High Singlet Oxygen Quantum Yield Research Articles

Accelerating the discovery of type Ⅱ photosensitizer: Experimentally validated machine learning models for predicting the singlet oxygen quantum yield of photosensitive molecule

Photodynamic therapy (PDT) is an emerging cancer treatment that mainly relies on photosensitizer (PS) to generate singlet oxygen for tumor destruction. Developing PSs with high singlet oxygen quantum yields (SO-QYs) requires extensive experimentation, limiting their rapid screening. Herein, to streamline this process, this study introduces several machine learning (ML) models that accurately predicts SO-QY across various experimental conditions. The models’ establishment is based on two feature matrices derived from Morgan fingerprints (MFPs) and descriptors (molecular descriptors and quantum chemical descriptors, MD_QCDs). Comparative and evaluative results indicate that the XGBoost model constructed with MFPs and the AdaBoost model constructed with MD_QCDs exhibit superior predictive performance, with R2 values of 0.8648 and 0.8460, respectively. Furthermore, by utilizing SHapley Additive exPlanations (SHAP) analysis and quantum chemistry, we analyzed that the iodine atoms and larger conjugated systems significantly influenced the SO-QY. Experimental validation, based on this analysis, demonstrates that our models not only possess excellent predictive capabilities but also exhibit strong interpretability. In summary, this work has established several interpretable models with outstanding predictive performance, which can aid in the more rapid screening of PSs, thus promoting their application in PDT.

Silicon phthalocyanines functionalized withaxial substituents targeting PSMA: synthesisand preliminary assessment of their potential for PhotoDynamic Therapy of prostate cancer.

Photodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitors are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)2 and SiPc-OSi(PSMAi)2. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si-O-C) bond for SiPc-PQ(PSMAi)2, and a silyloxy (Si-O-Si) bond for SiPc-OSi(PSMAi)2. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)2 showed a higher singlet oxygen quantum yield ΦΔ, higher fluorescence quantum yields ФF and better photostability than SiPc-OSi(PSMAi)2. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(-) PC3-FLU cells. However, SiPc-PQ(PSMAi)2 showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions.

Advancements of Porphyrin-Derived Nanomaterials for Antibacterial Photodynamic Therapy and Biofilm Eradication.

The threat posed by antibiotic-resistant bacteria and the challenge of biofilm formation has highlighted the inadequacies of conventional antibacterial therapies, leading to increased interest in antibacterial photodynamic therapy (aPDT) in recent years. This approach offers advantages such as minimal invasiveness, low systemic toxicity, and notable effectiveness against drug-resistant bacterial strains. Porphyrins and their derivatives, known for their high molar extinction coefficients and singlet oxygen quantum yields, have emerged as crucial photosensitizers in aPDT. However, their practical application is hindered by challenges such as poor water solubility and aggregation-induced quenching. To address these limitations, extensive research has focused on the development of porphyrin-based nanomaterials for aPDT, enhancing the efficacy of photodynamic sterilization and broadening the range of antimicrobial activity. This review provides an overview of various porphyrin-based nanomaterials utilized in aPDT and biofilm eradication in recent years, including porphyrin-loaded inorganic nanoparticles, porphyrin-based polymer assemblies, supramolecular assemblies, metal-organic frameworks (MOFs), and covalent organic frameworks (COFs). Additionally, insights into the prospects of aPDT is offered, highlighting its potential for practical implementation.

Lu, Sm, and Y-based double-decker phthalocyanines with enhanced photodynamic therapy performance

This paper focuses on the preparation of 3,5-di-tert-butylphenoxy substituted Lu, Sm, and Y-based double-decker phthalocyanines (Pcs), and investigation of their PDT properties. Briefly, 1,8,15,22-tetra-(3,5-di-tert-butylphenoxy) bisphthalocyanine derivatives (denoted LuPc2-3, SmPc2-4, YPc2-5) were synthesized by a two-step process. First, metal-free 1,8,15,22-tetra-(3,5-di-tert-butylphenoxy)phthalocyanine was prepared by tetramerization of 3,5-di-tert-butylphenoxy phthalonitrile, which is followed by reaction of different lanthanide salts with 1,8,15,22-tetra-(3,5-di-tert-butylphenoxy)bisphthalocyanine. The resultant double-decker Pcs were characterized in detail by UV–Vis, FT-IR, 1H NMR, fluorescence spectroscopy, MALDI-TOF MS, and elemental analysis. Strikingly, we report that double-decker phthalocyanines are not only photostable, but also exhibit relatively high singlet oxygen quantum yields of 0.96 (LuPc2-3), 0.91 (SmPc2-4) 0.87 (YPc2-5) and in THF.

