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Ferro-ferri-katophorite (IMA2016–008), ideally Na(NaCa)(Fe2+4Fe3+)(Si7Al)O22(OH)2, was found as xenocrysts up to 3 cm long and replacement rims around aegirine–augite in silicocarbonatite dykes cropping out in the Sierra de Maz, La Rioja province, NW Argentina. Ferro-ferri-katophorite is black and has vitreous lustre and a pale green streak. The new mineral is brittle, with perfect {110} cleavage and has a Mohs hardness of 6. The measured density is 3.32(1) g/cm3. In plane-polarised light it is strongly pleochroic, X = light greenish brown, Y = dark greyish brown and Z = dark greyish olive green. Absorption (very strong) is Z > Y > X. The orientation is: Z ∥ b, and X forms a small angle with [001]. Ferro-ferri-katophorite is biaxial (–), with α = 1.688(3), β = 1.697(3), γ = 1.698(3) and 2V(calc) = 36.7°. It is monoclinic, space group C2/m, a = 9.8270(7), b = 18.0300(8), c = 5.316(4) Å, β = 104.626(4)°, V = 911.4(6) Å3 and Z = 2. The strongest five lines in the powder X-ray diffraction pattern [d in Å (I)(hkl)] are: 8.416(100)(110), 3.135(50)(310), 2.815(26)(330), 2.720(18)(151) and 1.4422(15)($\bar{6}$61). The chemical composition is SiO2 43.08, TiO2 2.76, ZrO2 0.15, Al2O3 8.76, V2O3 0.07, Fe2O3 9.28, FeO 13.85, MnO 0.43, MgO 6.88, CaO 6.58, ZnO 0.06, Na2O 5.55, K2O 1.18, Cl 0.01, H2O calc 1.36, total 99.95 wt.%. The formula unit (confirmed by single-crystal structural analysis) is (Na0.74K0.23)Σ0.97(Ca1.08Na0.91Mn0.01)Σ2.00(Fe2+1.78Mg1.57Fe3+1.07Ti4+0.32Al0.19Mn2+0.04Zr0.01V3+0.01Zn0.01)Σ5.00(Si6.61Al1.39)Σ8.00O22(OH1.59O0.61)Σ2.00. Aluminium is strongly ordered at the T(1) site. Ferro-ferri-katophorite is the 9th species carrying the katophorite root name and is related to katophorite by the Fe2+ + Fe3+ → Mg2+ + Al3+ substitution. Type material was deposited at the Museo de Mineralogía “Stelzner”, Universidad Nacional de Córdoba, Argentina, under catalogue number MS003341.

The application of halogen bonding in pharmaceutical chemistry remains a challenge. In this work, novel halogen-bonded cocrystals based on azole antifungal active pharmaceutical ingredients (APIs) and the ditopic molecule 1,4-diiodotetrafluorobenzene are reported. Their crystal structural features, spectroscopic properties, and thermal stability were studied. The components are bound through I···N from the triazole moieties present in all of the compounds. The molecular electrostatic potential (MEP) surfaces and quantum theory of atoms in molecules (QTAIM) calculations are used to rationalize the presence of hydrogen and halogen bonds in the resulting structures and their energetic analysis. The relative halogen bond ability of the different groups of voriconazole, fluconazole, and itraconazole was analyzed using MEP surfaces, demonstrating this approach to be an interesting tool to predict halogen-bonding preferences., This research was funded by the MICIU/AEI of Spain (project PID2020-115637GB-I00 FEDER funds and project PID2021-1245720B-C32). MB and EM are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019-917S)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents., Grants Fondecyt 1180565, 1201880, 11200677, and 3210559. ANID/FONDAP/15110019.

This contribution describes an updated synthetic route along with full characterization of [{CpFe}2-p-Ph’] with p-Ph’: p-Bis{2,3,4,5tetramethylcyclopentadienyl}benzene). The complex reported here was characterized by 1H and 13C NMR, elemental analysis, the X-ray crystal structure, and Mössbauer spectroscopy. From the crystallographic analysis, it was found that both {CpFe} fragments are coordinated to opposite sites of the p-Ph’ ligand. In addition, the analysis through of 1H and 13C NMR spectroscopy, confirm that the synthesis and yield of just one isomer of this compound., We gratefully acknowledge the financial support from FONDECYT grant 1210827 (C. M-V), the Scheduled Tribes Welfare Department, Government of Karnataka, India for a student fellowship (Y.D.) to pursue a research stay at the Pontificia Universidad Católica de Chile. The authors are grateful to Professors Juan Manuel Manriquez and Ivonne Chavez for their advice, Dr. Ignasi Mata from ICMAB-CSIC for assistance with Mössbauer experiments., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Six new multicomponent solids of 9-ethyladenine and oxalic acid have been detected and characterized. The salt screening has been performed by mechanochemical and solvent crystallization processes. Single crystals of the anhydrous salts in 1:1 and 2:1 nucleobase:coformer molar ratio were obtained by solution crystallization and elucidated by single-crystal X-ray analysis. The supramolecular interactions observed in these solids have been studied using density functional theory (DFT) calculations and characterized by the quantum theory of “atoms in molecules” (QTAIM) and the noncovalent interaction plot (NCIPlot) index methods. The energies of the H-bonding networks observed in the solid state of the anhydrous salts in 1:1 and 2:1 nucleobase:coformer are reported, disclosing the strong nature of the charge assisted NH···O hydrogen bonds and also the relative importance of ancillary C–H··O H-bonds., M.B. and E.M. are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019- 917S) and Generalitat de Catalunya (2017SGR1687). M.B.-O. thanks the Vice-Rector for Research and International Relations of the University of the Balearic Islands for the financial support in setting up the single-crystal X-ray diffraction facility. A.F. thanks the MICIU/AEI from Spain for financial support (Projects CTQ2017-85821-R and PID2020-115637GB-I00, Feder funds).

