Understanding the neurological implications of acute and long COVID using brain organoids

As early as in the acute phase of the coronavirus disease 2019 about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature. In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their humanoerived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID

Enantiopure Double ortho-Oligophenylethynylene-Based Helical Structures with Circularly Polarized Luminescence Activity

We thank the Ministerio de Economia y Competitividad (CTQ2017-85454-C2-1-P and CTQ2017-85454-C2-2-P), Ministerio de Ciencia e Innovacion (PID2020-113059GB-C21 and PID2020-113059GB-C22) and Junta de Andalucia (P20.00162) (Spain) for funding and P.R. and A. O. G. also for FPU contracts. Funding for open access charge is acknowledged to Universidad de Granada / CBUA.We also thank Big&Open Data Innovation Laboratory (BODaI-Lab), University of Brescia, granted by Fondazione Cariplo and Regione Lombardia, for access to resources of Computing Center CINECA (Bologna), Italy. Support from the Italian MIUR (Grant No. 2017A4XRCA) is also acknowledged.In this paper, we describe the optical and chiroptical properties of an enantiopure multipodal ortho-oligophenylethynylene (S,S,S,S)-1 presenting four chiral sulfoxide groups at the extremes. The presence of these groups together with alkynes allows the coordination with carbophilic Ag(I), and/or oxophilic Zn(II) cations, yielding double helical structures in an enantiopure way. In this sense, different behaviors in absorption, fluorescence, ECD and CPL spectra have been found depending on the stoichiometry and nature of the metal. We have observed that Zn(II) coordination favors an intensity increase of the electronic circular dichroism (ECD) spectra of compound (S,S,S,S)-1 yielding an M-helicity in the ortho-oligophenylene ethynylene (o-OPE) backbone. On the other hand, ECD spectra of final Ag(I) complex shows two different bands with an opposite sign to the free ligand, thus giving the P-helical isomer. In addition, circularly polarized luminescence (CPL) exhibit an enhanced intensity and negative sign in both complexes. Computational studies were also carried out, supporting the experimental results.Spanish Government CTQ2017-85454-C2-1-P CTQ2017-85454-C2-2-PInstituto de Salud Carlos III Spanish Government European Commission PID2020-113059GB-C21 PID2020-113059GB-C22Junta de Andalucia European Commission P20.00162University of Brescia / CBUAFondazione CariploMinistry of Education, Universities and Research (MIUR) 2017A4XRCARegione Lombardi

Enantiopure double ortho-oligophenylethynylene-based helical structures with circularly polarized luminescence activity

In this paper, we describe the optical and chiroptical properties of an enantiopure multipodal ortho-oligophenylethynylene (S,S,S,S)-1 presenting four chiral sulfoxide groups at the extremes. The presence of these groups together with alkynes allows the coordination with carbophilic Ag(I), and/or oxophilic Zn(II) cations, yielding double helical structures in an enantiopure way. In this sense, different behaviors in absorption, fluorescence, ECD and CPL spectra have been found depending on the stoichiometry and nature of the metal. We have observed that Zn(II) coordination favors an intensity increase of the electronic circular dichroism (ECD) spectra of compound (S,S,S,S)-1 yielding an M-helicity in the ortho-oligophenylene ethynylene (o-OPE) backbone. On the other hand, ECD spectra of final Ag(I) complex shows two different bands with an opposite sign to the free ligand, thus giving the P-helical isomer. In addition, circularly polarized luminescence (CPL) exhibit an enhanced intensity and negative sign in both complexes. Computational studies were also carried out, supporting the experimental result

Simple and non-charged long-lived fluorescent intracellular organelle trackers

In this work we evaluated by FLIM microscopy the preferential accumulation of long-lived acridone derivatives in mitochondria and lysosomes, based on a new concept of non-protonable and non-charged groups carriers. Thus, thiophene ring has been proved to act as mithocondria carrier whereas pyridine derivative is preferentially accumulated into lisosomes.Ministerio de Economía y Competitividad for funding (CTQ2017-85454-C2-1-P and CTQ2017-85658-R).Junta de AndalucíaMinisterio de Economía y Competitivida

