Articles publicats en revistes (Química Inorgànica i Orgànica)
URI permanent per a aquesta col·leccióhttps://hdl.handle.net/2445/9245
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Enviaments recents
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Exploring hyperfine coupling in molecular qubits(Royal Society of Chemistry, 2025-05-23) Cardona, Joan; Solé, Albert; Mella, Pablo; Aravena Ponce, Daniel Alejandro; Ruiz-Hidalgo, Javier; Gómez Coca, Silvia; Ruiz Sabín, EliseoMolecular qubits represent a promising avenue for advancing quantum sensing and computing technologies, yet significant challenges remain in optimising their performance. Hyperfine coupling has a critical influence on molecular qubit properties. While previous studies have exhaustively investigated this phenomenon, a comprehensive understanding of the underlying mechanisms across different systems remains elusive. A benchmark test was performed using DFT to assess which methodology worked best to accurately predict hyperfine coupling constants in molecular qubits predominantly composed of VIV and CuII. We systematically analysed the decomposition of hyperfine coupling and examined how variations in coordination sphere and molecular geometry impact dipolar, isotropic and spin–orbit contributions. By modelling diverse systems, we demonstrate how molecular design can fine-tune hyperfine coupling contributions, either minimising overall interaction or enhancing coupling along specific axes. This study provides useful insights into the structure–property relationships governing hyperfine coupling mechanisms and assesses the accuracy of different choices of density functional, basis sets and relativistic corrections in the prediction of hyperfine coupling constants.Article
Time-optimal control of a solid-state spin amidst dynamical quantum wind(Springer Nature, 2024-11-05) Albareda, Guillermo; Guo, Guang-Can; Sun, Fang-Wen; Dong, Yang; Jiang, Wang; Gao, Xue-Dong; Yu, Cui; Liu, Yong; Zhang, Shao-Chun; Chen, Xiang-Dong; Moreira, Ibério de Pinho Ribeiro; Bofill i Villà, Josep M.; Sentis, Gael; Ramos, RamonTime-optimal control holds promise across the full spectrum of quantum technologies, where the rapid generation of unitary gates and state transformations is crucial to mitigate decoherence effects. In practical scenarios, quantum systems are always immersed in an external time-dependent field or potential, either owing to the inevitable influence of the environment or as a sought-after effect for enhanced coherence. The challenge then lies in finding the time-optimal approach to navigate quantum systems amidst dynamical ambient Hamiltonians, a pursuit that has proven elusive thus far. We showcase the implementation of arbitrary quantum state transformations and a universal set of single-qubit gates under a background Landau-Zener Hamiltonian. Leveraging the favorable coherence properties of timedomain Rabi oscillations, we achieve velocities surpassing the Mandelstam-Tamm quantum speed limit and significantly lower energy costs than those incurred by conventional quantum control techniques. These findings highlight a promising pathway to expedite and economize high-fidelity quantum operations.Article
Size-dependent antiferromagnetism and directobservation of Néel axes in NiO nanoparticles(Royal Society of Chemistry, 2025-07-19) Ara Escario, Jorge; Moya Álvarez, Carlos; García del Muro y Solans, Montserrat; Figueroa Garcia, Adriana Isabel; Aribó, Marta X.; Iglesias, Òscar; Kleibert, Armin; Labarta, Amílcar; Fraile Rodríguez, Arantxa; Batlle Gelabert, XavierA comprehensive understanding of antiferromagnetism in nanostructures confined in three dimensions remains elusive. This work addresses this fundamental issue by studying samples of highly crystalline single-phase NiO nanoparticles of 6, 20, and 34 nm average size, prepared by an optimized two-step synthesis. All the samples exhibit prominent antiferromagnetic behaviour with an overlapping superparamagnetic contribution due to uncompensated spins at the particle surface and at the crystallite boundaries within the particles, which becomes nearly undetectable for 34 nm particles. Using synchrotron X-ray photoemission electron microscopy combined with magnetic linear