Luminescent Transition Metal Complexes Research Articles

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications.

Luminescence imaging is a powerful and versatile technique for investigating cell physiology and pathology in living systems, making significant contributions to life science research and clinical diagnosis. In recent years, luminescent transition metal complexes have gained significant attention for diagnostic and therapeutic applications due to their unique photophysical and photochemical properties. In this Review, we provide a comprehensive overview of the recent development of luminescent transition metal complexes for bioimaging and biosensing applications, with a focus on transition metal centers with a d6, d8, and d10 electronic configuration. We elucidate the structure-property relationships of luminescent transition metal complexes, exploring how their structural characteristics can be manipulated to control their biological behavior such as cellular uptake, localization, biocompatibility, pharmacokinetics, and biodistribution. Furthermore, we introduce the various design strategies that leverage the interesting photophysical properties of luminescent transition metal complexes for a wide variety of biological applications, including autofluorescence-free imaging, multimodal imaging, organelle imaging, biological sensing, microenvironment monitoring, bioorthogonal labeling, bacterial imaging, and cell viability assessment. Finally, we provide insights into the challenges and perspectives of luminescent transition metal complexes for bioimaging and biosensing applications, as well as their use in disease diagnosis and treatment evaluation.

Controlling the Photophysical Properties of a Series of Isostructural d6 Complexes Based on Cr0, MnI, and FeII.

Development of first-row transition metal complexes with similar luminescence and photoredox properties as widely used RuII polypyridines is attractive because metals from the first transition series are comparatively abundant and inexpensive. The weaker ligand field experienced by the valence d-electrons of first-row transition metals challenges the installation of the same types of metal-to-ligand charge transfer (MLCT) excited states as in precious metal complexes, due to rapid population of energetically lower-lying metal-centered (MC) states. In a family of isostructural tris(diisocyanide) complexes of the 3d6 metals Cr0, MnI, and FeII, the increasing effective nuclear charge and ligand field strength allow us to control the energetic order between the 3MLCT and 3MC states, whereas pyrene decoration of the isocyanide ligand framework provides control over intraligand (ILPyr) states. The chromium(0) complex shows red 3MLCT phosphorescence because all other excited states are higher in energy. In the manganese(I) complex, a microsecond-lived dark 3ILPyr state, reminiscent of the types of electronic states encountered in many polyaromatic hydrocarbon compounds, is the lowest and becomes photoactive. In the iron(II) complex, the lowest MLCT state has shifted to so much higher energy that 1ILPyr fluorescence occurs, in parallel to other excited-state deactivation pathways. Our combined synthetic-spectroscopic-theoretical study provides unprecedented insights into how effective nuclear charge, ligand field strength, and ligand π-conjugation affect the energetic order between MLCT and ligand-based excited states, and under what circumstances these individual states become luminescent and exploitable in photochemistry. Such insights are the key to further developments of luminescent and photoredox-active first-row transition metal complexes.

Multiple Triplet Metal-Centered Jahn-Teller Isomers Determine Temperature-Dependent Luminescence Lifetimes in [Ru(bpy)3 ]2.

Understanding the factors that determine the luminescence lifetime of transition metal compounds is key for applications in photocatalysis and photodynamic therapy. Here we show that for (bpy = 2,2'-bipyridine), the generally accepted idea that emission lifetimes can be controlled optimizing the energy barrier from the emissive triplet metal-to-ligand charge-transfer (3 MLCT) state to the thermally-activated triplet metal-centered (3 MC) state or the energy gap between both states is a misconception. Further, we demonstrate that considering a single relaxation pathway determined from the minimum that is lowest in energy leads to wrong temperature-dependent emission lifetimes predictions. Instead, we obtain excellent agreement with experimental temperature-dependent lifetimes when an extended kinetic model that includes all the pathways related to multiple Jahn-Teller isomers and their effective reaction barriers is employed. These concepts are essential to correctly design other luminescent transition metal complexes with tailored emission lifetimes based on theoretical predictions.

Mehrere Triplett-Metall-zentrierte Jahn-Teller-Isomere bestimmen die temperaturabhängigen Lumineszenzlebensdauern in [Ru(bpy)3]2.

