Tautomerism and Rotamerism of Favipiravir and Halogenated Analogues in Solution and in the Solid State.

Favipiravir is an important selective antiviral against RNA-based viruses, and currently, it is being repurposed as a potential drug for the treatment of COVID-19. This type of chemical system presents different carboxamide-rotameric and hydroxyl-tautomeric states, which could be essential for interpreting its selective antiviral activity. Herein, the tautomeric 3-hydroxypyrazine/3-pyrazinone pair of favipiravir and its 6-substituted analogues, 6-Cl, 6-Br, 6-I, and 6-H, were fully investigated in solution and in the solid state through ultraviolet-visible, 1H nuclear magnetic resonance, infrared spectroscopy, and X-ray diffraction techniques. Also, a study of the gas phase was performed using density functional theory calculations. In general, the keto-enol balance in these 3-hydroxy-2-pyrazinecarboxamides is finely modulated by external and internal electrical variations via changes in solvent polarity or by replacement of substituents at position 6. The enol tautomer was prevalent in an apolar environment, whereas an increase in the level of the keto tautomer was favored by an increase in solvent polarity and, even moreso, with a strong hydrogen-donor solvent. Keto tautomerization was favored either in solution or in the solid state with a decrease in 6-substituent electronegativity as follows: H ≫ I ≈ Br > Cl ≥ F. Specific rotameric states based on carboxamide, "cisoide" and "transoide", were identified for the enol and keto tautomer, respectively; their rotamerism is dependent on the tautomerism and not the aggregation state.

Revealing the Elusive Structure and Reactivity of Iron Boride α-FeB.

Crystal structures can strongly deviate from bulk states when confined into nanodomains. These deviations may deeply affect properties and reactivity and then call for a close examination. In this work, we address the case where extended crystal defects spread through a whole solid and then yield an aperiodic structure and specific reactivity. We focus on iron boride, α-FeB, whose structure has not been elucidated yet, thus hindering the understanding of its properties. We synthesize the two known phases, α-FeB and ß-FeB, in molten salts at 600 and 1100 °C, respectively. The experimental X-ray diffraction (XRD) data cannot be satisfactorily accounted for by a periodic crystal structure. We then model the compound as a stochastic assembly of layers of two structure types. Refinement of the powder XRD pattern by considering the explicit scattering interference of the different layers allows quantitative evaluation of the size of these domains and of the stacking faults between them. We, therefore, demonstrate that α-FeB is an intergrowth of nanometer-thick slabs of two structure types, ß-FeB and CrB-type structures, in similar proportions. We finally discuss the implications of this novel structure on the reactivity of the material and its ability to perform insertion reactions by comparing the reactivities of α-FeB and ß-FeB as reagents in the synthesis of a model layered material: Fe2AlB2. Using synchrotron-based in situ X-ray diffraction, we elucidate the mechanisms of the formation of Fe2AlB2. We highlight the higher reactivity of the intergrowth α-FeB in agreement with structural relationships.

Novel complexes with ONNO tetradentate coumarin schiff-base donor ligands: x-ray structures, DFT calculations, molecular dynamics and potential anticarcinogenic activity.

The synthesis of eight novel Zn(II), Co(II), Cu(II), Ni(II) and Pt(II) complexes (2-9) derived from the ONNO tetradentate coumarin Schiff-Base donor ligands, L1 and the novel L2, was performed. All compounds were characterized by analytical, spectrometry and spectroscopy techniques. Complexes 2-4 were also characterized by DFT calculations and the structures of 5 and 6 were determined by single-crystal X-ray diffraction analysis. A cytotoxicity study was carried out through an MTT assay in the carcinogenic cell line HeLa and the noncarcinogenic cell lines HFF-1 and HaCaT. The results indicated that among all the evaluated compounds, 2 and 6 presented the best anticarcinogenic potential against HeLa cells with an IC50 of 3.5 and 4.1 µM, respectively. In addition, classical molecular dynamics simulations were performed on the synthesized coordination compounds bound to G4 DNA architectures in the scope of shedding light on their inhibition mode and the most conserved interactions that may lead to the biological activity of the compounds.

Bimetallic Trifluoroacetates as Precursors to Layered Perovskites A2MnF4 (A = K, Rb, and Cs).

