Fernando P Cossío

Fernando P Cossío
Universidad del País Vasco / Euskal Herriko Unibertsitatea | UPV/EHU · Organic Chemistry I

PhD

About

367
Publications
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8,582
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February 1988 - present
Universidad del País Vasco / Euskal Herriko Unibertsitatea
Position
  • Professor (Full)

Publications

Publications (367)
Article
Radio-frequency (RF) carpets with ultra-fine pitches are examined for ion transport in gases at atmospheric pressures and above. We develop new analytic and computational methods for modeling RF ion transport at densities where dynamics are strongly influenced by buffer gas collisions. An analytic description of levitating and sweeping forces from...
Article
Full-text available
The synthesis and isolation of one of the few examples of a π-extended diamagnetic phenazine dication have been achieved by oxidizing a phenanthrene-based dihydrophenazine precursor. The resulting dication was isolated and fully characterized, highlighting an aromatic distorted structure, generated by the conformational change upon the oxidation of...
Preprint
Full-text available
If neutrinos are their own antiparticles, the otherwise-forbidden nuclear reaction known as neutrinoless double beta decay ($\beta\beta 0\nu$) can occur, with a characteristic lifetime which is expected to be very long, making the suppression of backgrounds a daunting task. It has been shown that detecting (``tagging'') the Ba$^{+2}$ dication produ...
Article
Experimental and computational studies reveal the importance of isomerization pathways in the Staudinger reaction between ketenes and imines. In the studied cases, the stereochemistry is determined by the pre-cycloaddition isomerization step.
Article
We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development o...
Preprint
We report a measurement of the half-life of the ${}^{136}$Xe two-neutrino double beta decay performed with a novel direct background subtraction technique. The analysis relies on the data collected with the NEXT-White detector operated with ${}^{136}$Xe-enriched and ${}^{136}$Xe-depleted xenon, as well as on the topology of double-electron tracks....
Article
In a first instance, the effect of the microwave irradiation on the 1,3‐Dioxa‐[3,3]‐sigmatropic rearrangement of aryl allylic carbamates was investigated. Under these new conditions, the reaction acceleration was clearly highlighted compared to conventional heating conditions. Depending on the electronic nature of substituents on the aromatic group...
Article
Dimeric unnatural prolines can show emergent catalytic properties with respect to their monomeric analogues. When aldol reactions are studied, both monomeric and dimeric organocatalysts behave similarly, the stereocontrol shown by the dimers being additive with respect to their monomeric components. However, the ability of the dimers to promote Mic...
Article
Full-text available
Different densely substituted L‐ and D‐proline esters were prepared by asymmetric (3+2) cycloaddition reactions catalyzed by conveniently selected EhuPhos chiral ligands. The γ‐nitro‐2‐alkoxycarbonyl pyrrolidines thus obtained in either their endo or exo forms were functionalized and coupled to yield the corresponding γ‐dipeptides. The catalytic pr...
Article
Molecular entities whose fluorescence spectra are different when they bind metal cations are termed bicolour fluorescent molecular sensors. The basic design criteria of this kind of compounds are presented and the different fluorescent responses are discussed in terms of their chemical behaviour and electronic features. These latter elements includ...
Article
Full-text available
A bstract Next-generation neutrinoless double beta decay experiments aim for half-life sensitivities of ∼ 10 ²⁷ yr, requiring suppressing backgrounds to < 1 count/tonne/yr. For this, any extra background rejection handle, beyond excellent energy resolution and the use of extremely radiopure materials, is of utmost importance. The NEXT experiment ex...
Preprint
Full-text available
Next-generation neutrinoless double beta decay experiments aim for half-life sensitivities of ~$10^{27}$ yr, requiring suppressing backgrounds to <1 count/tonne/yr. For this, any extra background rejection handle, beyond excellent energy resolution and the use of extremely radiopure materials, is of utter importance. The NEXT experiment exploits di...
Article
Fluorescent tetracyclic imidazo[1,2‐a]pyri(mi)dines can be generated by microwave‐assisted high order (8+2) thermal cycloadditions between in situ formed benzynes and the corresponding bicyclic imidazo[1,2‐a]pyr(im)idines. These cycloadducts absorb and emit photons in the 400‐500 nm region and are efficiently uptaken by cells with low cytotoxicity....
