# Kinetic effects in singlet oxygen mediated oxidations by immobilized photosensitizers on silica

Maxime Lancel, Mikaël Lindgren, Cyrille Monnereau, Zacharias Amara

► To cite this version:

Maxime Lancel, Mikaël Lindgren, Cyrille Monnereau, Zacharias Amara. Kinetic effects in singlet oxygen mediated oxidations by immobilized photosensitizers on silica. Photochemical & Photobiological Sciences, 2023, 23 (1), pp.79-92. 10.1007/s43630-023-00502-5. hal-05136757

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<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
Kinetic Effects in Singlet Oxygen Mediated Oxidations by Immobilized Photosensitizers
on Silica

Maxime Lancel,<fnref n="1" /> Mikaël Lindgren,<fnref n="2" /> Cyrille Monnereau,<fnref n="3" />* Zacharias Amara<fnref n="1" />*

**Abstract:** Singlet oxygen (¹O₂) mediated photo-oxidations are important reactions involved in numerous processes in chemical and biological sciences. While most of the current research works have aimed at improving the efficiencies of these transformations either by increasing ¹O₂ quantum yields or by enhancing its lifetime, we establish herein that immobilization of a molecular photosensitizer onto silica surfaces affords significant, substrate dependant, enhancement in the reactivity of ¹O₂. Probing a classical model reaction (oxidation of Anthracene-9,10-dipropionic acid, ADPA or dimethylanthracene, DMA) with various spectrofluorimetric techniques, we it is here proposed that an interaction between polar substrates and the silica surface is responsible for the observed phenomenon. This discovery could have a direct impact on the design of future photosensitized ¹O₂ processes in various applications ranging from organic photochemistry to photobiology.

# 1 Introduction

Singlet oxygen (¹O₂) is a highly reactive species which can react with a large variety of biological components such as amino-acids, nucleic acids or unsaturated fatty acids through electrophilic additions.[1–3] It is used in medical applications such as photodynamic therapy.[4–6] It can also react with secondary metabolic pathways to produce bioactive natural products, some of which are of commercial interests, such as juglone,[7, 8] rose-oxide[9–11] or artemisinin.[12–16]. It is therefore a reagent of fundamental relevance not only to multiple aspects of biology but also to chemical synthesis where its atom-economical character makes it an appealing oxidant.[9, 17–21]

On a photophysical viewpoint, ¹O₂ can be generated by triplet-triplet collisional energy transfer between a photoexcited triplet sensitizer (photocatalyst) and ground state triplet oxygen.[22] The main strategies for improving ¹O₂ reactions developed so far have mainly focused on the structural modifications of organic or organometallic photosensitizers to achieve high quantum yields in ¹O₂ production.[23] This is typically done by structural modifications of the corresponding dye to enhance singlet-to-triplet intersystem crossing process at the excited state, most generally by increasing spin-orbit coupling through the introduction of heavy elements (halogens[1, 24–26] or transition metals[27]), low-lying n-π* transitions (aromatic ketones[28–30]) or various conformational (distorted π conjugated molecules[31–33]) and electronic (charge transfer mechanisms[32, 34] or excitonic couplings[35]) effects. Alternatively, ¹O₂ lifetime can be enhanced by using more compatible chemical environments[36] such as deuterated[37] or perhalogenated solvents, or supercritical carbon dioxide,[38] the latter having found interesting applications in organic synthesis and in green chemistry. Finally, plasmonic antenna effects have occasionally been used to maximize light absorption by the system and thereby, for a given ¹O₂ generation quantum efficiency, to maximize ¹O₂ production.[39–41] These strategies constitute the core and current paradigm in ¹O₂ mediated chemical transformations optimizations. Indeed a kinetic analysis of the different

<footnote n="1">¹Equipe Chimie Moléculaire, Laboratoire de Génomique, Bioinformatique et Chimie Moléculaire, (GBCM), EA 7528, Conservatoire national des arts et métiers, HESAM université, Paris, 75003, France</footnote>

<footnote n="2">² Faculty of Natural Sciences, Department of Physics, Norwegian University of Science and Technology, Gløshaugen, NO-7491 Trondheim, Norway</footnote>

<footnote n="3">³ ENS de Lyon, CNRS UMR 5182, Laboratoire de Chimie, University of Lyon, 69364 Lyon, France</footnote>

<footnote>*zacharias.amara@lecnam.net *cyrille.monnereau@ens-lyon.fr</footnote>
processes governing the efficiency of a simple oxidation reaction of a substrate A reveals that, in the steady-state approximation, the reaction rate d[A]/dt can be expressed as [42]

$$ - \frac{d[A]}{dt} = I_a \phi_{\Delta} k_r [A] / (k_d + k_r [A]) \qquad \text{eq 1} $$

Where [A] corresponds to substrate concentration, $I_a$ is the photon absorption rate by the sensitizer, $\phi_{\Delta}$ the $^1O_2$ generation quantum efficiency, $k_d$ is the solvent dependent deactivation rate of $^1O_2$ (reciprocal of the lifetime of $^1O_2$) and finally $k_r$ the kinetic constant associated to $^1O_2$ reaction with the substrate. In the three above-mentioned strategies, focus has been put on maximizing $\phi_{\Delta}$, minimizing $k_d$, or maximizing $I_a$ respectively. Yet, examination of the equation reveals that increasing the kinetic constant of $^1O_2$ addition onto a given substrate ($k_r$) is another possible strategy, although less easily addressable.

One way to increase $k_r$ is to create a confinement of $^1O_2$ with the substrate. This principle can be used to increase the so called “effective molarity” i.e., to create a local environment in which the catalyst-reactant-reagent of the system are kept in close vicinity, allowing the three components of the reaction to take place even when the mean free path of the reactive species (in the present case, $^1O_2$) is highly restricted. Such strategy, which is central (although not exclusive) in the working principle of many enzymatic systems [43–46] has been used as a blue-print in the design of many supramolecular catalysts [47]. It has also been applied in photochemistry on several occasions such as for example in supramolecular confinements, [48] but the design and synthesis of such complex catalysts involve a cost that may render it hardly relevant for practical industrial applications. We thought that immobilized photosensitizers on heterogeneous supports was an interesting cheaper and potentially beneficial strategy to approach this issue. In green chemistry, the development of heterogeneous catalysts is attractive for recycling purposes and is predominant in large-scale industrial processes. [49, 50] Organic transformations and in particular reactivity and selectivity are modified in heterogeneous catalysis due to substrate adsorption/desorption effects on the surface according to the Langmuir–Hinshelwood and the Eley–Rideal mechanisms. [51] In the case of photooxidation chemistry, a heterogenized photosensitizer must produce $^1O_2$ after absorption of light meaning that $^3O_2$ needs to diffuse in the heterogeneous structure and $^1O_2$ needs to diffuse away to encounter its target. The process is therefore considerably affected by the mass transfer properties of the system. In this work, we turned our attention on the heterogenization of photosensitizers on silica. The use of silica-based heterogeneous systems to produce $^1O_2$ such as photosensitizers immobilized on silica or mesoporous silica has been the subject of intense research efforts in the fields of photodynamic therapy, [52–55] water decontamination [56, 57] and organic synthesis. [58–66] However, although some of these works clearly underlined the benefits of surface immobilization of the photosensitizer, in particular in terms of recycling properties, [64–66] none provided evidence of the origin of an increased reactivity at the molecular level. In this context, our group previously reported the straightforward immobilization of various cationic photosensitizers on silica particles and there use as recyclable photocatalytic system in photooxidative transformations (Fig. 1). In these works, we noted a dramatic acceleration of reaction rates with substrates bearing polar functionalities. We postulated that such phenomena could be explained by confinements of reactive $^1O_2$ species and substrates at the surface of silica particles via “outer sphere effects”. [65] However, we also highlighted the surprisingly high enhancement in the stability of the immobilized photosensitizers. [66] Optical effects, such as the enhancement of photon residence times due to refractive properties of silica particles also come into play and understanding the exact origin of the kinetic effects appears to be relatively complex. We therefore report herein an in-depth mechanistic analysis, at the molecular
level, of these heterogeneous photochemical reaction systems using various spectroscopy techniques. In order to probe a solution or solid phase ¹O₂ reactivity, we took advantage of various direct and indirect spectroscopic techniques (direct ¹O₂ phosphorescence measurements, transient emission spectroscopy, in time monitoring of the photobleaching of ¹O₂ scavengers). Taking equation 1 as a kinetic model for the singlet oxygen mediated photoxydation reaction, it can be seen that, for a given photosensitizer (considering that φ<sub>Δ</sub> is unaffected by heterogenization) at a given concentration/absorbance, at a constant oxygen concentration and natural lifetime (common solvent, atmospheric pressure) and for a given substrate, at a constant initial concentration [A], the rate of substrate oxidation should be solely dependent on the apparent oxidation constant k<sub>r</sub>, in a pseudo-first order fashion. Thus, comparison of the oxidation rate for the native homogeneous molecular photosensitizer and the different supported version of this catalyst on micro- (MP) or nano- (NP) sized silica particle should enable systematic and straightforward evaluation on the effect of immobilization on the photooxidation kinetics. Starting from this work hypothesis, we show that the nature and extent of this effect is dependent not only on the nature of the photosensitizer (and more particularly on its affinity to the support) but also, and perhaps even more critically, on that of the substrate.

