Sulfanyl porphyrazines with morpholinylethyl periphery—synthesis, electrochemistry, and photocatalytic studies after deposition on titanium(Iv) oxide p25 nanoparticles

Article abstract of DOI:10.3390/molecules26082280

The syntheses, spectral UV–Vis, NMR, and electrochemical as well as photocatalytic properties of novel magnesium(II) and zinc(II) symmetrical sulfanyl porphyrazines with 2-(morpholin-4-yl)ethylsulfanyl peripheral substituents are presented. Both porphyrazine derivatives were synthe-sized in cyclotetramerization reactions and subsequently embedded on the surface of commercially available P25 titanium(IV) oxide nanoparticles. The obtained macrocyclic compounds were broadly characterized by ESI MS spectrometry, 1D and 2D NMR techniques, UV–Vis spectroscopy, and subjected to electrochemical studies. Both hybrid materials, consisting of porphyrazine derivatives embedded on the titanium(IV) oxide nanoparticles’ surface, were characterized in terms of particle size and distribution. Next, they were subjected to photocatalytic studies with 1,3-diphenylisobenzofuran, a known singlet oxygen quencher. The applicability of the obtained hybrid material consisting of titanium(IV) oxide P25 nanoparticles and magnesium(II) porphyrazine derivative was assessed in photocatalytic studies with selected active pharmaceutical ingredients, such as diclofenac sodium salt and ibuprofen.

