Publications by authors named "Clara Viñas"

154 Publications

Post-synthetic modification of a highly flexible 3D soft porous metal-organic framework by incorporating conducting polypyrrole: enhanced MOF stability and capacitance as an electrode material.

Chem Commun (Camb) 2021 Mar 8;57(20):2523-2526. Epub 2021 Feb 8.

Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus de la UAB, Bellaterra 08193, Spain.

Post-synthetic modification of a dynamic carborane-based soft porous crystal (1 ⊃ DMF) by in situ polymerization of pyrrole to polypyrrole (PPy) provided a permanently porous MOF/polypyrrole hybrid composite material that did not show the dynamic behavior of the mother MOF. Apart from stability, the introduction of conductive PPy in the composite material brings new properties to the otherwise non-conductive MOF.
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http://dx.doi.org/10.1039/d0cc07393hDOI Listing
March 2021

Noncovalently Linked Metallacarboranes on Functionalized Magnetic Nanoparticles as Highly Efficient, Robust, and Reusable Photocatalysts in Aqueous Medium.

ACS Appl Mater Interfaces 2020 Dec 7;12(50):56372-56384. Epub 2020 Dec 7.

Institut de Ciencia de Materials de Barcelona, ICMAB-CSIC, Campus UAB, E-08193 Bellaterra, Spain.

A successful homogeneous photoredox catalyst has been fruitfully heterogenized on magnetic nanoparticles (MNPs) coated with a silica layer, keeping intact its homogeneous catalytic properties but gaining others due to the easy magnetic separation and recyclability. The amine-terminated magnetic silica nanoparticles linked noncovalently to H[3,3'-Co(1,2-CBH)] (H[]), termed MSNPs-NH@H[], are highly stable and do not produce any leakage of the photoredox catalyst H[] in water. The magnetite MNPs were coated with SiO to provide colloidal stability and silanol groups to be tethered to amine-containing units. These were the MSNPs-NH on which was anchored, in water, the cobaltabis(dicarbollide) complex H[] to obtain MSNPs-NH@H[]. Both MSNPs-NH and MSNPs-NH@H[] were evaluated to study the morphology, characterization, and colloidal stability of the MNPs produced. The heterogeneous MSNP-NH@H[] system was studied for the photooxidation of alcohols, such as 1-phenylethanol, 1-hexanol, 1,6-hexanediol, or cyclohexanol among others, using catalyst loads of 0.1 and 0.01 mol %. Surfactants were introduced to prevent the aggregation of MNPs, and cetyl trimethyl ammonium chloride was chosen as a surfactant. This provided adequate stability, without hampering quick magnetic separation. The results proved that the catalysis could be speeded up if aggregation was prevented. The recyclability of the catalytic system was demonstrated by performing 12 runs of the MSNPs-NH@H[] system, each one without loss of selectivity and yield. The cobaltabis(dicarbollide) catalyst supported on silica-coated magnetite nanoparticles has proven to be a robust, efficient, and easily reusable system for the photooxidation of alcohols in water, resulting in a green and sustainable heterogeneous catalytic system.
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http://dx.doi.org/10.1021/acsami.0c17847DOI Listing
December 2020

Sunitinib-Containing Carborane Pharmacophore with the Ability to Inhibit Tyrosine Kinases Receptors FLT3, KIT and PDGFR-β, Exhibits Powerful In Vivo Anti-Glioblastoma Activity.

Cancers (Basel) 2020 Nov 18;12(11). Epub 2020 Nov 18.

Grupo de Química Orgánica Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay.

Malignant gliomas are the most common malignant and aggressive primary brain tumors in adults, the prognosis being-especially for glioblastomas-extremely poor. There are no effective treatments yet. However, tyrosine kinase receptor (TKR) inhibitors and boron neutron capture therapy (BNCT), together, have been proposed as future therapeutic strategies. In this sense in our ongoing project of developing new anti-glioblastoma drugs, we identified a sunitinib-carborane hybrid agent, , with both in vitro selective cytotoxicity and excellent BNCT-behavior. Consequently, we studied the ability of compound to inhibit TKRs, its promotion of cellular death processes, and its effects on the cell cycle. Moreover, we analyzed some relevant drug-like properties of , i.e., mutagenicity and ability to cross the blood-brain barrier. These results encouraged us to perform an in vivo anti-glioblastoma proof of concept assay. It turned out to be a selective FLT3, KIT, and PDGFR-β inhibitor and increased the apoptotic glioma-cell numbers and arrested sub-G1-phase cell cycle. Its in vivo activity in immunosuppressed mice bearing U87 MG human glioblastoma evidenced excellent anti-tumor behavior.
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http://dx.doi.org/10.3390/cancers12113423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698965PMC
November 2020

Magnetic Nanoparticles Fishing for Biomarkers in Artificial Saliva.

Molecules 2020 Aug 31;25(17). Epub 2020 Aug 31.

Inorganic Materials Laboratory, Institut de Ciencia de Materials de Barcelona (ICMAB-CSIC) Campus de la UAB, 08193 Bellaterra, Spain.

