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 (S1) and the triplet state (T1), resulting in improved and efficient intersystem crossing (ISC). Both PSs are highly effective in producing reactive oxygen species (ROS), including singlet oxygen and/or superoxide species. Additionally, they also demonstrate remarkably strong fluorescence emission. Indeed, in addition to providing exceptional photocytotoxicity, this emissive feature, generally lacking in other reported structures, allows for the precise monitoring of the PSs' distribution within specific cellular organelles even at nanomolar concentrations. These findings underscore the dual functionality of these PSs, serving as both fluorescent imaging probes and light-activated therapeutic agents, emphasizing their potential as versatile and multifunctional tools in the field of PDT.

Imidazo[1,2-a]pyridine and Imidazo[1,5-a]pyridine: Electron Donor Groups in the Design of D-π-A Dyes.

This work investigates the electron-donating capabilities of two 10-π electron nitrogen bridgehead bicyclic [5,6]-fused ring systems, imidazo[1,2-a]pyridine and imidazo[1,5-a]pyridine rings. Eight compounds with varying positions of electron-withdrawing moieties (TCF or DCI) coupled to the imidazopyridine ring were synthesized and studied. DCI-containing compounds (Ib-IVb) exhibited a purely dipolar nature with broad absorption bands, weak fluorescence, large Stokes shifts, and strong solvatochromism. In contrast, TCF-containing compounds (Ia-IVa) demonstrated diverse properties. Imidazo[1,2-a]pyridine derivatives Ia and IIa were purely dipolar, while imidazo[1,5-a]pyridine derivatives IIIa and IVa displayed a cyanine-like character with intense absorption and higher quantum yields of emission. The observed gradual red shift in optical properties with changing electron-donor groups (IIb < Ib < IIIb < IVb) and (IIa < Ia < IIIa < IVa) underscores the stronger electron-donor character of imidazo[1,5-a]pyridine compared to that of imidazo[1,2-a]pyridine. Furthermore, crystalline powders of imidazo[1,2-a]pyridine derivatives exhibited fluorescence despite minimal emission in solution. Two compounds (Ib and IVa) were successfully formulated into nanoparticles for potential in vivo imaging applications in zebrafish embryos.

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. Consequently, this simple yet efficient approach expands the catalog of known molecular engineering strategies for synthesizing heavy atom-free, dual redox-active, yet still emissive and synthetically accessible photosensitizers.

Modeling the polychromism of oxide minerals: The case of alexandrite and cordierite.

In this work, we investigate the spectroscopic properties of photochromic alexandrite and cordierite by TD-DFT. The objective is to assess the TD-DFT for the simulation of pleochroism (change of color depending on the crystallographic direction of the observation) and the change of color as a function of the light source. For these simulations, we compared an embedding where dangling bonds are saturated by hydrogen atoms and an electrostatic embedding. The electrostatic embedding provided numerically more stable results and allowed a good reproduction of the pleochroism of cordierite, based on a Fe2+-Fe3+ intervalence charge transfer transition. However, the pleochroism of alexandrite is not as well reproduced, suggesting that TD-DFT has some difficulties to reproduce the anisotropy of the transition dipole moment, an aspect that is not deeply documented in the literature.

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. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.

Correction: Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures.

Correction for 'Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures' by Marco Deiana et al., Nanoscale, 2021, 13, 13795-13808, https://doi.org/10.1039/D1NR02855C.

Tailoring the optoelectronic properties and dielectric profiles of few-layer S-doped MoO3 and O-doped MoS2 nanosheets: a first-principles study.

To gain insights into few layer (FL) van der Waals MoO3-xSx/MoS2-xOx heterostructures for photocatalytic applications, we analyze how the concentration (x) and location of anionic isovalent atom (S or O) substitutions impact their opto-electronic properties and high frequency dielectric constant profiles. By using density functional theory (DFT) calculations within the HSE06 functional, we show that the electronic band gap of FL MoO3-xSx decreases with increasing x, while the dielectric constant profile and absorption coefficient in the UV-vis range increase. The stronger band gap reductions are obtained when S-atoms are located in the internal bulk region of FL MoO3-xSx and in interaction with O-atoms of the neighboring layer. Moreover, the conduction and valence band (CB/VB) levels are shifted to higher energy values in the case of the edge location (external surface) of these S-atoms. Thanks to the determination of the thermodynamic diagrams of 4L MoO3-xSx and 6L MoS2-xOx, we propose optimal heterojunctions made of 4L MoO3-xSx with either single-layer (SL) or FL MoS2 with CB/VB levels compatible with a Z-scheme working principle and with potentials required for photocatalysis applications such as the photolysis of water into O2 and H2. This study combined with our previous theoretical investigations on bulk materials and SL provides a thorough analysis of SL-FL MoO3-xSx/MoS2 heterojunctions where the concentration and location of S-atoms in MoO3-xSx are key to design efficient materials for water photolysis.

