Singlet Oxygen Generation Quantum Research Articles

Non-peripheral octasubstituted zinc(II) phthalocyanines bearing pyridinepropoxy substituents – Antibacterial, anticancer photodynamic and sonodynamic activity

The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran – DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and S. epidermidis. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications.

A Photoinduced Annulation Strategy Towards a Novel Polycyclic Heteroaromatic Chromophore: Scope, Mechanism, Properties and Applications.

This article reports a detailed mechanistic and kinetic study of an unusual photoreaction leading to the (diazonia)tetrabenzonaphthacene skeleton. The photo‐triggered double intramolecular nucleophilic aromatic substitution (SNAr∗) has been investigated by varying the leaving groups. Photoreaction quantum yields have been determined and mechanistic insights have been supported by theoretical calculations using DFT and TD‐DFT methods. Additionally, we show that this light‐triggered formed diazonia constitutes a potent photosentitizer with a singlet oxygen generation quantum yield of 55 %, both in organic solvents and in water, which is an extremely relevant value in view of PDT applications or use as an oxidation photocatalyst in aqueous media. Once again, the experimental observations were supported by TD‐DFT calculations showing a large density of triplet states below the S1 excited state along with large spin‐orbit couplings. The reaction is not restricted to solutions but can also occur in solid PDMS matrices thus allowing for photochemical encoding of information that will progressively vanish upon prolonged UV‐exposure.

Hydrophilic Biocompatible Fluorescent Organic Nanoparticles as Nanocarriers for Biosourced Photosensitizers for Photodynamic Therapy.

Most photosensitizers of interest for photodynamic therapy-especially porphyrinoids and chlorins-are hydrophobic. To circumvent this difficulty, the use of nanocarriers is an attractive strategy. In this perspective, we have developed highly water-soluble and biocompatible fluorescent organic nanoparticles (FONPs) made from citric acid and diethyltriamine which are then activated by ethlynene diamine as nanoplatforms for efficient photosensitizers (PSs). Purpurin 18 (Pp18) was selected as a biosourced chlorin photosensitizer combining the efficient single oxygen generation ability and suitable absorption in the biological spectral window. The simple reaction of activated FONPs with Pp18, which contains a reactive anhydride ring, yielded nanoparticles containing both Pp18 and Cp6 derivatives. These functionalized nanoparticles combine solubility in water, high singlet oxygen generation quantum yield in aqueous media (0.72) and absorption both in the near UV region (FONPS) and in the visible region (Soret band approximately 420 nm as well as Q bands at 500 nm, 560 nm, 660 nm and 710 nm). The functionalized nanoparticles retain the blue fluorescence of FONPs when excited in the near UV region but also show deep-red or NIR fluorescence when excited in the visible absorption bands of the PSs (typically at 520 nm, 660 nm or 710 nm). Moreover, these nanoparticles behave as efficient photosensitizers inducing colorectal cancer cell (HCT116 and HT-29 cell lines) death upon illumination at 650 nm. Half maximal inhibitory concentration (IC50) values down to, respectively, 0.04 and 0.13 nmol/mL were observed showing the potential of FONPs[Cp6] for the PDT treatment of cancer. In conclusion, we have shown that these novel biocompatible nanoparticles, which can be elaborated from biosourced components, both show deep-red emission upon excitation in the red region and are able to produce singlet oxygen with high efficiency in aqueous environments. Moreover, they show high PDT efficiency on colorectal cancer cells upon excitation in the deep red region. As such, these functional organic nanoparticles hold promise both for PDT treatment and theranostics.

Exploring a Mitochondria Targeting, Dinuclear Cyclometalated Iridium (III) Complex for Image-Guided Photodynamic Therapy in Triple-Negative Breast Cancer Cells.