AbstractEin genaues Verständnis der Faktoren, welche die Lumineszenzlebensdauer von Übergangsmetallverbindungen bestimmen, ist für Anwendungen in der Photokatalyse und der photodynamischen Therapie von entscheidender Bedeutung. Die im Falle von [Ru(bpy)3]2+ (bpy=2,2’‐Bipyridin) allgemein akzeptierte Theorie besagt, dass die Emissionslebensdauer durch Optimierung der Energiebarriere zwischen dem emittierenden Triplett‐Zustand des Metall‐Liganden‐Ladungstransfers (3MLCT) und dem thermisch aktivierten Triplett‐Zustand des Metall‐Zentrums (3MC), oder der Energielücke zwischen beiden Zuständen gesteuert werden kann. Hier zeigen wir, dass dies nicht allgemeingültig ist. Darüber hinaus demonstrieren wir, dass die Betrachtung eines einzelnen Relaxationspfades, der vom energetisch niedrigsten Minimum aus bestimmt wird, zu falschen Vorhersagen der temperaturabhängigen Emissionslebensdauer führt. Stattdessen erhalten wir eine ausgezeichnete Übereinstimmung mit den experimentellen temperaturabhängigen Lebensdauern, wenn ein erweitertes kinetisches Modell herangezogen wird, welches alle Pfade im Zusammenhang mit mehreren Jahn–Teller‐Isomeren und ihren effektiven Reaktionsbarrieren beinhaltet. Diese Konzepte sind für das Design weiterer lumineszierender Übergangsmetallkomplexe mit individuell angepassten Emissionslebensdauern auf der Grundlage theoretischer Vorhersagen unerlässlich.

Quantum Yield of DNA Strand Breaks under Photoexcitation of a Molecular Ruby.

Photodynamic therapy (PDT) used for treating cancer relies on the generation of highly reactive oxygen species, for example, singlet oxygen 1 O2 , by light-induced excitation of a photosensitizer (PS) in the presence of molecular oxygen, inducing DNA damage in close proximity of the PS. Although many precious metal complexes have been explored as PS for PDT and received clinical approval, only recently, the potential of photoactive complexes of non-noble metals as PS has been discovered. Using the DNA origami technology that can absolutely quantify DNA strand break cross sections, we assessed the potential of the luminescent transition metal complex [Cr(ddpd)2 ]3+ (ddpd=N,N'-dimethyl-N,N'-dipyridine-2-ylpyridine-2,6-diamine) to damage DNA in an air-saturated aqueous environment upon UV/Vis illumination. The quantum yield for strand breakage, that is, the ratio of DNA strand breaks to the number of absorbed photons, was determined to 1-4 %, indicating efficient transformation of photons into DNA strand breaks by [Cr(ddpd)2 ]3+ .

Strategic Design of Luminescent Rhenium(I), Ruthenium(II), and Iridium(III) Complexes as Activity-Based Probes for Bioimaging and Biosensing.

The rapid development of responsive fluorescent probes has advanced optical imaging for biological research and biomedical applications. Among different sensing strategies, activity-based sensing, which exploits the unique reactivity of the target chemical species to achieve high chemoselectivity, has emerged as a promising paradigm for the development of responsive probes for selective molecular imaging. Luminescent transition metal complexes have received considerable attention for bioimaging and biosensing applications over the last decade due to their remarkable photophysical behavior including intense emission with large Stokes' shifts, long emission lifetimes, strong two-photon absorption, and high photostability. In this Review, we summarize the design strategies and applications of luminescent complexes of rhenium(I), ruthenium(II), and iridium(III) polypyridines as activity-based probes for the detection of various chemical species and bioactive molecules in live cells and organisms. The current challenges and future prospects of these complexes as activatable reagents for disease diagnosis and treatment are also discussed.

Luminescent and Photofunctional Transition Metal Complexes: From Molecular Design to Diagnostic and Therapeutic Applications.

There has been emerging interest in the exploitation of the photophysical and photochemical properties of transition metal complexes for diagnostic and therapeutic applications. In this Perspective, we highlight the major recent advances in the development of luminescent and photofunctional transition metal complexes, in particular, those of rhenium(I), ruthenium(II), osmium(II), iridium(III), and platinum(II), as bioimaging reagents and phototherapeutic agents, with a focus on the molecular design strategies that harness and modulate the interesting photophysical and photochemical behavior of the complexes. We also discuss the current challenges and future outlook of transition metal complexes for both fundamental research and clinical applications.

Cathodoluminescence imaging of cellular structures labeled with luminescent iridium or rhenium complexes at cryogenic temperatures

We report for the first time the use of two live-cell imaging agents from the group of luminescent transition metal complexes (IRAZOLVE-MITO and REZOLVE-ER) as cathodoluminescent probes. This first experimental demonstration shows the application of both probes for the identification of cellular structures at the nanoscale and near the native state directly in the cryo-scanning electron microscope. This approach can potentially be applied to correlative and multimodal approaches and used to target specific regions within vitrified samples at low electron beam energies.

Physico-chemical characterization studies of collagen labelled with Ru(II) polypyridyl complex

The rich luminescence behaviour exerted by transition metal complexes has found significant role in the development of biomolecular and cellular probes. The conjugation of fluorophore to a protein has its own advantage over the label-free system due to its high sensitivity. While numerous proteins have been labelled with either organic or inorganic fluorophores, the conjugation of luminescent transition metal complexes with collagen has not yet been attempted. Here, in this study, the conjugation of a Ru(II) polypyridyl complex with collagen was carried out and its physico-chemical characterization was studied. The conjugation of Ru(II) to collagen was characterized by UV-Visible, fluorescence and ATR-FT-IR spectroscopy. The conjugation of Ru(II) did not alter the triple helical structure of the collagen as evidenced from CD spectral data. The luminescence behaviour of the Ru-tagged collagen was found to be similar to that of the commercially available fluorescein isothiocyanate (FITC) tagged collagen with increase in luminescence upon addition of collagenase. Gel-based collagenase assay showed that the digestion of collagen can be vizualized using UV light due to intrinsic fluorophore tag without carrying out the staining-destaining processes. Energy dispersive X-Ray analysis (EDAX) confirms the presence of Ru in Ru-collagen fibrils. To the best of our knowledge, this is the first report on the conjugation of a Ru(II) complex with the fibrous protein collagen that exhibits similar property as of FITC-collagen and can be used as an alternative.

Photoactive and Luminescent Transition Metal Complexes as Anticancer Agents: A Guiding Light in the Search for New and Improved Cancer Treatments.

Cancer continues to be responsible for the deaths of more than 9 million people worldwide each year. Current treatment options are diverse, but low success rates, particularly for those with late-stage cancers, continue to be a problem for clinicians and their patients. The effort by researchers globally to find alternative treatment options is ongoing. In the present study, we focused on innovations in inorganic anticancer therapies, specifically those with photoactive and luminescent properties. Transition metals offer distinct advantages compared to wholly organic compounds in both chemotherapeutics and luminescence properties. Here we report on the characteristics that result from discrete structural changes that have been expertly used to fine-tune their properties, and how diverse inherent luminescent properties have been widely employed to monitor cellular localization to photodynamic therapy.

A Cyclodextrin-Hosted Ir(III) Complex for Ratiometric Mapping of Tumor Hypoxia In Vivo.

Hypoxia is considered as a key microenvironmental feature of solid tumors. Luminescent transition metal complexes particularly those based on iridium and ruthenium have shown remarkable potentials for constructing sensitive oxygen‐sensing probes due to their unique oxygen quenching pathway. However, the low aqueous solubility of these complexes largely retards their sensing applications in biological media. Moreover, it remains difficult so far to use the existing complexes typically possessing only one luminescent domain to quantitatively detect the intratumoral hypoxia degree. Herein, an Ir(III) complex showing red emissions is designed and synthesized, and innovatively encapsulated within a hydrophobic pocket of Cyanine7‐modified cyclodextrin. The Ir(III) complex enables the oxygen detection, while the cyclodextrin is used not only for improving the water solubility and suppressing the luminescence quenching effect of the surrounding aqueous media, but also for carrying Cyanine7 to establish a ratiometric oxygen fluorescence probe. 2D nuclear magnetic resonance is carried out to confirm the host–guest structure. The oxygen‐responsive ability of the resulting ratiometric probe is evaluated through in vitro cell and multicellular experiments. Further animal studies about tumor oxygen level mapping demonstrate that the probe can be successfully used for quantitatively visualizing tumor hypoxia in vivo.