dichroism, a determination of the antiferromagnetic Néel axis was obtained for a subset of individual 34 nm particles. No thermal fluctuations of the Néel axes are observed at room temperature; instead, they are stochastically aligned along easy directions compatible with the particle crystal facets resting on the substrate. Consequently, single domain states of two sublattices appear to prevail in this size range, in contrast with a seminal model predicting multi-sublattice arrangements. These findings provide significant insights into antiferromagnetism in nanostructures and open up new possibilities for data storage based on specific states of Néel axes.Article
Modulated spin dynamics of [Co_2] coordination helicates via differential strand composition(Royal Society of Chemistry, 2024-04-03) Barrios Moreno, Leoní Alejandra; Capó Serrano, Núria; Boulehjour, Hanae; Reta Mañeru, Daniel; Tejedor Ramos, Inés; Roubeau, Olivier; Aromí Bedmar, GuillemCoordination supramolecular chemistry provides a versatile entry into materials with functionalities of technological relevance at the nanoscale. Here, we describe how two different bis-pyrazolylpyridine ligands (L1 and L2) assemble with Co(II ) ions into dinuclear triple-stranded helicates, in turn, encapsulating different anionic guests. These constructs are described as (Cl@[Co2 (L1)3])3+ , (SiF6 @[Co 2(L1)(L2)3])2+ and (ClO4 @[Co 2(L2)3 ])3+ , as established by single-crystal X-ray diffraction. Extensive magnetic and calorimetric measurements, numerical treatments and theoretical calculations reveal that the individual Co(II) centers of these supramolecular entities exhibit field-induced slow relaxation of magnetization, dominated by direct and Raman mechanisms. While the small variations in the spin dynamics are not easily correlated with the evident structural differences among the three species, the specific heat measurements suggest two vibronic pathways of magnetic relaxation: one that would be associated with the host lattice and another linked with the guest.Article
Folate-Receptor-Targeted Gold Nanoparticles Bearing a DNA-Binding Anthraquinone(MDPI, 2025) Caballero Hernández, Ana Belén; Hodges, Nikolas J.; Hannon, Michael J.In recent years, anthraquinones have been widening their therapeutic opportunities given their numerous health benefits. The search for adequate delivery platforms to improve their pharmacokinetics leads us to propose herein folate-capped gold nanoparticles with an anthraquinone derivative attached onto their surface. Through a straightforward, two-step procedure, we obtained stable nanoparticles that can deliver anthraquinones selectively to cells overexpressing folate receptors. The new conjugates were highly toxic against two tumour cell lines, lung carcinoma A549 and cervical carcinoma HeLa, and showed significant in vitro targeting effects for FR+ HeLa cells. We anticipate that the convenience of this synthetic procedure could enable the future development of folate-targeted conjugates bearing highly active anthraquinone-derived drugs.Article
RNase H-sensitive multifunctional ASO-based constructs as promising tools for the treatment of multifactorial complex pathologies(Elsevier, 2024-06) Mata Ventosa, Aida; Vila Planas, Ariadna; Solsona Pujol, Aina; Dueña Pascuet, Jordi de la; Torrents, Maria; Izquierdo García, Eduardo; Pastor Anglada, Marçal; Pérez Torras, Sandra; Terrazas Martínez, MontserratCombined therapies play a key role in the fight against complex pathologies, such as cancer and related drug-resistance issues. This is particularly relevant in targeted therapies where inhibition of the drug target can be overcome by cross-activating complementary pathways. Unfortunately, the drug combinations approved to date –mostly based on small molecules– face several problems such as toxicity effects, which limit their clinical use. To address these issues, we have designed a new class of RNase H-sensitive construct (3ASO) that can be disassembled intracellularly upon cell entry, leading to the simultaneous release of three different therapeutic oligonucleotides (ONs), tackling each of them the mRNA of a different protein. Here, we used Escherichia coli RNase H1 as a model to study an unprecedented mode of recognition and cleavage, that is mainly dictated by the topology of our RNA·DNA-based hybrid construct. As a model system for our technology we have created 3ASO constructs designed to specifically inhibit the expression of HER2, Akt and Hsp27 in HER2+ breast cancer cells. These trifunctional ON tools displayed very low toxicity and good levels of antiproliferative activity in HER2+ breast cancer cells. The present study will be of great potential in the fight against complex pathologies involving multiple mRNA targets, as the proposed cleavable designs will allow the efficient single-dose administration of different ON drugs simultaneously.Article
Valorisation of Mixtures of Linear Alkenes using Cobalt-Mediated Isomerisation and Hydroformylation Chemistries(Royal Society of Chemistry, 2022-03-23) Martínez-Carrión, Alicia; Romero-Navarro, Andrés; Núñez Rico, José Luis; Gutiérrez, Albert; Grabulosa, Arnald; Vidal Ferran, AntonActive catalysts derived from cobalt and the Xantphos ligand were synthesised, characterised and tested in the
hydroformylation of pure linear alkenes or their mixtures. The preformed complex [Co2(CO)6(Xantphos)] showed similar
reactivity and selectivity towards aldehydes as the active catalyst formed in situ from equimolar amounts of [Co2(CO)8] and
Xantphos. In the case of oct-1-ene, the linear aldehyde was obtained with good chemo- and regio-selectivity (linear to
branched ratio was up to 75:25). For all octene isomers, tandem isomerisation-hydroformylation processes took place.
Regioselectivities for all the studied octene isomers remained practically constant, independently of the position or
geometry of the CC double bond in the starting material. Moreover, by-products were formed in similarly small amounts
for all the octene isomers. We also demonstrated that this chemistry is an interesting strategy for valorising mixtures of
linear hexenes, heptenes or octenes by transforming the initial mixture into one major aldehyde (addition of a CHO group
to the C1 carbon of the alkene skeleton, up to 73% selectivity). Moreover, these mixtures of alkenes were hydroformylated
with low final amounts of non-hydroformylated alkenes, hydrogenated alkenes and alcohols.
Article
Enhanced i-Motif Stability through Consecutive 2,2-Difluorocytidine Incorporation(Wiley-VCH, 2025-11-19) Domínguez, Arnau; Cabrero, Cristina; Gómez-Pinto, Irene; Fàbrega, Carmen ; Gargallo Gómez, Raimundo; Eritja i Casadellà, Ramon; González, Carlos; Aviñó Andrés, AnnaChemical modifications of nucleic acids are widely used to tune stability and functionality in therapeutic and nanotechnological applications. Among these, fluorinated cytidine derivatives such as 2-fluoro-arabinocytidine (2F-araC) and 2-fluoro-ribocytidine (2F-riboC) have been shown to influence i-motif structures differently, with 2F-araC strongly stabilizing and 2F-riboC exerting a mildly deleterious effect. In this study, we investigate the impact of gemcitabine (2-deoxy-2,2-difluorocytidine, dFdC) on i-motif stability. dFdC exhibits small effects in single or double substituted sequences, but a pronounced stabilization when multiple consecutive residues are incorporated. Thermal and pH-dependent analyses demonstrate that sequences containing fully substituted dFdC maintain i-motif folding at neutral pH and show enhanced thermal stability. Structural insights suggest that this stabilization arises from a combination of factors, such as hyperconjugative interactions, hydrogen bonding, and dipole alignment, while the adaptable sugar conformation mitigates destabilizing minor groove contacts observed in other more rigid modifications, such as 2-F-riboC. Cooperative interactions among adjacent dFdC residues and potential changes in hydration may play a key factor in reinforcing stability. These results highlight the unique capacity of dFdC to enhance i-motif robustness and suggest that strategically placed difluoro substitutions can be exploited to design i-motifs with improved stability, expanding their potential in biotechnology and therapeutic applications.Article
Catalysis of native chemical ligation and expressed protein ligation by alkylselenols(ACS Publications, 2025-12-02) Sánchez Campillo, Iván; Gratacòs i Batlle, Esther; Pérez García, Selene; Nguyen, Hong S.; Triola i Guillem, Gemma; Mootz, Henning D.; Blanco Canosa, Juan B.Article