Previous works: Kinetic effects with immobilized photosensitizers on silica

a) Principle: immobilization of cationic photosensitizers lead to enhanced reactivity

<figure><img src="image_2.png" /></figure>

b) Example of photosensitizers enabling this effect

<figure><img src="image_3.png" /></figure>

This work: Probing the kinetic effect via direct and indirect measurements

a) Direct detection of liquid phase ¹O₂ species

<figure><img src="image_4.png" /></figure>

b) Selective trapping of ¹O₂ species via polarity match

<figure><img src="image_5.png" /></figure>

**Fig. 1** Our previous work reported the enhancement of reactivity of polar substrates using immobilized photosensitizers on silica. The scope of the present study is to provide a better understanding of the origin of this effect at the molecular level using direct and indirect ¹O₂ spectroscopy measurements.
## 2 Materials and methods

### 2.1 General

Tris(2,2'-bipyridyl)ruthenium(II) Chloride Hexahydrate ([Ru(bpy)₃Cl₂]), [5,10,15,20-tetrakis(1-methyl-4-pyridinium)-porphyrin tetra-(p-toluenesulfonate) [TMPyP⁴⁺], Tetraphenylporphyrin [TPP] and Methylene Blue [MB] was purchased from TCI, micrometric silica was purchased from Masherey Nagel 60 M (0.04-0.063 mm), tetraethoxysilane was purchased from TCI, aqueous ammonia 28-30% was purchased from Merck. 3,3'-(Anthracene-9,10-diyl)dipropanoic acid (ADPA) and Dimethylanthracene (DMA) was purchased from Sigma Aldrich. Acetonitrile (spectrophotometric grade, 99.7+%) was purchased from Alfa Aesar, d3-acetonitrile and d₁-chloroform were purchased from Eurisotop. All commercial reagents and solvents were used as received.

### 2.2 Samples preparation

All samples were prepared to obtain a concentration of 0.78 µmol of photosensitizer per gram of silica support.

* **Immobilization on micrometric silica (0.04-0.063 mm)**

* **Immobilization general procedure:**

In a 250 mL flask, 1 g of micrometric silica was dispersed by magnetic stirring in freshly distilled water (100 mL) and 0.78 µmol of PS, by the intermediate of a stock solution of in water (c = 1 g/L), was added at room temperature. The mixture was stirred for 2 hours at room temperature and then filtered, washed 3 times with 15 mL distilled water, and the solid was dried in an oven at 60°C overnight to yield PS@SiO₂.

* **Immobilization on nanometric silica**

* **Synthesis of silica nanoparticles.**

SiO₂ nanoparticles were prepared using the Stöber method presented by Thomassen et al. [67] 200 mL of ethanol, 6 mL of distilled water and 10 mL of NH₄OH (28-30 %) were added in a 500 mL three-neck round bottom flask under stirring (700 rpm). Tetraethoxyorthosilane (8 mL) was added dropwise to the solution. The solution was left under stirring (700 rpm) for 48 hours at room temperature. Then, SiO₂ nanoparticles were removed by centrifugation (3 times, 6500 rpm, 45 minutes), redispersed in distilled water and freeze dried. Finally, around 1 g of SiO₂ nanoparticles were obtained with an average hydrodynamic size of 150 ± 45 nm to 190 ± 50 nm in number.

* **Immobilization general procedure**

100 mg of SiO₂ were dispersed in 100 mL of distilled water and 0.078 µmol was added from a stock solution of PS in water (c = 1 g/L). The mixture was allowed to stir for 2 hours. The particles were recovered by centrifugation (7000 rpm, 15 min) after 3 aqueous washes (3x20 mL) and then dried in a freeze drier to yield PS@SiO₂.

### 2.3 Steady state and transient spectroscopy

Luminescence spectra were measured using a Horiba-Jobin-Yvon Fluorolog-3® spectrofluorimeter, equipped with a three-slit double-grating excitation and emission monochromator with dispersions of 2.1 nm (1200 grooves.mm⁻¹). In the visible range [400-845 nm] the R928 detector was used for emission intensity measurements. Spectra were reference corrected for both the excitation source light intensity variation (lamp and grating) and the emission spectral response (detector and grating). In the case of degassed samples, measurements were performed in cuvettes equipped with a Young's valve after extensive degassing by three "freeze-pump-thaw" cycles. In all measurements, magnetic stirring was applied, using an electronic stirrer (Rank Brothers Ltd., Model 300).
Singlet-oxygen phosphorescence were recorded using a liquid nitrogen cooled, solid Indium/Gallium/Arsenic detector (850-1600 nm). In order to maximize ¹O₂ lifetime and phosphorescence signal d₃-acetonitrile and d₁-chloroform was used as a solvent in all cases. Luminescence signal was recorded irradiating Ru(bpy)₃²⁺ at 390 nm, TMPyP⁴⁺ and phenalenone at 410 nm, MB⁺ at 650 nm and TPP at 400 nm (excitation slits: 10 nm, emission slits: 14 nm. In order to improve signal-to-noise ratio, included spectra are the sum of 4 consecutive scans between 1240 and 1330 nm, integration interval of 1 nm, integration time of 1s).

Luminescence lifetime measurements were carried out in acetonitrile solutions of Ru(bpy)₃²⁺ or colloidal suspensions of Ru(bpy)₃²⁺@SiNPs, using two detection system. For short life-times (ns ranges) an IBH Time-Correlated Single Photon Counting (TCSPC) system was employed, with a 469 nm Nanoled excitation. The detection was based on emission monochromator (5000 M, Glaskow, UK) typically set to 16 nm bandwidth and a TBX-04D picosecond photon detection module. The IBH Data Station v 2.1 software was used for reconvolution fits. For longer life-times (µs - ms) and singlet oxygen detection, a tunable OPO laser (NT342A-SH-10-WW Ekspla, Lithuania) was used for excitation. Typically, pulses of energy 10 – 15 mJ were used. For transient recording, a PMT (R5509, Hamamatsu) and a bandpass interference filter with maximum transmission at 1272.5 nm and a long pass filter transmitting above 780 nm, were used in conjunction. An Infiniium BDSU Oscilloscope (Keysight, United States) was used to collect and monitor data. Time-gated electronics was used to control the time between the laser excitation and the recording of the luminescence transient. It is emphasized that this system cannot resolve time-responses (fluorescence, rapid phosphorescence) in the ns – 1 µs range, as it is optimized for singlet oxygen luminescence in the 10 µs - ms range. OriginPro 2018 software was used for post-data processing and graphical plotting. See Hageberg et al. [doi/pdf/10.1002/cptc.202300028] for more examples of singlet oxygen lifetime systems and theory of singlet oxygen kinetics in homogeneous media.

## 2.4 Evaluation of photocatalytic activity

For comparison of ¹O₂ generation efficiency using a ADPA as a scavenger, 2 mL of freshly prepared acetonitrile (alternatively : chloroform) solutions of 3,3'-(Anthracene-9,10-diyl)dipropanoic acid and of either PS homogeneous and on silica particles (at the same photosensitizer concentration) were placed in a 3 mL open quartz cuvette(1 X 1 X 3 cm), and stirred at 60 rpm for the whole irradiation period. Initial optical density of ADPA in the reaction mixture is of 0.1 at the irradiation wavelength, which was centered at 430 nm for experiments with Ru(bpy)₃²⁺, at 410 nm for experiments with TMPyP⁴⁺, at 652 nm for experiments with MB⁺ and at 400 nm for experiments with TPP. Entrance slits were set at 7 nm opening. This setup ensured a constant irradiation power throughout all the irradiations experiments. Conversion of ADPA scavenger upon reaction with the photogenerated oxygen was followed by continuous measurement of the luminescence signal of the latter (considering it linearly proportional to its concentration, which is valid in the investigated range of absorbance) every 60 or 120 minutes upon irradiation allowing to plot its evolution vs irradiation time. Between each point, the PS luminescence was monitored to verify potential PS deactivation. Fittings of the resulting plot can be found in the S3 part of the supporting information. The same procedure was applied using DMA as a scavenger, in chloroform exclusively. Methodology used for data interpretation is described in full in a previous report.[68]
## 3 Results and Discussion

We designed a study using three photosensitizers displaying increasing columbic interactions with silica and two different fluorescent probes enabling polar or non-polar interactions. The photosensitizers were immobilized onto silica micro- and nanoparticles to examine the role of the silica particles size in the photooxidation kinetics. In each case, the immobilized photosensitizer was prepared with an active site density (the quantity of photosensitizer adsorbed on the silica surface) of 0.78 µmol/g. All sensitizers were readily and quantitatively adsorbed on silica.

### 3.1 Singlet oxygen generation

In order to quantitatively understand the fate of the excitation of $^3O_2$ and production of $^1O_2$, we monitored the characteristic phosphorescence signal of $^1O_2$ upon photoexcitation. In order to maximize signal to noise ratio, CD$_3$CN was used in these experiments, because the longer $^1O_2$ lifetime in deuterated solvents and hence $^1O_2$ phosphorescence intensity can be detected with higher sensitivity. Also, we determined the $^1O_2$ phosphorescence signal in the presence of phenalenone to determine an apparent singlet oxygen quantum yield with ruthenium trisbipyridine (Ru(bpy)$_3$)$^{2+}$, tetrakis methyl pyridinium porphyrin (TMPyP$^{4+}$) and methylene blue (MB$^+$) and their heterogenized counterparts (active site density fixed at 0.78 µmol in all cases).

Surprisingly, while the Ru(bpy)$_3^{2+}$ solution showed an intense characteristic signal at 1277 nm this signal was markedly quenched for the supported catalyst (Fig. 2a). Using phenalenone as a reference, we determined a quantum yield of 0.62 for Ru(bpy)$_3^{2+}$, consistent with literature data. Meanwhile, $^1O_2$ phosphorescence intensity was quenched by ca 60% and 80% for Ru(bpy)$_3^{2+}$@SiNPs and Ru(bpy)$_3^{2+}$@SiMPs, respectively. With TMPyP$^{4+}$, an even stronger $^1O_2$ phosphorescence quenching was observed with the heterogenized photosensitizers (Fig. 2b). We estimated quantum yields of 0.94 for TMPyP$^{4+}$ which was quenched by ca 90% and 95% for TMPyP$^{4+}$@SiNPs and TMPyP$^{4+}$@SiMPs, respectively. However, obtained results were quite different with MB$^+$ (Fig. 2c). Indeed, a similar $^1O_2$ phosphorescence intensity, corresponding in a quantum yield of 0.72 was observed for MB$^+$ and MB$^+$@SiNPs demonstrating the absence of $^1O_2$ phosphorescence quenching in the latter. Similarly, only a moderate 10% drop was observed for MB$^+$@SiMPs.

<figure><img src="image_6.png" /><figcaption>**Fig. 2 (A)** $^1O_2$ phosphorescence intensity in presence of Ru(bpy)$_3^{2+}$ in solution and heterogenized in CD$_3$CN (OD = 0.1), **(B)** $^1O_2$ phosphorescence intensity in presence of TMPyP$^{4+}$ in solution and heterogenized in CD$_3$CN (OD = 0.1), **(C)** MB$^+$ in solution and heterogenized in CD$_3$CN (OD = 0.1).</figcaption></figure>

$^1O_2$ emission efficiency is intimately linked to the lifetime of this excited species, which is notoriously dependent on the nature of its environment, most importantly the solvent (hence our choice to use deuterated acetonitrile, the presence of C-H in this case or, even worse, O-H and N-H vibrators being prone to lower the signal intensity and thereby decrease signal-to-noise ratio), but also on every other element present in the reaction mixture that can
potentially detrimentally interact with this photogenerated excited state of molecular oxygen. Here, the presence
of free silanol groups at the surface of the catalyst support may play such a detrimental role.

