Kenneth Kam-Wing Lo

Luminescent polynuclear d10 metal complexes

A number of polynuclear d10 transition metal complexes have been found to exhibit interesting luminescence properties. The photoluminescence properties of polynuclear d10 metal complexes are highly diversified. In the presence of a wide range of bridging and ancillary ligands, the excited states of such complexes have been suggested to range from metal-to-ligand charge-transfer, ligand-to-metal charge-transfer, metal-centred to ligand-centred in nature. Recent work on the photophysical and photochemical properties, as well as the applications of this class of luminescent polynuclear d10 metal complexes will be described in this review article.

Recent advances in utilization of transition metal complexes and lanthanides as diagnostic tools

Abstract Based on the widely diverse coordination environment of transition metal complexes and lanthanides, and variation in the identities of coordinating ligands, synthesis of such complexes with desired molecular geometry can be realized. These compounds often possess remarkable and unique spectroscopic, photophysical and electrochemical properties which may be exploited in sensory and diagnostic applications. In this article, recent advances in the development and utilization of transition metal complexes and lanthanides as ion, molecular and other chemical sensors, nucleic acid probes, and other detection tools in related bioassays will be reviewed.

Design of luminescent polynuclear copper(I) and silver(I) complexes with chalcogenides and acetylides as the bridging ligands

Abstract A number of chalcogenido and alkynyl clusters of copper(I) and silver(I) with various nuclearities have been synthesized and characterized. All these clusters have been found to possess rich photophysical and photochemical properties. The phosphorescent states of the complexes have been shown to undergo facile photo-induced oxidative electron-transfer quenching reactions with a series of pyridinium acceptors, indicative of their highly reducing nature in the excited states. The lowest lying excited states of the clusters have been assigned to be an admixture of ligand-to-metal charge-transfer (LMCT) and metal-centered (d-s) transitions, which have also been supported by Fenske-Hall and ab initio molecular orbital calculations. The excited state properties of these cluster have also been probed by nanosecond laser flash photolysis studies.

Luminescent polynuclear metal acetylides

Abstract The photophysical and photochemical studies of polynuclear copper(I), silver(I), gold(I), rhenium(I) and platinum(II) acetylide complexes are reviewed. Based on the highly flexible bonding modes of the acetylides and the various coordination geometry of these metal centres, a number of polynuclear copper(I), silver(I), gold(I), rhenium(I) and platinum(II) acetylide complexes with very different molecular structures have been synthesized and characterized. These organometallic complexes also exhibit rich and remarkable photophysical and photochemical properties which are unique to the presence of the acetylide ligand. The fundamental understanding on the photophysical and photochemical properties of these luminescent organometallic complexes would lead to the production of novel luminescent materials and represent model systems in the development of light-emitting diodes, new materials with non-linear optical properties and liquid crystalline properties. In this review article, particular attention is focused on the electronic absorption spectroscopy, photoluminescence behaviour, excited-state assignments and photochemical properties of this class of luminescent acetylide complexes.

Development of luminescent iridium(III) polypyridine complexes as chemical and biological probes

A number of luminescent iridium(III) polypyridine complexes have been designed as molecular sensors owing to their rich photophysical properties such as intense, long-lived and environment-sensitive emission. In particular, many complexes exhibit emissive behavior that can be readily controlled using various Werner-type and cyclometalating ligands. In this Perspective, we review some recent examples of luminescent iridium(III) polypyridine complexes as probes for chemical and biological molecules using different strategies. The targets include proton, cations and anions, small molecules, nucleic acids and protein molecules. There is also a recent interest in luminescent iridium(III) polypyridine complexes as cellular probes and imaging reagents; selected examples in these areas are described.