Responsive Metal Complex Probes for Time-Gated Luminescence Biosensing and Imaging.

The development of reliable bioanalytical probes for selective and sensitive detection of particular analytes in biological systems is essential for better understanding the roles of the analytes in their native contexts. In the last two decades, luminescent metal complexes have greatly contributed to the development of such probes for biosensing and imaging due to their unique spectral and temporal properties, controllable cell membrane permeability, and cytotoxicity. Conjugating an analyte-activatable moiety to the metal complex luminophores allows the production of responsive metal complex probes for this analyte detection. Owing to their long-lifetime emissions, the responsive metal complex probes are accessible to the technique of time-gated luminescence (TGL) detection and imaging. With a delay time after pulsed excitation, the TGL technique allows for collection of only long-lived luminescence from responsive metal complex probes, while filtering out short-lived background autofluorescence, providing a background-free approach for the detection and imaging of the analyte at subcellular and/or molecular levels. Responsive metal complex probes, therefore, have emerged as complementary sensing and imaging tools of organic dye-based fluorescent probes for the in situ detection of analytes in complicated biological environments.In this Account, we describe the advances in the development of metal complex probes and their applications for TGL bioassays with particular focus on our efforts made in this field. We first introduce the photophysical/-chemical properties of luminescent metal complexes, including lanthanide (europium and terbium) and transition metal (ruthenium and iridium) complexes. The luminescence lifetimes (τ) of lanthanide and transition metal complexes are at micro/millisecond (μs/ms) and hundreds/thousands nanosecond (ns) levels, respectively. The emission lifetimes are significantly longer than the autofluorescence lifetime (τ < 10 ns) of biological samples. Such long-lived luminescence of these metal complexes enables our research on demonstrating responsive probes for background-free TGL detection of some reactive biomolecules, such as reactive oxygen/nitrogen species (ROS/RNS) and biothiols.We conclude this Account by outlining the future directions to further develop new generation responsive TGL probes for promoting their practical applications. The responsive TGL probes are expected to be translated for biomedical and/or (pre)clinical investigations of biomolecules in situ. Reversibility, lower toxicity, ability of excitation at longer wavelength, and potential to be translated are key criteria for the development of next-generation probes. We also anticipate that further development of responsive TGL probes will contribute to the bioassay in more challenging biological systems, such as plants that have significant higher background autofluorescence than animals.

Study of the structures and photophysical properties of 1,3-diaza-5-phosphacyclohexanes using density functional theory and optical spectroscopy

The steric and electronic structures of 1,3-diaza-5-phoaphacyclohexane with the pyridyl substituent at the phosphorus atom and a series of model 1,3-diaza-5-phosphacyclohexanes (potential ligands for the synthesis of luminescent transition metal complexes) were studied using IR and UV spectroscopy combined with quantum chemical calculations. Relationships between the electronic structures, spectral characteristics, and donor—acceptor properties of the substituents were revealed. The relationships can further be used for the target synthesis of complexes with specified optical properties.

Photophysics and photochemistry with Earth-abundant metals - fundamentals and concepts.

Recent exciting developments in the area of mononuclear photoactive complexes with Earth-abundant metal ions (Cu, Zr, Fe, Cr) for potential eco-friendly applications in (phosphorescent) organic light emitting diodes, in imaging and sensing systems, in dye-sensitized solar cells and as photocatalysts are presented. Challenges, in particular the extension of excited state lifetimes, and recent conceptual breakthroughs in substituting precious and rare-Earth metal ions (e.g. Ru, Ir, Pt, Au, Eu) in these applications by abundant ions are outlined with selected examples. Relevant fundamentals of photophysics and photochemistry are discussed first, followed by conceptual and instructive case studies.

Mechanochemical changes on cyclometalated Ir(iii) acyclic carbene complexes – design and tuning of luminescent mechanochromic transition metal complexes

A new class of luminescent cyclometalated Ir(iii) complexes with readily tunable mechanochromic properties derived from the mechanically induced trans-to-cis isomerization have been developed.

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response.

We herein describe the comprehensive investigation of the complexation behavior of a guanidinium-modified calix[5]arene pentaisohexyl ether (GC5A) with a variety of typical luminescent dyes. Fluorescein, eosin Y, rose bengal, tetraphenylporphine sulfonate and sulfonated aluminum phthalocyanine were employed as classical aggregation-induced quenching dyes. 2-(p-Toluidinyl)naphthalene-6-sulfonic acid and 1-anilinonaphthalene-8-sulfonic acid were selected as representatives of intramolecular charge-transfer dyes. Phosphated tetraphenylethylene was involved as the classical aggregation-induced emission dye. Sulfonated acedan representing one example of two-photon fluorescent probes, was also investigated. A ruthenium(II) complex with carboxylated bipyridyl ligands was included as a representative candidate of luminescent transition-metal complexes. We determined the association constants of the GC5A–dye complexes by fluorescence titration and discuss the complexation-induced photophysical changes. In addition, a comparison of the complexation behavior of GC5A with that of other macrocycles and potential applications according to the diverse photophysical responses are provided.

Luminescent complexes of 2,1,3-benzothiadiazole derivatives

The review prasents a survey of the synthesis and structures of luminescent transition metal complexes with 2,1,3-benzothiadiazole ligands. Specific noncovalent interactions involving 2,1,3-benzothiadiazole moieties, which have a significant effect on the crystal packing and properties of the complexes, are analyzed.

Application of density functional theory and optical spectroscopy for the prediction of the photophysical properties of Р-pyridylphospholanes

The spatial and electronic structure of a series of pyridyl-containing phospholanes, which are potential ligands for the synthesis of luminescent transition metal complexes, was studied using Raman, IR and UV spectroscopy in combination with quantum chemical calculations. A series of model 1-(pyridin-2-yl)phospholane derivatives with various substituents in the pyridyl fragment was considered. Correlations between electronic structure, spectral characteristics, as well as position and nature of substituents were revealed. The obtained results can be used for rational design of complexes with specified optical properties.

Luminescent Ruthenium(II) Polypyridine Complexes for a Wide Variety of Biomolecular and Cellular Applications.

Ruthenium(II) polypyridine complexes are one of the most extensively studied and developed systems in the family of luminescent transition-metal complexes. Notably, there has been a large amount of interest in the biological applications of these luminescent ruthenium(II) complexes because of their rich photophysical and photochemical properties. In this Viewpoint, we explore past and recent works on the possible biological and cellular applications of these promising complexes, with a focus on their use as bioimaging reagents, biomolecular probes, and phototherapeutic agents.

Super-Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore.

Combining luminescent transition metal complex with super-resolution microscopy is an excellent strategy for the long-term visualization of the dynamics of subcellular structures in living cells. However, it remains unclear whether iridium(III) complexes are applicable for a particular type of super-resolution technique, structured illumination microscopy (SIM), to image subcellular structures. Herein, an iridium(III) dye, to track mitochondrial dynamics in living cells under SIM is described. The dye demonstrates excellent specificity and photostability and satisfactory cell permeability. While using SIM to image mitochondria, an ≈80 nm resolution is achieved that allows the clear observation of the structure of mitochondrial cristae. The dye is used to monitor and quantify mitochondrial dynamics relative to lysosomes, including fusion involved in mitophagy, and newly discovered mitochondria-lysosome contact (MLC) under different conditions. The MLC remains intact and fusion vanishes when five receptors, p62, NDP52, OPTN, NBR1, and TAX1BP1, are knocked out, suggesting that these two processes are independent.