RESUMEN
This study presents the synthesis and characterization of phenazinium dyes with absorption ranging from red to far-red, as well as emission extending into the far-red to near-infrared (NIR) region. The procedure involves the post-functionalization of a triamino-phenazinium that was recently reported as a theranostic agent. The introduction of electron-withdrawing moieties is accomplished through acylation or aromatic nucleophilic substitution. For one of the obtained products, a further substitution step could be achieved with primary amines to tune the electron density of the phenazinium core. The isolated dyes exhibit promising features that hold potential for future applications as biological markers or therapeutic agents.
RESUMEN
The efficient, versatile, and straightforward synthesis of the first N-alkyl analogues of induline 3B (8a and 8b) is reported. Thanks to the introduction of lipophilic substituents and their attractive photophysical properties (far-red emission and production of singlet oxygen), phenazinium 8b can be used as a theranostic agent and shows, at very low concentrations (100 nM), a remarkable ability to (i) image cells and zebrafish embryos with high quality under both mono- (514 nm) and biphotonic (790 and 810 nm) excitations, (ii) efficiently and quickly penetrate cancer cells rather than healthy fibroblasts, and (iii) induce a total or almost total cancer cell death in vitro and in vivo after illumination (λexc = 540-560 nm). The molecular structure of 8b is based on a triamino-phenazinium core only, with no need for additional components, highlighting the emergence of a minimalistic and versatile class of fluorescent probes for targeted photodynamic cancer therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Fenazinas/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Fibroblastos/metabolismo , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/metabolismo , Colorantes Fluorescentes/efectos de la radiación , Humanos , Luz , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fenazinas/síntesis química , Fenazinas/metabolismo , Fenazinas/efectos de la radiación , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/efectos de la radiación , Medicina de Precisión/métodos , Oxígeno Singlete/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Pez CebraRESUMEN
The first example of diamino-benzoquinonediimine bearing both electron-donating and electron-withdrawing groups on the same 6-π electron subunit was synthesized using a straightforward one pot strategy. Photophysical analysis and theoretical calculations demonstrate that this unique substitution pattern is efficient to favour the establishment of a single tautomeric structure in solution.
RESUMEN
We have developed site-selective bromination on the mesityl substituents of 10,20-dimesityl-5,15-diazaporphyrins. Treatment of 10,20-dimesityl-5,15-diazaporphyrin and its nickel(ii) complex with a combination of AuBr3/AgOTf induced selective bromination on the mesityl groups. These brominated products can be employed for late-stage modification of the aryl substituents.
RESUMEN
Janus bis(N-heterocyclic carbenes) composed of a porphyrin core with two N-heterocyclic carbene (NHC) heads fused to opposite pyrroles were used as bridging ligands for the preparation of metal complexes. We first focused our attention on the synthesis of gold(i) chloride complexes [(NHC)AuCl] and investigated the substitution of the chloride ligand by acetylides to obtain the corresponding [(NHC)AuC[triple bond, length as m-dash]CR] complexes. Polyacetylides were then used to obtain molecular multiporphyrinic systems with porphyrins fused to only one NHC ligand, while main-chain organometallic polymers (MCOPs) were obtained when using Janus porphyrin bis(NHCs). Interestingly, MCOPs incorporating zinc(ii) porphyrins proved to be efficient as heterogeneous photocatalysts for the generation of singlet oxygen upon visible light irradiation.
RESUMEN
N-Alkylation significantly changes the electronic and optical properties, as well as the reactivity of nitrogen-containing π-conjugated molecules. In this study, it is found that treating 5,15-diazaporphyrins with methyl triflate selectively affords the corresponding N-methyl-5,15-diazaporphyrinium cations in good yield. N-Methylation substantially alters the electronic properties and reactivity of diazaporphyrins. The electron-accepting properties of the N-methyl-5,15-diazaporphyrinium cations are enhanced due to their lowered LUMO level. Stabilization of the LUMO energy enables regio- and stereoselective Diels-Alder reactions of the cationic diazaporphyrin with cyclopentadiene. N-Methylation also enhances the acidity of the inner NH protons, and thus, allows facile deprotonation to provide nitrogen-substituted isoporphyrin analogues with only one NH group in the central cavity.
RESUMEN
Diazachlorin and diazabacteriochlorin have been prepared through reduction of diazaporphyrin and their in vitro and in vivo activity in photodynamic therapy has been investigated.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Células MCF-7 , Modelos Moleculares , Fotoquimioterapia/métodos , Fotones , Fármacos Fotosensibilizantes/síntesis química , Pez CebraRESUMEN
Porphyrins are conjugated, stable chromophores with a central core that binds a variety of metal ions and an easily functionalized peripheral framework. By combining the catalytic, electronic or cytotoxic properties of selected transition metal complexes with the binding and electronic properties of porphyrins, enhanced characteristics of the ensemble are generated. This review article focuses on porphyrins bearing one or more peripheral transition metal complexes and discusses their potential applications in catalysis or biomedicine. Modulation of the electronic properties and intramolecular communication through coordination bond linkages in bis-porphyrin scaffolds is also presented.
Asunto(s)
Tecnología Biomédica/tendencias , Complejos de Coordinación/química , Electrónica/tendencias , Porfirinas/química , Catálisis , Estructura MolecularRESUMEN
Porphyrins fused to imidazolium salts across two neighboring ß-pyrrolic positions were used as N-heterocyclic carbene (NHC) precursors to anchor AuI -Cl complexes at their periphery. Synthesis of several thiolato-AuI complexes was then achieved by substituting chloride for thiolates. Photodynamic properties of these complexes were investigated: the data obtained show that the Au-S bonds could be cleaved upon irradiation. The proposed mechanism to explain the release of thiolate moiety involves the S atom oxidation by singlet oxygen generated in the course of irradiation. In view of photodynamic therapy (PDT) applications, these porphyrins fused to NHC-AuI complexes were tested as photosensitizers to kill MCF-7 breast cancer cells. Results show the important role played by the ancillary ligands (chloride versus thiolates) on the photodynamic effect.
RESUMEN
The human tissue kallikrein-7 (KLK7) is a chymotryptic serine protease member of tissue kallikrein family. KLK7 is involved in skin homeostasis and inflammation. Excess of KLK7 activity is also associated with tumor metastasis processes, especially in ovarian carcinomas, prostatic and pancreatic cancers. Development of Kallikrein 7 inhibitors is thus of great interest in oncology but also for treating skin diseases. Most of the developed synthetic inhibitors present several drawbacks such as poor selectivity and unsuitable physico-chemical properties for in vivo use. Recently, we described a practical sequence for the synthesis of imidazopyridine-fused [1,3]-diazepines. Here, we report the identification of pyrido-imidazodiazepinone core as a new potential scaffold to develop selective and competitive inhibitors of kallikrein-related peptidase 7. Structure-activity relationships (SAR), inhibition mechanisms and selectivity as well as cytotoxicity against selected cancer cell lines were investigated.