Magnetic nanoparticles (MNPs) were synthesized using the colloidal co-precipitation method and further coated with silica using the Stöber process. These were functionalized with carboxylic and amine functionalities for further covalent immobilization of antibodies on these MNPs. The procedure for covalent immobilization of antibodies on MNPs was developed using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) and -hydroxysuccinimide (NHS). The evaluation of the efficiency of the coupling reaction was carried out by UV-vis spectrophotometry. The developed antibodies coupled to MNPs were tested for the pre-concentration of two biomarkers tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10). Both biomarkers were assessed in the matrix based on phosphate-buffered saline solution (PBS) and artificial saliva (AS) to carry out the demonstration of the format assay. Supernatants were used to determine the number of free biomarkers for both studies. Reduction of the nonspecific saliva protein adsorption on the surface of the complex antibodies-MNPs to levels low enough to allow the detection of biomarkers in complex media has been achieved.
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http://dx.doi.org/10.3390/molecules25173968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504804PMC
August 2020

Bimodal Therapeutic Agents Against Glioblastoma, One of the Most Lethal Forms of Cancer.

Chemistry 2020 Nov 6;26(63):14335-14340. Epub 2020 Oct 6.

Grupo de Química Orgánica Medicinal, Instituto de Química Biológica (IQB), Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay.

About 95 % of people diagnosed with glioblastoma die within five years. Glioblastoma is the most aggressive central nervous system tumour. It is necessary to make progress in the glioblastoma treatment so that advanced chemotherapy drugs or radiation therapy or, ideally, two-in-one hybrid systems should be implemented. Tyrosine kinase receptors-inhibitors and boron neutron capture therapy (BNCT), together, could provide a therapeutic strategy. In this work, sunitinib decorated-carborane hybrids were prepared and biologically evaluated identifying excellent antitumoral- and BNCT-agents. One of the selected hybrids was studied against glioma-cells and found to be 4 times more cytotoxic than sunitinib and 1.7 times more effective than B-boronophenylalanine fructose complex when the cells were irradiated with neutrons.
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http://dx.doi.org/10.1002/chem.202002963DOI Listing
November 2020

Highlights on the Binding of Cobalta-Bis-(Dicarbollide) with Glucose Units.

Chemistry 2020 Nov 30;26(61):13935-13947. Epub 2020 Sep 30.

ICSM, Univ Montpellier, CEA, CNRS, ENSCM, 30207, Marcoule, France.

Metalla-bis-dicarbollides, such as the cobalta-bis-dicarbollide (COSAN) anion [Co(C B H ) ] , have attracted much attention in biology but a deep understanding of their interactions with cell components is still missing. For this purpose, we studied the interactions of COSAN with the glucose moiety, which is ubiquitous at biological interfaces. Octyl-glucopyranoside surfactant (C8G1) was chosen as a model as it self-assembles in water and creates a hydrated glucose-covered interface. At low COSAN content and below the critical micellar concentration (CMC) of C8G1, COSAN binds to C8G1 monomers through the hydrophobic effect. Above the CMC of C8G1, COSAN adsorbs onto C8G1 micelles through the superchaotropic effect. At high COSAN concentrations, COSAN disrupts C8G1 micelles and the assemblies become similar to COSAN micelles but with a small amount of solubilized C8G1. Therefore, COSAN binds in a versatile way to C8G1 through either the hydrophobic or superchaotropic effect depending on their relative concentrations.
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http://dx.doi.org/10.1002/chem.202002123DOI Listing
November 2020

-Carborane as a Novel Core for Periphery-Decorated Macromolecules.

Molecules 2020 Jun 18;25(12). Epub 2020 Jun 18.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Barcelona, Spain.

-CBH can perform as a novel core of globular periphery-decorated macromolecules. To do this, a new class of di and tetrabranched -carborane derivatives has been synthesized by a judicious choice of the synthetic procedure, starting with 9,10-I-1,7--CBH. The 2a-NPA (sum of the natural charges of the two bonded atoms) value for a bond, which is defined as the sum of the NPA charges of the two bonded atoms, matches the order of electrophilic reaction at the different cluster bonds of the icosahedral -and - carboranes that lead to the formation of B-I bonds. As for -carborane, most of the 2a-NPA values of B-H vertexes are positive, and their functionalization is more challenging. The synthesis and full characterization of dibranched 9,10-R-1,7--carborane (R = CHCHCH, HO(CH), Cl(CH), TsO(CH), CHCOO(CH), CHCOO(CH), N(CH), CHCHCH, and CHCN(CH)) compounds as well as the tetrabranched 9,10-R-1,7-R--CBH (R = CHCHCH, HO(CH)) are presented. The X-ray diffraction of 9,10-(HO(CH))-1,7--CBH and 9,10-(CHCHCH)-1,7--CBH, as well as their Hirshfeld surface analysis and decomposed fingerprint plots, are described. These new reported tetrabranched -carborane derivatives provide a sort of novel core for the synthesis of 3D radially grown periphery-decorated macromolecules that are different to the 2D radially grown core of the tetrabranched -carborane framework.
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http://dx.doi.org/10.3390/molecules25122814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356233PMC
June 2020

-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy.

Cells 2020 06 5;9(6). Epub 2020 Jun 5.

Grupo de Química Orgánica Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.

