Deciphering the H-Bonding Preference on Nucleoside Molecular Recognition through Model Copper(II) Compounds

The synthetic nucleoside acyclovir is considered an outstanding model of the natural nucleoside guanosine. With the purpose of deepening on the influence and nature of non-covalent interactions regarding molecular recognition patterns, three novel Cu(II) complexes, involving acyclovir (acv) and the ligand receptor N-(2-hydroxyethyl)ethylenediamine (hen), have been synthesized and thoroughly characterized. The three novel compounds introduce none, one or two acyclovir molecules, respectively. Molecular recognition has been evaluated using single crystal X-ray diffraction. Furthermore, theoretical calculations and other physical methods such as thermogravimetric analysis, infrared and UV-Vis spectroscopy, electron paramagnetic resonance and magnetic measurements have been used. Theoretical calculations are in line with experimental results, supporting the relevance of the [metal-N7(acv) + H-bond] molecular recognition pattern. It was also shown that (hen)O-H group is used as preferred H-donor when it is found within the basal coordination plane, since the higher polarity of the terminal (hen)O-H versus the N-H group favours its implication. Otherwise, when (hen)O-H occupies the distal coordination site, (hen)N-H groups can take overThis research was funded by Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades (MICIU) from Spain and co-funded with FEDER-EU (Projects No. PGC2018-102047-B-I00 and CTQ2017-85821-R); Junta de Andalucía (FQM-283), and University of Granada (Project ref. PPJIA2019-03)S

Ratphones: an affordable tool for highly controlled sound presentation in freely moving rats

[Abstract] Encoding and processing sensory information is key to understanding the environment and to guiding behavior accordingly. Characterizing the behavioral and neural correlates of these processes requires the experimenter to have a high degree of control over stimuli presentation. For auditory stimulation in animals with relatively large heads, this can be accomplished by using headphones. However, it has proven more challenging in smaller species, such as rats and mice, and has been only partially solved using closed-field speakers in anesthetized or head-restrained preparations. To overcome the limitations of such preparations and to deliver sound with high precision to freely moving animals, we have developed a set of miniature headphones for rats. The headphones consist of a small, skull-implantable base attached with magnets to a fully adjustable structure that holds the speakers and keeps them in the same position with respect to the ears

Diversidad de frutas sapotáceas en mercados agropecuarios de La Habana.

El objetivo del trabajo fue estudiar la diversidad de sapotáceas ofertadas en los mercados de Ciudad de La Habana, partiendo de la información tomada en tres mercados de Ciudad de La Habana con dimensiones variables, durante un año,. Los datos fueron recogidos por observación directa del producto en cada uno de ellos y completados mediante encuesta directa a los vendedores. Se evaluaron cinco variables: la especie, la fecha del muestreo, número de tarimas con la especie y número de tarimas totales que ofertaban productos agrícolas en cada mercado,  procedencia del producto y precio y la forma de la fruta, atendiendo a los  listados de descriptores. Los resultados mostraron que las especies de la familia Sapotaceae presentes en los mercados fueron el mamey colorado (Pouteria sapota),  el sapote o níspero (Manilkara  zapota), el canistel (Pouteria campechiana), el caimito (Chrysophyllum cainito) y caimitillo (Chrysophyllum oliviforme). El mamey colorado presentó la mayor frecuencia diaria y mensual. El calendario de distribución de especies sapotáceas en los mercados mostró que el mamey colorado se oferta todos años meses, el nispero o sapote  durante nueve meses, el canistel 10 meses y sólo cinco meses el caimito. Existe una complementariedad entre las diferentes frutas de la familia que ayuda a una distribución de las mismas a lo largo de todo el año

Anion–Cation Recognition Pattern, Thermal Stability and DFT-Calculations in the Crystal Structure of H2dap[Cd(HEDTA)(H2O)] Salt (H2dap = H2(N3,N7)-2,6-Diaminopurinium Cation)

We thank the Centre de Tecnologies de la Informació (CTI), Universitat de les Illes Balears for computational facilities. We also thank all projects for financial support.The proton transfer between equimolar amounts of [Cd(H2EDTA)(H2O)] and 2,6-diaminopurine (Hdap) yielded crystals of the out-of-sphere metal complex H2(N3,N7)dap [Cd(HEDTA)(H2O)]·H2O (1) that was studied by single-crystal X-ray diffraction, thermogravimetry, FT-IR spectroscopy, density functional theory (DFT) and quantum theory of “atoms-in-molecules” (QTAIM) methods. The crystal was mainly dominated by H-bonds, favored by the observed tautomer of the 2,6-diaminopurinium(1+) cation. Each chelate anion was H-bonded to three neighboring cations; two of them were also connected by a symmetry-related anti-parallel π,π-staking interaction. Our results are in clear contrast with that previously reported for H2(N1,N9)ade [Cu(HEDTA) (H2O)]·2H2O (EGOWIG in Cambridge Structural Database (CSD), Hade = adenine), in which H-bonds and π,π-stacking played relevant roles in the anion–cation interaction and the recognition between two pairs of ions, respectively. Factors contributing in such remarkable differences are discussed on the basis of the additional presence of the exocyclic 2-amino group in 2,6-diaminopurinium(1+) ion.This research was funded by the Excellence Network ‘Metal Ions in Biological Systems’ MetalBio CTQ2017-90802-REDT, the Research group FQM-283 (Junta de Andalucía) and MICIU/AEI of Spain (project CTQ2017-85821-R FEDER funds)

Novel Cd (II) Coordination Polymers Afforded with EDTA or Trans-1,2-Cdta Chelators and Imidazole, Adenine, or 9-(2-Hydroxyethyl) Adenine Coligands

Three mixed-ligands of Cd(II) coordination polymers were unintentionally obtained: {[Cd(µ3-EDTA)(Him)·Cd(Him)(H2O)2]·H2O}n (1), {[Cd(µ4-CDTA)(Hade)·Cd(Hade)2]}n (2), and {[Cd(µ3-EDTA)(H2O)·Cd(H9heade)(H2O)]·2H2O}n (3), having imidazole (Him), adenine (Hade) or 9-(2-hydroxyethyl)adenine (9heade) as the N-heterocyclic coligands. Compounds 2 and 3 were obtained by working with an excess of corresponding N-heterocyclic coligands. The single-crystal X-ray diffraction structures and thermogravimetric analyses are reported. The chelate moieties in all three compounds exhibit hepta-coordinated Cd centers, whereas the non-chelated Cd center is five-coordinated in 1 and six-coordinated in 2 and 3. Him and Hade take part in the seven-coordinated chelate moieties in 1 and 2, respectively. In contrast, 9heade is unable to replace the aqua ligand of the chelate [Cd (EDTA) (H2O)] moiety in 3. The thermogravimetric analysis (TGA) behavior of [Cd (H2EDTA) (H2O)]·2H2O in 1 and 3 leads to a residue of CdO, whereas the N-rich compound 2 yields CdO·Cd(NO3)2 as a residue. Density functional theory (DFT) calculations along with molecular electrostatic potential (MEP) and quantum theory of atoms-in-molecules computations were performed in adenine (compound 2) and (2-hydroxyethyl)adenine (compound 3) to analyze how the strength of the H-bonding and π-stacking interactions, respectively, are affected by their coordination to the Cd-metal centerThis research was funded by the Excellence Network “Metal Ions in Biological Systems” MetalBio CTQ2017-90802-REDT, the Research group FQM-283 (Junta de Andalucía), and MICIU/AEI of Spain (project CTQ2017-85821-R FEDER funds)S

Supramolecular, spectroscopic and computational analysis of weak interactions in some thiosemicarbazones derived from 5-acetylbarbituric acid

A new series of 5-acetylbarbituric based thiosemicarbazones (TSC) named 5-acetylbarbituric hydrazine-1-carbothioamide (1), N-methyl-(5-acetylbarbituric)hydrazine-1-carbothioamide (2), N-ethyl-(5-acetylbarbituric)hydrazine-1-carbothioamide (3), N,N-dimethyl-(5-acetylbarbituric)hydrazine-1-carbothioamide (4), N'-piperidine-(5-acetylbarbituric)-1-carbothiohydrazide (5) and N'-hexamethyleneimine-(5-acetylbarbituric)-1-carbothiohydrazide (6), has been synthesized from 5-acetylbarbituric acid and N-unsubstituted/substituted thiosemicarbazides. The synthesized compounds were well characterized by elemental analyses, FT-IR, 1H, 13C NMR and mass spectroscopic methods. Three-dimensional molecular structures of three compounds (1⋅DMSO, 2 and 6⋅H2O) were determined by single crystal X-ray crystallography, and an analysis of their supramolecular structure was carried out. The supramolecular features of the X-ray structure were also studied using Hirshfeld surface analysis. Finally, H-bonding networks observed in the solid state X-ray structures of 1⋅DMSO, 2, and 6⋅H2O and unconventional π-stacking dimers in 6⋅H2O were further analyzed by DFT calculations in combination with molecular electrostatic potential surfaces and combined QTAIM/NCIplot computational toolsFinancial support from the Network of Excellence “Metallic Ions in Biological Systems” CTQ2017-90802-REDT [Ministerio de Economía y Competitividad (Spain) and European Regional Development Fund (EU)], and the Xunta de Galicia (Spain) [Rede de Excelencia MetalBIO ED431D 2017/01]. MICIU/AEI of Spain (project CTQ2017-85821-R FEDER) is also acknowledged for financial supportS

Neuroprotective effects of fluorophore-labelled manganese complexes: determination of ROS production, mitochondrial membrane potential and confocal fluorescence microscopy studies in neuroblastoma cells

In this work, four manganese(II) complexes derived from the ligands H2L1-H2L4, that incorporate dansyl or tosyl fluorescent dyes, have been investigated in term of their antioxidant properties. Two of the manganese(II) complexes have been newly prepared using the asymmetric half-salen ligand H2L2 and the thiosemicarbazone ligand H2L3. The four organic strands and the manganese complexes have been characterized by different analytical and spectroscopic techniques. The study of the antioxidant behaviour of these two new complexes and other two fluorophore-labelled analogues was tested in SH-SY5Y neuroblastoma cells. These four model complexes 1–4 were found to protect cells from oxidative damage in this human neuronal model, by reducing the release of reactive oxygen species. Complexes 1–4 significantly improved cell survival, with levels between 79.1 ± 0.8% and 130.9 ± 4.1%. Moreover, complexes 3 and 4 were able to restore the mitochondrial membrane potential at 1 μM, with 4 reaching levels higher than 85%, similar to the percentages obtained by the positive control agent cyclosporin A. The incorporation of the fluorescent label in the complexes allowed the study of their ability to enter the human neuroblastoma cells by confocal microscopyThe research leading to these results has received funding from the following FEDER cofunded-grants. From Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01), 2018 GRC GI-1584 (ED431C 2018/13), MetalBIO Network (ED431D 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad IISCIII/PI19/001248. From Ministerio de Ciencia, Innovación y Universidades, MULTIMETDRUGS (RED2018-102471-T). From European Union, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOXS

Weak Interactions in Cocrystals of Isoniazid with Glycolic and Mandelic Acids

This research was funded by the Network of Excellence “Metallic Ions in Biological Systems” CTQ2017-90802-REDT [Ministerio de Economía y Competitividad (Spain) and European Regional Development Fund (EU)], and the Xunta de Galicia (Spain) [Rede de Excelencia MetalBIO ED431D 2017/01].Acknowledgments: We thank the “Centre de Tecnologies de la Informació” (CTI) at the Univeritat de les Illes Baleares for computational facilities.This work deals with the preparation of pyridine-3-carbohydrazide (isoniazid, inh) cocrystals with two -hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or d,l-mandelic acid (H2ma) resulted in the formation of cocrystals or salts of composition (inh) (H2ga) (1) and [Hinh]+[Hma]– (H2ma) (2) when reacted with isoniazid. An N0-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pinh) 1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. These prepared compounds were well characterized by elemental analysis, and spectroscopic methods, and their three-dimensional molecular structure was determined by single crystal X-ray crystallography. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems. Finally, Hirshfeld surface analysis and Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) have been performed to further characterize and rationalize the non-covalent interactions.Network of Excellence “Metallic Ions in Biological Systems” CTQ2017-90802-REDT [Ministerio de Economía y Competitividad (Spain) and European Regional Development Fund (EU)]Xunta de Galicia (Spain) [Rede de Excelencia MetalBIO ED431D 2017/01

The mechanistic foundation of Weber’s law

[Abstract] Although Weber's law is the most firmly established regularity in sensation, no principled way has been identified to choose between its many proposed explanations. We investigated Weber's law by training rats to discriminate the relative intensity of sounds at the two ears at various absolute levels. These experiments revealed the existence of a psychophysical regularity, which we term time-intensity equivalence in discrimination (TIED), describing how reaction times change as a function of absolute level. The TIED enables the mathematical specification of the computational basis of Weber's law, placing strict requirements on how stimulus intensity is encoded in the stochastic activity of sensory neurons and revealing that discriminative choices must be based on bounded exact accumulation of evidence. We further demonstrate that this mechanism is not only necessary for the TIED to hold but is also sufficient to provide a virtually complete quantitative description of the behavior of the rats