Disociación Homolítica y Heterolítica de enlaces O-H: Aplicaciones Prácticas e Implicaciones en Química, Física e Bioquímica

La presente memoria de Tesis Doctoral titulada “Disociación Homolítica y Heterolítica de enlaces O-H: Aplicaciones Prácticas e Implicaciones en Química, Física e Bioquímica” se encuentra dividida en tres capítulos bien diferenciados. En dos de ellos (Capítulos I y II) se desarrollan sistemas con grupos OH sensibles a rupturas homolíticas y heterolíticas. Los Capítulos I y III están organizados en varias secciones como son la introducción de las temáticas principales tratadas, describiendo los principales antecedentes relacionados con dichos temas, los objetivos a desarrollar en cada capítulo, la discusión de los resultados obtenidos y las conclusiones que se extraen de dicho trabajo. Por último, la parte experimental de cada capítulo describe los protocolos experimentales empleados en cada caso, así como la caracterización espectroscópica de los nuevos compuestos obtenidos y las medidas realizadas utilizando técnicas como voltametría cíclica (CV), dicroísmo circular (CD), luminiscencia circularmente polarizada (CPL) o dicroísmo circular vibracional (VCD). El Capítulo II se ha redactado siguiendo un formato ligeramente distinto. El uso de este nuevo formato se justifica de manera detallada en la sección de Introducción de dicho capítulo.Tesis Univ. Granada.El trabajo se ha realizado gracias a un contrato de investigación predoctoral del Programa de Formación del Profesorado Universitario (FPU) del Ministerio de Educación, Cultura y Deporte

Extended enantiopure ortho-phenylene ethylene (o-OPE)-based helical systems as scaffolds for supramolecular architectures: a study of chiroptical response and its connection to the CISS effect

We thank the Ministerio de Economia y Competitividad (CTQ2017-85454-C2-1-P), Ministerio de Ciencia en Innovacion (PID2020-113059GB-C21) and Junta de Andalucia (P20_00162) (Spain) for funding and P. R. and A. O. G. also for FPU contracts. We also thank the UGR CSIRC for access to computational facilities. We also thank Big&Open Data Innovation Laboratory (BODaI-Lab), University of Brescia, granted by Fondazione Cariplo and Regione Lombardia, for access to resources of Computing Center CINECA (Bologna), Italy. Support from the Italian MIUR (grant N. 2017A4XRCA) is also acknowledged. VM acknowledges a Fellowship from Ikerbasque, the Basque Foundation for Science.A novel synthetic strategy based on a bifunctional stapled chiral nucleus from which segments of different lengths can be added to both ends of o-phenylene ethynylenes (o-OPEs) has been developed to obtain a new type of foldamer and a novel chiral Pd2L2 metallacycle. For the first time, an enantiopure fully conjugated helical foldamer having 14 phenyl rings and 13 alkynes is reported. The folded structure has four complete loops and is able to host three Ag(I) cations in their cavity with high binding constants. The complete photophysical and chiroptical (ECD, CPL and VCD) characterization of these foldamers has shown that these molecules show intense chiroptical responses with dissymmetry ratios in the range of 10−2. Theoretical modeling of these systems reveals the origin of these remarkable responses and points out a potential connection with the chiral induced spin selectivity (CISS) effect. The magnetic dipole moment is proposed as a key physical variable connecting the chiroptical properties and CISS-based spin filtering properties observed in chiral compounds.Ministerio de Economia y Competitividad (Spain) CTQ2017-85454-C2-1-PMinisterio de Ciencia en Innovacion (Spain) PID2020-113059GB-C21Junta de Andalucia European Commission P20_00162Ministry of Education, Universities and Research (MIUR) 2017A4XRCAIkerbasque, the Basque Foundation for Scienc

O-H and (CO)N-H bond weakening by coordination to Fe(ii)

