Suchergebnisse

A theoretical study on some carboxylic acid dimers formed by positively or negatively charged molecules has been carried out by using DFT methods. The resulting dimers possess either a charge of +2 or −2. In addition, the corresponding neutral complexes have also been considered. The electron density distribution described by the atoms in molecules and the natural bond orbital methods, as well as the electric field maps of the systems, have been analyzed and compared without finding significant differences between the neutral and ionic complexes. The interaction energy along the dissociation path of the charged dimers shows both a local minimum and a local maximum, defining a stability region between them. When this energetic profile is recalculated by removing the repulsion between the charged groups, it resembles to those of the neutral molecules. Hence, the characteristics of the charged dimers are similar to those of the neutral ones: the addition of a repulsion term for the charged groups permits to retrieve the energetic profiles dependence with the distance in the charged system. The interacting quantum atom (IQA) method has been used to calculate the interaction energy terms, including the classic Coulombic term between the whole molecules and the corresponding of the carboxylic acid groups. The IQA results show repulsive electrostatic interactions when the whole molecules are considered in the ionic complexes, but attractive ones between the carboxylic groups in both neutral and ionic complexes. ; This work was supported by the Spanish Ministerio de Economía y Competitividad (Grants CSD2007-00041, ENE2012-36368-C02-02, ENE2015-63969, SEV2015-0496 and CTQ2015-63997-C2-2-P), the Catalan Government (Grant PRC 2014SGR-1643), and the Autonomous Community of Madrid (S2013/MIT2841, Fotocarbon). ; Peer reviewed

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). ; Peer reviewed

Recent findings unveil the pharmacological modulation of imidazoline I2 receptors (I2-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I2-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Moreover, LSL60101 induced hypothermia in mice while decreased pro-apoptotic FADD protein in the hippocampus. In vivo studies in the familial Alzheimer's disease 5xFAD murine model with the representative compound, revealed significant decreases in the protein expression levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in hippocampus. Overall, LSL60101 plays a neuroprotective role by reducing apoptosis and modulating oxidative stress. ; This work was supported by Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (Spain, PID2019-107991RB-I00, PID2019-106285RB), the Basque Government (IT1211/19) and Generalitat de Catalunya (GC) (2017SGR106). 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. 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), J.A.G.-S. is a member emeritus of the Institut d'Estudis Catalans (Barcelona, Catalonia). E.H.-H. is supported by a predoctoral scholarship (FPI/2102/2018; Consejería de Innovación, Investigación y Turismo del Gobierno de las Islas Baleares y del Fondo Social Europeo). M.R., T.D., and K.N. kindly acknowledge the project funded by the Ministry of Science and Technological Development of the Republic of Serbia, Contract No. 451-03-68/2020-14/200161, and HORISON 2020-COST-Action CA18133 ERNEST: European Research Network on Signal Transduction. E. M. acknowledges funding to Severo Ochoa: CEX2019-917S. M.I.L, A.L.M. and J.B. gratefully acknowledge support from Xunta de Galicia (ED431C 2018/21 and ED431G 2019/02) and European Regional Development Fund (ERDF). ; With funding from the Spanish government through the 'Severo Ochoa Centre of Excellence' accreditation (CEX2019-000917-S). ; Peer reviewed