Anticancer and Antibiotic Rhenium Tri- and Dicarbonyl Complexes: Current Research and Future Perspectives.

Organometallic compounds are increasingly recognized as promising anticancer and antibiotic drug candidates. Among the transition metal ions investigated for these purposes, rhenium occupies a special role. Its tri- and dicarbonyl complexes, in particular, attract continuous attention due to their relative ease of preparation, stability and unique photophysical and luminescent properties that allow the combination of diagnostic and therapeutic purposes, thereby permitting, e.g., molecules to be tracked within cells. In this review, we discuss the anticancer and antibiotic properties of rhenium tri- and dicarbonyl complexes described in the last seven years, mainly in terms of their structural variations and in vitro efficacy. Given the abundant literature available, the focus is initially directed on tricarbonyl complexes of rhenium. Dicarbonyl species of the metal ion, which are slowly gaining momentum, are discussed in the second part in terms of future perspective for the possible developments in the field.

Functionalizing Collagen with Vessel-Penetrating Two-Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia.

The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio-probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (ReI ) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, ReI -diimine complex already exhibits excellent emission yield (34%, λem   = 583 nm) and large two-photon absorption cross-sections (σ2   = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen-bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 µs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post-extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial-empowered phosphorescence sensing and imaging.

Mn3+-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment.

X-ray excited persistent luminescence (XEPL) imaging has attracted increasing attention in biomedical imaging due to elimination of autofluorescence, high signal-to-noise ratio and repeatable activation with high penetration. However, optical imaging still suffers from limited for high spatial resolution. Methods: Herein, we report Mn3+-rich manganese oxide (MnOx)-coated chromium-doped zinc gallogermanate (ZGGO) nanoparticles (Mn-ZGGOs). Enhanced XEPL and magnetic resonance (MR) imaging were investigated by the decomposition of MnOx shell in the environment of tumors. We also evaluated the tumor cell-killing mechanism by detection of reactive oxygen (ROS), lipid peroxidation and mitochondrial membrane potential changes in vitro. Furthermore, the in vivo biodistribution, imaging and therapy were studied by U87MG tumor-bearing mice. Results: In the tumor region, the MnOx shell is quickly decomposed to produce Mn3+ and oxygen (O2) to directly generate singlet oxygen (1O2). The resulting Mn2+ transforms endogenous H2O2 into highly toxic hydroxyl radical (·OH) via a Fenton-like reaction. The Mn2+ ions and ZGGOs also exhibit excellent T1-weighted magnetic resonance (MR) imaging and ultrasensitive XEPL imaging in tumors. Conclusion: Both the responsive dual-mode imaging and simultaneous self-supplied O2 for the production of 1O2 and oxygen-independent ·OH in tumors allow for more accurate diagnosis of deep tumors and more efficient inhibition of tumor growth without external activation energy.

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.

Novel photochromic inhibitor for mitotic kinesin Eg5 which forms multiple isomerization states.

The mitotic kinesin Eg5 is a plus-end directed homotetrameric molecular motor essential for the formation of bipolar spindles during cell division. Kinesin Eg5 is overexpressed in cancer cells and hence considered as a target for cancer therapy; the inhibitors specific for Eg5 have been developed as anticancer drugs. In this study, we synthesized a novel functional photoresponsive inhibitor composed of spiropyran and azobenzene derivatives to control Eg5 function with multistage inhibitory activity accompanied by the formation of different isomerization states. The photochromic inhibitor spiropyran-sulfo-azobenzene (SPSAB) exhibited three isomerization states: spiro (SP)-trans, merocyanine (MC)-cis and MC-trans, upon exposure to visible light, ultraviolet and in the dark, respectively. SPSAB-induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with photoisomerization among the three states. Among the three isomerization states of SPSAB, the SP-trans isomer showed potent inhibitory activity at an IC50 value of 30 µM in the basal ATPase assay. MC-trans and MC-cis exhibited less inhibitory activity at IC50 values of 38 and 86 µM, respectively. The results demonstrated that the novel photochromic inhibitor enabled precise control of Eg5 function at three different levels using light irradiation.

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.

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.

Quercetin-Loaded Luminescent Hydroxyapatite Nanoparticles for Theranostic Application in Monolayer and Spheroid Cultures of Cervical Cancer Cell Line In Vitro.