One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, and . We identified hybrid with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative , bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids and incubations rendering, and after neutron irradiation, higher BNCT-effects than . The attractive profile of developed hybrids makes them interesting agents for combined therapy.
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http://dx.doi.org/10.3390/cells9061408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349914PMC
June 2020

A Highly Water-Stable -Carborane-Based Copper Metal-Organic Framework for Efficient High-Temperature Butanol Separation.

J Am Chem Soc 2020 05 27;142(18):8299-8311. Epub 2020 Apr 27.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), E-08193 Bellaterra, Barcelona, Spain.

Biofuels are considered sustainable and renewable alternatives to conventional fossil fuels. Biobutanol has recently emerged as an attractive option compared to bioethanol and biodiesel, but a significant challenge in its production lies in the separation stage. The current industrial process for the production of biobutanol includes the ABE (acetone-butanol-ethanol) fermentation process from biomass; the resulting fermentation broth has a butanol concentration of no more than 2 wt% (the rest is essentially water). Therefore, the development of a cost-effective process for separation of butanol from dilute aqueous solutions is highly desirable. The use of porous materials for the adsorptive separation of ABE mixtures is considered a highly promising route, as these materials can potentially have high affinities for alcohols and low affinities for water. To date, zeolites have been tested toward this separation, but their hydrophilic nature makes them highly incompetent for this application. The use of metal-organic frameworks (MOFs) is an apparent solution; however, their low hydrolytic stabilities hinder their implementation in this application. So far, a few nanoporous zeolitic imidazolate frameworks (ZIFs) have shown excellent potential for butanol separation due to their good hydrolytic and thermal stabilities. Herein, we present a novel, porous, and hydrophobic MOF based on copper ions and carborane-carboxylate ligands, , for butanol recovery. exhibits excellent stability when immersed in organic solvents, water at 90 °C for at least two months, and acidic and basic aqueous solutions. We found that, like ZIF-8, is non-porous to water (type II isotherm), but it has higher affinity for ethanol, butanol, and acetone compared to ZIF-8, as suggested by the shape of the vapor isotherms at the crucial low-pressure region. This is reflected in the separation of a realistic ABE mixture in which recovers butanol more efficiently compared to ZIF-8 at 333 K.
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http://dx.doi.org/10.1021/jacs.0c01008DOI Listing
May 2020

Too Persistent to Give Up: Aromaticity in Boron Clusters Survives Radical Structural Changes.

J Am Chem Soc 2020 May 5;142(20):9396-9407. Epub 2020 May 5.

Institut de Ciència de Materials de Barcelona, Consejo Superior de Investigaciones Cientı́ficas, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

-CBH isomerizes to -CBH upon heating at 400 °C. Deboronation in -CBH is a relatively easy process, whereas it is more difficult in -CBH. These two experimental facts indicate that -CBH is thermodynamically more stable than -CBH. On the other hand, it is widely accepted that -boranes and -carboranes are aromatic compounds. In this work, we relate the difficulty in the deboronation of the carboranes with their stability and aromaticity. We do this by combining lab work and DFT calculations. Computationally, our results show that the higher thermodynamic stability of -CBH is not related to aromaticity differences but to the location of the C atoms in the carborane structure. It is also demonstrated that the aromaticity observed in -boranes and -carboranes is also present in their counterparts, and consequently, we conclude that aromaticity in boron clusters survives radical structural changes. Further, sandwich metallocenes (e.g., ferrocene) and sandwich metallabis(dicarbollides) (e.g., [Co(CBH)]) have traditionally been considered to be similar. Here it is shown that they are not. Metallabis(dicarbollides) display global aromaticity, whereas metallocenes present local aromaticity in the ligands. Remarkable and unique is the double probe given by H and B NMR tracing the reciprocally antipodal endocyclic open face H and B. These magnetic studies have permitted one to correlate both nuclei and relate them to a diatropic current in the plane at the middle of the -[CBH]. This observation is the first unique evidence that proves experimentally the existence of diatropic currents, and thence aromaticity, in clusters and is comparable to the existence of diatropic currents in planar aromatic compounds. Additionally, heteroboranes with two carbon atoms have been compared to heterocycles with two nitrogen or boron atoms, e.g., CBH carboranes versus planar NCH diazines or [BCH] diboratabenzenes, thereby proving the higher persistence of the aromaticity of the tridimensional compounds in heteroatom-substituted species. This research accounts very well for the "paradigm for the electron requirements of clusters", in which a -cluster that is aromatic upon addition of 2e becomes also an aromatic -species, and explains the informative schemes by Rudolph and Williams.
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http://dx.doi.org/10.1021/jacs.0c02228DOI Listing
May 2020

Blue Emitting Star-Shaped and Octasilsesquioxane-Based Polyanions Bearing Boron Clusters. Photophysical and Thermal Properties.

Molecules 2020 Mar 7;25(5). Epub 2020 Mar 7.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus U.A.B., 08193 Bellaterra, Barcelona, Spain.

High boron content systems were prepared by the peripheral functionalisation of 1,3,5-triphenylbenzene (TPB) and octavinylsilsesquioxane (OVS) with two different anionic boron clusters: -dodecaborate (B) and cobaltabisdicarbollide (COSAN). TPB was successfully decorated with three cluster units by an oxonium ring-opening reaction, while OVS was bonded to eight clusters by catalysed metathesis cross-coupling. The resulting compounds were spectroscopically characterised, and their solution-state photophysical properties analysed. For TPB, the presence of COSAN dramatically quenches the fluorescence emission (λ = 369 nm; Φ = 0.8%), while B-substituted TPB shows an appreciable emission efficiency (λ = 394 nm; Φ = 12.8%). For octasilsesquioxanes, the presence of either COSAN or B seems to be responsible for ∼80 nm bathochromic shift with respect to the core emission, but both cases show low emission fluorescence (Φ = 1.4-1.8%). In addition, a remarkable improvement of the thermal stability of OVS was observed after its functionalisation with these boron clusters.
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http://dx.doi.org/10.3390/molecules25051210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179457PMC
March 2020

A fast and simple B-C bond formation in metallacarboranes avoiding halometallacarboranes and transition metal catalysts.

Dalton Trans 2020 Mar 28;49(11):3525-3531. Epub 2020 Feb 28.

Institut de Ciència de Materials de Barcelona - CSIC, Campus UAB, 08193, Bellaterra, Barcelona, Spain.

An electrophilic substitution on metallacarboranes by using a stabilized carbocation that can be made in situ is reported for the first time. This new synthetic methodology provides a new perspective on easy metallacarborane derivatization with organic fragments, which enhances the properties of both fragments and widens their possible applications.
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http://dx.doi.org/10.1039/c9dt04695jDOI Listing
March 2020

Metallacarboranes as Photoredox Catalysts in Water.

Chemistry 2020 Apr 24;26(22):5027-5036. Epub 2020 Mar 24.

Institut de Ciencia de Materials de Barcelona, ICMAB-CSIC, Campus UAB, 08193, Bellaterra, Spain.

Metallacarboranes with the shape of the Greek letter θ, such as [Co(C B H ) ] , were tested, for the first time, as efficient photoredox catalysts in the oxidation of aromatic and aliphatic alcohols in water. Their efficiency is linked to their high solubility in water, their high oxidizing power (Co ), and their absence of fluorescence on excitation, among others. In most of the studied examples, using a catalyst load of 0.4 mol % gave high yields of 90-95 % with selectivity greater than 99 %. By reducing the catalyst load to 0.01 mol %, quantitative conversion of reactants to products was achieved, in some cases with greater than 99 % yield, high catalyst efficiency reaching a turnover number of 10 000, and a higher yield with a 45 times lower concentration of catalyst. The metallacarboranes can be recovered easily by precipitation on addition of [NMe ]Cl. A pathway for the photoredox-catalyzed oxidation of alcohols is proposed.
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http://dx.doi.org/10.1002/chem.201905395DOI Listing
April 2020

Atomistic Simulations of COSAN: Amphiphiles without a Head-and-Tail Design Display "Head and Tail" Surfactant Behavior.

Angew Chem Int Ed Engl 2020 02 3;59(8):3088-3092. Epub 2020 Jan 3.

Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus de la UAB, 08193, Bellaterra, Spain.

Cobaltabisdicarbollide (COSAN) anions have an unexpectedly rich self-assembly behavior, which can lead to vesicles and micelles without having a classical surfactant molecular architecture. This was rationalized by the introduction of new terminology and novel driving forces. A key aspect in the interpretation of COSAN behavior is the assumption that the most stable form of these ions is the transoid rotamer, which lacks a "hydrophilic head" and a "hydrophobic tail". Using implicit solvent DFT calculations and MD simulations we show that in water, 1) the cisoid rotamer is the most stable form of COSAN and 2) this cisoid rotamer has a well-defined hydrophilic polar region ("head") and a hydrophobic apolar region ("tail"). In addition, our simulations show that the properties of this rotamer in water (interfacial affinity, micellization) match those expected for a classical surfactant. Therefore, we conclude that the experimental results for the COSAN ions can now be understood in terms of its amphiphilic molecular architecture.
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http://dx.doi.org/10.1002/anie.201913257DOI Listing
February 2020

Efficient blue light emitting materials based on m-carborane-anthracene dyads. Structure, photophysics and bioimaging studies.

Biomater Sci 2019 Dec 16;7(12):5324-5337. Epub 2019 Oct 16.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus U.A.B., 08193, Bellaterra, Barcelona, Spain.

Efficient monosubstitution of the non-iodinated, mono-iodinated and di-iodinated m-carborane cluster at one C has led to the preparation of three single organic molecule-carborane dyads (4-6), which exhibited exceptional fluorescence properties with quantum yield values of 100% in solution, for all of them, with maxima around 415 nm, which correspond to the locally excited state (LE) emission. These results suggest that simply linking the m-carborane fragment to one anthracene unit through a CH spacer produces a significant enhancement of the fluorescence in the final fluorophore, probably due to the free rotation of the anthracene linked to the C. Besides, the presence of one or two iodine atoms linked to boron atoms does not cause any influence on the photophysical properties of the dyads, as it is confirmed by TD-DFT calculations. Notably, the three conjugates show good fluorescence efficiency in the aggregate state with quantum yields in the range of 19-23%, which could be ascribed to the presence of CH, particularly for 4, and the iodine atoms in 5 and 6, which prevent π-π stacking. All these results indicate that our dyads are extremely good emitters in solution while maintaining the emission properties in the aggregate state. Crystal packing, fingerprint plot analysis, and TD-DFT calculations for the three compounds support these results. Confocal microscopy studies show that 6 is the best-internalized compound by HeLa cells via endocytosis, although 4 and 5 also presented a high fluorescence intensity emission. Moreover, due to the blue emission, this compound is an excellent candidate to be applied as a fluorescent dye in bioimaging studies.
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http://dx.doi.org/10.1039/c9bm00903eDOI Listing
December 2019

Carboranylanilinoquinazoline EGFR-inhibitors: toward 'lead-to-candidate' stage in the drug-development pipeline.

Future Med Chem 2019 09;11(17):2273-2285

Laboratorio de Química Orgánica Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.

Carboranylanilinoquinazoline-hybrids, developed for boron neutron capture therapy, have demonstrated cytotoxicity against murine-glioma cells with EGFR-inhibition ability. In addition, their adequate aqueous/metabolic stabilities and ability to cross blood-brain barrier make them good leads as to become antiglioma drugs. Analyze drug-like properties of representative carboranylanilinoquinazolines. To expand carboranylanilinoquinazolines therapeutic spectrum, we studied their ability to act against glioma-mammal cells, U-87 MG and other tyrosine kinase-overexpress cells, HT-29. Additionally, we predicted theoretically and studied experimentally drug-like properties, in other words, organization for economic cooperation and development-recommended toxicity-studies and, due to some aqueous-solubility problems, and vehicularization for oral and intravenous administrations. We have identified a promising drug-candidate with broad activity spectrum, appropriate drug-like properties, adequate toxicological behavior and able ability to be loaded in suitable vehicles.
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http://dx.doi.org/10.4155/fmc-2019-0060DOI Listing
September 2019

A Reversible Phase Transition of 2D Coordination Layers by B-H∙∙∙Cu(II) Interactions in a Coordination Polymer.

Molecules 2019 Sep 3;24(17). Epub 2019 Sep 3.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), 08193 Bellaterra, Spain.

Materials that combine flexibility and open metal sites are crucial for myriad applications. In this article, we report a 2D coordination polymer (CP) assembled from CuII ions and a flexible -carborane-based linker [Cu(L1)(Solv)]•xSolv (1-DMA, 1-DMF, and 1-MeOH; L1: 1,7-di(4-carboxyphenyl)-1,7-dicarba-closo-dodecaborane). 1-DMF undergoes an unusual example of reversible phase transition on solvent treatment (i.e., MeOH and CHCl). Solvent exchange, followed by thermal activation provided a new porous phase that exhibits an estimated Brunauer-Emmett-Teller (BET) surface area of 301 m g and is capable of a CO uptake of 41 cm g. The transformation is reversible and 1-DMF is reformed on addition of DMF to the porous phase. We provide evidence for the reversible process being the result of the formation/cleavage of weak but attractive B-H∙∙∙Cu interactions by a combination of single-crystal (SCXRD), powder (PXRD) X-ray diffraction, Raman spectroscopy, and DFT calculations.
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http://dx.doi.org/10.3390/molecules24173204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751501PMC
September 2019

Dual Binding Mode of Metallacarborane Produces a Robust Shield on Proteins.

Chemistry 2019 Oct 9;25(55):12820-12829. Epub 2019 Sep 9.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193, Bellaterra, Barcelona, Spain.

An inorganic sandwich molecule, Na[Co(C B H ) ], able to produce vesicles through self-assembly and known to produce strong dihydrogen-bond interactions with amine groups is capable of interacting with proteins. This dual non-bonding ability of Na[Co(C B H ) ] is what makes this molecule unique: it can be firmly anchored to a protein surface and is capable of extending over it. To prove this, the widely available bovine serum albumin (BSA), which has many pendant amino groups in its structure, has been taken as the model protein. It has been found that around 100 molecules of Na[Co(C B H ) ] preserve the native structure of BSA, while endorsing it with a significantly increased stability with respect to chemical- and thermal-induced denaturation due to efficient encapsulation. The advantages of this encapsulation technique are two-fold; the first is its simplicity as it relies on the anchoring capacity of Na[Co(C B H ) ] to the surface of the protein through the amine-containing residues and the second is its self-assembling capacity allowing it to spread across the surface. The dense shield of protection offered by Na[Co(C B H ) ] has been demonstrated by the inhibition of BSA pseudo-esterase activity, which indicates that the inorganic corset around BSA protects its reactive surface residues, thereby preventing their acetylation.
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http://dx.doi.org/10.1002/chem.201902796DOI Listing
October 2019

Are the Accompanying Cations of Doping Anions Influential in Conducting Organic Polymers? The Case of the Popular PEDOT.

Chemistry 2019 Nov 24;25(63):14308-14319. Epub 2019 Sep 24.

Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.

Conducting organic polymers (COPs) are made of a conjugated polymer backbone supporting a certain degree of oxidation. These positive charges are compensated by the doping anions that are introduced into the polymer synthesis along with their accompanying cations. In this work, the influence of these cations on the stoichiometry and physicochemical properties of the resulting COPs have been investigated, something that has previously been overlooked, but, as here proven, is highly relevant. As the doping anion, metallacarborane [Co(C B H ) ] was chosen, which acts as a thistle. This anion binds to the accompanying cation with a distinct strength. If the binding strength is weak, the doping anion is more prone to compensate the positive charge of the polymer, and the opposite is also true. Thus, the ability of the doping anion to compensate the positive charges of the polymer can be tuned, and this determines the stoichiometry of the polymer. As the polymer, PEDOT was studied, whereas Cs , Na , K , Li , and H as cations. Notably, with the [Co(C B H ) ] anions, these cations are grouped into two sets, Cs and H in one and Na , K , and Li in the second, according to the stoichiometry of the COPs: 2:1 EDOT/[Co(C B H ) ] for Cs and H , and 3:1 EDOT/[Co(C B H ) ] for Na , K , and Li . The distinct stoichiometries are manifested in the physicochemical properties of the COPs, namely in the electrochemical response, electronic conductivity, ionic conductivity, and capacitance.
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http://dx.doi.org/10.1002/chem.201902708DOI Listing
November 2019

The key to controlling the morphologies of quantum nanocrystals: spherical carborane ligands.

Chem Commun (Camb) 2019 Aug;55(66):9817-9820

Institut de Ciencia de Materials de Barcelona, Campus de la UAB, Bellaterra, 08193, Spain.

By minor structure modification of spherical carborane ligands, in a similar synthetic procedure, large morphological changes are produced in Quantum Nanocrystals (QNCs). The spheres are icosahedral C2B10H12 molecules with binding sites on the carbon, and the QNCs produced are Quantum Dots, Rods, Rings and Tetrapods. These QNCs demonstrated high stability and impeccable emissive properties for more than a year.
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http://dx.doi.org/10.1039/c9cc03941dDOI Listing
August 2019

Icosahedral carboranes as scaffolds for congested regioselective polyaryl compounds: the distinct distance tuning of C-C and its antipodal B-B.

Chem Commun (Camb) 2019 Aug 3;55(61):8927-8930. Epub 2019 Jul 3.

Institut de Ciència de Materials de Barcelona, ICMAB-CSIC Campus U.A.B., 08193 Bellaterra, Spain.

Four-fold aryl substituted o-carborane derivatives with defined patterns of substitution at the antipodal region of the cluster carbon atoms have been achieved. It is proven that this region is congested but lacks steric hindrance. Also, the two antipodal sites C-C and B9-B12 are affected very distinctly by electron donor substituents.
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http://dx.doi.org/10.1039/c9cc04526kDOI Listing
August 2019

Periphery Decorated and Core Initiated Neutral and Polyanionic Borane large molecules: Forthcoming and Promising properties for medicinal applications.

Curr Med Chem 2019 Jun 3. Epub 2019 Jun 3.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Barcelona. Spain.

A mini-review based on radial growing macromolecules and core initiated Borane periphery decorated with o-carboranes and metallacarboranes that has been developed in the authors laboratories is reported. The review is divided into four sections; three of them are related to the design and synthesis of these large boron-containing molecules and the fourth deals with the unique properties of anionic metallacarborane molecules that provide a glimpse of their potential for their promising use in medicinal applications. Their unique stability along with their geometrical and electronic properties, as well as the precise steric structure of 1,2-closo-C2B10H12 (o-carborane) that has the potential for the incorporation of many substituents: at the carbon (Cc), at the boron and at both carbon and boron vertices, suggests this cluster as an innovative building block or platform for novel applications that cannot be achieved with organic hydrocarbon compounds. Poly(aryl-ether) dendrimers grown from fluorescent cores, such as 1,3,5-triarylbenzene or meso-porphyrins, have been decorated with boron clusters to attain rich boron containing dendrimers. Octasilsesquioxane cubes have been used as a core for its radial growth to get boron-rich large molecules. The unique properties of cobaltabisdicarbollide cluster include: i) self-assembly in water to produce monolayer nano-vesicles, ii) crossing lipid bilayer membranes, iii) interacting with membrane cells, iv) facilitating its visualization within cells by Raman and fluorescence techniques and v) their use as molecular platform for "in vivo" imaging are discussed in detail.
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http://dx.doi.org/10.2174/0929867326666190603123838DOI Listing
June 2019

Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy.

Nanomedicine 2019 08 3;20:101986. Epub 2019 May 3.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), 08193 Bellaterra, Spain. Electronic address:

The potential biomedical applications of the MNPs nanohybrids coated with m-carboranylphosphinate (1-MNPs) as a theranostic biomaterial for cancer therapy were tested. The cellular uptake and toxicity profile of 1-MNPs from culture media by human brain endothelial cells (hCMEC/D3) and glioblastoma multiform A172 cell line were demonstrated. Prior to testing 1-MNPs' in vitro toxicity, studies of colloidal stability of the 1-MNPs' suspension in different culture media and temperatures were carried out. TEM images and chemical titration confirmed that 1-MNPs penetrate into cells. Additionally, to explore 1-MNPs' potential use in Boron Neutron Capture Therapy (BNCT) for treating cancer locally, the presence of the m-carboranyl coordinated with the MNPs core after uptake was proven by XPS and EELS. Importantly, thermal neutrons irradiation in BNCT reduced by 2.5 the number of cultured glioblastoma cells after 1-MNP treatment, and the systemic administration of 1-MNPs in mice was well tolerated with no major signs of toxicity.
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http://dx.doi.org/10.1016/j.nano.2019.03.008DOI Listing
August 2019

Slow-spin relaxation of a low-spin S = 1/2 Fe carborane complex.

