Atomistic molecular simulations of Aβ-Zn conformational ensembles

The amyloid-forming Aβ peptide is able to interact with metal cations to form very stable complexes that influence fibril formation and contribute to the onset of Alzheimer's disease. Multiple structures of peptides derived from Aβ in complex with different metals have been resolved experimentally to provide an atomic-level description of the metal-protein interactions. However, Aβ is intrinsically disordered, and hence more amenable to an ensemble description. Molecular dynamics simulations can now reach the timescales needed to generate ensembles for these type of complexes. However, this requires accurate force fields both for the protein and the protein-metal interactions. Here we use state-of-the-art methods to generate force field parameters for the Zn(II) cations in a set of complexes formed by different Aβ variants and combine them with the Amber99SB*-ILDN optimized force field. Upon comparison of NMR experiments with the simulation results, further optimized with a Bayesian/Maximum entropy approach, we provide an accurate description of the molecular ensembles for most Aβ-metal complexes. We find that the resulting conformational ensembles are more heterogeneous than the NMR models deposited in the Protein Data Bank.Financial support comes from Eusko Jaurlaritza (Basque Government) through the project IT1584-22 and from the Spanish Ministry of Science and Universities through the Office of Science Research (MINECO/FEDER) through grant PID2021-127907NB-I00. DDS acknowledges the Spanish Ministry of Science and Universities for a Ramón y Cajal contract (Grant RYC-2016-19590)

Building machine learning assisted phase diagrams: Three chemically relevant examples

In this work, we present a systematic procedure to build phase diagrams for chemically relevant properties by the use of a semi-supervised machine learning technique called uncertainty sampling. Concretely, we focus on ground state spin multiplicity and chemical bonding properties. As a first step, we have obtained single-eutectic-point-containing solid–liquid systems that have been suitable for contrasting the validity of this approach. Once this was settled, on the one hand, we built magnetic phase diagrams for several Hooke atoms containing a few electrons (4 and 6) trapped in spheroidal harmonic potentials. Changing the parameters of the confinement potential, such as curvature and anisotropy, and interelectronic interaction strength, we have been able to obtain and rationalize magnetic phase transitions flipping the ground state spin multiplicity from singlet (nonmagnetic) to triplet (magnetic) states. On the other hand, Bader’s analysis is performed upon helium dimers confined by spherical harmonic potentials. Covalency is studied using descriptors as the sign for Δρ(rC) and H(rC), and the dependency on the degrees of freedom of the system is studied, i.e., potential curvature ω2 and interatomic distance R. As a result, we have observed that there may exist a covalent bond between He atoms for short enough distances and strong enough confinement. This machine learning procedure could, in principle, be applied to the study of other chemically relevant properties involving phase diagrams, saving a lot of computational resources.This work has been carried out in the Theoretical Chemistry Group http://www.ehu.eus/chemistry/theory/category/1_group/ in the Faculty for Chemical Sciences of the University of the Basque Country and the Donostia International Physics Center (DIPC) in the frame of the project from the Basque Government GV IT1254-19 (October 07, 2019). The SGI/IZO-SGIker UPV/EHU is gratefully acknowledged for generous allocation of computational resources

Rules governing metal coordination in Aβ–Zn(ii) complex models from quantum mechanical calculations

Transition metals directly contribute to the neurotoxicity of the aggregates of the amyloid-forming Aβ peptide. The understanding and rationalization of the coordination modes of metals to Aβ amyloid is, therefore, of paramount importance to understand the capacity of a given metal to promote peptide aggregation. Experimentally, multiple Aβ–metal structures have been resolved, which exhibit different modes of coordination in both the monomeric and oligomeric forms of Aβ. Although Zn(II) metalloproteins are very abundant and often involve cysteine residues in the first coordination shell, in the case of Aβ–Zn(II), though, Zn(II) is coordinated by glutamic/aspartic acid and/or histidine residues exclusively, making for an interesting case study. Here we present a systematic analysis of the underlying chemistry on Aβ–Zn(II) coordination, where relative stabilities of different coordination arrangements indicate that a mixture of Glu/Asp and His residues is favored. A detailed comparison between different coordination shell geometries shows that tetrahedral coordination is generally favored in the aqueous phase. Our calculations show an interplay between dative covalent interactions and electrostatics which explains the observed trends. Multiple structures deposited in the Protein Data Bank support our findings, suggesting that the trends found in our work may be transferable to other Zn(II) metalloproteins with this type of coordination.The authors gratefully acknowledge the financing of the MINECO project (PID2021-127907NB-I00) founded by the Spanish Ministry of Science and Innovation, and the financing from the Basque Government (IT1584-22). The authors also thank the IZO-SGI SGIker (UPV/EHU/ERDF,EU) and DIPC for technical and human support and for the allocation of computational resources. D. D. S. receives support from a Ramón y Cajal contract (RYC-2016-19590) from the Spanish Ministry of Science and Innovation. J. A. thankfully acknowledges the University of the Basque Country for the scholarship for the completion of a masters degree in the academic years 2020/2021–2021/2022 and the Donostia International Physics Center for a summer internship

