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Functionalized upconverting nanoparticles (UCNPs) are promising theragnostic nanomaterials for simultaneous therapeutic and diagnostic purposes. We present two types of non-toxic eosin Y (EY) nanoconjugates derived from UCNPs as novel nanophotosensitizers (nano-PS) and deep-tissue bioimaging agents employing light at 800 nm. This excitation wavelength ensures minimum cell damage, since the absorption of water is negligible, and increases tissue penetration, enhancing the specificity of the photodynamic treatment (PDT). These UCNPs are uniquely qualified to fulfil three important roles: as nanocarriers, as energy-transfer materials, and as contrast agents. First, the UCNPs enable the transport of EY across the cell membrane of living HeLa cells that would not be possible otherwise. This cellular internalization facilitates the use of such EY-functionalized UCNPs as nano-PS and allows the generation of reactive oxygen species (ROS) under 800 nm light inside the cell. This becomes possible due to the upconversion and energy transfer processes within the UCNPs, circumventing the excitation of EY by green light, which is incompatible with deep tissue applications. Moreover, the functionalized UCNPs present deep tissue NIR-II fluorescence under 808 nm excitation, thus demonstrating their potential as bioimaging agents in the NIR-II biological window.

The generation of sulfonyl radicals has long been known as a flexible strategy in a wide range of different sulfonylative transformations. Meanwhile their use in alkylation processes has been somehow limited due to their inherent difficulty in evolving to less-stable radicals after sulfur dioxide extrusion. Herein we report a convenient strategy that involves gem-difluorinated sulfinates as an “upgrading-mask”, allowing these precursors to decompose into their corresponding alkyl radicals. The electron–donor character of sulfinates in the formation of an electron donor–acceptor (EDA) complex with transient iminium ions is displayed, achieving the first example of a stereocontrolled light-driven insertion of gem-difluoro derivatives into unsaturated aldehydes. This methodology is compatible with flow conditions, maintaining identical levels of enantiocontrol, Financial support was provided by the European Research Council (ERC-CoG, contract number: 647550), Spanish Government (RTI2018-095038-B-I00), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367)

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-P, Instituto de Salud Carlos III Spanish Government European Commission PID2020-113059GB-C21 PID2020-113059GB-C22, Junta de Andalucia European Commission P20.00162, University of Brescia / CBUA, Fondazione Cariplo, Ministry of Education, Universities and Research (MIUR) 2017A4XRCA, Regione Lombardia

The combination of photocatalysis with other ground state catalytic systems have attracted much attention recently due to the enormous synthetic potential offered by a dual activation mode. The use of N-heterocyclic carbene (NHC) as organocatalysts emerged as an important synthetic tool. Its ability to harness umpolung reactivity by the formation of the Breslow intermediate has been employed in the synthesis of thousands of biologically important compounds. However, the available coupling partners are relatively restricted, and its combination with other catalytic systems might improve its synthetic versatility. Thus, merging photoredox and N-heterocyclic carbene (NHC) catalysis has emerged recently as a powerful strategy to develop new transformations and give access to a whole new branch of synthetic possibilities. This review compiles the NHC catalyzed methods mediated by light, either in the presence or absence of an external photocatalyst, that have been described so far, and aims to give an accurate overview of the potential of this activation mode, L.M. acknowledges the Autonomous Community of Madrid (CAM) for the financial support (PEJD-2019-PRE/AMB-16640 and SI1/PJI/ 2019-00237) and for an “Atracción de Talento Investigador” contract (2017-T2/AMB-5037)

A Pd-catalyzed C(sp3)–C(sp) bond formation for the direct functionalization of cyclobutenes with alkynes has been achieved, suggesting (DFT and control experiments) an unusual pathway of oxidative addition in tertiary iodoalkanes.

Two glycosylated flavonoids, the quercetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside and myricetin-3-O-β-d-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside, were isolated from the CH2Cl2/MeOH fraction of Syzygium jambos (L.) Alston, Myrtaceae. The structures of these compounds were elucidated by spectroscopic means. The cytotoxicity of the compounds was evaluated against the RAW 264.7 cell lines by the lactate dehydrogenase assay. All analyzed compounds were less cytotoxic than the positive control (actinomycin D, CC50 = 0.008 μM). The anti-inflammatory and anti-arthritic activities were evaluated by measuring inflammatory parameters in murine models. The two glycosylated flavonoids inhibited the production of tumor necrosis factor-α in RAW 264.7 cell line with IC50 of 1.68 and 1.11 μM, respectively. In addition, all flavonoids decreased the levels of tumor necrosis factor-α, C-reactive protein, and fibrinogen at a dose of 5 mg/kg in murine models, This work was supported by the National Herbarium of Bolivia and the Fundación de la Universidad Autónoma de Madrid (FUAM)

Subphthalocyanine (SubPc) chemistry has been limited so far by their high sensitivity toward strong nucleophiles. In particular, the substitution of the axial chlorine atom by a nucleophilic group in the case of less‐reactive SubPcs, such as those bearing electron‐withdrawing peripheral substituents, presents some limitations and requires harsh conditions. By taking advantage of the electrophilic character of DIBAL‐H, it has been possible to prepare for the first time SubPc‐hydride derivatives that exhibit high reactivity as hydroboration reagents of aldehydes. This hydride transfer requires using a typical carbonyl activator (trimethylsilyl triflate) and only one equivalent of aldehyde, affording SubPcs with an axial benzyloxy group in good yield. This transformation has proven to be a useful alternative method for the axial functionalisation of dodecafluoroSubPc, a paradigmatic SubPc derivative, by using electrophiles for the first time. Considering the increasing interest in SubPcs as electron‐acceptor semiconductors with remarkable absorption in the visible range to replace fullerene in organic photovoltaic (OPV) devices, it is of the utmost importance to develop new synthetic methodologies for their axial functionalisation., For the first time subphthalocyanine‐hydride derivatives that exhibit high reactivity as hydroboration reagents of aldehydes have been prepared. This transformation has proven to be a useful alternative method for the axial functionalisation of dodecafluoro‐subphthalocyanines using electrophiles. Considering the increasing interest in SubPcs as electron‐acceptor semiconductors to replace fullerene in organic photovoltaic devices, it is of the utmost importance to develop new synthetic methodologies for their axial functionalisation.

