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.

Influence of Chemical Modifications of the Crystallophore on Protein Nucleating Properties and Supramolecular Interactions Network.

Crystallophores are lanthanide complexes that have demonstrated outstanding induction of crystallization for various proteins. This article explores the effect of tailored modifications of the crystallophore first generation and their impact on the nucleating properties and protein crystal structures. Through high-throughput crystallization experiments and dataset analysis, we evaluated the effectiveness of these variants, in comparison to the first crystallophore generation G1. In particular, the V1 variant, featuring a propanol pendant arm, demonstrated the ability to produce new crystallization conditions for the proteins tested (hen-egg white lysozyme, proteinase K and thaumatin). Structural analysis performed in the case of hen egg-white lysozyme along with Molecular Dynamics simulations, highlights V1's unique behavior, taking advantage of the flexibility of its propanol arm to explore different protein surfaces and form versatile supramolecular interactions.

Island restoration to rebuild seabird populations and amplify coral reef functioning.

Mobile organisms like seabirds can provide important nutrient flows between ecosystems, but this connectivity has been interrupted by the degradation of island ecosystems. Island restoration (via invasive species eradications and the restoration of native vegetation) can reestablish seabird populations and their nutrient transfers between their foraging areas, breeding colonies, and adjacent nearshore habitats. Its diverse benefits are making island restoration increasingly common and scalable to larger islands and whole archipelagos. We identified the factors that influence breeding seabird abundances throughout the Chagos Archipelago in the Indian Ocean and conducted predictive modeling to estimate the abundances of seabirds that the archipelago could support under invasive predator eradication and native vegetation restoration scenarios. We explored whether the prey base exists to support restored seabird populations across the archipelago, calculated the nitrogen that restored populations of seabirds might produce via their guano, and modeled the cascading conservation gains that island restoration could provide. Restoration was predicted to increase breeding pairs of seabirds to over 280,000, and prey was predicted to be ample to support the revived seabird populations. Restored nutrient fluxes were predicted to result in increases in coral growth rates, reef fish biomasses, and parrotfish grazing and bioerosion rates. Given these potential cross-ecosystem benefits, our results support island restoration as a conservation priority that could enhance resilience to climatic change effects, such as sea-level rise and coral bleaching. We encourage the incorporation of our estimates of cross-ecosystem benefits in prioritization exercises for island restoration.

Restauración en islas para reconstruir las poblaciones de aves marinas y amplificar la funcionalidad de los arrecifes de coral Resumen Los organismos móviles como las aves marinas pueden proporcionar flujos importantes de nutrientes entre los ecosistemas, aunque esta conectividad ha sido interrumpida por la degradación de los ecosistemas isleñas. La restauración de islas (por medio de la erradicación de especies invasoras y la restauración de la vegetación nativa) puede reestablecer las poblaciones de aves marinas y su transferencia de nutrientes entre las áreas de forrajeo, las colonias reproductoras y los hábitats adyacentes a la costa. Los diferentes beneficios de la restauración de islas hacen que sea cada vez más común y escalable a islas más grandes y archipiélagos completos. Identificamos los factores que influyen sobre la abundancia de aves reproductoras en todo el archipiélago de Chagos en el Océano Índico y realizamos un modelo predictivo para estimar la abundancia de aves que podría soportar el archipiélago bajo escenarios de la erradicación de un depredador invasor y la restauración de la vegetación nativa. Exploramos si existe la base de presas para soportar las poblaciones restauradas de aves marinas en el archipiélago, calculamos el nitrógeno que las poblaciones restauradas podrían producir mediante el guano y modelamos la conservación en cascada que podría proporcionar la restauración de la isla. Se pronosticó que la restauración incrementaría las parejas reproductoras a más de 280,000 y que las presas serían las suficientes para soportar las poblaciones restauradas de aves marinas. También se pronosticó que los flujos restaurados de nutrientes resultarían en un incremento de la tasa de crecimiento de los corales, la biomasa de los peces del arrecife y las tasas de bio­erosión y de alimentación de los peces loro. Dados estos beneficios potenciales entre los ecosistemas, nuestros resultados respaldan a la restauración de islas como una prioridad de conservación que podría incrementar la resiliencia a los efectos del cambio climático, como el incremento en el nivel del mar y el blanqueamiento de los corales. Promovemos que se incorporen nuestras estimaciones de los beneficios transecosistémicos dentro de los ejercicios de priorización para la restauración de islas.