Few electron systems confined in Gaussian potential wells and connection to Hooke atoms

In this work, we have computed and implemented one-body integrals concerning Gaussian confinement potentials over Gaussian basis functions. Then, we have set an equivalence between Gaussian and Hooke atoms and we have observed that, according to singlet and triplet state energies, both systems are equivalent for large confinement depth for a series of even number of electrons n = 2, 4, 6, 8 and 10. Unlike with harmonic potentials, Gaussian confinement potentials are dissociative for small enough depth parameter; this feature is crucial in order to model phenomena such as ionization. In this case, in addition to corresponding Taylor-series expansions, the first diagonal and sub-diagonal Pade approximant were also obtained, useful to compute the upper and lower limits for the dissociation depth. Hence, this method introduces new advantages compared to others.This research was funded by Eusko Jaurlaritza (the Basque Government), through Consolidated Group Project No. IT1254-19 and IT1584-22. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF and ESF) is gratefully acknowledged

Aufbau principle and singlet-triplet gap in spherical Hooke atoms

Singlet and triplet spin state energies for three-dimensional Hooke atoms, that is, electrons in a quadratic confinement, with even number of electrons (2, 4, 6, 8, 10) is discussed using Full-CI and CASSCF type wavefunctions with a variety of basis sets and considering perturbative corrections up to second order. The effect of the screening of the electron–electron interaction is also discussed by using a Yukawa-type potential with different values of the Yukawa screening parameter (λee = 0.2, 0.4, 0.6, 0.8, 1.0). Our results show that the singlet state is the ground state for two and eight electron Hooke atoms, whereas the triplet is the ground spin state for 4-, 6-, and 10-electron systems. This suggests the following Aufbau structure 1s < 1p < 1d with singlet ground spin states for systems in which the generation of the triplet implies an inter-shell one-electron promotion, and triplet ground states in cases when there is a partial filling of electrons of a given shell. It is also observed that the screening of electron–electron interactions has a sizable quantitative effect on the relative energies of both spin states, specially in the case of two- and eight-electron systems, favoring the singlet state over the triplet. However, the screening of the electron–electron interaction does not provoke a change in the nature of the ground spin state of these systems. By analyzing the different components of the energy, we have gained a deeper understanding of the effects of the kinetic, confinement and electron–electron interaction components of the energy.This research was funded by Eusko Jaurlaritza (the Basque Government), through Consolidated Group Project No. IT1584-22, PIBA19-0004, and 2019-CIEN-000092-01, and the Spanish MINECO/FEDER Projects No. PGC2018-097529-B-100, PGC2018-098212-B-C21, EUIN2017-88605, and EUR2019-103825. Eloy Ramos-Cordoba acknowledges funding from the Juan de la Cierva program IJCI-2017-34658. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF, and ESF) is gratefully acknowledged

Chemical Upcycling of PET Waste towards Terephthalate Redox Nanoparticles for Energy Storage