Four novel alkali-manganese(II) trifluoroacetates were synthesized, and their potential as self-fluorinating precursors to layered perovskites A2MnF4 (A = K, Rb, and Cs) was demonstrated. Na2Mn(tfa)4, K4Mn2(tfa)8, Rb4Mn2(tfa)8·0.23H2O, and Cs3Mn2(tfa)7(tfaH) (tfa = CF3COO- and tfaH = CF3COOH) were grown as single crystals, and their crystal structures solved using X-ray diffraction. Chemically pure K4Mn2(tfa)8, Rb4Mn2(tfa)8·0.23H2O, and Cs3Mn2(tfa)7(tfaH) were also prepared in polycrystalline form as confirmed by thermal analysis and powder X-ray diffraction. Thermolysis of these powders yielded the isostructural series K2MnF4, Rb2MnF4, and Cs2MnF4 at low temperatures (≈200-300 °C). Trifluoromethyl groups belonging to the trifluoroacetato ligands served as the fluorine source, thereby eliminating the need for external fluorinating agents. K2MnF4 and Rb2MnF4 were obtained as single-phase powders, whereas Cs2MnF4 crystallized along with CsMnF3. Access to polycrystalline Cs2MnF4 coupled to Rietveld analysis enabled elucidation of the crystal structure of this ternary fluoride, which had remained elusive. Findings presented in this article expand the synthetic accessibility of polycrystalline A2MnF4 fluorides, for which a scarce number of routes is available in the literature.

Chemoenzymatic Total Synthesis and Structural Revision of Ampelomins B, D, E, and epi-Ampelomin B.

Enantioselective synthesis of ampelomin B and epi-ampelomin B, D, and E was accomplished starting from toluene, through a chemoenzymatic sequence, in which stereoselective hydrogenation, Mitsunobu reaction, and regio- and stereoselective nucleophilic opening of an epoxide were used as the main transformations. Structural revision and absolute configuration of the natural compounds were carried out.

Rubidium-Alkaline-Earth Trifluoroacetate Hybrids as Self-Fluorinating Single-Source Precursors to Mixed-Metal Fluorides.

Three novel bimetallic hybrid crystals featuring rubidium-alkaline-earth metal pairs and trifluoroacetato ligands were synthesized, and their utility as self-fluorinating single-source precursors to the corresponding mixed-metal fluorides was demonstrated. Rb2Mg2(tfa)6(tfaH)2·3H2O, RbCa(tfa)3, and RbSr2(tfa)5 (tfa = CF3COO-; tfaH = CF3COOH) were synthesized in both single-crystal and polycrystalline forms via solvent evaporation. Their crystal structures were solved using single-crystal X-ray diffraction (XRD), and chemical purity was confirmed using thermal analysis (TGA/DTA). Metal-oxygen-metal connectivity in Rb2Mg2(tfa)6(tfaH)2·3H2O was restricted to four-metal building blocks. In contrast, RbCa(tfa)3 and RbSr2(tfa)5 were found to be extended inorganic hybrids ( Cheetham et al. Chem. Commun. 2006 , 0 , 4780 - 4795 ) exhibiting infinite metal connectivity in three and two dimensions, respectively. Systematic analysis of the coordination modes of the trifluoroacetato ligand revealed its ability to bridge alkali and alkaline-earth metals. Rietveld analysis of powder X-ray diffraction data (PXRD) showed that thermal decomposition of Rb2Mg2(tfa)6(tfaH)2·3H2O and RbCa(tfa)3 under inert atmosphere yielded crystalline RbMgF3 and RbCaF3, respectively. This solid-state transformation occurred without the need for an external fluorinating agent because the trifluoromethyl group acted as a built-in fluorine source. Solid-state and solution thermolysis of Rb2Mg2(tfa)6(tfaH)2·3H2O provided access to the hexagonal and cubic polymorphs of the fluoroperovskite RbMgF3, respectively. Findings reported in this article highlight that bimetallic trifluoroacetates offer unique features from the standpoint of both crystal lattice topology and reactivity.

Inhibition of C. albicans Dimorphic Switch by Cobalt(II) Complexes with Ligands Derived from Pyrazoles and Dinitrobenzoate: Synthesis, Characterization and Biological Activity.

Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized and characterized. The single-crystal X-ray diffraction structure was determined for one of the ligands and one of the complexes. The analysis and spectral data showed that all the cobalt complexes had octahedral geometries, which was supported by DFT calculations. The complexes and their free ligands were evaluated against fungal strains of Candida albicans and emerging non-albicans species and epimastigotes of Trypanosoma cruzi. We obtained antifungal activity with a minimum inhibitory concentration (MIC) ranging from 31.3 to 250 µg mL-1. The complexes were more active against C. krusei, showing MIC values between 31.25 and 62.5 µg mL-1. In addition, some ligands (L1-L6) and complexes (5 and Co(OAc)2 · 4H2O) significantly reduced the yeast to hypha transition of C. albicans at 500 µg mL-1 (inhibition ranging from 30 to 54%). Finally, the complexes and ligands did not present trypanocidal activity and were not toxic to Vero cells. Our results suggest that complexes of cobalt(II) with ligands derived from pyrazoles and dinitrobenzoate may be an attractive alternative for the treatment of diseases caused by fungi, especially because they target one of the most important virulence factors of C. albicans.

General Method for the Synthesis of (-)-Conduritol C and Analogs from Chiral Cyclohexadienediol Scaffolds.

An efficient and facile general method for the synthesis of conduritol C analogs, taking advantage of an enantioselective biocatalysis process of monosubstituted benzenes, is described. The absolute stereochemical patterns of the target molecules (−)-conduritol C, (−)-bromo-conduritol C, and (−)-methyl-conduritol C were achieved by means of chemoenzymatic methods. The stereochemistry present at the homochiral cyclohexadiene-cis-1,2-diols derived from the arene biotransformation and the enantioselective ring opening of a non-isolated vinylepoxide derivative permitted the absolute configuration of the carbon bearing the hydroxyl groups at the target molecules to be established. All three conduritols and two intermediates were crystallized, and their structures were confirmed by X-ray diffraction. The three conduritols and intermediates were isostructural. The versatility of our methodology is noteworthy to expand the preparation of conduritol C analogs starting from toluene dioxygenase (TDO) monosubstituted arene substrates.

Bimetallic Trifluoroacetates as Single-Source Precursors for Alkali-Manganese Fluoroperovskites.

Alkali-manganese(II) trifluoroacetates were synthesized, and their potential as single-source precursors for the solid-state and solution-phase synthesis of AMnF3 fluoroperovskites (A = Na, K, Rb, Cs) was demonstrated. Crystals of Na2Mn2(tfa)6(tfaH), K2Mn2(tfa)6(tfaH)2·H2O, Rb2Mn2(tfa)6·H2O, and CsMn(tfa)3 (tfa = trifluoroacetato) were grown via solvent evaporation and their crystal structures solved using single-crystal X-ray diffraction (XRD). Chemical purity was confirmed using thermal analyses (TGA/DTA) and Rietveld analysis of powder XRD patterns. Thermal decomposition of Na2Mn2(tfa)6(tfaH), K2Mn2(tfa)6(tfaH)2·H2O, Rb2Mn2(tfa)6·H2O, and CsMn(tfa)3 in both the solid state and solution phase yielded crystalline, single-phase NaMnF3, KMnF3, RbMnF3, and CsMnF3 fluoroperovskites, respectively. Nanocrystals (<100 nm) and submicrocrystals (<500 nm) were obtained in a mixture of high-boiling-point organic solvents. Crystal structures of bimetallic trifluoroacetates displayed a variety of building blocks, coordination environments of the alkali atoms, and coordination modes of the trifluoroacetato ligand. Alkali-fluorine interactions ranging from chemical bonds to short contacts were observed throughout the series. The coordination flexibility of the trifluoroacetato ligand was attributed to the ability of the -CF3 groups to interact with alkali atoms over a broad range of distances. The synthetic approach described in this investigation provides a starting point to expand the library of fluorinated single-source precursors suitable for solution-phase routes to mixed-metal fluorides.

Open-Framework Structures of Anhydrous Sr(CF3COO)2 and Ba(CF3COO)2.

Anhydrous Sr(CF3COO)2 and Ba(CF3COO)2 open-framework structures featuring three-dimensional connectivity of metal-oxygen polyhedra were crystallized from a mixture of water and CF3COOH. Crystallization was induced via evaporation of the solvent mixture under a dry nitrogen flow. This approach differs from that routinely employed for crystallization of metal trifluoroacetates, which achieves solvent evaporation by heating under air and yields hydrated salts. Thermogravimetric and differential thermal analysis as well as single-crystal and synchrotron powder X-ray diffraction were employed to characterize the alkaline-earth trifluoroacetate products. Neither thermal analysis nor single-crystal X-ray diffraction detected the presence of crystallization water molecules, demonstrating these trifluoroacetates can be obtained in anhydrous form. Single-crystal X-ray diffraction studies showed that Sr(CF3COO)2 and Ba(CF3COO)2 are isostructural and crystallize in the rhombohedral R3̅ space group. Both compounds belong to the class of organic-inorganic extended hybrids and exhibit an open-framework structural motif with three-dimensional connectivity of the metal-oxygen polyhedra and one-dimensional channels along the c axis. The channels are decorated with the trifluoromethyl groups of the trifluoroacetate ligands, and their average (minimum) diameters are ∼3.75 (2.60) and 3.45 (2.25) Å for Sr(CF3COO)2 and Ba(CF3COO)2, respectively. This size range is comparable to the kinetic diameter of small molecules such as hydrogen (2.3 Å). Chemical substitution of barium for strontium affects not only the diameter of the channels but also the spatial arrangement of the trifluoromethyl groups within the channels and the coordination environment of the metal atoms. The different coordination requirements of the strontium and barium atoms are accommodated through the displacement of one of the two chemically distinct trifluoroacetate ligands relative to the metal center.

