*2.3. TiO<sup>2</sup> Deposition and Characterization*

Titanium(IV) oxide (TiO2) nanoparticles have often been utilized in diverse studies as carriers for photosensitizers [62,63]. Among many titanium(IV) oxide types, the commercially available P25, consisting of a mixture of crystal phases of anatase and rutile, is the most popular. Herein, the hybrid materials, type Pz@P25, were prepared by depositing porphyrazine **4** or **5** on the surface of TiO<sup>2</sup> nanoparticles. The solutions of macrocycles were added to titania suspension, sonicated, and mixed for 72 h, yielding **4**@P25 and **5**@P25, respectively. The resulting hybrid materials contained 5% (*w*/*w*) of the macrocycle. The sizes and the dispersities of the obtained nanomaterials were subjected to the detailed analyses using a NanoSight LM10 instrument (sCMOS camera, 405 nm laser), equipped with a nanoparticle tracking analysis system. The diameters of the obtained hybrid materials were assessed and compared with the pure TiO<sup>2</sup> nanoparticles. The results are presented in Table 3.

**Table 3.** The particle size distribution of P25, **4**@P25, and **5**@P25.


<sup>a</sup> Calculated according to the formula PDI = (SD/mean diameter)<sup>2</sup> [64].

Considering the measured particle size values, strong agglomeration of the hybrid nanoparticles was observed. The mean particle sizes of the **4**@P25 and **5**@P25 were four times higher than the unmodified P25 (74.8 ± 7.7 nm). This could suggest that the deposition of the macrocycles strongly influences the titanium(IV) oxide nanoparticles. In addition, in both cases, the calculated polydispersity indices were below 0.2, which indicated that the distributions of nanoparticles within the studied hybrid materials are monodisperse. It also seems that the presence of sulfanyl porphyrazines on the surface of P25 nanoparticles hampers the electrostatic interactions between Pz@P25 nanoparticles and allows obtaining Pz@P25 of specific diameters.

#### *2.4. Photocatalysis*

All hybrid materials were assessed for their photocatalytic oxidation abilities. These properties were studied with the use of a known singlet oxygen quencher, 1,3 diphenylisobenzofurane (DPBF), according to previously presented procedures [20,65]. In the UV–Vis spectrum, the decrease in the DPBF absorption band at 413 nm over a period of time results from the transformation of DPBF towards the new product, which is 1,2-dibenzoylbenzene (Scheme 2).

Measurements were performed in DMF at ambient temperature, and with the use of red-light LED lamps (665 nm). The intensity of light was adjusted to 10 mW/cm<sup>2</sup> . The irradiations were conducted in a 10 mm quartz cuvette equipped with a magnetic stirrer. The results of photocatalytic reactions were evaluated with the use of UV–Vis spectrophotometry.

O

O O

[O] [O]

O

**Scheme 2.** The oxidation of 1,3-diphenylisobenzofurane to 1,2-dibenzoylbenzene.

The photocatalytic oxidations of DPBF were performed using three types of materials: **4**@P25, **5**@P25, and unmodified P25. Their catalytic activity was assessed by recording the UV–Vis scans within the range of 250–800 nm for 8 min, and every 2 min. The **4**@P25 hybrid material containing magnesium(II) sulfanyl porphyrazine deposited on the surface of TiO<sup>2</sup> nanoparticles revealed the highest photocatalytic activity. Moderate activity was noted for **5**@P25 and the lowest activity for the unmodified P25 (Figure 5). In the case of **5**@P25 nanoparticles, the linear plots of DPBF absorbance were decreasing with time, which indicates that the photooxidation process follows the first-order kinetics (Figure 5D). In the parallel study, the R<sup>2</sup> value measured for **4**@P25 hybrid material and P25 nanoparticles slightly deviated from unity.

O O

**Figure 5.** The UV–Vis spectra for the oxidation of DPBF in dimethylformamide in the presence of **4**@P25 (**A**), **5**@P25 (**B**), and P25 (**C**) as catalysts over a period of time. (**D**) the plots of DPBF absorbance in time in the presence of **4**@P25 (blue), **5**@P25 (green), and P25 (grey); DPBF—1,3-diphenylisobenzofurane.

The results obtained in the photocatalytic oxidation study with DPBF indicated the **4**@P25 hybrid material as a candidate for further photocatalytic study with selected active pharmaceutical ingredients (APIs): diclofenac sodium salt and ibuprofen. Both APIs are

common non-steroidal anti-inflammatory drugs, and therefore constitute an important component of drug-related pollutants in water. What is essential is that the UV–Vis method can be employed for the photodegradation study of both APIs. The photodegradation study was performed in the same conditions as previously established for the photooxidation of DPBF. The results are presented in Figure 6. In the UV–Vis spectra, decreases in both APIs absorbances over a period of time were observed, which indicates the photodegradation of the studied compounds. For this reason, the obtained hybrid material **4**@P25 can be considered an efficient heterogenic catalyst for further photooxidation studies of diverse organic compounds.

**Figure 6.** The UV–Vis spectra of photooxidation of diclofenac sodium salt (**A**) and ibuprofen (**B**) in dimethylformamide with **4**@P25 as a catalyst over a period of time.

#### **3. Materials and Methods**

*3.1. Materials and Instruments*

λ δ All the reactions described in this paper were conducted under argon. Before attempting the reaction, the glassware was oven-dried (at 140 ◦C). All solvents were rotary evaporated under vacuum at or below 40 ◦C. All reaction temperatures reported in the experimental section refer to the external bath temperatures. The reactions were performed on a Heidolph MR Hei-Tec, equipped with Radleys Heat-On heating mantle. All solvents and reagents were obtained from commercial suppliers (Merck, Darmstadt, Germany; TCI, Zwijndrecht, Belgium, and Fluorochem, Hadfield, UK), and used without any further purification, unless otherwise stated. Melting points were measured with the use of a Stuart Bibby apparatus (Triad Scientific, Staffordshire, UK) and are uncorrected. Flash column chromatography was performed on a Merck neutral aluminum oxide gel, whereas thinlayer chromatography (TLC) was performed on aluminum oxide F254 plates (Merck) and visualized with a UV lamp (λmax 254 or 365 nm). UV–Vis spectra were recorded with the use of an Ocean Optics USB 2000+ spectrometer (Ocean Opitics Inc., Largo, FL, USA). <sup>1</sup>H NMR and <sup>13</sup>C NMR spectra were recorded using Bruker Avance 400 and 500 (Bruker, Karlsruhe, Germany) spectrometers. Chemical shifts (δ) are specified in parts per million (ppm) and are referenced against a residual solvent peak (pyridine-*d*5), whereas coupling constants (*J*) are calculated in Hertz (Hz). The abbreviations *s*, *t*, and *m* refer to singlet, triplet, and multiplet, respectively. Mass spectra (ESI MS) were performed in the Wielkopolska Centre of Advanced Technologies, Adam Mickiewicz University in Poznan, Poland.

#### *3.2. Synthesis*

**2,3-Bis[2-(morpholin-4-ylo)ethylsulfanyl]-(2***Z***)-butene-1,4-dinitrile (3)** is a known compound synthesized and characterized earlier in our group [20]: dimercaptomaleonitrile disodium salt (558 mg; 3.0 mmol) (**1**), 4-(2-chloroethyl)morpholine hydrochloride (1.396 g; 7.5 mmol) (**2**) and K2CO<sup>3</sup> (4.140 g; 30.0 mmol) were mixed in DMF (30 mL) at 60 ◦C for 24 h under argon. Next, the reaction mixture was cooled to room temperature and filtered through Celite, then the filtrate was evaporated with toluene to a dry solid residue. Crude

solid was subjected to a flash column chromatography with Al2O<sup>3</sup> (DCM:CH3OH; 50:1) to give **3** as yellow crystals (810 mg; 71% yield).

**{2,3,7,8,12,13,17,18-Octakis[2-(morpholin-4-yl)ethylsulfanyl]porphyrazinato} magn esium(II) (4)**: magnesium turnings (45 mg; 1.88 mmol) and iodide (1 crystal) were suspended in *n*-butanol (15 mL) and refluxed for 6 h in an inert atmosphere. After the reaction mixture was cooled to room temperature, compound **3** (692 mg; 1.88 mmol) was added and the mixture was refluxed for 18 h. Next the mixture was filtrated through Celite and the solvents were evaporated with toluene to a dry solid. Crude product was purified by column chromatography on Al2O<sup>3</sup> (DCM:MeOH, 50:1) to give porphyrazine **4** (110 mg; 16% yield) as a green-blue solid: mp 113-116 ◦C; R*<sup>f</sup>* (DCM:MeOH:N(C2H5)3, 10:1:0.1) 0.42. UV–Vis (DCM): λmax, nm (logε) 375 (4.68), 497 (3.91), 671 (4.71). <sup>1</sup>H NMR (400 MHz; pyridine-*d*5): δ*H*, ppm 2.60 (*s*, 32H, morph-CH2), 3.11 (*s*, 16H, CH2), 3.67 (*s*, 32H, morph-CH2), 4.64 (*t*, 3 *J* = 10.0 Hz, 16H, CH2). <sup>13</sup>C NMR (100 MHz; pyridine-*d*5): δ*C*, ppm 33.5; 54.5; 60.0; 67.5; 141.9; 158.4. HRMS ESI (pos): calc. for C64H97N16O8S8Mg *m*/*z* 1497.5291 [M + H]<sup>+</sup> ; found *m*/*z* 1497.5340 [M + H]<sup>+</sup> .

**{2,3,7,8,12,13,17,18-Octakis[2-(morpholin-4-yl)ethylsulfanyl]porphyrazinato} zinc(II) (5)**: dimercaptomaleonitrile **3** (700 mg; 1.9 mmol), Zn(OAc)<sup>2</sup> (175 mg, 0.95 mmol) and DBU (142 µL, 0.95 mmol) in *n*-pentanol (4 mL) were refluxed in an inert atmosphere for 18 h. Next, the reaction mixture was filtrated through Celite and the filtrate was evaporated with toluene to dryness. Crude solid was purified by column chromatography with Al2O<sup>3</sup> (DCM:MeOH; 50:1→10:1) to give porphyrazine **5** (90 mg; 12%) as a dark green solid: mp 121–123 ◦C; R*<sup>f</sup>* (DCM:MeOH:N(C2H5)3, 10:1:0.1) 0.57. UV–Vis (DCM): λmax, nm (logε) 373 (4.79); 668 (4.71). <sup>1</sup>H NMR (500 MHz; pyridine-*d*5): δ*H*, ppm 2.54–2.63 (*m*, 32H, morph-CH2), 3.09 (*s*, 16H, CH2), 3.63–3.69 (*m*, 32H, morph-CH2), 3.81–3.89 (*m*, 16H, CH2). <sup>13</sup>C NMR (125 MHz; pyridine-*d*5): δ*C*, ppm 33.34; 54.37; 59.88; 67.38; 141.92; 157.34. HRMS ESI (pos): calc. for C64H97N16O8S8Zn *m*/*z* 1539.4721 [M+H]<sup>+</sup> ; found *m*/*z* 1539.4756 [M + H]<sup>+</sup> .

## *3.3. Electrochemical Studies*

The electrochemical studies were performed with a Metrohm Autolab PGSTAT128N potentiostat (Metrohm, Herisau, Switzerland). The data acquisition and storage were driven by Metrohm Nova 2.1.4 software (Metrohm). The measurements were obtained with the use of a glassy carbon (GC) working electrode (area = 0.071 cm<sup>2</sup> ), Ag wire (pseudoreference electrode), and a platinum wire (counter electrode). Before each procedure, the GC electrode was polished with aqueous 50 nm Al2O<sup>3</sup> slurry (purchased from Sigma-Aldrich) using a polishing cloth and was subsequently washed in an ultrasonic bath with deionized water for 10 min to remove inorganic impurities. Ferrocene/ferrocenium couple (Fc/Fc<sup>+</sup> ) was applied as an internal standard. The solvent (dichloromethane) containing a supporting electrolyte (0.1 M tetrabutylammonium perchlorate (TBAP)) in a glass cell (volume 10 mL) was deoxygenated by purging nitrogen gas for 10 min prior to each experiment. All electrochemical experiments were carried out at 22 ◦C. The solvent and reagent were purchased from Sigma-Aldrich Chemie GmbH, Steinheim, Germany.