Sustained, Reversible, and Adaptive Non-Equilibrium Steady States of a Dissipative DNA-Based System(Wiley-VCH, 2025-10-20) Nicholas, James D.; Grosso, Erica del; deMello, Andrew J.; Puigmartí-Luis, Josep; Ricci, Francesco, 1977-; Sorrenti, AlessandroInspired by nature, researchers have developed several chemical fuel-driven supramolecular systems aimed at achieving improved kinetic control over their formation and functions. Alongside, DNA-based systems regulated by energy-dissipating mechanisms have been reported. However, the majority of these systems rely on batchwise additions of chemical fuels to closed reactors, resulting in transient non-equilibrium states that differ fundamentally from the sustained and highly adaptable non-equilibrium steady states (NESS) maintained by living systems through continuous energy dissipation. Here, we demonstrate sustained NESS of a dissipative DNA strand-displacement reaction achieved through the continuous supply of an RNA fuel to an open semi-batch reactor, using a custom automated setup that enables tunable fuel infusion rates and in situ analysis. Similar to biological NESS, our system dynamically adapts in real-time to subtle variations in fuel supply, achieving different steady-state levels of the strand-displacement reaction. Our approach demonstrates remarkable on-the-fly control over a dissipative DNA nanosystem, unachievable when working under batch conditions. Importantly, by fitting the experimental data to a kinetic model of the reaction network, we were able to confirm that the observed steady states correspond to true non-equilibrium compositions of the system.Article
Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides(ACS Publications, 2024-10-30) Sánchez Campillo, Iván; Blanco Canosa, Juan B.Native chemical ligation (NCL) ligates two unprotected peptides in an aqueous buffer. One of the fragments features a C-terminal α-thioester functional group, and the second bears an N-terminal cysteine. The reaction mechanism depicts two steps: an intermolecular thiol–thioester exchange resulting in a transient thioester, followed by an intramolecular S-to-N acyl shift to yield the final native peptide bond. Although this mechanism is well established, the direct observation of the transient thioester has been elusive because the fast intramolecular rearrangement prevents its accumulation. Here, the use of α-selenoester peptides allows a faster first reaction and an early buildup of the intermediate, enabling its quantification and the kinetic monitoring of the first and second steps. The results show a correlation between the steric hindrance in the α-thioester residue and the rearrangement rate. In bulky residues, the S-to-N acyl shift has a significant contribution to the overall reaction rate. This is particularly notable for valine and likely for other similar β-branched amino acids.Article
Computational Study of a Copper-Catalyzed Synthesis of Fluoroalcohols from Alkylboranes and Ketones(American Chemical Society, 2025-09-03) Gómez-Mudarra, Francisco A.; Aullón López, Gabriel; Jover Modrego, JesúsFluoroalcohols are a class of organic compounds containing one or more fluorine atoms together with an alcohol group in their molecular structure. These fluorinated species have a wide range of applications due to their unique properties and are used in medicine and electronics. Herein, we propose a new synthetic procedure, promoted by a copper(I) catalyst, for preparing fluoroalcohols from alkylboranes and symmetric ketones. The reaction has been computationally explored to propose a plausible mechanism, which allows identifying the rate-limiting step and quantitatively evaluating the electronic effects of each substrate on the overall reactivity. These DFT calculations suggest that the combination of electron-poor ketones with electron-rich alkylboranes produce the most efficient catalytic systems for preparing fluoroalcohols. Microkinetic modeling of the studied systems allow the prediction of the activation barrier limit to achieve fully functional reactions and multilinear regression techniques provide a methodology to estimate the overall reaction barriers in a simple manner, opening the way for proposing new catalytic systems.Article