Structural disorder in AMoO4 (A = Ca, Sr, Ba) scheelite nanocrystals.

The crystal structure of sub-15 nm AMoO4 (A = Ca, Sr, Ba) scheelite nanocrystals has been investigated using a dual-space approach that combines Rietveld and pair distribution function (PDF) analysis of synchrotron X-ray diffraction data. Rietveld analysis yields an average crystal structure in which the Mo-O bond distance exhibits an anomalously large contraction (2.8%) upon chemical substitution of Ba(2+) for Ca(2+). Such a dependence on chemical composition contradicts the well-known rigid character of Mo(VI)-O bonds and the resulting rigidity of MoO4 tetrahedra in scheelites. Unlike Rietveld, PDF analysis yields a local crystal structure in which the Mo-O bond distance shows a negligible contraction (0.4%) upon going from Ba(2+) to Ca(2+) and, therefore, appears independent of the chemical composition. Analysis of the anisotropic displacement parameters of the oxygen atom reveals that the disagreement between the average and local structural models arises from the presence of static orientational disorder of the MoO4 tetrahedra. Rietveld analysis averages the random rotations of the MoO4 tetrahedra across the scheelite lattice yielding an apparent Mo-O bond distance that is shorter than the true bond distance. In contrast, PDF analysis demonstrates that the structural integrity of the MoO4 tetrahedra remains unchanged upon chemical substitution of the alkaline-earth cation, and that their orientational disorder is accommodated through geometric distortions of the AO8 dodecahedra.

Reactivity of bi- and monometallic trifluoroacetates towards amorphous SiO2.

The reactivity of alkali-manganese(II) and alkali trifluoroacetates towards amorphous SiO2 (a-SiO2) was studied in the solid-state. K4Mn2(tfa)8, Cs3Mn2(tfa)7(tfaH), KH(tfa)2, and CsH(tfa)2 (tfa = CF3COO-) were thermally decomposed under vacuum in fused quartz tubes. Three new bimetallic fluorotrifluoroacetates of formulas K4Mn3(tfa)9F, Cs4Mn3(tfa)9F, and K2Mn(tfa)3F were discovered upon thermolysis at 175 °C. K4Mn3(tfa)9F and Cs4Mn3(tfa)9F feature a triangular-bridged metal cluster of formula [Mn3(µ3-F)(µ2-tfa)6(tfa)3]4-. In the case of K2Mn(tfa)3F, fluoride serves as an inverse coordination center for the tetrahedral metal cluster K2Mn2(µ4-F). Fluorotrifluoroacetates may be regarded as intermediates in the transformation of bimetallic trifluoroacetates to fluoroperovskites KMnF3, CsMnF3, and Cs2MnF4, which crystallized between 250 and 600 °C. Decomposition of these trifluoroacetates also yielded alkali hexafluorosilicates K2SiF6 and Cs2SiF6 as a result of the fluorination of fused quartz. The ability to fluorinate fused quartz was observed for monometallic alkali trifluoroacetates as well. Hexafluorosilicates and heptafluorosilicates K3SiF7 and Cs3SiF7 were obtained upon thermolysis of KH(tfa)2 and CsH(tfa)2 between 200 and 400 °C. This ability was exploited to synthesize fluorosilicates under air by simply reacting alkali trifluoroacetates with a-SiO2 powder.

Expanding the synthetic toolbox to access pristine and rare-earth-doped BaFBr nanocrystals.

A new synthetic route to access pristine and rare-earth-doped BaFBr nanocrystals is described. Central to this route is an organic-inorganic hybrid precursor of formula Ba5(CF2BrCOO)10(H2O)7 that serves as a dual-halogen source. Thermolysis of this precursor in a mixture of high-boiling point organic solvents yields spherical BaFBr nanocrystals (≈20 nm in diameter). Yb:Er:BaFBr nanocuboids (≈26 nm in length) are obtained following the same route. Rare-earth-doped nanocrystals display NIR-to-visible photon upconversion under 980 nm excitation. The temperature-dependence of the green emission from Er3+ may be exploited for optical temperature sensing between 150 and 450 K, achieving a sensitivity of 1.1 × 10-2 K-1 and a mean calculated temperature of 300.9 ± 1.5 K at 300 K. The synthetic route presented herein not only enables access to unexplored upconverting materials but also, and more importantly, creates the opportunity to develop solution-processable photostimulable phosphors based on BaFBr.

Efficient Access to the Iboga Skeleton: Optimized Procedure to Obtain Voacangine from Voacanga africana Root Bark.

Iboga alkaloids are a group of monoterpenoid indole alkaloids with promising and intriguing biological activities. Ibogaine is the representative member of the series and has become widely known as a potent atypical psychedelic with promising effects to treat substance use disorder. Nowadays, an efficient and scalable enantioselective total synthesis of ibogaine and related iboga alkaloids is still lacking, so direct extraction from natural sources or semi-synthetic schemes are the methods of choice to obtain them in a preparative scale. In particular, ibogaine can be obtained either by a low yielding direct isolation from Tabernanthe iboga or using a semi-synthetic procedure from voacangine, an iboga alkaloid occurring in a higher yield in the root bark of Voacanga africana. In this work, we describe an optimized process to obtain voacangine from V. africana root bark as a precursor of the iboga scaffold. Using a direct acetone-based extraction procedure (0.5 kg of root bark), voacangine was isolated in ∼0.8% of root bark dried weight, while the major alkaloids isolated from the bark were identified as iboga-vobasinyl dimers (∼3.7%) such as voacamine and voacamidine. Since these alkaloids contain the voacangine moiety in their structure, the cleavage of the dimers was further optimized, affording an extra amount of voacangine in ∼50% isolated molar yield. In this manner, the total amount of voacangine obtained by application of the whole procedure to the plant material (extraction and dimer cleavage) could almost duplicate the content originally found in the root bark.

Absolute structure of (3aS,5S,7aS,7bS,9aR,10R,12aR,12bS)-7b-hy-droxy-4,4,7a,9a,12a-penta-methyl-10-[(2'R)-6-methyl-heptan-2-yl]-2,8,9-trioxo-octa-deca-hydro-benzo[d]indeno-[4,5-b]azepin-5-yl acetate from 62-year-old crystals.

The structure of the title compound, C32H51NO6, was determined from 62-year-old crystals at room temperature and refined with 100 K data in a monoclinic (C2) space group. This compound with a triterpenoid structure, now confirmed by this study, played an important role in the determination of the structure of lanosterol. The mol-ecules pack in linear O-H⋯O hydrogen-bonded chains along the short axis (b), while parallel chains display weak van der Waals inter-actions that explain the needle-shaped crystal morphology. The structure exhibits disorder of the flexible methyl-heptane chain at one end of the main mol-ecule with a small void around it. Crystals of the compounds were resistant to data collection for decades with the available cameras and Mo Kα radiation single-crystal diffractometer in our laboratory until a new instrument with Cu Kα radiation operating at 100 K allowed the structure to be solved and refined.

Crystal structure and Hirshfeld surface analysis of poly[tris-(µ4-benzene-1,4-di-carboxyl-ato)tetra-kis-(di-methyl-formamide)-trinickel(II)]: a two-dimensional coordination network.

The crystal structure of the title compound, [Ni3(C8H4O4)3(C3H7NO)4], is a two-dimensional coordination network formed by trinuclear linear Ni3(tp)3(DMF)4 units (tp = terephthalate = benzene-1,4-di-carboxyl-ate and DMF = di-methyl-formamide) displaying a characteristic coordination mode of acetate groups in polynuclear metal-organic compounds. Individual trinuclear units are connected through tp anions in a triangular network that forms layers. One of the DMF ligands points outwards and provides inter-actions with equivalent planes above and below, leaving the second ligand in a structural void much larger than the DMF mol-ecule, which shows positional disorder. Parallel planes are connected mainly through weak C-H⋯O, H⋯H and H⋯C inter-actions between DMF mol-ecules, as shown by Hirshfeld surface analysis.

Pt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cells.

Searching for a more effective chemotherapy for the treatment of Human African trypanosomiasis, the disease caused by the parasite Trypanosoma brucei, and cancer, in the current work five new [PtII(L)(dppf)](PF6) compounds, with HL = 8-hydroxyquinoline derivatives and dppf = 1,1'-bis(diphenylphosphino)ferrocene, were synthesized and fully characterized. Crystal structures of three compounds were solved by XRD. The compounds displayed fairly good activity against bloodstream T. brucei, with IC50 values in the submicromolar range (IC50: 0.14-0.93 µM), and good selectivity towards the pathogen (SI: 11 - 48) with respect to mammalian macrophages (cell line J774). Coordination to the {Pt-dppf} moiety led, in most cases, to an enhancement of the activity in respect to the bioactive ligands (11 to 41 fold). Cytotoxicity was assessed against wildtype (A2780) and cisplatin-resistance (A2780cisR) ovarian cancer cell lines. Four [PtII(L)(dppf)](PF6) compounds were more active (IC50: 1.2-4.4 µM) than cisplatin (IC50: 26.0 µM) on A2780 cells and showed far superior activity than the reference drug against A2780cisR cells. Platinum levels in A2780 cells showed poor correlation between cellular uptake and the cytotoxic activity. All the complexes interacted with DNA and the most active ones induced reactive oxygen species (ROS) formation which suggested that the mechanism of action for these complexes may be mediated by oxidative stress and interaction with DNA that could act as a potential molecular target for this type of complexes. Some complexes of this series could be considered new hits for the development of prospective agents against trypanosomatid parasites and ovarian cancer.

Room-Temperature Broadband Light Emission from Hybrid Lead Iodide Perovskite-Like Quantum Wells: Terahertz Spectroscopic Investigation of Metastable Defects.

The properties of mid-band-gap electronic states are central to the potential application of self-assembled, hybrid organic-inorganic perovskite-like quantum wells in optoelectronic technologies. We investigate broadband light emission from mid-band-gap states in fast-forming hybrid organic lead iodide quantum wells at room temperature. By comparing temperature- and intensity-dependent photoluminescence (PL) spectra emitted from butyl ammonium spaced inorganic layers, we propose that structural defects in a metastable material phase trap excitons and cause broadband light emission spanning wavelengths between 600 and 1000 nm. We use temperature-dependent terahertz time-domain spectroscopy to correlate changes in the subgap PL emission with changes in the chemical bonding of the inorganic octahedral layer. Our results provide new fundamental physical insights into the array of mechanisms capable of inducing broadband light emission from low-dimensional perovskite-like materials central to their application in future optoelectronic technologies and novel spectroscopic tools to characterize these states.

Crystal structure and Hirshfeld surface analysis of lapachol acetate 80 years after its first synthesis.

Lapachol acetate [systematic name: 3-(3-methyl-but-2-en-yl)-1,4-dioxonaph-thalen-2-yl acetate], C17H16O4, was prepared using a modified high-yield procedure and its crystal structure is reported for the first time 80 years after its first synthesis. The full spectroscopic characterization of the mol-ecule is reported. The mol-ecular conformation shows little difference with other lapachol derivatives and lapachol itself. The packing is directed by inter-molecular π-π and C-H⋯O inter-actions, as described by Hirshfeld surface analysis. The former inter-actions make the largest contributions to the total packing energy in a ratio of 2:1 with respect to the latter.

Four interpenetrating hydrogen-bonded three-dimensional networks in divanillin.

The crystal structure of divainillin (systematic name: 6,6'-dihydroxy-5,5'-dimethoxy-[1,1'-biphenyl]-3,3'-dicarbaldehyde), C16H14O6, was determined from laboratory powder X-ray diffraction data using the software EXPO2013 (direct methods) and WinPSSP (direct-space approach). Divanillin molecules crystallize in the orthorhombic space group Pba2 (No. 32), with two molecules per unit cell (Z' = 1/2). Each divanillin molecule, with twofold symmetry, is linked through strong alcohol-aldehyde hydrogen bonds to four equivalent molecules, defining a three-dimensional hydrogen-bonding network, with rings made up of six divanillin units (a diamond-like arrangement). Each molecule is also connected through π-π interactions to a translation-equivalent molecule along c. Four consecutive molecules stacked along [001] belong to four different three-dimensional hydrogen-bonding networks defining a quadruple array of interpenetrating networks. This complex hydrogen-bonding array is proposed as an explanation for the aging process experienced by divanillin powders.