An amine functionalized C3‐symmetric benzotrithiophene (BTT) monomer has been designed and synthetized in order to form pH responsive one‐dimensional supramolecular polymers in aqueous media. While most of the reported studies looked at the effect of pH on the size of the aggregates, herein, a detailed mechanistic study is reported, carried out upon modifying the pH to trigger the formation of positively charged ammonium groups. A dramatic and reversible change in the polymerization mechanism and size of the supramolecular fibers is observed and ascribed to the combination of Coulombic repulsive forces and higher monomer solubility. Furthermore, the induced frustrated growth of the fibers is further employed to finely control the one‐dimensional supramolecular polymerisation and copolymerization processes., The synthesis and self‐assembly in aqueous media of an amine functionalized C3‐symmetric benzotrithiophene is reported. A dramatic change in the polymerization mechanism and size of the supramolecular fibers is observed upon modifying the pH, which is further employed to finely control the one‐dimensional supramolecular polymerization and copolymerization processes.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catalysis, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/abs/10.1021/acscatal.9b02768, The Supporting Information (experimental procedures, spectral data, and complete DFT studies) is available (PDF) free of charge on the ACS Publications website at DOI: 10.1021/acscatal.9b02768., We report on a regioselective, stereodivergent catalytic hydroarylation of unsymmetrical dialkyl alkynes with arylboronic acids that allows highly selective access to either the E or Z diastereoisomer of trisubstituted alkenes. The E selectivity is achieved through syn-carbopalladation of the alkyne by Ar–Pd species followed by protodepalladation in which a 2-pyridyl sulfonyl (SO2Py) directing group enables complete control of the regioselectivity. Access to the complementary stereochemistry is achieved through a tandem Pd/Ir sequence, which includes hydroarylation and E→Z photoisomerization. Finally, facile removal of the directing group by reduction, Julia–Kocienski olefination, or Cu-catalyzed C(sp3)–C(sp2) or C(sp3)–C(sp3) cross coupling allows for the selective preparation of stereodefined olefins and dienes, We thank the Spanish Ministerio de Economía, Industria y Competitividad and Fondo Europeo de Desarrollo Regional (Project: CTQ2015-66954-P, MINECO/FEDER, UE) and Ministerio de Ciencia, Innovación y Universidades (Agencia Estatal de Investigación)/FEDER (Project: PGC2018-098660−B-I00) for financial support. J.C. thanks the Ministerio de Educación, Cultura y Deporte (MECD), for a FPU fellowship. M.T.Q. thanks MINECO for a Juan de la Cierva Incorporación fellowship. The Centro de Computación Científica (UAM) is acknowledged for generous allocation of computer time

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/abs/10.1021/acs.orglett.9b01523. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b01523. Experimental procedures and spectral data for all new compounds (PDF): https://pubs.acs.org/doi/suppl/10.1021/acs.orglett.9b01523/suppl_file/ol9b01523_si_001.pdf, A general method for the construction of seven-membered rings through Pd-catalyzed C(sp2)-H carbonylation at the remote ϵ-position of γ-arylpropylamine derivatives, including chiral α-amino acids, has been developed using Mo(CO)6 as the CO source, furnishing richly functionalized benzo[c]azepin-1-one derivatives. The readily removable N-SO2Py protecting/directing group provides high levels of chemo-, regio- and diastereoselectivity. Furthermore, this method is amenable to the postsynthetic modification of complex molecules such as small peptides, We thank the Spanish Ministerio de Economía y Competitividad (Project CTQ2015-66954-P, MINECO/FEDER, UE) for financial support. M.M.-M. thanks MINECO for a FPI predoctoral fellow-ship. N.R. thanks the European Commission for a Marie Curie Ca-reer Integration Grant (CIG: CHAAS-304085). Prof. Inés Alonso (Departamento de Química Orgánica, UAM) is gratefully acknowl-edged for helpful discussions

The pyrrolidine ring is a privileged structural motif in synthetic and medicinal chemisty. This review aims to highlight the high versatility of the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides for access to different types of stereochemical patterns in enantioselective pyrrolidine synthesis. Special attention will be paid to stereodivergent procedures giving rise to different stereoisomers from the same starting materials, We acknowledge the Spanish Ministerio de Economía, Industria y Competitividad (Grant CTQ2015-66954-P, MINECO/FEDER, UE) and FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación (Grant PGC2018-098660-B-I00) for financial support

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de Lectura: 24-06-2021, Esta Tesis tiene embargado el Acceso al Texto completo hasta el 24-12-2022

A straightforward methodology for the regioselective synthesis of pyrazoles has been developed by a domino sequence based on a photoclick cycloaddition followed by a photocatalyzed oxidative deformylation reaction. Distinguishing features of this protocol include an unprecedented photoredox-catalyzed Norrish type fragmentation under green-light irradiation and the use of α,β-unsaturated aldehydes as synthetic equivalents of alkynes, where the aldehyde is acting as a novel photoremovable directing group, This work was supported by the MINECO (CTQ2014-53894-R and CTQ2017-85454-C2-2-P) and FEDER/MICIU (PGC2018-098660-B-I00) of Spain. L.O.-R. thanks MINECO for a FPI fellowship, and A.P.-E. thanks CAM for a postdoctoral fellowship

Cycloaddition reactions, in particular Diels‐Alder reactions, have attracted a lot of attention from organic chemists since they represent one of the most powerful methodologies for the construction of carbon‐carbon bonds. In particular, inverse‐electron‐demand hetero‐Diels‐Alder reactions have been an important breakthrough for the synthesis of heterocyclic compounds. Among all their variants, the organocatalytic enantioselective version has been widely explored since the asymmetric construction of diversely functionalized scaffolds under reaction conditions encompassed within the green chemistry field is of great interest. In this review, a profound revision on the latest advances on the organocatalytic asymmetric inverse‐electron demand hetero‐Diels‐Alder reaction is shown., In this review, a profound revision on the latest advances on the organocatalytic asymmetric inverse‐electron demand hetero‐Diels‐Alder reaction is shown.

