Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)₂(IP-4T)](PF₆)₂ with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1 , comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived ³ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug.     

Excited-State THz Vibrations in Aggregates of PtII Complexes Contribute to the Enhancement of Near-Infrared Emission Efficiencies**

The exploration of deactivation mechanisms for near-infrared(NIR)-emissive organic molecules has been a key issue in chemistry, materials science and molecular biology. In this study, based on transient absorption spectroscopy and transient grating photoluminescence spectroscopy, we demonstrate that the aggregated Pt^II complex 4H (efficient NIR emitter) exhibits collective out-of-plane motions with a frequency of 32 cm⁻¹ (0.96 THz) in the excited states. Importantly, similar THz characteristics were also observed in analogous Pt^II complexes with prominent NIR emission efficiency. The conservation of THz motions enables excited-state deactivation to proceed along low-frequency vibrational coordinates, contributing to the suppression of nonradiative decay and remarkable NIR emission. These novel results highlight the significance of excited-state vibrations in nonradiative processes, which serve as a benchmark for improving device performance.     

Conformational Dynamics in the Core of Human Y145Stop Prion Protein Amyloid Probed by Relaxation Dispersion NMR

Microsecond to millisecond timescale backbone dynamics of the amyloid core residues in Y145Stop human prion protein (PrP) fibrils were investigated by using ¹⁵N rotating frame (R_1ρ) relaxation dispersion solid-state nuclear magnetic resonance spectroscopy over a wide range of spin-lock fields. Numerical simulations enabled the experimental relaxation dispersion profiles for most of the fibril core residues to be modelled by using a two-state exchange process with a common exchange rate of 1000 s⁻¹, corresponding to protein backbone motion on the timescale of 1 ms, and an excited-state population of 2 %. We also found that the relaxation dispersion profiles for several amino acids positioned near the edges of the most structured regions of the amyloid core were better modelled by assuming somewhat higher excited-state populations (∼5–15 %) and faster exchange rate constants, corresponding to protein backbone motions on the timescale of ∼100–300 μs. The slow backbone dynamics of the core residues were evaluated in the context of the structural model of human Y145Stop PrP amyloid.     

Photo-induced energy and charge transfer dynamics in Y6 dimers

Y6 (BTP-4F) is one of the novel non-fullerene acceptors and its photo-physics significantly affects the efficiency of organic solar cells. Here, the photo-induced energy and charge transfer (CT) dynamics in four typical dimers (Y, C, S1, and S2)-TYPE from Y6 films are revealed by combining electronic structure theory calculations, rate theories, and quantum dynamics simulations. The rate theories show that in ground-state CT processes the Y-TYPE is bipolar with the largest rate among all dimers, and in excitation energy transfer the triplet rates are about 10⁵ smaller than the singlet ones, however, the singlet rates can reach 10¹³s⁻¹, which may lead to the rate theories invalid. The stochastic Schrödinger equation based on the diabatic Hamiltonian is thus adopted to reveal excited-state dynamics. The results show that three of the four dimers are H-aggregate except for S1-TYPE with J-aggregate property. However, these J/H-aggregate properties are excited-state dependent, for instance, the Y-TYPE becomes J-aggregate in the second excited-state. Furthermore, CT states are strongly mixed with the first two excited states, which can dramatically impact the energy transfer. Indeed, the dynamic simulations clarify that the excited-state energy relaxation mediated by CT states can be performed in the first 20 fs, and the CT-state population is even non-negligible in the quasi-stationary distribution.     

Phosphorescent Cationic Iridium (III) Complexes with 1,3,4-Oxadiazole Cyclometalating Ligands:Solvent-Dependent Excited-State Dynamics

To elucidate the nature of low-lying triplet states and the effect of ligand modifications on the excited-state properties of functional cationic iridium complexes,the solventdependent excited-state dynamics of two phosphorescent cationic iridium (III) complexes,namely[Ir (dph-oxd)₂(bpy)]PF₆( 1 ) and[Ir (dph-oxd)₂(pzpy)]PF₆( 2 ),were investigated by femtosecond and nanosecond transient absorption spectroscopy.Upon photoexcitation to the metal-to-ligand charge-transfer (MLCT) states,the excited-state dynamics shows a rapid process (τ=0.7-3 ps) for the formation of solvent stabilized ³MLCT states,which significantly depends on the solvent polarity for both 1 and 2 .Sequentially,a relatively slow process assigned to the vibrational cooling/geometrical relaxation and a long-lived phosphorescent emissive state is identified.Due to the different excited-state electronic structures regulated by ancillary ligands,the solvation-induced stabilization of the ³MLCT state in 1 is faster than that in 2 .The present results provide a better sight of excited-state relaxation dynamics of ligand-related iridium (III) complexes and solvation effects on triplet manifolds.     