Photodynamic therapy (PDT) has emerged as an efficient and noninvasive treatment approach utilizing laser-triggered photosensitizers for combating cancer. Within this rapidly advancing field, iridium-based photosensitizers with their dual functionality as both imaging probes and PDT agents exhibit a potential for precise and targeted therapeutic interventions. However, most reported classes of Ir(III)-based photosensitizers comprise mononuclear iridium(III), with very few examples of dinuclear systems. Exploring the full potential of iridium-based dinuclear systems for PDT applications remains a challenge. Herein, we report a dinuclear Ir(III) complex (IRDI) along with a structurally similar monomer complex (IRMO) having 2-(2,4-difluorophenyl)pyridine and 4'-methyl-2,2'-bipyridine ligands. The comparative investigation of the mononuclear and dinuclear Ir(III) complexes showed similar absorption profiles, but the dinuclear derivative IRDI exhibited a higher photoluminescence quantum yield (Φp) of 0.70 compared to that of IRMO (Φp = 0.47). Further, IRDI showed a higher singlet oxygen generation quantum yield (Φs) of 0.49 compared to IRMO (Φs = 0.28), signifying the enhanced potential of the dinuclear derivative for image-guided photodynamic therapy. In vitro assessments indicate that IRDI shows efficient cellular uptake and significant photocytotoxicity in the triple-negative breast cancer cell line MDA-MB-231. In addition, the presence of a dual positive charge on the dinuclear system facilitates the inherent mitochondria-targeting ability without the need for a specific targeting group. Subcellular singlet oxygen generation by IRDI was confirmed using Si-DMA, and light-activated cellular apoptosis via ROS-mediated PDT was verified through various live-dead assays performed in the presence and absence of the singlet oxygen scavenger NaN3. Further, the mechanism of cell death was elucidated by an annexin V-FITC/PI flow cytometric assay and by investigating the cytochrome c release from mitochondria using Western blot analysis. Thus, the dinuclear complex designed to enhance spin-orbit coupling with minimal excitonic coupling represents a promising strategy for efficient image-guided PDT using iridium complexes.

Protein Photodamaging Activity and Photocytotoxic Effect of an Axial-Connecting Phosphorus(V)porphyrin Trimer.

An axial-connecting trimer of the porphyrin phosphorus(V) complex was synthesized to evaluate the relaxation process of the photoexcited state and the photosensitizer activity. The photoexcitation energy was localized on the central unit of the phosphorus(V)porphyrin trimer. The photoexcited state of the central unit was relaxed through a process similar to that of the monomer phosphorus(V)porphyrin. The excited state of this axially connected type of phosphorus(V)porphyrin trimer was not deactivated through intramolecular electron transfer. The singlet oxygen generation quantum yield of the trimer was almost the same as that of the monomer. The phosphorus(V)porphyrin, trimer, and monomer bound to human serum albumin and oxidized the tryptophan residue via singlet oxygen generation and electron transfer during visible light irradiation. The photocytotoxicity of these phosphorus(V)porphyrins on two cell lines was examined. The monomer induced photocytotoxicity; however, the trimer did not show cytotoxicity with or without photoirradiation. In summary, the photoexcited state of the trimer was almost the same as that of the monomer, and these phosphorus(V)porphyrins demonstrated a similar protein-photodamaging activity. The difference in association between the photosensitizer molecules and cells is the key factor of phototoxicity by these phosphorus(V)porphyrins.

Synthesis, Electrochemical and Photochemical Properties of Sulfanyl Porphyrazine with Ferrocenyl Substituents.

Ferrocene is useful in modern organometallic chemistry due to its versatile applications in material sciences, catalysis, medicinal chemistry, and diagnostic applications. The ferrocene moiety can potentially serve many purposes in therapeutics and diagnostics. In the course of this study, (6-bromo-1-oxohexyl)ferrocene was combined with dimercaptomaleonitrile sodium salt to yield a novel maleonitrile derivative. Subsequently, this compound was subjected to an autocyclotetramerization reaction using the Linstead conditions in order to obtain an octaferrocenyl-substituted magnesium(II) sulfanyl porphyrazine. Following that, both compounds-the maleonitrile derivative and the porphyrazine derivative-were subjected to physicochemical characterization using UV-Vis, ES-TOF, MALDI-TOF, and one-dimensional and two-dimensional NMR spectroscopy. Moreover, the sulfanyl porphyrazine was subjected to various photophysical studies, including optical absorption and emission measurements, as well as the evaluation of its photochemical properties. Values of singlet oxygen generation quantum yields were obtained in different organic solvents. The electrochemical properties of the synthesized compounds were studied using cyclic voltammetry. According to the electrochemical results, the presence of electron-withdrawing oxohexyl groups attached to ferrocene afforded significantly more positive oxidation potentials of the ferrocene-based redox process up to 0.34 V vs. Fc+/Fc.