Over 30 million ton of poly(ethylene terephthalate) (PET) is produced each year and no more than 60% of all PET bottles are reclaimed for recycling due to material property deteriorations during the mechanical recycling process. Herein, a sustainable approach is proposed to produce redox-active nanoparticles via the chemical upcycling of poly(ethylene terephthalate) (PET) waste for application in energy storage. Redox-active nanoparticles of sizes lower than 100 nm were prepared by emulsion polymerization of a methacrylic-terephthalate monomer obtained by a simple methacrylate functionalization of the depolymerization product of PET (i.e., bis-hydroxy(2-ethyl) terephthalate, BHET). The initial cyclic voltammetry results of the depolymerization product of PET used as a model compound show a reversible redox process, when using a 0.1 M tetrabutylammonium hexafluorophosphate/dimethyl sulfoxide electrolyte system, with a standard redox potential of −2.12 V vs. Fc/Fc+. Finally, the cycling performance of terephthalate nanoparticles was investigated using a 0.1 M TBAPF6 solution in acetonitrile as electrolyte in a three-electrode cell. The terephthalate anode electrode displays good cycling stability and performance at high C-rate (i.e., ≥5C), delivering a stable specific discharge capacity of 32.8 mAh.g−1 at a C-rate of 30 C, with a capacity retention of 94% after 100 cycles. However, a large hysteresis between the specific discharge and charge capacities and capacity fading are observed at lower C-rate (i.e., ≤2C), suggesting some irreversibility of redox reactions associated with the terephthalate moiety, in particular related to the oxidation process.NC would like to thank the University of the Basque Country for funding through a specialization of research staff fellowship (ESPDOC 19/99). JD thanks WBI International and the Gobierno Vasco/Eusko Jaurlaritza (IT 999–16) for fundings. NG acknowledges the funding from the European Union’s Horizon 2020 framework programme under the Marie Skłodowska-Curie agreement No. 101028682

One- and Two-Electron Reductions in MiniSOG and their Implication in Catalysis

The unconventional bioorthogonal catalytic activation of anticancer metal complexes by flavin and flavoproteins photocatalysis has been reported recently. The reactivity is based on a two-electron redox reaction of the photoactivated flavin. Furthermore, when it comes to flavoproteins, we recently reported that site mutagenesis can modulate and improve this catalytic activity in the mini Singlet Oxygen Generator protein (SOG). In this paper, we analyze the reductive half-reaction in different miniSOG environments by means of density functional theory. We report that the redox properties of flavin and the resulting reactivity of miniSOG is modulated by specific mutations, which is in line with the experimental results in the literature. This modulation can be attributed to the fundamental physicochemical properties of the system, specifically (i) the competition of single and double reduction of the flavin and (ii) the probability of electron transfer from the protein to the flavin. These factors are ultimately linked to the stability of flavin‘s electron-accepting orbitals in different coordination modes.We acknowledge the Basque Government – Eusko Jaurlaritza (IT1254-19, IT1584-22, IkasC-2021-1-0252 (A.Z.), PIBA_2021_1_0034 (L.S.)), University of the Basque Country UPV/EHU (PIF19/244), Spanish State Research Agency (PID2019-109111RB-I00 (L.S., E.R. O.A.), PGC2018-097529-B-100 (X.L., E.F.), and FPU20/00688 (O.A.)) and Diputación Foral de Gipuzkoa (RED 2021) for financial support and the SGi/IZO-SGIker UPV/EHU for generous allocation of computational resources. Prof. Jesus Ugalde is acknowledged for fruitful discussions about electron transfer processes. L.S. thanks the Spanish Multi-MetDrugs RED2018-102471-T. This work was performed under the Severo Ochoa Centres of Excellence Programme run by the Spanish State Research Agency, CEX2018-000867-S (DIPC)

Hydrogen Tunneling in Catalytic Hydrolysis and Alcoholysis of Silanes

[EN] An unprecedented quantum tunneling effect has been observed in catalytic Si-H bond activations at room temperature. The cationic hydrido-silyl-iridium(III) complex, {Ir[SiMe(o-C6H4SMe)(2)](H)(PPh3)(THF)}[BAr4F], has proven to be a highly efficient catalyst for the hydrolysis and the alcoholysis of organosilanes. When triethylsilane was used as a substrate, the system revealed the largest kinetic isotopic effect (KIESi-H/Si-D=346 +/- 4) ever reported for this type of reaction. This unexpectedly high KIE, measured at room temperature, together with the calculated Arrhenius preexponential factor ratio (A(H)/A(D)=0.0004) and difference in the observed activation energy [(EaD -EaH )=34.07 kJ mol(-1)] are consistent with the participation of quantum tunneling in the catalytic process. DFT calculations have been used to unravel the reaction pathway and identify the rate-determining step. Aditionally, isotopic effects were considered by different methods, and tunneling effects have been calculated to be crucial in the process.This research was supported by the Universidad del Pais Vasco (UPV/EHU) (GIU13/06), Ministerio de Economia y Competitividad (PID2019-111281GB-00), Gobierno Vasco (IT1880-19 and IT1254-19). Technical and human support provided by IZO-SGI, SGIKER (UPV/EHU, MICINN, GV/EJERDF and ESF), is gratefully acknowledged for assistance and generous allocation of computational resources. N.A. is grateful to Diputacion Foral de Gipuzkoa (OF215/2016), and M.A.H. and Z.F. to IKERBASQUE for funding. We would like to thank Dr. Eugene E. Kwan for his support and fruitful discussion using PyQuiver program

Síntesis, caracterización y estudio de nuevos materiales magnéticos con el ligando 1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hidroxi-3-metoxi-5-metilbencil)ciclotetradecano (H4L)

[EN]The aim of this work is the synthesis and characterization of coordination compounds with a compartmental polydentate Mannich base-type ligand 1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hydroxy-3-methoxy-5-methylbenzyl)cyclo-tetradecane (H4L) and different metal centers that could show magnetic properties. The objectives of this work are divided in two parts. In first place, the synthesis of complexes that behave as Single Molecule Magnets (SMMs) was sought. In second place, CuII complexes were synthesized to understand the effect of the structure in the magnetic properties of these complexes, i.e. to establish magneto-structural correlations. In the present work, the synthesis and structural characterization of a novel tetranuclear centrosymmetric CuII complex with general formula [{(OAc)Cu(µ-OAc)Cu}(µ-L){Cu(µ-OAc)Cu(OAc)}]·2CHCl3·MeOH (2) is described. The determination of its 3D structure by X-ray diffraction shows a triple diphenoxo-acetate bridge among CuII-CuII ions. The magnetic susceptibility studies reveal ferromagnetic interactions with a coupling constant of 40 cm-1. This work also includes the synthesis and structural characterization of two novel tetranuclear complexes: [{(NO3)2Dy(µ-OAc)Zn}(µ-L){Zn(µ-OAc)Dy(NO3)2}] ·2CHCl3·XH2O (3) and [Zn2(µ-H2L)2(µ-succinato)Dy2(NO3)2](NO3)2·6MeOH·2H2O (4) both of which are centrosymmetric. The structural analysis of compounds 3 and 4 carried out by X-ray diffraction determines that the ZnII-DyIII ions are connected by a triple diphenoxo-acetate and a diphenoxo-succinate bridges respectively. The AC magnetic measurements for complex 3 show a single molecule magnet behavior with an energy barrier (Ueff) of 49 K for the reversal of the magnetization in accordance with Arrhenius fitting.[ES]Este trabajo tiene como objetivo la síntesis y caracterización de compuestos de coordinación formados por un ligando polidentado compartimental tipo base de Mannich 1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hidroxi-3-metoxi-5-metilbencil)ciclotetradecano (H4L) y varios centros metálicos que puedan mostrar propiedades magnéticas. Los objetivos que se persiguen son dos. En primer lugar, se ha buscado la síntesis de complejos que puedan mostrar propiedades de molécula imán (SMM, Single Molecule Magnet) y en segundo lugar se han sintetizado complejos de CuII para entender el efecto de la estructura en las propiedades magnéticas de estos complejos, es decir establecer correlaciones magneto-estructurales. En este trabajo se incluye la síntesis y caracterización estructural de un complejo tetranuclear de CuII, centrosimétrico, con formula general [{(OAc)Cu(µ-OAc)Cu}(µ-L){Cu(µ-OAc)Cu(OAc)}]·2CHCl3·MeOH (2). Mediante difracción de rayos X en monocristal se ha conseguido la estructura de este compuesto que muestra un triple puente difenoxo-acetato entre átomos CuII-CuII. El estudio de las propiedades magnéticas presenta un comportamiento ferromagnético con un valor de acoplamiento de 40 cm-1. También se incluye la síntesis y caracterización estructural de dos nuevos compuestos centrosimétricos tetranucleares ZnII-DyIII de formula general [{(NO3)2Dy(µ-OAc)Zn}(µ-L){Zn(µ-OAc)Dy(NO3)2}]·2CHCl3·XH2O (3) y [Zn2(µ-H2L)2(µ-succinato)Dy2(NO3)2](NO3)2·6MeOH·2H2O (4). Del análisis estructural del compuesto 3 se determina que los átomos ZnII-DyIII forman un triple puente difenoxo-acetato, mientras que el compuesto 4, muestra un triple puente difenoxo-succinato. El análisis de las propiedades magnéticas del complejo 3 muestra un comportamiento de molécula imán con una barrera de energía (Ueff) para la inversión de la magnetización de 49 K calculada mediante el ajuste lineal de Arrhenius