Chem Commun (Camb) 2019 Mar;55(26):3825-3828

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Barcelona, Spain.

In this communication, we report the first evidence of slow-spin relaxation of a low-spin FeIII carborane complex. Iron S = 1/2 complexes showing such behaviour are particularly appealing as qubit candidates because they fulfil some of the main requirements to reach long decoherence times, such as moderate magnetic anisotropy, small spin, metal element mainly with zero-nuclear spin and furthermore, large versatility to introduce chemical modifications.
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http://dx.doi.org/10.1039/c9cc01123dDOI Listing
March 2019

All inorganic coordination polymers have been made possible with the m-carboranylphosphinate ligand.

Dalton Trans 2018 Oct;47(41):14785-14798

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Spain.

New examples of 1D coordination polymers (CPs) and complexes containing the purely inorganic carboranylphosphinate ligand [1-OPH(O)-1,7-closo-C2B10H11]- are reported. The reaction of Na[1-OPH(O)-1,7-closo-C2B10H11] salt with MCl2 (M = Mn, Co, Ni, Cu, Zn and Cd) in MeOH or EtOH leads to compounds 1-8. All compounds have been exhaustively characterized by analytical and spectroscopic techniques. X-ray analysis and spectroscopy characterization revealed the differences between the isolated compounds: 1D polymeric chains (CPs) with carboranylphosphinate ligand bridges have been obtained with MnII, CdII or ZnII centres, whereas compounds with low nuclearity have been isolated with CuII, CoII and NiII. No polymeric structures were obtained in the CoII and NiII complexes due to the higher affinity of these metals for water than that for the m-carboranylphosphinate and accordingly, these complexes generate supramolecular hydrophobic/hydrophilic structures. The reactivity of manganese polymer 1 with water leads to the breakage of the polymer with the formation of a new mononuclear compound 2, and that in methanol leads back to the initial polymer 1. However, the reactivity of polymer 1 with 2,2'-bpy maintains the core present in the initial polymer, leading to the CP 3, which in methanol/water medium produces species of lower nuclearity. The magnetic properties of the compounds studied show weak antiferromagnetic coupling.
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http://dx.doi.org/10.1039/c8dt03264eDOI Listing
October 2018

Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN].

Chemistry 2018 Nov 9;24(65):17239-17254. Epub 2018 Nov 9.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Barcelona, Spain.

After uptake by U87 MG and A375 cancer cells, cobaltabisdicarbollide [COSAN] distributes between membrane and nucleus and presents no relevant cytotoxicity against both cell lines even for long incubation times. The cytotoxicity of Na[COSAN] was also tested towards one normal cell line, the V79 fibroblasts, in order to ascertain the noncytotoxic profile of the compound. As the cell's nucleus contains DNA, the interaction between [COSAN] and double-stranded calf thymus DNA (CT-dsDNA) has been investigated. There is a strong interaction between both molecules forming a nanohybrid CT-dsDNA-[COSAN] biomaterial, which was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks ascribed to the oxidation/reduction of Co at a formal potential of -1.444 V and it can be accumulated at a surface-immobilized DNA layer of glassy carbon electrodes. The equilibrium surface-binding constants (K /K ), which confirm that [COSAN] interacts with DNA by an intercalative or electrostatic mode, depending on the ionic strength of the solution, were estimated. In addition, high binding affinity of Na[COSAN] to proteins was observed by B{ H} NMR and confirmed in vivo. Finally, biodistribution studies of [COSAN] in normal mice were run. After administration, Na[COSAN] was distributed into many organs but mainly accumulated in the reticuloendothelial system (RES), including liver and spleen. After 1 h, the formation of aggregates by plasma protein interaction plays a role in the biodistribution profile; the aggregates accumulate mostly in the lungs. Na[COSAN], which displays low toxicity and high uptake by relevant cancer cells accumulating boron within the nucleus, could act as a suitable compound for further developments as boron neutron capture therapy (BNCT) agents.
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http://dx.doi.org/10.1002/chem.201803178DOI Listing
November 2018

Carborane-BODIPY Dyads: New Photoluminescent Materials through an Efficient Heck Coupling.

Chemistry 2018 Oct 19;24(58):15622-15630. Epub 2018 Sep 19.

Department of Chemistry, University of Turin, Via P. Giuria 7, 10125, Torino, Italy.

A small library of carborane-BODIPY/aza-BODIPY dyads were efficiently synthesized by means of a novel convergent synthetic approach, the key step of which is a Pd-catalyzed Heck coupling reaction. The structural characterization and photoluminescence properties of the newly synthesized dyads were evaluated. The presence of the carborane did not significantly alter the photophysical patterns of the BODIPY or aza-BODIPY in the final fluorophores, but it produced a decrease of the emission fluorescent quantum yields that was in the range from 1.4 % for aza-BODIPY to 48 % for BODIPY-dyads. The carborane-BODIPY dyads were successfully incorporated into cells, especially compounds 2, 4 and 13, demonstrating their cytoplasmic localization. The fluorescent and biocompatibility properties make these compounds good candidates for in vitro cell tracking.
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http://dx.doi.org/10.1002/chem.201802901DOI Listing
October 2018

An Unprecedented Stimuli-Controlled Single-Crystal Reversible Phase Transition of a Metal-Organic Framework and Its Application to a Novel Method of Guest Encapsulation.