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied., M.B. and E.M. are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019-917S) and Generalitat de Catalunya (2017SGR1687). A.F. thanks the MICIU/AEI from Spain for financial support (Projects CTQ2017-85821-R and PID2020-115637GB-I00, Feder funds).

In this work, we describe the successful preparation of a series of cocrystals of the modified nucleobase 1-ethyluracil with different coformers in a 1:1 or 2:1 (nucleobase:coformer) ratio including urea (URE) or some compounds containing carboxylic and hydroxyl groups such as l-malic acid (MAL), l-tartaric acid (TAR), 2-hydroxybenzoic acid (SAL), 4-hydroxybenzoic acid (4HB), and 2,4-dihydroxybenzoic acid (DHB). The influence of the hydroxyl substituent on the alkyl chain for 1·TAR and 1·SAL cocrystals or the phenyl ring for 1·SAL, 1·4HB, and 1·DHB multicomponent solids was studied. All of the compounds were characterized by powder X-ray diffraction, FT-IR, and thermal methods. Moreover, for those whose single-crystal structures could be determined, computational studies were also performed to investigate the factors that may affect the cocrystal formation, the recurrent motifs, and the energies associated with the H-bonding interactions using DFT calculations and a combination of the quantum theory of atoms in molecules (QTAIM) and the noncovalent interaction index (NCIplot) computational tools., This work has been carried out through MINECO/FEDER grant ENE2015-63969. M.B. and E.M. are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019-917S) and the Generalitat de Catalunya (2017SGR1687). M.B.-O. thanks the Vice-Rector for Research and International Relations of the University of the Balearic Islands for financial support in setting up the single-crystal X-ray diffraction facility. A.F. thanks the MICIU/AEI from Spain for financial support (Project CTQ2017-85821-R, Feder funds).

Two novel organic-inorganic decavanadate materials with protonated amines were prepared from acidified aqueous solution and characterized by single crystal X-Ray diffraction, thermogravimetric analysis and IR spectroscopy. (C6N2H9)4[H2V10O28]·4H2O (I) and (C7H9NF)4[H2V10O28]·2H2O (II), were isolated in single-crystal form. For both compounds, the crystal packing is governed by the formation of various non-covalent intermolecular forces between decavanadate anions, organic cations and water molecules. For both compounds, Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to in the crystal packing for both compounds are from O⋅⋅⋅H/H⋅⋅⋅O and H⋅⋅⋅H bonds. Furthermore, topological study of weak non-covalent interactions properties was theoretically carried out using DFT. The determined HOMO and LUMO levels were to estimate the charge transfer within the structure. The photoluminescence properties and UV–Vis absorption spectra have also been investigated. Both (I) and (II) possess photoluminescence properties and produce blue and green emissions, respectively, upon irradiation with violet light., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Co-doped titanium dioxide was synthesized by doping with manganese (Mn) and cerium (Ce) through a sol-gel method for the degradation of diclofenac (DCF). The synthesized products were successfully characterized by X-ray diffraction (XRD), Raman spectroscopy, Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Nitrogen physisorption at 77 K, X-ray photoelectron spectroscopy (XPS), UV–Vis diffuse reflectance (UV-DRS), photoluminescence spectroscopy (PL) and total organic carbon (TOC). It was shown that co-doping increased the specific surface area, improved the visible light absorption and extended the lifetime of photogenerated charge carriers. Furthermore, the results of the photocatalytic experiments show that the photodegradation rate of diclofenac can be approached by pseudo first-order kinetics and it followed the Langmuir-Hinshelwood model very well. The co-doped catalyst with 0.6% Mn and 1% Ce molar ratios appeared to be the most photoactive catalyst with 94% of DCF removal and an apparent rate constant of 0.012 min−1.