Pyridinethiolate-Capped CdSe Quantum Dots for Red-Light-Driven H2 Production in Water.

The utilization of low-energy sunlight to produce renewable fuels is a subject of great interest. Here we report the first example of metal chalcogenide quantum dots (QDs) capped with a pyridinethiolate carboxylic acid (pyS-COOH) for red-light-driven H2 production in water. The precious-metal-free system is robust over 240 h, and achieves a turnover number (TON) of 43910±305 (vs Ni) with a rate of 31570±1690 μmol g-1 h-1 for hydrogen production. In contrast to the inactive QDs capped with other thiolate ligands, the CdSe-pyS-COOH QDs give a significantly higher singlet oxygen quantum yield [ΦΔ (1O2)] in solution.

Boosting the in-vitro effectiveness of photodynamic therapy on MCF-7 breast cancer cells with encapsulated malachite green by silica nanoparticles

Photodynamic therapy (PDT) is a promising cancer treatment strategy utilizing photosensitizers (PS) and light to generate singlet oxygen, with Malachite Green (MG) showing high singlet oxygen quantum yield. Effective delivery of MG to the target tissue remains a key challenge. Encapsulation techniques have been investigated to improve PS delivery, minimize PS leakage, inhibit diaphorase-induced reduction, and mitigate PS-related toxicity. Silica nanoparticles (SiNPs) offer favorable characteristics for drug delivery in PDT and serve as promising delivery carriers. In this study, SiNPs were synthesized and employed as carriers for MG. The size and shape of nanoparticles were determined using Transmission Electron Microscopy (TEM). A range of concentrations of MG were applied to MCF-7 breast cancer cells in order to evaluate the cytotoxicity of both naked and encapsulated MG. This helped identify the most effective concentrations and exposure durations required to induce damage under red laser light (Intensity ∼110 mW/cm2). The results indicated that SiNPs-encapsulated MG exhibited superior efficacy compared to naked MG, with a concentration efficacy increase of +50 % and an exposure time efficacy increase of +45 %. This underlines the enhanced capability of encapsulated MG to eliminate MCF-7 cells when compared to naked MG. The application of synthesized SiNPs for MG delivery improved the effectiveness of photodynamic therapy by augmenting MG bioavailability in target cells.

Asymmetric heptamethine cyanine dye for viscosity detection and photodynamic therapy

In this work, we disclose the new optical property of Cy7-TCF, an asymmetric heptamethine cyanine in which the indole donor is coupled to the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) acceptor, as an effective PDT rendering it responsive to near-infrared (NIR) light at 850 nm. Upon activation, Cy7-TCF exhibits a remarkably high singlet oxygen quantum yield (ΦΔ = 1.84 in a 50 % glycerol/PBS system), producing both fluorescence and singlet oxygen for effective PDT. Additionally, Cy7-TCF displays cancer cell specificity, leveraging viscosity changes, while showing negligible dark cytotoxicity. Flow cytometry analysis confirms PDT-induced cell apoptosis. Under NIR light activation, Cy7-TCF emerges as a promising dual-functional agent, serving as a theranostic tool for NIR imaging-guided PDT.

Antibacterial Properties of Rose Bengal Conjugated to Hyaluronic Acid.

Dental diseases, including conditions affecting oral structures, have become more common due to unhealthy lifestyle choices. Traditional antibiotic treatments face challenges related to the development of antibiotic resistance in bacteria. Photodynamic antibacterial chemotherapy is emerging as a promising alternative using photosensitizers to generate reactive oxygen species upon exposure to light. This article examines the photosensitizer Rose Bengal (RB) immobilized in hyaluronic acid (HA) for prolonged antibacterial action. The RB-HA conjugate demonstrated a molar ratio of approximately three RB residues to each of the ten units of HA. RB-HA exhibited a high singlet oxygen quantum yield (ΔΦ = 0.90), suggesting its efficacy in photodynamic treatment. A photostability analysis revealed slower photobleaching of RB-HA, which is essential for prolonged application. Under visible light and ultrasonic treatment, RB-HA exhibited effective antibacterial activity against Gram-positive S. aureus and Gram-negative E. coli bacteria for at least 80 days. The gradual release of RB ensured sustained bactericidal concentration. The study establishes RB-HA as a promising candidate for antimicrobial photodynamic and sonodynamic therapy in dental and other medical fields, providing enhanced stability and prolonged antibacterial efficacy.

