Iridium(III) complexes decorated with silicane-modified rhodamine: near-infrared light-initiated photosensitizers for efficient deep-tissue penetration photodynamic therapy.

Meeting the demand for efficient photosensitizers in photodynamic therapy (PDT), a series of iridium(III) complexes decorated with silicane-modified rhodamine (Si-rhodamine) was meticulously designed and synthesized. These complexes demonstrate exceptional PDT potential owing to their strong absorption in the near-infrared (NIR) spectrum, particularly responsive to 808 nm laser stimulation. This feature is pivotal, enabling deep-penetration laser excitation and overcoming depth-related challenges in clinical PDT applications. The molecular structures of these complexes allow for reliable tuning of singlet oxygen generation with NIR excitation, through modification of the cyclometalating ligand. Notably, one of the complexes (4) exhibits a remarkable ROS quantum yield of 0.69. In vivo results underscore the efficacy of 4, showcasing significant tumor regression at depths of up to 8.4 mm. This study introduces a promising paradigm for designing photosensitizers capable of harnessing NIR light effectively for deep PDT applications.

Ligand Regulation Strategy to Modulate ROS Nature in a Rhodamine-Iridium(III) Hybrid System for Phototherapy.

The efficacy of photodynamic therapy (PDT) is highly dependent on the photosensitizer features. The reactive oxygen species (ROS) generated by photosensitizers is proven to be associated with immunotherapy by triggering immunogenic cell death (ICD) as well. In this work, we establish a rhodamine-iridium(III) hybrid model functioning as a photosensitizer to comprehensively understand its performance and potential applications in photodynamic immunotherapy. Especially, the correlation between the ROS generation efficiency and the energy level of the Ir(III)-based excited state (T1'), modulated by the cyclometalating (C∧N) ligand, is systematically investigated and correlated. We prove that in addition to the direct population of the rhodamine triplet state (T1) formed through the intersystem crossing process with the assistance of a heavy Ir(III) metal center, the fine-tuned T1' state could act as a relay to provide an additional pathway for promoting the cascade energy transfer process that leads to enhanced ROS generation ability. Moreover, type I ROS can be effectively produced by introducing sulfur-containing thiophene units in C∧N ligands, providing a stronger M1 macrophage-activation efficiency under hypoxia to evoke in vivo antitumor immunity. Overall, our work provides a fundamental guideline for the molecular design and exploration of advanced transition-metal-based photosensitizers for biomedical applications.

Multifunctional bisalkynylplatinum(II) bipyridine complexes with rhodamine-like ligands featuring near-infrared phosphorescence and delayed fluorescence.

A series of platinum(II) bipyridine complexes with two rhodamine-like alkynyl (Rhodyne) ligands were developed to show chemo-induced "ON-OFF" switching capabilities with exceptional near-infrared phosphorescence and delayed fluorescence. This study contributes to the design of versatile photosensitizers with multiple functionalities, including metal ion and biomolecule sensing, photodynamic therapy, and optoelectronics.

Structure-property relationships of photofunctional diiridium(II) complexes with tetracationic charge and an unsupported Ir-Ir bond.

In contrast to the extensively studied dirhodium(II) complexes and iridium(III) complexes, neutral or dicationic dinuclear iridium(II) complexes with an unsupported ligand are underdeveloped. Here, a series of tetracationic dinuclear iridium(II) complexes, featuring the unsupported Ir(II)-Ir(II) single bond with long bond distances (2.8942(4)-2.9731(4) Å), are synthesized and structurally characterized. Interestingly, compared to the previous unsupported neutral or dicationic diiridium(II) complexes, our DFT and high-level DLPNO-CCSD(T) results found the largest binding energy in these tetracationic complexes even with the long Ir(II)-Ir(II) bond. Our study further reveals that London dispersion interactions enhance the stability cooperatively and significantly to overcome the strong electrostatic repulsion between two half dicationic metal fragments. This class of complexes also exhibit photoluminescence in solution and solid states, which, to our knowledge, represents the first example of this unsupported dinuclear iridium(II) system. In addition, their photoreactivity involving the generation of iridium(II) radical monomer from homolytic cleavage was also explored. The experimental results of photophysical and photochemical behaviours were also correlated with computational studies.

The switchable phosphorescence and delayed fluorescence of a new rhodamine-like dye through allenylidene formation in a cyclometallated platinum(ii) system.

A new rhodamine-like alkyne-substituted ligand (Rhodyne) was designed to coordinate a cyclometallated platinum(ii) system. The chemo-induced "ON-OFF" switching capabilities on the spirolactone ring of the Rhodyne ligand with an end-capping platinum(ii) metal centre can modulate the interesting acetylide-allenylidene resonance. The long-lived 3IL excited state of Rhodyne in its ON state as an optically active opened form was revealed via steady-state and time-resolved spectroscopy studies. Exceptional near-infrared (NIR) phosphorescence and delayed fluorescence based on a rhodamine-like structure were observed at room temperature for the first time. The position of the alkyne communication bridge attached to the platinum(ii) unit was found to vary the lead(ii)-ion binding mode and also the possible resonance structure for metal-mediated allenylidene formation. The formation of a proposed allenylidene resonance structure was suggested to rationalize these phenomena.

A Deep-Red to Near Infrared (NIR) Fluorescent Probe Based on a Sulfur-Modified Rhodamine Derivative with Two Spirolactone Rings.

We report the synthesis, characterization, and photophysical and ion-binding properties of deep-red to near-infrared (NIR) fluorescent rhodamine derivatives, bearing two spirolactone rings and substitution of the oxygen atoms in the xanthene ring with sulfur atoms (1-S). The diastereoisomeric cis- and trans-forms of the rhodamine derivative were separated and the cis-form (cis-1-S) was structurally characterized by X-ray crystallography. Upon treatment with Hg2+ ion, cis-1-S was converted into the dual spirolactone ring-opened species, resulting in significant color change and fluorescence enhancement. Substitution of the oxygen atoms with sulfur and extended π-conjugation across the fused six-membered rings upon the two rings-opening processes in the presence of Hg2+ ion led to a significant red-shift of absorption (623 nm) and fluorescence (706 nm) peaks, compared to the ordinary rhodamine. Furthermore, the intracellular Hg2+ -sensing properties of the cis-1-S have been studied by confocal microscopy.

Enhancing the ROS generation ability of a rhodamine-decorated iridium(iii) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy.

The endoplasmic reticulum (ER) is a very important organelle responsible for crucial biosynthetic, sensing, and signalling functions in eukaryotic cells. In this work, we established a strategy of ligand regulation to enhance the singlet oxygen generation capacity and subcellular organelle localization ability of a rhodamine-decorated iridium(iii) complex by variation of the cyclometallating ligand. The resulting metal complex showed outstanding reactive oxygen species generation efficiency (1.6-fold higher than that of rose bengal in CH3CN) and highly specific ER localization ability, which demonstrated the promise of the metal-based photo-theranostic agent by simultaneously tuning the photochemical/physical and biological properties. Additionally, low dark cytotoxicity, high photostability and selective tumour cell uptake were featured by this complex to demonstrate it as a promising candidate in photodynamic therapy (PDT) applications. In vivo near infrared fluorescence (NIRF) imaging and tumour PDT were investigated and showed preferential accumulation at the tumour site and remarkable tumour growth suppression, respectively.

Ligand Mediated Luminescence Enhancement in Cyclometalated Rhodium(III) Complexes and Their Applications in Efficient Organic Light-Emitting Devices.

A series of luminescent cyclometalated rhodium(III) complexes have been designed and prepared. The improved luminescence property is realized by the judicious choice of a strong σ-donor cyclometalating ligand with a lower-lying intraligand (IL) state that would raise the d-d excited state and introduction of a lower-lying emissive IL excited state. These complexes exhibit high thermal stability and considerable luminescence quantum yields as high as up to 0.65 in thin film, offering themselves as promising light-emitting materials in OLEDs. Respectable external quantum efficiencies of up to 12.2% and operational half-lifetimes of over 3000 h at 100 cd m-2 have been achieved. This work demonstrates a breakthrough as the first example of an efficient rhodium(III) emitter for OLED application and opens up a new avenue for diversifying the development of OLED materials with rhodium metal being utilized as phosphors.

A New Quinone Based Fluorescent Probe for High Sensitive and Selective Detection of Biothiols and Its Application in Living Cell Imaging.

In view of the vital role of biothiols in many physiological processes, the development of simple and efficient probe for the detection of biothiols is of great medical significance. In this work, we demonstrate the use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), which respond rapidly to biothiols especially to glutathione, as a new fluorescent probe for the selective detection and bioimaging of biothiols. This new fluorescent probe can distinguish glutathione from cysteine and homocysteine easily under physiological concentration and detect glutathione quickly within three minutes. This probe exhibits high selectivity to biothiols and the detection limit was determined to be 3.08 × 10-9 M for glutathione, 8.55 × 10-8 M for cysteine, and 2.17 × 10-9 M for homocysteine, respectively. The sensing mechanism was further explored by density functional theory (DFT) and nuclear magnetic resonance (NMR) experiment; results showed that the interaction forces between the probe and biothiols were electrostatic interaction. In addition, the probe has been successfully applied to the detection of biothiols in Eca9706 cells by fluorescence confocal imaging technology.

Synthesis and study of Au(iii)-indolizine derivatives: turn-on luminescence by photo-induced controlled release.

The photo- and structural properties of a series of Au(iii) indolizine complexes were determined. Controlled release of halogenated indolizine derivatives from the corresponding Au(iii) complexes was achieved by photoinduced C-X bond formation, which provided turn-on luminescence with an increase in emission intensity of up to 67 times.

Versatile Strategy To Generate a Rhodamine Triplet State as Mitochondria-Targeting Visible-Light Photosensitizers for Efficient Photodynamic Therapy.

Through the use of a rhodamine-appended chelate, bpy-Rho, a versatile strategy has been demonstrated to readily form mitochondria-targeting photosensitizers via the incorporation of a variety of luminescent transition-metal systems, M-Rho, such as Re(I), Ir(III), Pt(II), and Rh(III). The emission from the rhodamine singlet excited state and the transition-metal triplet excited state is partially quenched by the depopulation of them into the dark rhodamine triplet excited state. The generation of the triplet excited state of a rhodamine moiety endows the complexes with mitochondria-targeting photosensitizing ability to form singlet oxygen (1O2) for use as a photodynamic therapy (PDT) agent upon visible-light irradiation. The combination of the rhodamine organic dye and luminescent transition-metal centers in such hybrid systems exhibits the synergistic merits for the biological applications, including low dark cytotoxicity, selective tumor cell uptake, high molar absorptivity suitable for low-energy excitation in the visible region, and high photostability. The corresponding in vitro photocytotoxicity and in vivo photo-antitumor efficacy have also been studied to demonstrate the potential PDT application of M-Rho.

Alkynylplatinum(II) Terpyridine System Coupled with Rhodamine Derivative: Interplay of Aggregation, Deaggregation, and Ring-Opening Processes for Ratiometric Luminescence Sensing.

The synthesis and characterization of a platinum(II) terpyridine system tethered with a latent organic dye of rhodamine derivative as colorimetric and luminescent sensory moiety is reported to show selective Hg2+ ion sensing behavior. The interplay of aggregation/deaggregation behavior of the alkynylplatinum(II) terpyridine complex and the ring-opening process of rhodamine derivative was investigated. The spectral change of aggregation near-infrared emission at 800 nm and rhodamine fluorescence at 585 nm provides a possible ratiometric luminescence measurement. Morphological studies from transmission electron microscopy and scanning electron microscopy images showing nanospherical structures confirmed the aggregation in the absence of Hg2+ ion.

Rhodol Derivatives as Selective Fluorescent Probes for the Detection of HgII Ions and the Bioimaging of Hypochlorous Acid.

Invited for this month's cover picture is the group of Professor Keith Man-Chung Wong from the Southern University of Science and Technology (P.R. China). The cover picture illustrates a novel rhodol-based fluorescence probe from the structural combination of rhodamine and fluorescein motifs. Read the full text of their Full Paper at 10.1002/open.201700154.

Rhodol Derivatives as Selective Fluorescent Probes for the Detection of HgII Ions and the Bioimaging of Hypochlorous Acid.

Two sensors, 1 with a spirolactone group and 2 with a spirolactam group containing a phenyl isothiocyanate moiety, based on rhodol, were designed and synthesized in order to obtain materials with excellent optical properties for the detection of environmentally and biologically important Hg2+ and hypochlorous acid (HClO) ions. The crystal structure of 1 revealed two moieties, a rhodamine-like portion with a spirolactone and a fluorescein-like portion without a spirolactone. In the absence of analyte, 1 produced an optical output with a maximum absorption and emission at 475 and 570 nm, respectively, which was attributed to the fluorescein-like moiety without a spirolactone. In contrast, the rhodamine-like moiety containing a spirolactone was activated by the addition of H+ or Hg2+ ions, and 1 yielded new absorption and emission peaks at 530 and 612 nm, respectively. Further functionalization with a phenyl isothiocyanate group afforded 2, a fluorescent probe for HClO. High selectivity and sensitivity towards the hypochlorite ion were anticipated, owing to the stoichiometric and irreversible formation of a thiosemicarbazide group, which led to dramatic fluorescence responses. With good functionality at physiological pH, probe 2 was successfully used to image HClO in HeLa cells.

New perspectives of cobalt tris(bipyridine) system: anti-cancer effect and its collateral sensitivity towards multidrug-resistant (MDR) cancers.

Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells. Consistently, our reported anti-cancer functions of cobalt complexes 1-6 towards multidrug-resistant cancers have suggested the protective and non-toxic properties of cobalt metal-ions based compounds in anti-cancer therapies. As demonstrated in xenograft mouse model, our results also confirmed the identified cobalt complex 2 was able to suppress tumor growth in vivo. The anti-cancer effect of the cobalt complex 2 was further demonstrated to be exerted via the induction of autophagy, cell cycle arrest, and inhibition of cell invasion and P-glycoprotein (P-gp) activity. These data have provided alternative metal ion compounds for targeting drug resistance cancers in chemotherapies.

Luminescent Bis-Cyclometalated Gold(III) Complexes with Alkynyl Ligands of Hexaphenylbenzene and Hexabenzocoronene Derivatives and Their Supramolecular Assembly.

A series of luminescent bis-cyclometalated gold(III) complexes with different nuclearities and various alkynyl ligands derived from hexaphenylbenzene (HPB) and hexabenzocoronene (HBC) have been synthesized. The energies of the low-energy metal-perturbed intraligand (IL) π-π*(R-C^N^C) absorptions of the HPB-alkynyl gold(III) complexes have been fine-tuned by attaching various substituent groups to the bis-cyclometalating ligands. Similarly, the metal-perturbed 3 IL [π→π*(R-C^N^C)] emissions of the complexes show energy shifts according to the electronic nature of the bis-cyclometalating ligands. On the contrary, the absorption and emission spectra of the HBC-alkynyl gold(III) complex have been assigned as dominated by the IL transitions of the HBC-alkynyl unit, as supported by transient absorption studies. The supramolecular assembly morphologies of the gold(III) complexes have been studied by TEM and SEM, along with comparisons across different complexes based on the molecular structures, and their assembly processes monitored by concentration-dependent and variable-temperature 1 H NMR spectroscopy studies.

Luminescent Dinuclear Bis-Cyclometalated Gold(III) Alkynyls and Their Solvent-Dependent Morphologies through Supramolecular Self-Assembly.

A series of luminescent bis-cyclometalated gold(III) complexes containing bridging alkynyl ligands of different natures has been synthesised and characterised. The photophysical properties of the complexes have been investigated through electronic absorption spectroscopy and emission studies. The vibronic emission bands are found to originate from the triplet intraligand (IL) π-π* excited states of the bis-cyclometalating ligands with some mixing of 3 IL π-π* character of the alkynyl ligands. The electrochemical study of a nonsymmetric dinuclear complex shows two successive reduction processes originating from the reductions of the two different cyclometalating ligands. The complexes are found to undergo supramolecular self-assembly processes driven by π-π stacking and hydrophobic/hydrophilic interactions to give honeycomb nanostructures, as revealed from the SEM images. Solvent-dependent morphological transformations have also been observed, which have been studied by SEM and 1 H NMR spectroscopy.

Contrasted photochromic and luminescent properties in dinuclear Pt(ii) complexes linked through a central dithienylethene unit.

We disclose two unprecedented complexes built with a central dithienylethene photochrome connecting two cyclometalated Pt(ii) moieties either on the reactive carbon atoms or on the lateral non-reactive carbon atoms of the photochrome. The two systems show vastly different properties that are rationalised thanks to quantum-chemical calculations.

Helical Self-Assembly and Photopolymerization Properties of Achiral Amphiphilic Platinum(II) Diacetylene Complexes of Tridentate 2,6-Bis(1-alkylpyrazol-3-yl)pyridines.

Amphiphilic platinum(II) diacetylene complexes of the 2,6-bis(1-butylpyrazol-3-yl)pyridine pincer ligand were designed and synthesized. Helical fibrous nanostructures were obtained through supramolecular assembly of the achiral platinum(II) diacetylene complexes via intermolecular hydrogen bonding, amphiphilic effects, Pt···Pt interactions, and π-π stacking interactions. In situ post-photopolymerization of the diacetylene unit was shown to occur in the preorganized helical fibers.

Self-assembly of alkynylplatinum(II) terpyridine amphiphiles into nanostructures via steric control and metal-metal interactions.

A series of mono- and dinuclear alkynylplatinum(II) terpyridine complexes containing the hydrophilic oligo(para-phenylene ethynylene) with two 3,6,9-trioxadec-1-yloxy chains was designed and synthesized. The mononuclear alkynylplatinum(II) terpyridine complex was found to display a very strong tendency toward the formation of supramolecular structures. Interestingly, additional end-capping with another platinum(II) terpyridine moiety of various steric bulk at the terminal alkyne would lead to the formation of nanotubes or helical ribbons. These desirable nanostructures were found to be governed by the steric bulk on the platinum(II) terpyridine moieties, which modulates the directional metal-metal interactions and controls the formation of nanotubes or helical ribbons. Detailed analysis of temperature-dependent UV-visible absorption spectra of the nanostructured tubular aggregates also provided insights into the assembly mechanism and showed the role of metal-metal interactions in the cooperative supramolecular polymerization of the amphiphilic platinum(II) complexes.