Influence of the Linker Chemistry on the Photoinduced Charge-Transfer Dynamics of Hetero-dinuclear Photocatalysts

To optimize light-driven catalytic processes, light-mediated multi-electron transfer dynamics in molecular dyads need to be studied and correlated with structural changes focusing on the catalytically active metastable intermediates. Here, spectro-electrochemistry has been employed to investigate the structure-dependent photoelectron transfer kinetics in catalytically active intermediates of two Ru−Rh catalysts for light-driven NAD⁺ reduction. The excited-state reactivity of short-lived intermediates was studied along different photoreaction pathways by resonance Raman and time-resolved transient absorption spectro-electrochemistry with sub-picosecond time resolution under operando conditions. The results demonstrate, for the first time, how the bridging ligand serves as a (multi-)electron storage structure, mediates the strength of the electronic coupling of catalytic and photocenter and impacts the targeted electron transfer as well as parasitic electron-transfer kinetics.     

Nonradiative Excited-State Decay via Conical Intersection in Graphene Nanostructures

Chemical groups are known to tune the luminescent efficiencies of graphene-related nanomaterials, but some species, including the epoxide group (−COC−), are suspected to act as emission-quenching sites. Herein, by performing nonadiabatic excited-state dynamics simulations, we reveal a fast (within 300 fs) nonradiative excited-state decay of a graphene epoxide nanostructure from the lowest excited singlet (S₁) state to the ground (S₀) state via a conical intersection (CI), at which the energy difference between the S₁ and S₀ states is approximately zero. This CI is induced after breaking one C−O bond at the −COC− moiety during excited-state structural relaxation. This study ascertains the role of epoxide groups in inducing the nonradiative recombination of the excited electron-hole, providing important insights into the CI-promoted nonradiative de-excitations and the luminescence tuning of relevant materials. In addition, it shows the feasibility of utilizing nonadiabatic excited-state dynamics simulations to investigate the photophysical processes of the excited states of graphene nanomaterials.     

Time-Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE-Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA-BQ, by a one-step reaction. 4TPA-BQ presents aggregation-induced emission features. Owing to the aggregation-induced reactive oxygen species generated and a sufficiently small ΔE_ST, 4TPA-BQ shows a satisfactorily high ¹O₂ generation efficiency of 97.8 %. In vitro and in vivo experiments confirmed that 4TPA-BQ exhibited potent photodynamic antibacterial performance against ampicillin-resistant Escherichia coli with good biocompatibility in a short time (15 minutes). When the incubation duration persisted long enough (12 hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time-dependent fluorescence-guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA-BQ reveals new design principles for the implementation of efficient PSs in clinical applications.     

Spin–Orbit Charge-Transfer Intersystem Crossing (ISC) in Compact Electron Donor–Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents

Spin–orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield Φ_T=60 %) was observed, with a triplet state lifetime (τ_T=436 μs) much longer than that accessed with the conventional heavy atom effect (τ_T=62 μs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the ¹CT/³LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC₅₀=75 nm ), with a negligible dark toxicity (EC₅₀=78.1 μm ) compared with the conventional heavy atom PSs (dark toxicity, EC₅₀=6.0 μm, light toxicity, EC₅₀=4.0 nm ). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.     

