Ferroptosis is an iron-dependent lipid-peroxidation-driven mechanism of cell death and a promising therapeutic target to eradicate cancer cells. In this study, we discovered that boronic acid-derived ...salicylidenehydrazone (BASHY) dyes are highly efficient singlet-oxygen photosensitizers (PSs; ΦΔ up to 0.8) that induce ferroptosis triggered by photodynamic therapy. The best-performing BASHY dye displayed a high phototoxicity against the human glioblastoma multiform U87 cell line, with an IC50 value in the low nanomolar range (4.40 nM) and a remarkable phototoxicity index (PI > 22,700). Importantly, BASHY dyes were shown to accumulate in lipid droplets (LDs) and this intracellular partition was found to be essential for the enhanced phototoxicity and the induction of ferroptosis through lipid peroxidation. The safety and phototoxicity of this platform were validated using an in vivo zebrafish model (Danio rerio)
The irradiation of 2-aryl-4-(
-3'-aryl-allylidene)-5(4
)-oxazolones
with blue light (456 nm) in the presence of Ru(bpy)
(BF
)
(bpy = 2,2'-bipyridine, 5% mol) gives the unstable ...cyclobutane-bis(oxazolones)
by 2+2-photocycloaddition of two oxazolones
. Each oxazolone contributes to the formation of
with a different C=C bond, one of them reacting through the exocyclic C=C bond, while the other does so through the styryl group. Treatment of unstable cyclobutanes
with NaOMe/MeOH produces the oxazolone ring opening reaction, affording stable styryl-cyclobutane bis(amino acids)
. The reaction starts with formation of the T
excited state of the photosensitizer
Ru*(bpy)
, which reacts with S
of oxazolones
through energy transfer to give the oxazolone T
state
(oxa*)-
, which is the reactive species and was characterized by transient absorption spectroscopy. Measurement of the half-life of
(oxa*)-
for
,
and
shows large values for
and
(10-12 μs), while that of
is shorter (726 ns). Density functional theory (DFT) modeling displays strong structural differences in the T
states of the three oxazolones. Moreover, study of the spin density of T
state
(oxa*)-
provides clues to understanding the different reactivity of 4-allylidene-oxazolones described here with respect to the previously reported 4-arylidene-oxazolones.
A series of boronic acid derived salicylidenehydrazone (BASHY) complexes was prepared and photophysically characterized. The dye platform can be modified by (a) electronic tuning along the ...cyanine-type axis via modification of the donor–acceptor pair and (b) functional tuning via the boronic acid residue. On the one hand, approach (a) allows the control of photophysical parameters such as Stokes shift, emission color, and two-photon-absorption (2PA) cross section. The resulting dyes show emission light-up behavior in nonpolar media and are characterized by high fluorescence quantum yields (ca. 0.5–0.7) and brightness (ca. 35000–40000 M–1 cm–1). Moreover, the 2PA cross sections reach values in the order of 200–300 GM. On the other hand, the variation of the dye structure through the boronic acid derived moiety (approach (b)) enables the functionalization of the BASHY platform for a broad spectrum of potential applications, ranging from biorelevant contexts to optoelectronic materials. Importantly, this functionalization is generally electronically orthogonal with respect to the dye’s photophysical properties, which are only determined by the electronic structure of the cyanine-type backbone (approach (a)). Rare exceptions to this generalization are the presence of redox-active residues (such a triphenylamine or pyrene). Finally, the advantageous photophysics is complemented by a significant photostability.
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•A natural Fe2O3 compound was effectively employed as stable heterogeneous PMS activator.•Hormuz Red Soil (HRS) was fully characterized (XRF, DLS, XRD, EDX, TEM, SEM, XPS, ...BET).•Diclofenac degradation and bacterial inactivation was achieved at minute-range.•EPR and scavenger tests revealed a dominant radical mechanism, with small 1O2 participation.•HRS was stable in 5 reuse tests and effective as a supported catalyst in continuous mode.
A natural, ferruginous material, Hormuz Red Soil (HRS), was used as a catalyst for decontamination and disinfection via PMS activation. The HRS was fully characterized (morphological, structural, chemical properties) and was mainly comprised of α-Fe2O3. Complete degradation and 88.6% mineralization of Diclofenac (DCF) was achieved in the HRS/PMS process (10 mg/L HRS, 75 mg/L PMS) within 8 min at neutral pH, while sulfate and chloride did not inhibit the process. E. coli and Enterococcus sp. were rapidly inactivated in shorter timeframe than DCF. The rapid purification was attributed to SO4∙-, less to 1O2 and almost insignificant HO∙ participation; the degradation mechanisms and transformation pathways were fully elucidated by scavenging tests/EPR, and LC/MS, respectively. Considering potential applications, HRS was supported on alginate beads (HRSB), maintaining high activity and high reusability (x5 reuse). Finally, a continuous-flow, packed-bed process with HRSB/PMS was assessed, where DCF degradation and mineralization was reached within 2 min HRT.
The irradiation of (Z)-2-phenyl-4-aryliden-5(4H)-oxazolones 1 in deoxygenated CH2Cl2 at 25 °C with blue light (465 nm) in the presence of Ru(bpy)3(BF4)2 (5% mole ratio) as a triplet photocatalyst ...promotes the 2+2 photocycloaddition of the CC bonds of the 4-arylidene moiety, thus allowing the completely regio- and stereoselective formation of cyclobutane-bis(oxazolone)s 2 as single stereoisomers. Cyclobutanes 2 have been unambiguously characterized as the μ-isomers and contain two E-oxazolones coupled in an anti-head-to-head form. The use of continuous-flow techniques in microreactors allows the synthesis of cyclobutanes 2 in only 60 min, compared with the 24–48 h required in batch mode. Ring opening of the oxazolone heterocycle in 2 with a base affords the corresponding 1,2-diaminotruxinic bis-amino esters 3, which are also obtained selectively as μ-isomers. The ruthenium complex behaves as a triplet photocatalyst, generating the reactive excited state of the oxazolone via an energy-transfer process. This reactive excited state has been characterized as a triplet diradical 3(E/Z)-1* by laser flash photolysis (transient absorption spectroscopy). This technique also shows that this excited state is the same when starting from either (Z)- or (E)-oxazolones. Density functional theory calculations show that the first step of the 2+2 cycloaddition between 3(E/Z)-1* and (Z)-1 is formation of the C(H)–C(H) bond and that (Z) to (E) isomerization takes place at the 1,4-diradical thus formed.
Intramolecular excited triplet state interactions in diastereomeric compounds composed of a benzophenone chromophore (ketoprofen) and various hydrogen donor moieties (tetrahydrofuran, ...isopropylbenzene) have been investigated by laser flash photolysis. The rate constants for hydrogen abstraction by excited triplet benzophenone are in the order of 104−105 s-1, with the highest reactivity for the tetrahydrofuran residue. A remarkable diastereodifferentiation, expressed in the triplet lifetimes of the carbonyl chromophore (e.g., 1.6 versus 2.7 μs), has been found for these compounds. With an alkylaromatic moiety as donor, related effects have been observed, albeit strongly dependent on the length of the spacer. The reactivity trend for the initial hydrogen transfer step is paralleled by the quantum yields of the overall photoreaction. The biradicals, formed via remote hydrogen abstraction, undergo intramolecular recombination to macrocyclic ring systems. The new photoproducts have been isolated and characterized by NMR spectroscopy. The stereochemistry of the macrocycles, which contain up to four asymmetric carbons, has been unambiguously assigned on the basis of single-crystal structures and/or NOE effects. Interestingly, a highly regio- and stereoselective macrocyclization has been found for the ketoprofen−tetrahydrofuran conjugates, where hydrogen abstraction from the less substituted carbon is exclusive; cisoid ring junction is always preferred over the transoid junction. The photoreaction is less regioselective for compounds with an isopropylbenzene residue. The reactivity and selectivity trends have been rationalized by DFT (B3LYP/6-31G*) calculations.
A remarkable stereodifferentiation has been observed in the interaction between the excited triplet state of carprofen (CP) and human serum albumin (HSA). Time-resolved measurements using laser flash ...photolysis reveal the presence of two components with different lifetimes in triplet decay. This is explained by complexation of CP to the two possible HSA binding sites. The shorter-lived components are ascribed to the CP/HSA complexes in site I, where stereodifferentiation is more important (τR/τS ca. 4). This is correlated with formation of a dehalogenated photoproduct upon steady-state photolysis.
The aim of this study was to evaluate the water disinfection capability of new immobilized photocatalysts based on the organic photosensitizer Rose Bengal (RB) supported on glass wool and with two ...different photocatalyst load (RB_GW_0.22 and RB_GW_0.02). Tests were carried out under different operating conditions in a solar simulator at 30 W/m2 average UV-A irradiation. Isotonic water (IW) (with 9 g/L NaCl), simulated tap water (STW) and simulated urban wastewater effluent (SUWWE) spiked with Escherichia coli and Enterococcus faecalis (106 CFU/mL initial concentrations) were used as water model microbial strains. The mere effect of only irradiance was also investigated as reference of the photocatalytic performance over both bacteria. Results showed that RB_GW_0.22 presented high inactivation for E. faecalis, reaching 6 Log Reduction Value (LRV) in 2 min in IW and STW at pH 5 and 6 in comparison with only irradiance (60 min). In SUWWE, the effect of RB_GW_0.22 was also better for E. faecalis inactivation (60 min), compared to that produced in E. coli (120 min) and without the presence of the photocatalyst (where total inactivation was not achieved after 120 min of treatment). Ecotoxicity (ISO 11348–3:2007) and phytotoxicity (EN ISO 18763:2020) tests of the treated water were also assessed and results showed any significant effect, concluding that the use of RB_GW_0.22 is a promising solar photocatalytic treatment for urban wastewater reclamation and reuse.
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•A novel immobilized Rose Bengal on glass wool (RB_GW) was developed for water disinfection.•RB_GW at two load of RB showed significant antibacterial capability (0.22%>>0.02%).•Gram (+) E. faecalis showed higher susceptibility to RB_GW than gram (-) E. coli.•> 5 LRV of both bacteria after 2 h of irradiance (30 W/m2) by RB_GW_0.22 in SUWW.•Low or null eco- or phyto-toxicity detected for treated SUWW with RB_GW_0.22.
•Superior E. coli disinfection efficacy occurred by unactivated PMS vs. PDS/H2O2.•Kinetic, biochemical, and genetic analyses defined the inactivation path.•SO4•− was the pivotal ROS, generated by the ...reaction between PMS & biomolecules.•External oxidation leads to cell envelope disruption and intracellular attacks.•Mutants’ tests uncovered gene responses induced by intracellular radical pathways.
This study examined the antimicrobial efficacy of peroxymonosulfate (PMS) against bacteria, using Escherichia coli (E. coli) as a model organism. Our investigation delineates the complex mechanisms exerted by unactivated PMS. Thus, an initial redox reaction between PMS and the target biomolecules of bacteria generates SO4•− as the pivotal reactive species for bacterial inactivation; to a lesser extent, •OH, 1O2, or O2•− may also participate. Damage generated during oxidation was identified using an array of biochemical techniques. Specifically, redox processes are promoted by PMS and SO4•− targets and disrupt various components of bacterial cells, predominantly causing extracellular damage as well as intracellular lesions. Among these, external events are the key to cell death. Finally, by employing gene knockout mutants, we uncovered the role of specific gene responses in the intracellular damage induced by radical pathways. The findings of this study not only expand the understanding of PMS-mediated bacterial inactivation but also explain the ten-fold higher effectiveness of PMS than that reported for H2O2. Hence, we provide clear evidence that unactivated PMS solutions generate SO4•− in the presence of bacteria, and consequently, should be considered an effective disinfection method.
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Abstract
The light‐gated organocatalysis via the release of 4‐
N
,
N
‐dimethylaminopyridine (DMAP) by irradiation of the Ru(bpy)
2
(DMAP)
2
2+
complex with visible light was investigated. As model ...reaction the acetylation of benzyl alcohols with acetic anhydride was chosen. The pre‐catalyst releases one DMAP molecule on irradiation at wavelengths longer than 455 nm. The photochemical process was characterized by steady‐state irradiation and ultrafast transient absorption spectroscopy. The latter enabled the observation of the
3
MLCT state and the spectral features of the penta‐coordinated intermediate Ru(bpy)
2
(DMAP)
2+
. The released DMAP catalyzes the acetylation of a wide range of benzyl alcohols with chemical yields of up to 99 %. Control experiments revealed unequivocally that it is the released DMAP which takes the role of the catalyst.
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