Chapter
In this chapter, the main aspects that govern the relationship between aromaticity (as well as antiaromaticity) and molecular orbitals (MOs) are presented and discussed. The Hückel and Möbius theories are discussed first. The main concepts derived from this theoretical level are transferred to the self-consistent field-MO (SCF-MO, canonical orbital...
Article
Photodynamic therapy has been used to treat a variety of diseases, however there is a continuous search for new biocompatible photosensitizers. Herein, we demonstrate for the first time that imidazo[1,2‐ a ]pyrimidine compounds are able to generate singlet oxygen species, and can act as photosensitizers in the intracellular environment. Our results...
Article
Full-text available
A plethora of preclinical evidences suggests that pharmacological targeting of epigenetic dysregulation is a potent strategy to combat human diseases. Nevertheless, the implementation of epidrugs in clinical practice is very scarce and mainly limited to haematological malignancies. In this review, we discuss cutting-edge strategies to foster the ch...
Article
Full-text available
Observation of the neutrinoless double β decay is the only practical way to establish that neutrinos are their own antiparticles¹. Because of the small masses of neutrinos, the lifetime of neutrinoless double β decay is expected to be at least ten orders of magnitude greater than the typical lifetimes of natural radioactive chains, which can mimic...
Article
Full-text available
Background and aims: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical and pharmacological approaches are ineffective, and liver transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) and histone deacetylase 6 inhibitors (HDAC6is)...
Article
A mild, metal-free bromination method of arenes has been developed using the combination of bis(trifluoroacetoxy)iodobencene and trimethylsilyl bromide. In situ formation of dibromo(phenyl)-λ3-iodane (PhIBr2) is proposed as reactive intermediate. This methodology using PIFA-TMSBr has been applied with success to a great number of substrates (25 exa...
Article
Full-text available
An efficient and simple synthesis of novel trisubstituted 1H-pyrroles 4a-q via 1,3-dipolar cycloaddition of Δ3-trifluoromethyloxazolones 2a-d with both chromium and tungsten alkynyl Fischer carbene complexes (1a-h) is described. An unexpected and unreported -CF3 group elimination process was observed in the pyrrole structure. Our experimental and t...
Article
Full-text available
Designed repeat proteins catalyze the 1,3-dipolar reaction between an imine and a deficient dipolarophile in THF solution to form unnatural nitroproline esters, a reaction that no enzyme can catalyze. NMR studies and mutation experiments show that both acidic and basic residues can catalyze the reaction. The diastereocontrol of the reaction depen...
Preprint
Neutrinoless double beta decay ($\beta\beta0\nu$) is a putative nuclear decay that can occur if, and only if, neutrinos are their own antiparticles. Due to the smallness of neutrino masses, the lifetime of $\beta\beta0\nu$ is expected to be larger than $10^{26}$ yr, and the tiny expected signals are deeply buried in backgrounds associated with the...
Article
Chlorosulfates are molecules that have been known about for over a century, though their chemistry has not evolved much since then. The transformation of chlorosulfates into sultones is an example of new reactivity of this type of sulfur‐containing compound. The illustration shows a teacher explaining on the blackboard this transformation occurring...
Presentation
In this work, we present a new route to modify basalt fibers based on the synthesis of peptides, natural and unnatural, through ring-opening polymerization process.
Article
The so‐called Securinega alkaloids constitute a class of tetracyclic biologically active specialised metabolites isolated principally from subtropical plants belonging to the Phyllanthaceae family. Following a strategy based on alternative hypotheses for their biosynthesis, an easy and time‐efficient divergent synthesis enabled access to twelve of...
Article
Chlorosulfate derivatives are interesting reagents that have been traditionally used to get other sulfur‐containing compounds by formal nucleophilic substitution of the chlorine atom. Here, we describe a different mode of reactivity of alkyne‐containing chlorosulfates to get sultones, the sulfur analogues of lactones. The complex skeletal rearrange...
Article
The catalytic enantioselective 1,3-dipolar cycloaddition between imino esters and electrophilic alkenes, employing chiral metal complexes derived from copper(I) and silver(I) salts and (S)-DM- or (S)-DTBM-Segphos as ligands resulted diasterodivergently giving either exo- or endo-cycloadducts, respectively. The effect of the functional group of the...
Conference Paper
Histone deacetylase 6 (HDAC6) is a protein modifier that is an increasingly attractive pharmacological target. Interestingly, the observation that the HDAC6 knock-out mouse is not lethal, in contrast to those undergoing complete loss of class I, II and III HDACs, suggests that specific HDAC6 inhibitors may be better tolerated than pan-HDAC inhibito...
Conference Paper
Histone deacetylase 6 (HDAC6) is a protein modifier that is an increasingly attractive pharmacological target. Interestingly, the observation that the HDAC6 knock-out mouse is not lethal, in contrast to those undergoing complete loss of class I, II and III HDACs, suggests that specific HDAC6 inhibitors may be better tolerated than pan-HDAC inhibito...
Poster
In this Communication, our recent results on biomolecules with Huisgenase activity will be presented. The reaction tested consists of a formal (3+2) cycloaddition between in situ formed azomethine ylides and p-deficient alkenes to yield unnatural proline ester derivatives (Figure 1). The behavior of both Nmetallated and NH-azomethine ylides has bee...
Poster
In this contribution, we present our preliminary results1 on the design, chemical synthesis and experimental validation of novel molecules that can be used as sensors in Single Molecular Fluorescence Imaging (SMFI) of Ba2+ and related cations. Very recently, the NEXT collaboration2 has demonstrated that SMFI can be used in the detection (in aqueous...
Poster
In this contribution, is described a tandem reaction from 1- arylallyl alcohols involving an initial carbamoylation reaction followed by an unexpected metal-free 1,3- dioxa-[3,3]-sigmatropic rearrangement for a nonconventional access to linear allyl carbamates.1
Poster
The bioconjugation of DNA oligonucleotides, through amide bond coupling, has been extensively used in applications of biotechnological interest. Here we include biosensors, microarrays, DNA-polymer hybrids, or even commercial kits that rely on the function and specificity of DNA. Monitoring the chemical reaction is essential to evaluate the efficie...
Article
La La Ligand! Lanthanum(III) complexes incorporating enantiopure PyBOX ligands are suitable catalysts for the enantioselective trifluoromethylation of β‐oxo esters in the presence of hypervalent iodine Togni reagent. DFT calculations reveal that the enantioselectivity of the reaction stems from the rigid coordination pattern around the metallic cen...
Article
A highly enantioselective catalytic method for the synthesis of quaternary α‐trifluoromethyl derivatives of 3‐oxo esters is described. The reaction uses lanthanum (III) triflate and chiral pybox‐type C2‐symmetric ligands to generate intermediate La(III) complexes that incorporate an enolate moiety of the starting 3‐oxo ester and the trifluoromethyl...
Conference Paper
Histone deacetylase 6 (HDAC6) is a protein modifier that is an increasingly attractive pharmacological target. Interestingly, the observation that the HDAC6 knock-out mouse is not lethal, in contrast to those undergoing complete loss of class I, II and III HDACs, suggests that specific HDAC6 inhibitors may be better tolerated than pan-HDAC inhibito...
Article
Full-text available
An unexpected 1,3-dioxa[3,3]-sigmatropic oxo-rearrangement during the treatment of aryl- and alkenyl-substituted allylic alcohols with activated isocyanates is reported. The reorganization of bonds is highly dependent on the electron density of the aromatic ring and the nature of isocyanate used. This metal-free tandem reaction from branched allyl...
Article
All possible demethylation reactions of a diverse family of quaternary alkaloids by means of DFT calculations are here described. We aim to develop a rational model that allows explanation of the high selectivity observed experimentally and predicts the occurrence of new alkaloid derivatives. To this end, we have performed detailed analysis of the...
Article
NMR-based techniques are supposed to be incapable of distinguishing pure crystalline chemical enantiomers. However, through systematic studies of cross-polarization magic angle spinning (CP-MAS) NMR in ‎a series of aminoacids, we have found a rather unexpected behavior in the intensity pattern of optical isomers in hydrogen/nitrogen nuclear polariz...
Article
The mechanism of the cyclopropanation of alkanes with diazocompounds catalyzed by ClFeIII-porphyrin, [ClFeII-porphyrin]-, and FeII-porphyrin has been investigated by density functional theory calculations. The obtained results indicate that the only viable catalyst is the FeII-porphyrin, whose catalytic cycle involves a stepwise multistate (singlet...
Article
The organocatalytic properties of unnatural α‐amino acids are reviewed. Post translational derivatives of natural α‐amino acids include 4‐hydroxy‐L‐proline and 4‐amino‐L‐proline scaffolds, as well as proline homologues. Synthetic unnatural α‐amino acid‐based organocatalysts whose activity has been reviewed in this paper include β‐alkyl alanines, al...
Article
Full-text available
The (3+2) cycloaddition between azomethine ylides and alkenes is an efficient, convergent and stereocontrolled method for the synthesis of unnatural pyrrolidine and proline scaffolds. In this review, the application of this reaction to the synthesis of enantiopure organometallic ligands for asymmetric catalysis is presented first. These new EhuPhos...
Article
An efficient and alternative synthesis of exo-imidazolidin-2-one dienes is described. A condensation reaction was carried out with bis-imino derivatives, diacetyl, and triphosgene, affording symmetrically N,N-disubstituted dienes. The use of alkyl methyl α-diketones led to the formation of nonsymmetrical dienes, which underwent isomerization to pro...
Article
Full-text available
Herein, we present a fast, efficient and general one-pot method for the synthesis of ¹¹C-labelled compounds via the Negishi cross-coupling reaction. Our approach, based on the in situ formation of [¹¹C]CH3ZnI and subsequent reaction with aryl halides or triflates, has proven efficient to synthesize [¹¹C]thymidine, a biologically relevant compound w...
Article
Organocatalyzed (4+2) cycloadditions (Diels-Alder reactions) are reviewed in this manuscript. Among the different catalytic alternatives, reactions involving α,β-unsaturated ketones and alkenes are considered. In these processes, substituted cyclohexanones are obtained via HOMO activation generated by amine organocatalysis that generate transient d...
Article
1,3‐Dipolar cycloadditions (1,3‐DC) between imino esters (as precursors of N‐metallated azomethine ylides) and pi‐deficient alkenes are promoted by cooperative asymmetric Lewis acid‐ Brønsted base catalysis. The components of these catalytic pairs are silver salts derived from enantiopure commercially available BINOL‐based phosphoric acids and Cinc...
Article
Full-text available
In this work, we have studied computationally the N-demethylation reaction of methylamine, dimethylamine and trimethylamine as archetypal examples of primary, secondary and tertiary amines catalyzed by high field low spin Fe-containing enzymes such as cytochromes P450. Using DFT calculations, we have obtained that the expected C-H hydroxylation pro...
Article
A new three-component diastereo- and enantioselective cyclization reaction is described. The reaction takes place between a ketone, a carboxylic acid and a nitroalkene to yield a bicyclic octahydro-2H-indol-2-one scaffold possessing three chiral centers. This reaction involves a rearrangement of the nitro group under simple thermal conditions. A pl...
Article
Full-text available
A new three-component diastereo- and enantioselective cyclization reaction is described. The reaction takes place between a ketone, a carboxylic acid and a nitroalkene to yield a bicyclic octahydro-2H-indol-2-one scaffold possessing three chiral centers. This reaction involves a rearrangement of the nitro group under simple thermal conditions. A pl...
Article
The reactivity of nitrogen mustard mechlorethamine (mec) with purine bases towards formation of mono- (G-mec and A-mec) and dialkylated (AA-mec, GG-mec and AG-mec) adducts has been studied using density functional theory (DFT). In order to have a complete overview of DNA-alkylation processes, direct chloride substitution and formation through activ...
Article
Meso-aryl expanded porphyrins present a structural versatility that allows them to achieve different topologies with distinct aromaticities. Several studies appeared in the literature studying these topological switches from an experimental and theoretical point of view. Most of these publications include density functional theory calculations, bei...
Article
Full-text available
A novel catalytic system based on covalently modified DNA is described. This catalyst promotes 1,3-dipolar reactions between azomethine ylides and maleimides. The catalytic system is based on the distortion of the double helix of DNA by means of the formation of Pt(II) adducts with guanine units. This distortion, similar to that generated in the in...
Article
The reaction of chiral N-tert-butanesulfinyl aldimines with β-keto acids under basic conditions at room temperature proceeds with high levels of diastereocontrol, leading to β-amino ketones in high yields. Based on DFT calculations, an eight-membered cyclic transition state involving coordination of the lithium atom to the oxygens of carboxylate an...
Conference Paper
Stereoregular polymns. have attracted great attention since the first report reported by Natta to prep. isotactic polyprolylene. Given the almost limitless opportunities of ligand /metal combinations, it is not surprising that transition metal and organometallic catalysts have dominated the field. Nevertheless, their substantial toxicity and sensit...
Article
Full-text available
Although organometallic catalysts have shown great ability to promote stereocontrolled polymerization reactions, their substantial toxicity and other drawbacks are accelerating the development of organic catalysts. To date, organic catalysts have demonstrated some ability to promote stereocontrolled polymerizations. However, none of them has been a...
Article
The use of alkenyl arenes as dipolarophiles in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides is reported. Under appropriate reaction conditions with a CuI or AgI catalyst either the exo or the endo adduct was obtained with high stereoselectivity. This process provides efficient access to highly enantiomerically enriched 4-...
Article
The use of alkenyl arenes as dipolarophiles in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides is reported. Under appropriate reaction conditions with a CuI or AgI catalyst either the exo or the endo adduct was obtained with high stereoselectivity. This process provides efficient access to highly enantiomerically enriched 4-...
Conference Paper
Our group have developed an offspring of densely substituted unnatural L- and D- pyrrolidine derivatives 3 and 4 with endo- or exo- diastereoselectivity, respectively, in high enantioselectivities.[1] Encouraged by the efficiency of Proline-based organocatalysts in several C-C bond transformations, these novel densely substituted pyrrolidines (3 an...
Conference Paper
The synthesis of novel hybrid ferrocenylpyrrolidine ligands La* and Lb* via [3+2] cycloadditions has been described by our group.¹ Both ligands in turn provided densely substituted unnatural L- and D- proline derivatives in a stereodivergent manner. The powerful feature of having nitro and ester groups gives the opportunity to orthogonally synthesi...
Article
The N-demethylation reactions of N,N,N-trimethylpropan-1-ammonium and N,N-dimethyl-, and N-methylpropan-1-aminium cations in the presence of (AcO)2(imidazole)2(H2O)Fe=O complex have been studied by density functional theory. These transformations are suitable models for the N-demethylation of tri-, di-, and monomethylated lysine residues of histone...
Article
A donor-stabilized 1,3-disila-2,4-diazacyclobutadiene presents an exceptionally short nonbonded Si⋅⋅⋅Si distance (2.23 Å), which is as short as that of Si=Si bonds (2.15–2.23 Å). Theoretical investigations indicate that there is no bond between the two silicon atoms, and that the unusual geometry can be related to a significant coulomb repulsion be...
Article
A donor-stabilized 1,3-disila-2,4-diazacyclobutadiene presents an exceptionally short nonbonded Si⋅⋅⋅Si distance (2.23 Å), which is as short as that of Si=Si bonds (2.15–2.23 Å). Theoretical investigations indicate that there is no bond between the two silicon atoms, and that the unusual geometry can be related to a significant coulomb repulsion be...
Article
The reactivity of cisplatin towards different nucleophiles has been studied using density functional theory (DFT). Water was considered first in order to analyze the factors governing the transformation of cisplatin into more electrophilic aquated species by means of activation strain model. It was found that the selectivity and reactivity of cispl...
Article
This reaction is based on a [3,3]-allyl cyanate sigmatropic rearrangement via isocyanate intermediate which is trapped by several nucleophiles, opening the way for the preparation of chiral functionalized compounds such as the ?-ureido allylsilanes or carbamate derivatives.
Article
The enantioselective Taniaphos·silver fluoride-catalyzed enantioselective 1,3-dipolar cycloaddition using 2,2-dimethoxyacetaldehyde derived imino esters and maleimides is described. The employment of this complex allows the reaction in the absence of an extra base giving high yields and ee of the corresponding endo-cycloadducts. Calculations perfor...