Functional and Basis Set Dependence for Time-Dependent Density Functional Theory Trajectory Surface Hopping Molecular Dynamics: Cis-Azobenzene Photoisomerization

Within three functionals (TD-B3LYP, TD-BHandHLYP, and TD-CAM-B3LYP) in combination with four basis sets (3-21g, 6-31g, 6-31g(d), and cc-pvdz), global switching (GS) trajectory surface hopping molecular dynamics has been performed for cis-to-trans azobenzene photoisomerization up to the S₁(nπ*) excitation. Although all the combinations show artificial double-cone structure of conical intersection between ground and first excited states, simulated quantum yields and lifetimes are in good agreement with one another; 0.6 (±5%) and 40.5 fs (±10%) by TD-B3LYP, 0.5 (±10%) and 35.5 fs (±4%) by TD-BHandHLYP, and 0.44 (±9%) and 35.2 fs (±10%) by TD-CAM-B3LYP. By analyzing distributions of excited-state population decays, hopping spots, and typical trajectories with performance of 12 functional/basis set combinations, it has been concluded that functional dependence for given basis set is slightly more sensitive than basis set dependence for given functional. The present GS on-the-fly time-dependent density functional theory (TDDFT) trajectory surface hopping simulation can provide practical benchmark guidelines for conical intersection driven excited-state molecular dynamics simulation involving in large complex system within ordinary TDDFT framework. © 2019 Wiley Periodicals, Inc.     

Identification of Crucial Photosensitizing Factors to Promote CO2-to-CO Conversion

The sensitizing ability of a catalytic system is closely related to the visible-light absorption ability, excited-state lifetime, redox potential, and electron-transfer rate of photosensitizers (PSs), however it remains a great challenge to concurrently mediate these factors to boost CO₂ photoreduction. Herein, a series of Ir(III)-based PSs ( Ir-1 – Ir-6 ) were prepared as molecular platforms to understand the interplay of these factors and identify the primary factors for efficient CO₂ photoreduction. Among them, less efficient visible-light absorption capacity results in lower CO yields of Ir-1 , Ir-2 or Ir-4 . Ir-3 shows the most efficient photocatalytic activity among these mononuclear PSs due to some comprehensive parameters. Although the K_obs of Ir-3 is ≈10 times higher than that of Ir-5 , the CO yield of Ir-3 is slightly higher than that of Ir-5 due to the compensation of Ir-5 ’s strong visible-light-absorbing ability. Ir-6 exhibits excellent photocatalytic performance due to the strong visible-light absorption ability, comparable thermodynamic driving force, and electron transfer rate among these PSs. Remarkably, the CO₂ photoreduction to CO with Ir-6 can achieve 91.5 μmol, over 54 times higher than Ir-1 , and the optimized TON_C-1 can reach up to 28160. Various photophysical properties of the PSs were concurrently adjusted by fine ligand modification to promote CO₂ photoreduction.     

Time‐Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE‐Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA‐BQ, by a one‐step reaction. 4TPA‐BQ presents aggregation‐induced emission features. Owing to the aggregation‐induced reactive oxygen species generated and a sufficiently small ΔE_ST, 4TPA‐BQ shows a satisfactorily high ¹O₂ generation efficiency of 97.8 %. In vitro and in vivo experiments confirmed that 4TPA‐BQ exhibited potent photodynamic antibacterial performance against ampicillin‐resistant Escherichia coli with good biocompatibility in a short time (15 minutes). When the incubation duration persisted long enough (12 hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time‐dependent fluorescence‐guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA‐BQ reveals new design principles for the implementation of efficient PSs in clinical applications.     

The Effect of Biological Substrates on the Ultrafast Excited-state Dynamics of Zinc Phthalocyanine Tetrasulfonate in Solution

Zinc phthalocyanine tetrasulfonate (ZnPcS₄), a potential photosensitizer for photodynamic therapy (PDT), has been studied using femtosecond laser spectroscopy. The excited-state dynamics in water have been found to be fast (<80 ps) and dominated by intermolecular aggregation. Since the proposed mechanism for PDT is energy transfer from the triplet excited state of the photosensitizer to triplet O₂ creating singlet O₂, the short lifetime is expected to be unfavorable for producing singlet O₂. This leads to the suggestion that the presence of biological substrates may have an effect on the excited-state dynamics. To test this hypothesis, the lifetimes of the ex-cited states of ZnPcS₄ have been directly measured in the presence of a model membrane, n-hexadecyltrimethylammonium bromide (CTAB). The excited-state dynamics of ZnPcS₄ in buffer solutions and with human serum albumin (HSA) have also been measured. The presence of HSA and CTAB increases the excited-state lifetime significantly relative to that observed in water. The longer lifetime of ZnPcS4 in CTAB (>1 ns) indicates that the micellar surface favors monomer formation. By increasing the excited-state lifetime, the surface substantially in-creases the photosensitizing potential of ZnPcS₄.     

