Anthracene-Fused Oligo-BODIPYs: a new class of π-extended NIR-absorbing materials

Large π-conjugated systems are key in the area of molecular materials. Herein, we prepare via AuI - catalyzed cyclization a series of fully π-conjugated anthracene-fused oligo-BODIPYs. Their structural and optoelectronic properties were studied by several techniques, ranging from X-ray, UV/Vis, and cyclic voltammetry to transient absorption spectroscopy. As a complement, their electronic structures were explored by means of Density Functional Theory (DFT) calculations. Depending on the size and shape of the π-conjugated skeleton, unique features—such as face-to-face supramolecular organization, NIR absorption and fluorescence as well as strong electron accepting character—were noted. All in all, the aforementioned features render them valuable for technological applicationsments We gratefully acknowledge financial support from the Spanish MICINN through Projects PID2020-116490GB-I00 (Porphyrinoids) and TED2021-131255B-C43 (PERSOLAR). We also thank financial support to the Comunidad de Madrid (MAD2D-CM) and MICINN through project “Materiales disruptivos bidimensionales (2D)” within the Plan de recuperación, transformación y resiliencia (Materiales avanzados). IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, Grant SEV2016-0686). J.L. acknowledges MECD, Spain, for a F.P.U. fellowship. European Commission under the Marie Sklodowska-Curie Action Cofund 2015 (EU project 713366-InterTalentum) is acknowledged for the support for G.D.S. Generous allocation of computational time from the Centro de Computación Científica UAM is gratefully acknowledged. Work in Erlangen was supported by the Deutsche Forschungsgemeinschaft (DFG) through SFB 953 project B10 and the Bavarian Collaborative Research Project “Solar Technologies go Hybrid” (SolTech

Glycosylated BODIPY- Incorporated Pt(II) Metallacycles for Targeted and Synergistic Chemo-Photodynamic Therapy

Pt(II)-BODIPY complexes combine the chemotherapeutic activity of Pt(II) with the photocytotoxicity of BODIPYs. Additional conjugation with targeting ligands can boost the uptake by cancer cells that overexpress the corresponding receptors. We describe two Pt(II) triangles, 1 and 2, built with pyridyl BODIPYs functionalized with glucose (3) or triethylene glycol methyl ether (4), respectively. Both 1 and 2 showed higher singlet oxygen quantum yields than 3 and 4, due to the enhanced singlet-to-triplet intersystem crossing. To evaluate the targeting effect of the glycosylated derivative, in vitro experiments were performed using glucose transporter 1 (GLUT1)-positive HT29 and A549 cancer cells, and noncancerous HEK293 cells as control. Both 1 and 2 showed higher cellular uptake than 3 and 4. Specifically, 1 was selective and highly cytotoxic toward HT29 and A549 cells. The synergistic chemo- and photodynamic behavior of the metallacycles was also confirmed. Notably, 1 exhibited superior efficacy toward the cisplatin-resistant R-HepG2 cellsFinancial support from Spanish MINECO (PID2020- 116490GB-I00 and PID2020-115801RB-C21) is acknowledged. We also thank financial support to the Comunidad de Madrid (MAD2D-CM) and MICINN (“Planes complementarios, Materiales Avanzados”). IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Program for Centres of Excellence in R&D (MINECO, Grant SEV2016-0686). E.Y.X. thanks The Chinese University of Hong Kong for support through the Impact Postdoctoral Fellowship Schem

