Clive Yik-Sham Chung

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.

Proof-of-principle concept for label-free detection of glucose and α-glucosidase activity through the electrostatic assembly of alkynylplatinum(II) terpyridyl complexes.

A two-component platinum(II) complex-polymer ensemble has been demonstrated for label-free spectroscopic detection of glucose and α-glucosidase activity, based on the electrostatic assembly of cationic platinum(II) complex molecules onto a glucose-bound anionic polymer.

Selective label-free detection of G-quadruplex structure of human telomere by emission spectral changes in visible-and-NIR region under physiological condition through the FRET of a two-component PPE-SO3−–Pt(II) complex ensemble with Pt⋯Pt, electrostatic and π–π interactions

The formation of polymer–metal complex aggregates and the FRET between PPE-SO3− and several water-soluble cationic alkynylplatinum(II) complexes are revealed from UV-vis, steady-state emission and time-resolved emission decay studies. From the Stern–Volmer plots, [Pt{tpy(C6H4CH2NMe3-4)-4′}(CCC6H5)](OTf)2 (2) is found to be the most efficient quencher of PPE-SO3− at both low and high concentrations. This has been ascribed to its low steric bulkiness and the stronger interactions with PPE-SO3−, and hence the largest association constant with PPE-SO3−, as well as the largest Forster radius, R0, among the complexes studied. The PPE-SO3−–2 ensemble has been employed in the detection of human telomere in aqueous buffer solution (50 mM KH2PO4, pH 6.8) and found to have better selectivity than the ensemble containing [Pt(tpy)(CCC6H4CH2NMe3-4)](OTf)2 (1), which has a smaller association constant with PPE-SO3− and R0 value than 2. By modulation of the aggregation/deaggregation of the polymer–metal complex aggregates and hence the FRET from the PPE-SO3− donor to the aggregated forms of 2 as acceptor, the PPE-SO3−–2 ensemble has been demonstrated for the sensitive and selective label-free detection of human telomere via the monitoring of emission spectral changes over the visible-NIR region. Ratiometric emission of PPE-SO3−–2 ensemble at 620 and 795 nm has been shown to distinguish the G-quadruplex structure formed by human telomeric DNA from those of other G-quadruplex-forming sequences.

Dual pH‐ and Temperature‐Responsive Metallosupramolecular Block Copolymers with Tunable Critical Micelle Temperature by Modulation of the Self‐Assembly of NIR‐Emissive Alkynylplatinum(II) Complexes Induced by Changes in Hydrophilicity and Electrostatic Effects

Terpyridylplatinum(II)-based metallosupramolecular triblock copolymers with hydrophilic alkynyl ligands have been synthesised and characterised. As a result of the intrinsic properties of Pluronics, reversible temperature-induced micellisation occurred at high temperature leading to aggregation of the platinum(II) complex moieties through Pt⋅⋅⋅Pt and π-π interactions, resulting in significant UV/Vis absorption and near-infrared (NIR) emission spectral changes. The critical micelle temperatures of the complexes were found to vary from 21 to 30 °C due to differences in the hydrophilicity of the alkynyl ligands and the electrostatic repulsions between the positively charged platinum(II) complex moieties. One of the complexes with pH-responsive CH2NMe2 groups on the alkynyl ligand was found to show NIR emission that is sensitive to both pH and temperature. Such dual-responsive behaviour has been ascribed to the modulation of the self-assembly of the complex moieties by temperature-induced micellisation and the changes in the hydrophilicity as well as electrostatic interactions upon protonation/deprotonation of the CH2NMe2 groups on the alkynyl ligand.

Reversible thermo-responsive luminescent metallo-supramolecular triblock copolymers based on platinum(II) terpyridyl chromophores with unusual aggregation behaviour and red-near-infrared (NIR) emission upon heating

Two platinum(II) terpyridyl-based metallo-supramolecular triblock copolymers, [ClPt(tpy)PEO-PPO-PEO(tpy)PtCl](OTf)(2) (1) and [(Ph-C≡C)Pt(tpy)PEO-PPO-PEO(tpy)Pt(C≡C-Ph)](OTf)(2) (2), have been synthesized and characterized. The two complexes were found to aggregate with PtPt and/or π-π interactions at high temperature, which have not been reported so far, as revealed by UV/Vis absorption, emission and (1)H NMR study. This is due to the formation of spherical micelles driven by the PEO-PPO-PEO copolymers at temperatures above the critical micelle temperature, which was confirmed by TEM and DLS. The red-near-infrared (NIR) emission of the complexes can be switched on and off by at least ten cycles of heating and cooling, suggesting that the micellization was highly reversible.