Green-Light Activation of Push–Pull Ruthenium(II) Complexes

Synthesis, characterization, electrochemistry, and photophysics of homo- and heteroleptic ruthenium(II) complexes [Ru(cpmp)₂]²⁺ ( 2²⁺ ) and [Ru(cpmp)(ddpd)]²⁺ ( 3²⁺ ) bearing the tridentate ligands 6,2’’-carboxypyridyl-2,2’-methylamine-pyridyl-pyridine (cpmp) and N,N’-dimethyl-N,N’-dipyridin-2-ylpyridine-2,6-diamine (ddpd) are reported. The complexes possess one ( 3²⁺ ) or two ( 2²⁺ ) electron-deficient dipyridyl ketone fragments as electron-accepting sites enabling intraligand charge transfer (ILCT), ligand-to-ligand charge transfer (LL'CT) and low-energy metal-to-ligand charge transfer (MLCT) absorptions. The latter peak around 544 nm (green light). Complex 2²⁺ shows ³MLCT phosphorescence in the red to near-infrared spectral region at room temperature in deaerated acetonitrile solution with an emission quantum yield of 1.3 % and a ³MLCT lifetime of 477 ns, whereas 3²⁺ is much less luminescent. This different behavior is ascribed to the energy gap law and the shape of the parasitic excited ³MC state potential energy surface. This study highlights the importance of the excited-state energies and geometries for the actual excited-state dynamics. Aromatic and aliphatic amines reductively quench the excited state of 2²⁺ paving the way to photocatalytic applications using low-energy green light as exemplified with the green-light-sensitized thiol–ene click reaction.     

Photophysics of Anionic Bis(4H-imidazolato)CuI Complexes

In this paper, the photophysical behavior of four panchromatically absorbing, homoleptic bis(4H-imidazolato)Cu^I complexes, with a systematic variation in the electron-withdrawing properties of the imidazolate ligand, were studied by wavelength-dependent time-resolved femtosecond transient absorption spectroscopy. Excitation at 400, 480, and 630 nm populates metal-to-ligand charge transfer, intraligand charge transfer, and mixed-character singlet states. The pump wavelength-dependent transient absorption data were analyzed by a recently established 2D correlation approach. Data analysis revealed that all excitation conditions yield similar excited-state dynamics. Key to the excited-state relaxation is fast, sub-picosecond pseudo-Jahn-Teller distortion, which is accompanied by the relocalization of electron density onto a single ligand from the initially delocalized state at Franck-Condon geometry. Subsequent intersystem crossing to the triplet manifold is followed by a sub-100 ps decay to the ground state. The fast, nonradiative decay is rationalized by the low triplet-state energy as found by DFT calculations, which suggest perspective treatment at the strong coupling limit of the energy gap law.     

DNA-Targeting RuII-Polypyridyl Complex with a Long-Lived Intraligand Excited State as a Potential Photodynamic Therapy Agent

Subtle ligand modifications on Ru^II-polypyridyl complexes may result in different excited-state characteristics, which provides the opportunity to tune their photo-physicochemical properties and subsequently change their biological functions. Here, a DNA-targeting Ru^II-polypyridyl complex (named Ru1 ) with highly photosensitizing ³IL (intraligand) excited state was designed based on a classical DNA-intercalator [Ru(bpy)₂(dppz)] ⋅ 2 PF₆ by incorporation of the dppz (dipyrido[3,2-a:2′,3′-c]phenazine) ligand tethered with a pyrenyl group, which has four orders of magnitude higher potency than the model complex [Ru(bpy)₂(dppz)] ⋅ 2 PF₆ upon light irradiation. This study provides a facile strategy for the design of organelle-targeting Ru^II-polypyridyl complexes with dramatically improved photobiological activity.     