One touch is all it takes: the supramolecular interaction between ubiquitin and lanthanide complexes revisited by paramagnetic NMR and molecular dynamics.

The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize the affinity of two lanthanide complexes for ubiquitin. As the interaction process is dynamic, the acquired NMR data only reflect the time average of the different steps. We have used molecular dynamics (MD) simulations to get a deeper insight into the detailed interaction scenario at the microsecond scale. This NMR/MD approach enabled us to establish that the tris-dipicolinate complex interacts specifically with arginines and lysines, while the crystallophore explores the protein surface through weak interactions with carboxylates. These observations shed new light on the dynamic interaction properties of these complexes, which will ultimately enable us to propose a crystallization mechanism.

Temperature-dependent NIR-CPL spectra of chiral Yb(III) complexes.

Chiral, enantiopure Yb(III) complexes exhibit circularly polarized luminescence (CPL) in the near infrared (NIR) wavelength region. This CPL is quantified by the dissymmetry factor (glum). The excited state 2F5/2 consists of six mJ' states degenerated in three Stark levels, due to the crystal-field splitting (CFS), which are populated in accordance with the Boltzmann distribution. Consequently, room temperature CPL spectra are the sum of various - either positive or negative - contributions, that are practically impossible to quantify. To address this issue, an advanced setup enabling CPL measurements over a broad temperature range (300 to 4 K) has been developed. The interrelation of CFS, glum and temperature was explored using a pair of enantiopure Yb(III) complexes, highlighting the individual contribution of each crystal-field sublevel to the overall CPL spectrum, as anticipated by simulations performed in the framework of multireference wave-functions. Hence, the CPL spectra of chiral lanthanide complexes were found to be indeed strongly temperature-dependent, as is the glum dissymmetry factor, as a consequence of the variation in thermal sublevel population.

Targeted, Molecular Europium(III) Probes Enable Luminescence-Guided Surgery and 1 Photon Post-Surgical Luminescence Microscopy of Solid Tumors.

Discrete luminescent lanthanide complexes represent a potential alternative to organic chromophores due to their tunability of optical properties, insensitivity to photobleaching, and large pseudo-Stokes shifts. Previously, we demonstrated that the lack of depth penetration of UV excitation required to sensitize discrete terbium and europium complexes can be overcome using Cherenkov radiation emitted by clinically employed radioisotopes in situ. Here, we show that the second-generation europium complexes [Eu(III)(pcta-PEPA2)] and [Eu(III)(tacn-pic-PEPA2)] (Φ = 57% and 76%, respectively) lower the limit of detection (LoD) to 1 nmol in the presence of 10 µCi of Cherenkov emitting isotopes, 18F and 68Ga. Bifunctionalization provides access to cysteine-linked peptide conjugates with comparable brightness and LoD. The conjugate, [Eu(tacn-(pic-PSMA)-PEPA2)], displays high binding affinity to prostate-specific membrane antigen (PSMA)-expressing PC-3 prostate cancer cells in vitro and can be visualized in the membrane-bound state using confocal microscopy. Biodistribution studies with the [86Y][Y(III)(tacn-(pic-PSMA)-PEPA2)] analogue in a mouse xenograft model were employed to study pharmacokinetics. Systemic administration of the targeted Cherenkov emitter, [68Ga][Ga(III)(PSMA-617)], followed by intratumoral injection or topical application of 20 or 10 nmol [Eu(III)(tacn-(pic-PSMA)-PEPA2)], respectively, in live mice resulted in statistically significant signal enhancement using conventional small animal imaging (620 nm bandpass filter). Optical imaging informed successful tumor resection. Ex vivo imaging of the fixed tumor tissue with 1 and 2 photon excitation further reveals the accumulation of the administered Eu(III) complex in target tissues. This work represents a significant step toward the application of luminescent lanthanide complexes for optical imaging in a clinical setting.

Ocean iron fertilization may amplify climate change pressures on marine animal biomass for limited climate benefit.

Climate change scenarios suggest that large-scale carbon dioxide removal (CDR) will be required to maintain global warming below 2°C, leading to renewed attention on ocean iron fertilization (OIF). Previous OIF modelling has found that while carbon export increases, nutrient transport to lower latitude ecosystems declines, resulting in a modest impact on atmospheric CO2 . However, the interaction of these CDR responses with ongoing climate change is unknown. Here, we combine global ocean biogeochemistry and ecosystem models to show that, while stimulating carbon sequestration, OIF may amplify climate-induced declines in tropical ocean productivity and ecosystem biomass under a high-emission scenario, with very limited potential atmospheric CO2 drawdown. The 'biogeochemical fingerprint' of climate change, that leads to depletion of upper ocean major nutrients due to upper ocean stratification, is reinforced by OIF due to greater major nutrient consumption. Our simulations show that reductions in upper trophic level animal biomass in tropical regions due to climate change would be exacerbated by OIF within ~20 years, especially in coastal exclusive economic zones (EEZs), with potential implications for fisheries that underpin the livelihoods and economies of coastal communities. Any fertilization-based CDR should therefore consider its interaction with ongoing climate-driven changes and the ensuing ecosystem impacts in national EEZs.

High trophic level feedbacks on global ocean carbon uptake and marine ecosystem dynamics under climate change.

Despite recurrent emphasis on their ecological and economic roles, the importance of high trophic levels (HTLs) on ocean carbon dynamics, through passive (fecal pellet production, carcasses) and active (vertical migration) processes, is still largely unexplored, notably under climate change scenarios. In addition, HTLs impact the ecosystem dynamics through top-down effects on lower trophic levels, which might change under anthropogenic influence. Here we compare two simulations of a global biogeochemical-ecosystem model with and without feedbacks from large marine animals. We show that these large marine animals affect the evolution of low trophic level biomasses, hence net primary production and most certainly ecosystem equilibrium, but seem to have little influence on the 21st-century anthropogenic carbon uptake under the RCP8.5 scenario. These results provide new insights regarding the expectations for trophic amplification of climate change through the marine trophic chain and regarding the necessity to explicitly represent marine animals in Earth System Models.

Tuning the Photophysical Properties of Aza-BODIPYs in the Near-Infrared Region by Introducing Electron-Donating Thiophene Substituents.

This study presents the synthesis, the spectroscopic and electrochemical properties of new bis- and tetra-substituted azaboron-dipyrromethene (aza-BODIPY) dyes substituted by different electron donating groups connected to the aza-BODIPY core through a thiophene unit. In line with theoretical calculations, experimental measurements point out the positive impact of the thiophene group that behave as a secondary donor group leading to an enhancement of the intramolecular charge transfer process in comparison to previously reported aza-BODIPY dyes. This heterocycle has also been found to tune the oxidative potential and to stabilize the electro-generated species.

Design of Bifunctional Pyclen-Based Lanthanide Luminescent Bioprobes for Targeted Two-Photon Imaging.

In the past, Lanthanide Luminescent Bioprobes (LLBs) based on pyclen-bearing π-extended picolinate antennas were synthesized and demonstrated well-adapted optical properties for biphotonic microscopy. The objective of this work is to develop a strategy to design bifunctional analogues of the previously studied LLBs presenting an additional reactive chemical group to allow their coupling to biological vectors to reach deep in vivo targeted two-photon bioimaging. Herein, we elaborated a synthetic scheme allowing the introduction of a primary amine on the para position of the macrocyclic pyridine unit. The photophysical and bioimaging studies demonstrate that the introduction of the reactive function does not alter the luminescent properties of the LLBs paving the way for further applications.

Ytterbium(III) Complex with Photochromic Ruthenium(II) Acetylide Ligand: All Visible Light Photoswitching of NIR Luminescence.

We report a ruthenium(II) bisacetylide complex bearing a photochromic dithienylethene (DTE) acetylide arm and a coordinating bipyridyl on the trans acetylide unit. Its coordination with Yb(TTA)3 centers (TTA = 2-thenoyltrifluoroacetonate) produces a bimetallic complex in which the dithienylethene isomerization is triggered by both ultraviolet (UV) light absorbed by the DTE unit and 450 nm excitation in a transition of the organometallic moiety. The redox behavior arising from the ruthenium(II) bisacetylide system is fully investigated by cyclic voltammetry and spectroelectrochemistry, revealing a lack of stability of the DTE-closed oxidized state preventing effective redox luminescence switching. On the other hand, the photoswitching of ytterbium(III) near-infrared (NIR) emission triggered by the photochromic reaction is fully operational. The electronic structure of this complex in its different states characterized by strong electronic coupling between the DTE and the ruthenium(II)-based moieties leading to metal-assisted photochromic behavior were rationalized with the help of time-dependent density functional theory (TD-DFT) calculations.

Distributive Nd-to-Yb Energy Transfer within Pure [YbNdYb] Heterometallic Molecules.

Facile access to site-selective hetero-lanthanide molecules will open new avenues in the search of novel photophysical phenomena based on Ln-to-Ln' energy transfer (ET). This challenge demands strategies to segregate efficiently different Ln metal ions among different positions in a molecule. We report here the one-step synthesis and structure of a pure [YbNdYb] (1) coordination complex featuring short Yb···Nd distances, ideal to investigate a potential distributive (i.e., from one donor to two acceptors) intramolecular ET from one Nd3+ ion to two Yb3+ centers within a well-characterized molecule. The difference in ionic radius is the mechanism allowing to allocate selectively both types of metal ion within the molecular structure, exploited with the simultaneous use of two ß-diketone-type ligands. To assist the photophysical investigation of this heterometallic species, the analogues [YbLaYb] (2) and [LuNdLu] (3) have also been prepared. Sensitization of Yb3+ and Nd3+ in the last two complexes, respectively, was observed, with remarkably long decay times, facilitating the determination of the Nd-to-Yb ET within the [YbNdYb] composite. This ET was demonstrated by comparing the emission of iso-absorbant solutions of 1, 2, and 3 and through lifetime determinations in solution and solid state. The comparatively high efficiency of this process corroborates the facilitating effect of having two acceptors for the nonradiative decay of Nd3+ created within the [YbNdYb] molecule.

Al(III) and Ga(III) Bisphenolate Azadipyrromethene-Based "N2O2" Complexes as Efficient NIR-Fluorophores.

Aza-boron-dipyrromethenes (Aza-BODIPYs) are an increasingly studied class of fluorophores. They can be seen as an azadipyrromethene ("aza-DIPY") ligand rigidified by a metalloid, a boron atom. Based on this idea, a series of complexes of group 13 metals (aluminum and gallium) have been synthesized and characterized. The impact of the metal and of the nature of the substituents of aza-DIPY core were investigated. The photophysical and electrochemical properties were determined, and an X-ray structure of an azaGaDIPY was obtained. These data reveal that azaGaDIPY and azaAlDIPY exhibit significant red-shifted fluorescence compared to their analogue aza-BODIPY. Their emission can go up to 800 nm for the maximum emission length and up to NIR-II for the emission tail. This, associated with their electrochemical stability (no metal release whether oxidized or reduced) makes them a promising class of fluorophores for optical medical imaging. Moreover, X-ray structure and molecular modeling studies have shown that this redshift seems to be more due to the geometry around the boron/metal than to the nature of the metal.

Multifunctional Helicene-Based Ytterbium Coordination Polymer Displaying Circularly Polarized Luminescence, Slow Magnetic Relaxation and Room Temperature Magneto-Chiral Dichroism.

The combination of physical properties sensitive to molecular chirality in a single system allows the observation of fascinating phenomena such as magneto-chiral dichroism (MChD) and circularly polarized luminescence (CPL) having potential applications for optical data readout and display technology. Homochiral monodimensional coordination polymers of YbIII were designed from a 2,15-bis-ethynyl-hexahelicenic scaffold decorated with two terminal 4-pyridyl units. Thanks to the coordination of the chiral organic chromophore to Yb(hfac)3 units (hfac- =1,1,1,5,5,5-hexafluoroacetylaconate), efficient NIR-CPL activity is observed. Moreover, the specific crystal field around the YbIII induces a strong magnetic anisotropy which leads to a single-molecule magnet (SMM) behaviour and a remarkable room temperature MChD. The MChD-structural correlation is supported by computational investigations.

Femtosecond Spectroscopy and Nonlinear Optical Properties of aza-BODIPY Derivatives in Solution.

The fast relaxation processes in the excited electronic states of functionalized aza-boron-dipyrromethene (aza-BODIPY) derivatives (1-4) were investigated in liquid media at room temperature, including the linear photophysical, photochemical, and nonlinear optical (NLO) properties. Optical gain was revealed for nonfluorescent derivatives 3 and 4 in the near infrared (NIR) spectral range under femtosecond excitation. The values of two-photon absorption (2PA) and excited-state absorption (ESA) cross-sections were obtained for 1-4 in dichloromethane using femtosecond Z-scans, and the role of bromine substituents in the molecular structures of 2 and 4 is discussed. The nature of the excited states involved in electronic transitions of these dyes was investigated using quantum-chemical TD-DFT calculations, and the obtained spectral parameters are in reasonable agreement with the experimental data. Significant 2PA (maxima cross-sections ∼2000 GM), and large ESA cross-sections ∼10-20  m2 of these new aza-BODIPY derivatives 1-4 along with their measured high photostability reveal their potential for photonic applications in general and optical limiting in particular.

Circularly polarized luminescence of Eu(III) complexes with chiral 1,1'-bi-2-naphtol-derived bisphosphate ligands.

The interest for lanthanide circularly polarized luminescence (CPL) has been quickly growing for 10 years. However, very few of these studies have involved correlation between the dissymmetry factor (glum ) and the chemical modifications in a series of chiral ligands. Four polymeric compounds of Eu(III) were prepared by using a series of binaphtyl derivatives for which the size of the π system as well as the number of stereogenic elements (i.e., the binaphtyl moiety) are modulated. The resulting {[Eu(hfac)3 ((S)/(R)-Lx )]}n (x = 1 and 3) and {[Eu(hfac)3 ((S,S,S)/(R,R,R)-Lx )]}n (x = 2 and 4) have been characterized by powder X-ray diffraction by comparison with the X-ray structures on single crystal of the Dy(III) analogs. In solution, the structure of the complexes is deeply modified and becomes monomeric. The nature of the ligand induces change in the shape of the CPL spectra in CH2 Cl2 solution. Furthermore, a large |glum | = 0.12 of the magnetic-dipole transition for the [Eu(hfac)3 ((S,S,S)/(R,R,R)-L2 )] complex involving the ligand with three stereogenic elements and an extended 𝜋 system has been measured. This report also shows CPL measurements in solid state for the series of {[Eu(hfac)3 ((S)/(R)-Lx )]}n (x = 1 and 3) and {[Eu(hfac)3 ((S,S,S)/(R,R,R)-Lx )]}n (x = 2 and 4) polymers.

Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change.

While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (±4% SD) under low emissions and 17% (±11% SD) under high emissions by 2100, with an average 5% decline for every 1 °C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.

Near-infrared dyes for two-photon absorption in the short-wavelength infrared: strategies towards optical power limiting.

This work provides an overview of the recent advances in the field of two-photon absorbing chromophores active in the short-wavelength infrared (SWIR) spectral range. Herein the common strategies and main structure-property relationships that lead to near-infrared (NIR) electronic absorption of chromophores are described. A complete review of the molecules that feature two-photon absorption (2PA) beyond 1100 nm is presented for the purpose of further use in optical power limiting applications in the SWIR band. Recent progress in the development of optical power limiting in this particular spectral region is reported with emphasis on the use of the two-photon induced excited state absorption (ESA) process as an optical power limiting enhancer.

Excited State Properties of Lanthanide(III) Complexes with a Nonadentate Bispidine Ligand.

EuIII , TbIII , GdIII and YbIII complexes of the nonadentate bispidine derivative L2 (bispidine=3,7-diazabicyclo[3.3.1]nonane) were successfully synthesized and their emission properties studied. The X-ray crystallography reveals full encapsulation by the nonadentate ligand L2 that enforces to all LnIII cations a common highly symmetrical capped square antiprismatic (CSAPR) coordination geometry (pseudo C4v symmetry). The well-resolved identical emission spectra in solid state and in solution confirm equal structures in both media. As therefore expected, this results in long-lived excited states and high emission quantum yields ([EuIII L2 ]+ , H2 O, 298 K, τ=1.51 ms, ϕ=0.35; [TbIII L2 ]+ , H2 O, 298 K, τ=1.95 ms, ϕ=0.68). Together with the very high kinetic and thermodynamic stabilities, these complexes are a possible basis for interesting biological probes.

Benzothiadiazole-Substituted Aza-BODIPY Dyes: Two-Photon Absorption Enhancement for Improved Optical Limiting Performances in the Short-Wave IR Range.

Aza-boron dipyrromethenes (aza-BODIPYs) presenting a benzothiadiazole substitution on upper positions are described. The strong electron-withdrawing effect of the benzothiadiazole moiety permits enhancement of the accepting strength and improves the delocalization of the aza-BODIPY core to attain a significant degree of electronic communication between the lower donating groups and the upper accepting groups. The nature of the intramolecular charge transfer is studied both experimentally and theoretically. Linear spectroscopy highlighted the strongly redshifted absorption and emission of the synthesized molecules with recorded fluorescence spectra over 1000 nm. Nonlinear optical properties were also investigated. Strong enhancement of the two-photon absorption of the substituted dyes compared with the unsubstituted one (up to 4520 GM at 1300 nm) results in an approximately 15-20 % improvement of the optical power limiting performances. These dyes are therefore a good starting point for further improvement of optical power limiting in the short-wave IR range.