Supramolecular Assembly of Achiral Alkynylplatinum(II) Complexes and Carboxylic β-1,3-Glucan into Different Helical Handedness Stabilized by Pt⋅⋅⋅Pt and/or π-π Interactions

Two-component ensembles of alkynylplatinum(II) terpyridine (tpy) complexes and carboxylic β-1,3-glucan (CurCOOH) have been investigated by using spectroscopic and microscopic techniques, as well as time-dependent UV/Vis absorption and circular dichroism (CD) experiments. Microscopic images of [Pt(tpy){C≡CC6 H4 (CH2 NMe3 -4)}](OTf)2 (1) have revealed spherical nanostructures, whereas helical fibrous structures of different lengths, depending on the concentration of complex 1 and CurCOOH, were observed. The helical assemblies have been found to show low-energy metal-metal-to-ligand charge transfer (MMLCT) absorption and triplet MMLCT ((3) MMLCT) emission, which are indicative of Pt⋅⋅⋅Pt and/or π-π interactions between the complex 1 molecules. Interestingly, the ensemble has been demonstrated to show different handedness and even a change in handedness over time under different experimental conditions. Low temperatures, low concentrations of CurCOOH, high concentrations of complex 1, or successive addition of CurCOOH into complex 1 solution favor the formation of right-handed helical assemblies, whereas high temperatures, high concentrations of CurCOOH, low concentrations of complex 1, or single-batch addition of CurCOOH into complex 1 solution result in a fast chiroptical inversion of the ensemble solution, giving rise to the left-handed helical assemblies as the dominant species. The results have been rationalized by considering the competing kinetically and thermodynamically controlled assembly-elongation of the ensemble, which leads to the formation of right-handed and left-handed helical assemblies, respectively. The change in the handedness of the ensemble has been demonstrated to stem from the formation of two-component assemblies with supramolecular interactions, in contrast to the template- induced chiral amplification commonly observed in other systems.

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.

Simple and Versatile Preparation of Luminescent Amphiphilic Platinum(II)‐containing Polystyrene Complexes With Transformable Nanostructures Assisted by Pt⋅⋅⋅Pt and π–π Interactions

Platinum(II)-containing polystyrene (PS) complexes have been synthesized by dehydrohalogenation of α-alkyne-PS and chloroplatinum(II) precursors with different functionalities on the terpyridine ligands. Through modulation of the hydrophilicity/hydrophobicity of the terpyridine ligands and hence the overall amphiphilicity of the complexes, the complexes can undergo self-assembly into various superstructures with remarkable luminescence properties in different solution mixtures, as revealed by electron microscopy, UV/Vis absorption and emission spectroscopy. Pt⋅⋅⋅Pt and/or π-π interactions among the platinum(II) terpyridine moieties are found to play substantial roles in the stabilization of the superstructures and the turn-on/off of the triplet metal-metal-to-ligand charge transfer (3 MMLCT) emission of the complexes.

Versatile Histochemical Approach to Detection of Hydrogen Peroxide in Cells and Tissues Based on Puromycin Staining

Hydrogen peroxide (H2O2) is a central reactive oxygen species (ROS) that contributes to diseases from obesity to cancer to neurodegeneration but is also emerging as an important signaling molecule. We now report a versatile histochemical approach for detection of H2O2 that can be employed across a broad range of cell and tissue specimens in both healthy and disease states. We have developed a first-generation H2O2-responsive analogue named Peroxymycin-1, which is based on the classic cell-staining molecule puromycin and enables covalent staining of biological samples and retains its signal after fixation. H2O2-mediated boronate cleavage uncages the puromycin aminonucleoside, which leaves a permanent and dose-dependent mark on treated biological specimens that can be detected with high sensitivity and precision through a standard immunofluorescence assay. Peroxymycin-1 is selective and sensitive enough to image both exogenous and endogenous changes in cellular H2O2 levels and can be exploited to profile resting H2O2 levels across a panel of cell lines to distinguish metastatic, invasive cancer cells from less invasive cancer and nontumorigenic counterparts, based on correlations with ROS status. Moreover, we establish that Peroxymycin-1 is an effective histochemical probe for in vivo H2O2 analysis, as shown through identification of aberrant elevations in H2O2 levels in liver tissues in a murine model of nonalcoholic fatty liver disease, thus demonstrating the potential of this approach for studying disease states and progression associated with H2O2. This work provides design principles that should enable development of a broader range of histochemical probes for biological use that operate via activity-based sensing.