Efficient Intersystem Crossing Research Articles

Recent Progress in Thermally Activated Delayed Fluorescence Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) is a rapidly growing discipline that is expected to become an encouraging noninvasive therapeutic strategy for cancer treatment. In the PDT process, an efficient intersystem crossing (ISC) process for photosensitizers from the singlet excited state (S1) to the triplet excited state (T1) is critical for the formation of cytotoxic reactive oxygen species and improvement of PDT performance. Thermally activated delayed fluorescence (TADF) molecules featuring an extremely small singlet-triplet energy gap and an efficient ISC process represent an enormous breakthrough for the PDT process. Consequently, the development of advanced TADF photosensitizers has become increasingly crucial and pressing. The most recent developments in TADF photosensitizers aimed at enhancing PDT efficiency for bio-applications are presented in this review. TADF photosensitizers with water dispersibility, targeting ability, activatable ability, and two-photon excitation properties are highlighted. Furthermore, the future challenges and perspectives of TADF photosensitizers in PDT are proposed.

Altering central atoms and bromination sites of phosphorescence units to control ultralong organic room temperature phosphorescence

We report two strategies to expand the library of Phosphorescence Units, including altering the central atom and bromination. Directed by these two strategies, numerous new Phosphorescence Units can be designed. Due to the limitation of organic synthesis and commercial availability, eight organic units (BCz, NBF, BNT, BrBCz-1, BrBCz-2, BrBCz-3, BrBCz-4 and BrBNT) were obtained to verify our proposed methods and study the impact of central atoms and bromination sites on organic room temperature phosphorescence. Considering BCz, NBF and BNT (Group Ⅰ) together, when the central atom is N or S, the room temperature phosphorescence is on as BCz and BNT have higher ISC (Intersystem Crossing) efficiency than NBF; from N to S, phosphorescence wavelength red shifts because the T1 energy level is closely related to the central atom and the lifetime shortens due to different ISC efficiency. Considering BCz, BrBCz-1, BrBCz-2 and BrBCz-3 (Group Ⅱ), bromination and different bromination sites on the benzene ring matters much to ISC efficiency but little to the intrinsic T1 energy level, leading to dramatical increase of phosphorescence intensity, sharp drop of phosphorescence lifetime and subtle change of phosphorescence wavelength (color). Considering BrBCz-4 and BrBNT (Group Ⅲ), bromination on the naphthalene moiety greatly affects both ISC efficiency and the intrinsic T1 energy level, resulting in dramatical increase of phosphorescence intensity, sharp drop of phosphorescence lifetime and significant red shift of phosphorescence color. Therefore, BNT, BrBCz-1, BrBCz-2, BrBCz-3, BrBCz-4 and BrBNT can be regarded as new Phosphorescence Units while NBF cannot be. To our best knowledge, this work for the first time gives design suggestions of organic room temperature materials from the atomic level. This work may give a deep insight into organic phosphorescence from the perspective of Phosphorescence Units and lay foundation for their future applications.

Insights into the Excited State Dynamics of Donor–Acceptor Organic Photosensitizer for Precise Deep‐Brain Two‐Photon Photodynamic Therapy

AbstractOrganic photosensitizer with both large two‐photon absorption (σ) and efficient intersystem crossing (ISC) offers incomparable advantages in precise two‐photon photodynamic therapy. However, the current design strategy cannot achieve efficient ISC without compromising σ. Here, very efficient ISC and ultrahigh σ in organic photosensitizer (PFBT) for precise cerebrovascular two‐photon photodynamic therapy is simultaneously achieved. A hybridized local and charge‐transfer (1HLCT) excited state in PFBT, formed by incorporating benzothiadiazole into a typical polyfluorene (PF), is the key to initiating efficient ISC while bringing substantial σ enhancement (25 000 GM vs 10 000 GM) compared to PF. Mechanism studies identify that 1HLCT produces large spin‐orbit coupling and tiny singlet‐triplet energy gaps, together generating efficient ISC. These properties afford PFBT nanophotosensitizer a ≈2000‐fold increase in two‐photon photodynamic therapy efficiency than clinically‐used Photofrin, enabling in vivo deep‐brain cerebrovascular imaging and closure with unprecedented precision.