The encapsulation of an organic dye, 10-phenylphenothiazine (PTH), in the inner cavity of single-walled carbon nanotubes (SWNTs) as a breaking heterogenization strategy is presented. The PTH@oSWNT material was microscopically and spectroscopically characterized, showing intense photoemission when illuminated with visible light at the nanoscale. Thus, PTH@oSWNT was employed as a heterogeneous photocatalyst in single electron transfer dehalogenation reactions under visible light irradiation. The material showed an enhanced photocatalytic activity, achieving turnover numbers as high as 3200, with complete recyclability and stability for more than eight cycles. Computational calculations confirm that electronic communication between both partners is established because, upon illumination, an electron of the excited PTH is transferred from the πsystem of the molecule to the delocalized π-cloud of the SWNT, thus justifying the enhanced photocatalytic activity, Financial support was provided by the European Research Council (ERC-CoG, contract number: 647550), the Spanish Government (RTI2018-095038-B-I00, PID2019-110091GB-I00), and the “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367). M.B. wishes to thank the Spanish Government for a Juan de la Cierva contract (IJC2019-042157-I). A.M.-S. acknowledges support by the Comunidad Autónoma de Madrid under grant 2016-T2/IND1660

Despite the emergence of catalytic C(sp3 )−H arylation at the remote δ-position via challenging six-membered ring cyclometalation, the requirement of blocking the more reactive γ-position represents a restricting limitation. The use of the removable N-(2-pyridyl)sulfonyl directing group provides a viable solution to this challenge, expanding the scope of the Pd-catalyzed δ-C−H arylation of α-amino acid and amine derivatives with (hetero)aryl iodides. This method is compatible with complex, multifunctional structures at either reaction partner. Experimental and density functional theory studies provide insights about the underlying factors controlling site selectivity, We thank the Ministerio de Economía, Industria y Competitividad (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER, UE) (Project CTQ2015-66954-P) and Ministerio de Ciencia e Innovación (MICINN)/FEDER, UE (Agencia Estatal de Investigación/Project PGC2018- 098660-B-I00) for the financial support

The asymmetric synthesis of chiral polycyclic ethers by an intramolecular [2+2] photocycloaddition is described. This process proceeded through a photocatalytically active iminium ion-based charge transfer (CT) complex under visible light irradiation. In this way a stereocontrolled [2+2] photocycloaddition is enabled leading to tricyclic products with good enantiomeric ratios, Financial support was provided by the European Research Council (ERC-CoG, Contract No. 647550), the Spanish Government (RTI2018-095038-B-I00, PID2019-110091GB-I00), ‘‘Comunidad de Madrid’’, and European Structural Funds (S2018/NMT-4367)

Tetracyanobuta-1,3-diene (TCBD) is a powerful and versatile electron-acceptor moiety widely used for the preparation of electroactive conjugates. While many reports addressing its electron-accepting capability have appeared in the literature, significantly scarcer are those dealing with its chemical modification, a relevant topic which allows to broaden the chemical space of this interesting functional unit. Here, we report on the first example of a high-yielding cyano-Diels-Alder (CDA) reaction between TCBD, that is, where a nitrile group acts as a dienophile, and an anthryl moiety, that is, acting as a diene. The resulting anthryl-fused-TCBD derivative, which structure was unambiguously identified by X-ray diffraction, shows high thermal stability, remarkable electron-accepting capability, and interesting electronic ground- and excited-state features, as characterized by a thorough theoretical, electrochemical, and photophysical investigation. Moreover, a detailed kinetic analysis of the intramolecular CDA reaction transforming the anthryl-TCBD-based reactant into the anthryl-fused-TCBD product was carried out at different temperatures.

On-surface synthesis has emerged as a powerful tool for the construction of large, planar, π-conjugated structures that are not accessible through standard solution chemistry. Among such solid-supported architectures, graphene nanoribbons (GNRs) hold a prime position for their implementation in nanoelectronics due to their manifold outstanding properties. Moreover, using appropriately designed molecular precursors, this approach allows the synthesis of functionalized GNRs, leading to nanostructured hybrids with superior physicochemical properties. Among the potential “partners” for GNRs, porphyrins (Pors) outstand due to their rich chemistry, robustness, and electronic richness, among others. However, the use of such π-conjugated macrocycles for the construction of GNR hybrids is challenging and examples are scarce. Herein, singly and doubly Por-capped GNR segments presenting a commensurate and triply-fused GNR–Por heterojunction are reported. The study of the electronic properties of such hybrid structures by high-resolution scanning tunneling microscopy, scanning tunneling spectroscopy, and DFT calculations reveals a weak hybridization of the electronic states of the GNR segment and the Por moieties despite their high degree of conjugation., Singly and doubly porphyrin-capped graphene nanoribbon segments are reported and their electronic properties are studied by high-resolution scanning tunneling microscopy and spectroscopy, and DFT calculations.

An environmentally benign protocol for the generation of nitrones from benzylic secondary amines via catalyst-free oxidation of secondary amines using H2O2 in MeOH or CH3CN is described. This methodology provides a selective access to a variety of C-aryl nitrones in yields of 60 to 93%. Several studies have been performed to shed light on the reaction mechanism and the role of the solvent, We thank FEDER/Ministerio de Ciencia, Innovación y Universidades−Agencia Estatal de Investigación (Grant PGC2018-098660-B-I00) and CAPES (Finance Code 001), CNPq (310514/2018-5), FAPEMIG for financial support

The recent development of organic polaritonic solar cells, in which sunlight absorbers and photon modes of a resonator are hybridized as a result of their strong coupling, has revealed the potential this interaction offers to control and enhance the performance of these devices. In this approach, the photovoltaic cell is built in such a way that it also behaves as an optical cavity supporting spectrally well-defined resonances, which match the broad absorption bands of the dyes employed. Herein we focus on the experimental and theoretical analysis of the specific spectral and angular optical absorption characteristics of a broadband light harvester, namely a subphthalocyanine, when operating in the ultrastrong coupling regime. We discuss the implications of having a broad distribution of oscillator strengths and demonstrate that rational design of the layered structure is needed to optimize both the spectral and the angular response of the sunlight harvester dye

Nanotubes are a fascinating kind of self‐assembled structure which have a wide interest and potential in supramolecular chemistry. We demonstrated that nanotubes of defined dimensions can be produced from dinucleobase monomers through two decoupled hierarchical cooperative processes: cyclotetramerization and supramolecular polymerization. Here we analyze the role of peripheral amide groups, which can form an array of hydrogen bonds along the tube axis, on this self‐assembly process. A combination of 1H NMR and CD spectroscopy techniques allowed us to analyze quantitatively the thermodynamics of each of these two processes separately. We found out that the presence of these amide directors is essential to guide the polymerization event and that their nature and number have a strong influence, not only on the stabilization of the stacks of macrocycles, but also on the supramolecular polymerization mechanism., The supramolecular self‐assembly process was compared for a set of guanine‐cytosine rod‐like dinucleobase monomers having a different number of peripheral amides, which revealed that these hydrogen‐bonding directing groups are essential to trigger and guide the stacking of Watson‐Crick‐bonded macrocycles into tubular nanostructures. These groups also have a strong influence on both nanotube stability, increasing with the number of peripheral amides, and on the polymerization mechanism, which can switch from cooperative to non‐cooperative.

