The interaction of amino acids with macrocyclic pH probes of pseudopeptidic nature

The fluorescence quenching, by a series of amino acids, of pseudopeptidic compounds acting as probes for cellular acidity has been investigated. It has been found that amino acids containing electron-rich aromatic side chains like Trp or Tyr, as well as Met quench the emission of the probes mainly via a collisional mechanism, with Stern–Volmer constants in the 7–43 M−1 range, while other amino acids such as His, Val or Phe did not cause deactivation of the fluorescence. Only a minor contribution of a static quenching due to the formation of ground-state complexes has been found for Trp and Tyr, with association constants in the 9–24 M−1 range. For these ground-state complexes, a comparison between the macrocyclic probes and an open chain analogue reveals the existence of a moderate macrocyclic effect due to the preorganization of the probes in the more rigid structure

Development of lessons on chemical and biological reactors in Moodle platform

En este proyecto docente se han desarrollado una serie de actividades académicamente dirigidas dedicadas a los reactores químicos y biológicos, en concreto, se ha empleado una herramienta denominada lección que se encuentra disponible a través de la plataforma virtual Moodle, dichas lecciones se basan en una serie de ventanas secuenciales que permiten profundizar en todos los conceptos fundamentales de los reactores químicos y/o biológicos y, a través de diversas cuestiones complementarias sobre el tema, incluidas durante el desarrollo de dicha lección, permite al alumno realizar un aprendizaje más activo que favorece la consolidación de los conceptos de forma gradual. Previo al estudio de los reactores químicos y/o biológicos es necesario tener en cuenta diversos aspectos químicos, físicos, matemáticos, biológicos e ingenieriles que han de considerarse para desarrollar los aspectos fundamentales básicos para poder alcanzar dicho objetivo y se pretende facilitar esta labor al alumnado con el empleo de las lecciones elaboradas. Previamente a la elaboración de las lecciones se ha realizado una importante labor de preparación y síntesis de toda la información, posteriormente se han desarrollado diferentes lecciones para los conceptos tratados en cada uno de los temas implicados en la elaboración de este proyecto docente y tras una profunda revisión se han puesto a disposición de los alumnos.In this teaching project have developed a series of academic activities devoted to the chemical and biological reactors, in particular, it has been using a tool called lesson which is available through the Moodle virtual platform, these lessons are based on a series of sequential windows allowing to delve into all the fundamental concepts of chemical and/or biological reactors and through various complementary on the theme, including issues during the development of this lesson, students perform a more active learning that promotes the consolidation of concepts gradually. Prior to the study of chemical reactors and/or biological is necessary to take account of various chemical, physical, mathematical, biological and engineering aspects that are to be considered to develop the basic fundamentals to achieve the aim and is intended to facilitate this work to the students with the use of elaborate lessons. Important preparation work has been prior to the preparation of the lessons and synthesis of information, have subsequently developed different lessons for the concepts dealt with in each of the issues involved in the development of this educational project and after a thorough review have been available to the students

Ratiometric fluorescence sensing of phenylalanine derivatives by synthetic macrocyclic receptors

The supramolecular analytical behavior of eight pseudopeptidic fluorescent receptors (1a-c, 2a-c, 3, 4) has been studied. The receptors are either macrocyclic or open chain derivatives based on the naphthalene chromophore. The ability of 1-4 for the molecular recognition of amino acids (as Z-protected derivatives) has been evaluated in dichloromethane. The signal observed corresponds to a fluorescence emission of turn-on type. The preferential binding of all the receptors for phenylalanine (Phe) over aliphatic amino acids (Ala, Val) by a factor of 3-4 has been found. Among the family of studied fluorescent molecules, two macrocyclic receptors (1a and 1b) display high exciplex emissions and great fluorescence changes both at long (fluorescence quenching at 390 nm) and short wavelengths (fluorescence enhancement at 340 nm). This feature makes the macrocycles 1a and 1b potentially practical as fluorescent ratiometric sensors for Phe. As a proof of concept, 1a and 1b have been assayed as analytical tools for the identification of model samples enriched with Phe, mimicking the concentrations found in the pathology phenylketonuria (PKU). This result opens the door to the development of new Phe-sensing sensors based on the exciplex signaling mechanism as a new strategy for the analysis of aminoacidemias. © 2009 Elsevier B.V. All rights reserved

Unraveling the Molecular Recognition of Amino Acid Derivatives by a Pseudopeptidic Macrocycle: ESI-MS, NMR, Fluorescence, and Modeling Studies