The high yield synthesis, characterization and biological trials of a family of compounds containing the pyrazole core (E)-3,5-dimethyl-1-(4-R-phenyl)-4-(phenyldiazenyl)-1H-pyrazoles (with R = 4-CH3O (1), 4-CH3 (2), 4-H (3), 4-F (4), 4-Cl (5), 4-CF3 (6), 4-CN (7), 4-NO2 (8), 3-Cl (9), 3-NO2 (10), 2-Cl (11) and C6F5 (12)) are reported. Hammett correlations were found for the experimental and theoretical computed data, showing the dependence of all the obtained results on the donor or acceptor nature of the R substituent. In this sense, the absorption wavelength does decrease as the electron-withdrawing character of the substituent increases. Furthermore, the wavelength intensity does follow a Hammett correlation with the sigma donor character of the substituents. The compounds were characterized using MP, EA, UV–vis, FT-IR, 1H NMR, 13C NMR including bidimensional NMR experiments (HMBC and HMQC). The structures of 4, 5 and 8 were successfully elucidated by means of X-Ray diffraction. Pyrazole based dyes are known in pharmacological areas. Therefore, biological activity of all these structures were tested against cancer cell lines over a wide library of cell lines (60), including leukemia, colon and brain cancer, showing that the compounds have anticancer activity, which expands the knowledge of this kind of dyes as targets for this critical application. Finally, quantum calculations were carried out in order to give a rational explanation to the observed UV–vis absorption bands and FT-IR signals. As shown, it is possible to tune the molecular/electronic structure of the synthesized dyes by means of changing the R substituent in the structure.

Recent findings unveil the pharmacological modulation of imidazoline I

This contribution describes an updated synthetic route to 3,6-dihydro-as-indacene along with full characterization of all inter­mediates. The title compound is prepared by Mannich condensation of 2-methylfuran with formaldehyde and dimethylamine hydrochloride, quaternization of the resulting amine with methyl iodide, and conversion into the ammonium hydroxide salt by treatment with silver oxide in water. Subsequent Hoffmann elimination and [6,6]-cycloaddition through pyrolysis produces a furanocyclophane, which after photooxidation, intramolecular cycloaddition, and dehydration with sodium carbonate affords 2,3,6,7-tetrahydro-1,8-dione-as-indacene. Reduction of this diketone gives a mixture of alcohols, which after dehydration under slightly basic or acidic conditions produces 3,6-dihydro-as-indacene. The structure is confirmed by X-ray diffraction, and all intermediates are characterized by means of 1H and 13C NMR spectroscopy., The authors are grateful for the financial support from Fondo Nacional de Desarrollo Cientifico y Tecnologico, Chile (FONDECYT) (Grants 1161297, EQM120021, EQM130032, EQM150102), the Pontificia Universidad Catolica de Chile (PUC) (Grant 3913-541-81), the Scheduled Tribes Welfare Department, Government of Karnataka, India for a student fellowship (Y.D.) to pursue a research stay at the Pontificia Uni-versidad Catolica de Chile. E.M. (ICMAB) acknowledges the Severo Ochoa Program, Ministerio de Economia y Competitividad (MINECO) (SEV-2015-0496).

I2 receptors (I2-IR) are widely distributed in the central nervous system. I2-IR ligands are associated with a neuroprotective effect but, as I2-IR structure remains unknown, the discovery of better and more selective ligands is necessary to understand the pharmacological and molecular implications of I2-IR. Recently, we described a new imidazoline-structure family which showed high affinity and selectivity for I2-IR. In vivo studies in mice indicated a neuroprotective role and revealed beneficial effects in behaviour and cognition with a murine model of neurodegeneration, senescence-accelerated prone mouse (SAMP8). Herein, we report a novel non-imidazoline-structure of bicyclic α-iminophosphonates family with high affinities for I2-IR. In vivo studies in 5X-FAD mice (a transgenic representative model of AD) and SAMP8 mice (a model of neurodegeneration linked to aging) showed an improvement in behaviour and cognition, a reduction of AD hallmarks and of neuroinflammation markers for the mice treated with the lead compound B06. After evaluating several pathways associated with neurodegeneration, we demonstrated that CaN pathway plays a critical role on the neuroprotective effects of I2-IR ligands on SAMP8 mice model. To rule out warnings of the novel family, we calculated DMPK and physicochemical properties for the novel bicyclic α-iminophosphonates. As well, we carried out drug metabolism, safety studies and in vivo pharmacokinetics for lead compound B06. In summary, we present a novel family of I2-IR ligands, its effectiveness in in vivo models and the possible neuroprotective molecular mechanism mediated by them. This highlights that the modulation of I2-IR by bicyclic α-iminophosphonates may open a new therapeutic venue for unmet neurodegenerative conditions.

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared., This research was funded by MICIU/FEDER, Spain (RTI2018-093974-B-I00).