Triplet properties and intersystem crossing mechanism of PtAg28 nanocluster sensitizers achieving low threshold and efficient photon upconversion.

Ligand-protected metal nanoclusters have emerged as a promising platform for providing sensitizers for triplet-triplet annihilation upconversion (TTA-UC). Herein, we report [PtAg28(BDT)12]4- (PtAg28; BDT = 1,3-benzenedithiolate) as a sensitizer enabling TTA-UC at low excitation intensities. PtAg28 exhibits a long-lived triplet state (approximately 7 μs) generated with a 100% intersystem crossing (ISC) quantum yield. The mechanism driving this efficient ISC was unveiled with the aid of theoretical calculations. Specifically, the S1-T1 ISC reveals a small spin-orbit coupling (SOC) matrix element, attributed to their similar electron configuration. In contrast, the T2 state, which is energetically close to S1, features a hole distribution derived from the Py superatomic orbital of the icosahedral Pt@Ag12 core. This distribution enables direct SOC based on the orbital angular momentum change from the S1 state with a Pz-derived hole distribution. Consequently, the efficient ISC was rationalized by the S1 → T2 → T1 pathway. The T1 state possesses a metal core-to-surface metal charge transfer character, facilitating triplet energy transfer and conferring superior sensitization ability. Leveraging these characteristics, the combination of PtAg28 sensitizer with a 9,10-diphenylanthracene annihilator/emitter attained an extremely low UC threshold of 0.81 mW cm-2 at 532 nm excitation, along with efficient green-to-blue TTA-UC with an internal quantum yield (ΦUCg) of 12.2% (50% maximum). This results in a pseudo-first-order TTA process with strong UC emission under 1-sun conditions.

Solvent-polarity dependence of ultrafast excited-state dynamics of trans-4-nitrostilbene.

Ultrafast excited-state dynamics of the simplest nitrostilbenes, namely trans-4-nitrostilbene (t-NSB), was studied in solvents of various polarities with ultrafast broadband time-resolved fluorescence and transient absorption spectroscopies, and by quantum-chemical computations. The results revealed that the initially excited S1(ππ*) state deactivation dynamics is strongly influenced by the solvent polarity. Specifically, the t-NSB S1-state lifetime decreases by three orders of magnitude from ∼60 ps in high-polarity solvents to ∼60 fs in nonpolar solvents. The strong solvent-polarity dependence arises from the differences in dipole moments among the S1 and relevant states, including the major intersystem crossing (ISC) receiver triplet states, and therefore, the solvent polarity can modulate their relative energies and ISC rates. In nonpolar solvents, the sub-100 fs lifetime is due to a combination of efficient ISC and internal conversion. In medium-polarity solvents, the S1-state population decays via a competing ISC relaxation mechanism in a biphasic manner, and the ISC rates are found to obey the inverse energy gap law of the strong coupling case. In high-polarity solvents, the S1 state is stabilized to a much lower energy such that ISC becomes energetically infeasible, and the S1 state decays via barrier crossing along the torsion angle of the central ethylenic bond to the nonfluorescent perpendicular configuration. Regardless of the initial S1-state deactivation pathways in various solvents, the excited-state population is ultimately trapped in the metastable T1-state perpendicular configuration, at which a slower ISC occurs to bring the system to the ground state and bifurcate into either trans or cis form of NSB.

Promoting intersystem crossing by charge transfer state of dimers for persistent room temperature phosphorescence

Efficient intersystem crossing (ISC) is essential for phosphorescence emission. The charge transfer (CT) state is traditionally constructed by highly twisted donor-acceptor type structures to facilitate the ISC process. However, the highly twisted structural properties limit the diversity of room-temperature phosphorescence (RTP) molecules. By establishing the CT state in the intermolecular dimers structure, the dependence on the distorted donor-acceptor in the single-molecule design can be well eliminated. Based on this strategy, three novel pure organic luminescent molecules with long afterglow and mechanochromic luminescence (MCL) property were designed and synthesized. All of those exhibited triple emission, including prompt fluorescence (PF), delayed fluorescence (DF) and persistent RTP (pRTP) emission. In particular, CzC4-PhCN showed great potential for application in the field of anti-counterfeiting with its ultralong phosphorescent lifetime of 862 ms. Single crystal analysis and theoretical calculation revealed that the formation of CT states of intermolecular dimers effectively reduced ΔEST and promoted ISC process. This study would be highly instructive for realizing efficient ISC process and high-efficiency pRTP emission in pure organic systems.