In order to confirm this hypothesis of a support-induced quenching of singlet oxygen intensity, we performed
singlet oxygen lifetime experiments measurements, by measuring in-time decay of the 1277 nm centered
luminescence, on two of the studied systems, namely for Ru(bpy)₃²⁺@SiNPs, which we compared to that obtained
with the native ruthenium complex in solution (Fig. 3). For the pure ruthenium solution a dominant lifetime decay
contribution with a characteristic τ = 115.6 ± 0.9 μs, reasonably close to reported values for the natural lifetime of
fluorescence of singlet oxygen in acetonitrile (τ approx. 80 μs,[69] highly dependent on the quality of the
acetonitrile and the presence of contaminants like water in particular). In the deaerated solution, this long-lived
contribution disappeared and only a much shorter lifetime contribution was dominating, which correspond well
with that of the ruthenium complex phosphorescence measured at 620 nm in similar excitation conditions (Fig.
3b). (τ = 917 ± 3.0 ns was recorded in separate TC SPC measurement; data not shown.) It can be concluded that
this signal comes from some residual phosphorescence of the Ru(bpy)₃²⁺ with the tail of the luminescence spectrum
extending into the NIR. When Ru(bpy)₃²⁺@SiNPs was considered, this signal became dominant, and only a smaller
contribution of ¹O₂ was seen which could be fitted to a bi exponential model, with a shorter τ₁ = 3.4 ± 0.5 μs
(Amplitude Weight, AW=65%) and longer τ₂ = 68.6 ± 5 μs (AW=35%) contribution (Fig. 3b). Again, in deaerated
solutions, these long lifetime contributions disappear from the signal and only the Ru(bpy)₃²⁺ luminescence signal
remains. Altogether these observations are consistent with our hypothesis of a reduced ¹O₂ lifetime being at the
origin of the marked decrease in ¹O₂ phosphorescence signals for almost all supported catalysts. However, the
minor contribution of a longer lifetime, again close to the reported value for ¹O₂ in pure acetonitrile solution, might
in our opinion be indicative of partial (reversible) leaching of the photosensitizer as a result from its desorption
from the silica based support upon dispersion into acetonitrile. This may explain while quenching is less severe
when MB⁺ based heterogeneous systems are considered (monocationic species, weaker adsorption), than with
Ru(bpy)₃²⁺ based systems (dicationic) and why highest quenching efficiency is seen for TMPyP₄⁺ (tetracationic).

<figure><img src="image_7.png" /><figcaption>**Fig. 3** Transient ¹O₂-luminescence of (A) Ru(bpy)₃²⁺ (10 µM; black dotted line) and (B) RuNP (Ru(bpy)₃²⁺@SiNP; 0.5 mg/ml) (red dotted line). Excitation was at 469 nm and the emission detected at 1275 nm. The solid green lines are fits with polyexponential models, providing us with the lifetimes as depicted in the text. The dashed blue line is the signal obtained after thoroughly deaerating the very same samples with Ar, underlining the disappearance of singlet oxygen associated signal in both cases, and the presence of a short lifetime contribution corresponding to the tail of Ru(bpy)₃²⁺ phosphorescence signal</figcaption></figure>
In order to verify the validity of our hypothesis we reproduced similar experiments in CDCl₃ with Ru(bpy)₃²⁺ and MB⁺ with homogeneous and heterogenized photosensitizers (Fig. 4). CDCl₃ being a solvent with considerably less eluting power than acetonitrile, it was expected to consistently reduce leaching of the adsorbed dyes from the silica support. In both cases, the ¹O₂ signal was completely quenched using heterogenized photosensitizers, in good agreement with the above-mentioned effect of surface environment on ¹O₂ lifetime and our expectation of a stronger adsorption of the photocatalyst onto the silica surface. For MB⁺ especially, MB⁺@SiNPs and MB⁺@SiMPs exhibited an important quenching, which was not the case when the experiments were carried out in CD₃CN.

<figure><img src="image_8.png" /><figcaption>**Fig. 4** ¹O₂ phosphorescence intensity in presence of (A) Ru(bpy)₃²⁺ (OD = 0.1) and (B) MB⁺ in solution and heterogenized in CDCl₃ (OD = 0.1)</figcaption></figure>

To summarize, immobilization of all photocatalysts on silica supports (MP or NP) leads to at least a partial quenching of the ¹O₂ phosphorescence intensity, to an extent that is both critically dependent on the nature of the photosensitizers (polycationic species being the most quenched), the nature of the solvent (acetonitrile resulting in partial leaching of the PS), and, although to a lesser extent, to that of the support (quenching being more effective on microparticle supports than on nanoparticles). Altogether, these studies bring compelling evidence that ¹O₂ stability (and thus lifetime) is severely affected by the local environment where it is generated, and that, in the present case, the presence of free silanols on the surface of the support has highly detrimental consequence on this parameter.

## 3.2 In-situ monitoring of the photooxidative reactivity

In order to assess to which extent this surface-induced singlet oxygen quenching may affect the photocatalytic efficiency of the heterogenized catalysts, we next compared the photoreactivity of ¹O₂ with anthracene derivatives under homogeneous and heterogeneous conditions with Ru(bpy)₃²⁺, TMPyP⁴⁺ and MB⁺ in two different solvents (CH₃CN and CHCl₃). In addition, we tested tetraphenylporphyrin (TPP) as a non-ionic soluble probe, which only weakly interacts with silica due to acid-base interactions. The photoinduced bleaching of the ¹O₂ scavengers, ADPA (anthracene dipropionic acid) or DMA (dimethyl anthracene), which evolve into a nonfluorescent endoperoxide products upon reaction with ¹O₂, was used as a monitoring tool (Scheme 1) allowing easy in-time following of the photocatalytic process (endoperoxide formation) upon *in situ* continuous irradiation of isoabsorbing mixtures of the various photosensitizing systems. In these studies, ADPA, a dianionic anthracene derivative that should strongly adsorb onto the silica surfaces, was used as a first model substrate, while DMA, a highly apolar component that should not adsorb onto the surface in our solvation conditions, was chosen as a
second one. Systematic comparisons of their respective reactivity were thus performed, in order to evaluate the incidence on support/substrate interaction on the catalytic efficiency.

<figure><img src="image_9.png" /><figcaption>**Scheme 1** (A) Photoinduced bleaching of ADPA after reaction with $^1O_2$; (B) Photoinduced bleaching of DMA after reaction with $^1O_2$</figcaption></figure>

The ADPA photobleaching reaction was monitored in time, by continuous measurement of anthracene luminescence decay, upon irradiation of the catalytic system at an excitation wavelength of 430 nm for $Ru(bpy)_3^{2+}$, 414 nm for $TMPyP^{4+}$ and 652 nm for $MB^+$. With these protocols in hand, and after linearization of the luminescence decay data according to a first order kinetic model (See Equation 1), it was possible to estimate the evolution in the kinetic constant of $^1O_2$ addition onto the anthracene scavenger resulting from immobilization of the cationic photocatalysts onto silica. In the case of the $Ru(bpy)_3^{2+}$ supported system compared to the reference homogeneous system (at the same photosensitizer concentration and incident light intensity), we observed an enhancement of the kinetic constants $k_{Ru@SiMPs}$ and $k_{Ru@SiNPs}$ by a factor of 16 and 10 (Fig. 5a). A similar increase in ADPA fluorescence decay was observed with immobilized $TMPyP^{4+}$ with enhancement of the kinetic constants $k_{TMPyP@SiMPs}$ and $k_{TMPyP@SiNPs}$ by a factor of 18 and 6 respectively (Fig. 5b). Finally, and somewhat surprisingly in regard with the contrasted results obtained in $^1O_2$ phosphorescence experiments with $MB^+$ based systems, a rapid ADPA fluorescence decay was observed with $MB^+$ supported on microparticles with an enhancement of the kinetic constant $k_{MB@SiMPs}$ by an impressive factor of 22. Such high enhancement of the catalytic efficiency was not observed with $MB^+$@SiNPs with enhancement of the kinetic constant by a more modest factor of 1.85 (Fig. 5c). To sum up, when there exists an adsorption between the substrate and the catalytic support, photooxidation catalytic efficiency seems to be much increased in the heterogenized catalysts, which might appear counterintuitive considering the much decreased $^1O_2$ lifetime clearly assessed in these systems. In other words, the advantage in bringing the substrate in close vicinity to the photocatalytic center seems to surpass the disadvantage in having a marked reduced lifetime for the catalytically active species. Furthermore, with $MB^+$@SiNPs we carried out an experiment in order to verify the role of the $MB^+$ charge density on silica on the ADPA photooxidation kinetics. We compared the reactivity of $MB^+$@SiNPs 0.39 µmol/g in addition of the previous experiment with $MB^+$@SiNPs where the active site density was 0.78 µmol/g. We observed that lower MB density charge participate to reduce the efficiency of the ADPA fluorescence decay. Indeed, we observe a 4.4 time decrease of the kinetic constant of
MB⁺@SiNPs 0.39 µmol/ g in comparison with MB⁺@SiNPs 0.78 µmol/g (See ESI). On the other hand, TPP has no positive charge and cannot be strongly adsorbed onto silica surface by electrostatic interactions in such eluotropic solvents as acetonitrile. We compared the reactivity of homogeneous and “pseudo-immobilized” TPP in the presence of silica microparticles (0.78 µmol/g) in acetonitrile. In striking contrast to its related tetracationic counterpart TMPyP⁴⁺, only little acceleration of the ADPA decay was observed with TPP@SiMPs which corresponds to a two-fold increase of the kinetic constant in comparison with homogeneous TPP (Fig. 5d, far from the factor 18 obtained with TMPyP⁴⁺ in otherwise identical conditions). This mild acceleration suggests that weak interactions between the silica surface and porphyrin (through hydrogen bonding between the donor free base porphyrin and the acceptor silanol) may be enough to immobilize a small proportion of TPP on the surface.

<figure><img src="image_10.png" /></figure>

<figure><img src="image_11.png" /><figcaption>**Fig. 5 (A)** In-time monitoring of the emission intensity of ADPA luminescence in CH₃CN upon photoillumination at 430 nm; Ru(bpy)₃²⁺ (red squares); Ru(bpy)₃²⁺@SiMPs (0.78 µmol/ g, green circles); Ru(bpy)₃²⁺@SiNPs (0.78 µmol/ g, blue triangles) (B) In-time monitoring of the emission intensity of ADPA luminescence in CH₃CN upon photoillumination at 410 nm; TMPyP⁴⁺ (red triangles); Phenalenone (black circles); TMPyP⁴⁺@SiMPs (0.78 µmol/ g, green triangles); TMPyP⁴⁺@SiNPs (0.78 µmol/ g, blue squares) (C) In-time monitoring of the emission intensity of ADPA luminescence in CH₃CN upon</figcaption></figure>
photoillumination at 652 nm; Phenalenone (black triangles); MB⁺ (red squares); MB⁺@SiMPs (0.78 µmol/ g, green circles); MB⁺@SiNPs (0.78 µmol/ g, blue triangles); (D) In-time monitoring of the emission intensity of ADPA luminescence in CH₃CN upon photoillumination at 400 nm; Phenalenone (black triangles); TPP (red squares); TPP@SiMPs (0.78 µmol/ g, green circles).

We next decided to compare the fluorescence decay of ADPA in CHCl₃, where adsorption of both the photocatalysts and ADPA substrate should be strongly enhanced. In that case, an enhancement of the kinetic constants kRu@SiMPs and kRu@SiNPs was observed to be a factor of 19 and 36, respectively in comparison with soluble Ru(bpy)₃²⁺(Fig. 6a). Similar improvement of ¹O₂ reactivity was observed with MB⁺ with enhancement of kinetic constants kMB@SiMPs and kMB@SiNPs by 10 and 27, respectively (Fig. 6b). All these results are in agreement with our abovementioned hypothesis of a favorable effect of substrate and catalyst co-adsorption on the photoinduced oxidation kinetics.

<figure><img src="image_12.png" /><figcaption>**Fig. 6 (A)** In-time monitoring of the emission intensity of ADPA luminescence in CHCl₃ upon photoillumination at 430 nm; Ru(bpy)₃²⁺ (red squares); Ru(bpy)₃²⁺@SiMPs (0.78 µmol/ g, green circles); Ru(bpy)₃²⁺@SiNPs (0.78 µmol/ g, blue triangles)

**Fig. 6 (B)** In-time monitoring of the emission intensity of ADPA luminescence in CHCl₃ upon photoillumination at 652 nm; MB⁺ (red squares); MB⁺@SiMPs (0.78 µmol/ g, green circles); MB⁺@SiNPs (0.78 µmol/ g, blue triangles).</figcaption></figure>

Interestingly, results were completely different by monitoring the fluorescence decay of DMA upon similar treatments as for ADPA. With Ru(bpy)₃²⁺, the homogeneous PS clearly outperformed the heterogenized PS with kinetic constants 5 time and 4.4 time higher than kRu@SiMPs and kRu@SiNPs, respectively (Fig. 7a). Similarly, the DMA fluorescence decay was significantly faster with the homogeneous MB⁺ than MB⁺@SiMPs and MB⁺@SiNPs (Fig. 7b). MB⁺ kinetic constants were 38 time higher than kMB@SiMPs and 7.9 time higher than kMB@SiNPs.
<figure><img src="image_13.png" /><figcaption>**Fig. 7 (A)** In-time monitoring of the emission intensity of DMA luminescence in CHCl<sub>3</sub> upon photoillumination at 430 nm; Ru(bpy)<sub>3</sub><sup>2+</sup> (red squares); Ru(bpy)<sub>3</sub><sup>2+</sup>@SiMPs (0.78 µmol/ g, green triangles); Ru(bpy)<sub>3</sub><sup>2+</sup>@SiNPs (0.78 µmol/ g, blue circles) (B) In-time monitoring of the emission intensity of DMA luminescence in CHCl<sub>3</sub> upon photoillumination at 652 nm; MB<sup>+</sup> (red squares); MB<sup>+</sup>@SiMPs (0.78 µmol/ g, green circles), MB<sup>+</sup>@SiNPs (0.78 µmol/ g, blue triangles).</figcaption></figure>

These experiments shed light on the relevance of non-covalent interactions between polar substrates and silica particles. These interactions favor a close proximity between substrates and $^1O_2$ produced at the surface of silica particles, which in turn has a drastic effect on the reactivity of $^1O_2$ when immobilized photosensitizers on silica are used. However, with non-polar substrates, this substrate-silica interaction is reduced. In this case, the photooxidation process with supported photosensitizers is less efficient. Similarly, the catalyst-to-support interactions also have a crucial importance on the outcome of the photocatalytic reaction. A final definitive confirmation of this feature was obtained when comparing the photocatalytic efficiency of TPP with and without silica.

Thus, as a general explanation, we propose that substrate polarity and an efficient Coulombic adsorption of the photosensitizer are key to observe an acceleration of the $^1O_2$ mediated photooxidation process with the heterogenized systems. ADPA is a polar substrate and can interact with silica particles. At the surface of silica, we demonstrated that $^1O_2$ is confined, as its lifetime is reduced by orders of magnitudes in comparison to what is observed with homogeneous photosensitizers (Scheme 2). Thus, the proximity between polar substrates and $^1O_2$ is improved which enables to enhance photooxidation kinetics. In this regard, results obtained with the ADPA fluorescence decay monitoring and the measurement of $^1O_2$ phosphorescence intensity are reversely correlated, photosensitizers exhibiting a rapid ADPA decay show an important $^1O_2$ quenching as well.

Conversely, experiments carried out with DMA confirm the importance of the substrate polarity to observe an acceleration effect with immobilized photosensitizers. With DMA, these silica-substrate interactions are significantly reduced, which explain the inefficiency of the heterogenized photosensitizers in this specific case,
and an opposite correlation is noticed: in that case, decrease of the $^1O_2$ phosphorescence signal translates into a drop in catalytic efficiency.

<figure><img src="image_14.png" /><figcaption>**Scheme 2** Putative mechanism to explain kinetics observed using heterogenized photosensitizers with polar and apolar substrates.</figcaption></figure>

## 4 Conclusion

To conclude, we demonstrated that the straightforward immobilization of photosensitizers on silica particles represents an efficient strategy to improve the reactivity of singlet oxygen mediated photooxidations. We observed that such improvements were caused by specific interactions between polar substrate and silica particles. This allowed to enhance the proximity between substrates and $^1O_2$ produced at the surface of silica particles leading to drastic improvement of photooxidation kinetics. Heterogenized photosensitizers represents an interesting green alternative to soluble photosensitizers with in addition good stability and recyclability features. The present work suggests that such heterogenized systems might be particularly relevant when oxidation of highly polar substrates are involved, such as carboxylic acides, amines, alcohols or phosphate substituents as contained in many naturally or pharmaceutically occurring molecules. We believe that this work provides relevant insights on the parameters influencing the photosensitization properties of supported photooxygenation catalysts, and may pave the way for further developments in this field.

**Acknowledgements** The French Ministry of Higher Education, Research and Innovation and Doctoral School "Sciences des Métiers de l'Ingénieur" (ED 432) are gratefully acknowledged for a PhD scholarship attributed to M.L. Z.A. is grateful to the French National Research Agency (ANR-21-CE07-0030 and ANR-21-CE29-0028) for funding.

**Author contributions** The manuscript was written through the contributions of all authors and all authors have read and agreed to the final version of the manuscript.

**Declarations**

**Conflict of interest** The authors declare no competing financial interest.
References

1. DeRosa M (2002) Photosensitized singlet oxygen and its applications. Coordination Chemistry Reviews 233-234:351-371. https://doi.org/10.1016/S0010-8545(02)00034-6

2. Foote CS, Wexler S (1964) Singlet Oxygen. A Probable Intermediate in Photosensitized Autoxidations. J Am Chem Soc 86:3880-3881. https://doi.org/10.1021/ja01072a061

3. Di Mascio P, Martinez GR, Miyamoto S, Ronsein GE, Medeiros MHG, Cadet J (2019) Singlet Molecular Oxygen Reactions with Nucleic Acids, Lipids, and Proteins. Chem Rev 119:2043-2086. https://doi.org/10.1021/acs.chemrev.8b00554

4. Monro S, Colón KL, Yin H, Roque J, Konda P, Gujar S, Thummel RP, Lilge L, Cameron CG, McFarland SA (2019) Transition Metal Complexes and Photodynamic Therapy from a Tumor-Centered Approach: Challenges, Opportunities, and Highlights from the Development of TLD1433. Chem Rev 119:797-828. https://doi.org/10.1021/acs.chemrev.8b00211

5. Ogilby PR (2010) Singlet oxygen: there is indeed something new under the sun. Chem Soc Rev 39:3181. https://doi.org/10.1039/b926014p

6. Bogoeva V, Siksjo M, Sæterbø KG, Melø TB, Bjørkøy A, Lindgren M, Gederaas OA (2016) Ruthenium porphyrin-induced photodamage in bladder cancer cells. Photodiagnosis and Photodynamic Therapy 14:9-17. https://doi.org/10.1016/j.pdpdt.2016.01.012

7. Griffiths J, Chu K-Y, Hawkins C (1976) Photosensitised oxidation of 1-naphthols. J Chem Soc, Chem Commun 676. https://doi.org/10.1039/c39760000676

8. Takizawa S, Aboshi R, Murata S (2011) Photooxidation of 1,5-dihydroxynaphthalene with iridium complexes as singlet oxygen sensitizers. Photochem Photobiol Sci 10:895. https://doi.org/10.1039/c0pp00265h

9. Ohloff G (1975) Singlet oxygen: a reagent in organic synthesis. In: Bruylants A, Ghosez L, Viehe HG (eds) Organic Synthesis. Butterworth-Heinemann, pp 481-502

10. Ravelli D, Protti S, Neri P, Fagnoni M, Albini A (2011) Photochemical technologies assessed: the case of rose oxide. Green Chem 13:1876-1884. https://doi.org/10.1039/c0gc00507j

11. Terra JCS, Desgranges A, Monnereau C, Sanchez EH, De Toro JA, Amara Z, Moores A (2020) Photocatalysis Meets Magnetism: Designing Magnetically Recoverable Supports for Visible-Light Photocatalysis. ACS Appl Mater Interfaces 12:24895-24904. https://doi.org/10.1021/acsami.0c06126

12. Covello PS (2008) Making artemisinin. Phytochemistry 69:2881-2885. https://doi.org/10.1016/j.phytochem.2008.10.001

13. Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Jiang H, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528-532. https://doi.org/10.1038/nature12051

14. Lévesque F, Seeberger PH (2012) Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin. Angew Chem Int Ed 51:1706-1709. https://doi.org/10.1002/anie.201107446

15. Amara Z, Bellamy JFB, Horvath R, Miller SJ, Beeby A, Burgard A, Rossen K, Poliakoff M, George MW (2015) Applying green chemistry to the photochemical route to artemisinin. Nature Chem 7:489-495. https://doi.org/10.1038/nchem.2261

16. Kopetzki D, Lévesque F, Seeberger PH (2013) A Continuous-Flow Process for the Synthesis of Artemisinin. Chemistry - A European Journal 19:5450-5456. https://doi.org/10.1002/chem.201204558

17. Montagnon T, Tofi M, Vassilikogiannakis G (2008) Using Singlet Oxygen to Synthesize Polyoxygenated Natural Products from Furans. Acc Chem Res 41:1001-1011. https://doi.org/10.1021/ar800023v

18. Ghogare AA, Greer A (2016) Using Singlet Oxygen to Synthesize Natural Products and Drugs. Chem Rev 116:9994-10034. https://doi.org/10.1021/acs.chemrev.5b00726

19. Richard J-A (2009) Singlet Oxygen. Synlett 2009:1187-1188. https://doi.org/10.1055/s-0028-1088111

20. Al-Nu'airat J, Oluwoye I, Zeinali N, Altarawneh M, Dlugogorski BZ (2021) Review of Chemical Reactivity of Singlet Oxygen with Organic Fuels and Contaminants. Chem Rec 21:315-342. https://doi.org/10.1002/tcr.202000143

21. Pibiri I, Buscemi S, Palumbo Piccionello A, Pace A (2018) Photochemically Produced Singlet Oxygen: Applications and Perspectives. ChemPhotoChem 2:535-547. https://doi.org/10.1002/cptc.201800076

22. Schmidt R (2006) Photosensitized Generation of Singlet Oxygen. Photochemistry and Photobiology 82:1161-1177. https://doi.org/10.1562/2006-03-03-IR-833

23. Mehraban N, Freeman HS (2015) Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production. Materials 8:4421-4456. https://doi.org/10.3390/ma8074421
24. Sánchez-Arroyo AJ, Palao E, Agarrabeitia AR, Ortiz MJ, García-Fresnadillo D (2016) Towards improved halogenated BODIPY photosensitizers: clues on structural designs and heavy atom substitution patterns. *Phys Chem Chem Phys* 19:69–72. https://doi.org/10.1039/C6CP06448E

25. Gorman A, Killoran J, O'Shea C, Kenna T, Gallagher WM, O'Shea DF (2004) In Vitro Demonstration of the Heavy-Atom Effect for Photodynamic Therapy. *J Am Chem Soc* 126:10619–10631. https://doi.org/10.1021/ja047649e

26. Mettra B, Liao YY, Gallavardin T, Armagnat C, Pitrat D, Baldeck P, Bahers TL, Monnereau C, Andraud C (2018) A combined theoretical and experimental investigation on the influence of the bromine substitution pattern on the photophysics of conjugated organic chromophores. *Phys Chem Chem Phys* 20:3768–3783. https://doi.org/10.1039/C7CP06535C

27. Ashen-Garry D, Selke M (2014) Singlet Oxygen Generation by Cyclometalated Complexes and Applications. *Photochemistry and Photobiology* 90:257–274. https://doi.org/10.1111/php.12211

28. Arnbjerg J, Paterson MJ, Nielsen CB, Jørgensen M, Christiansen O, Ogilby PR (2007) One- and Two-Photon Photosensitized Singlet Oxygen Production: Characterization of Aromatic Ketones as Sensitizer Standards. *J Phys Chem A* 111:5756–5767. https://doi.org/10.1021/jp0711971

29. Westberg M, Bregnhøj M, Etzerodt M, Ogilby PR (2017) No Photon Wasted: An Efficient and Selective Singlet Oxygen Photosensitizing Protein. *J Phys Chem B* 121:9366–9371. https://doi.org/10.1021/acs.jpcb.7b07831

30. Oliveros E, Suardi-Murasecco P, Aminian-Saghafi T, Braun AM, Hansen H-J (1991) 1H-Phenalen-1-one: Photophysical Properties and Singlet-Oxygen Production. *Helvetica Chimica Acta* 74:79–90. https://doi.org/10.1002/hlca.19910740110

31. Galán LA, Castán JMA, Dalinot C, Marqués PS, Blanchard P, Maury O, Cabanetos C, Bahers TL, Monnereau C (2020) Theoretical and experimental investigation on the intersystem crossing kinetics in benzothioxanthene imide luminophores, and their dependence on substituent effects. *Phys Chem Chem Phys* 22:12373–12381. https://doi.org/10.1039/D0CP01072C

32. Zhang X, Wang Z, Hou Y, Yan Y, Zhao J, Dick B (2021) Recent development of heavy-atom-free triplet photosensitizers: molecular structure design, photophysics and application. *J Mater Chem C* 9:11944–11973. https://doi.org/10.1039/D1TC02535J

33. Yan Y, Sukhanov AA, Bousquet MHE, Guan Q, Zhao J, Voronkova VK, Escudero D, Barbon A, Xing Y, Gurzadyan GG, Jacquemin D (2021) Does Twisted π-Conjugation Framework Always Induce Efficient Intersystem Crossing? A Case Study with Benzo[b]- and [a]Phenanthrene-Fused BODIPY Derivatives and Identification of a Dark State. *J Phys Chem B* 125:6280–6295. https://doi.org/10.1021/acs.jpcb.1c03189

34. Zhao J, Chen K, Hou Y, Che Y, Liu L, Jia D (2018) Recent progress in heavy atom-free organic compounds showing unexpected intersystem crossing (ISC) ability. *Org Biomol Chem* 16:3692–3701. https://doi.org/10.1039/C8OB00421H

35. Galán LA, Andrés Castán JM, Dalinot C, Marqués PS, Galiana J, Blanchard P, Andraud C, Dumont E, Maury O, Cabanetos C, Monnereau C, Le Bahers T (2021) Exploring the Concept of Dimerization-Induced Intersystem Crossing: At the Origins of Spin-Orbit Coupling Selection Rules. *J Phys Chem B* 125:8572–8580. https://doi.org/10.1021/acs.jpcb.1c05082

36. Bregnhøj M, Westberg M, Minaev BF, Ogilby PR (2017) Singlet Oxygen Photophysics in Liquid Solvents: Converging on a Unified Picture. *Acc Chem Res* 50:1920–1927. https://doi.org/10.1021/acs.accounts.7b00169

37. Ogilby PR, Foote CS (1982) Chemistry of singlet oxygen. 36. Singlet molecular oxygen ($^1\Delta_g$) luminescence in solution following pulsed laser excitation. Solvent deuterium isotope effects on the lifetime of singlet oxygen. *J Am Chem Soc* 104:2069–2070. https://doi.org/10.1021/ja00371a067

38. Bourne RA, Han X, Poliakoff M, George MW (2009) Cleaner Continuous Photo-Oxidation Using Singlet Oxygen in Supercritical Carbon Dioxide. *Angewandte Chemie* 121:5426–5429. https://doi.org/10.1002/ange.200901731

39. Mendoza C, Désert A, Chateau D, Monnereau C, Khrouz L, Lerouge F, Andraud C, M. Monbaliu J-C, Parola S, Heinrichs B (2020) Au nanobipyramids@mSiO₂ core–shell nanoparticles for plasmon-enhanced singlet oxygen photooxygenations in segmented flow microreactors. *Nanoscale Advances* 2:5280–5287. https://doi.org/10.1039/D0NA00533A

40. Gellé A, Price GD, Voisard F, Brodusch N, Gauvin R, Amara Z, Moores A (2021) Enhancing Singlet Oxygen Photocatalysis with Plasmonic Nanoparticles. *ACS Appl Mater Interfaces* 13:35606–35616. https://doi.org/10.1021/acsami.1c05892

41. Macia N, Kabanov V, Heyne B (2020) Rationalizing the Plasmonic Contributions to the Enhancement of Singlet Oxygen Production. *J Phys Chem C* 124:3768–3777. https://doi.org/10.1021/acs.jpcb.9b10724

42. Wilkinson F, Helman WP, Ross AB (1995) Rate Constants for the Decay and Reactions of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution. An Expanded and Revised
Compilation. Journal of Physical and Chemical Reference Data 24:663-677.
https://doi.org/10.1063/1.555965

43. Kitajima N, Umehara Y, Son A, Kondo T, Tanabe K (2018) Confinement of Singlet Oxygen Generated from Ruthenium Complex-Based Oxygen Sensor in the Pores of Mesoporous Silica Nanoparticles. Bioconjugate Chem 29:4168-4175. https://doi.org/10.1021/acs.bioconjchem.8b00811

44. Ramamurthy V (2000) Controlling photochemical reactions via confinement: zeolites. Journal of Photochemistry and Photobiology C: Photochemistry Reviews 1:145-166. https://doi.org/10.1016/S1389-5567(00)00010-1

45. Natarajan A, Kaanumalle LS, Jockusch S, Gibb CLD, Gibb BC, Turro NJ, Ramamurthy V (2007) Controlling Photoreactions with Restricted Spaces and Weak Intermolecular Forces: Exquisite Selectivity during Oxidation of Olefins by Singlet Oxygen. J Am Chem Soc 129:4132-4133. https://doi.org/10.1021/ja070086x

46. Naim K, Nair ST, Yadav P, Shanavas A, Neelakandan PP (2018) Supramolecular Confinement within Chitosan Nanocomposites Enhances Singlet Oxygen Generation. ChemPlusChem 83:418-422.
https://doi.org/10.1002/cplu.201800041

47. Kirby AJ (1996) Enzyme Mechanisms, Models, and Mimics. Angewandte Chemie International Edition in English 35:706-724. https://doi.org/10.1002/anie.199607061

48. Cacciapaglia R, Di Stefano S, Mandolini L (2004) Effective Molarities in Supramolecular Catalysis of Two-Substrate Reactions. Acc Chem Res 37:113-122. https://doi.org/10.1021/ar020076v

49. Friend CM, Xu B (2017) Heterogeneous Catalysis: A Central Science for a Sustainable Future. Acc Chem Res 50:517-521. https://doi.org/10.1021/acs.accounts.6b00510

50. Heveling J (2012) Heterogeneous Catalytic Chemistry by Example of Industrial Applications. J Chem Educ 89:1530-1536. https://doi.org/10.1021/ed200816g

51. Chorkendorff I, Niemantsverdriet JW (2017) Concepts of Modern Catalysis and Kinetics. John Wiley & Sons

52. Yang Y, Zeng Z, Almatrafi E, Huang D, Zhang C, Xiong W, Cheng M, Zhou C, Wang W, Song B, Tang X, Zeng G, Xiao R, Li Z (2022) Core-shell structured nanoparticles for photodynamic therapy-based cancer treatment and related imaging. Coordination Chemistry Reviews 458:214427.
https://doi.org/10.1016/j.ccr.2022.214427

53. Ding B, Shao S, Yu C, Teng B, Wang M, Cheng Z, Wong K-L, Ma P, Lin J (2018) Large-Pore Mesoporous-Silica-Coated Upconversion Nanoparticles as Multifunctional Immunoadjuvants with Ultrahigh Photosensitizer and Antigen Loading Efficiency for Improved Cancer Photodynamic Immunotherapy. Advanced Materials 30:1802479. https://doi.org/10.1002/adma.201802479

54. Maldonado-Carmona N, Ouk T-S, Leroy-Lhez S (2022) Latest trends on photodynamic disinfection of Gram-negative bacteria: photosensitizer's structure and delivery systems. Photochem Photobiol Sci 21:113-145.
https://doi.org/10.1007/s43630-021-00128-5

55. Noreen S, Maqbool A, Maqbool I, Shafique A, Khan MM, Junejo Y, Ahmed B, Anwar M, Majeed A, Abbas M, Naveed M, Madni A (2022) Multifunctional mesoporous silica-based nanocomposites: Synthesis and biomedical applications. Materials Chemistry and Physics 285:126132.
https://doi.org/10.1016/j.matchemphys.2022.126132

56. Cheng C, Tan X, Lu D, Wang L, Sen T, Lei J, El-Toni AM, Zhang J, Zhang F, Zhao D (2015) Carbon-Dot-Sensitized, Nitrogen-Doped TiO₂ in Mesoporous Silica for Water Decontamination through Nonhydrophobic Enrichment-Degradation Mode. Chemistry – A European Journal 21:17944-17950.
https://doi.org/10.1002/chem.201502301

57. García-Fresnadillo D (2018) Singlet Oxygen Photosensitizing Materials for Point-of-Use Water Disinfection with Solar Reactors. ChemPhotoChem 2:512-534. https://doi.org/10.1002/cptc.201800062

58. Chen X-F, Ng DKP (2021) β-Cyclodextrin-conjugated phthalocyanines as water-soluble and recyclable sensitizers for photocatalytic applications. Chem Commun 57:3567-3570.
https://doi.org/10.1039/D1CC00713K

59. Ronzani F, Costarramone N, Blanc S, Benabbou AK, Bechec ML, Pigot T, Oelgemöller M, Lacombe S (2013) Visible-light photosensitized oxidation of α-terpinene using novel silica-supported sensitizers: Photoxygenation vs. photodehydrogenation. Journal of Catalysis 303:164-174.
https://doi.org/10.1016/j.jcat.2013.04.001

60. Body N, Lefebvre C, Eloy P, Haynes T, Hermans S, Riant O (2023) Impact of silica nanoparticles architectures on the photosensitization of O₂ by immobilized Rose Bengal. Journal of Photochemistry and Photobiology A: Chemistry 440:114648. https://doi.org/10.1016/j.jphotochem.2023.114648

61. Mendoza C, Emmanuel N, Páez CA, Dreesen L, Monbaliu J-CM, Heinrichs B (2018) Improving Continuous Flow Singlet Oxygen Photoxygenation Reactions with Functionalized Mesoporous Silica Nanoparticles. ChemPhotoChem 2:890-897. https://doi.org/10.1002/cptc.201800148

62. Xu J, Pelluau T, Monnereau C, Guari Y, Bonneviot L, Rodríguez-Pizarro M, Albela B (2023) Incorporation of methylene blue into mesoporous silica nanoparticles for singlet oxygen generation. New J Chem 47:1861-1871. https://doi.org/10.1039/D2NJ04835C
63. Soria-Castro SM, Lebeau B, Cormier M, Neunlist S, Daou TJ, Goddard J-P (2020) Organic/Inorganic Heterogeneous Silica-Based Photoredox Catalyst for Aza-Henry Reactions. European Journal of Organic Chemistry 2020:1572–1578. https://doi.org/10.1002/ejoc.201901382

64. Blanchard V, Asbai Z, Cottet K, Boissonnat G, Port M, Amara Z (2020) Continuous Flow Photo-oxidations Using Supported Photocatalysts on Silica. *Org Process Res Dev* 24:822–826. https://doi.org/10.1021/acs.oprd.9b00420

65. Tambosco B, Segura K, Seyrig C, Cabrera D, Port M, Ferroud C, Amara Z (2018) Outer-Sphere Effects in Visible-Light Photochemical Oxidations with Immobilized and Recyclable Ruthenium Bipyridyl Salts. ACS Catal 8:4383–4389. https://doi.org/10.1021/acscatal.8b00890

66. Lancel M, Gomez C, Port M, Amara Z (2021) Performances of Homogeneous and Heterogenized Methylene Blue on Silica Under Red Light in Batch and Continuous Flow Photochemical Reactors. *Frontiers in Chemical Engineering* 3:

67. Thomassen LCJ, Aerts A, Rabolli V, Lison D, Gonzalez L, Kirsch-Volders M, Napierska D, Hoet PH, Kirschhock CEA, Martens JA (2010) Synthesis and Characterization of Stable Monodisperse Silica Nanoparticle Sols for *in Vitro* Cytotoxicity Testing. *Langmuir* 26:328–335. https://doi.org/10.1021/la902050k

68. Galland M, Le Bahers T, Banyasz A, Lascoux N, Duperray A, Grichine A, Tripier R, Guyot Y, Maynadier M, Nguyen C, Gary-Bobo M, Andraud C, Monnereau C, Maury O (2019) A “Multi-Heavy-Atom” Approach toward Biphotonic Photosensitizers with Improved Singlet-Oxygen Generation Properties. *Chemistry – A European Journal* 25:9026–9034. https://doi.org/10.1002/chem.201901047

69. Bregnhøj M, Westberg M, Jensen F, Ogilby PR (2016) Solvent-dependent singlet oxygen lifetimes: temperature effects implicate tunneling and charge-transfer interactions. *Phys Chem Chem Phys* 18:22946–22961. https://doi.org/10.1039/C6CP01635A