Julia R. Shakirova

Polymer micelles are established nanocarriers for hydrophobic molecules, but their use as hosts for sensors of physiological parameters remains underexplored. This work investigates the incorporation of phosphorescent transition metal complexes into block copolymer micelles and examines how composition and structure affect micellar stability and photophysical properties. The study also evaluates their potential as a novel class of oxygen nanosensors with lifetime‐based response. Micelles are prepared from block copolymers of poly(ethylene glycol) (PEG) with diverse hydrophobic blocks: polystyrene (PS ₃₅ ‐ b ‐PEG ₁₁₅ ), poly(methyl methacrylate) (PMMA ₅₅ ‐ b ‐PEG ₉₅ ), polybutadiene (PBd ₉₀ ‐ b ‐PEG ₁₁₅ ), polydimethylsiloxane (PDMS ₁₅ ‐ b ‐PEG ₁₁₅ ), and polycaprolactone (PCL ₄₅ ‐ b ‐PEG ₁₁₅ ). Six phosphorescent complexes, including three Pt(II) and three Ir(III) species, serve as payloads. Screening of “complex@block copolymer” pairs based on sedimentation stability, phosphorescence decay, and oxygen sensitivity identifies Ir3 @PCL ₄₅ ‐ b ‐PEG ₁₁₅ loaded with 2 wt.% of Ir3 as the optimal biosensing system. For this system, loading efficiency, size distribution, cross‐sensitivity to environmental parameters, Stern–Volmer plots, and MTT cytotoxicity are assessed. Confocal microscopy and phosphorescence lifetime imaging microscopy (PLIM) demonstrate efficient internalization into CHO‐K1 and HeLa cells. The sensor shows distinct lifetime responses under hypoxic, normoxic, and intermediate oxygenation, enabling quantitative intracellular oxygen sensing with pO ₂ resolution of 35–40 mm Hg in both cell monolayers and suspensions.

In this contribution, we present an efficient synthetic method for obtaining Re(I) mixed-ligand bis-diimine dicarbonyl complexes of general formula [Re(NN1)(NN_i)(CO)₂]OTf (NN1 = neocuproine), starting from bis-acetonitrile rhenium(I) precursor [Re(NN1)(CO)₂(NCMe)₂]OTf. This method allows introduction of different diimine ligands, which contain fused moieties and electron-withdrawing functional groups. All complexes obtained demonstrate deep red to near-infrared (NIR) emission both in solution and in the solid state, achieving 845 nm. The ³MLCT character of the emissive excited state was confirmed by TD-DFT calculations of the electronic structures for the complexes considered.

A series of five Pt(II) complexes Pt1 - Pt5 containing (N^∧N^∧C) pincer ligands and alkynyl-styrene were synthesized and characterized using mass spectrometry, NMR spectroscopy, and X-ray crystallography. The complexes exhibit phosphorescence in dilute dichloromethane solution from the excited state of mixed LLCT and MLCT character, which for all but one complex may be ascribed to emissions from isolated chromophore molecules. In contrast, in the solid state, emission occurs from the aggregated chromophores and displays a strong bathochromic shift into the NIR area, which is characteristic for aggregation-induced emission (AIE). The complexes readily take part in the RAFT polymerization reaction with polyvinylpyrrolidone to yield water-soluble amphiphilic block copolymers containing 4-6 complex molecules in the hydrophobic block. The copolymers are luminescent and display a solvent-dependent photophysical behavior. In organic solvents, their photophysical characteristics are nearly identical to those observed for the complexes in DCM, which is indicative of the absence of intramolecular aggregation in the polymeric chain. In aqueous media, the copolymer molecules form nanospecies of the micellar type, which exhibit AIE behavior due to intermolecular aggregation of the mononuclear chromophores. DFT and TD DFT calculations yield the emission parameters, which fit well with the suggested models of platinum chromophore behavior in solutions, solid state, and in the chains of block copolymers.

The idea of preparation a water‐soluble Pt‐containing AIEgen was successfully realized by direct reversible addition‐fragmentation transfer copolymerization of a Pt(II) complex (LPtPV) containing a vinyl group and polyvinylpyrrolidone (p(VP)). The resulting block‐copolymer p(VP‐b‐LPtPV) containing 5–8 Pt(II) chromophores exhibits intriguing photophysical properties—strong solvent and concentration dependence of absorption and emission characteristics. Various physicochemical and analytical methods (NMR spectroscopy, XRD analysis, ESI‐MS, AUC, DLS, ICP‐OES, GPC, viscometry, TEM) were used to characterize the initial complex, its binuclear analogs, p(VP) and p(VP‐b‐LPtPV). The obtained data indicate that the photophysical properties of the latter are dictated by the type of aggregation process rather than solvatochromic effects. It is shown that at low concentration in organic solvents, the platinum chromophores aggregation is either absent (dimethylformamide) or occurs predominantly at intramolecular level (MeCN), whereas in aqueous media, p(VP‐b‐LPtPV) readily aggregates into micellar‐type nanoparticles with a hydrophilic p(VP) corona and a hydrophobic Pt‐containing core, in which strong intra‐ and intermolecular Pt···Pt and/or π···π interactions result in a significant red shift of absorption and emission down to 600 and 816 nm, respectively. Despite of emission shift into NIR area where emission is commonly quenched by nonradiative vibrational relaxation, an increase in the emission quantum yield occurs in complete agreement with the typical aggregation‐induced emission (AIE) emitters’ behavior. Quantum mechanics/molecular mechanics simulations of aggregation processes also confirm the trends in the relationship between aggregation mode and photophysical behavior, particularly, in the variations of energy gaps between the ground state of the AIEgens and their excited singlet and triplet states.

The idea of preparation a water-soluble Pt-containing AIEgen successfully realized by direct RAFT copolymerization of a Pt(II) complex ( LPtPV ) containing a vinyl group and polyvinylpyrrolidone ( p(VP) ). The resulting block-copolymer p(VP- b -LPtPV) containing 5-8 Pt(II) chromophores exhibits intriguing photophysical properties - strong solvent and concentration dependence of absorption and emission characteristics. Various physicochemical and analytical methods (NMR spectroscopy, XRD analysis, ESI-MS, AUC, DLS, ICP-OES, GPC, viscometry, TEM) were used to characterize the initial complex, its binuclear analogues, p(VP) and p(VP- b -LPtPV) . The obtained data indicate that the photophysical properties of the latter are dictated by the type of aggregation process rather than solvatochromic effects. It is shown that at low concentration in organic solvents the platinum chromophores aggregation is either absent (DMF) or occurs predominantly at intramolecular level (MeCN), whereas in aqueous media p(VP- b -LPtPV) readily aggregates into micellar-type nanoparticles with a hydrophilic p(VP) corona and a hydrophobic Pt-containing core, in which strong intra- and intermolecular Pt···Pt and/or π···π interactions result in a significant redshift of absorption and emission down to 600 nm and 816 nm, respectively. Despite of emission shift into NIR area where it is commonly quenched by nonradiative vibrational relaxation increase in emission quantum yield occurs in complete agreement with typical features of AIE emitters. Quantum mechanics/molecular mechanics simulations of aggregation processes also confirm the trends in the relationship between aggregation mode and photophysical behavior, particularly, in the variations of energy gaps between the ground state of the AIEgens and their excited singlet and triplet states.

A series of structurally similar trinuclear macrocyclic copper(I) and silver(I) pyrazolate complexes bearing various short-bite diphosphine R₂PCH(R')PR₂ ligands are reported. Upon diphosphine coordination, the planar geometry of the initial complexes undergoes bending along the line between two metal atoms coordinated to the phosphorus moieties. The complexes based on dcpm ligands (R = cyclohexyl, R' = H, Ph) do not exhibit dynamic behavior in solution at room temperature on the ³¹P NMR time scale as it was previously observed for similar trinuclear copper complexes bearing the dppm (R = Ph, R' = H) scaffold. All copper(I) complexes exhibit thermally activated delayed fluorescence (TADF) behavior in the solid state. Importantly, the use of aliphatic substituents on the phosphorus atoms instead of aromatic ones leads to an almost double increase in the quantum efficiency (Φ_PL) of photoluminescence by eliminating nonradiative decay from the ³LC^Ph states of the dppm aromatic rings. The higher donating ability of the substituents in the pyrazolate ligand (CF₃ vs CH₃) lowers the energy of the metal-centered excited state, allowing for a significant metal impact on the T₁ state. Finally, the Ag(I) complex displays an emission efficiency of approximately 14%, being the highest among known trinuclear silver(I) pyrazolate homometallic derivatives.

Monitoring of intracellular pH is of great importance since deviation of this parameter from the "normal" magnitudes can be considered as an indicator of various pathologies. Thus, the development of new efficient and biocompatible sensors suitable for application in biological systems and capable of quantitative pH estimation remains an urgent chemical task. Herein, we report the synthesis of a series of phosphorescent rhenium [Re(NN)(CO)₂(PR₃)₂]⁺ complexes based on the NN diimine ligands containing pH-responsive carboxylic groups and styrene-containing phosphine ligands. The complexes, which display the highest pH sensitivity, were copolymerized with polyvinylpyrrolidone using the RAFT protocol to impart water solubility and to protect the chromophores from interaction with molecular oxygen. The resulting copolymers show an emission lifetime response onto pH variations in the physiological range. Cellular experiments with Chinese hamster ovary cells (CHO-K1) reveal easy internalization of the probes in cell culture and an approximately uniform distribution in cells, with some preference for location in acidic compartments (late endosomes and lysosomes). Using nigericin to homogenize intra- and extracellular pH, we built a calibration of lifetime versus pH in live CHO-K1 cells. Analysis of the phosphorescence lifetime imaging microscopy (PLIM) data confirms the applicability of the obtained sensors for monitoring the intracellular pH in cell cultures.

In the present report, a novel dual pH‐O₂ sensor based on covalent conjugate of rhodamine 6G and cyclometalated iridium complex with poly(vinylpyrrolidone‐block‐vinyltetrazole) copolymer is reported. In model physiological solutions the sensor chromophores display independent phosphorescent and fluorescent lifetime responses onto variations in oxygen concentration and pH, respectively. Colocalization studies on Chinese hamster ovary cells demonstrate the preferential localization in endosomes and lysosomes. The fluorescent lifetime imaging microscopy‐phosphorescent lifetime imaging microscopy (FLIM‐PLIM) experiments show that the phosphorescent O₂ sensor provides unambiguous information onto hypoxia versus normoxia cell status as well as semi‐quantitative data on the oxygen concentration in cells in between these two states. However, the results of FLIM measurements indicate that dynamic lifetime interval of the sensor (≈0.5 ns between pH values 5.0 and 8.0) is insufficient even for qualitative estimation of pH in living cells because half‐width of lifetime distribution in the studied samples is higher than the sensor dynamic interval. Nevertheless, the variations in rhodamine emission intensity are much higher and allow rough discrimination of acidic and neutral cell conditions. Thus, the results of this study indicate that the suggested approach to the design of dual pH‐O₂ sensors makes possible to prepare the biocompatible and water‐soluble conjugate with fast cellular uptake.