Reusable radiochromic hackmanite with gamma exposure memory.

Radiochromic films are used as position-sensitive dose meters in e.g. medical physics and radiation processing. The currently available films like those based on lithium-10,12-pentacosdiynoate or leucomalachite green are either toxic or non-reusable, or both. There is thus a great need for a sustainable solution for radiochromic detection. In the present work, we present a suitable candidate: hackmanite with the general formula Na8Al6Si6O24(Cl,S)2. This material is known as a natural intelligent material capable of changing color when exposed to ultraviolet radiation or X-rays. Here, we show for the first time that hackmanites are also radiochromic when exposed to alpha particles, beta particles (positrons) or gamma radiation. Combining experimental and computational data we elucidate the mechanism of gamma-induced radiochromism in hackmanites. We show that hackmanites can be used for gamma dose mapping in high dose applications as well as a memory material that has the one-of-a-kind ability to remember earlier gamma exposure. In addition to satisfying the requirements of sustainability, hackmanites are non-toxic and the films made of hackmanite are reusable thus showing great potential to replace the currently available radiochromic films.

The structural origin of the efficient photochromism in natural minerals.

SignificanceNatural photochromic minerals have been reported by geologists for decades. However, the understanding of the photochromism mechanism has a key question still unanswered: What in their structure gives rise to the photochromism's reversibility? By combining experimental and computational methods specifically developed to investigate this photochromism, this work provides the answer to this fundamental question. The specific crystal structure of these minerals allows an unusual motion of the sodium atoms stabilizing the electronic states associated to the colored forms. With a complete understanding of the photochromism mechanism in hand, it is now possible to design new families of stable and tunable photochromic inorganic materials-based devices.

Electronic structures of the MoS2/TiO2 (anatase) heterojunction: influence of physical and chemical modifications at the 2D- or 1D-interfaces.

To tackle the challenge of CO2 photoreduction, semiconducting layered transition metal dichalcogenides like MoS2 have attracted much attention due to their tunable 2D nano-structures. By using advanced periodic density functional theory calculations (HSE06 functional), we provide a systematic quantification of the optoelectronic properties of various interfacial heterostructures composed of 2H-MoS2 and anatase TiO2. We systematically determine the band gaps, and conduction band (CB) and valence band (VB) positions to figure out the nature of the heterojunction. Two main surface orientations of anatase TiO2 particles, (101) and (001), are considered with 2D-MoS2 nanosheets or nanoribbons forming either a 2D physical (van der Waals) or through a 1D chemical interface. The possibility to chemically modify the MoS2/TiO2 interface, either by sulfidation or hydration, and its effect on the electronic structure are deeply investigated. These modifications in the heterostructure lead to important changes in the electronic properties and charge transfer between the two materials which impact both photon absorption properties and charge carrier dynamics suspected to influence in turn the photocatalytic activity. While a type I hetrojunction is found for the 1D chemical interface, a type II heterojunction with appropriate CB/VB positions for CO2 reduction and H2O oxidation is identified for the 2D physical interface which could lead to the targeted Z-scheme mechanism with strong potential interest in photocatalysis applications.

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. In contrast to the BTI, these thionated analogs display an almost fully quenched fluorescence emission, in agreement with the formation of highly populated triplet states. Indeed, the sequential thionation on the BTI scaffold induces torsion of its skeleton reducing the singlet-triplet energy gaps and enhancing the spin-orbit coupling. These potential PSs show potent cancer-cell ablation under light irradiation while remaining non-toxic under dark condition owing to a photo-cytotoxic mechanism that we believe simultaneously involves singlet oxygen and superoxide species, which could be both characterized in vitro. Our study demonstrates that this simple site-selected thionated platform is an effective strategy to convert conventional carbonyl-containing fluorophores into phototherapeutic agents for anticancer PDT.

