Photodynamic Therapy Using a Heavy-Atom-Free G‑Quadruplex-Targeted Photosensitizer to Efficiently Regress Rhabdomyosarcoma Tumors In Vivo.

Rhabdomyosarcoma is a highly aggressive soft tissue cancer that predominantly affects children and adolescents. Current treatment outcomes are poor, highlighting the urgent need for potent therapeutic alternatives. Preclinical research on photodynamic therapy (PDT) continues to gain attention as a promising and minimally invasive treatment strategy.

G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage.

G-quadruplex (G4)-targeted photosensitizers (PSs) are advancing precision oncology by confining DNA damage to malignant cells while sparing healthy tissue. Yet, molecular-level studies on the mechanisms and dynamics of G4 structure damage under PSs light-activation are limited. Here, we introduce DBI-POE, an activatable, heavy-atom-free PS derived from the G4-specific sulfur-substituted dibenzothioxanthene imide (S-DBI) and modified with a hydrophilic, bio-compatible polyoxyethylene (POE) side chain.

Light-Activated Molecules Targeting G-Quadruplex Nucleic Acids.

Phototherapies harness light's spatial and temporal precision to noninvasively modulate biomolecular interactions, providing a powerful platform for precision oncology. This approach is particularly effective in targeting disease-associated molecular structures such as G-quadruplexes (G4s), noncanonical nucleic acid conformations found in oncogene promoters and telomeres. These unique structures can impede DNA polymerase progression along the duplex, triggering DNA damage that ultimately compromises genomic stability.

Organelle-Specific Thiochromenocarbazole Imide Derivative as a Heavy-Atom-Free Type I Photosensitizer for Biomolecule-Triggered Image-Guided Photodynamic Therapy.

Modern photodynamic therapy (PDT) demands next-generation photosensitizers (PSs) that overcome heavy-atom dependency and enhance efficacy beyond traditional, highly oxygen-dependent type II mechanisms. We introduce herein , as a thiochromenocarbazole imide derivative designed for type I photodynamic action. Upon light activation, efficiently favors superoxide (O) and PS-centered radical formation instead of singlet oxygen (O) generation.

Navigating Ball Mill Specifications for Theory-to-Practice Reproducibility in Mechanochemistry.

The rising prospects of mechanochemically assisted syntheses hold promise for both academia and industry, yet they face challenges in understanding and, therefore, anticipating respective reaction kinetics. Particularly, dependencies based on variations in milling equipment remain little understood and globally overlooked. This study aims to address this issue by identifying critical parameters through kinematic models, facilitating the reproducibility of mechanochemical reactions across the most prominent mills in laboratory settings, namely planetary and mixer mills.

Heavy-atom-free π-twisted photosensitizers for fluorescence bioimaging and photodynamic therapy.

As the field of preclinical research on photosensitizers (PSs) for anticancer photodynamic therapy (PDT) continues to expand, a focused effort is underway to develop agents with innovative molecular structures that offer enhanced targeting, selectivity, activation, and imaging capabilities. In this context, we introduce two new heavy-atom-free PSs, DBXI and DBAI, characterized by a twisted π-conjugation framework. This innovative approach enhances the spin-orbit coupling (SOC) between the singlet excited state (S) and the triplet state (T), resulting in improved and efficient intersystem crossing (ISC).

Expanding the Use of Benzothioxanthene Imides to Photochemistry: Eco-Friendly Aerobic Oxidation of Sulfides to Sulfoxides.

The sulfoxide moiety is one of the most commonly utilized groups in pharmaceutical and industrial chemistry. The need for sustainability and easy accessibility to sulfoxide moieties is deemed necessary, due to its ubiquity in natural products and potentially pharmaceutically active compounds. In this context, we report herein a sustainable, aerobic and environmentally friendly photochemical protocol based on the use of a benzothioxathene imide as the photocatalyst to selectively oxidize sulfides under mild irradiation (456 nm), in very low catalyst loading (0.

Driving Triplet State Population in Benzothioxanthene Imide Dyes: Let's twist!

Controlling the formation of photoexcited triplet states is critical for many (photo)chemical and physical applications. Here, we demonstrate that a permanent out-of-plane distortion of the benzothioxanthene imide (BTI) dye promotes intersystem crossing by increasing spin-orbit coupling. This manipulation was achieved through a subtle chemical modification, specifically the bay-area methylation.