Full text of DOI:10.3390/molecules26082280

molecules
Article
Sulfanyl Porphyrazines with Morpholinylethyl
Periphery—Synthesis, Electrochemistry, and Photocatalytic
Studies after Deposition on Titanium(IV) Oxide
P25 Nanoparticles
Tomasz Koczorowski * , Wojciech Szczolko , Anna Teubert and Tomasz Goslinski 1
1
,
1
2
1
Chair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences,
Grunwaldzka 6, 60-780 Poznan, Poland; wszczolko@wp.pl (W.S.); tomasz.goslinski@ump.edu.pl (T.G.)
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Z. Noskowskiego 12, 61-704 Poznan, Poland;
ateubert@ibch.poznan.pl
2
*
Correspondence: tkoczorowski@ump.edu.pl
Abstract: The syntheses, spectral UV–Vis, NMR, and electrochemical as well as photocatalytic prop-
erties of novel magnesium(II) and zinc(II) symmetrical sulfanyl porphyrazines with 2-(morpholin-4-
yl)ethylsulfanyl peripheral substituents are presented. Both porphyrazine derivatives were synthe-
sized in cyclotetramerization reactions and subsequently embedded on the surface of commercially
available P25 titanium(IV) oxide nanoparticles. The obtained macrocyclic compounds were broadly
characterized by ESI MS spectrometry, 1D and 2D NMR techniques, UV–Vis spectroscopy, and sub-
jected to electrochemical studies. Both hybrid materials, consisting of porphyrazine derivatives em-
bedded on the titanium(IV) oxide nanoparticles’ surface, were characterized in terms of particle size
and distribution. Next, they were subjected to photocatalytic studies with 1,3-diphenylisobenzofuran,
a known singlet oxygen quencher. The applicability of the obtained hybrid material consisting of
titanium(IV) oxide P25 nanoparticles and magnesium(II) porphyrazine derivative was assessed in
photocatalytic studies with selected active pharmaceutical ingredients, such as diclofenac sodium
salt and ibuprofen.
ꢀ
ꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀ
ꢁꢂꢃꢄꢅꢆ
Citation: Koczorowski, T.; Szczolko,
W.; Teubert, A.; Goslinski, T. Sulfanyl
Porphyrazines with
Morpholinylethyl
Periphery—Synthesis,
Electrochemistry, and Photocatalytic
Studies after Deposition on
Titanium(IV) Oxide P25
Nanoparticles. Molecules 2021, 26,
2
280. https://doi.org/10.3390/
molecules26082280
Keywords: catalysis; electrochemistry; morpholine; porphyrazine; titanium(IV) oxide
Academic Editor: Ana Margarida
Gomes da Silva
1
. Introduction
Porphyrazines (Pzs) are synthetic tetrapyrrole macrocyclic molecules, known as aza-
analogues of porphyrins. Their physicochemical properties can be tuned by the exchange
of the central metal cation or by peripheral substitution [ ]. Substituted porphyrazines
reveal high absorption in the UV–Vis region and good effectiveness for singlet oxygen
generation. In addition, they are usually soluble in organic solvents [ ]. Their unique
physicochemical properties, including optical and electrochemical ones, make them useful
in biosensing [ ], photocatalysis [ ], nonlinear optics [ ], and biomedicine, where they
can be considered as photosensitizers for photodynamic therapy [ ]. Amino and sul-
Received: 29 March 2021
Accepted: 13 April 2021
Published: 15 April 2021
1
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
2–5
6
7
8
9
fanyl porphyrazines can be obtained from a cyclotetramerization reaction starting from
diaminomaleonitrile or dimercaptomaleonitrile disodium salt derivatives, respectively.
Porphyrazines peripherally substituted with sulfanyl moieties have been studied widely
Copyright: © 2021 by the authors.
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over the last twenty years. They are well-soluble in common organic solvents [10–12]
and present interesting optical [13 14] and electrochemical properties, and have therefore
been applied as sensing materials in technology [15 21]. Other applications of sulfanyl
Pzs concern photodynamic therapy (PDT) [22 24], wastewater treatment [25 27], and
,
,
–
–
–
catalysis [28–31]. Symmetrical octa-substituted sulfanyl porphyrazines, unlike their un-
symmetrical derivatives, usually present low singlet oxygen generation quantum yields,
4
.0/).
and therefore their biological activities are limited [32
,
33]. Recently, many symmetrical and
Molecules 2021, 26, 2280. https://doi.org/10.3390/molecules26082280
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 2280
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unsymmetrical magnesium(II) and zinc(II) sulfanyl porphyrazines with bulky dendrimeric
periphery were synthesized and evaluated in terms of their suitability for photodynamic
therapy (PDT) [34–38]. In addition, some sulfanyl porphyrazines and phthalocyanines
with morpholinyl moieties were studied as photosensitizers for PDT and photodynamic
antimicrobial chemotherapy (PACT) and revealed promising potential [39–41].
Due to the presence of an expanded aromatic system in porphyrazines, they are
often highly hydrophobic, and therefore less soluble or even insoluble in water. Thus,
diverse methods, using specific carriers, have been employed to allow porphyrazines and
related compounds to form stable suspensions in aqueous solutions. The carriers most
widely applied in medicine and technology are liposomes [24
oxide nanoparticles [44 46], and polymeric nanomaterials [47]. Among the metal oxide
nanoparticles, one of the most interesting is titanium(IV) oxide nanoparticles (TiO ), which
,42,43], metal and metal
–
2
have unique photochemical features. Uncoated TiO nanoparticles are photoactive only
2
when irradiated with UV light. However, TiO nanocarriers coated with photoactive
2
compounds, like porphyrinoid macrocycles, when irradiated with light of an appropriate
energy, can absorb light and participate in energy transfer, and thus more effectively take
part in photochemical reactions [48–50].
Herein, we present the synthesis, spectral UV–Vis, NMR, and electrochemical as
well as photocatalytic properties of novel magnesium(II) and zinc(II) symmetrical sul-
fanyl porphyrazines with 2-(morpholin-4-yl)ethylsulfanyl peripheral substituents. The
synthesized macrocyclic compounds were embedded on the surface of commercially
available P25 titanium(IV) oxide nanoparticles. The obtained grafted hybrid material
was subjected to photocatalytic studies with 1,3-diphenylisobenzofuran, a known singlet
oxygen quencher, and with diclofenac sodium salt and ibuprofen as examples of active
pharmaceutical ingredients.
2. Results and Discussion
2.1. Synthesis and Physicochemical Characterization
The synthetic pathway was based on the alkylation reaction of commercially available
mercaptomaleonitrile disodium salt (
) in dimethylformamide (DMF), and with potassium carbonate as a base, which led to
compound (Scheme 1) [20 51]. Next, the Linstead macrocyclization reaction of with mag-
nesium butanolate as a base in n-butanol led to novel symmetric sulfanyl magnesium(II)
porphyrazine 52]. Simultaneously, compound was also used in the macrocyclization
1) with 4-(2-chloroethyl)morpholine hydrochloride
(
2
3
,
3
4
[
3
reaction with Zn(OAc) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in n-pentanol to
2
give zinc(II) porphyrazine 5 [53].
RS
SR
R:
O
N
N
-
+
+
O
O
N
N
N
N
N
N
N
S Na
RS
RS
SR
SR
S
S
+
N
(i)
(ii) or (iii)
+
N
M
N
N
O
-
-
H
S Na
Cl
N
N
N
Cl
1
2
3
4
5
M=Mg
M=Zn
RS
SR
◦
Scheme 1. Reagents and conditions: (i) K CO , DMF, 60 C, 24 h; (ii) Mg(n-BuO) , n-butanol, reflux, 24 h; (iii) Zn(OAc) ,
2
3
2
2
DBU, n-pentanol, reflux, 24 h; DBU—1,8-diazabicyclo[5.4.0]undec-7-ene, DMF—dimethylformamide.
All synthesized novel macrocyclic compounds were characterized using various ana-
lytical techniques, including high-resolution mass spectra (ESI), one- and two-dimensional
NMR spectroscopy, and UV–Vis spectrophotometry. Notably, Pzs 4 and 5 have very low
◦
◦
melting points at 113–116 C and 121–123 C, respectively, which is relatively low compared
◦
with other sulfanyl and amino porphyrazines that melt over 300 C [20,54].

Molecules 2021, 26, 2280
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In the UV–Vis spectra of porphyrazines
4
and
5
in dichloromethane, two intensive
bands were found: a Soret or B band in the range of 250–400 nm, and a Q band between
00 and 800 nm (Figure 1). Magnesium(II) Pz revealed strong absorption Soret and Q
bands with maxima at 375 m and 671 nm, whereas zinc(II) Pz maxima appeared at 373 and
68 nm, respectively. The only difference between the UV–Vis spectra of and was noted
6
4
5
6
4
5
in the region between 450 and 550 nm, where, for Pz 4, only a weak absorption maximum
at 497 nm appeared. A similar effect was noted before for sulfanyl porphyrazines with
peripheral phthalimide motifs [38].
Figure 1. The UV–Vis spectrum of Pz 4 (black line) and Pz 5 (red line) in dichloromethane.
In the NMR spectra of porphyrazines
4
and
5
, which were recorded in pyridine-d , four
5
1
distinguishable signals in the aliphatic region were noted in the H NMR, whereas there
were six signals in the 13C NMR (four aliphatic and two aromatic, originating from pyrrolyl
1
1
rings of macrocycle, see Supplementary Materials). The two-dimensional technique H- H
COSY NMR was used to assist allocation and analysis of protons within ethylsulfanyl and
morpholinyl substituents. Signal shift analyses performed for Pz
4 and Pz 5 indicated
similarities for two morpholinyl proton signals and one of two methylene signals within
the ethylene linker. A slight difference in the shifts of signals was noted for another
methylene group within the ethylene linker. These methylene protons appeared as a singlet
at 4.64 ppm for Pz
in the H NMR spectra of Pz
4
, and as a multiplet in the range of 3.81–3.89 ppm for Pz
5. In addition,
1
4
and , the proton signals were generally up-field shifted
5
in comparison with those in the structure of symmetrical magnesium(II) phthalocyanine
with eight 2-(morpholin-4-yl)ethoxy substituents [39]. This finding could be explained by
a higher electronegativity of oxygen atoms than sulfur present in the peripheries of both
groups of macrocycles.
2.2. Electrochemistry
The electrochemical study was performed to assess the electrochemical properties of
the obtained porphyrazines, aiming to propose their prospective potential applicabilities.
The cyclic (CV) and differential pulse (DPV) voltammetry measurements were conducted
in organic solvent (dichloromethane), with the addition of supporting electrolyte: 0.1 M
tetrabutylammonium perchlorate. The classic three-electrode system was employed with
the glassy carbon working electrode. Due to the use of Ag wire as a pseudo-reference
electrode, the ferrocene was added as an internal standard, and all results were adjusted to
the ferrocene/ferrocenium peak potential. In the CV experiments, the scan potential range

Molecules 2021, 26, 2280
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was set between 50 and 250 mV/s. The obtained results are presented in Figures 2 and 3
and Table 1.
In the voltammograms recorded for both porphyrazines 4 and 5, four redox peak poten-
tials were noted. Almost all redox peaks observed in the CV voltammograms are irreversible
due to the aggregation-disaggregation behavior of porphyrazines in dichloromethane; thus,
redox pairs can be observed only in the DPV measurements. A similar phenomenon was
previously observed for iron(II) porphyrazine bearing identical periphery to both herein
studied Pzs [20]. However, the oxidation peaks (IV) at 0.62 V for Pz
were noted in the DPV voltammogram only when the applied potential was increasing over
time from 2.0 to 0.7 V. Conversely, when the applied potential was decreasing over time,
oxidation peaks were not observed (Figures 2 and 3). The oxidation peak currents were at
least five times higher than the highest reduction peak ( ) in the case of both porphyrazines
Figures 2 and 3). Such a high oxidation peak current could also be a result of an aggrega-
tion phenomenon, which was previously observed for other sulfanyl porphyrazines [15].
Notably, the peak potentials of zinc(II) porphyrazine shifted to more negative potentials
(Table 1), which is the result of different
4 and 0.53 V for Pz 5
−
I
(
5
in comparison with magnesium(II) complex
metal cations present inside their cores [55].
4
Figure 2. The cyclic and differential pulse voltammograms of porphyrazine
4 in 0.1 M TBAP/DCM. The DPV parameters:
modulation amplitude 20 mV and step rate 5 mV·s−1
.
Figure 3. The cyclic and differential pulse voltammograms of porphyrazine
5 in 0.1 M TBAP/DCM. The DPV parameters:
modulation amplitude 20 mV and step rate 5 mV·s−1
.

Molecules 2021, 26, 2280
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Measurements performed for amino porphyrazines in dichloromethane indicated
+
that the first oxidation peak appears below 0 V vs. Fc/Fc [56
,
57]. A different situation
was observed when alkyl- or phenylsulfanyl substituents were present in the macrocyclic
periphery. Then, peaks shifted toward positive values due to a strong electron-withdrawing
effect [55,58]. The oxidation peak potentials (IV) of Pzs 4 and 5 comply with this rule.
Table 1. The electrochemical data of porphyrazines 4 and 5.
MPz(
MPz(
I
−2)
/
MPz
MPz
(−1)
/
MPz(0)
MPz
III
MPz(0)
/
MPz
/
−3)
(−2)
(−1)
(+1)
Pz
II
IV
E1/2 [V]
vs. Fc/Fc
4
5
−1.95
−2.02
−1.33
−0.70
−0.74
0.62
+
+
E1/2 [V]
vs. Fc/Fc
−1.34
0.53
In order to calculate the HOMO-LUMO energy levels in compounds such as por-
phyrinoid macrocycles, electrochemical measurements were used. The electrochemical
energy gap (Egap el) was calculated by determining the onset potentials of first oxidation
and first reduction processes originating from the porphyrazine ring with the use of the
following equations:
EHOMO = −(Vonset ox − VFOC + 4.8) eV,
ELUMO = −(Vonset red − VFOC + 4.8) eV,
Egap el = (ELUMO − EHOMO) eV
In the above equations, VFOC stands for the ferrocene half-wave potential, Vonset ox is
assigned as the Pz oxidation onset, and Vonset red represents the Pz reduction onset. For all
these values (eV), the calculations of the first oxidation and the first reduction were adjusted
to the ferrocene’s energy level at
potential for normal hydrogen electrode (NHE) at
and a value of 0.2 eV versus NHE for the potential of ferrocene standard [59
calculated electrochemical energy gap was slightly higher for magnesium(II) porphyrazine
than for zinc(II) complex 5 (Figure 4 and Table 2).
−
4.8 eV. The value of 4.8 eV refers to a standard electrode
4.6 eV on the zero vacuum level scale,
60]. The
−
,
4
Figure 4. The HOMO-LUMO energy levels estimated for electrochemical data for porphyrazines
and 5.
4
At the same time as the previous calculations, we calculated the optical band gaps
Egap opt) based on the UV–Vis spectra Q band onsets, according to the equation E =
(
hc/λonset
[
61]. Both electrochemical and optical energy gaps, which we obtained, were
subsequently compared and are presented in Table 2. The optical band gaps (Egap opt
)

Molecules 2021, 26, 2280
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for porphyrazines
4
and
5
were found to be in agreement with those obtained from
electrochemical measurements within approx. 0.2 eV.
Table 2. The optical and electrochemical HOMO-LUMO band gaps for porphyrazines 4 and 5.
λmax [nm]
Optical Band Gap
Electrochemical Band
λonset [nm]
Soret
Q Band
Egap opt [eV]
Gap Egap el [eV]
4
5
375
373
671
820
850
1.51
1.46
1.32
1.26
668
2
.3. TiO Deposition and Characterization
2
Titanium(IV) oxide (TiO ) nanoparticles have often been utilized in diverse studies as
2
carriers for photosensitizers [62,63]. Among many titanium(IV) oxide types, the commer-
cially 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 nanoparticles. The solutions of macrocycles were
2
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 anal-
yses 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 nanoparticles. The results are presented
2
in Table 3.
Table 3. The particle size distribution of P25, 4@P25, and 5@P25.
Material
Measured Particle Size (nm)
74.8 ± 7.7
Polydispersity Index a
P25
0.17
0.13
0.15
4
@P25
@P25
327.4 ± 15.5
5
322.5 ± 28.2
a
2
Calculated according to the formula PDI = (SD/mean diameter) [64].
Considering the measured particle size values, strong agglomeration of the hybrid
nanoparticles was observed. The mean particle sizes of the @P25 and @P25 were four
times higher than the unmodified P25 (74.8 7.7 nm). This could suggest that the de-
4
5
±
position of the macrocycles strongly influences the titanium(IV) oxide nanoparticles. In
addition, in both cases, the calculated polydispersity indices were below 0.2, which in-
dicated 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
2
of red-light LED lamps (665 nm). The intensity of light was adjusted to 10 mW/cm .
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.

Molecules 2021, 26, 2280
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O
[
O]
[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:
@P25, @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 @P25
hybrid material containing magnesium(II) sulfanyl porphyrazine deposited on the surface
of TiO nanoparticles revealed the highest photocatalytic activity. Moderate activity was
4
5
4
2
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
2
the parallel study, the R value measured for
slightly deviated from unity.
4@P25 hybrid material and P25 nanoparticles
Figure 5. The UV–Vis spectra for the oxidation of DPBF in dimethylformamide in the presence of
and P25 ( ) as catalysts over a period of time. ( ) the plots of DPBF absorbance in time in the presence of
@P25 (green), and P25 (grey); DPBF—1,3-diphenylisobenzofurane.
4@P25 (A 5@P25 (B),
),
C
D
4@P25 (blue),
5
The results obtained in the photocatalytic oxidation study with DPBF indicated the
@P25 hybrid material as a candidate for further photocatalytic study with selected active
4
pharmaceutical ingredients (APIs): diclofenac sodium salt and ibuprofen. Both APIs are

Molecules 2021, 26, 2280
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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
All the reactions described in this paper were conducted under argon. Before at-
◦
tempting 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 thin-
layer 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
1
of an Ocean Optics USB 2000+ spectrometer (Ocean Opitics Inc., Largo, FL, USA). H NMR
and 13C 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 ), whereas coupling constants
5
(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
,3-Bis[2-(morpholin-4-ylo)ethylsulfanyl]-(2Z)-butene-1,4-dinitrile (3) is a known
compound synthesized and characterized earlier in our group [20]: dimercaptomaleonitrile
2
disodium salt (558 mg; 3.0 mmol) (
1
), 4-(2-chloroethyl)morpholine hydrochloride (1.396 g;
◦
7
2
.5 mmol) (
2
) and K CO (4.140 g; 30.0 mmol) were mixed in DMF (30 mL) at 60 C for
2
3
4 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

Molecules 2021, 26, 2280
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solid was subjected to a flash column chromatography with Al O (DCM:CH OH; 50:1) to
2
3
3
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 sus-
pended 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 sol-
vents were evaporated with toluene to a dry solid. Crude product was purified by column
chromatography on Al O (DCM:MeOH, 50:1) to give porphyrazine
4
(110 mg; 16% yield)
2
3
◦
as a green-blue solid: mp 113-116 C; R (DCM:MeOH:N(C H ) , 10:1:0.1) 0.42. UV–Vis
f
2
5 3
1
(
DCM): λmax, nm (logε) 375 (4.68), 497 (3.91), 671 (4.71). H NMR (400 MHz; pyridine-d ):
5
δ
H, ppm 2.60 (s, 32H, morph-CH ), 3.11 (s, 16H, CH ), 3.67 (s, 32H, morph-CH ), 4.64 (t,
2 2 2
3
13
J = 10.0 Hz, 16H, CH2). C NMR (100 MHz; pyridine-d5):
δ
C, ppm 33.5; 54.5; 60.0; 67.5;
+
1
41.9; 158.4. HRMS ESI (pos): calc. for C H N O S Mg m/z 1497.5291 [M + H] ; found
64
97 16
8 8
+
m/z 1497.5340 [M + H] .
2,3,7,8,12,13,17,18-Octakis[2-(morpholin-4-yl)ethylsulfanyl]porphyrazinato} zinc(II)
5): dimercaptomaleonitrile (700 mg; 1.9 mmol), Zn(OAc) (175 mg, 0.95 mmol) and
DBU (142 L, 0.95 mmol) in n-pentanol (4 mL) were refluxed in an inert atmosphere for
8 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 Al O
{
(
3
2
µ
1
2
3
(
1
(
DCM:MeOH; 50:1
→
10:1) to give porphyrazine
5
(90 mg; 12%) as a dark green solid: mp
) 373
H, ppm 2.54–2.63 (m, 32H, morph-
◦
21–123 C; R (DCM:MeOH:N(C H ) , 10:1:0.1) 0.57. UV–Vis (DCM): λmax, nm (log
ε
f
2
5 3
1
4.79); 668 (4.71). H NMR (500 MHz; pyridine-d ):
δ
5
1
3
CH ), 3.09 (s, 16H, CH ), 3.63–3.69 (m, 32H, morph-CH ), 3.81–3.89 (m, 16H, CH ).
C
2
2
2
2
NMR (125 MHz; pyridine-d5): δC, ppm 33.34; 54.37; 59.88; 67.38; 141.92; 157.34. HRMS ESI
+
+
(
pos): calc. for C H N O S Zn m/z 1539.4721 [M+H] ; found m/z 1539.4756 [M + H] .
64 97 16 8 8
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
2
with the use of a glassy carbon (GC) working electrode (area = 0.071 cm ), Ag wire (pseudo-
reference electrode), and a platinum wire (counter electrode). Before each procedure, the
GC electrode was polished with aqueous 50 nm Al O slurry (purchased from Sigma-
2
3
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 ) 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.
3
.4. Deposition of Porphyrazines on TiO P25 Nanoparticles
2
Studied porphyrazines were deposited on P25 Aeroxide®® titanium(IV) oxide (TiO2)
nanoparticles using the chemical deposition method [50]. In general, porphyrazine
4 or
5
in the amount of 5 mg was added to a dispersion of 100 mg P25 nanoparticles (sized
approx. 21 nm) in 20 mL of dichloromethane:methanol mixture (1:1, v/v). After the reaction
mixture had been stirred for 72 h, the solvents were evaporated on a rotary evaporator.
Next, the obtained hybrid material was air dried for 24 h. The ratio of the macrocycle to
the P25 TiO was 1:20 (w/w).
2
The hybrid materials were subjected to nanoparticle size measurements using a
Malvern Panalytical NanoSight LM10 instrument (Malvern, UK), equipped with sCMOS
camera, and 405 nm laser. The data acquisition and storage were provided by Nanoparticle
Tracking Analysis (NTA) 3.2 Dev Build 3.2.16 software (Malvern, UK). Throughout, the