Exploitation of the Dual-emissive Properties of Cyclometalated Iridium(III)–Polypyridine Complexes in the Development of Luminescent Biological Probes†

There has been fast-growing interest in utilizing iridium(III)– polypyridine complexes as new luminescent sensors for analytes, including protons, halide ions, metal cations, oxygen, and biomolecules. These complexes display changes in their emission intensities and lifetimes upon analyte binding. Although the emission maxima exhibit small shifts in some cases, the emission profiles and spectral characteristics of the luminescent probes basically remain the same. Compared to common metal-to-ligand charge-transfer (MLCT) emitters, such as the ruthenium(II)– and osmium(II)–polypyridine systems, iridium(III)–polypyridine complexes exhibit emissive states that are very sensitive to their ligands and local environment, resulting in distinct emission features. However, it appears that this behavior has not been utilized in the current array of sensors available. Whilst dual emission is not uncommon for iridium(III)–polypyridine complexes in glass at low temperature, it is very rare in fluid solutions under ambient conditions. We believe that an attractive approach to the development of new iridium(III)-based luminescent probes would be the utilization of novel complexes that display environment-responsive dualemissive properties. Herein we report a series of novel dual-emissive cyclometalated iridium(III)–polypyridine complexes that serve as luminescent sensors for various biological receptors. The complex [Ir(ppy-CH2NH-C4H9)2(bpy-CONH-C2H5)](PF6) (1; Hppy-CH2NH-C4H9 = 2-(4-(N-(n-butyl)aminomethyl)phenyl)pyridine; bpy-CONH-C2H5 = 4-(N-(ethyl)aminocarbonyl)-4’-methyl-2,2’-bipyridine; Scheme 1) was synthesized from the reaction of the aldehyde complex [Ir(ppyCHO)2(bpy-CONH-C2H5)](PF6) (Hppy-CHO = 4-(2-pyridyl)benzaldehyde) with n-butylamine in refluxing methanol, followed by reduction with NaBH3CN. Upon irradiation, 1 exhibited intense and long-lived luminescence (Table 1). Interestingly, it showed dual emission in fluid solutions at room temperature, with a high-energy (HE) structured band at about 500 nm (to = 1.1–2.5 ms) and a low-energy (LE) broad band/shoulder at approximately 593–619 nm (to = 0.1– 0.3 ms; Table 1). The possibility of emissive impurities in the samples was excluded on the basis of the characterization data. In degassed nonpolar solvents such as CH2Cl2, the emission intensity of the LE band was higher than or comparable to that of the HE band, whilst in more polar solvents such as CH3CN and CH3OH, it became much weaker; in aqueous buffer the spectrum was dominated by the HE band (Figure 1). The intensities of both the HE and LE emission features were reduced in aerated solutions, with the former being more sensitive to quenching by oxygen. As a result, the LE band became dominant in aerated solutions, except in the case of aqueous buffer. Addition of trifluoroacetic acid (TFA) to an aerated solution of the complex in CH2Cl2 shifted the LE emission band to a shorter wavelength (ca. 574 nm) and the HE feature was eventually embedded into the broad LE band. Interestingly, the amine-free analogue complex [Ir(ppy)2(bpy-CONH-C2H5)](PF6) (1a ; Hppy = 2-phenylpyridine) did not display dual emission in fluid solutions (Table 1). The only broad band of this complex at around 609–632 nm was insensitive to the presence of TFA and has been assigned to a charge-transfer (CT) state of mixed MLCT (dp(Ir)!p*(N^N)) and ligand-to-ligand Scheme 1. Structures of complexes 1–4.

Luminescent Rhenium(I) and Iridium(III) Polypyridine Complexes as Biological Probes, Imaging Reagents, and Photocytotoxic Agents