Dissecting the Triplet-State Properties and Intersystem Crossing Mechanism of the Ligand-Protected Au13 Superatom.

Icosahedral Au13 nanoclusters are among the most typical superatoms and are of great interest as promising building blocks for nanocluster-assembled materials. Herein, the key parameters involved in the intersystem crossing (ISC) process of [Au13(dppe)5Cl2]3+ (Au13; dppe = 1,2-bis(diphenylphosphino)ethane) were characterized. Quenching experiments using aromatic compounds revealed that the T1 energy of Au13 is 1.63 eV. An integrative interpretation of our experimental results and the relevant literature uncovered important facts concerning the Au13 superatom: the ISC quantum yield is unity due to the ultrafast ISC (∼1012 s-1), the lowest absorption band includes contributions of direct singlet-triplet transitions, and there exists a large S1-T1 gap of 0.73 eV. To explain the efficient ISC, the El-Sayed rule was applied to the superatomic orbitals corresponding to the excited-state hole/electron distributions obtained from theoretical calculations. The strong spin-orbit coupling between the S1 and T2-T4 states offers a reasonable explanation for the ultrafast ISC.

Triplet Generation Through Singlet Fission in Metal-Organic Framework: An Alternative Route to Inefficient Singlet-Triplet Intersystem Crossing.

High quantum yield triplets, populated by initially prepared excited singlets, are desired for various energy conversion schemes in solid working compositions like porous MOFs. However, a large disparity in the distribution of the excitonic center of mass, singlet-triplet intersystem crossing (ISC) in such assemblies is inhibited, so much so that a carboxy-coordinated zirconium heavy metal ion cannot effectively facilitate the ISC through spin-orbit coupling. Circumventing this sluggish ISC, singlet fission (SF) is explored as a viable route to generating triplets in solution-stable MOFs. Efficient SF is achieved through a high degree of interchromophoric coupling that facilitates electron super-exchange to generate triplet pairs. Here we show that a predesigned chromophoric linker with extremely poor ISC efficiency (kISC) but form triplets in MOF in contrast to the frameworks that are built from linkers with sizable kISC but . This work opens a new photophysical and photochemical avenue in MOF chemistry and utility in energy conversion schemes.

Triplet Generation Through Singlet Fission in Metal‐Organic Framework: An Alternative Route to Inefficient Singlet‐Triplet Intersystem Crossing

AbstractHigh quantum yield triplets, populated by initially prepared excited singlets, are desired for various energy conversion schemes in solid working compositions like porous MOFs. However, a large disparity in the distribution of the excitonic center of mass, singlet‐triplet intersystem crossing (ISC) in such assemblies is inhibited, so much so that a carboxy‐coordinated zirconium heavy metal ion cannot effectively facilitate the ISC through spin‐orbit coupling. Circumventing this sluggish ISC, singlet fission (SF) is explored as a viable route to generating triplets in solution‐stable MOFs. Efficient SF is achieved through a high degree of interchromophoric coupling that facilitates electron super‐exchange to generate triplet pairs. Here we show that a predesigned chromophoric linker with extremely poor ISC efficiency (kISC) but form triplets in MOF in contrast to the frameworks that are built from linkers with sizable kISC but . This work opens a new photophysical and photochemical avenue in MOF chemistry and utility in energy conversion schemes.

Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer.

Designing heavy-atom-free triplet photosensitizers (PSs) is a challenge for the efficient photodynamic therapy (PDT) of cancer. Helicenes are twisted polycyclic aromatic hydrocarbons (PAHs) with an efficient intersystem crossing (ISC) that is proportional to their twisting angle. But their difficult syntheses and weak absorption profile in the visible spectral region restrict their use as heavy-atom-free triplet PSs for PDT. On the other hand, boron-containing PAHs, BODIPYs are highly recognized for their outstanding optical properties. However, planar BODIPY dyes has low ISC and thus they are not very effective as PDT agents. We have designed and synthesized fused compounds containing both BODIPY and hetero[5]helicene structures to develop red-shifted chromophores with efficient ISC. One of the pyrrole units of the BODIPY core was also replaced by a thiazole unit to further enhance the triplet conversion. All the fused compounds have helical structure, and their twisting angles are also increased by substitutions at the boron centre. The helical structures of the BODIPY-hetero[5]helicenes were confirmed by X-ray crystallography and DFT structure optimization. The designed BODIPY-hetero[5]helicenes showed superior optical properties and high ISC with respect to [5]helicene. Interestingly their ISC efficiencies increase proportionally with their twisting angles. This is the first report on the relationship between the twisting angle and the ISC efficiency in twisted BODIPY-based compounds. Theoretical calculations showed that energy gap of the S1 and T1 states decreases in BODIPY-hetero[5]helicene as compared to planar BODIPY. This enhances the ISC rate in BODIPY-hetero[5]helicene, which is responsible for their high generation of singlet oxygen. Finally, their potential applications as PDT agents were investigated, and one BODIPY-hetero[5]helicene showed efficient cancer cell killing upon photo-exposure. This new design strategy will be very useful for the future development of heavy-atom-free PDT agents.

The three kingdoms-Photoinduced electron transfer cascades controlled by electronic couplings.

Excited states are the key species in photocatalysis, while the critical parameters that govern their applications are (i) excitation energy, (ii) accessibility, and (iii) lifetime. However, in molecular transition metal-based photosensitizers, there is a design tension between the creation of long-lived excited (triplet), e.g., metal-to-ligand charge transfer (3MLCT) states and the population of such states. Long-lived triplet states have low spin-orbit coupling (SOC) and hence their population is low. Thus, a long-lived triplet state can be populated but inefficiently. If the SOC is increased, the triplet state population efficiency is improved-coming at the cost of decreasing the lifetime. A promising strategy to isolate the triplet excited state away from the metal after intersystem crossing (ISC) involves the combination of transition metal complex and an organic donor/acceptor group. Here, we elucidate the excited state branching processes in a series of Ru(II)-terpyridyl push-pull triads by quantum chemical simulations. Scalar-relativistic time-dependent density theory simulations reveal that efficient ISC takes place along 1/3MLCT gateway states. Subsequently, competitive electron transfer (ET) pathways involving the organic chromophore, i.e., 10-methylphenothiazinyl and the terpyridyl ligands are available. The kinetics of the underlying ET processes were investigated within the semiclassical Marcus picture and along efficient internal reaction coordinates that connect the respective photoredox intermediates. The key parameter that governs the population transfer away from the metal toward the organic chromophore either by means of ligand-to-ligand (3LLCT; weakly coupled) or intra-ligand charge transfer (3ILCT; strongly coupled) states was determined to be the magnitude of the involved electronic coupling.

Understanding remarkably high triplet quantum yield in thione analogs of perylenediimide: A detailed theoretical study.

The diverse and tunable electronic structures of perylenediimide (PDI), together with its high thermal and chemical stability, make the compound suitable for applications in bioimaging, electrical, and optical devices. However, a large singlet-triplet gap (ΔES-T) and almost zero spin-orbit coupling (SOC) between the lowest excited singlet (S1) and triplet (T1) restrict intersystem crossing (ISC) in highly fluorescent pristine PDI, yielding a near zero triplet quantum yield (ΦT). Interestingly, a thione analogs of PDI with varied S content (mS-PDIs, m = 1-4) was experimentally shown to yield ΦT ∼ 1.0 through efficient ISC. Time-dependent optimally-tuned range-separated hybrid calculations are performed to rationalize the experimentally observed red-shifted optical absorption and also the remarkably high ISC with almost zero radiative fluorescence reported for these mS-PDIs. To this end, the relative energies of low-lying excited singlets Sn (n = 1, 2) and a few triplets Tn(n = 1-3), along with their nature (nπ* or ππ*), are assessed for each of the mS-PDIs studied in chloroform. To our surprise and contrary to the earlier reports, both S1 and T1 are found to be of the same ππ* character, originating from the highest occupied to lowest unoccupied orbital transition, which, therefore, leads to a still large ΔES-T and vanishingly small SOC, as expected from the identical wavefunction symmetry. Increasing S content lowers S1(ππ*) due to a greater extent of π-delocalization, which well complements and supports the observed red-shift. More importantly, the T2 (or T3) closely lying to the S1 is of nπ* and, therefore, produces a relatively smaller ΔES-T and larger SOC. Detailed kinetics analysis suggests S1(ππ*) → T2(nπ*) is the primary ISC channel for all mS-PDIs, which is responsible for the remarkably high ΦT observed. In addition, comparable SOC and ΔES-T produce similar ISC rates for all mS-PDIs.

Heptamethine Cyanine Dyes with Ultra‐Efficient Excited‐State Nonradiative Decay for Synergistic Photothermal Immunotherapy

AbstractOrganic dyes in the excited singlet state (S1) decay via intersystem crossing (ISC) to the triplet state, radiative dissipation as fluorescence, or nonradiative decay for thermal deactivation. Although many studies are conducted to improve ISC and fluorescence efficiency, few have optimized S1 decay via thermal deactivation, which is crucial for designing photothermal agents. A strategy for inhibiting radiative decay and ISC by introducing electron withdraw groups (EWGs) into the meso position of heptamethine cyanines (Cy7) is reported here, which allows S1 energy decay via nonradiative relaxation. The decrease in the electron density of Cy7 caused by EWGs improved the photostability, which is important for biological applications because conventional cyanine dyes are easily photobleached. The EWG substitutes acted as efficient rotation groups with low‐energy barriers, narrowing the energy gap between S1 and the ground state and considerably improving the photothermal conversion efficiency (PCE). The PCE of CF3cy with the strongest EWG is increased up to 83%. Liposome is used as a carrier to improve the biocompatibility and tumor retention of CF3cy, which is combined with the toll‐like receptor agonist resiquimod (R848) for synergistic photothermal immunotherapy against both primary and distant tumors and elicits a long‐lasting immunological memory effect.

Does Twisted Molecular Structure Always Induce Intersystem Crossing? A Case Study with Near-IR Absorbing 1,8-Diazabicyclo[5.4.0]undec-7-ene-fused Naphthaldiimide.

Heavy atom-free organic chromophores showing absorption in the near-IR region with intersystem crossing (ISC) ability are important for applications in various fields, e.g., photocatalysis and photodynamic therapy. Herein, we studied the photophysical property of a naphthalenediimide (NDI) derivative, in which the NDI chromophore is fused with pentacyclic 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), which shows a strong charge-transfer (CT) absorption band (S0 → 1CT transition) in the near-IR region of 600-740 nm. The effect of extended π-conjugation framework in NDI-DBU compared with the derivative of mono-amino substitution (NDI-NH-Br) was studied by steady-state and nanosecond transient absorption (ns-TA) spectra, electron paramagnetic resonance (EPR) spectroscopy, and theoretical computations. The fluorescence is almost completely quenched for NDI-DBU (ΦF = 1.0%) as compared with NDI-NH-Br (ΦF = 24% in toluene). However, the ISC of NDI-DBU is poor, and the singlet oxygen quantum yield was determined as ΦΔ = 9% versus ΦΔ = 57% for NDI-NH-Br, although the compound has significantly twisted molecular structure. The ns-TA spectral study showed a long-lived triplet excited state (τT = 132 μs) in NDI-DBU, with T1 energy of 1.20-1.44 eV, and the ISC is via the S2 → T3 path, which is verified by theoretical calculations. This study displayed that the twisting of molecular geometry does not always assure efficient ISC.

Structurally Flexible Au-Cu Alloy Nanoclusters Enabling Efficient Triplet Sensitization and Photon Upconversion.

Ligand-protected noble-metal nanoclusters exhibit an innately triplet nature and have been recently recognized as emerging platforms for triplet sensitizers of photon upconversion (UC) via triplet-triplet annihilation. Herein, we report that a structurally flexible Au-Cu alloy nanocluster, [Au4Cu4(S-Adm)5(DPPM)2]+ (Au4Cu4; S-Adm = 1-adamantanethiolate, DPPM = bis(diphenylphosphino)methane), exhibited favorable sensitizer properties and superior UC performance. Contrary to the structurally rigid Au2Cu6(S-Adm)6(TPP)2 (Au2Cu6, TPP = triphenylphosphine), Au4Cu4 exhibited significantly better sensitizer characteristics, such as a near-unity quantum yield for intersystem crossing (ISC), long triplet lifetime (ca. 8 μs), and efficient triplet energy transfer (TET). The efficient ISC of Au4Cu4 was attributed to the practically negligible activation barriers during the ISC process, which was caused by the spin-orbit interaction between the two isoenergetic isomers predicted by theoretical calculations. A series of aromatic molecules with different triplet energies were used as acceptors to reveal the driving force dependence of the TET rate constant (kTET). This dependency was analyzed to evaluate the triplet energy and sensitization ability of the alloy nanoclusters. The results showed that the maximum value of kTET for Au4Cu4 was seven times larger than that for Au2Cu6, which presumably reflects the structural/electronic fluctuations of Au4Cu4 during the triplet state residence. The combination of the Au4Cu4 sensitizer and the 9,10-diphenylanthracene (DPA) annihilator/emitter achieved UC with internal quantum yields of 14% (out of 50% maximum) and extremely low threshold intensities (2-26 mWcm-2). This performance far exceeds that of Au2Cu6 and is also outstanding among the organic-inorganic hybrid nanomaterials reported so far.

Origins of Molecular-Twist-Triggered Intersystem Crossing in Functional Perylenediimides: Singlet-Triplet Gap versus Spin-Orbit Coupling.

Singlet-triplet gap (ΔES-T) and spin-orbit coupling (SOC) primarily govern intersystem crossing (ISC)-mediated photo- and electro-luminescence processes. Structural-twist in organic molecules is known to improve ISC efficiency. However, how and to what extent a twist affects the ΔES-T and SOC are not yet fully understood. In this work, the impact of molecular-twist on these energetics governing ISC is unveiled in a series of highly fluorescent prototype perylenediimides (PDIs) in dichloromethane implementing reliable quantum-chemical calculations. While S1 → T1 ISC remains suppressed with increasing twist, a relatively larger decrease in ΔES-T together with a modest increase in SOC results in enhanced S1 →T2 ISC. Significantly modulated ISC rates are predicted in a few experimentally relevant -CN- and -Br-substituted PDIs, where twist of varied extent arises naturally depending on substituent's chemical nature, numbers, and positions. This study uncovers the critical role of molecular-twist in tailoring ISC and thereby helps designing functional organic triplet-generating materials.

Revisiting the Dynamics of Triplet Formation in Anthraquinones.

Triplet formation pathways in 9,10-anthraquinone (AQ) and its hydroxy derivative, 1-hydroxyanthraquinone (HAQ), are studied theoretically. Dynamics simulations on the model singlet-triplet potential energy surfaces within the linear vibronic coupling framework are performed to elucidate possible internal conversion (IC) and intersystem crossing (ISC) pathways in these molecules. An ultrafast IC decay from the "bright" S4 to S1 followed by efficient ISC via S1-T4 and S1-T5 pathways fosters a high triplet quantum yield (ΦT = 0.90) in AQ. In HAQ, a new nonradiative channel of "barrierless" excited-state intramolecular proton transfer (ESIPT) opens up and competes with the IC decay to S1 upon photoexcitation to the "bright" S2. Extremely fast ESIPT on S2 reduces the efficiency of triplet formation via possible ISC pathways involving S1 and S2, resulting in a low ΦT (=0.17).

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

Sonosensitized Aggregation-Induced Emission Dots with Capacities of Immunogenic Cell Death Induction and Multivalent Blocking of Programmed Cell Death-Ligand 1 for Amplified Antitumor Immunotherapy

Sonosensitized Aggregation-Induced Emission Dots with Capacities of Immunogenic Cell Death Induction and Multivalent Blocking of Programmed Cell Death-Ligand 1 for Amplified Antitumor Immunotherapy

Emerging Designs of Aggregation-Induced Emission Agents for Enhanced Phototherapy Applications

Emerging Designs of Aggregation-Induced Emission Agents for Enhanced Phototherapy Applications