Síntesis, caracterización y estudio de nuevos materiales magnéticos con el ligando 1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hidroxi-3-metoxi-5-metilbencil)ciclotetradecano (H4L)

[EN]The aim of this work is the synthesis and characterization of coordination compounds with a compartmental polydentate Mannich base-type ligand 1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hydroxy-3-methoxy-5-methylbenzyl)cyclo-tetradecane (H4L) and different metal centers that could show magnetic properties. The objectives of this work are divided in two parts. In first place, the synthesis of complexes that behave as Single Molecule Magnets (SMMs) was sought. In second place, CuII complexes were synthesized to understand the effect of the structure in the magnetic properties of these complexes, i.e. to establish magneto-structural correlations. In the present work, the synthesis and structural characterization of a novel tetranuclear centrosymmetric CuII complex with general formula [{(OAc)Cu(µ-OAc)Cu}(µ-L){Cu(µ-OAc)Cu(OAc)}]·2CHCl3·MeOH (2) is described. The determination of its 3D structure by X-ray diffraction shows a triple diphenoxo-acetate bridge among CuII-CuII ions. The magnetic susceptibility studies reveal ferromagnetic interactions with a coupling constant of 40 cm-1. This work also includes the synthesis and structural characterization of two novel tetranuclear complexes: [{(NO3)2Dy(µ-OAc)Zn}(µ-L){Zn(µ-OAc)Dy(NO3)2}] ·2CHCl3·XH2O (3) and [Zn2(µ-H2L)2(µ-succinato)Dy2(NO3)2](NO3)2·6MeOH·2H2O (4) both of which are centrosymmetric. The structural analysis of compounds 3 and 4 carried out by X-ray diffraction determines that the ZnII-DyIII ions are connected by a triple diphenoxo-acetate and a diphenoxo-succinate bridges respectively. The AC magnetic measurements for complex 3 show a single molecule magnet behavior with an energy barrier (Ueff) of 49 K for the reversal of the magnetization in accordance with Arrhenius fitting.[ES]Este trabajo tiene como objetivo la síntesis y caracterización de compuestos de coordinación formados por un ligando polidentado compartimental tipo base de Mannich 1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hidroxi-3-metoxi-5-metilbencil)ciclotetradecano (H4L) y varios centros metálicos que puedan mostrar propiedades magnéticas. Los objetivos que se persiguen son dos. En primer lugar, se ha buscado la síntesis de complejos que puedan mostrar propiedades de molécula imán (SMM, Single Molecule Magnet) y en segundo lugar se han sintetizado complejos de CuII para entender el efecto de la estructura en las propiedades magnéticas de estos complejos, es decir establecer correlaciones magneto-estructurales. En este trabajo se incluye la síntesis y caracterización estructural de un complejo tetranuclear de CuII, centrosimétrico, con formula general [{(OAc)Cu(µ-OAc)Cu}(µ-L){Cu(µ-OAc)Cu(OAc)}]·2CHCl3·MeOH (2). Mediante difracción de rayos X en monocristal se ha conseguido la estructura de este compuesto que muestra un triple puente difenoxo-acetato entre átomos CuII-CuII. El estudio de las propiedades magnéticas presenta un comportamiento ferromagnético con un valor de acoplamiento de 40 cm-1. También se incluye la síntesis y caracterización estructural de dos nuevos compuestos centrosimétricos tetranucleares ZnII-DyIII de formula general [{(NO3)2Dy(µ-OAc)Zn}(µ-L){Zn(µ-OAc)Dy(NO3)2}]·2CHCl3·XH2O (3) y [Zn2(µ-H2L)2(µ-succinato)Dy2(NO3)2](NO3)2·6MeOH·2H2O (4). Del análisis estructural del compuesto 3 se determina que los átomos ZnII-DyIII forman un triple puente difenoxo-acetato, mientras que el compuesto 4, muestra un triple puente difenoxo-succinato. El análisis de las propiedades magnéticas del complejo 3 muestra un comportamiento de molécula imán con una barrera de energía (Ueff) para la inversión de la magnetización de 49 K calculada mediante el ajuste lineal de Arrhenius