Nanoscale materials have been explored as better alternatives to conventional therapeutic agents in cancer theranostics in the recent period due to efficacy in overcoming biological, biomedical, and biophysical barriers. Analysis on the ability of copper nanocluster (CuNC)-doped hydroxyapatite nanoparticles (Cu-HXNPs) as suitable nanocarriers for anticell proliferative application was carried out. Having high adsorption capacity, the Cu-HXNPs could be loaded with the anticancer drug quercetin, which is a polyphenolic flavonoid compound, and were used as nanocarriers to be applied on HeLa (cancer cells) and HEK-293 (normal cells). The drug release profile was found to be pH-dependent, where maximum release of quercetin from quercetin-loaded Cu-HXNPs was observed in acidic pH as compared to physiological pH. The Cu-HXNPs could release quercetin, which could effectively decline proliferation of cancer cells via generation of reactive oxygen species. Moreover, the released quercetin significantly altered the cell cycle pattern and triggered the cells to undergo apoptosis. Additionally, the efficacy of Cu-HXNPs as a nanocarrier to release quercetin on 3D spheroids of HeLa had been checked, which demonstrated significant reduction in the viability of 3D spheroids. The luminescent CuNCs used for doping HXNPs endowed the nanocarrier with the imaging property, which was an excellent feature in confirming their uptake by the cells. Thus, the study suggested Cu-HXNPs to be a beneficial nanocarrier for both bioimaging and therapeutic purpose in the field of cancer theranostics.

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.

Photofunctional Cyclometalated Iridium(III) Polypyridine Complexes Bearing a Perfluorobiphenyl Moiety for Bioconjugation, Bioimaging, and Phototherapeutic Applications.

In this article, we report the design, synthesis, and characterization of a series of cyclometalated iridium(III) polypyridine complexes containing a perfluorobiphenyl (PFBP) moiety [Ir(N^C)2(bpy-PFBP)](PF6) (bpy-PFBP = 4-(S-(perfluoro-(1,1'-biphenyl)-4-yl)-N-mercaptoethylaminocarbonyloxymethyl)-4'-methyl-2,2'-bipyridine; HN^C = 2-phenylpyridine (Hppy) (1a), 2-(4-hydroxymethylphenyl)pyridine (Hppy-CH2OH) (2a), 2-((1,1'-biphenyl)-4-yl)pyridine (Hpppy) (3a), 2-((4'-hydroxymethyl-1,1'-biphenyl)-4-yl)pyridine (Hpppy-CH2OH) (4a), 2-phenylquinoline (Hpq) (5a), 2-(4-hydroxymethylphenyl)quinoline (Hpq-CH2OH) (6a)). Their PFBP-free counterparts [Ir(N^C)2(bpy-C4)](PF6) (bpy-C4 = 4-(N-n-butylaminocarbonyloxymethyl)-4'-methyl-2,2'-bipyridine; HN^C = Hppy (1b), Hppy-CH2OH (2b), Hpppy (3b), Hpppy-CH2OH (4b), Hpq (5b), Hpq-CH2OH (6b)) were also prepared for comparison studies. Upon irradiation, all the complexes displayed intense and long-lived greenish-yellow to orange luminescence in solutions under ambient conditions and in low-temperature alcohol glass. Reactions of the PFBP complexes with peptides containing the FCPF sequence via the π-clamp-mediated cysteine conjugation afforded luminescent peptide conjugates that exhibited rich photophysical properties. Using complex 3a as an example, we demonstrated that the conjugation of complexes to organelle-targeting peptides is an effective means to modulate their intracellular localization behavior, which was further shown to be important to their performance in photodynamic therapy. The results of this work will contribute to the development of photofunctional transition metal complexes as theranostic agents.

Luminescent Re(I)/Au(I) Species As Selective Anticancer Agents for HeLa Cells.

A series of neutral and cationic heterotrimetallic complexes of the type fac-[Re(CO)3(bipy(CC)2-(AuL)2)X]n, where bipy(CC)2 is 4,4'-alkynyl-2,2'-bipyridine; L is either triphenylphosphine (PPh3), [1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene] (IPr), or tert-butyl isocyanide (CNtBu); and X is a chloride (n = 0) or acetonitrile (n = 1), were synthesized and characterized together with their Re(I) precursors, i.e., fac-[Re(CO)3(bipy(CC)2)X]n. X-ray diffraction of complexes 1, 3, and 6 corroborated the expected octahedral and linear distribution of the ligands along the Re(I) and Au(I) centers, respectively. Luminescent studies showed that all the complexes displayed a broad emission band centered between 565 and 680 nm, corresponding to a 3MLCT from the Re(I) to the diimine derivative. The presence of the gold fragment coordinated to the diimine ligand shifted in all cases the emission maxima toward higher energies. Such an emission difference could be potentially used for assessing the precise moment of interaction of the probe with the biological target if the gold fragment is implicated. Antiproliferative studies in cancer cells, A549 (lung cancer) and HeLa (cervix cancer), showed a generalized selectivity toward HeLa cells for those heterotrimetallic species incubated at longer times (72 vs 24 h). ICP-MS spectrometry revealed the greater cell internalization of cationic vs neutral species. Preliminary fluorescence microscopy experiments showed a different behavior of the complexes in HeLa and A549 cell lines. Whereas the complexes in A549 were randomly distributed in the outside of the cell, those incubated with HeLa cells were located close to the cellular membrane, suggesting some type of interaction, and possibly explaining their cellular selectivity when it comes to the antiproliferative activity displayed in the different cell lines.