Cationized orthogonal triad as a photosensitizer with enhanced synergistic antimicrobial activity

Single-molecule-based synergistic phototherapy holds great potential for antimicrobial treatment. Herein, we report an orthogonal molecular cationization strategy to improve the reactive oxygen species (ROS) and hyperthermia generation of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Cationic pyridine (Py) is introduced at the meso‑position of the asymmetric Cy7 with intramolecular charge transfer (ICT) to construct an atypical electron-transfer triad, which reduces ΔES1-S0, circumvents rapid charge recombination, and simultaneously enhances intersystem crossing (ISC) based on spin-orbit charge-transfer ISC (SOCT-ISC) mechanism. This unique molecular construction produces anti-Stokes luminescence (ASL) because the rotatable CN bond enriched in high vibrational-rotational energy levels improves hot-band absorption (HBA) efficiency. The obtained triad exhibits higher singlet oxygen quantum yield and photothermal conversion efficiency compared to indocyanine green (ICG) under irradiation above 800 nm. Cationization with Py enables the triad to target bacteria via intense electrostatic attractions, as well as biocidal property against a broad spectrum of bacteria in the dark. Moreover, the triad under irradiation can enhance biofilm eradication performance in vitro and statistically improve healing efficacy of MRSA-infected wound in mice. Thus, this work provides a simple but effective strategy to design small-molecule photosensitizers for synergistic phototherapy of bacterial infections. Statement of SignificanceWe developed an orthogonal molecular cationization strategy to enhance the reactive oxygen species and thermal effects of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Specifically, cationic pyridine (Py) was introduced at the meso‑position of the asymmetric Cy7 to construct an atypical electron-transfer triad, which reduced ΔES1-S0, circumvented rapid charge recombination, and simultaneously enhanced intersystem crossing (ISC). This triad, with a rotatable CN bond, produced anti-Stokes luminescence due to hot-band absorption. The triad enhanced antimicrobial performance and statistically improved the healing efficacy of MRSA-infected wounds in mice. This site-specific cationization strategy may provide insights into the design of small molecule-based photosensitizers for synergistic phototherapy of bacterial infections.

Supramolecular engineering cascade regulates NIR-II J-aggregates to improve photodynamic therapy.

Rational design of small organic molecule-based NIR-II photosensitizers (PSs) with high singlet oxygen quantum yield in aqueous solution for deep tissue imaging and cancer therapy still presents challenges. Herein, we devised a general synthesis strategy to obtain six NIR-II region PSs with tunable aggregation states by adjusting the steric effect, and all PSs possess longer NIR absorption/emission wavelengths with tails extending beyond 1200 nm. Notably, ATX-6 possessed a singlet oxygen quantum yield of 38.2% and exhibited concentration-dependent J-aggregation properties upon self-assembly in an aqueous solution. What's more, supramolecular engineering with DSPE-PEG2000 further enhanced its degree of J-aggregation, which was attributed to the dimer-excited reduction of the energy levels of the single-linear/triple-linear states and the facilitation of intersystem crossover processes. In addition, ATX-6 NPs showed superior photodynamic therapy effects and great potential in high-contrast in vivo bioimaging of the NIR-II region. These results provide valuable insights for achieving the diagnostic and therapeutic integration of tumors.

Theoretical study on the photophysical properties of thiophene-fused-type BODIPY series molecules in fluorescence imaging and photodynamic therapy.