Tuning Excited-State Properties of [2.2]Paracyclophane-Based Antennas to Ensure Efficient Sensitization of Lanthanide Ions or Singlet Oxygen Generation.

The multistep synthesis of original antennas incorporating substituted [2.2]paracyclophane (pCp) moieties in the π-conjugated skeleton is described. These antennas, functionalized with an electron donor alkoxy fragment (A1) or with a fused coumarin derivative (A2), are incorporated in a triazacyclonane macrocyclic ligand L1 or L2, respectively, for the design of Eu(III), Yb(III), and Gd(III) complexes. A combined photophysical/theoretical study reveals that A1 presents a charge transfer character via through-space paracyclophane conjugation, whereas A2 presents only local excited states centered on the coumarin-paracyclophane moiety, strongly favoring triplet state population via intersystem crossing. The resulting complexes EuL1 and YbL2 are fully emissive in red and near-infrared, respectively, whereas the GdL2 complex acts as a photosensitizer for the generation of singlet oxygen.

Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures.

Light-activated functional materials capable of remote control over duplex and G-quadruplex (G4) nucleic acids formation at the cellular level are still very rare. Herein, we report on the photoinduced macrocyclisation of a helicenoid quinoline derivative of binaphthol that selectively provides easy access to an unprecedented class of extended heteroaromatic structures with remarkable photophysical and DNA/RNA binding properties. Thus, while the native bisquinoline precursor shows no DNA binding activity, the new in situ photochemically generated probe features high association constants to DNA and RNA G4s. The latter inhibits DNA synthesis by selectively stabilizing G4 structures associated with oncogenic promoters and telomere repeat units. Finally, the light sensitive compound is capable of in cellulo photoconversion, localizes primarily in the G4-rich sites of cancer cells, competes with a well-known G4 binder and shows a clear nuclear co-localization with the quadruplex specific antibody BG4. This work provides a benchmark for the future design and development of a brand-new generation of light-activated target-selective G4-binders.

2D MoO3-xSx/MoS2 van der Waals Assembly: A Tunable Heterojunction with Attractive Properties for Photocatalysis.

Two-dimensional (2D) van der Waals (vdW) heterostructures currently have attracted much attention in widespread research fields where semiconductor materials are key. With the aim of gaining insights into photocatalytic materials, we use density functional theory (DFT) calculations within the HSE06 functional to analyze the evolution of optoelectronic properties and high-frequency dielectric constant profiles of various 2D MoO3-xSx/MoS2 heterostructures modified by chemical and physical approaches. Although the MoO3/MoS2 heterostructure is a type III heterojunction associated with a metallic character, we found that exchanging the terminal oxo atoms of the MoO3-xSx single layer (SL) with sulfur enables shifting its CB position above the VB position of the MoS2 SL. This trend gives rise to a type II heterojunction where the band gap and charge transfer within the two layers are driven continuously by the S concentration in the MoO3-xSx SL. This fine-tuning leads to a versatile type II heterostructure proposed to provide a direct Z-scheme system valuable for photocatalytic water splitting.

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. Although the SOC relies on complex relativistic phenomena, theoreticians have, with time, developed increasingly sophisticated and efficient approaches to gain access to a satisfactory evaluation of its magnitude. However, recent works have highlighted the remarkable and somehow unexpected efficiency of dimers of small conjugated molecules in terms of ISC quantum yields, whose origin has not been completely investigated. In this work, we bring a coupled experimental and theoretical analysis of the origin of the unusually large ISC efficiency on a series of such dimers that differ by their nature (covalent or supramolecular). We show that considering the dynamical nature of the SOC, and especially its dependence on angular orientations between the dimer subunits sometimes overlooked in the literature, it is necessary to rationalize some counterintuitive experimental observations. This combined experimental and theoretical work paves the way for new molecular engineering rules for SOC control.

Spin-orbital coupling and slow phonon effects enabled persistent photoluminescence in organic crystal under isomer doping.

When periodically packing the intramolecular donor-acceptor structures to form ferroelectric-like lattice identified by second harmonic generation, our CD49 molecular crystal shows long-wavelength persistent photoluminescence peaked at 542 nm with the lifetime of 0.43 s, in addition to the short-wavelength prompt photoluminescence peaked at 363 nm with the lifetime of 0.45 ns. Interestingly, the long-wavelength persistent photoluminescence demonstrates magnetic field effects, showing as crystalline intermolecular charge-transfer excitons with singlet spin characteristics formed within ferroelectric-like lattice based on internal minority/majority carrier-balancing mechanism activated by isomer doping effects towards increasing electron-hole pairing probability. Our photoinduced Raman spectroscopy reveals the unusual slow relaxation of photoexcited lattice vibrations, indicating slow phonon effects occurring in ferroelectric-like lattice. Here, we show that crystalline intermolecular charge-transfer excitons are interacted with ferroelectric-like lattice, leading to exciton-lattice coupling within periodically packed intramolecular donor-acceptor structures to evolve ultralong-lived crystalline light-emitting states through slow phonon effects in ferroelectric light-emitting organic crystal.

Investigation of the K4[Fe(CN)6]-Mediated Mono- and Bis-Palladium-Catalyzed Cyanation of the Benzothioxanthene Core.

The pallado-catalyzed cyanation of benzothioxanthene imide (BTXI) derivatives is explored herein. Once optimized on the monobromo BTXI, 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. As well as impacting the structural, photo physical and electrochemical properties of the BTXI core, nitrile moieties were successfully used as orthogonal protecting groups, thus opening doors to new design principles.

What does graphitic carbon nitride really look like?

Graphitic carbon nitrides (g-CNs) have become popular light absorbers in photocatalytic water splitting cells. Early theoretical work on these structures focused on fully polymerized g-C3N4. Experimentally, it is known that the typically employed melamine polycondensation does not go toward completion, yielding structures with ∼15 at% hydrogen. Here, we study the conformational stability of "melon", with the [C6N9H3]n structural formula using DFT. Referencing to a 2D melon sheet, B3LYP-dDsC and PBE-MBD computations revealed the same qualitative trend in stability of the 3D structures, with several of them within 5 kJ mol-1 per tecton. Fina's orthorhombic melon is the most stable of the studied conformers, with Lotsch' monoclinic melon taking an intermediate value. Invoking a simple Wannier-Mott-type approach, Fina's and Lotsch' structures exhibited the lowest optical gaps (2.8 eV), within the error margin of the experimental value (2.7 eV). All conformers yielded gaps below that of the monolayer's (3.2 eV), suggesting Jelley-type ("J") aggregation effects.

σ-Conjugation and H-Bond-Directed Supramolecular Self-Assembly: Key Features for Efficient Long-Lived Room Temperature Phosphorescent Organic Molecular Crystals.

Long-lived room temperature phosphorescence from organic molecular crystals attracts great attention. Persistent luminescence depends on the electronic properties of the molecular components, mainly π-conjugated donor-acceptor (D-A) chromophores, and their molecular packing. Here, a strategy is developed by designing two isomeric molecular phosphors incorporating and combining a bridge for σ-conjugation between the D and A units and a structure-directing unit for H-bond-directed supramolecular self-assembly. Calculations highlight the critical role played by the two degrees of freedom of the σ-conjugated bridge on the chromophore optical properties. The molecular crystals exhibit RTP quantum yields up to 20 % and lifetimes up to 520 ms. The crystal structures of the efficient phosphorescent materials establish the existence of an unprecedented well-organization of the emitters into 2D rectangular columnar-like supramolecular structure stabilized by intermolecular H-bonding.

Two-Photon Absorbing AIEgens: Influence of Stereoconfiguration on Their Crystallinity and Spectroscopic Properties and Applications in Bioimaging.

This paper aims at designing chromophores with efficient aggregation-induced emission (AIE) properties for two-photon fluorescence microscopy (2PFM), which is one of the best-suited types of microscopy for the imaging of living organisms or thick biological tissues. Tetraphenylethylene (TPE) derivatives are common building blocks in the design of chromophores with efficient AIE properties. Therefore, in this study, extended TPE AIEgens specifically optimized for two-photon absorption (2PA) are synthesized and the resulting (E/Z) isomers are separated using chromatography on chiral supports. Comparative characterization of the AIE properties is performed on the pure (Z) and (E) isomers and the mixture, allowing us, in combination with powder X-ray diffraction and solid-state NMR, to document a profound impact of crystallinity on solid-state fluorescence properties. In particular, we show that stereopure AIEgens form aggregates of superior crystallinity, which in turn exhibit a higher fluorescence quantum yield compared to diastereoisomers mixtures. Preparation of stereopure organic nanoparticles affords very bright fluorescent contrast agents, which are then used for cellular and intravital two-photon microscopy on human breast cancer cells and on zebrafish embryos.