Organic Room Temperature Phosphorescence Materials for Biomedical Applications.

Organic room temperature phosphorescence (RTP) materials have drawn increasing attention due to their unique features, especially the long emission lifetime for applications in biomedicine. In this review, we provide an overview of the recent developments of organic RTP materials applied in the biomedicine field. First, we introduce the basic mechanism of phosphorescence and subsequently we present various strategies of modulating the lifetime and efficiency of room temperature organic phosphorescence. Next, we summarize the progress of organic RTP materials in biological applications, including bioimaging, anti-cancer and antibacterial therapies. Finally, we provide an outlook with regard to the challenges and future perspectives in the field.

Functionalized Upconversion Nanoparticles for Targeted Labelling of Bladder Cancer Cells.

Bladder cancer is the ninth most common cancer worldwide. Due to a high risk of recurrence and progression of bladder cancer, every patient needs long-term surveillance, which includes regular cystoscopy, sometimes followed by a biopsy of suspicious lesions or resections of recurring tumours. This study addresses the development of novel biohybrid nanocomplexes representing upconversion nanoparticles (UCNP) coupled to antibodies for photoluminescent (PL) detection of bladder cancer cells. Carrying specific antibodies, these nanoconjugates selectively bind to urothelial carcinoma cells and make them visible by emitting visible PL upon excitation with deeply penetrating near-infrared light. UCNP were coated with a silica layer and linked to anti-Glypican-1 antibody MIL38 via silica-specific solid-binding peptide. Conjugates have been shown to specifically attach to urothelial carcinoma cells with high expression of Glypican-1. This result highlights the potential of produced conjugates and conjugation technology for further studies of their application in the tumour detection and fluorescence-guided resection.

A Luminescent Amine-Functionalized Metal-Organic Framework Conjugated with Folic Acid as a Targeted Biocompatible pH-Responsive Nanocarrier for Apoptosis Induction in Breast Cancer Cells.

Folic acid amine-functionalized metal-organic framework (FOLA@NH2-Eu:TMU-62) with luminescent properties loaded with 5-fluorouracil (5-Fu), as an anticancer medication, was used to construct a new cancer targeted drug delivery system in the present study. The 5-Fu release from this targeted carrier along with MTT assay and trypan blue dye exclusion test results also exhibited pH-controlled characteristics of the given carrier in acidic environments, which is very suitable for targeting solid tumors. Then, the inhibitory action of 5-Fu-loaded FOLA@NH2-Eu:TMU-62 for Michigan Cancer Foundation-7 (MCF7) cell migration was explored according to scratch wound healing assays. Based on the results, the FOLA@NH2-Eu:TMU-62 carrier was not toxic for MCF-10A normal cells, but it was significantly toxic for MCF-7 breast cancer ones, revealing that the FOLA@NH2-Eu:TMU-62 carrier could be utilized in accurate cancer treatments through apoptotic pathways with higher reactive oxygen species compared with 5-Fu alone. This cancer-targeted design of FOLA@NH2-Eu:TMU-62 could thus pave the way for synergistic effects of targeting as well as organized release capabilities.

Therapeutic Potential of Two Visible Light Responsive Luminescent photoCORMs: Enhanced Cellular Internalization Driven by Lipophilicity.

Herein we report the synthesis, characterization, and cellular internalization properties of two visible-light active luminescent Mn-based photoCORMs. The enhanced membrane permeability of the photoactive Mn carbonyl complex (photoCORM) derived from a designed lipophilic ligand namely, [Mn(CO)3(Imdansyl)(L1)](CF3SO3) (1) (where L1 = a diazabutadiene-based ligand containing two highly lipophilic adamantyl motifs, Imdansyl = dansylimidazole) promoted rapid internalization within human colorectal adenocarcinoma (HT-29) cells compared to [Mn(CO)3(Imdansyl)(L2)](CF3SO3) (2) (where L2 = a diazabutadiene ligand bearing two hydrophilic 1,3,5-triazaadamantyl group). Colocalization experiments using membrane stain indicate different extents of localization of the two CO complexes within the cellular matrix. Visible-light triggered CO release from the lipophilic photoCORM induced caspase-3/7 activation on HT-29 cells, which was detected using confocal microscopy. The rapid accumulation of the lipophilic photoCORM 1 in the cellular membrane resulted in more efficient CO-induced cell death compared to the hydrophilic analogue 2.