As a class of photosensitizers (PSs) with dual functions of photodynamic therapy (PDT) and fluorescence imaging, the relationship between the structure and dual-function of thiophene-fused-type BODIPY dyes has not been studied in depth before. We found that the thiophene-fused-type BODIPY triplet photosensitizer is produced according to the energy level matching rule and the introduction of the thiophene ring significantly reduces the energy gap ΔEST between singlet and triplet states, as revealed by our investigation of the excited state structures and energies of thieno-fused BODIPY dyes. At the same time, a tiny ΔEST also results in a greatly enhanced intersystem crossing (ISC) rate, kISC. The kISC value of MeO-BODIPY, having the highest singlet oxygen quantum yield (ΦΔ), is the largest. Substitution with a strong electron donor N,N-dimethylaminophenyl (DMA) leads to the vertical configuration in the T1 state. The small ΔE (0.0029 eV) between the HOMO and HOMO-1 triggers the photo induced electron transfer (PET) of inhibiting ISC and fluorescence. When thieno-fused BODIPYs react with pyrrole, the increase of π-conjugation and smaller ΔEHOMO-LUMO explain the redshift in emission wavelength of thieno-pyrrole-fused BODIPY. The more planar configuration of the S1 state and the stronger oscillator intensity reflect a higher fluorescence quantum yield (ΦF). The extension of π-conjugation can cause molecules to transition to higher-level singlet excited states (Sn states, n ≥ 1) after absorbing energy and reduce the energy level of the excited state, resulting in multiple channels and favoring 1O2 production for thieno-pyrrole-fused BODIPYs with electron-withdrawing groups at the para-position of the phenyl groups. Due to ΔES0-T1 < 0.980 eV, the substitution of electron-donating groups cannot produce 1O2. In this work, we have revealed the mechanism of ISC and the fluorescence emission process in the thiophene-fused-type BODIPY dye, which has provided a theoretical foundation and guidance for the future design of BODIPY-based heavy-atom-free PSs for molecular applications in PDT.

Synthesis of phenanthroline substituted five-nuclear phthalocyanine zinc complex and exploring of photochemical and sono-photochemical properties

Sono-photodynamic therapy (SPDT) which is the combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) is an alternative and efficient method among cancer treatments achieving high singlet oxygen quantum yield. This study aimed to synthesize Schiff base substituted Zn phthalocyanine containing phenanthroline group to obtain suitable sono-photosensitizer. The target phthalocyanine (4) was obtained by cyclotetramerization reaction of phenanthroline-Zn(II) complex substituted phthalonitrile (3) with zinc acetate. The synthesized compounds were characterized by various spectroscopic techniques including FT-IR, Mass, UV–Vis, and 1H NMR spectroscopy. The singlet oxygen quantum yield was calculated in both photochemical and sono-photochemical method for compound 4. While the ΦΔ value was calculated as 0.72 for photochemical method, the ΦΔ value reached to 0.98 for sono-photochemical method.

Versatile phototheranostic system: Aza-BODIPY-based nanoparticles with B,O-chelated core and diiodine

The heavy atom effect is widely recognized for its ability to enhance the photodynamic effect, but it also gives rise to concerns about fluorescence quenching and low photothermal conversion efficiency. In this study, we introduced iodine atoms into B,O-chelated aza-BODIPY and coated them with DSPE-PEG2000 to achieve high singlet oxygen quantum yields (64.9 %), while simultaneously maintaining excellent fluorescence emission (Φ = 0.94 %) and photothermal conversion capability (PCE = 33.8 %). The B,O-chelated aza-BODIPY derivative shows a remarkable synergistic and improved phototherapy therapeutic performance mainly by the innovative enhancement of the π-conjugated structure from the B,O-chelated structure and partial weakening of intermolecular π-π stacking from the steric hindrance of iodine atoms, which was validated through in vivo and in vitro tumor diagnosis and elimination experiments, utilizing state-of-the-art fluorescence imaging, photoacoustic imaging, and photothermal imaging for multimodal imaging-guided photodynamic therapy and photothermal therapy. This groundbreaking approach effectively overcomes the limitations of the traditional heavy atom effect, and presents a pioneering perspective on constructing a versatile phototheranostic system for precise and efficient tumor treatment. By effectively addressing the challenges posed by the heavy atom effect and maximizing the capabilities of the photosensitizer, we pave the way for more accurate and effective approaches in combating tumors.

Photodynamic antimicrobial chemotherapy activities of phthalocyanine-antibiotic conjugates against bacterial biofilms and interactions with extracellular polymeric substances

This study sheds light on how to rationally design efficient photodynamic antimicrobial chemotherapy (PACT) agents by covalently linking phthalocyanines (Pcs) as photosensitizers with an antibiotic: Ciprofloxacin (CIP). Pcs used are zinc (II) 3-(4-((3,17,23-tris(4-(Benzo(d)thiazol-2-yl] thiol) phthalocyanine-9-yl) oxy) phenyl) propanoic acid (1) and zinc (II) 3-(4-(3,17,23-tris(3-(4-(triphenylphosphine) butyl) benzo[d]thiazol-3-ium bromide phthalocyanine-9-yl) oxy) phenyl) propanoic acid (2). High singlet oxygen quantum yields are observed in the presence of CIP. Square wave voltammetry was used to analyse the Pc-CIP uptake by bacteria biofilms of Streptococcus pneumoniae (S. pneumonia) and Escherichia coli (E. coli). Electrochemical impedance spectroscopy and scanning electron spectroscopy were used to study the stability of the biofilms in the presence Pc-CIP complexes and when exposed to light. Raman and time of flight-secondary ion mass spectrometry (TOF-SIMS) are used to identify the breakdown of cellular components of the biofilm and penetration of the Pc-CIP into the biofilms, respectively.