Gastric cancer is one of the deadliest cancers in modern societies, so there is a high level of interest in discovering new drugs for this malignancy. Previously, we demonstrated the ability of tryptophanol-derived polycyclic compounds to activate the tumor suppressor protein p53, a relevant therapeutic target in cancer. In this work, we developed a novel series of enantiomerically pure tryptophanol-derived small molecules to target human gastric adenocarcinoma (AGS) cells. From an initial screening of fourteen compounds in AGS cell line, a hit compound was selected for optimization, leading to two derivatives selective for AGS gastric cells over other types of cancer cells (MDA-MB-231, A-549, DU-145, and MG-63). More importantly, the compounds were non-toxic in normal cells (HEK 293T). Additionally, we show that the growth inhibition of AGS cells induced by these compounds is mediated by apoptosis. Stability studies in human plasma and human liver microsomes indicate that the compounds are stable, and that the major metabolic transformations of these molecules are mono- and di-hydroxylation of the indole ring., This research was funded by FCT (Fundação para a Ciência e a Tecnologia) through iMed.ULisboa (UIDB/04138/2020), CQE (UID/QUI/00100/2020), project PTDC/QUI-QOR/29664/ 2017, principal investigator grants CEECIND/02001/2017 (A. M. M. Antunes), and CEECIND/03143/ 2017 (L. M. Gonçalves), and PhD fellowships SFRH/BD/117931/2016 (M. Espadinha) and PD/BD/ 143126/2019 (V. Barcherini), and funded by Severo Ochoa FunFuture CEX2019-917-S.

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared.

Lactose intolerance is a pathology caused by lactase enzyme deficiency, usually produced in the intestinal cells provoking symptoms as abdominal pain, bloating, diarrhea, gas and nausea. Gaxilose, 4-O-β-D galactopyranosyl-d-xylose, is used as a diagnostic drug for a non-invasive method for hypolactasia diagnosis. To date, no definitive guide for identifying gaxilose and distinguishing between crystalline forms is available. Data have been collected from a number of different analytical techniques in order to provide a full characterization of the compound and a simple method to discriminate between two solid forms., E. Molins and M. Benito thank to Severo Ochoa FunFuture project (MICINN, CEX2019-917S) and Generalitat de Catalunya (2017SGR1687).

Gold and silver nanoparticles were synthesized via mild alkoxide reduction of Ag+ and AuCl4- in water, under alkaline conditions. Three non-toxic polyols (glycerin, β-cyclodextrin (βCD), and a polymer (of β-cyclodextrin)) were employed in each case as reducing and capping agent. TEM analysis revealed larger nanoparticles when glycerin was used, followed by β-cyclodextrin, and finally by the polymer. Different numbers of population maxima in nanoparticles size distribution from one alkoxide to another were observed and such variation was dependent on alkoxide’s structure complexity. In UV–Vis spectra the typical bands for gold and silver nanoparticles were detected. ζ-potential measurements showed more electrostatically stable capping layer for glycerin and βCD. For the polymer, the stability of the layer should be a result of bulk effects. On the other hand, Ag-Au bi-metallic nanoparticles with core–shell structure were obtained using glycerin and β-cyclodextrin, whereas a mixture of gold and silver nanoparticles was the result with the polymer. The latter was corroborated via TEM images, EDX, UV–Vis, ζ-potential, and DLS measurements. A systematic study was carried out to elucidate the influence of the different alkoxide molecules on the properties of the resulting nanoparticles., Financial support by FONDECYT 3160144, 1201880, 1180565, ANID/FONDAP/15110019, and CONICYT doctoral fellowship number 21160394 grants is acknowledged. Millennium Science Initiative of the Ministry of Economy, Development and Tourism-Chile grant Nuclei on Catalytic Processes towards Sustainable Chemistry (CSC) is also acknowledged. ICMAB thanks the Severo Ochoa Program (MINECO, SEV- 2015-0496) Ministerio de Ciencia y Competitividad, Grant ENE2015-63969.

The synthesis and characterization of the full family of 11 pyrazoles were performed by means of UV–Vis, FTIR, 1H NMR, 13C NMR, two-dimensional NMR experiments and DFT simulations. As pyrazoles are known for showing diverse biological actions, they were also tested in the NCI-60 cancer cell line panel, showing moderate to good activity against different cell lines. Furthermore, the anti-proinflammatory activity test of a set of pyrazoles of the form (E)-4-((4-bromophenyl)diazenyl)-3,5-dimethyl-1-R-phenyl-1H-pyrazole was performed, this is based on the study of the blockage of the increase in intracellular [Ca2+] observed in response to platelet-activating factor (PAF) treatment of four pyrazoles (i.e. 6, 8, 9 and 10), which successfully displayed [Ca2+] channel inhibition. Therefore, the obtained intracellular [Ca2+] signal results indicate that the pyrazole family characterized in this study, in particular compounds 6 and 10, are potent blockers of the PAF-initiated Ca2+ signaling that mediates the hyperpermeability typically observed during the development of inflammation., FONDECYT 1201880, 1171118, 1180565. Millennium Science Initiative of the Ministry of Economy, Development and Tourism, Chile, grant Nuclei on Catalytic Processes towards Sustainable Chemistry (CSC). ANID/FONDAP/15110019. Universidad del Atlántico (primera convocatoria interna, que otorga apoyo económico para el desarrollo de trabajos de grado en investigación formativa – nivel pregrado y postgrado).