Synthesis and Rational design of Europium and Lithium Doped Sodium Zinc Molybdate with Red Emission for Optical Imaging.

Highly efficient fluorescent and biocompatible europium doped sodium zinc molybdate (NZMOE) nanoprobes were successfully synthesized via Polyol method. Non-radiative defect centres get reduced with Li+ co-doping in NZMOE nanoprobes. XRD spectra and Rietveld refinement confirmed successful incorporation of lithium ion and crystallinity was also improved with Li+ co-doping. The shape of phosphor is rod shaped, as determined by TEM. Significant enhancement in photoluminescence intensity was observed with 266, 395 and 465 nm excitations. Profound red emission was recorded for 5 at% Li+ co-doped NZMOE nanoprobes with 266 nm excitation. It shows high asymmetry ratio (~15), color purity (94.90%) and good quantum efficiency (~70%). Judd Ofelt parameters have been calculated to measure intensity parameters and radiative transition rates. In order to measure biocompatibility of the nanoprobes, cytotoxicity assays were performed with HePG2 cells. The fluorescence emitted from phosphor material treated HePG2 cells was also measured by Laser Scanning Confocal Microscopy. The bright red fluorescence in HePG2 cells treated with very low concentration (20 µg/ml) of phosphor material indicates that it could be a promising phosphor for biological detection or bio-imaging.

Photophysical and Cellular Imaging Studies of Brightly Luminescent Osmium(II) Pyridyltriazole Complexes.

The series of complexes [Os(bpy)3- n(pytz) n][PF6]2 (bpy = 2,2'-bipyridyl, pytz = 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole, 1 n = 0, 2 n = 1, 3 n = 2, 4 n = 3) were prepared and characterized and are rare examples of luminescent 1,2,3-triazole-based osmium(II) complexes. For 3 we present an attractive and particularly mild preparative route via an osmium(II) η6-arene precursor circumventing the harsh conditions that are usually required. Because of the high spin-orbit coupling constant associated with the Os(II) center the absorption spectra of the complexes all display absorption bands of appreciable intensity in the range of 500-700 nm corresponding to spin-forbidden ground-state-to-3MLCT transitions (MLCT = metal-to-ligand charge transfer), which occur at significantly lower energies than the corresponding spin-allowed 1MLCT transitions. The homoleptic complex 4 is a bright emitter (λmaxem = 614 nm) with a relatively high quantum yield of emission of ∼40% in deoxygenated acetonitrile solutions at room temperature. Water-soluble chloride salts of 1-4 were also prepared, all of which remain emissive in aerated aqueous solutions at room temperature. The complexes were investigated for their potential as phosphorescent cellular imaging agents, whereby efficient excitation into the 3MLCT absorption bands at the red side of the visible range circumvents autofluorescence from biological specimens, which do not absorb in this region of the spectrum. Confocal microscopy reveals 4 to be readily taken up by cancer cell lines (HeLa and EJ) with apparent lysosomal and endosomal localization, while toxicity assays reveal that the compounds have low dark and light toxicity. These complexes therefore provide an excellent platform for the development of efficient luminescent cellular imaging agents with advantageous photophysical properties that enable excitation and emission in the biologically transparent region of the optical spectrum.

Tracking mitochondrial dynamics during apoptosis with phosphorescent fluorinated iridium(iii) complexes.

Mitochondria are the control centers of apoptosis. To study mitochondrial dynamics during apoptosis, four phosphorescent fluorinated iridium(iii) complexes (Ir1-Ir4) were designed and synthesized. The complexes' emission maxima, phosphorescent quantum yields, and phosphorescent lifetimes are tuned by the degree of fluorination of the ligand. The complexes exhibit excellent photostability and low (photo)cytotoxicity in HeLa cells. As the complexes are cationic and lipophilic, they localize in mitochondria and enter cells through an energy-independent pathway. In comparison with commercially available mitochondrial trackers (e.g., MTR), Ir1-Ir4 exhibit high specificity to mitochondria even in fixed cells. Due to these outstanding properties, the complexes were successfully used to track mitochondrial dynamics during apoptosis.

An iridium complex-based probe for photoluminescence lifetime imaging of human carboxylesterase 2 in living cells.

A novel photoluminescence lifetime probe (Ir-TB) has been developed for the detection and imaging of hCE2 in living cells. A large lifetime increase by around 300 ns after the enzymatic reaction makes it an ideal tool to distinguish hCE2-hydrolyzed probes from those non-hydrolyzed ones via PLIM for the first time.