The binding between a pseudopeptidic macrocyclic naphthalenophane and different N-protected amino acid derivatives has been thoroughly studied by ESI-MS, NMR, fluorescence, and molecular modeling. Careful NMR titration experiments led to the characterization of the intermolecular noncovalent interactions, reflecting a slight side chain and l-stereoselectivity of the host−guest complexes. The data suggest the formation of an intimate ionic pair after the proton transfer from the carboxylic substrate to the amino macrocycle. Additional intermolecular interactions like H-bonding and π−π contacts are also important. This receptor shows a stronger interaction with substrates bearing aromatic rings, either in the side chain or in the N-protecting group. Besides, for N-Z-Phe-OH, a moderate enantioselectivity has been observed. Mass spectrometry suggests the formation of supramolecular complexes with stoichiometries higher than 1:1. The dual nature of the fluorescence emission of the macrocyclic receptor allowed determining binding constants and pertinent thermodynamic parameters. On the basis of the experimental data (NMR titrations, intermolecular ROESY, VT-NMR) and with the help of molecular modeling, a reasonable structure for the supramolecular complexes can be proposed, in which the interactions with the naphthyl ring of the receptor play a fundamental role in the strength and selectivity of the molecular recognition event

Synthetic Macrocyclic Peptidomimetics as Tunable pH Probes for the Fluorescence Imaging of Acidic Organelles in Live Cells

Acid test: Macrocyclic compounds that comprise a 9,10-anthracene subunit linked by a C2-symmetric peptidomimetic chain (see formula) are useful as fluorescent probes in a pH range of biomedical interest. Changes in the size of the macrocycle (n=3,4,6,8) produce a shift in the pKa values. Experiments with live mouse macrophage cells show the selective localization of the probe in the acidic organelles (see differential interference contrast image)

Identification of a Nonanuclear {Co^II₉} Polyoxometalate Cluster as a Homogeneous Catalyst for Water Oxidation

The polyanion of formula {Co₉(H₂O)₆(OH)₃(HPO₄)₂(PW₉O₃₄)₃}^16– (<b>Co₉</b>) contains a central nonacobalt core held together by hydroxo and hydrogen phosphate bridges and supported by three lacunary Keggin-type polyphosphotungstate ligands. Our data demonstrate that <b>Co₉</b> is a homogeneous catalyst for water oxidation. Catalytic water electrolysis on fluorine-doped tin oxide coated glass electrodes occurs at reasonable low overpotentials and rates when <b>Co₉</b> is present in a sodium phosphate buffer solution at neutral pH. We carried out our experiments with an excess of 2,2′-bipyridyl as the chelating agent for free aqueous Co^II ions, in order to avoid the formation of a cobalt oxide film on the electrode, as observed for other polyoxometalate catalysts. In these conditions, no heterogeneous catalyst forms on the anode, and it does not show any deposited material or significant catalytic activity after a catalytic cycle. <b>Co₉</b> is also an extremely robust catalyst for chemical water oxidation. It is able to continuously catalyze oxygen evolution during days from a buffered sodium hypochlorite solution, maintaining constant rates and efficiencies without any significant apparition of fatigue

Evolution of antibody titers after two doses of mRNA Pfizer-BioNTech vaccine and effect of the third dose in nursing home residents.

ObjectivesWe evaluated the IgG antibody titer against SARS-CoV-2 in 196 residents of a Spanish nursing home after the second dose of the BNT162b2 vaccine and the evolution of this titer over time. The role of the third dose of the vaccine on immune-response is also analysed in 115 of participants.MethodsVaccine response was evaluated 1, 3 and 6 months after second dose of Pfizer-BioNTech COVID-19 Vaccine and 30 days after booster vaccination. Total anti-RBD (receptor binding domain) IgG immunoglobulins were measured to assess response. Six month after the second dose of vaccine and previously to the booster, T-cell response was also measured in 24 resident with different antibody levels. T-spot Discovery SARS-CoV-2 kit was used to identify cellular immunogenicity.ResultsAs high as 99% of residents demonstrated a positive serological response after second dose. Only two patients showed no serologic response, two men without records of previous SARS-CoV-2 infection. A higher immune response was associated with prior SARS-CoV-2 infection regardless of the gender or age. The anti-S IgG titers decreased significantly in almost all the participants (98.5%) after six months of vaccination whatever previous COVID-infection. The third dose of vaccine increased antibody titers in all patients, although initial vaccination values were not restored in the majority of cases.ConclusionThe main conclusion of the study is that vaccine resulted in good immunogenicity in this vulnerable population. Nevertheless more data are needed on the long-term maintenance of antibody response after booster vaccination

Triplet Excited State Behavior of Naphthalene-Based Pseudopeptides in the Presence of Energy Donors

In this work, the triplet state behavior of naphthalene-based pseudopeptides with amide-based macrocyclic or lateral chain substructures has been investigated in the presence of benzophenone and/or biphenyl, as suitable energy-donating chromophores. Their behavior has been compared with that of 1,4-dimethylnaphthalene as model compound. In all the cases, the triplet–triplet absorption of naphthalene is detected by transient absorption spectroscopy, upon selective excitation of benzophenone at 355 nm. The kinetics of formation and decay of this species is markedly slower in the pseudopeptides, due to retardation of triplet–triplet energy transfer and exciplex formation. Finally, the delayed fluorescence detected in the model naphthalene is absent in the pseudopeptides. The concept can, in principle, be exploited for the study of excited-state interactions in supramolecular systems