextrin to form a water-soluble curcumin complex, named NDS27, in which potential anti-inflammatory effects were demonstrated in cellular and in vivo models. Herein, we investigated for the first time its direct free radicals scavenging activity on DPPH/ABTS assays as well as on hydroxyl, superoxide anion, and peroxyl radical species. The ability of NDS27 to quench singlet oxygen, produced by rose bengal photosensitization, was studied, as was the inhibiting effect on the enzyme-catalyzed oxidation of the co-substrate, luminol analog (L012), using horseradish peroxidase (HRP)/hydrogen peroxide (H₂O₂) system. Finally, docking was performed to study the behavior of NDS27 in the active site of the peroxidase enzyme.

Herein, nine square planar trans-arylbis(triphenylphosphine)palladium halides (PdX(PPh₃)₂Ar) were synthesized and fully characterized. The molecular structure of two complexes (1 and 2) have been determined by both X-ray diffraction and described thanks to Hirshfeld surface analysis. Investigation of the antioxidant activities showed that most of the complexes exhibit a strong dose-dependent radical scavenging activity towards DPPH radical as well as in the ABTS radical scavenging test. Complexes 1 [PdI(PPh₃)₂(4-MeOC₆H₄)] and 3 [PdCl(PPh₃)₂(4-MeOC₆H₄)] showed the highest activity in the DPPH assay with EC₅₀ values of 1.14 ± 0.90 and 1.9 ± 0.87 µM, respectively. In contrast, for the ABTS assay, quercetin (5.56 ± 0.97 µM) was slightly more efficient than the three complexes 1 (5.78 ± 0.98 µM), 2 (7.01 ± 0.98 µM), and 3 (11.12 ± 0.94 µM). The use of kinetic studies as a powerful parameter shows that complexes 1, 2, and 3 displayed the best antioxidant efficiency. The antioxidant effect of the nine palladium complexes has been also evaluated on the enzyme-catalyzed oxidation of the L012 probe (using HRP/H₂O₂) by using a chemiluminescence technique. As with the last model, complexes 1, 2, and 3 showed the best activity, with EC50 values of 3.56 ± 1.87, 148 0.71, and 5.8 ± 2.60 µM, respectively. Interestingly, those complexes (1, 2, and 3) even exhibited a higher dose-dependent activity than the quercetin (7.06 ± 2.56 µM) used as a standard. Taken together, the combined results reveal that the antiradical and enzyme (HRP) inhibitory activity of complexes decrease following the ligand order of p-OMePh > p-OAcPh >> Ph.

The title compound 3-(2,4,6-timethyl-phenylamino)-but-2-enoate was obtained by condensation reaction of ethyl acetoacetate and 2,4,6-trimethyl-phenylamine. X-ray structural analysis identified the structure of the synthetized β-enaminoester, NMR spectroscopy complemented it, and the structure stabilized by intramolecular interactions. The intermolecular contacts were further analysed by the mapping of contacts descriptors dnorm, de, di, the shape-by-Shape index and surface property by electrostatic potential mapped on the Hirshfeld surface (HS). Data from density functional theory (DFT) was compared to experimental results for this process. Global reactivity factors such electronegativity, chemical hardness, potential, and softness were calculated using DFT. The effects of the molecular environment were accessed by analysing the electrostatic potentials surface mapped over the HS and the 3D-topology of energy frameworks. As a potential bioactive molecule, the physicochemical and ADME-Tox predictions were performed suggesting that compound 3 could be considered as promising drug candidate.