Coherent Vibration and Femtosecond Dynamics of the Platinum Complex Oligomers upon Intermolecular Bond Formation in the Excited State

Femtosecond time-resolved absorption and picosecond time-resolved emission measurements were carried out for highly concentrated aqueous solutions of K₂[Pt(CN)₄] to investigate excited-state dynamics of the [Pt(CN)₄²⁻] oligomers formed with metallophilic interactions. Time-resolved absorption spectra exhibit complicated dynamics that are represented with five time constants. Among them, the 90-ps and 400-ps dynamics were assigned to the S₁ → T₁ intersystem crossing of the trimer and tetramer coexisting in the solution by comparison with the fluorescence decays. Clear oscillations of transient absorption were observed in the first few picoseconds, and the frequency-detected-wavelength 2D analysis revealed that the 135-cm⁻¹ and 65-cm⁻¹ oscillations arise from the Pt–Pt stretch motions of the S₁ trimer and S₁ tetramer, respectively. The obtained time-resolved spectroscopic data provide a clear view of the excited-state dynamics of the [Pt(CN)₄²⁻] oligomers in the femto-/picosecond time region.     

Monitoring intracellular pH fluctuation with an excited-state intramolecular proton transfer-based ratiometric fluorescent sensor

Intracellular pH is a key parameter related to various biological and pathological processes. In this study, a ratiometric pH fluorescent sensor ABTT was developed harnessing the amino-type excited-state intramolecular proton transfer (ESIPT) process. Relying on whether the ESIPT proceeds normally or not, ABTT exhibited the yellow fluorescence in acidic media, or cyan fluorescence in basic condition. According to the variation, ABTT behaved as a promising sensor which possessed fast and reversible response to pH change without interference from the biological substances, and exported a steady ratiometric signal (I₄₇₈/I₅₄₆). Moreover, due to the ESIPT effect, large Stokes shift and high quantum yield were also exhibited in ABTT. Furthermore, ABTT was applied for monitoring the pH changes in living cells and visualizing the pH fluctuations under oxidative stress successfully. These results elucidated great potential of ABTT in understanding pH-dependent physiological and pathological processes.     

Solvent-Dependent Stabilization of a Charge Transfer State is the Key to Ultrafast Triplet State Formation in an Epigenetic DNA Nucleoside

2’-Deoxy-5-formylcytidine (5fdCyd), a naturally occurring nucleoside found in mammalian DNA and mitochondrial RNA, exhibits important epigenetic functionality in biological processes. Because it efficiently generates triplet excited states, it is an endogenous photosensitizer capable of damaging DNA, but the intersystem crossing (ISC) mechanism responsible for ultrafast triplet state generation is poorly understood. In this study, time-resolved mid-IR spectroscopy and quantum mechanical calculations reveal the distinct ultrafast ISC mechanisms of 5fdCyd in water versus acetonitrile. Our experiment indicates that in water, ISC to triplet states occurs within 1 ps after 285 nm excitation. PCM-TD-DFT computations suggest that this ultrafast ISC is mediated by a singlet state with significant cytosine-to-formyl charge-transfer (CT) character. In contrast, ISC in acetonitrile proceeds via a dark ¹nπ* state with a lifetime of ∼3 ps. CT-induced ISC is not favored in acetonitrile because reaching the minimum of the gateway CT state is hampered by intramolecular hydrogen bonding, which enforces planarity between the aldehyde group and the aromatic group. Our study provides a comprehensive picture of the non-radiative decay of 5fdCyd in solution and new insights into the factors governing ISC in biomolecules. We propose that the intramolecular CT state observed here is a key to the excited-state dynamics of epigenetic nucleosides with modified exocyclic functional groups, paving the way to study their effects in DNA strands.     

Membrane-Anchoring Photosensitizer with Aggregation-Induced Emission Characteristics for Combating Multidrug-Resistant Bacteria

Traditional photosensitizers (PSs) show reduced singlet oxygen (¹O₂) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non-targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water-dispersible membrane anchor (TBD-anchor) PS with aggregation-induced emission is designed and synthesized to generate ¹O₂ on the bacterial membrane. TBD-anchor showed efficient antibacterial performance towards both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin-resistant S. aureus (MRSA) when they were exposed to 0.8 μm of TBD-anchor at a low white light dose (25 mW cm⁻²) for 10 minutes. TBD-anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug-resistant bacteria.