New N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)-ethane-1,2-diamine derivatives bearing covalently linked OH and (CO)NH groups have been synthesized. The coordination of those pendant hydroxyl/amide groups to a Fe(ii) metal center is demonstrated both in solution, even in the presence of chloride as the counterion, and in solid state, by means of X-ray diffraction crystal structures. As a result of this coordination, the experimental bond dissociation free energies (BDFE) of O-H and (CO)N-H bonds are remarkably diminished down to 76.0 and 80.5 kcal mol respectively, which is also in agreement with DFT-based theoretical calculations. These BDFE values are in the range of commonly used hydrogen-atom donor reagents. The strategy presented here allows an unequivocal evaluation of the influence of metal coordination in X-H bond weakening in organic solvents which could be easily extended to other metal centers.We thank the Ministerio de Economía y Competitividad (MINECO, Spain) (CTQ2014-53598-R) and Junta de Andalucía (FQM2012-790). S. R. thanks the MECD for FPU predoctoral fellowship. A. M. and A. G. C. thank the MINECO for IJCI-2016-27793 and RyC-2013-12943 contracts

Auswirkungen des Stabex-Systems auf die Stabilität der Exporterlöse - Eine empirische Analyse zum Nutzen partieller Stabilisierungselemente

Dyes with near-red emission are of great interest because of their undoubted advantages for use as probes in living cells. In-depth knowledge of their photophysics is essential for employment of such dyes. In this article, the photophysical behavior of a new silicon-substituted xanthene, 7-hydroxy-5,5-dimethyl-10-(<i>o</i>-tolyl)­dibenzo­[<i>b</i>,<i>e</i>]­silin-3­(5<i>H</i>)-one (<b>2-Me TM</b>), was explored by means absorption, steady-state, and time-resolved fluorescence. First, the near-neutral pH, ground-state acidity constant of the dye, p<i>K</i>_N‑A, was determined by absorbance and steady-state fluorescence at very low buffer concentrations. Next, we determined whether the addition of phosphate buffer promoted the excited-state proton-transfer (ESPT) reaction among the neutral and anion form of <b>2-Me TM</b> in aqueous solutions at near-neutral pH. For this analysis, both the steady-state fluorescence method and time-resolved emission spectroscopy (TRES) were employed. The TRES experiments demonstrated a remarkably favored conversion of the neutral form to the anion form. Then, the values of the excited-state rate constants were determined by global analysis of the fluorescence decay traces recorded as a function of pH, and buffer concentration. The revealed kinetic parameters were consistent with the TRES results, exhibiting a higher rate constant for deprotonation than for protonation, which implies an unusual low value of the excited-state acidity constant <i>pK</i>*_N‑A and therefore an enhanced photoacid behavior of the neutral form. Finally, we determined whether <b>2-Me TM</b> could be used as a sensor inside live cells by measuring the intensity profile of the probe in different cellular compartments of HeLa 229 cells

Extended enantiopure ortho-phenylene ethylene (o-OPE)-based helical systems as scaffolds for supramolecular architectures: a study of chiroptical response and its connection to the CISS effect

A novel synthetic strategy based on a bifunctional stapled chiral nucleus from which segments of different lengths can be added to both ends of o-phenylene ethynylenes (o-OPEs) has been developed to obtain a new type of foldamer and a novel chiral Pd2L2 metallacycle. For the first time, an enantiopure fully conjugated helical foldamer having 14 phenyl rings and 13 alkynes is reported. The folded structure has four complete loops and is able to host three Ag(i) cations in their cavity with high binding constants. The complete photophysical and chiroptical (ECD, CPL and VCD) characterization of these foldamers has shown that these molecules show intense chiroptical responses with dissymmetry ratios in the range of 10(-2). Theoretical modeling of these systems reveals the origin of these remarkable responses and points out a potential connection with the chiral induced spin selectivity (CISS) effect. The magnetic dipole moment is proposed as a key physical variable connecting the chiroptical properties and CISS-based spin filtering properties observed in chiral compounds