Nuevos sistemas de colorantes orgánicos para aplicaciones láser y biofotónicas

La presente Tesis Doctoral titulada NUEVOS COLORANTES ORGÁNICOS PARA APLICACIONES LÁSER Y BIOFOTÓNICAS está dirigida al diseño y síntesis de nuevos sistemas basados en colorantes orgánicos, principalmente BODIPYs, con propiedades fotofísicas optimizadas para su aplicación como láseres. Los complejos dipirrometano BF2, o BODIPYs, constituyen un área de investigación emergente, debido a sus buenas y fácilmente modulables propiedades fotofísicas y a sus numerosas e importantes aplicaciones, dentro de las cuales se enmarca esta Tesis Doctoral. La Memoria consta de una introducción general y un breve resumen de los antecedentes más relevantes relacionados con los objetivos de la misma. Seguidamente, se recogen los aspectos claves planteados en este trabajo, la estructura de la Memoria y las técnicas empleadas para su desarrollo. A continuación, se divide la Tesis en cinco capítulos, recogiéndose en los cuatro primeros una serie de artículos publicados sobre los resultados obtenidos, y en el cuarto también se recoge parte del trabajo de investigación pendiente de publicación. Finalmente, en el quinto capítulo se resume el trabajo desarrollado en la estancia pre-doctoral realizada en la Universidad de Guanajuato, México, bajo la dirección del Prof. Peña Cabrera. El Capítulo 1 consiste en una recopilación de tres artículos en los cuales se describe el diseño y síntesis de una serie de nuevos colorantes halogenados sencillos y la evaluación de sus propiedades fotofísicas y de sus aplicaciones. A través de reacciones de sustitución electrófila aromática en diferentes cromóforos comerciales, BODIPYs, perilenos, cumarinas y rodaminas, se han logrado obtener nuevos colorantes fluorados con mayor fotoestabilidad y emisión láser que sus precursores no fluorados. En los otros dos artículos se detalla la halogenación selectiva de BODIPYs, lo que ha permitido obtener cloro- y yodo-BODIPYs mono-, di- y polihalogenados. Estos haloBODIPYs, además de ser versátiles precursores sintéticos, han resultado ser eficientes láseres de colorante, derivados clorados, o excelentes generadores de oxígeno singlete, derivados yodados, con posible aplicación en TFD. En el Capítulo 2 se detalla la síntesis de tres nuevos colorantes BODIPY, con emisión en la zona roja del espectro. Estos nuevos cromóforos presentan una emisión láser en torno a 620 nm y una fotoestabilidad superior a la de otros colorantes comerciales con emisión en la misma región espectral. El Capítulo 3 consta de dos artículos, en los que se aborda la síntesis de nuevos O- y E-BODIPYs mediante la introducción de diferentes grupos carboxilatos y acetilenos, respectivamente, en el átomo de boro de una serie colorantes comerciales. Estos nuevos derivados presentan una fotoestabilidad y emisión láser muy superior a sus precursores tanto en líquido como incorporados en matrices poliméricas, lo que potencia su uso en diferentes aplicaciones. Seguidamente, en el Capítulo 4 se trata la síntesis de una serie de cassettes con absorción pancromática y alta eficiencia láser, por combinación, en una misma molécula, de varios colorantes orgánicos como perilenos, cumarinas y BODIPYs. De esta forma, se han sintetizado sistemas multicromofóricos que, tras excitación a 355 nm, presentan una mejor fotoestabilidad y emisión láser en la región roja del espectro que algunos colorantes comerciales empleados como referencia en esa región. Además, la disposición ortogonal entre los fragmentos de BODIPYs que forman uno de los complejos multicromofóricos, permite que dicho sistema presente un comportamiento dual, pudiendo utilizarse como sonda fluorescente y generador de oxígeno singlete. El trabajo desarrollado tiene un carácter marcadamente multidisciplinar y no hubiera sido posible sin la colaboración de otros grupos de investigación de los profesores Santiago de la Moya Cerero, Iñigo López-Aberloa, Jorge Bañuelos Prieto, Eduardo Peña-Cabrera, Norman A. García y el Dr. José Luis Chiara

Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores

Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF2 azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.European Union's Horizon 2020 research and innovation program, under the Marie-Sklodowska-Curie grantDepto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu

Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores

Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF2 azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells

Annulative π-extension of BODIPYs made easy <i>via</i> gold(<scp>i</scp>)-catalyzed cycloisomerization

Here we report gold(i)-catalyzed cycloisomerization as a new powerful synthetic tool for the preparation of pi-extended BODIPY derivatives. The catalytic system (PPh3AuCl)-Au-F/AgSbF(6)enables the synthesis of [b]-[2,1]naphtho-fused-BODIPYs (2a-2c) under mild conditions, in excellent yields and short reaction times. The reaction is totally regioselective to the 6-endo-dig product and for the alpha-position of the BODIPY, which is both the kinetically and thermodynamically favored pathway, as supported by the free energy profile calculated by means of Density Functional Theory (DFT). Moreover, this methodology also allows the synthesis of two new families of [b]-aryl-fused-BODIPYs, namely, [3,4]phenanthro- (2eand2f) and [1,2]naphtho-fused (2g) BODIPYs. Their molecular and electronic structures were established by NMR and UV-vis spectroscopies as well as single-crystal X-ray diffraction analysis. As can be noted from the X-ray structures,2a,2eand2gpresent interesting structural differences at both the molecular and packing level. Interestingly, despite being isomers, the UV/vis spectra of2aand2grevealed significant differences in their electronic structures. The origin of this finding was studied by Time-Dependent DFT calculations. Calculated DFT Nuclear Independent Chemical Shift (NICS(0)) values also supported the different electronic structures of2aand2g.Spanish Ministerio de Economia y Competitividad (MINECO)European Commission under the Marie Sklodowska-Curie Action Cofund (EU project)Depto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu

Synthesis, aggregation, and photophysical properties of amphiphilic BODIPY-Pt(II) metallacycles

The construction of metallo-organic macrocycles using transition metals and optoelectronically active donor ligands is a very active area of research due to the potential applicability of these structures as sensors or as drugs for combined photodynamic/chemotherapy treatments. Herein, we report on the synthesis, photophysical properties, and aggregation behavior of a triangular Pt(II)-assembled metallo-supramolecular complex built by the coordination-driven assembly of a BODIPY functionalized with two pyridines at the 2,6 positions and an (R, R)-phenylalanine dipeptide moiety in the meso position. This hydrophilic group provides the metallacycle with water-solubility and self-assembly capabilities, which result in the formation of robust nanoparticles in aqueous solutions with a 50 nm average size.Spanish Ministerio de Economia y Competitividad (MINECO)Depto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu

Annulative p-extension of BODIPYs made easy via gold(I)-catalyzed cycloisomerization

Here we report gold(i)-catalyzed cycloisomerization as a new powerful synthetic tool for the preparation of π-extended BODIPY derivatives. The catalytic system PPhF3AuCl/AgSbF6 enables the synthesis of [b]-[2,1]naphtho-fused-BODIPYs (2a-2c) under mild conditions, in excellent yields and short reaction times. The reaction is totally regioselective to the 6-endo-dig product and for the α-position of the BODIPY, which is both the kinetically and thermodynamically favored pathway, as supported by the free energy profile calculated by means of Density Functional Theory (DFT). Moreover, this methodology also allows the synthesis of two new families of [b]-aryl-fused-BODIPYs, namely, [3,4]phenanthro- (2e and 2f) and [1,2]naphtho-fused (2g) BODIPYs. Their molecular and electronic structures were established by NMR and UV-vis spectroscopies as well as single-crystal X-ray diffraction analysis. As can be noted from the X-ray structures, 2a, 2e and 2g present interesting structural differences at both the molecular and packing level. Interestingly, despite being isomers, the UV/vis spectra of 2a and 2g revealed significant differences in their electronic structures. The origin of this finding was studied by Time-Dependent DFT calculations. Calculated DFT Nuclear Independent Chemical Shift (NICS(0)) values also supported the different electronic structures of 2a and 2gFinancial support from Spanish MINECO (CTQ2017-85393-P) is acknowledged. IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686). J. L. acknowledges MECD, Spain, for a F.P.U. fellowship. The European Commission under the Marie Sklodowska-Curie Action Cofund 2015 (EU project 713366-InterTalentum) is acknowledged for the support for G.D.S. Generous allocation of computational time from the Centro de Computación Científica UAM is gratefully acknowledge

Double click macrocyclization with Sondheimer diyne of aza-dipyrrins for B–F_ree bioorthogonal imaging

Sequential azide/diyne cycloadditions proved highly effective for the macrocyclization of a bis-azido aza-dipyrrin. Macrocyclic aza-dipyrrin could be produced in 30 min at rt in water with changes in fluorescence intensity and lifetimes measurable upon reaction. Live cell microscopy showed that aza-dipyrrins were suitable for confocal and STED super-resolution imaging and a bioorthogonal response to macrocyclization could be detected in cellular compartments. These results will encourage a broader examination of the sensing and imaging uses of aza-dipyrrins.Science Foundation IrelandEuropean Union (EU)Depto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu

Negishi reaction in BODIPY dyes. Unprecedented alkylation by palladium-catalyzed C–C coupling in boron dipyrromethene derivatives

Negishi reactions of 3-halogen and 3,5-dihalogen substituted BODIPYs with different organozinc reagents are reported as the first examples of this valuable palladium-catalyzed C–C coupling reaction into the family of the BODIPY dyes. It is demonstrated that the Negishi coupling is especially useful for obtaining interesting alkylated BODIPYs, including synthetically-valuable asymmetrically-3,5-disubstituted BODIPYs.Ministerio de Economía, Comercio y Empresa (España)Depto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu