Steve Po-Yam Li

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.

Induced self-assembly and disassembly of water-soluble alkynylplatinum(II) terpyridyl complexes with “switchable” near-infrared (NIR) emission modulated by metal–metal interactions over physiological pH: demonstration of pH-responsive NIR luminescent probes in cell-imaging studies

Water-soluble alkynylplatinum(II) terpyridine complexes, [Pt{tpy(C6H4CH2NMe3-4)-4′}(CC–Ar)](OTf)2 [Ar = C6H3–(OH)2-3,5 (1), C6H4OH-4 (2), C6H3–(OMe)2-3,5 (3)], have been synthesized and characterized. The photophysical and electrochemical properties of the complexes have been studied. Complex 1 has been found to undergo aggregation at low pHs, leading to metal–metal and/or π–π interactions and the emergence of a triplet metal-metal-to-ligand charge transfer (3MMLCT) emission in the near-infrared (NIR) region, the intensity of which has been enhanced 1350-fold over that at physiological pH. Such ‘switchable’ NIR emission of complex 1 was employed in cell-imaging experiments. The pH response of the 3MMLCT emission of complex 1 in cellular compartments has been studied using experiments with fixed Madin–Darby canine kidney (MDCK) cells, while live cell-imaging experiments revealed that complex 1 could function as a NIR luminescent probe for the tracking of the location of acidic organelles such as lysosomes.

Utilization of the photophysical and photochemical properties of phosphorescent transition metal complexes in the development of photofunctional cellular sensors, imaging reagents, and cytotoxic agents

Although the interactions of phosphorescent transition metal complexes with biological molecules such as DNA and proteins have been extensively investigated, there is a rapidly emerging area of research that focuses specifically on the cellular uptake of phosphorescent transition metal complexes and their applications as cellular reagents such as biosensors for ions and small molecules, and bioimaging reagents for organelles and tissues. This interest stems from the rich phosphorescence properties, and in some cases the controllable photochemical reactivity of transition metal complexes, which complement fluorescent organic dyes and luminescent lanthanide chelates. In this review article, we briefly introduce the fundamental photophysical properties of phosphorescent transition metal complexes and explain the reasons why the complexes are attractive candidates as cellular reagents. Very recent applications of these complexes in biosensing and imaging in an intracellular environment using different strategies are also summarized. Additionally, phosphorescent transition metal complexes with potential therapeutic applications are highlighted in this article.

Design of cyclometalated iridium(III) polypyridine complexes as luminescent biological labels and probes

The interesting emission properties of cyclometalated iridium(III) polypyridine complexes, originated from a range of excited states, have been well documented. The intense and long-lived emission of these complexes has been exploited in various areas of research including photovoltaic cells, chemosensors, and light-emitting devices. Additionally, there is an emerging interest in the applications of these luminescent complexes in various biological studies. In this paper, we summarize our recent work on the utilization of luminescent cyclometalated iridium(III) polypyridine complexes as biomolecular and cellular probes.

Installing an additional emission quenching pathway in the design of iridium(III)-based phosphorogenic biomaterials for bioorthogonal labelling and imaging

We report the synthesis, characterization, photophysical and electrochemical behaviour and biological labelling applications of new phosphorogenic bioorthogonal probes derived from iridium(III) polypyridine complexes containing a 1,2,4,5-tetrazine moiety. In contrast to common luminescent cyclometallated iridium(III) polypyridine complexes, these tetrazine complexes are almost non-emissive due to effective Förster resonance energy transfer (FRET) and/or photoinduced electron transfer (PET) from the excited iridium(III) polypyridine unit to the appended tetrazine moiety. However, they exhibited significant emission enhancement upon reacting with (1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) (ca. 19.5-121.9 fold) and BCN-modified bovine serum albumin (BCN-BSA) (ca. 140.8-1133.7 fold) as a result of the conversion of the tetrazine unit to a non-quenching pyridazine derivative. The complexes were applied to image azide-modified glycans in live cells using a homobifunctional crosslinker, 1,13-bis((1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonylamino)-4,7,10-trioxatridecane (bis-BCN).

Synthesis and Electrochemical, Photophysical, and Self-Assembly Studies on Water-Soluble pH-Responsive Alkynylplatinum(II) Terpyridine Complexes

A series of water-soluble pH-responsive alkynylplatinum(II) terpyridine complexes have been synthesized and characterized. The electronic absorption, emission, and electrochemical properties of the complexes have been studied. The self-assembly processes of representative complexes in aqueous media, presumably through Pt···Pt and/or π-π interactions, have been investigated by concentration- and temperature-dependent UV-vis absorption measurements and dynamic light scattering experiments. Interestingly, some of the complexes have been found to undergo induced self-assembly and disassembly in aqueous media through modulation of the pH value of the solutions, resulting in remarkable UV-vis absorption and emission spectral changes. The emission spectral changes have been rationalized by the change in the hydrophilicity of the complexes, electrostatic repulsion among the complex molecules, and/or the extent of photoinduced electron transfer (PET) quenching upon protonation/deprotonation of the pH-responsive groups on the complexes. By simple modifications of the chemical structures of the complexes, induced self-assembly/disassembly of the complexes can occur at different and/or multiple pH regions, thus allowing the probing of changes at the desired pH region by triplet metal-metal-to-ligand charge-transfer emission of the complexes in the near-infrared (NIR) region. Fixed-cell imaging experiments have further demonstrated the potential of this class of complexes as pH-responsive NIR luminescent probes in vitro, while the NIR emissions of the complexes from live cells have been found to show good differentiation of acidic organelles such as lysosomes from other cellular compartments.

Design of a Water-Soluble Hybrid Nanocomposite of CdTe Quantum Dots and an Iridium Complex for Photoinduced Charge Transfer

We report the use of an organo-iridium dye conjugated with a water-soluble copolyethylenimine polymer, allowing the hybrid material to be used in combination with thioacid-coated CdTe quantum dots in an aqueous medium. When they are combined, hot carrier cooling observed in the pure quantum-dot case is heavily suppressed indicating fast (ps) electron transfer on a timescale that competes with non-radiative (Auger) relaxation.

Chapter 5:Luminescent Transition-Metal Complexes as Biomolecular and Cellular Probes

The photophysical and photochemical properties of luminescent transition-metal complexes have been attracting much interest for several decades.1 Many of these properties would allow the complexes to be exploited as useful biological labels and probes; for example, the emission of many transition-me...

Luminescent iridium(III) polypyridine PEG complexes: Synthesis, photophysical, and biological properties

We report the synthesis, characterization, and photophysical properties of a class of luminescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N⁁C)<inf>2</inf>(bpy-CONH-PEG<inf>n</inf>)](PF<inf>6</inf>) (HN⁁C = Hppy (1a), HN⁁C = Hpq (2a), HN⁁C = Hpba (3a)). The discrete PEG complexes [Ir(N⁁C)<inf>2</inf>(bpy-CONH-dPEG<inf>24</inf>)](PF<inf>6</inf>) (HN⁁C = Hppy (1b), HN⁁C = Hpq (2b), HN⁁C = Hpba (3b)) and the PEG-free complexes [Ir(N⁁C)<inf>2</inf>(bpy-CONH-Et)](PF<inf>6</inf>) (HN⁁C = Hppy (1c), HN⁁C = Hpq (2c), HN⁁C = Hpba (3c)) have also been prepared for comparison studies. The lipophilicity of the complexes has been determined by shake-flask method. We have also investigated the cytotoxicity and cellular uptake of these complexes by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and laser-scanning confocal microscopy, respectively. The results illustrated that the nondiscrete PEG complexes can act as biological imaging reagents with low cytotoxicity. Co-localization experiments using an endocytic marker Alexa Fluor 633-labeled transferrin revealed the involvement of endosomes in the uptake of the complexes by the human cervix epithelioid carcinoma (HeLa) cells. Since the aldehyde groups of the pba complexes 3a-c are reactive toward primary amines, they have been conjugated to bovine serum albumin (BSA) and the resulting conjugates have been isolated, purified, and its photophysical properties studied. Complexes 3a and 3b serve as new luminescent PEGylation reagents.