Tripodanthus acutifolius, commonly known as Jamillo, is an herbal remedy used in traditional Andean medicine to treat joint problems, such as sprains, dislocations, and rheumatic pain. This study aimed to evaluate the in vitro and in vivo anti-inflammatory and anti-arthritic activity of the aqueous extract and isolated compounds of T. acutifolius. A bioguided phytochemical analysis based on NMR/MS was performed to identify the compounds of the aqueous extract from T. acutifolius. The anti-inflammatory and anti-arthritic activity were evaluated by measuring inflammatory parameters (TNF-α, C-reactive protein, and fibrinogen) in murine models. The chemical structure determination led to the identification of four flavonoids: (E)-2’,4’-dihydroxy-6’-methoxy-chalcone (1), 6,2’,4’-trimethoxyflavone (2), 5,3’,4’-trihydroxy-6,7,8-trimethoxyflavone (3), and 5,4’-dihydroxy-6,7,8-trimethoxyflavone (4). All compounds inhibited the production of TNF-α in the RAW 264.7 cell line, with IC50 values of 0.78, 1.43, 5.73, and 9.71 μM, respectively. In addition, all flavonoids decreased the levels of TNF-α, C-reactive protein, and fibrinogen at a concentration of 5 mg/kg in murine models. Our research shows that these compounds isolated from T. acutifolius have anti-inflammatory and anti-arthritic properties, providing scientific evidence for the traditional use of this plant species.

Herein, we describe the first on-surface preparation of porphyrin nanotapes (Por NTs) on a gold surface. Structural and electronic characterization reveals that the Por NTs carry one unpaired electron at each end, which leads to magnetic end states. This study provides an alternative and versatile route to the fabrication of Por NTs and a detailed atomic-scale characterization of their structural and electronic properties., Porphyrin nanotapes (Por NTs) are promising structures for their use as molecular wires thanks to a high degree of π-conjugation, low HOMO—LUMO gaps, and exceptional conductance. Such structures have been prepared in solution, but their on-surface synthesis remains unreported. Here, meso–meso triply fused Por NTs have been prepared through a two-step synthesis on Au(111). The diradical character of the on-surface formed building block PorA2, a phenalenyl π-extended ZnIIPor, facilitates intermolecular homocoupling and allows for the formation of laterally π-extended tapes. The structural and electronic properties of individual Por NTs are addressed, both on Au(111) and on a thin insulating NaCl layer, by high-resolution scanning probe microscopy/spectroscopy complemented by DFT calculations. These Por NTs carry one unpaired electron at each end, which leads to magnetic end states. Our study provides a versatile route towards Por NTs and the atomic-scale characterization of such tapes., This work was supported by the Swiss National Science Foundation under Grant No. 200020_182015, the European Union's Horizon 2020 research and innovation programme under grant agreement number 785219 (Graphene Flagship Core 2), the Office of Naval Research (N00014-18-1-2708), MINECO, CTQ2017-85393-P (Phthalophoto, T.T.), and PID2020-116490GB-I00 (Porphyrinoids, T.T., G.B.). IMDEA Nanociencia also acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686). R.R. and N.L. are grateful for funding from the EU-FET Open H2020 Mechanics with Molecules project (grant 766864).

Herein, an asymmetric organocatalytic aza-Michael addition reaction of ketimines to nitroolefins is presented. The use of 2-hydroxybenzophenone imine improves the enantioselective addition of N-centered nucleophiles to nitroalkenes by means of intramolecular hydrogen bond formation at the imine moiety. Moreover, the versatility of the process is demonstrated under both batch and flow conditions, showing the synthesis of a large variety of nitroamine derivatives with excellent yields and enantioselectivities. In addition, we applied this methodology to the formal synthesis of VNI, a drug-like scaffold for the treatment of Chagas disease, We acknowledge the financial support by the Spanish Govern ment (RTI2018-095038-B-I00) and ERC (ERC-CG, 647550, ERC-PoC, Contract No. 861930)

The β-fructofuranosidase from the yeast Schwanniomyces occidentalis (Ffase) produces potential prebiotic fructooligosaccharides (FOS) by self-transfructosylation of sucrose, being one of the highest known producers of 6-kestose. The use of Green Solvents (GS) in biocatalysis has emerged as a sustainable alternative to conventional organic media for improving product yields and generating new molecules. In this work, the Ffase hydrolytic and transfructosylating activity was analysed using different GS, including biosolvents and ionic liquids. Among them, 11 were compatible for the net synthesis of FOS. Besides, two glycerol derivatives improved the yield of total FOS. Interestingly, polyols ethylene glycol and glycerol were found to be efficient alternative fructosyl-acceptors, both substantially decreasing the sucrose fructosylation. The main transfer product of the reaction with glycerol was a 62 g L−1 isomeric mixture of 1-O and 2-O-β-D-fructofuranosylglycerol, representing 95% of all chemicals generated by transfructosylation. Unexpectedly, the non-terminal 2-O fructo-conjugate was the major molecule catalysed during the process, while the 1-O isomer was the minor one. This fact made Ffase the first known enzyme from yeast showing this catalytic ability. Thus, novel fructosylated compounds with potential applications in food, cosmetics, and pharmaceutical fields have been obtained in this work, increasing the biotechnological interest of Ffase with innocuous GS., This work was supported by the Spanish Ministry of Science, Innovation, and Universities [Grants: RTI2018-096037-B-I00, RTI2018-093431-B-I00 and PID2019-105838RB-C3-2] and of Economy and Competitiveness [BIO2016-76601-C3-2-R], as well as Fundación Ramón Areces [XIX Call of Research Grants in Life and Material Sciences]. Besides, funding has been received from the Gobierno de Aragón (E37_20R) and the European Regional Development Fund (ERDF). Centro de Biología Molecular Severo Ochoa was benefited from an institutional grant from Fundación Ramón Areces. Mr D. Piedrabuena and Mr A. Leal-Duaso were the recipient of a doctoral fellowship from the Spanish Ministry of Education, Culture, and Sports [FPU014/01004 and FPU014/04338].

Mechanistic insights into the factors that control chemoselectivity in competing C(sp2 )–H and C(sp3 )–H activation pathways in the palladium-catalyzed carbonylative cyclization of γ-arylated valine type derivatives, gained by experimental observations and DFT studies, have been leveraged to reverse the remarkable selectivity of Pd for arene C(sp2 )–H activation over C(sp3 )–H cleavage. These studies suggest that ε-C(sp2 )–H bond cleavage is significantly faster and more reversible than the γ-C(sp3 )–H bond activation, whereas subsequent AcOH/CO exchange and CO insertion from the C(sp3 )-palladacycle lead to more stable intermediates from which the reaction is irreversible. Control of chemoselectivity has been achieved by playing on the reaction conditions to favour thermodynamic over kinetic control. Addressing this fundamental limitation of C–H functionalization under Pd-catalysis has enabled the access to different heterocyclic frameworks (i.e., γ-lactams instead of benzazepinone skeletons) from the same starting substrate, We thank the Ministerio de Economía, Industria y Competitividad (Project CTQ2015-66954-P, MINECO/FEDER, UE) and Ministerio de Ciencia, Innovación y Universidades/ FEDER (Agencia Estatal de Investigación/Project PGC2018- 098660-B-I00) for financial support

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 10-11-2021, EL presente trabajo ha sido financiado por el Ministerio de Economía y Competitividad (MINECO CTQ2012-35790; MINECO/FEDER, UE CTQ2015-66954-P y MINECO/FEDER, UE PGC2018-098660-B-I00)

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de Lectura: 16-09-2021, Esta tesis tiene embargado el acceso al texto completo hasta el 16-03-2023, Durante las últimas décadas, los materiales porosos han despertado gran interés tanto a nivel científico como tecnológico, debido a su gran variedad de aplicaciones en diversos campos de estudio. Entre ellos, los polímeros orgánicos porosos son un tipo de materiales muy atractivos debido a que sus propiedades pueden ser modulables mediante el diseño y la selección adecuada de sus bloques de construcción. En la presente Tesis Doctoral se han diseñado y desarrollado nuevos materiales orgánicos porosos POPs (Porous Organic Polymers) y han sido utilizados en catálisis heterogénea y como sensores de derivados nitro aromáticos. En primer lugar, se han sintetizado una serie de unidades con simetría C3, en particular derivados de triindol, N1,N3,N5-trifenilbenceno-1,3,5-trimetilamina y truxenona, para ser utilizados como monómeros en la preparación de POPs. Para ello se emplearon diversas metodologías de acoplamiento C-C (Yamamoto, Suzuki-Miyaura y acoplamientos catalizados por ácidos de Lewis). Estos materiales porosos se estudiaron como catalizadores en diferentes reacciones activadas con luz (acoplamiento dehidrogenativo aza-Henry, oxidación de alcoholes bencílicos, acoplamiento oxidativo de bencil amina oxidación de α-terpineno). Se ha estudiado también su reciclabilidad en diferentes ciclos de reacción. Los POPs obtenidos se evalúan también como posibles sensores para la detección de compuestos tóxicos en concreto hacia compuestos nitroaromáticos, During the last decades, porous materials have aroused great interest at both scientific and technological levels, due to their wide variety of applications in various fields of study. Among them, porous organic polymers are a very attractive type of materials because their properties can be modulated by the design and proper selection of their building blocks. In this doctoral thesis, new porous organic materials have been designed and developed POPs (Porous Organic Polymers) capable of being used in heterogeneous catalysis and as sensors for nitro aromatic derivatives. First, a series of units with C3 symmetry have been synthesized, in particular triindole, N1,N3,N5-triphenylbenzene-1,3,5-trimethylamine and truxenone to be used as monomers in the preparation of POPs. For this purpose, various C-C coupling methodologies (Yamamoto, Suzuki-Miyaura and Lewis acid-catalyzed couplings) were employed. These porous materials have been studied in different lightactivated reactions (aza-Henry dehydrogenation coupling, oxidation of benzyl alcohols, oxidative coupling of benzyl amine oxidation of α-terpinene). Their recyclability in different reaction cycles is also studied. The POPs obtained were also evaluated as possible sensors for the detection of toxic compounds in particular towards nitroaromatic compounds

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 28-05-2021

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 06-10-2021, Amines and amino acids are common structural motifs present in a wide number of natural products, biologically active molecules, and highly valuable organic materials. Over the last years, the transition metal-catalyzed functionalization of C–H bonds has emerged as one of the most direct strategies for the post-synthetic modification of this organic features. This dissertation outlines our efforts in the development of novel C–H bond functionalization processes that allow the derivatization of amine derivatives in further positions. For that purpose, we have explored the potential of the 2-pyridylsulfonyl (NSO2Py) group as directing group in long-range Pd-catalyzed C–H functionalization processes, achieving high levels of regio- and chemoselectivity. In particular, we have achieved: - The construction of seven-membered heterocycles, concretely benzazepinone derivatives, through a carbonylative cyclization strategy in 􀁈��-position of γ-arylpropyl amine derivatives. - A switchable site-selective methodology in the carbonylative cyclization reaction of γ- aryl-valine type derivatives to obtain benzazepinone or γ-lactam derivatives, through a combination of DFT and experimental mechanistical studies. - The direct introduction of an (hetero)aryl ring in the δ-position of alkyl amine and amino acid derivatives, independently of the substitution pattern along the side-chain. - The selective δ-acetoxylation of alkyl amine derivatives employing PhI(OAc)2 as both oxidant and acetate source, This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO, Grant CTQ2015-66954-P, MINECO/FEDER, UE) and the Spanish Ministerio de Ciencia Innovación y Universidades/FEDER (Agencia Estatal de Investigación/Project PGC2018-098660-B-I00). I also thank MINECO for a FPI predoctoral fellowship (2016- 2021)

Photodynamic therapy (PDT) is becoming a promising way to treat various kinds of cancers, with few side effects. Porphyrinoids are the most relevant photosensitizers (PS) in PDT, because they present high extinction coefficients, biocompatibility, and excellent photochemical behavior. To maximize therapeutic effects, polymer‐PS conjugates, and PS‐loaded nanoparticles have been developed, with insights in improving tumor delivery. However, some drawbacks such as non‐biodegradability, multistep fabrication, and low reagent loadings limit their clinical application. A novel strategy, noted by some authors as the “one‐for‐all” approach, is emerging to circumvent the use of additional delivery agents. This approach relies on the self‐assembly of amphiphilic PS to fabricate nanostructures with improved transport properties. In this review we focus on different rational designs of porphyrinoid PS to achieve some of the following attributes in nanoassembly: i) selective uptake, through the incorporation of recognizable biological vectors; ii) responsiveness to stimuli; iii) combination of imaging and therapeutic functions; and iv) multimodal therapy, including photothermal or chemotherapy abilities., PDT improved: Self‐assembled photosensitizers (PS) built through the “one‐for‐all” approach can help to overcome the disadvantages of traditional nanodelivery systems. This minireview aims to show the potential of this emerging strategy highlighting different rational designs of porphyrinoid PS to achieve nanosystems with improved therapeutic effects, such as selective uptake, responsiveness to stimuli, nanotheranostics abilities and multimodal therapy.

openaire: EC/H2020/794536/EU//BiHyOMat Funding Information: We acknowledge the provision of facilities and technical support by Aalto University Bioeconomy Facilities and OtaNano – Nanomicroscopy Center (Aalto-NMC) and funding from the Jane and Aatos Erkko Foundation. The authors also thank Sofia Julin and Heini Ijäs from Department of Bioproducts and Biosystems, Aalto University, for providing DNA origami samples. IMDEA Nanociencia also acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, grant SEV-2016-0686). Funding Information: We acknowledge the Academy of Finland (286845, 308578), the Magnus Ehrnrooth Foundation, and the Marie Sklodowska-Curie grant (794536). MINECO-Feder funds (CTQ2017-85393-P (TT), CTQ-2014-53673-P and CTQ-2017-89539-P (AdlE), and PCIN-2017-042/EuroNanoMed2017-191, TEMPEAT (TT)). Publisher Copyright: © 2021 American Chemical Society. Design and synthesis of novel photosensitizer architectures is a key step toward new multifunctional molecular materials. Photoactive Janus-type molecules provide interesting building blocks for such systems by presenting two well-defined chemical functionalities that can be utilized orthogonally. Herein a multifunctional phthalocyanine is reported, bearing a bulky and positively charged moiety that hinders their aggregation while providing the ability to adhere on DNA origami nanostructures via reversible electrostatic interactions. On the other hand, triethylene glycol moieties render a water-soluble and chemically inert corona that can stabilize the structures. This approach provides insight into the molecular design and synthesis of Janus-type sensitizers that can be combined with biomolecules, rendering optically active biohybrids.

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de Lectura: 20-07-2021, La financiación de este trabajo ha provenido del Ministerio de Economía y Competitividad (CTQ2016-78557-R y PID2019-104125RB-I00)

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 20-11-2020, Esta tesis tiene embargado el acceso al texto completo hasta el 20-05-2022

Three carbamidocyclophanes, A, F and V, and carbamidocylindrofridin A were isolated from the cultured freshwater cyanobacterium Cylindrospermum stagnale, collected in the Canary Islands. The chemical structures of these compounds were elucidated through NMR, HRMS and ECD spectroscopy. The absolute configuration of carbamidocyclophane A was confirmed using X-ray-diffraction. All compounds showed apoptotic capacity against the SK-MEL-1, SK-MEL-28 and SK-MEL-31 tumour cells. Carbamidocylindrofridin A had the highest anti-tumour potential, with an IC50 of 1 ± 0.3 μM in the SK-MEL-1 cell line, This work was supported by the Fundación de la Universidad Autónoma de Madrid (FUAM)

Ethno-pharmacological relevance: Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta “Huacatay” is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. Aim of the study: The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. Materials and methods: Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. Results: Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 μg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 μM for compound 1 and 7.91–9.87 μM for compound 2. Conclusions: The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfort, This work was supported by the National Herbarium of Bolivia and the Fundación de la Universidad Autónoma de Madrid (FUAM)

In the scientific race to build up photoactive electron donor‐acceptor systems with increasing efficiencies, little is known about the interplay of their building blocks when integrated into supramolecular nanoscale arrays, particularly in aqueous environments. Here, we describe an aqueous donor‐acceptor ensemble whose emergence as a nanoscale material renders it remarkably stable and efficient. We have focused on a tetracationic zinc phthalocyanine (ZnPc) featuring pyrenes, which shows an unprecedented mode of aggregation, driven by subtle cooperation between electrostatic and π–π interactions. Our studies demonstrate monocrystalline growth in solution and a symmetry‐breaking intermolecular charge transfer between adjacent ZnPcs upon photoexcitation. Immobilizing a negatively charged fullerene (C60) as electron acceptor onto the monocrystalline ZnPc assemblies was found to enhance the overall stability, and to suppress the energy‐wasting charge recombination found in the absence of C60. Overall, the resulting artificial photosynthetic model system exhibits a high degree of preorganization, which facilitates efficient charge separation and subsequent charge transport., The synergy between different non‐covalent interactions is modulated to achieve supramolecular hybrids as electron donor‐acceptor photoactive systems consisting of a tetracationic zinc(II) phthalocyanine and anionic water‐soluble fullerenes. In the resulting monocrystalline assemblies, all the fundamental processes of natural photosynthesis are operative and give rise to highly efficient artificial photosynthetic systems.

Ethno–pharmacological relevance The genus Artemisia spp. is well known for its anti–infectious properties and its high content in anti–infectious compounds, like the well–known sweet wormwood (Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. Aim of the study The aim of this study is to investigate the anti–HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. Materials and methods Antiviral activity of isolated compounds and extracts was evaluated in HIV–1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV–1 and VSV pseudotyped HIV–1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV–1 or NF–κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. Results Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. glutinosa displayed anti–HIV activity in vitro, although ethanolic extract was more powerful (IC50 14.62 μg/mL). Bio–guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2’, 4’–trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV–1 replication in vitro with IC50 values between the middle nanomolar and the low micromolar range. Their anti–HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF–κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. Conclusion We describe here the anti–HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in the treatment of different diseases. Besides, the presence of several compounds with dual and different mechanisms of action could prove useful in the treatment of HIV–1 infection, since it could aid to overcome drug resistances and simplify drug therapy. This work is a further step in understanding the anti–infectious activity of wormwood species and their use in treating infectious diseases., Graphical abstract Image 1, Highlights • Artemisia campestris subsp. glutinosa (Besser) Batt. ethanolic and aqueous extracts inhibit HIV–1 replication in vitro. • Two terpenes, damsin and canrenone, and four flavonoids, 6,2’,4’–trimethoxyflavone, acerosin, cardamonin and xanthomicrol have been isolated from the active anti–HIV fractions. • Acerosin and xanthomicrol inhibit viral entry while damsin, canrenone, 6, 2’, 4’–trimethoxyflavone and xanthomicrol, and also acerosin, show activity in HIV–1 transcription. • Flavonoids displayed also an antioxidant effect which showed no correlation with the transcriptional activity. • All the isolated compounds acted through cellular targets, cellular receptors and transcription factors, suggesting their potential involvement in other diseases.

