Unveiling the Versatility of Coumarin-Integrated with Phenanthroline/Thiabendazole-Based EuIII Complexes for Smart LEDs, Vapoluminescence, and Bioimaging Applications.

Narrow band red-emitting phosphors based on organo-Eu(III) complexes prove their energetic features with surprising performance in smart red/white LEDs, sensing, and biological fields. In this report, a series of unique Eu(III) complexes have been synthesized with coumarin integrated with a class of phenanthroline(Phen)/thiabendazole(TBZ) based ancillary ligands and dibenzoyl methane (DBM)/2-theonyl trifluoroacetone (TTA) as an anionic ligand. The computational study reveals that the TBZ/Phen-based neutral ligands are superior energy harvesters to those other reported analogue neutral ligands. All the Eu-complexes demonstrated outstanding red emission due to electric dipole (ED) transition (5D0 → 7F2) in solid, solution, and thin film with high quantum yield (QY). Theoretical analysis (TD-DFT) and experimental findings describe that the energy transfer (ET) from the ligand's triplet level to the Eu(III) ion is completely occurring. The Eu(III) complexes can potentially be used to fabricate intense hybrid white and red LEDs. All of the fabricated red LEDs revealed high luminous efficiency of radiation (LER) values. The fabricated blue LED based hybrid white LEDs displayed remarkable performance with a low correlated color temperature (5634 K), high color rendering index 88%, and CIE values (x = 0.33; y = 0.342) for 3Eu. By interaction with acid-base vapors, Eu-complexes displayed effectively alterable on-off-on luminescence. Further, cellular imaging shows that Eu-complexes can be a potential biomarker for cancer cell lines.

A sequential dual-locked luminescent copper nanocluster probe for tumor cell imaging and killing.

A sequential dual-locked luminescent copper nanoclusters (CuNCs) probe was designed and synthesized for the specific imaging and selective killing of tumor cells. This nanoprobe was prepared by first forming a Fe3+-coupled tannic acid (TA)-stabilized CuNCs (CuNCs-FeIII), which is in quenching state due to the electron transfer between CuNCs and Fe3+, and then coating a protectable layer of hyaluronic acid (HA) on the surface of CuNCs-FeIII to form the final dual-locked nanoprobe (CuNCs-FeIII@HA). When the nanoprobe of CuNCs-FeIII@HA target enter the tumor cells through CD44-HA receptor, HAase will first digest the HA layer of the nanoprobes, and then, GSH over-expressed in tumor cells will reduce Fe3+ to Fe2+, thus restoring the fluorescence emission of CuNCs and at the same time killing the tumor cells with the hydroxyl free radicals (∙OH) produced by the Fenton reaction between Fe2+ and H2O2. This sequential dual-locked luminescent nanoprobe of CuNCs-FeIII@HA has been successfully used for the specific imaging and selective killing of tumor cells.

Assessment of luminescent copper nanomaterials as anti-germs, anti-proliferation efficiencies using green nano-strategy.

For the first time, we suggest using leaf extract from Ocimum americanum as the economically viable bio-fabrication of copper nanomaterials. The residuals of leaf extract bio-capping provide the stability of the nanomaterials in-situ. UV-Vis and XRD confirmed the formation, with the UV-Vis spectrum of Cu-NMs revealing a surface plasmon resonance characteristic peak at 350 nm. FT-IR analysis was employed to examine the functional groups. FE-SEM with EDX was used to assess the morphology and carry out an elemental analysis of the nanomaterials. Diffusion and MTT assays were used to study the antimicrobial and anticancer activities. The synthesized copper nanomaterials exhibited in-vitro cytotoxicity against human skin cancer (A431) cell lines. Green nanomaterial was examined against the methylene blue dye, photodegradation was reduced by up to 90.6% within 50 minutes. The copper nanomaterials synthesized in our study exhibit promising applications in biomedicine and environmental pollution research.

Poly-vinyl-pyrrolidone capped luminescent zinc oxide nanocomposites as excellent tools for germicidal and photo-catalytic performances.