Sonophotochemical and photochemical efficiency of thiazole-containing metal phthalocyanines and their gold nanoconjugates.

This study presents the synthesis of some metal {M = Zn(II), Lu(III), Si(IV)} phthalocyanines bearing chlorine and 2-(4-methylthiazol-5-yl) ethoxy groups at peripheral or axial positions. The newly synthesized metal phthalocyanines were characterized by applying FT-IR, 1H NMR, mass, and UV-Vis spectroscopic approaches. Additionally, the surface of gold nanoparticles was modified with zinc(II) and silicon(IV) phthalocyanines. The resultant nanoconjugates were characterized using TEM images. Moreover, the effect of metal ions and position of substituent, and gold nanoparticles on the photochemical and sonophotochemical properties of the studied phthalocyanines was investigated. The highest singlet oxygen quantum yield was obtained for the lutetium phthalocyanine by applying photochemical and sonophotochemical methods. However, the linkage of the zinc(II) and silicon(IV) phthalocyanines to the surface of gold nanoparticles improved significantly their singlet oxygen generation capacities.

Synthesis and biological evaluation of bi-modal BODIPY-conjugated Hoechst applicable for Auger-electron and photodynamic cancer therapy

Current therapeutic approaches to cancer are not fully effective, and so development of more effective treatment is needed. Auger-electron therapy and photodynamic therapy have attracted marked attentions as a promising strategy in cancer treatment. In this study, we synthesized [125I]BH-2/BH-2, which comprised Hoechst and 2,6-diiodo-substituted BODIPY, and evaluated its usefulness as a bi-modal agent for Auger-electron/photodynamic therapy by comparison with the previously reported compound [125I]BH/BH. [125I]BH-2 was obtained at a 13% radiochemical yield. [125I]BH-2 showed similar uptake into the nucleus to [125I]BH, suggesting that Hoechst can function as a nuclear localization tag. HeLa cell viabilities were reduced in both cells exposed to [125I]BH-2 and [125I]BH. γ-H2AX foci in HeLa cells exposed to [125I]BH-2 or [125I]BH were increased in a dose-dependent manner, indicating that DNA double-strand breaks may have occurred. No significant difference was observed between [125I]BH-2 and [125I]BH at these investigations. For PDT application, BH-2 showed a higher singlet oxygen quantum yield (ΦΔ) and caused superior photo-induced cytotoxicity in HeLa cells compared with BH. These results suggest that bi-modal [125I]BH-2/BH-2 can cause anti-tumor effects with Auger-electron and photodynamic therapy.

FRET-based two-photon benzo[a] phenothiazinium photosensitizer for fluorescence imaging-guided photodynamic therapy

To overcome the conflict between the long-wavelength excitation and high singlet oxygen quantum yield of photosensitizers, we conjugated a two-photon fluorophore, tetrahydroquinoxaline coumarin (TQ), and an efficient photodynamic therapeutic agent, benzo[a]phenothiazinium (NBS-NH2), through a hexamethylene linker to build a two-photon photosensitizer, TQ-NBS. In TQ-NBS, TQ served as an energy donor and NBS-NH2 acted as an energy acceptor; and TQ-NBS was a Förster resonance energy transfer (FRET) cassette with a 92.8% efficiency. The large two-photon absorption cross-section of TQ allowed photosensitizer TQ-NBS to work in a 900 nm two-photon excitation (TPE) mode, which greatly benefited the deep tissue penetration in PDT treatment. Meanwhile, the excellent phototoxicity and near-infrared fluorescence of NBS-NH2 was kept in TQ-NBS under a TPE mode via a FRET process. Photosensitizer TQ-NBS exhibited a high phototoxic efficacy in living cells and tumor-bearing mice.

The photodynamic activity properties of a series of structurally analogous tetraarylporphyrin, chlorin and N-confused porphyrin dyes and their Sn(IV) complexes

A series of tetraarylporphyrin, -chlorin and N-confused porphyrin dyes with 4‑methoxy‑meso-aryl rings (1-Por, 1-Chl and 1-NCP) and their Sn(IV) complexes (1-SnPor, 1-SnChl and 1-SnNCP) have been synthesized and characterized. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.67, 0.71 and 0.85 for 1-SnPor, 1-SnChl and 1-SnNCP, respectively. The photodynamic activities of 1-Por, 1-Chl, 1-NCP, 1-SnPor, 1-SnChl and 1-SnNCP were determined against MCF-7 breast cancer cells through illumination with Thorlabs 625 or 660 nm (240 or 280 mW.cm−2) light emitting diodes (LEDs) for 20 min. The IC50 values for 1-SnChl and 1-SnNCP lie between 1.4 − 6.1 and 1.6 − 4.8 µM upon photoirradiation with the 660 and 625 nm LEDs, respectively, while higher values of >10 µM were obtained for 1-SnPor and the free base dyes. In a similar manner, 1-SnChl and 1-SnNCP were found to also have significantly higher photodynamic antimicrobial activity against planktonic Gram-(+) Staphylococcus aureus and Gram-(−) Escherichia coli bacteria than the other dyes studied. Upon illumination with Thorlabs 625 and 660 nm LEDs for 75 min, Log10 reduction values of 7.62 and > 2.40−3.69 were obtained with 1 and 5 µM solutions, respectively.

Efficient Spin-Orbit Charge-Transfer Intersystem Crossing and Slow Intramolecular Triplet-Triplet Energy Transfer in Bodipy-Perylenebisimide Compact Dyads and Triads.

Bodipy (BDP)-perylenebisimide (PBI) donor-acceptor dyads/triad were prepared to study the spin-orbit charge-transfer intersystem crossing (SOCT-ISC). For BDP-PBI-3, in which BDP was attached at the imide position of PBI, higher singlet oxygen quantum yield (ΦΔ =85 %) was observed than the bay-substituted derivative BDP-PBI-1 (ΦΔ =30 %). Femtosecond transient absorption spectra indicate slow Förster resonance energy transfer (FRET; 40.4 ps) and charge separation (CS; 1.55 ns) in BDP-PBI-3, while for BDP-PBI-1, CS takes 2.8 ps. For triad BDP-PBI-2, ultrafast FRET (149 fs) and CS (4.7 ps) process were observed, the subsequent charge recombination (CR) takes 5.8 ns and long-lived 3 PBI* (179.8 μs) state is populated. Nanosecond transient absorption spectra of BDP-PBI-3 show that the CR gives upper triplet excited state (3 BDP*) and subsequently, via a slow intramolecular triplet energy transfer (14.5 μs), the 3 PBI* state is finally populated, indicating that upper triplet state is involved in SOCT-ISC. Time-resolved electron paramagnetic resonance spectroscopy revealed that both radical pair ISC (RP ISC) and SOCT-ISC contribute to the ISC. A rare electron spin polarization of (e, e, e, e, e, e) was observed for the triplet state formed via the RP ISC mechanism, due to the S-T+1 /T0 states mixing.

Rational design of β-carboline as an efficient type I/II photosensitizer to enable hypoxia-tolerant chemo-photodynamic therapy

Photodynamic therapy (PDT) is a clinically approved treatment for cancer due to its high spatiotemporal selectivity and non-invasive modality. However, its therapeutic outcomes are always limited to the severe hypoxia environment of the solid tumor. Herein, two novel photosensitizers HY and HYM based on naturally antitumor alkaloids β-carboline were designed and synthesized. Through a series of experiments, we found HY and HYM can produce type II ROS (singlet oxygen) after light irradiation. HYM had higher singlet oxygen quantum yield and molar extinction coefficient than HY, as well as type I PDT behavior, which further let us find that HYM could exhibit robust phototoxicity activities in both normoxia and hypoxia. Meanwhile, HYM showed tumor-selective cytotoxicity with minimal toxicity toward normal cells. Notably, thanks to HYM's hypoxia-tolerant type I/II PDT and tumor selective chemotherapy, HYM showed synergistic inhibitory effect on tumor growth (inhibition rate > 91%). Our research provides a promising photosensitizer for hypoxia-tolerant chemo-photodynamic therapy, and may also give a novel molecular skeleton for photosensitizer design.