Novel fluorescent mono-Br-BODIPYs as potential theranostic agents and their nanoscale zeolitic imidazolate framework delivery systems

The development of bifunctional theranostic agents based on biocompatible organic luminophores is a priority for the scientific community. We have obtained new mono-Br-substituted BODIPYs (Br-BDPs) with an optimal combination of fluorescence quantum yield (0.48 ÷ 0.63) and singlet oxygen generation quantum yield (0.32 ÷ 0.51) in different nature solvents. A detailed analysis of the structure of α-Br-BDP, β-Br-BDP, and β'-Br-BDP dyes, their spectral properties depending on the position of the bromine atom attachment and the solvent nature, as well as the aggregation behavior of the dyes in water/THF solvent mixture are presented. We also selected the conditions for the host–guest encapsulation of β-Br-BDP in zeolitic imidazolate framework (ZIF-8). The resulting nanoscale β-Br-BDP@ZIF-8 delivery systems exhibit intense fluorescence. The release of the β-Br-BDP luminophore from the β-Br-BDP@ZIF-8 systems into model lipid structures in phosphate buffer pH 5.0 – 6.0 occurs on average after 24 – 50 h. These results form the basis for the further development of new theranostic drugs based on Br-BDP luminophores for fluorescence diagnostics (FD) and photodynamic therapy (PDT).

Tuning Photochemical and Photophysical Properties of P(V) Phthalocyanines.

The ability of P(V) phthalocyanines (Pcs) for efficient singlet oxygen (SO) generation was demonstrated for the first time by the example of unsubstituted and α- and β-octabutoxy-substituted P(V)Pcs with hydroxy, methoxy and phenoxy ligands in the apical positions of the octahedral P centre. Variation of substituents in Pc ring and P(V) axial ligands allows careful tuning of photophysical and photochemical properties. Indeed, a combination of BuO groups in the β-positions of the Pc ring and PhO groups as axial ligands provides significant SO generation quantum yields up to 90%; meanwhile, the values of SO generation quantum yields for others investigated compounds vary from 27 to 55%. All the complexes, except α-substituted P(V)Pc, demonstrate fluorescence with moderate quantum yields (10-16%). The introduction of electron-donating butoxy groups, especially in the α-position, increases the photostability of P(V)Pcs. Moreover, it has been shown in the example of β-BuO-substituted P(V) that the photostability depends on the nature of axial ligands and increases in the next row: OPh < OMe < OH. The presence of oxy/hydroxy axial ligands on the P(V) atom makes it possible to switch the photochemical and photophysical properties of P(V)Pcs by changing the acidity of the media.

Mitochondria-targeted biotin-conjugated BODIPYs for cancer imaging and therapy.

Two BODIPY-biotin conjugates KDP1 and KDP2 are designed and synthesized for targeted PDT applications. Both have good absorption with a high molar absorption coefficient and decent singlet oxygen generation quantum yields. The photosensitizers KDP1 and KDP2 were found to be localized in the mitochondria with excellent photocytotoxicity of up to 18.7 nM in MDA-MB-231 breast cancer cells. The cell death predominantly proceeded through the apoptosis pathway via ROS production.

Medium viscosity effect on the fluorescent properties of arrays consisting of two BODIPY chromophores axially bound to a Sn(IV)porphyrin via a phenolate bridge

The arrays consisting of two BODIPY chromophores axially bound to a Sn(IV)Porphyrin via a phenolate bridge have been synthesized and characterized. Photophysical properties of obtained systems have been investigated in aqua medium with different viscosity due to the addition of glycerin. The fluorescence quantum yield of the triad upon excitation at different wavelengths, as well as its lifetime and singlet oxygen generation quantum yield in an excited state, has been determined. It has been shown that if in the triad composition the fluorescent properties of the BODIPY fragment are weakened in all studied media, then the fluorescent properties of the porphyrin fragment depend on the properties of the medium. Quenching of the BODIPY fluorescence and the porphyrin fluorescence enhancement in viscous media or increasing of the triad’s ability to generate singlet oxygen in water is the result of photo-induced electron transfer from the phenolate to the porphyrin fragment. The efficiency of electron transfer and, consequently, the efficiency of quenching depend on the conformational mobility of the ligandin the triad, i.e. on the relative position of the phenolic and indacene fragments, which gives the designed triad the properties of a fluorescent molecular rotor. The best efficiency of the triad as a fluorescence molecular rotor has been obtained in the low viscosity range from 1 to 4 cP.

π-Expanded pyrazinoporphyrins for photocatalysis: How many rings are required?

A series of π-expanded pyrazinoporphyrins were successfully prepared and tested as sensitizers for photocatalytic aerobic sulfides oxidation. 2,3-Diaminoporphyrin derivative was used as a key intermediate for the preparation of porphyrins fused with naphtho-, phenanthrene-, phenanthroline- and acenaphthoquinone fragments and the structures of the obtained compounds were proved by detailed analysis of NMR. The peculiarities and limitations of the condensation of diaminoporphyrin with a set of corresponding aromatic quinones were investigated. Gradual bathochromic shift of absorption bands was observed in the series of the prepared compounds, correlating with the gradual expansion of the macrocycle aromatic system. The photostability of the obtained photosensitizers was tested prior to their application as photocatalysts. The photocatalytic performance of the obtained π-expanded pyrazinoporphyrins was investigated in the aerobic oxidation of thioanisole and revealed the increase of the activity with the expansion of the π-system of the molecule. Complete conversion of the substrate and over 98% selectivity was achieved with 10−2 mol% catalyst loading, that correspond to turnover number (TON) ca. 10,000. The maximal TON = 89,000 could be reached with 10−3 mol% catalyst loading. The measurements of the singlet oxygen generation quantum yields along with the DFT analysis of perturbation of the molecular orbitals of the photosensitizers was performed. The latter analysis revealed the presence of orbitals with predominant localization either at porphyrin macrocycle or at peripheral polyaromatic part of the molecule, allowing to expect charge separation upon photoexcitation.

Metal or metal-free phthalocyanines containing morpholine substituents: synthesis, spectroscopic and photophysicochemical properties

The phthalonitrile (3) and its peripherally tetra 4-(3-morpholinophenoxy) substituted metal-free (4), lead(II) (5) and zinc(II) (6) phthalocyanine derivatives were synthesized. The structures of 3-6 were confirmed by FT-IR, 1H-NMR, MALDI-TOF mass, UV-vis and fluorescence spectral data. The solubility and aggregation behaviors of 4-6 were determined in dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), chloroform (CHCl3) and dichloromethane (CH2Cl2). The observed sharp absorptions were evidence of formation of non-aggregated phthalocyanine species at the studied concentration. The effects of the substituent and central metal ions (metal-free, zinc or lead) on spectroscopic and photophysicochemical properties were determined. Their photophysicochemical properties such as fluorescence quantum yields and lifetimes, singlet oxygen generation and photodegradation quantum yields were investigated in DMSO. The fluorescence spectra of metal-free (4) and lead(II) (5) phthalocyanines were not recorded due to negligible fluorescence emissions of these phthalocyanines. The zinc(II) phthalocyanine (6) had 0.17 fluorescence quantum yield (ΦF) and 1.42 fluorescence lifetime (τF). The phthalocyanines (4-6) had 0.18, 0.41, 0.52 singlet oxygen quantum yields (ΦΔ) and 0.51, 3.90, 0.46 photodegradation quantum yields (ΦΔ), respectively. The zinc(II) phthalocyanine (6) in particular could be a potential Type II photosensitizer candidate for photodynamic therapy in cancer treatment.

Zinc(II) Sulfanyltribenzoporphyrazines with Bulky Peripheral Substituents—Synthesis, Photophysical Characterization, and Potential Photocytotoxicity

The study’s aim was to synthesize new unsymmetrical sulfanyl zinc(II) porphyrazines and subject them to physicochemical and electrochemical characterization and also an initial acute toxicity assessment. The procedure was initiated from a commercially available dimercaptomaleonitrile disodium salt and o-phthalonitrile using Linstead’s macrocyclization reaction conditions, which led to magnesium(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents. The obtained macrocycle was demetallated with trifluoroacetic acid and subsequently remetallated with zinc(II) acetate toward the zinc(II) porphyrazine derivative. The zinc(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents was then subjected to the reduction reaction with LiAlH4, yielding zinc(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylthio substituents. The new zinc(II) tribenzoporphyrazines were characterized by UV-Vis spectroscopy, various NMR techniques (1HNMR, 13CNMR, 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC), and mass spectrometry. In the UV-Vis spectra, both macrocycles revealed characteristic Soret and Q-bands, whose positions were dependent on the solvent used for the measurements. Zinc(II) tribenzoporphyrazines were studied using electrochemical and photochemical methods, including the singlet oxygen generation assessment. Both zinc(II) porphyrazines revealed high singlet oxygen generation quantum yield values of up to 0.59 in DMSO, which indicates their potential photosensitizing potential for photodynamic therapy. In addition, new derivatives were subjected to a Microtox® bioluminescence assay.

Luminescent iridium(III) dipyrrinato complexes: synthesis, X-ray structures, and DFT and photocytotoxicity studies of glycosylated derivatives.

A series of luminescent Ir(III) dipyrrinato complexes were synthesized having various aromatic chromophores at the C-5 position of dipyrrin ligands. The presence of different chromophores on the Ir(III) dipyrrinato complexes altered their optical properties and produced strong emission in the red to NIR region (680-900 nm) with huge Stokes shifts (5910-7045 cm-1). TD-DFT studies indicated significant charge distribution between dipyrrin ligands and Ir-cyclometalated units in all the molecules. X-ray crystal structures revealed an octahedral geometry of the Ir(III) center in the complex. The in vitro studies of the glycosylated Ir(III) complexes revealed strong photoluminescence with maximum Stokes shifts, and they showed significant photocytotoxicity in skin keratinocyte (HaCaT) and lung adenocarcinoma (A549) cells. The singlet oxygen generation quantum yields of glycosylated Ir(III) complexes were in the range of 70-78% in water. The estimated IC50 values were between 17 and 25 μM after light exposure, and confocal microscopy revealed significant localization of the glycosylated Ir(III) complexes in the endoplasmic reticulum (ER) of cancer cells. The neutral Ir(III) dipyrrinato complexes are promising tracking agents for cellular imaging in the biological window and for photodynamic therapy (PDT) applications.

Pluronic stabilized conjugated polymer nanoparticles for NIR fluorescence imaging and dual phototherapy applications

• Pluronic stabilized conjugated polymer nanoparticles (CP-NP-Plu) are prepared. • CP-NP-Plu present photothermal conversion efficiency of 61% under NIR irradiation. • 2-fold increase of singlet oxygen generation quantum yield due to encapsulation with Plu • NIR fluorescence imaging ability validated at single nanoparticle level. Besides their intensive application as solar photovoltaic materials, low bandgap conjugated polymers have been recently exploited in cell imaging and phototherapeutic applications due to their photoactivity in the near-infrared (NIR) spectral domain, also known as the “biologically transparent window”. Herein, Poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole) (PCPDTBT) conjugated polymer was used to prepare novel NIR activatable theranostic nanoparticles, via nanoprecipitation method, for fluorescence imaging and dual photothermal-photodynamic therapy (PTT-PDT) applications. To overcome the drawback of hydrophobicity of PCPDTBT, the approach of encapsulating the obtained nanoparticles with a layer of Pluronic F127 amphiphilic block co-polymer was herein applied. The Pluronic layer not only provides excellent colloidal stability, but also ensures enhanced fluorescence emission, improved photothermal heating and singlet oxygen generation ability of the nanoparticles in aqueous dispersion. Specifically, upon irradiation with a NIR laser at 785 nm, the obtained nanoparticles exhibit good thermal response and excellent photostability leading to a photothermal conversion efficiency of 61%. Moreover, a near two-fold increase in the singlet oxygen generation quantum yield due to encapsulation with Pluronic is also detected. Furthermore, fluorescence imaging measurements on single nanoparticle immobilized on glass substrate reveal their potential as fluorescence contrast agents. The enhanced fluorescence and improved therapeutic properties of our nanoparticles suggest the possibility to be employed as NIR activatable theranostic agents via dual phototherapy combined with high-resolution fluorescence tracking.

Heavy-Atom Free spiro Organoboron Complexes As Triplet Excited States Photosensitizers for Singlet Oxygen Activation.

Herein, we present a new strategy for the development of efficient heavy-atom free singlet oxygen photosensitizers based on rigid borafluorene scaffolds. Physicochemical properties of borafluorene complexes can be easily tuned through the choice of ligand, thus allowing exploration of numerous organoboron structures as potent 1O2 sensitizers. The singlet oxygen generation quantum yields of studied complexes vary in the range of 0.55–0.78. Theoretical calculations reveal that the introduction of the borafluorene moiety is crucial for the stabilization of a singlet charge transfer state, while intersystem crossing to a local triplet state is facilitated by orthogonal donor–acceptor molecular architecture. Our study shows that quantitative oxidation of selected organic substrates can be achieved in 20–120 min of irradiation with only 0.05 mol % loading of a photocatalyst.

Luminescent Neutral Cyclometalated Iridium(III) Complexes Featuring a Cubic Polyhedral Oligomeric Silsesquioxane for Lipid Droplet Imaging and Photocytotoxic Applications

New neutral iridium(III) complexes featuring a cubic polyhedral oligomeric silsesquioxane (POSS) unit, [Ir(N∧C)2(L1-POSS)] [HN∧C = 2-phenylpyridine (Hppy; 1), 2-phenylbenzothioazole (Hbt; 2), and 2-(1-naphthyl)benzothiazole (Hbsn; 3); L1-POSS = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-heptakis(isobutyl)POSS-propyl carbamate], were designed and synthesized. Their POSS-free counterparts, [Ir(N∧C)2(L1)] [L1 = (E)-N-(4-hydroxymethylphenyl)-1-(2-hydroxyphenyl)methanimine; HN∧C = Hppy (1a), Hbt (2a), and Hbsn (3a)], and the poly(ethylene glycol) (PEG) derivatives [Ir(N∧C)2(L1-PEG)] [L1-PEG = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-[2-[ω-methoxypoly(1-oxapropyl)]ethyl]carbamate; HN∧C = Hppy (1b), Hbt (2b), and Hbsn (3b)] were also prepared. The photophysical, photochemical, and biological properties of the POSS complexes were compared with those of their POSS-free and PEG-modified counterparts. Upon irradiation, all of these complexes displayed orange-to-red emission and long emission lifetimes under ambient conditions. The bsn complexes 3, 3a, and 3b exhibited the highest singlet oxygen (1O2) generation quantum yields (ΦΔ = 0.85-0.86) in aerated CH3CN. Laser-scanning confocal microscopy images revealed that complexes 1-3 and 1a-3a showed exclusive lipid-droplet staining upon cellular uptake, while the PEG derivatives 1b-3b displayed lysosomal localization. Complex 3 was utilized to study various lipid-droplet-related biological events including lipid-droplet accumulation under oleic acid stimulation, the movement of lipid droplets, and preadipocyte differentiation. Notably, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the ppy complexes 1 and 1b and the bt complexes 2 and 2b were noncytotoxic both in the dark and upon irradiation at 450 nm for 5 min (IC50 > 200 μM), while the bsn complexes 3, 3a, and 3b showed low dark cytotoxicity (IC50 = 52.9 to >200 μM) and high photocytotoxicity (IC50 = 1.1-5.3 μM). The cellular uptake, internalization mechanisms, and cell death pathways of these complexes were also investigated. This work not only offers promising luminescent probes for lipid droplets through the structural modification of iridium(III) complexes but also paves the way to the construction of new reagents for theranostics.

Quantitative Structure-Property Relationship Modelling for the Prediction of Singlet Oxygen Generation by Heavy-Atom-Free BODIPY Photosensitizers*.

Heavy‐atom‐free sensitizers forming long‐living triplet excited states via the spin‐orbit charge transfer intersystem crossing (SOCT‐ISC) process have recently attracted attention due to their potential to replace costly transition metal complexes in photonic applications. The efficiency of SOCT‐ISC in BODIPY donor‐acceptor dyads, so far the most thoroughly investigated class of such sensitizers, can be finely tuned by structural modification. However, predicting the triplet state yields and reactive oxygen species (ROS) generation quantum yields for such compounds in a particular solvent is still very challenging due to a lack of established quantitative structure‐property relationship (QSPR) models. In this work, the available data on singlet oxygen generation quantum yields (ΦΔ) for a dataset containing >70 heavy‐atom‐free BODIPY in three different solvents (toluene, acetonitrile, and tetrahydrofuran) were analyzed. In order to build reliable QSPR model, a series of new BODIPYs were synthesized that bear different electron donating aryl groups in the meso position, their optical and structural properties were studied along with the solvent dependence of singlet oxygen generation, which confirmed the formation of triplet states via the SOCT‐ISC mechanism. For the combined dataset of BODIPY structures, a total of more than 5000 quantum‐chemical descriptors was calculated including quantum‐chemical descriptors using density functional theory (DFT), namely M06‐2X functional. QSPR models predicting ΦΔ values were developed using multiple linear regression (MLR), which perform significantly better than other machine learning methods and show sufficient statistical parameters (R=0.88–0.91 and q2=0.62–0.69) for all three solvents. A small root mean squared error of 8.2 % was obtained for ΦΔ values predicted using MLR model in toluene. As a result, we proved that QSPR and machine learning techniques can be useful for predicting ΦΔ values in different media and virtual screening of new heavy‐atom‐free BODIPYs with improved photosensitizing ability.

Nipagin-Functionalized Porphyrazine and Phthalocyanine-Synthesis, Physicochemical Characterization and Toxicity Study after Deposition on Titanium Dioxide Nanoparticles P25.

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.

Singlet oxygen generation by porphyrins and metalloporphyrins revisited: A quantitative structure-property relationship (QSPR) study

Porphyrins and metalloporphyrins are used as photosensitizers in photocatalysis, photodynamic therapy (PDT), disinfection, degradation of persistent pollutants and other applications. Their mechanism of action involves intersystem crossing to triplet excited state followed by formation of singlet oxygen (1O2), which is a highly reactive species and mediates various oxidative processes. The design of advanced sensitizers based on porphyrin compounds have attracted significant attention in recent years. However, it is still difficult to predict the efficiency of singlet oxygen generation for a given structure. Our goal was to develop a quantitative structure-property relationship (QSPR) model for the fast virtual screening and prediction of singlet oxygen quantum yields for pophyrins and metalloporphyrins. We performed QSPR analysis of a dataset containing 32 compounds, including various porphyrins and their analogues (chlorins and bacteriochlorins). Quantum-chemical descriptors were calculated using Density Functional Theory (DFT), namely B3LYP and M062X functionals. Three different machine learning methods were used to develop QSPR models: random forest regression (RFR), support vector regression (SVR), and multiple linear regression (MLR). The optimal QSPR model «structure – singlet oxygen generation quantum yield» obtained using RFR method demonstrated high determination coefficient for the training set (R2 = 0.949) and the highest predicting ability for the test set (pred_R2 = 0.875). This proves that the developed QSPR method is realiable and can be directly applied in the studies of singlet oxygen generation both for free base porphyrins and their metal complexes. We believe that QSPR approach developed in this study can be useful for the search of new poprhyrin photosensitizers with enhanced singlet oxygen generation ability.