Crystallographic and Computational Analysis of Oxyma B Cocrystals with Nitrogen-Containing Coformers: The Relevant Role of n → π* Interactions in Their Diverse Supramolecular Architectures(American Chemical Society) Jemai, Mahdi; Barbas Cañero, Rafael; Barceló-Oliver, Miquel; Marouani, Houda; Albericio Palomera, Fernando; Frontera, Antonio; Prohens López, RafaelThree new cocrystals of Oxyma-B, an important racemization suppressor for peptide synthesis, with 6-methylquinoline (I), 2,3,5,6-tetramethylpyrazine (II), and 1,10-phenanthroline (III) were synthesized and their single crystal structures analyzed. They show a rich network of noncovalent interactions, including classical and nonclassical hydrogen bonds (CH···O, OH···N, CH···N), CH···π, π-stacking, and, notably, lone pair···π (n → π*) interactions. Distinctive supramolecular synthons were identified, including the R22(7) motif found in both 6-methylquinoline/Oxyma-B and 2,3,5,6-tetramethylpyrazine/Oxyma-B cocrystals. In 1,10-phenanthroline/Oxyma-B, larger ring motifs such as R44(20) and R55(24) were observed, further supported by additional synthons of types R12(5) and R12(6). Hirshfeld surface analysis and density functional theory (DFT) calculations, including MEP surface, QTAIM, and NCIplot analyses, were carried out to quantify the intermolecular contributions and rationalize the experimental findings with a focus on the cooperative role of hydrogen bonding, π-stacking, and lone pair···π (n → π*) interactions in stabilizing and shaping the architectures of these new multicomponent crystalline materials.Article
Kinetico-mechanistic insights into the photodynamic process of AuI complexes with the CNC6H4NNC6H5 (iso-Ph) azobenzene ligand(Royal Society of Chemistry, 2025-01) Raïch Panisello, Ot; Jover Modrego, Jesús; Puigjaner, Cristina; Ferrer García, Montserrat; Martínez López, Manuel, 1957-A family of neutral isocyanide monoazo AuI complexes [AuCl(iso-Ph)], [Au(C6F5)(iso-Ph)] and [Au(C[triple bond, length as m-dash]Cpy)(iso-Ph)] (iso-Ph being CN–C6H4–N[double bond, length as m-dash]N–Ph) and a closely related cationic bisazo symmetrical derivative, [Au(iso-Ph)2](OTf), have been prepared. All the compounds have been structurally characterized using the conventional techniques HRMS, NMR, UV-Vis and IR spectroscopy. Moreover, the structure of the [AuCl(iso-Ph)] compound has been determined by XRD. These compounds undergo more efficient trans-to-cis photoisomerisation upon irradiation at 365 nm than that of the free iso-Ph ligand. The reverse cis-to-trans thermal process has been investigated using different solvents, temperatures and pressures to determine the values of the activation parameters and thus, the corresponding isomerisation mechanism. A change in the operating mechanism (from charge-separated rotational to inversional) has been observed upon going from the monoazo to the bisazo compounds. This effect has been attributed to the difference in the electronic density at the AuI centre in the transition state between the unsymmetrical and the symmetrical species.Article
Confronting positions: para- vs. meta-functionalization in triindole for p-type air-stable OTFTs(Elsevier, 2024-05-01) Cuadrado Santolaria, Alba; Bujaldón Carbó, Roger; Fabregat, Clara; Puigdollers i González, Joaquim; Velasco Castrillo, DoloresThe 5,10,15-trihexyl-10,15-dihydro-5H-diindolo[3,2-a:3′,2′-c]carbazole core, namely triindole, is well-known for its prominent hole-transporting properties and air stability. The functionalization of this core is also rather versatile, which allows the modulation of its properties by anchoring targeted scaffolds to different positions, e.g. 3,8,13 (para with respect to the nitrogens), 2,7,12 (analogously meta) or the nitrogen heteroatoms. Therefore, triindole excels as a pivotal semiconductor to be exploited in long-lasting organic thin-film transistors (OTFTs). This report aims to shed light on the effect of functionalizing whether para or meta positions with sulfurated moieties, in the pursuit of an enhanced performance in OTFTs. Remarkably, meta-substituted derivatives outshone their para- counterparts in terms of thermal, optical, intermolecular arrangement and semiconductor properties, claiming mobility values up to 2 × 10−3 cm2 V−1 s−1 and a shelf lifetime beyond the analyzed period of 5 months. Analysis of the thin films by grazing incidence X-ray diffraction (GIRXD) and atomic force microscopy (AFM) revealed that the meta-substitution also induces a higher degree of order and better morphology, further corroborating the potential of this structural approach.Article