A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression.

Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation.

From Textile Coloring to Light-emitting Electrochemical Devices: Upcycling of the Isoviolanthrone Vat Dye.

Produced at ton scale, vat dyes are major environmental pollutants generated by the textile industry. However, they represent ideal and accessible candidates for chemical upcycling since they are usually composed of large π-conjugated scaffolds. Based on the valorization of "old" products, waste or even contaminant into high-added value goods, this concept can be easily transposed to the laboratories.

Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy.

Photodynamic therapy is a clinically approved anticancer modality that employs a light-activated agent (photosensitizer) to generate cytotoxic reactive oxygen species (ROS). There is therefore a growing interest for developing innovative photosensitizing agents with enhanced phototherapeutic performances. Herein, we report on a rational design synthetic procedure that converts the ultrabright benzothioxanthene imide (BTI) dye into three heavy-atom-free thionated compounds featuring close-to-unit singlet oxygen quantum yields.

Exploring the Concept of Dimerization-Induced Intersystem Crossing: At the Origins of Spin-Orbit Coupling Selection Rules.

Singlet-triplet interconversions (intersystem crossing, ISC) in organic molecules are at the basis of many important processes in cutting-edge photonic applications (organic light-emitting devices, photodynamic therapy, etc.). Selection rules for these transitions are mainly governed by the spin-orbit coupling (SOC) phenomenon.

Reducing Non-Radiative Voltage Losses by Methylation of Push-Pull Molecular Donors in Organic Solar Cells.

Organic solar cells are approaching power conversion efficiencies of other thin-film technologies. However, in order to become truly market competitive, the still substantial voltage losses need to be reduced. Here, the synthesis and characterization of four novel arylamine-based push-pull molecular donors was described, two of them exhibiting a methyl group at the para-position of the external phenyl ring of the arylamine block.

Investigation of the K[Fe(CN)]-Mediated Mono- and Bis-Palladium-Catalyzed Cyanation of the Benzothioxanthene Core.

The pallado-catalyzed cyanation of benzothioxanthene imide () derivatives is explored herein. Once optimized on the monobromo , mild reaction conditions were successfully applied to the dibromo derivative affording two regioisomers that have been isolated and structurally solved. Additional hydrogen-deuterium exchange experiments were carried out to support a proposed mechanism involving the formation of a five-membered palladacycle intermediate in the bay area.

Anisotropic confinement of chromophores induces second-order nonlinear optics in a nanoporous photonic metamaterial.

Second-order nonlinear optics is the base for a large variety of devices aimed at the active manipulation of light. However, physical principles restrict its occurrence to non-centrosymmetric, anisotropic matter. This significantly limits the number of base materials exhibiting nonlinear optics.

Synthesis, characterization and use of benzothioxanthene imide based dimers.

The synthesis of benzothioxanthene imide based dimers is reported herein. Subtle chemical modifications were carried out and their impact on the optical and electrochemical properties was investigated for a better structure-property relationship analysis. The icing on the cake was that these new structures were used as light emitting materials for the fabrication and demonstration of the first BTXI-based OLEDs.

Triphenylamine/Tetracyanobutadiene-Based π-Conjugated Push-Pull Molecules End-Capped with Arene Platforms: Synthesis, Photophysics, and Photovoltaic Response.

π-Conjugated push-pull molecules based on triphenylamine and 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) have been functionalized with different terminal arene units. In solution, these highly TCBD-twisted systems showed a strong internal charge transfer band in the visible spectrum and no detectable photoluminescence (PL). Photophysical and theoretical investigations revealed very short singlet excited state deactivation time of ≈10 ps resulting from significant conformational changes of the TCBD-arene moiety upon photoexcitation, opening a pathway for non-radiative decay.

Theoretical and experimental investigation on the intersystem crossing kinetics in benzothioxanthene imide luminophores, and their dependence on substituent effects.

In spite of their remarkable luminescence properties, benzothioxanthene imide (BTXI, an imide containing rylene chromophores) derivatives have been largely overlooked compared to their perylene bisimide and naphthalene bisimide counterparts. Thus, their detailed photophysics are much less understood. In this paper, we show how relatively simple structural modifications of the backbone of BTXIs can lead to impressive variations in their inter-system crossing kinetics.

Modulation of circularly polarized luminescence through excited-state symmetry breaking and interbranched exciton coupling in helical push-pull organic systems.

π-Helical push-pull dyes were prepared and their (chir)optical properties were investigated both experimentally and computationally. Specific fluorescent behaviour of bis-substituted system was observed with unprecedented solvent effect on the intensity of circularly polarized luminescence (CPL, dissymmetry factor decreasing from 10 to 10 with an increase in solvent polarity) that was linked to a change in symmetry of chiral excited state and suppression of interbranched exciton coupling. The results highlight the potential of CPL spectroscopy to study and provide a deeper understanding of electronic photophysical processes in chiral π-conjugated molecules.

Indeno[1,2-b]thiophene End-capped Perylene Diimide: Should the 1,6-Regioisomers be systematically considered as a byproduct?

Usually considered as a byproduct, the 1,6-dibrominated PDI has rarely been functionalized for the preparation of electro-active conjugated molecules, particularly in the field of organic photovoltaics. In light of the literature, one can ask oneself: Does a 1,7-isomer based functional molecule systematically perform better than its 1,6-analogue? To answer this question, we report herein the synthesis and direct comparison of two indeno[1,2-b]thiophene (IDT) end-capped perylene diimide regioisomers (PDI) (1,6 and 1,7) used as non-fullerene acceptors in organic solar cells. It turned out that in our case, ie, when blended with the well-known PTB7-Th donor polymer, higher performance was reached for devices made with the 1,6-analogue.

Arylamine Based Photoactive Push-Pull Molecular Systems: A Brief Overview of the Chemistry "Made in Angers".

This mini review aims at taking stock of some arylamine based push-pull chromophores developed in the "Systèmes Conjugués Linéaires" (SCL) group at the University of Angers. Selected examples highlight more than a decade of design principles and strategies implemented to afford simple and accessible soluble molecular donors as active material for organic solar cells (OSCs).

Direct (Hetero)Arylation Polymerization of a Spirobifluorene and a Dithienyl-Diketopyrrolopyrrole Derivative: New Donor Polymers for Organic Solar Cells.

The synthesis and preliminary evaluation as donor material for organic photovoltaics of the poly(diketopyrrolopyrrole-spirobifluorene) () is reported herein. Prepared via homogeneous and heterogeneous direct (hetero)arylation polymerization (DHAP), through the use of different catalytic systems, conjugated polymers with comparable molecular weights were obtained. The polymers exhibited strong optical absorption out to 700 nm as thin-films and had appropriate electronic energy levels for use as a donor with .

Spectroscopic Engineering toward Near-Infrared Absorption of Materials Containing Perylene Diimide.

The ability to tune the dye structure synthetically has been crucial in the development of materials with tailored properties for given applications. In this contribution, a series of discrete molecules are reported, which are constructed from the perylene diimide (PDI) chromophore and three dyes, namely thienyl diketopyrrolopyrrole (DPP ), pyridyl diketopyrrolopyrrole (DPP ), and thienoisoindigo (TII). Through the choice of dye molecule and linking of the dye and PDI through conjugated acetylene bridges, the light-harvesting characteristics can be engineered to exhibit optical absorption in the range 300-900 nm.

Thermally induced crystallization, hole-transport, NLO and photovoltaic activity of a bis-diarylamine-based push-pull molecule.

The synthesis of a molecule constituted of two diarylamine-based push-pull chromophores covalently linked via their nitrogen atom is described. Comparison of the electronic properties with the parent monomer shows that dimerization has negligible influence on the electronic properties of the molecule but exerts a dramatic impact on the capacity of the material to self-reorganize. Application of thermal annealing to thin films induces the crystallization under original morphologies, a process accompanied by a partial bleaching of the absorption in the visible range and by a huge increase of hole-mobility.

Enantiopure versus Racemic Naphthalimide End-Capped Helicenic Non-fullerene Electron Acceptors: Impact on Organic Photovoltaics Performance.

Impact of the enantiopurity on organic photovoltaics (OPV) performance was investigated through the synthesis of racemic and enantiomerically pure naphthalimide end-capped helicenes and their application as non-fullerene molecular electron acceptors in OPV devices. A very strong increase of the device performance was observed by simply switching from the racemic to the enantiopure forms of these π-helical non-fullerene acceptors with power conversion efficiencies jumping from 0.4 to about 2.