Adv Mater 2018 May 30:e1800726. Epub 2018 May 30.

Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193, Bellaterra, Spain.

The flexibility and unexpected dynamic behavior of a third-generation metal-organic framework are described for the first time. The synthetic strategy is based on the flexibility and spherical shape of dipyridyl-based carborane linkers that act as pillars between rigid Co/BTB (BTB: 1,3,5-benzenetricarboxylate) layers, providing a 3D porous structure (1). A phase transition of the solid can be induced to generate a new, nonporous 2D structure (2) without any loss of the carborane linkers. The structural transformation is visualized by snapshots of the multistep single-crystal-to-single-crystal transformation by single-crystal and powder X-ray diffraction. Poor hydrogen bond acceptors such as MeOH, CHCl or supercritical CO induce such a 3D to 2D transformation. Remarkably, the transformation is reversible and the 2D phase 2 is further converted back into 1 by heating in dimethylformamide. The energy requirements involved in such processes are investigated using periodic density functional theory calculations. As a proof of concept for potential applications, encapsulation of C is achieved by trapping this molecule during the reversible 2D to 3D phase transition, whereas no adsorption is observed by straight solvent diffusion into the pores of the 3D phase.
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http://dx.doi.org/10.1002/adma.201800726DOI Listing
May 2018

Fluorescent BODIPY-Anionic Boron Cluster Conjugates as Potential Agents for Cell Tracking.

Bioconjug Chem 2018 05 25;29(5):1763-1773. Epub 2018 Apr 25.

Instituto de Ciencia de Materiales de Barcelona (ICMAB-CSIC) , Campus de la UAB , E-08193 Bellaterra , Barcelona , Spain.

A series of novel fluorescent BODIPY-anionic boron cluster conjugates bearing [BH] (5, 6), [3,3'-Co(1,2-CBH)] (7, 8), and [3,3'-Fe(1,2-CBH)] (9) anions have been readily synthesized from meso-(4-hydroxyphenyl)-4,4-difluoro-4-bora-3 a,4 a-diaza- s-indacene (BODIPY 4), and their structure and photoluminescence properties have been assessed. Linking anionic boron clusters to the BODIPY (4) does not alter significantly the luminescent properties of the final fluorophores, showing all of them similar emission fluorescent quantum yields (3-6%). Moreover, the cytotoxicity and cellular uptake of compounds 5-9 have been analyzed in vitro at different concentrations of B (5, 50, and 100 μg B/mL) using HeLa cells. At the lowest concentration, none of the compounds shows cytotoxicity and they are successfully internalized by the cells, especially compounds 7 and 8, which exhibit a strong cytoplasmic stain indicating an excellent internalization efficiency. To the best of our knowledge, these are the first BODIPY-anionic boron cluster conjugates developed as fluorescent dyes aiming at prospective biomedical applications. Furthermore, the cellular permeability of the starting BODIPY (4) was improved after the functionalization with boron clusters. The exceptional cellular uptake and intracellular boron release, together with the fluorescent and biocompatibility properties, make compounds 7 and 8 good candidates for in vitro cell tracking.
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http://dx.doi.org/10.1021/acs.bioconjchem.8b00204DOI Listing
May 2018

Structural and dielectric properties of cobaltacarborane composite polybenzimidazole membranes as solid polymer electrolytes at high temperature.

Phys Chem Chem Phys 2018 Apr;20(15):10173-10184

Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

The conductivity of a series of composite membranes, based on polybenzimidazole (PBI) containing the metallacarborane salt M[Co(C2B9H11)2], M[COSANE] and tetraphenylborate, M[B(C6H5)4], M[TPB] both anions having the same number of atoms and the same negative charge, has been investigated. Different cations (M = H+, Li+ and Na+) have been studied and the composite membranes have been characterized by water uptake, swelling ratios, ATR FT-IR, thermogravimetric analysis and electrochemical impedance spectroscopy to explore the dielectric response and ion dynamics in composite membranes. Our results show that conductivity increases with increasing temperature and it is higher for H+ than for Li+ and Na+ for all temperatures under study. The mobility of Li+ is greater in [COSANE]- than in [TPB]- composite PBI@membranes while for Na+ it is the opposite. The temperature dependence of the conductivity of the composite was followed by a typical Arrhenius behaviour with two different regions: (1) between 20 and 100 °C, and (2) between 100 and 150 °C. Using the analysis of electrode polarization (EP) based on the Thrukhan theory we have calculated the ionic diffusion coefficients and the density of carriers. From the double logarithmic plot of the imaginary part of the conductivity (σ'') versus frequency in the entire range of temperatures studied we have determined for each sample at each temperature, the frequency values of the onset (fON) and full development of electrode polarization (fMAX), respectively, which permit us to calculate static permittivity.
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http://dx.doi.org/10.1039/c8cp00372fDOI Listing
April 2018