On-the-Fly Synthesis of Freestanding Spin-Crossover Architectures With Tunable Magnetic Properties(Wiley-VCH, 2025-06-13) Ngo, Anh Tuan; Aguilà Avilés, David; Vale, João Pedro; Sevim, Semih; Mattera, Michele; Díaz-Marcos, Jordi; Pons, Ramon; Aromí Bedmar, Guillem; Jang, Bumjin; Pané, Salvador; Mayor, Tiago Sotto; Palacios-Corella, Mario; Puigmartí-Luis, JosepSpin-crossover (SCO) molecular-based switches have shown promise across a range of applications since their discovery, including sensing, information storage, actuators, and displays. Yet limited processability remains a barrier to their real-world implementation, as traditional methods for integrating SCO materials into polymer matrices are often complex, expensive, and prone to producing uneven material distributions. Herein, we demonstrate how 3D flow-focusing chemistry enables unprecedented control for the direct fabrication of SCO composite materials, addressing key challenges in processability, scalability, and cost. By using a 3D coaxial flow-focusing microfluidic device, we simultaneously synthesize [Fe(Htrz)2(trz)](BF4) and achieve its homogeneous incorporation into alginate fibers in a continuous manner. The device’s versatility allows for precise manipulation of the reaction-diffusion (RD) zone, resulting in SCO composite fibers with tunable physicochemical and magnetic properties. Additionally, we demonstrate the ability to isolate these fibers as freestanding architectures and highlight the potential for printing them with defined shapes. Finally, we show that the 3D control of the RD zone granted by continuous flow microfluidic devices offers precise spatiotemporal control over the distribution of SCO complexes within the fibers, effectively encoding SCO materials into them. SCO-encoded fibers can seamlessly combine adaptability and functionality, offering innovative solutions for application-specific customization.Article
Encapsulation Enhances the Quantum Coherence of a Solid‐State Molecular Spin Qubit(Wiley-VCH, 2025-09-01) Swain, Abinash; Barrios Moreno, Leoní Alejandra; Nelyubina, Yulia; Teat, Simon J.; Roubeau, Olivier; Novikov, Valentin; Aromí Bedmar, GuillemSpins within molecules benefit from the atomistic control of synthetic chemistry for the realization of qubits. One advantage is that the quantum superpositions of the spin states encoding the qubit can be coherently manipulated using electromagnetic radiation. The main challenge is the fragility of these superpositions when qubits are to partake of solid-state devices. We address this issue with a supramolecular approach for protecting molecular spin qubits against decoherence. The molecular qubit [Cr(ox)3]3− has been encapsulated inside the diamagnetic triple-stranded helicate [Zn2L3]4+ (L is a bis-pyrazolylpyridine ligand). The quantum coherence of the protected qubit is then analyzed with pulsed EPR spectroscopy and compared with the unprotected qubit, both in solution and in the solid state. Crucially, the spin–spin relaxation in the solid state has been examined within diamagnetic crystal lattices of the isostructural ([Al(ox)3]@[Zn2L3])+ or [Al(ox)3]3- assemblies, respectively, doped with the Cr3+ qubit in two different (<10%) concentrations. The study unveils a surprising increase of the phase memory time of the qubit upon encapsulation only in the solid. Spin-lattice relaxation times also exhibit a significant enhancement, as established from inversion recovery pulse sequences and from slow relaxation of the magnetization of the protected qubit, not featured by the free qubit.Article