We report the synthesis and theoretical study of two new colorimetric chemosensors with special selectivity and sensitivity to Ni

Imidazoline I

The reaction of adenine with 2-chloropyrimidine yields as a major product the unexpected N7-(2-pyrimidyl)-adenine (1) and as a minor one N9-(2-pyrimidyl)-adenine (2). Both compounds have been characterized by X-ray diffraction analysis. Moreover, we report the formation of a 1:1 co-crystal (3) composed by compound (1) and adenine that was formed serendipitously during the synthesis of (1). Unexpectedly, the treatment of (1) with Brönsted acids like HCl or HNO3 causes the opening of the imidazole ring of the N7-substituted adenine, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine (4–7) which we have X-ray characterized in its neutral, (4), monoprotonated [nitrate salt (6)] and diprotonated forms [hydrochloride salt (5) and, also, a tetrachlorozincate salt (7)]. Finally, we have used compound (5) as ligand to synthesize and X-ray characterize its complexes with Ir(III) and Ag(I) (compounds (8) and (9), respectively), where the latter is a 2D coordination polymer and the former is a discrete mononuclear complex. We have studied the supramolecular assemblies formed in the solid state by using density functional theory (DFT) calculations. Finally, DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA., We thank the MINECO/AEI from Spain for financial support (project numbers CTQ2017-85821-R, ENE2015-63969-C3-3-R, BIO2016-78057-R and SEV2015-0496, FEDER funds and CTQ2017-90802-REDT). We also thank the Direcció General de Recerca i Innovació del Govern Balear (AAEE039/2017) for funding. We thank the CTI (UIB) for computational facilities and allocation of computer time. We thank the Vice-Rector for Research and International Relations of the University of the Balearic Islands for the financial support in setting up the single-crystal X-ray diffraction facility.

N-Methyl-D-aspartate receptors (NMDARs) are crucial for the normal function of the central nervous system (CNS), and fundamental in memory and learning-related processes. The overactivation of these receptors is associated with numerous neurodegenerative and psychiatric disorders. Therefore, NMDAR is considered a relevant therapeutic target for many CNS disorders. Herein, we report the synthesis and pharmacological evaluation of a new scaffold with antagonistic activity for NMDAR. Specifically, a chemical library of eighteen 1-aminoindan-2-ol tetracyclic lactams was synthesized and screened as NMDAR antagonists. The compounds were obtained by chiral pool synthesis using enantiomerically pure 1-aminoindan-2-ols as chiral inductors, and their stereochemistry was proven by X-ray crystallographic analysis of two target compounds. Most compounds reveal NMDAR antagonism, and eleven compounds display IC values in a Ca entry-sensitive fluo-4 assay in the same order of magnitude of memantine, a clinically approved NMDAR antagonist. Docking studies suggest that the novel compounds can act as NMDAR channel blockers since there is a compatible conformation with MK-801 co-crystallized with NMDAR channel. In addition, we show that the tetracyclic 1-aminoindan-2-ol derivatives are brain permeable and non-toxic, and we identify promising hits for further optimization as modulators of the NMDAR function., This work was supported by FCT (Fundaç~ao para a Ci^encia e a Tecnologia, I.P.) through iMed.ULisboa (UID/DTP/04138/2019), Principal Researcher grant CEECIND/01772/2017 (M. M. M. Santos), and PhD fellowships SFRH/BD/117931/2016 (M. Espadinha) and SFRH/BD/121664/2016 (R. Lopes). Financial support from FCT and Portugal 2020 to the Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa e RNEM; LISBOA-01-0145- FEDER-402-022125) is also acknowledged. M.I.R.-F. thanks funding from the Spanish Ministry of Science, Innovation and Universities (grant RTI2018-093955-B-C21) and the technical assistance of Ms. Cristina Tortosa (European contract for young professionals). C.d.l.R. thanks funding from Instituto de Salud Carlos III, Madrid, Spain (grant PI16/01041 and PhD fellowship FI17/00079 for L. Viejo).