A general catalytic anti-hydroarylation of electron-deficient internal alkynes compatible with both electron-poor and electron-rich aryl reagents is reported. This selectivity is achieved through a sequential syn-carbopalladation of the alkyne by an Ar-Pd species, followed by a tandem, Ir-photocatalyzed, counter-thermodynamic E → Z isomerization. The use of ortho-substituted boronic acids enables direct access to pharmaceutically relevant heterocyclic cores via a cascade process. Mechanistic insight into the involvement of Ar-Pd versus Pd-H as an active species is provided, We thank the Ministerio de Economía, Industria y Competitividad (CTQ2015-66954-P, MINECO/FEDER, UE and FEDER/Ministerio de Ciencia, Innovación y Universidades- ́ Agencia Estatal de Investigación/Proyecto PGC2018-098660- ́ B-I00) for financial support

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura:16-07-2020, Esta Tesis tiene embargado el acceso al texto completo hasta el 16-01-2022, La detección de resistencias, por parte de los microorganismos, a los antiinfeciosos durante las últimas décadas han provocado la necesidad de desarrollo nuevos fármacos, con el fin de hacerlos frente, los productos naturales han servidos como base para el tratamiento de enfermedades desde el principio de los tiempos. A pesar del descenso en este tipo de investigación durante los años 90 por partes de las industrias farmacéuticas, actualmente vuelve a haber un repunte en la búsqueda de nuevos candidatos y cabeza de series de fuente natural debido a la especificidad que poseen sobre las dianas biológicas. La tesis que se presenta engloba un conjunto de proyectos con el objetivo de encontrar nuevos candidatos a través de distintas estrategia en la búsqueda de nuevos fármacos desde la naturaleza a la optimización de un candidato por síntesis química. En el primer capítulo se ha aislado un alcaloide con esqueleto terpénico en el cual se ha elucidado su estructura: con técnicas de espectroscopia de RMN, espectrometría de masas junto con el estudio de su susceptibilidad biológica antibiótica y antifúngica. En el segundo capítulo se ha optimizado por síntesis química un cabeza de serie denominado fenildihidracina con actividad antifúngica por estudios de estructuras actividad junto con estudios de toxicidad bastante prometedores. En el tercer capítulo se ha puesto a punto la síntesis de derivados del ácido murámico y con ellos se han sintetizado unas serie de cores para final mente unirlos y formar distintos glicomiméticos a través de reacciones de click chemistry, El trabajo descrito en esta memoria se ha desarrollado en el marco de los proyectos de colaboración entre la Fundación de la Universidad Autónoma de Madrid (FUAM) y la Empresa Valoralia I más D y proyectos del Plan Nacional de I+D+i.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catalysis, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/full/10.1021/acscatal.0c01413, An asymmetric aminocatalytic activation strategy to obtain enantioenriched cyclobutanes through [2 + 2] photocycloaddition under visible light irradiation is presented. This metal-free process does not require the use of any external photocatalyst, as it is catalyzed by a simple diamine which, upon condensation with an enone substrate, forms an iminium ion intermediate that absorbs in the visible light region. The direct excitation of such an intermediate leads to a charge transfer (CT) excited state that unlocks a stereocontrolled intermolecular photocycloaddition with good enantiomeric and diastereoisomeric ratios and high yields. Finally, DFT calculations and experiments were performed to support the charge transfer behavior and the mechanistic proposal, Financial support was provided by the European Research Council (ERC-CoG, Contract No. 647550), the Spanish Government (RTI2018-095038–B-I00), “Comunidad de Madrid”, and European Structural Funds (S2018/NMT-4367)

Dynamic and reversible non‐covalent interactions endow synthetic systems and materials with smart adaptive functions that allow them to response to diverse stimuli, interact with external agents, or repair structural defects. Inspired by the outstanding performance and selectivity of DNA in living systems, scientists are increasingly employing Watson−Crick nucleobase pairing to control the structure and properties of self‐assembled materials. Two sets of complementary purine‐pyrimidine pairs (guanine:cytosine and adenine:thymine(uracil)) are available that provide selective and directional H‐bonding interactions, present multiple metal‐coordination sites, and exhibit rich redox chemistry. In this review, we highlight several recent examples that profit from these features and employ nucleobase interactions in functional systems and materials, covering the fields of energy/electron transfer, charge transport, adaptive nanoparticles, porous materials, macromolecule self‐assembly, or polymeric materials with adhesive or self‐healing ability., Inspired by DNA: H‐bonding interactions between complementary nucleobases, namely G : C and A : T(U), as well as their coordination to metals can be employed for the generation of functional systems and materials with potential applications in diverse fields, including photosynthetic models, porous materials, chemical sensing, drug delivery, or self‐healable polymer networks.

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fchem. 2020.00306/full#supplementary-material, In this work we describe the linear and non-linear (chiro)optical properties of an enantiopure bis-perylenediimide (PDI) cyclohexane derivative. This compound exhibits upconversion based on a two-photon absorption (TPA) process with a cross-section value of 70 GM together with emission of circularly polarized luminescence (CPL), showing a glum in the range of 10−3. This simple structure represents one of the scarce examples of purely organic compounds combining both TPA and CPL responses, together with large values of molar absorptivity and fluorescence quantum yield with emission in the 500–600 nm. Self-assembly induced by introduction of a poor solvent allows for a spectacular shift of the emission into the near-infrared (NIR, 650–750 nm) by formation of well-defined rotationally displaced dimers. Therefore, we are here presenting a versatile platform whose optical properties can be simply tuned by self-assembly or by functionalization of the electron-deficient aromatic core of PDIs., Ministerio de Ciencia, Innovacion y Universidades PG2018-101181-B-I00, Spanish Government CTQ2017-85454-C2-1-P, European Research Council (ERC) ERC-2015-STG-677023, MINECO RyC-2013-12943, Spanish Government, Portuguese Foundation for Science and Technology, POCI, European Union (EU) PTDC/NAN-MAT/29317/2017 PTDC/QUI-QFI/29319/2017 UIDB/00100/2020

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 20-04-2020, Esta tesis tiene embargado el acceso al texto completo hasta el 20-10-2021, La presente tesis ha sido realizada en el Departamento de Química Orgánica de la Universidad Autónoma de Madrid, bajo la supervisión del Prof. Dr. José Julián Alemán Lara. La financiación de este trabajo ha provenido del Consejo Europeo de Investigación (ERC-CG, número de contrato 647550), del Ministerio de Economía y Competitividad (CTQ-2015-64561-R y RTI2018-095038- B-I00), de la “Comunidad de Madrid” y de los Fondos Estructurales y de Inversión Europeos (S2018/NMT-4367)

This is the peer reviewed version of the following article: Rigotti, T., Asenjo‐Pascual, J., Martín‐Somer, A., Milán Rois, P., Cordani, M., Díaz‐Tendero, S., ... & Alemán. Boron Dipyrromethene (BODIPY) as Electron‐Withdrawing Group in Asymmetric Copper‐Catalyzed [3+ 2] Cycloadditions for the Synthesis of Pyrrolidine‐Based Biological Sensors. Advanced Synthesis & Catalysis Volume 362, Issue 6, 17 March 2020, Pages 1345-1355 , which has been published in final form at https://doi.org/10.1002/adsc.201901465. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions, In this work, we describe the use of Boron Dipyrromethene (BODIPY) as electron-withdrawing group for activation of double bonds in asymmetric copper-catalyzed [3+2] cycloaddition reactions with azomethine ylides. The reactions take place under smooth conditions and with high enantiomeric excess for a large number of different substituents, pointing out the high activation of the alkene by using a boron dipyrromethene as electron-withdrawing group. Experimental, theoretical studies and comparison with other common electron-withdrawing groups in asymmetric copper-catalyzed [3+2] cycloadditions show the reasons of the different reactivity of the boron dipyrromethene derivatives, which can be exploited as a useful activating group in asymmetric catalysis. Additional experiments show that the so obtained pyrrolidines can be employed as biocompatible biosensors, which can be located in the endosomal compartments and do not present toxicity in three cell lines, This work was supported by the Spanish Government (RTI2018‐095038‐B‐I00, CTQ2016‐76061‐P, SAF2017‐87305‐R), Comunidad de Madrid (IND2017/IND‐7809), and co‐financed by European Structural and Investment Fund. We acknowledge the generous allocation of computing time at the CCC (UAM). Financial support from the Spanish Ministry of Economy and Competitiveness, through the ‘‘Maria de Maeztu’’ Program of Excellence in R&D (MDM‐2014‐0377), is also acknowledged. Asociación Española Contra el Cáncer, and IMDEA Nanociencia acknowledge support from the ′Severo Ochoa′ Programme for Centres of Excellence in R&D (MINECO, Grant SEV‐2016‐0686). P.M.R thanks the Ministry of Economy, Industry and competitiveness of Spain for the FPI grant (BES‐2017.082521). A.M.S. thanks CAM for a postdoctoral contract (2016‐T2/IND‐1660)

Electronic version of an article published as Journal of Porphyrins and Phthalocyanines, Vol 24, N.01n03, 2020, pp. 33-42. DOi: https://doi.org/10.1142/S1088424619300167 © World Scientific Publishing Company. https://www.worldscientific.com/doi/abs/10.1142/S1088424619300167, In this small review article, we provide an overview of the different self-assembled systems and materials created so far by rationally organizing fluorosubphthalocyanines in a non-centrosymmetric fashion, which allows access to novel polarly ordered liquid crystalline materials that can be aligned in the presence of electric fields and that exhibit permanent or switchable (i.e. ferroelectric) polarization, We would like to thank all collaborators who enthusiastically contributed to the development of the science presented in this review. Funding from MINECO CTQ2017-84727-P (DGR) and CTQ2017-85393-P (TT) is gratefully acknowledged.

The current study presents a direct CF2H radical addition to C=N bonds predicated on the photocatalytic activation of commercially available zinc difluoromethanesulfinate. The mild conditions in place lead to impressive structural diversity, as quinoxalinones and dibenzazepines, among others, are successfully functionalized, Financial support was provided by the European Research Council (ERC-CoG, contract number: 647550), Spanish Government (RTI2018-095038-B-I00), ‘‘Comunidad de Madrid’’ and European Structural Funds (S2018/NMT-4367)

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 14-02-2020, Esta tesis tiene embargado el acceso al texto completo hasta el 14-08-2021, En esta tesis doctoral se han desarrollado nuevos fotosensibilizadores para su aplicación en terapia fotodinámica. Este tratamiento aplica luz del espectro visible, sobre una molécula fotosensible capaz de activar el oxígeno molecular presente en el entorno celular, produciendo especies activadas citotóxicas de oxígeno, como oxígeno singlete, capaces de inducir muerte celular. Concretamente se han preparado fotosensibilizadores de segunda generación de tipo porfirinoide basados en ftalocianinas de Zn(II) (Zn(II)Pcs). En concreto, en este trabajo hemos elegido como objetivo la preparación de Zn(II)Pcs formadas por dos tipos de isoindoles con diferente sustitución, denominadas comúnmente como A2B2, que pueden presentar dos variantes estructurales, es decir, ABAB y AABB. Estas geometrías altamente orientadas, permiten combinar sustituyentes hidrófobos e hidrófilos para dar lugar a anfífilos con la capacidad de interaccionar con medios lipófilos celulares así como facilitar el transporte en medios acuosos. La Parte 1 de esta tesis doctoral está orientada a la preparación de Zn(II)Pcs ABAB. La síntesis en todos los casos está dirigida por el uso de un ftalonitrilo que presenta grupos voluminosos que impiden la formación de la especie AABB. Estos grupos voluminosos, además, poseen unidades fluoradas que dotan a la estructura final de unas características electrónicas peculiares. Esta particular sustitución, no solo evita fenómenos de agregación, unos de los principales factores limitantes del uso de macrociclos porfirinoides en terapia fotodinámica, sino que además potencia la capacidad de las ftalocianinas para producir especies reactivas de oxígeno, como oxígeno singlete. Hemos sido capaces de combinar este patrón de sustitución con sustituyentes hidrófilos formando anfífilos. La introducción de sustituyentes con cadenas de tipo polietilenglicol destruye eficientemente cultivos celulares in vitro de cáncer de piel y de cuello de útero, y se ha demostrado cómo el patrón de sustitución ABAB es más efectivo que otros dentro de la misma familia (A3B y A4). Por otra parte, la incorporación de grupos funcionales cargados positivamente convierte estos compuestos en antimicrobianos frente S. aureus y E. coli. En la Parte 2 de esta tesis doctoral se ha trabajado con Zn(II)Pcs de tipo AABB, las cuales se han preparado utilizando un conector binaftol que evita la formación de especies ABAB. En este caso el conectol binaftol presenta quiralidad por restricción conformacional, lo que ha permitido obtener Zn(II)Pcs quirales que pueden ser estudiadas y caracterizadas por dicroísmo circular. Este tipo de compuestos pueden presentar cierta capacidad de auto-ensamblaje dependiendo del medio elegido, y que está influida por el conector quiral. De nuevo la incorporación de sustituyentes hidrófilos permite la formación de especies anfifílicas, de tal forma que la organización inducida en medio acuoso ha dado lugar a la formación de nanoestructuras de tipo micelar o vesicular, mientras que en medios más apolares como puede ser el interior celular, se encuentran molecularmente disueltas. Concretamente se han preparado derivados AABB funcionalizados con cargas positivas, efectivos en la inactivación de bacterias Gram positivas y Gram negativas. Además, también se ha decorado el conector binaltol con cadenas de polietilenglicol y se ha hecho un estudio en profundidad de su capacidad de organización en medios polares como el agua.

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgáncia. Fecha de lectura: 13-02-2020