New series of mononuclear β-diketonate cerium(iii) field induced single-molecule magnets(Royal Society of Chemistry, 2024-05-08) Tubau Ribot, Ànnia; Gómez Coca, Silvia; Speed Castro, Saskia; Font Bardia, Ma. Mercedes; Vicente Castillo, RamónFive new β-diketonate Ce3+ mononuclear complexes, [Ce(Btfa)3(H2O)2] (1), [Ce(Btfa)3(phen)] (2), [Ce (Btfa)3(bipy)] (3), [Ce(Btfa)3(terpy)] (4) and [Ce(Btfa)3(bathophen)(DMF)] (5), where Btfa− = 4,4,4-trifluoro-1- phenyl-1,3-butanedionate, phen = 1,10-phenanthroline, bipy = 2,2’-bipyridyl, terpy = 2,2’:6’,2’’-terpyridine and bathophen = 4,7-diphenyl-1,10-phenanthroline, have been synthesized and structurally characterized through X-ray diffraction of single crystals. The central Ce3+ atom displays a coordination number of 8 for 1, 2 and 3 and of 9 for 4 and 5. Under a 0 T external magnetic field, none of the given compounds exhibits single molecule magnet (SMM) behaviour. However, a small magnetic field, between 0.02 and 0.1 T, is enough for all the compounds to exhibit slow relaxation of the magnetization. A comprehensive magnetic analysis, with experimental magnetic data and ab initio calculations, was undertaken for all the complexes, and the study highlights the significance of the different spin relaxation mechanisms that must be considered for a Ce3+ lanthanide ion.Article
A site-specific MiniAp4-Trastuzumab conjugate prevents brain metastasis(American Chemical Society, 2025-03-03) Masmudi-Martín, Mariam; Oller Salvia, Benjamí; Perea, María; Teixidó Turà, Meritxell; Valiente, Manuel; Giralt Lledó, Ernest; Sánchez-Navarro, MacarenaMonoclonal antibodies (mAbs) are changing cancer treatments. However, the presence of the blood–brain barrier (BBB) and the blood–tumor barrier (BTB) limits the use of mAbs to treat brain cancer or brain metastasis. Molecules that hijack endogenous transport mechanisms on the brain endothelium (brain shuttles) have been shown to increase the transport of large molecules and nanoparticles across the BBB. Among these shuttles, protease-resistant peptides such as MiniAp-4 are particularly efficient. Here, we report the synthesis, characterization, and evaluation of site-specific mAb–brainshuttle antibody conjugates (ASC) based on the anti-HER2 mAb trastuzumab (Tz) and four molecules of MiniAp-4. The ASCs preserve the binding and cell cycle arrest capacity of Tz. MiniAp-4 ASC displays enhanced transport across an in vitro BBB cellular model with respect to Tz and Tz conjugated to Angiopep-2, the brain shuttle that has advanced the most in clinical trials. More importantly, evaluation of Tz-MiniAp4 in a murine brain metastasis model demonstrated that the protease-resistant peptide showed preferential transport across the BBB/BTB, displaying a marked therapeutic effect and protecting against metastasis development. The technology described herein could be applied to any antibody of interest to treat central nervous system-related diseases. MiniAp-4 enhances the brain transport of the monoclonal antibody trastuzumab, preventing brain metastasis.Article
A Leap from Diradicals to Tetraradicals by Topological Control of π-Conjugation.(American Chemical Society, 2024-09-20) Betkhoshvili, Sergi; Poater i Teixidor, Jordi; Moreira, Ibério de Pinho Ribeiro; Bofill i Villà, Josep M.In this work, we explore the series of diradical(oid)s based on 2,2′-(5,11-dihydroindolo[3,2-b]carbazole-3,9-diyl)-dimalononitrile (further referred to as PH). Hydrogen atoms in the central benzenoid (CB) ring of PH are substituted by the seriesof substituents with various lengths of π-conjugated chain and electron-donating or electron-withdrawing properties to study howthey modulate the diradical character of the parent compound. The diradical character of molecules increases up to 88−89% by twogroups doubly bonded to both sides of the CB ring of PH in para relative positions. This breaks the direct π-conjugation betweenunpaired electrons that gives rise to two radical centers and restricts the minimal polyradical identity of the compound todiradical. We show that diradicals and tetraradicals can be designed, and their polyradical character can be modulated by controlling the topology of π-conjugation as long as there is sufficient aromatic stabilization. Henceforth, the bridge between diradicals and tetraradicals is established, leading to the tetraradical(oid) molecule, which has been predicted to have narrow low-spin to high-spin energy gaps in our recent Letter.