Molecules 2021, 26, 2280
10 of 13
nanoparticles’ dispersions were diluted with water (1 mg in 1 mL) to obtain the operating
◦
range of nanoparticle concentration. The measurements were performed at 25.0
and at the syringe pump infusion rate set to 100 µL/min.
±
0.1 C,
3.5. Photocatalytic Studies
The photocatalytic studies were performed using a red-light LED lamp (EcoEnergy,
2
Gda n´ sk, Poland) at wavelength 665 nm, and a power adjusted to 10 mW/cm with the
use of an Optel radiometer. The measurements were conducted in a 10 mm quartz cu-
0
vette in N,N -dimethylformamide (DMF). In the experiments with a reference standard
1
,3-diphenylisobenzofurane (DPBF), 1 mL of 0.1 mM DPBF solution in DMF was mixed
with 1 mL of TiO dispersion in DMF (0.1 mg/mL). In the experiments with active pharma-
2
ceutical ingredients (diclofenac sodium salt and ibuprofen), DPBF was replaced by 1 mL of
0
.3 mM diclofenac sodium salt solution in DMF or 1 mL of 1.5 mM ibuprofen solution in
DMF. The irradiations of mixtures were performed with an LED lamp within 8 min. The
UV–Vis spectra were recorded every 2 min on an Ocean Optics USB 2000+ spectrometer
(
Ocean Optics Inc., Largo, FL, USA).
4. Conclusions
Two novel sulfanyl magnesium(II) and zinc(II) porphyrazines with morpholinylethyl
periphery were synthesized in the cyclotetramerization reaction using a dimercaptoma-
leonitrile derivative. The obtained macrocyclic compounds were broadly characterized
by ESI MS spectrometry, 1D and 2D NMR techniques, and UV–Vis spectroscopy. Both
porphyrazines were subjected to electrochemical studies. Subsequently, the obtained por-
phyrazines were embedded on titanium(IV) oxide nanoparticles’ surface and characterized
in terms of particle size and distribution. The obtained hybrid materials’ applicability was
assessed in photocatalytic studies with a singlet oxygen quencher (DPBF) and selected
drug active pharmaceutical ingredients (diclofenac sodium salt and ibuprofen). In the
UV–Vis and NMR studies, the characteristic features of porphyrazines were confirmed. The
electrochemical studies revealed four irreversible redox processes for both porphyrazines.
In addition, the calculated electrochemical band gap values were found to be in agreement
with the optical ones. Interestingly, the obtained hybrid materials presented four times
higher particle sizes compared with unmodified titanium(IV) oxide P25 nanoparticles and
were monodispersive. The
photocatalytic tests with 1,3-diphenylisobenzofurane, and it was therefore used in the pho-
tooxidation studies of diclofenac sodium salt and ibuprofen. The @P25 material revealed
4@P25 material was found to be the most active in comparative
4
good photocatalytic potential. For this reason, it can be considered in future photocatalytic
experiments with various organic compounds and active pharmaceutical ingredients as a
potential hybrid material for the photodegradation of various organic pollutants.
1
Supplementary Materials: The following are available online: Figure S1. H NMR spectrum of
4
in
1
3
pyridine-d . # indicates solvent residual peaks. Figure S2. C NMR spectrum of
indicates solvent residual peaks. Figure S3. H- H COSY NMR spectrum of
4 in pyridine-d . #
5
5
1
1
4 in pyridine-d . Figure
5
1
S4. H NMR spectrum of
5
in pyridine-d . * indicates solvent residual peaks and # stands for water
5
13
residual. Figure S5. C NMR spectrum of
5 in pyridine-d . * indicates solvent residual peaks. Figure
5
1
1
S6. H- H COSY NMR spectrum of 5 in pyridine-d .
5
Author Contributions: Conceptualization, T.K.; methodology, T.K.; investigation, T.K., W.S. and A.T.;
writing—original draft preparation, T.K.; writing—review and editing, W.S. and T.G.; visualization,
A.T.; supervision, T.G.; funding acquisition, T.G. All authors have read and agreed to the published
version of the manuscript.
Funding: This research was funded by National Science Centre, Poland under Grant No. 2016/21/B/
NZ9/00783.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.

Molecules 2021, 26, 2280
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Data Availability Statement: Not applicable.
Acknowledgments: This study was supported by the National Science Centre, Poland under Grant
No. 2016/21/B/NZ9/00783 and the European Fund Regional Development Fund No. UDA-
POIG.02.01.00-30-182/09. The authors thank Beata Kwiatkowska and Rita Kuba for excellent technical
assistance.
Conflicts of Interest: The authors declare no conflict of interest
Sample Availability: Samples of the compounds 3, 4, and 5 are available from the authors.
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