In this work, we report extensive experimental and theoretical investigations on a new series of PbII coordination polymers exhibiting extended supramolecular architectures, namely [Pb2(LI)(NCS)4]n (1), [Pb(HLII)I2]n (2), [Pb(LIII)I]n (3) and [Pb(HLIV)(NO3)2]n·nMeOH (4), which were self-assembled from different PbII salts and various pyridine-hydrazine based linkers, namely 1,2-bis(pyridin-3-ylmethylene)hydrazine (LI), (pyridin-4-ylmethylene)isonicotinohydrazide (HLII), 1-(pyridin-2-yl)ethylidenenicotinohydrazide (HLIII) and phenyl(pyridin-2-yl)methylenenicotinohydrazide (HLIV), respectively. It is recognized that the origin of self-assembling is fundamentally rooted in a dual donor (6s2/6p0 hybridized lone electron pair) and electrophilic behaviour of PbII. This allows production of extended topologies from a 1D polymeric chain in 4 through a 2D layer in 2 to the 3D frameworks in 1 and 3, predominantly due to the cooperative action of both covalent and non-covalent tetrel interactions of the overall type Pb–X (X = O, N, S, I). Counterintuitively, the latter, seemingly weak interactions, have appeared to be even stronger than the typical covalent bonds due to the presence of a bunch of supportive London dispersion dominated contacts: π⋯π, Lp⋯π, C–H⋯O, C–H⋯I, C–H⋯H–C as well as more typical mainly electrostatically driven N–H⋯O or N/O–H⋯O hydrogen bonds. It is revealed that the constituting generally strong tetrel type Pb–X (X = O, N, S, I) bonds, though dominated by a classic Coulomb term, are therefore characterized by a very important London dispersion constituent, extremely strong relativistic effects and the two way dative-covalent Pb ↔ X electron charge delocalization contribution as revealed by the Extended Transition State Natural Orbital for Chemical Valence (ETS-NOCV) charge and energy decomposition scheme. It unravels that the pyridine-hydrazine linkers are also excellent London dispersion donors, and that together with the donor–acceptor properties of the heavy (relativistic) PbII atoms and nucleophilic counterions lead to extended self-assembling of 1–4., We are grateful to the University of Maragheh for the financial support of this research. The publication has been prepared with the support from the “RUDN University Program 5-100” (recipient F. I. Zubkov, synthesis of the ligands). DFT calculations were partially performed using the PL-Grid Infrastructure and resources provided by the ACC Cyfronet AGH (Cracow, Poland). A. M. Kirillov acknowledges the FCT and Portugal 2020 (LISBOA-01-0145-FEDER-029697 and UIDB/00100/2020). ICMAB acknowledges the Severo Ochoa Program (MINECO, SEV-2015-0496). M. P. Mitoraj acknowledges the financial support from the Polish National Science Center within the Sonata Bis Project 2017/26/E/ST4/00104.

We report the synthesis and theoretical study of two new colorimetric chemosensors with special selectivity and sensitivity to Ni2+ and Cu2+ ions over other metal cations in the CH3CN/H2O solution. Compounds (E)-4-((2-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (A) and (E)-4-((3-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (B) exhibited a drastic color change from yellow to colorless, which allows the detection of the mentioned metal cations through different techniques. The interaction of sensors with these metal ions induced a new absorption band with a hypsochromic shift to the characteristic signal of the free sensors. A theoretical study via time-dependent density functional theory (TD-DFT) was performed. This method has enabled us to reproduce the hypsochromic shift in the maximum UV–vis absorption band and explain the selective sensing of the ions. For all of the systems studied, the absorption band is characterized by a π → π* transition centered in the ligand. Instead of Ni2+ and Cu2+ ions, the transition is set toward the σ* molecular orbital with a strong contribution of the 3dx2-y2 transition (π → 3dx2-y2). These absorptions imply a ligand-to-metal charge transfer (LMCT) mechanism that results in the hypsochromic shift in the absorption band of these systems., This work was supported by CONICYT-Chile under FONDECYT-Chile project nos. 1201880, 1180565, and 1180017; PIA CCTEAFB170007; and FONDEQUIP EQM 160070. This work was also supported by ANID/FONDAP/15110019, and the Millennium Science Initiative of the Ministry of Economy, Development and Tourism, Chile, grant Nuclei on Catalytic Processes towards Sustainable Chemistry (CSC). SEV2015-0496.

Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure−activity relationship (3D-QSAR) studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer’s disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer’s disease. Therefore, bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions., We strongly acknowledge the advice of Dr Andrés G. Fernández (our mentor in the CaixaImpulse 2018 program) for unvaluable advice. This study was supported by the Ministerio de Economía y Competitividad of Spain (SAF2016-3307) and the Basque Government (IT1211- 19). The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434) under agreement CI18-00002. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union’s Horizon 2020 research and innovation programme. C.G.-F, F. V., C. E., S. R-A., A. B. and M. P. belong to 2017SGR106 (Generalitat de Catalunya). J. A. G.-S. is a member emeritus of the Institut d’Estudis Catalans. Financial support was provided for F. V. (University of Barcelona, APIF_2017), S. R.-A. (Generalitat de Catalunya, 2018FI_B_00227), A. B. (Institute of Biomedicine UB_2018), C. M. (Marie Sklodowska-Curie Actions Individual Fellowships H2020-MSCA-IF-2016, ID747487), and E. H.-H. (Consejería de Innovación, Investigación y Turismo del Gobierno de las Islas Baleares y del Fondo Social Europeo, FPI/2102/2018). MR, TD and KN kindly acknowledge Ministry of Science and Technological Development of the Republic of Serbia, Project Contract No. 172033, and HORISON2020- COST-Action CA18133 ERNEST: European Research Network on Signal Transduction.

Plasmonic nanoparticles, especially gold ones, have been widely employed as photosensitizers in photoelectrovoltaic or photocatalytic systems. To improve the system’s performance, a greater interaction of the nanoparticles with the semiconductor, generally TiO2, is desired. Moreover, this performance is enhanced when an efficient covering of TiO2 surface by the sensitizer is achieved. The Brust-Schiffrin-like methods are of the most employed approaches for nanoparticles synthesis. In a traditional approach, the reduction of the gold precursor is performed in the presence of a stabilizer (typically a thiol molecule) free in solution. A second step in which the obtained nanoparticles are anchored to the semiconductor surface is necessary in the case of photosensitive applications. Drawbacks like steric hindrance turn more difficult the covering of the semiconductor’s surface by nanoparticles. In this paper, we report a variation of this methodology, where the linker is previously anchored to the TiO2 nanopa...

A short synthesis of an enantiopure pyrrolobenzodiazepine (PBD) dilactam featuring early installation of the C2-C3 unsaturation is reported. An enantioselective cooperative catalytic cascade followed by self-disproportionation of enantiomers via sublimation afforded the enantiopure 2,3-dihydro-1H-pyrrole key intermediate, 1. N-Acylation followed by reduction and lactam formation furnished the PBD dilactam.

High surface area titania lyogels have been prepared, thermally transformed into TiO2 polymorphs at 400–850 °C, and decorated by ball milling with preformed Au nanoparticles of ca. 2 nm to ensure the same contact points at the metal–support interphase. The best performance in the photogeneration of hydrogen from gaseous water–ethanol under dynamic conditions in a fixed bed reactor has been obtained with the lyogel calcined at 550 °C, with a hydrogen photoproduction rate of 19.8 mmol H2 g−1 h−1 under an irradiance of 80 mW cm−2 and GHSV = 26 000 h−1. This photocatalyst contains 84% anatase and 16% rutile polymorphs, very similar to the standard P25. A series of photocatalysts prepared by lyophilization of a mixture of the titania gel and the preformed Au nanoparticles and calcination under the same conditions has resulted in samples with Au nanoparticles up to 18 nm strongly interacting with TiO2. The presence of Au nanoparticles in the composite lyogel has strongly retarded the transformation of anatase into rutile. The results have shown that the TiO2 polymorph has a greater influence than the Au nanoparticle size on the photoproduction of hydrogen.

Nitrogen compounds are widely investigated due to their pharmacological properties such as antihypertensive, antinociceptive, antibacterial, antifungal, analgesic, anticancer and inhibition activities and lately even as pesticide. In this context, we present the synthesis of new compounds: (E)-6-(3,4-dimethoxyphenyl)-3-(3-(3,4-dimethoxyphenyl)acryloyl)-1-(4-R-phenyl)- 5,6-dihydropyridazin-4(1H)-one (with R = H(1), -Cl(2), -Br(3), I(4) and COOH(5)) that was carried out by reaction of (1E, 6E)-1,7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione with a substituted phenylamine with general formula p-R-C6H4 NH2 (R = H (1), Cl (2), -Br(3), I(4) and COOH(5)). This is the first synthesis report of a pyridazinone using as precursors a curcuminoid derivative and a diazonium salt formed in situ. All compounds were characterized by EA, FT-IR, UV–Vis, Emission,1H- and13C-NMR spectroscopy and the crystalline and molecular structure of 4 was solved by X-rays diffraction method. DFT and TD-DFT quantum chemical calculations were also employed to characterize the compounds and provide a rational explanation to the spectroscopic properties. To assess the biological activity of the systems, we focused on pesticide tests on compound 2, which showed an inhibitory effect in plant growth of Agrostis tenuis Higland.

The methyl-substituted Nazarov reagent 4 stereoselectively reacts with Nind-Boc indoloquinolizidine lactams to give the expected H-3/H-15 cis pentacyclic yohimbine-type adducts when using DBU as the base. However, a dramatic change of the facial selectivity was observed when the reaction was performed in the presence of Cs2CO3, leading to the corresponding trans adducts. This annulation is the key step of an stereocontrolled synthesis of the 17a-carba-analog of the heteroyohimbine alkaloid akuammigine. Theoretical calculations were used to rationalize the facial selectivity of these double Michael addition reactions.

The fac-[Re(CO)3(4,4′-dimethyl-2,2′-bpy)L]PF6 (C2) complex have been recently reported as a useful fluorophore for walled cells (yeasts and bacteria) without the need of antibodies. In the present work, we report the structural parameters of the C2 complex, where L is an ancillary ligand E-2-((3-amino-pyridin-4-ylimino)-methyl)-4,6-di-tert-butylphenol, which presents an intramolecular hydrogen bond (IHB). The C2 crystals were obtained by slow evaporation of a dichloromethane solution, yielding yellow blocks. The crystal structure solution of the complex C2 showed a monoclinic crystal system and discrete organometallic cations and PF6 − as the counter ion, with partially occupation of solvent molecules (CH2Cl2). The complex C2 having a fac-geometry of the three carbonyl ligands, possesses the following bond distances Re–C(CO): Re1–C24, 1.87(8) A; Re1–C25, 1.58(12) A and Re1–C26, 1.90(8) A. The distorted octahedral geometry observed in the C2 structure is due to the C(CO)–Re1–N1(imine) angle for the three carbonyls that are significantly different. The Re–N1 bond distance of 2.16(4) A corresponds to the nitrogen coordination of the pyridine fragment of the ancillary ligand L, completing the octahedral geometry. Here we complement the C2 descriptions due to the considerable biological interest of its use as d6 metal fluorophore in walled cells (i.e., yeast and bacteria). DFT calculations were performed including scalar and spin–orbit (SO) relativistic effects with agree often reasonably well with experimental X-ray data. Through frequency calculations we estimated the strength of the intramolecular hydrogen bond (with a OH···N distance of 2.621 A) accounting for near 40 kcal/mol, indicating that is a strong hydrogen bond which contributes to the molecular stability. In addition, we observed the L electron-withdrawing effect on the rhenium core. The agreement between the observed and computed bond distances and angles brings confidence on the choice of the computed models and level of theory. These kind of Rhenium (I) complexes designed to develop novel fluorophores suitable for biological applications.

Stereoconvergent cyclocondensation reactions of (R)- or (S)-phenylglycinol with appropriately substituted cyclohexanone-based δ-keto esters are the key steps of short synthetic routes to enantiopure 5-, 7-, and 5,7-substituted cis-decahydroquinolines. The factors governing the stereoselectivity of the cyclocondensation are discussed. The potential of the methodology is illustrated by a protecting-group-free synthesis of the phlegmarine-type Lycopodium alkaloid (-)-cermizine B.

A new series of cadmium(II) and zinc(II) coordination polymers, formulated as {[Cd1.5(μ-L)(μ-CH3COO)(μ-N3)(CH3OH)]·3CH3OH}n (1), {[Zn(μ-L)Br]·CH3OH}n (2), {[Zn(μ-L)I]·CH3OH}n (3), {[Zn(μ-L)(N3)]·C2H5OH}n (4), and [Zn2(μ-L)2(μ-N3)2]n (5), was self-assembled from the metal(II) acetates (or nitrates), a multifunctional pyridine-hydrazone building block {HL = 2-benzoylpyridine-isonicotinoylhydrazone}, and auxiliary ligands selected from NaN3, KBr, or KI. All products 1–5 were isolated as stable crystalline solids and were fully characterized by elemental analysis, IR spectroscopy, and single-crystal X-ray diffraction. Although in all compounds the pyridine-hydrazone blocks L1− simultaneously act as μ-spacers and N2,O-chelators (adopting the enolic = N N C O form), the structures of 1–5 are modulated by the type of an auxiliary ligand and thus vary from ladder-like double chains in 1 and zigzag 1D chains in 2–4 to intricate 2D layers in 5. Topological analysis of the underlying metal-organic networks revealed the 2C1 (in 2–4) and hcb (in 5) topologies, while a decorated ladder was identified in 1. Besides, the structure of 1 revealed an interesting example of cyclic hexameric (CH3OH)6 clusters formed by H-bonding interactions between adjacent methanol molecules of crystallization. The role of hydrogen bonds, π⋯π interactions, and presence of solvent molecules of crystallization was analyzed from the structural data and by Hirshfeld surface analysis.

Photocatalytic performance is highly dependent on the nature and dispersion of the active sites, playing a crucial role in the optoelectronic and charge-transfer processes. Here, we report stabilized isolated iron on MCM-41 as a highly active catalyst for a photoredox reaction. The unique nature of the single-atom centers exhibit a trichloroethylene conversion per iron site that is almost 5 times higher than that of TiO2. Advanced characterization and theoretical calculations indicate the generation of hydroxyl radicals, through a photoinduced ligand-to-metal charge-transfer mechanism, which act as hole scavengers that lead to the formation of intermediate oxo–iron species (Fe═O). This intermediate species is the key step in promoting the photocatalytic reactions. Understanding the mechanistic photoredox pathway in isolated active site materials is imperative for developing highly efficient nonprecious photocatalysts for environmental or energy applications.

The synthesis of a metalled double-helix containing exclusively silver-mediated C*-C* base pairs is reported herein (C* = N1hexylcytosine). Remarkably, it is the first crystal structure containing infinite and consecutive C*-AgI-C* base pairs that form a double helix. The AgI ion occupies the center between two C* residues with N(3)-Ag bond distances of 2.1 A and short AgI-AgI distances (3.1 A) suggesting an interesting argentophilic attraction as a stabilization source of the helical disposition. The solid state structure is further stabilized by metal-mediated base-pairs, hydrogen bonding and π-stacking interactions. Moreover, the angle N(3)-Ag-N(3) is almost linear in the [Ag(N1hexylcytosine)2]+ motif and the bases are not coplanar thus generating a double strand helical aggregate in the solid state. The noncovalent and argentophilic interactions have been rationalized by means of DFT calculations.