Alternate antibiotics developed through the involvement of nanomaterials are gaining interest due to their economical and lower toxicity concerns. A newly developed biopolymer-based polyvinylpyrrolidone/zinc oxide (PVP/ZnO) nanocomposite (NCs) was efficiently synthesized by an environment-friendly approach, utilizing onion and garlic peel extract as a bio-surfactant, zinc acetate as the source, PVP as the stabilizing agent, and sodium hydroxide as the precipitant. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) investigations verified the crystalline properties of ZnO, PVP, and PVP/ZnO-based NCs. The structure of the biopolymer-linked ZnO particles interpolated inside the PVP array was seen to have a layered and flaky structure, as validated by field emission scanning electron microscopy (FE-SEM) analysis, which revealed its occurrence in the nanometer range. The XRD examination verified that the surface topographical image of PVP/ZnO NCs had an average thickness of 21 nm. The PVP/ZnO nanocrystals demonstrated exceptional photocatalytic efficacy, with a breakdown rate of 88% and almost 92% for the methylene blue dye. Therefore, the PVP/ZnO matrix exhibits superior antibacterial activity compared to other extracts, resulting in greater microbial suppression. The results above indicate that the ZnO-intercalated PVP array has a stronger reinforcing effect than other components. Hence, PVP/ZnO nanocrystals exhibit enormous potential as a favorable substance for environmental and biomedical intentions.

Tracking Plasma Membrane Damage Using a Ruthenium(II) Complex Phosphorescent Indicator Paired with Cholesterol.

Long-term in situ plasma membrane-targeted imaging is highly significant for investigating specific biological processes and functions, especially for the imaging and tracking of apoptosis processes of cells. However, currently developed membrane probes are rarely utilized to monitor the in situ damage of the plasma membrane. Herein, a transition-metal complex phosphorescent indicator, Ru-Chol, effectively paired with cholesterol, exhibits excellent properties on staining the plasma membrane, with excellent antipermeability, good photostability, large Stokes shift, and long luminescence lifetime. In addition, Ru-Chol not only has the potential to differentiate cancerous cells from normal cells but also tracks in real time the entire progression of cisplatin-induced plasma membrane damage and cell apoptosis. Therefore, Ru-Chol can serve as an efficient tool for the monitoring of morphological and physiological changes in the plasma membrane, providing assistance for drug screening and early diagnosis and treatment of diseases, such as immunodeficiency, diabetes, cirrhosis, and tumors.

Pt(II) Bis(pyrrole-imine) complexes: Luminescent probes and cytotoxicity in MCF-7 cells†.

Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ355nmExcitation). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.

A Water-Soluble Wavy Coordination Polymer of Cu(II) as a Turn-On Luminescent Probe for Histidine and Histidine-Rich Proteins/Peptides.

Histidine plays an essential role in most biological systems. Changes in the homeostasis of histidine and histidine-rich proteins are connected to several diseases. Herein, we report a water-soluble Cu(II) coordination polymer, labeled CuCP, for the fluorimetric detection of histidine and histidine-rich proteins and peptides. Single-crystal structure determination of CuCP revealed a two-dimensional wavy network structure in which a carboxylate group connects the individual Cu(II) dimer unit in a syn-anti conformation. The weakly luminescent and water-soluble CuCP shows turn-on blue emission in the presence of histidine and histidine-rich peptides and proteins. The polymer can also stain histidine-rich proteins via gel electrophoresis. The limits of quantifications for histidine, glycine-histidine, serine-histidine, human serum albumin (HSA), bovine serum albumin, pepsin, trypsin, and lysozyme were found to be 300, 160, 600, 300, 600, 800, 120, and 290 nM, respectively. Utilizing the fluorescence turn-on property of CuCP, we measured HSA quantitatively in the urine samples. We also validated the present urinary HSA measurement assay with existing analytical techniques. Job's plot, 1H NMR, high-resolution mass spectrometry (HRMS), electron paramagnetic resonance (EPR), fluorescence, and UV-vis studies confirmed the ligand displacement from CuCP in the presence of histidine.

Guest-host doped strategy for constructing ultralong-lifetime near-infrared organic phosphorescence materials for bioimaging.

Organic near-infrared room temperature phosphorescence materials have unparalleled advantages in bioimaging due to their excellent penetrability. However, limited by the energy gap law, the near-infrared phosphorescence materials (>650 nm) are very rare, moreover, the phosphorescence lifetimes of these materials are very short. In this work, we have obtained organic room temperature phosphorescence materials with long wavelengths (600/657-681/732 nm) and long lifetimes (102-324 ms) for the first time through the guest-host doped strategy. The guest molecule has sufficient conjugation to reduce the lowest triplet energy level and the host assists the guest in exciton transfer and inhibits the non-radiative transition of guest excitons. These materials exhibit good tissue penetration in bioimaging. Thanks to the characteristic of long lifetime and long wavelength emissive phosphorescence materials, the tumor imaging in living mice with a signal to background ratio value as high as 43 is successfully realized. This work provides a practical solution for the construction of organic phosphorescence materials with both long wavelengths and long lifetimes.

A Dinuclear Osmium(II) Complex Near-Infrared Nanoscopy Probe for Nuclear DNA.

With the aim of developing photostable near-infrared cell imaging probes, a convenient route to the synthesis of heteroleptic OsII complexes containing the Os(TAP)2 fragment is reported. This method was used to synthesize the dinuclear OsII complex, [{Os(TAP)2}2tpphz]4+ (where tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2''-h:2‴,3'''-j]phenazine and TAP = 1,4,5,8- tetraazaphenanthrene). Using a combination of resonance Raman and time-resolved absorption spectroscopy, as well as computational studies, the excited state dynamics of the new complex were dissected. These studies revealed that, although the complex has several close lying excited states, its near-infrared, NIR, emission (λmax = 780 nm) is due to a low-lying Os → TAP based 3MCLT state. Cell-based studies revealed that unlike its RuII analogue, the new complex is neither cytotoxic nor photocytotoxic. However, as it is highly photostable as well as live-cell permeant and displays NIR luminescence within the biological optical window, its properties make it an ideal probe for optical microscopy, demonstrated by its use as a super-resolution NIR STED probe for nuclear DNA.

Ratiometric Luminescence Detection of Copper(I) by a Resonant System Comprising Two Antenna/Lanthanide Pairs.

Selective and sensitive detection of Cu(I) is an ongoing challenge due to its important role in biological systems, for example. Herein, we describe a photoluminescent molecular chemosensor integrating two lanthanide ions (Tb3+ and Eu3+) and respective tryptophan and naphthalene antennas onto a polypeptide backbone. The latter was structurally inspired from copper-regulating biomacromolecules in Gram-negative bacteria and was found to bind Cu+ effectively under pseudobiological conditions (log KCu+ = 9.7 ± 0.2). Ion regulated modulation of lanthanide luminescence in terms of intensity and long, millisecond lifetime offers perspectives in terms of ratiometric and time-gated detection of Cu+. The role of the bound ion in determining the photophysical properties is discussed with the aid of additional model compounds.

Mannosylation of pH-sensitive liposomes promoted cytoplasmic delivery of protein to macrophages: green fluorescent protein (GFP) performed as an endosomal escape tracer.

Conventional non-pH-sensitive liposomes for cytoplasmic delivery of protein suffer from poor efficiency. Here we investigated mannosylated pH-sensitive liposomes (MAN-PSL) for cytoplasmic delivery of protein to macrophages RAW 264.7 using PSL and non-pH-sensitive liposomes for comparison. We characterised the pH-dependent fluorescence of green fluorescent protein (GFP) and encapsulated it in liposomes as an intracellular trafficking tracer. GFP showed a reversed 'S'-shaped pH-fluorescence curve with a dramatic signal loss at acidic pH. GFP stored at 4 °C with light protection showed a half-life of 10 days (pH 5-8). The entrapment efficiency of GFP was dominated by the volume ratio of intraliposomal core to external medium for thin-film hydration. Mannosylation did not affect the pH-responsiveness of PSL. Confocal microscopy elucidated that mannosylation promoted the cellular uptake of PSL. For both these liposomes, the strongest, homogeneously distributed GFP fluorescence in the cytoplasm was found at 3 h, confirming efficient endosomal escape of GFP. Conversely, internalisation of non-pH-sensitive liposomes was slow (peaked at 12 h) and both Nile Red and GFP signals remained weak and punctuated in the cytosol. In conclusion, GFP performed as a probe for endosome escape of liposomal cargo. Mannosylation facilitated the internalisation of PSL without compromising their endosomal escape ability.

Ultrastable Tb-Organic Framework as a Selective Sensor of Phenylglyoxylic Acid in Urine.

Industrial pollution and harmful chemicals seriously affect environment and human health. Styrene is a common air toxicant with widespread exposure sources, including smoking, automobile exhaust, and plastic pollutants. Phenylglyoxylic acid (PGA) is a typical biomarker for exposed styrene. Therefore, it is crucial to quickly identify and quantitatively detect PGA. Herein, an ultrastable terbium metal-organic framework (Tb-MOF 1) was developed, and the luminescence film (1/PLA) consisting of polylactic acid (PLA) and 1 was fabricated as a sensor for rapid detection of PGA. The sensor possesses the advantages of efficient detection [limit of detection (LOD) is 1.05 × 10-4 mg/mL] and rapid response speed (less than 10 s) for PGA in urine. Furthermore, this sensor exhibits high stability, outstanding anti-interference ability, and excellent recyclability. Based on this film technology, a paper-based probe was then developed for portable and convenient detection. The probe could easily distinguish different concentrations of PGA under the naked eye toward practical sensing applications. Meanwhile, photoinduced electron transfer was demonstrated to be responsible for the luminescence sensing. Hence, this study indicates that Tb-MOF is a promising material to detect PGA for evaluating the effect of styrene on the body.

Seeking Illumination: The Path to Chemiluminescent 1,2-Dioxetanes for Quantitative Measurements and In Vivo Imaging.

Chemiluminescence is a fascinating phenomenon that evolved in nature and has been harnessed by chemists in diverse ways to improve life. This Account tells the story of our research group's efforts to formulate and manifest spiroadamantane 1,2-dioxetanes with triggerable chemiluminescence for imaging and monitoring important reactive analytes in living cells, animals, and human clinical samples. Analytes like reactive sulfur, oxygen and nitrogen species, as well as pH and hypoxia can be indicators of cellular function or dysfunction and are often implicated in the causes and effects of disease. We begin with a foundation in binding-based and activity-based fluorescence imaging that has provided transformative tools for understanding biological systems. The intense light sources required for fluorescence excitation, however, introduce autofluorescence and light scattering that reduces sensitivity and complicates in vivo imaging. Our work and the work of our collaborators were the first to demonstrate that spiroadamantane 1,2-dioxetanes had sufficient brightness and biological compatibility for in vivo imaging of enzyme activity and reactive analytes like hydrogen sulfide (H2S) inside of living mice. This launched an era of renewed interest in 1,2-dioxetanes that has resulted in a plethora of new chemiluminescence imaging agents developed by groups around the world. Our own research group focused its efforts on reactive sulfur, oxygen, and nitrogen species, pH, and hypoxia, resulting in a large family of bright chemiluminescent 1,2-dioxetanes validated for cell monitoring and in vivo imaging. These chemiluminescent probes feature low background and high sensitivity that have been proven quite useful for studying signaling, for example, the generation of peroxynitrite (ONOO-) in cellular models of immune function and phagocytosis. This high sensitivity has also enabled real-time quantitative reporting of oxygen-dependent enzyme activity and hypoxia in living cells and tumor xenograft models. We reported some of the first ratiometric chemiluminescent 1,2-dioxetane systems for imaging pH and have introduced a powerful kinetics-based approach for quantification of reactive species like azanone (nitroxyl, HNO) and enzyme activity in living cells. These tools have been applied to untangle complex signaling pathways of peroxynitrite production in radiation therapy and as substrates in a split esterase system to provide an enzyme/substrate pair to rival luciferase/luciferin. Furthermore, we have pushed chemiluminescence toward commercialization and clinical translation by demonstrating the ability to monitor airway hydrogen peroxide in the exhaled breath of asthma patients using transiently produced chemiluminescent 1,2-dioxetanedione intermediates. This body of work shows the powerful possibilities that can emerge when working at the interface of light and chemistry, and we hope that it will inspire future scientists to seek out ever brighter and more illuminating ideas.

KLa(0.95-x)GdxF4:Eu3+ hexagonal phase nanoparticles as luminescent probes for in vitro Huh-7 cancer cell imaging.

A facile chemical route is reported for synthesizing red-emitting photoluminescent/MRI multi-functional KLa(0.95-x)GdxF4:Eu3+ (x = 0 to 0.4) bio-compatible nanomaterials for targeted in vitro tumor imaging. Hexagonal phase pure nanoparticles show a significant and systematic change in morphology with enhanced photoluminescence due to the substitution of La3+ with Gd3+ ions. Single phase ß-KLa(0.95-x)GdxF4:Eu3+ exhibits multifunctional properties, both intense red emission and strong paramagnetism for high-contrast bioimaging applications. These silica capped magnetic/luminescent nanoparticles show long-term colloidal stability, optical transparency in water, strong red emission, and low cytotoxicity. The cellular uptake of coated nanoparticles was investigated in liver cancer cell line Huh-7. Our findings suggest that these nanoparticles can serve as highly luminescent imaging probes for in vitro applications with potential for in vivo and live cell imaging applications.

A bioluminescent probe for in vivo imaging of pyroglutamate aminopeptidase in a mouse model of inflammation.

Pyroglutamate aminopeptidase (PGP) specifically cleaves the peptide bond of pyroglutamic acid linked to the N-terminal end of a polypeptide or protein. Previous studies showed that PGP was associated with several physiological processes and diseases especially those involving inflammation. Utilizing a 'caging' strategy, we designed and synthesized a bioluminescence probe (PBL) with a limit-of-detection of 3.7 * 10-4 mU/mL. In vivo imaging in a mouse model of inflammatory liver disease revealed that the probe has excellent sensitivity and selectivity and provides a powerful tool for studying the physiological and pathological processes involving PGP.

Luminescent cyclometalated platinum(ii) complexes with acyclic diaminocarbene ligands: structural, photophysical and biological properties.

Four new cyclometalated Pt(ii) complexes bearing acyclic diaminocarbene (ADC) ligands, [Pt(C^N)Cl{C(NHXyl)(NHR)}] [C^N = 2,6-difluorophenylpyridine (dfppy), phenylquinoline (pq); R = Pr 3a, 4a, CH2Ph 3b, 4b], were prepared by the nucleophilic attack on the isocyanide [Pt(C^N)Cl(CNXyl)] (C^N = dfppy 1, pq 2) by the corresponding amine RNH2 (R = Pr, CH2Ph). Complexes 3 show in their 1H NMR spectra in CDCl3 a notable concentration dependence, with a clear variation of the δH (NHXyl) signal, suggesting an assembling process implying donor-acceptor NHXylCl bonding, also supported by 1D-PGSE (Pulse Field Gradient Spin Echo) and 2D-DOSY (Diffusion Ordered Spectroscopy) NMR experiments in solution and X-ray diffraction studies. The intermolecular interactions in compounds 3a and 3b were studied by using Hirshfeld surface analysis and Non-Covalent Interaction (NCI) methods on their X-ray structures. Their photophysical properties were investigated by absorption and emission spectroscopies and also by TD-DFT calculations performed on 3a and 4b. These complexes show green (3) or orange (4) phosphorescence, attributed to a mixed 3IL/3MLCT excited state. The carbene ligand does not affect the emission maxima but it produces an increase of the quantum yields in relation to the isocyanide in the precursors. In fluid solutions, the emission is not concentration-dependent, but the complexes may show aggregation induced emission as detailed for complexes 3a and 4a. In addition, cytotoxicity studies in the human cell lines A549 (lung carcinoma) and HeLa (cervix carcinoma) showed good activity for these complexes and 3a, 3b and 4a exhibit a strong effect on DNA electrophoretic mobility. To the best of our knowledge, compounds 3 and 4 represent the first examples of cycloplatinated complexes bearing acyclic diamino carbenes with antiproliferative properties.

Tetraphenylpyrazine-Based Luminescent Metal-Organic Framework for Chemical Sensing of Carcinoids Biomarkers.

A new non-interpenetrated three-dimensional (3D) pillared-layered TPP-based LMOF [Zn3(TPyTPP)0.5(BDC)3]·8DMF (denoted as Zn-MOF 1) was successfully prepared (TPyTPP = tetrakis(4-(pyridin-4-yl)phenyl)pyrazine and H2BDC = 1,4-benzenedicarboxylic acid). Zn-MOF 1 was characterized by single-crystal X-ray diffraction, PXRD, IR, N2 adsorption, thermogravimetric analysis, and luminescent spectrum. Impressively, luminescent sensing studies reveal that activated Zn-MOF 1 not only displays excellent luminescence-quenching efficiency with the values of high Ksv and low LODs toward 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA), respectively, but also possesses outstanding sensing characteristics in terms of fast response, high sensitivity, and specific selectivity. Zn-MOF 1 performs as efficient sensing of carcinoid biomarkers to provide a fresh detection platform for the diagnosis of carcinoids. In addition, the sensing mechanism was also explored on the basis of ultraviolet-visible (UV-vis) absorption, DFT calculations, and structural analysis.

Upconversion Luminescent Nanostructure with Ultrasmall Ceramic Nanoparticles Coupled with Rose Bengal for NIR-Induced Photodynamic Therapy.

We designed a biodegradable hybrid nanostructure for near-infrared (NIR)-induced photodynamic therapy (PDT) using an ultrasmall upconversion (UC) phosphor (ß-NaYF4:Yb3+, Er3+ nanoparticle: NPs) and a hydrocarbonized rose bengal (C18RB) dye, a hydrophobized rose bengal (RB) derivative. The UC-NPs were encapsulated along with C18RB in the hydrophobic core of the micelle composed of poly(ethylene glycol) (PEG)-block-poly(ε-caprolactone) (PCL). The UC-NPs were well shielded from the aqueous environment, owing to the encapsulation in the hydrophobic PCL core, to efficiently emit green UC luminescence by avoiding the quenching by the hydroxyl groups. The hydrophobic part of C18 of C18RB worked well to be involved in the PCL core and located RB on the surface of the PCL core, making the efficient absorption of green light and the emission of singlet oxygen to surrounding water possible. Moreover, as the location is covered by PEG, the direct contact of RB to cells is prohibited to avoid their irradiation-free toxic effect on the cells. The hybrid nanostructure proved to be degradable by the hydrolysis of PEG-b-PCL. This degradation potentially results in renal excretion by the decomposition of the nanostructure into sub-10 nm size particles and makes them viable for clinical uses. These nanostructures can potentially be used for PDT of cancer in deep tissues.

Mitochondria-Targeting Click-Derived Pyridinyltriazolylmethylquinoxaline-Based Y-Shaped Binuclear Luminescent Ruthenium(II) and Iridium(III) Complexes as Cancer Theranostic Agents.

Due to several negative issues, market available drugs have been gradually losing their importance in the treatment of cancer. With a view to discover suitable drugs capable of diagnosing as well as inhibiting the growth of cancer cells, we have aspired to develop a group of theranostic metal complexes which will be (i) target specific, (ii) cytoselective, thus rendering the normal cell unaffected, (iii) water-soluble, (iv) cancer cell permeable, and (v) luminescent, being beneficial for healing the cancer eternally. Therefore, to reach our goal, we have prepared novel Ru(II)- and Ir(III)-based bimetallic and hetero bimetallic scaffolds using click-derived pyridinyltriazolylmethylquinoxaline ligands followed by metal coordination. Most of the compounds have displayed significant cytoselectivity against colorectal adenocarcinoma (Caco-2) and epithiloid cervical carcinoma (HeLa) cells with respect to normal human embryonic kidney cells (HEK-293) compared to cisplatin [cis-diamminedichloroplatinum(II)] along with excellent binding efficacy with DNA as well as serum albumin. Complex [(η6-p-cymene)(η5-Cp*)RuIIIrIIICl2(K2-N,N-L)](PF6)2 [RuIrL] exhibited the best cytoselectivity against all the human cancer cells and was identified as the most significant cancer theranostic agent in terms of potency, selectivity, and fluorescence quantum yield. Investigation of the localization of complex [Ir2L] and [RuIrL] in the more aggressive colorectal adenocarcinoma cell HT-29 indicates that mitochondria are the key cellular target for destroying cancer cells. Mitochondrial dysfunction and G2/M phase cell cycle arrest in HT-29 cell were found to be involved in the apoptotic cell death pathway induced by the test complexes [Ir2L] and [RuIrL]. These results validate the concept that these types of complexes will be reasonably able to exert great potential for tumor diagnosis as well as therapy in the near future.

Dinuclear phosphorescent rhenium(I) complexes as potential anticancer and photodynamic therapy agents.

Chemotherapeutic agents that affect lysosomal functions represent a promising strategy for selective tumor therapy and overcoming drug resistance. In this work, two dinuclear phosphorescent rhenium(i) tricarbonyl complexes (DRe1 and DRe2) containing carboline derivatives have been synthesized, characterized and explored as potential chemotherapeutic and photodynamic therapy agents. The two dinuclear rhenium(i) complexes have good intrinsic phosphorescence properties and can label the lysosomes in cancer cells. Both dinuclear rhenium(i) complexes show potent anticancer activities toward several tested cancer cells. Moreover, they also have marked inhibitory activities against cisplatin-resistant human lung carcinoma cells (A549R), with complex DRe2 displaying 16-fold higher activity than cisplatin. Mechanism studies reveal that complex DRe2 can induce cancer cells to overproduce reactive oxygen species (ROS), including superoxide anion radicals, which leads to lysosomal membrane permeabilization (LMP) and subsequent cell apoptosis. Additionally, both DRe1 and DRe2 display significant phototoxicity under light (425 nm) irradiation in A549 cells, with phototoxicity index values of 60.8 and 41.8, respectively. Therefore, these two dinuclear organometallic rhenium(i) tricarbonyl complexes are potential anticancer agents for combined chemo-photodynamic therapy.