Although the interactions of transition metal complexes with biological molecules have been extensively studied, the use of luminescent transition metal complexes as intracellular sensors and bioimaging reagents has not been a focus of research until recently. The main advantages of luminescent transition metal complexes are their high photostability, long-lived phosphorescence that allows time-resolved detection, and large Stokes shifts that can minimize the possible self-quenching effect. Also, by the use of transition metal complexes, the degree of cellular uptake can be readily determined using inductively coupled plasma mass spectrometry. For more than a decade, we have been interested in the development of luminescent transition metal complexes as covalent labels and noncovalent probes for biological molecules. We argue that many transition metal polypyridine complexes display triplet charge transfer ((3)CT) emission that is highly sensitive to the local environment of the complexes. Hence, the biological labeling and binding interactions can be readily reflected by changes in the photophysical properties of the complexes. In this laboratory, we have modified luminescent tricarbonylrhenium(I) and bis-cyclometalated iridium(III) polypyridine complexes of general formula [Re(bpy-R(1))(CO)3(py-R(2))](+) and [Ir(ppy-R(3))2(bpy-R(4))](+), respectively, with reactive functional groups and used them to label the amine and sulfhydryl groups of biomolecules such as oligonucleotides, amino acids, peptides, and proteins. Additionally, using a range of biological substrates such as biotin, estradiol, and indole, we have designed luminescent rhenium(I) and iridium(III) polypyridine complexes as noncovalent probes for biological receptors. The interesting results generated from these studies have prompted us to investigate the possible applications of luminescent transition metal complexes in intracellular systems. Thus, in the past few years, we have developed an interest in the cytotoxic activity, cellular uptake, and bioimaging applications of these complexes. Additionally, we and other research groups have demonstrated that many transition metal complexes have facile cellular uptake and organelle-localization properties and that their cytotoxic activity can be readily controlled. For example, complexes that can target the nucleus, nucleolus, mitochondria, lysosomes, endoplasmic reticulum, and Golgi apparatus have been identified. We anticipate that this selective localization property can be utilized in the development of intracellular sensors and bioimaging reagents. Thus, we have functionalized luminescent rhenium(I) and iridium(III) polypyridine complexes with various pendants, including molecule-binding moieties, sugar molecules, bioorthogonal functional groups, and polymeric chains such as poly(ethylene glycol) and polyethylenimine, and examined their potentials as biological reagents. This Account describes our design of luminescent rhenium(I) and iridium(III) polypyridine complexes and explains how they can serve as a new generation of biological reagents for diagnostic and therapeutic applications.

Iridium(III) complexes as therapeutic and bioimaging reagents for cellular applications

There is an emerging interest in applying inorganic and organometallic transition metal complexes to biomolecular and cellular studies. The cytotoxic effects of these complexes on various cancer and normal cells have been examined. Many of these complexes display intense, long-lived, and environment-sensitive emission, rendering them useful live-cell imaging reagents. Of particular interest are iridium(III) complexes, which possess a diversity of molecular structures with intriguing biological activity and photophysical properties. In this review article, we summarize recent work using iridium(III) complexes as anticancer drugs and cellular imaging reagents. We focus on the cytotoxic activity, cellular uptake efficiency and mechanisms, and intracellular distribution properties of these complexes. Additionally, we describe the applications of luminescent iridium(III) complexes in intracellular sensing for ions and small molecules, gene-delivery, and cancer cell detection.

Luminescent Cyclometalated Iridium(III) Polypyridine Di-2-picolylamine Complexes: Synthesis, Photophysics, Electrochemistry, Cation Binding, Cellular Internalization, and Cytotoxic Activity

A series of luminescent cyclometalated iridium(III) polypyridine complexes containing a di-2-picolylamine (DPA) moiety [Ir(N^C)(2)(phen-DPA)](PF(6)) (phen-DPA = 5-(di-2-picolylamino)-1,10-phenanthroline) (HN^C = 2-phenylpyridine, Hppy (1a), 2-(4-methylphenyl)pyridine, Hmppy (2a), 2-phenylquinoline, Hpq (3a), 4-(2-pyridyl)benzaldehyde, Hpba (4a)) and their DPA-free counterparts [Ir(N^C)(2)(phen-DMA)](PF(6)) (phen-DMA = 5-(dimethylamino)-1,10-phenanthroline) (HN^C = Hppy (1b), Hmppy (2b), Hpq (3b), Hpba (4b)) have been synthesized and characterized, and their photophysical and electrochemical properties investigated. Photoexcitation of the complexes in fluid solutions at 298 K and in alcohol glass at 77 K resulted in intense and long-lived luminescence. The emission of the complexes has been assigned to a triplet metal-to-ligand charge-transfer ((3)MLCT) (dπ(Ir) → π*(N^N)) or triplet intraligand ((3)IL) (π → π*) (N^C) excited state and with substantial mixing of triplet amine-to-ligand charge-transfer ((3)NLCT) (n → π*) (N^N) character, depending on the identity of the cyclometalating and diimine ligands. Electrochemical measurements revealed an irreversible amine oxidation wave at ca. +1.1 to +1.2 V vs saturated calomel electrode, a quasi-reversible iridium(IV/III) couple at ca. +1.2 to +1.6 V, and a reversible diimine reduction couple at ca. -1.4 to -1.5 V. The cation-binding properties of these complexes have been studied by emission spectroscopy. Upon binding of zinc ion, the iridium(III) DPA complexes displayed 1.2- to 5.4-fold emission enhancement, and the K(d) values determined were on the order of 10(-5) M. Jobs plot analysis confirmed that the binding stoichiometry was 1:1. Additionally, selectivity studies showed that the iridium(III) DPA complexes were more sensitive toward zinc ion among various transition metal ions examined. Furthermore, the cytotoxicity of these complexes toward human cervix epithelioid carcinoma cells have been studied by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay and their cellular-uptake properties by inductively coupled plasma mass spectrometry and laser-scanning confocal microscopy.

Luminescent Dendritic Cyclometalated Iridium(III) Polypyridine Complexes: Synthesis, Emission Behavior, and Biological Properties

Luminescent dendritic cyclometalated iridium(III) polypyridine complexes [{Ir(N--C)(2)}(n)(bpy-n)](PF(6))(n) (HN--C = 2-phenylpyridine, Hppy, n = 8 (ppy-8), 4 (ppy-4), 3 (ppy-3); HN--C = 2-phenylquinoline, Hpq, n = 8 (pq-8), 4 (pq-4), 3 (pq-3)) have been designed and synthesized. The properties of these dendrimers have been compared to those of their monomeric counterparts [Ir(N--C)(2)(bpy-1)](PF(6)) (HN--C = Hppy (ppy-1), Hpq (pq-1)). Cyclic voltammetric studies revealed that the iridium(IV/III) oxidation and bpy-based reduction occurred at about +1.24 to +1.29 V and -1.21 to -1.27 V versus SCE, respectively, for all the complexes. The molar absorptivity of the dendritic iridium(III) complexes is approximately proportional to the number of [Ir(N--C)(2)(N--N)] moieties in one complex molecule. However, the emission lifetimes and quantum yields are relatively independent of the number of [Ir(N--C)(2)(N--N)] units, suggesting negligible electronic communications between these units. Upon photoexcitation, the complexes displayed triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(bpy-n)) emission. The interaction of these complexes with plasmid DNA has been investigated by agarose gel retardation assays. The results showed that the dendritic iridium(III) complexes, unlike their monomeric counterparts, bound to the plasmid, and the interaction was electrostatic in nature. The lipophilicity of all the complexes has been determined by reversed-phase high-performance liquid chromatography (HPLC). Additionally, the cellular uptake of the complexes by the human cervix epithelioid carcinoma (HeLa) cell line has been examined by inductively coupled plasma mass spectrometry (ICP-MS), laser-scanning confocal microscopy, and flow cytometry. Upon internalization, all the complexes were localized in the perinuclear region, forming very sharp luminescent rings surrounding the nuclei. Interestingly, in addition to these rings, HeLa cells treated with the dendritic iridium(III) complexes showed specific labeled compartments, which have been identified to be the Golgi apparatus. Furthermore, the cytotoxicity of these iridium(III) complexes has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay.