Syntheses, structural characterization, DNA-cleavage and antioxidant features of the new tetra-substituted organo-soluble non-peripherally CoII, CuII, ZnII and MgII phthalocyanines

Article abstract of DOI:10.1080/00958972.2019.1648795

This paper encompasses the synthesis, structural characterization, and evaluation of supercoiled pBR322 plasmid DNA-cleavage and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging properties of newly synthesized tetra-substituted Co^II (5),

Full text of DOI:10.1080/00958972.2019.1648795

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: https://www.tandfonline.com/loi/gcoo20
Syntheses, structural characterization, DNA-
cleavage and antioxidant features of the new
tetra-substituted organo-soluble non-peripherally
CoII, CuII, ZnII and MgII phthalocyanines
Halise Yalazan, Burak Barut, Gülpınar Sarkı, Beytullah Ertem, Yasemin
Ünver, Arzu Özel & Halit Kantekin
To cite this article: Halise Yalazan, Burak Barut, Gülpınar Sarkı, Beytullah Ertem, Yasemin Ünver,
Arzu Özel & Halit Kantekin (2019): Syntheses, structural characterization, DNA-cleavage and
antioxidant features of the new tetra-substituted organo-soluble non-peripherally CoII, CuII, ZnII and
MgII phthalocyanines, Journal of Coordination Chemistry, DOI: 10.1080/00958972.2019.1648795
To link to this article: https://doi.org/10.1080/00958972.2019.1648795
Published online: 06 Aug 2019.
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JOURNAL OF COORDINATION CHEMISTRY
https://doi.org/10.1080/00958972.2019.1648795
Syntheses, structural characterization, DNA-cleavage and
antioxidant features of the new tetra-substituted organo-
soluble non-peripherally CoII, CuII, ZnII and MgII
phthalocyanines
a
b
a
c
a
€
€
Halise Yalazan , Burak Barut , Gulpınar Sarkı , Beytullah Ertem , Yasemin Unver ,
Arzu Ozel and Halit Kantekina
b,d
€
b
aDepartment of Chemistry, Karadeniz Technical University, Trabzon, Turkey; Faculty of Pharmacy,
c
Department of Biochemistry, Karadeniz Technical University, Trabzon, Turkey; Vocational School of
d
Health Services, Karadeniz Technical University, Trabzon, Turkey; Drug and Pharmaceutical
Technology Application and Research Center, Karadeniz Technical University, Trabzon, Turkey
ABSTRACT
ARTICLE HISTORY
Received 23 April 2019
Accepted 12 July 2019
This paper encompasses the synthesis, structural characterization,
and evaluation of supercoiled pBR322 plasmid DNA-cleavage and
DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging properties
of newly synthesized tetra-substituted CoII (5), CuII (6), ZnII (7) and
MgII (8) phthalocyanines bearing 4-methyl-N-(4-morpholinophe-
nyl)benzenesulfonamide units at non-peripheral sites of phthalo-
cyanine skeleton. The structural characterization of these new
metallated phthalocyanines were performed via UV-vis, elemental
analysis, FT-IR (ATR sampling accessory), 1H-NMR and 13C-NMR
spectroscopic techniques (for 7 and 8) and MALDI-TOF mass spec-
tral data. The new compounds (5–8) exhibited good solubility in
common organic solvents, and as well as no sort of aggregation
was perceived at studied concentrations and solvents. Compound
7 indicated oxidative photocleavage activities in the presence of
H2O2, indicating the conversion of supercoiled pBR322 plasmid
DNA to nicked circular form (19.90%) and linear form (4.40%).
Compound 5 displayed the highest radical scavenging activities
among the tested compounds. The DPPH-radical scavenging per-
KEYWORDS
Cobalt(II) phthalocyanine;
4-morpholinoaniline; tosyla-
tion; plasmid DNA;
antioxidant
centages of
5
ranged from 85.35 2.45% (12.5 mM) to
95.38 1.44% (100mM). These compounds are favorable for fur-
ther research, owing to a broad range of biological and pharma-
ceutical activities of morpholine scaffold.
CONTACT Beytullah Ertem
bertem@ktu.edu.tr
Supplemental data for this article is available online at https://doi.org/10.1080/00958972.2019.1648795
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

2
H. YALAZAN ET AL.
1. Introduction
Metallophthalocyanines (MPcs), which are metal-coordinated macrocycles of free-base
phthalocyanines (Pcs), have been of great attraction for years due to their versatility
and perfect features in terms of light, thermal and chemical stability, genuine electro-
chemical [1], photophysical–chemical [2, 3] and catalytic performance [4], also as the
spectacular metal-coordination characteristics [5–10]. Both Pcs and MPcs are utilized in
the area of material science such as photosensitizing agents in photodynamic therapy
of diverse cancer diseases [11–13], liquid crystals [14, 15], dyes [16], photovoltaics [17],
gas sensors [18], nonlinear optical materials [19], electrochromic devices [20], dye-sen-
sitized solar cells [21], Langmuir Blodgett films [22], enzyme inhibition [23] and fluores-
cence “off–on–off” sensor [24]. Owing to their intense colors, MPcs have been great
materials especially for the production of dyes and pigments for a long time. The total
production of MPcs is nearly 80,000 tones throughout the world and its total manufac-
turing cost price is over one billion U.S. dollars [25, 26]. The solubility of the phthalo-
cyanine compounds plays a critical role to evaluate these synthetic aromatic
heterocycles in the field of material science summarized above. Another critical factor
to employ these products in the above-mentioned applications is to prevent the
aggregation of Pcs or MPcs, which is formed by p–p stacking interactions of Pc rings.
By the incorporation of four 4-methyl-N-(4-morpholinophenyl)benzenesulfonamide
moieties into the non-peripheral positions of phthalocyanine skeleton, we obtained
new tetra-substituted non-peripheral MPcs, which are carrying the morpholine and
tosylated tertiary aromatic amine functionalities on the same molecular structure. As it
is well known, morpholine moiety has nitrogen and oxygen atoms inside a heterocyc-
lic six-membered ring and its numerous derivatives are utilized in diverse pharmaceut-
ical and biological applications comprising antimalarial, antidepressant, antitumor, HIV-
protease inhibitors, antiparasitic, antiinflammatory, local anesthetic, anticancer, anal-
gesic, antifungal, appetite suppressant, selective inhibition of protein kinase C, antitu-
berculosis and hypolipidemic activities [27–32]. Morpholine scaffold is also a useful
starting compound and extensively used in organic synthesis as well [33].
It is well-known that DNA is the crucial target in the research and development of
chemotherapeutic agents. The transition metal compounds as chemotherapeutic
agents have increased in recent years due to their DNA-interaction properties. If these

JOURNAL OF COORDINATION CHEMISTRY
3
agents interact with DNA, DNA-damage can occur in cancer cells and effects on cell
proliferation and gene mutations that can trigger cell death [34].
As previously stated that the compounds carrying morpholine skeleton have the
potential to be employed in biological and pharmaceutical applications, we designed
a new study to examine the DNA-cleavage and antioxidant properties following the
syntheses and structural verification of the new tetra-substituted phthalocyaninato
cobalt(II) (5), copper(II) (6), zinc(II) (7) and magnesium(II) (8) compounds bearing 4-
methyl-N-(4-morpholinophenyl)-benzenesulfonamide moieties at a-positions (non-per-
ipheral sites) of the Pc core. Coupled with the results of DNA-cleavage and antioxidant
properties, we found that zinc(II) Pc (7) has a potential utilization in the oxidative pho-
tocleavage and cobalt(II) (5) has remarkable radical scavenging activities.
2. Experimental
2.1. Chemicals and instrumentation
Instrumentation and materials as well as chemicals are provided as Supplementary
Information. 3-Nitrophthalonitrile (3) was synthesized by the procedure cited [35].
2.2. DNA-cleavage studies
DNA-cleavage studies provided as Supplementary Information.
2.3. DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay
DPPH radical scavenging assay part provided as Supplementary Information.
2.4. Syntheses
2.4.1. 4-Methyl-N-(4-morpholinophenyl)benzenesulfonamide (2)
Under nitrogen atmosphere, 4-morpholinoaniline (1) (1.0 g, 5.61 mmol) was dissolved
in dry pyridine (20 mL) inside a 50 mL round bottom flask and deaerated a couple of
times. At ꢀ5 ꢁC, p-toluenesulfonyl chloride (TsCI) (1.069 g, 5.61 mmol) in dry pyridine
(10 mL) was dropwise added to the flask content within 30 min. When the dropwise
addition of TsCI solution was over, a color change was observed in the reaction mix-
ture from dark red-brownish to purple. Thereafter, the stirring continued under a nitro-
gen stream at ꢀ5 ꢁC for 4 h and the stirring was maintained for one night at room
temperature. Then, the reaction mixture was stirred during the addition of crushed ice
(150 g) at room temperature for 3 h. Following that, concentrated HCl acid (54 mL) was
added dropwise in 30 min to maintain the acidity of the mixture and subsequently,
the aqueous solution extracted with chloroform (4 ꢂ 25 mL). The collected chloroform
solvent over the aqueous layer was dried by the addition of anhydrous Na2SO4. The
combined extract was vaporized by a rotary evaporator to remove chloroform to
obtain 2 as a pale purple solid. Yield: 1.28 g (68.8%), m.p. 187–189 ꢁC. Elemental ana-
lysis: Calc. (%) for C17H20N2O3S: C, 61.42; H, 6.06; N, 8.43; S, 9.65. Found: C, 60.47; H,
5.82; N, 8.58; S, 9.48. FT-IR: tmax (cmꢀ1): 3154 (N–H), 3035 (C–H aromatic),

4
H. YALAZAN ET AL.
2967–2919–2900 (CH3), 1599 (C¼C), 1511, 1450, 1336–1158 (SO2-tosyl group), 1263,
1
1239, 1115, 1090, 1051 (N–H), 918, 807, 738, 661. H-NMR (d in ppm, CDCl3): 8.88 (s,
1H, N–H), 7.61–7.59 (d, 2H, Tosyl, Ar–H), 7.22–7.20 (d, 2H, Tosyl, Ar–H), 7.01–6.97 (d,
2H, Ar–H), 6.83–6.79 (d, 2H, Ar–H), 3.88–3.86 (t, 4H, O–CH2), 3.13–3.11 (t, 4H, N–CH2),
2.38 (s, 3H, CH3). 13C-NMR (d in ppm, CDCl3): 148.70, 148.43, 132.96, 129.01, 126.10,
110.52, 107.91, 107.39, 106.19, 105.91, 67.17–66.62–64.93 (O–CH2), 50.12–49.83–49.65
(N–CH2), 22.31–21.59–20.59 (Ar–CH3). MALDI-TOF MS m/z: calculated: 332.42; found:
332.07 [M]þ.
2.4.2.
N-(2,3-Dicyanophenyl)-4-methyl-N-(4-morpholinophenyl)benzenesulfona-
mide (4)
4-Methyl-N-(4-morpholinophenyl)benzenesulfonamide (2) (1.28 g, 3.98 mmol) and 3-
nitrophtalonitrile (3) (0.69 g, 3.98 mmol) were dissolved in dry DMF (15 mL) in the
Schlenk system. After efficient stirring 15 min at 55 ꢁC, anhydrous K2CO3 (1.65 g,
12.00 mmol) was added to the solution by portion wise over 2 h and was degassed
under the N2(g) flow. The reaction mixture was then heated at 55 ꢁC for 138 h and
completion of the reaction was monitored by thin layer chromatography (TLC). After
completion of the reaction, the reaction mixture was cooled to room temperature and
following the addition of crushed ice (200 g) and then stirred efficiently for 2 h at the
same temperature. Later, the stirring mixture was filtered off and dried in vacuo.
Subsequently, the dicyano derivative 4 was purified via crystallization using ethyl alco-
hol. After filtration, 4 was dried in a vacuum desiccator, following the washing with
cold ethanol. Color: Light brown. Yield: 0.75 g (42.4%), m.p. 190–194 ꢁC. Elemental ana-
lysis: Calc. (%) for C25H22N4O3S: C, 65.48; H, 4.84; N, 12.22; S, 6.99. Found (%): C, 64.94;
H, 4.77; N, 11.96; S, 6.75. FT-IR, tmax (cmꢀ1): 3073–3054 (Aromatic C–H), 2967–2920
(CH3), 2233 (CꢃN), 1583 (C ¼ C), 1512, 1466, 1451, 1362–1165 (SO2-tosyl group), 1281,
1239, 1123, 1089, 926, 820, 735, 668. 1H-NMR (d in ppm, CDCl3): 7.94–7.89 (m, 2H,
Tosyl, Ar–H), 7.73–7.65 (m, 2H, Tosyl, Ar–H), 7.32–7.21 (m, 3 H, Ar–H), 6.80–6.72 (m, 4H,
Ar–H), 3.83–3.80 (t, 4H, O–CH2), 3.17–3.15 (t, 4H, N–CH2), 2.45 (s, 3H, CH3). 13C-NMR (d
in ppm, CDCl3): 151.20, 145.73, 144.84, 135.45, 134.67, 133.76, 132.37, 130.47, 130.15,
129.80, 128.45, 117.89, 117.84, 115.40 (CꢃN), 114.79, 113.58, 66.64–65.84 (O–CH2),
48.29 (N–CH2), 21.69 (Ar–CH3). MALDI-TOF MS m/z: calculated: 458.53; found:
458.17 [M]þ.
2.4.3. Syntheses of non-peripherally metallophthalocyanines (5–8)
The dicyano derivative 4 (0.1 g, 0.218 mmol), anhydrous metal salts [CoC12 (14.15 mg,
0.109 mmol, for 5); CuCl2 (14.76 mg, 0.109 mmol, for 6); Zn(OAc)2 (20.00 mg,
0.109 mmol, for 7); MgC12 (10.38 mg, 0.109 mmol, for 8)], dry n-amyl alcohol (3.0 mL)
and DBU f1,8-diazabicyclo[5.4.0]undec-7-eneg (catalytic amount was employed) were
added into a standard Schlenk tube. Then, the content of the Schlenk tube was deaer-
ated by the flow of inert N2(g) and heated at 160 ꢁC for 17 h. As the content of the
Schlenk tube was cooled to room temperature, ethanol (10 mL) was added to the
green reaction mixture to maintain the precipitation of the synthesized compound
and was stirred for 1 h. Subsequently, the precipitated crude compounds were filtered
off and kept inside a vacuum desiccator until they were dried up. Finally, the

JOURNAL OF COORDINATION CHEMISTRY
5
synthesized new metallated phthalocyanines (5–8) depurated by basic alumina-packed
column chromatography with chloroform for 5 and 6 and chloroform:ethanol solvent
mixture (50:2.5 v/v) for 7, and (5:1 v/v) for 8. The collected organic solvent mixture
was removed by rotary evaporation and dried in vacuo to obtain the corresponding
non-peripheral tetra-substituted metallophthalocyanines as dark (5, 6 and 7) or light
green (8) solids.
2.4.3.1. Non-peripherally phthalocyaninato cobalt(II) (5). Color: Dark green. Yield:
25.0 mg (24.2%), m.p. >300 ꢁC. Elemental analysis: Calc. (%) for C100H88N16O12S4Co: C,
63.45; H, 4.69; N, 11.84; S, 6.78. Found (%): C, 62.91; H, 4.57; N, 11.58; S, 6.39. FT-IR,
tmax (cmꢀ1): 3065 (Aromatic C–H), 2955–2917 (CH3), 1602, 1507, 1478, 1449,
1351–1161 (SO2–tosyl group), 1120, 1090, 928, 813, 761, 662. UV-vis (CHC13), kmax, nm
(loge): 327 (4.84), 607 (4.42) and 671 (5.01). MALDI-TOF MS m/z: calculated: 1893.07;
found: 1893.23 [M]þ.
2.4.3.2. Non-peripherally phthalocyaninato copper(II) (6). Color: Dark green. Yield:
40.0 mg (38.6%), m.p. >300 ꢁC. Elemental analysis: Calc. (%) for C100H88N16O12S4Cu: C,
63.29; H, 4.67; N, 11.81; S, 6.76. Found (%): C, 62.45; H, 4.64; N, 11.56; S, 6.37. FT-IR,
tmax (cmꢀ1): 3065–3034 (Aromatic C–H), 2953–2919 (CH3), 1600, 1508, 1449,
1352–1161 (SO2–tosyl group), 1121, 1090, 928, 813, 764, 661. UV-vis (CHC13), kmax, nm
(loge): 344 (4.71), 612 (4.35) and 680 (5.01). MALDI-TOF MS m/z: calculated: 1897.68;
found: 1897.11 [M]þ.
2.4.3.3. Non-peripherally phthalocyaninato zinc(II) (7). Color: Dark green. Yield:
41.0 mg (39.5%), m.p. >300 ꢁC. Elemental analysis: Calc. (%) for C100H88N16O12S4Zn: C,
63.23; H, 4.67; N, 11.80; S, 6.75. Found (%): C, 62.53; H, 4.62; N, 11.66; S, 6.44. FT-IR,
tmax (cmꢀ1): 3044 (Aromatic C–H), 2956–2920 (CH3), 1606, 1509, 1488, 1449,
1332–1159 (SO2–tosyl group), 1118, 1087, 926, 813, 762, 660. 1H-NMR (d in ppm,
CDCl3): 7.81–7.60 (m, 20H, Ar–H), 7.30–7.25 (m, 4H, Ar–H), 6.85–6.79 (m, 20H, Ar–H),
3.79–3.76 (t, 16H, O–CH2), 3.16–3.14 (t, 16H, N–CH2), 2.48 (s, 12H, CH3). 13C-NMR (d in
ppm, CDCl3): 150.48, 147.58, 146.58, 143.78, 143.33, 140.56, 137.68, 136.30, 132.96,
130.29, 129.87, 129.74, 128.11, 124.63, 120.84, 112.16, 105.82, 102.30, 100.97,
66.85–66.77–66.56–65.83
(O–CH2),
48.94–48.54–48.42
(N–CH2),
22.68–22.59–21.70–21.52–20.81 (Ar–CH3). UV-vis (CHCl3), kmax, nm (loge): 350 (4.60),
617 (4.28) and 684 (4.99). MALDI-TOF MS m/z: calculated: 1899.52; found:
1899.22 [M]þ.
2.4.3.4. Non-peripherally phthalocyaninato magnesium (II) (8). Color: Light green.
Yield: 30.0 mg (29.8%), m.p. >300 ꢁC. Elemental analysis: Calc. (%) for
C100H88N16O12S4Mg: C, 64.63; H, 4.77; N, 12.06; S, 6.90. Found (%): C, 64.18; H, 4.51; N,
11.76; S, 6.63. FT-IR, tmax (cmꢀ1): 3044 (Aromatic C–H), 2956–2917–2894 (CH3), 1606,
1509, 1483, 1332–1159 (SO2-tosyl group), 1234, 1119, 1084, 926, 813, 752, 661. 1H-
NMR (d in ppm, CDCl3): 7.75–7.53 (m, 22H, Ar–H), 7.31–7.25 (m, 4H, Ar–H), 6.91–6.78
(m, 18H, Ar–H), 3.89–3.82 (t, 16H, O–CH2), 3.18–3.15 (t, 16H, N–CH2), 2.46 (s, 12H, CH3).
13C-NMR (d in ppm, CDCl3): 150.63, 148.82, 148.24, 144.22, 143.76, 142.93, 139.56,

6
H. YALAZAN ET AL.
Figure 1. Synthetic pathway and chemical structures of the precursor dicyano compound 4 and
metallated phthalocyanines 5–8.

JOURNAL OF COORDINATION CHEMISTRY
7
139.44, 137.62, 132.91, 132.62, 130.41, 129.79, 129.71, 128.02, 126.19, 123.37, 104.86,
103.63, 66.74–65.83 (O–CH2), 48.67 (N–CH2), 21.68 (Ar–CH3). UV-vis (CHC13), kmax, nm
(loge): 355 (4.56), 619 (4.27) and 686 (5.00). MALDI–TOF MS m/z: calculated: 1858.43;
found: 1858.13 [M]þ.
3. Results and discussion
3.1. Syntheses and structural verification
The synthetic procedures of newly synthesized tetra-substituted CoII (5), CuII (6), ZnII
(7) and MgII (8) phthalocyanines fused 4-methyl-N-(4-morpholinophenyl)benzenesulfo-
namide units at their non-peripheral positions are illustrated in Figure 1. In this work,
we obtained new organo-soluble metallated phthalocyanines which exhibited good
solubility in dichloromethane (DCM), chloroform (CHCl3), N,N-dimethylformamide
(DMF), tetrahydrofuran (THF), ethyl acetate (EtOAc), and dimethylsulfoxide (DMSO)
because of the substitution of 4-methyl-N-(4-morpholinophenyl)benzenesulfonamide
units at non-peripheral sites of phthalocyanine core. To verify the structural character-
ization, we benefited from some spectroscopic techniques, including MALDI-TOF mass
spectral data (Dithranol (DIT) for 7 and 8 and 2,5-dihydroxybenzoic acid (DHB) for 5
and 6 were used as the matrixes), UV-vis and FT-IR (ATR sampling accessory tech-
1
nique), H-NMR and 13C-NMR along with elemental analysis.
Starting from 4-morpholinoaniline (1), we obtained the tosylated compound 2, 4-
methyl-N-(4-morpholinophenyl)benzenesulfonamide, with 68.8% yield by adaptation of
the tosylation reaction according to literature [36]. The proton NMR signal associated
with the NH2 group of 1 vanished and a new proton NMR resonance peak belonging
to the N–H functionality was observed as a singlet signal integrating one proton at
1
d ¼ 8.88 ppm for 2 after the tosylation reaction achieved. The other H-NMR peaks of
2 were resonated at 7.61–7.59 (Tosyl, Ar–H), 7.22–7.20 (Tosyl, Ar–H), 7.01–6.97 (Ar–H),
6.83–6.79 (Ar–H), 3.88–3.86 (O–CH2), 3.13–3.11 (N–CH2) and 2.38 ppm (CH3). The carbon
atom peaks belonging to the aromatic rings resonated at 148.70, 148.43, 132.96,
129.01, 126.10, 110.52, 107.91, 107.39, 106.19 and 105.91 ppm in the 13C-NMR spec-
trum of 2. Other carbon atom resonances of 2 were observed at 67.17–66.62–64.93
(O–CH2), 50.12–49.83–49.65 (N–CH2) and 22.31–21.59–20.59 ppm (Ar–CH3) in the 13C-
NMR spectrum. Another indication that the tosylation reaction plainly succeeded is the
evanescence of the primary amine (NH2) vibration of 1 and the existence of new vibra-
tional signals of 2 related to the tosyl group at t ¼ 1336 and 1158 cmꢀ1 (SO2-tosyl
group) and secondary amine (N–H) functionality at t ¼ 3154 and 1051 cmꢀ1 in the FT-
IR spectrum of 2. Accompanied with slight changes, the rest of the infrared vibrations
of 2 were similar to those of the starting compound 1. The mass spectral data meas-
ured with the MALDI-TOF method and the molecular ion peak (MIP) of 2 was detected
at m/z ¼ 332.07 [M]þ (Figure S1 in the Supplementary Material).
N-(2,3-Dicyanophenyl)-4-methyl-N-(4-morpholinophenyl)benzenesulfonamide,
new precursor phthalonitrile compound 4, was obtained from the reaction of 4-
methyl-N-(4-morpholinophenyl)benzenesulfonamide 2, 3-nitrophtalonitrile and
the
3
anhydrous K2CO3 in the existence of dry DMF under an inert nitrogen atmosphere
with 42.4% yield after the purification process. As the synthesis of targeted

8
H. YALAZAN ET AL.
phthalonitrile compound 4 was accomplished successfully from the reaction of tosy-
lated derivative 2, a new vibrational peak was detected at t ¼ 2233 cmꢀ1 belonging to
the CꢃN functional group instead of the vibration signals regarding the N–H function-
ality at t ¼ 3154 and 1051 cmꢀ1 in the vibrational spectra of 2, which was a good sign
of the formation of phthalonitrile derivative 4. One of the best indications of the
achievement of base-catalyzed aromatic nitro-displacement reaction of 3-nitrophthalo-
nitrile 3 in terms of NMR spectroscopy is to see CꢃN resonance peak at 115.40 ppm in
the 13C-NMR spectrum of 4 and the disappearance of the singlet resonance signal of
1
N–H proton, which was resonated at 8.88 ppm in the H-NMR spectrum of 2 (Figure
S2 in the Supplementary Material). Other FT-IR, 1H-NMR and 13C-NMR spectral data
were similar to that of the tosylated compound 2 with slight changes. In the MALDI-
TOF spectrum of 4, MIP was detected at m/z ¼ 458.17 [M]þ (Figure S1 in the
Supplementary Material).
We synthesized the targeted new metallated Pcs [CoII (5), CuII (6), ZnII (7) and MgII
(8)] through the cyclotetramerization reaction of the precursor dicyano compound 4
with CoC12 for 5, CuC12 for 6, Zn(OAc)2 for 7 and MgC12 for 8 in dry n-amyl alcohol
and the catalytic effect of the strong base DBU at 160 ꢁC for 17 h under a N2(g) stream
with moderate yields after the purifying column chromatography processes. In the
case of new phthalocyaninato metal complexes 5–8, the evanescence of the CꢃN
functionality at 2233 cmꢀ1 in the vibrational spectra of phthalonitrile derivative 4 is
among the best structural corroboration methods. Likewise, the resonance peak asso-
ciated with CꢃN groups at 115.40 ppm in the 13C-NMR spectrum of 4 was also evan-
esced after the syntheses of the corresponding metal complexes as well. Since 5 and
6 have paramagnetic transition metal ions inside the center of their phthalocyanine
1
core, their NMR measurements precluded. Except for some little chemical shifts, H-
NMR and 13C-NMR spectra of 7 and 8 were similar to that of 4. According to the
MALDI-TOF mass spectral data, the parent molecular ion peaks were detected at m/
z ¼ 1893.23 [M]þ for 5, 1897.11 [M]þ for 6, 1899.22 [M]þ for 7 and 1858.13 [M]þ for 8
(Figure S3 in the Supplementary Material for 7 and 8). Coupled with synthesis proce-
dures, all spectral data including elemental analysis results are in good harmony with
the suggested chemical compounds.
3.2. Electronic absorption spectra
As remarked previously that the cyclotetramerization reaction of the dicyano com-
pound 4 succeeded and metallated phthalocyanines were obtained, the electronic
absorption spectra of MPcs 5–8 give us some considerable evidence in addition to the
spectroscopic data summarized above. To put it another way, the characteristic B-
(Soret) and Q-bands in UV-vis spectra (measured at room temperature in chloroform
at 1 ꢂ 10ꢀ5 M concentration) of MPcs 5–8 were easily identified at first glance. The
absorptions related with B-band were seen at 327 nm (loge ¼ 4.84) for 5, 344 nm
(loge ¼ 4.71) for 6, 350 nm (loge ¼ 4.60) for 7 and 355 nm (loge ¼ 4.56) for 8. In addition
to intense and sharp Q-band absorptions, shoulders were observed at lower wave-
lengths as well. The shoulders accompanied with narrow and intense Q-bands can be
attributable to the charge-transfer transitions from ligand-to-metal and/or metal-to-

JOURNAL OF COORDINATION CHEMISTRY
9
Figure 2. Supercoiled pBR322 plasmid DNA properties of CoPc (5). Lane 1: DNA control; lane 2: 5
(12.5 lM); lane 3: 5 (25 lM); lane 4: 5 (12.5 lM) þ irradiation; lane 5: 5 (25lM) þ irradiation; lane
6: 5 (12.5 lM) þ H2O2 (0.4 M); lane 7: 5 (25lM) þ H2O2 (0.4 M); lane 8: 5 (12.5 lM) þ H2O2
(0.4 M) þ irradiation; lane 9: 5 (25lM) þ H2O2 (0.4 M) þ irradiation; lane 10: H2O2 (0.4 M); lane 11:
H2O2 (0.4 M) þ irradiation.
ligand [36]. The specific Q-bands were seen at 607 nm (loge ¼ 4.42) and 671 nm
(loge ¼ 5.01) for 5, 612 nm (loge ¼ 4.35) and 680 nm (loge ¼ 5.01) for 6, 617 nm
(loge ¼ 4.28) and 684 nm (loge ¼ 4.99) for 7 and 619 nm (loge ¼ 4.27) and 686 nm
(loge ¼ 5.00) for 8. In light of the UV-vis spectra of the studied phthalocyanine metal
complexes 5–8, the single and intense Q-bands exhibited that all measured MPcs 5–8
under the circumstances summarized above had D4h point group with monomeric
species (no aggregation) of metallophthalocyanines [3, 37].
3.3. DNA-cleavage studies
The hydrolytic, oxidative and photo supercoiled (SC) pBR322 plasmid DNA cleavage
features of the new non-peripherally tetra-substituted organo-soluble CoII 5, CuII 6,
ZnII 7 and MgII 8 phthalocyanines were investigated using agarose gel electrophoresis.
It is well-known that when single-strand cleavage of SC forms nicked circular (NC)
form, double-strand cleavage of SC occurs linear form (LN) that moves between SC
and NC [38]. The results of hydrolytic, oxidative and photo DNA cleavage properties of
5–8 at 12.5 and 25 mM are presented in Figures 2–5 and analyzed using Image Lab
Version 4.0.1 Software. SC showed single-band in the absence of compounds or agent
[hydrogen peroxide (H2O2)] as a negative control, as shown in Figures 2–5 (lane 1).
Figure 2 demonstrated that 5 did not show any considerable cleavage effects against
plasmid DNA under our conditions. In Figure 3, 6 was almost inactive in the dark
(lanes 2 and 3) but the compound had oxidative photocleavage activities with irradi-
ation at 700 nm (17.5 mW/cm2, 15 min) in the presence of H2O2 showing the conver-
sion of SC to NC and LN (lanes 8 and 9) owing to reactive oxygen species which have
been generated by phthalocyanines under irradiation. It is well-known that oxidative
activator such as H2O2 is important to begin the cleavage process. NC (19.90%) and
LN (4.40%) were observed and SC (75.70%) diminished on increasing concentrations of
7 at 25 mM in the presence of H2O2 and irradiation at 700 nm (17.5 mW/cm2, 15 min)
(Figure 4, lane 9). In Figure 5, 8 had no hydrolytic, oxidative and photo activities
against SC. Barut et al. reported that water-soluble morpholine substituted Zn(II)
phthalocyanine had significant cleavage properties at 25, 50 and 100 mM [39]. In add-
ition, Sankarganesh et al. reported that Cu(II) and Zn(II) complexes with 4-(1-(4-mor-
pholinophenyl)ethylideneamino)pyrimidine-5-carbonitrile) had moderate cleavage
activities against calf-thymus DNA [40].

10
H. YALAZAN ET AL.
Figure 3. Supercoiled pBR322 plasmid DNA cleavage properties of CuPc (6). Lane 1: DNA control;
lane 2: 6 (12.5 lM); lane 3: 6 (25 lM); lane 4: 6 (12.5 lM) þ irradiation; lane 5: 6 (25 lM) þ irradi-
ation; lane 6: 6 (12.5 lM) þ H2O2 (0.4 M); lane 7: 6 (25 lM) þ H2O2 (0.4 M); lane 8: 6 (12.5 lM) þ
H2O2 (0.4 M) þ irradiation; lane 9: 6 (25 lM) þ H2O2 (0.4 M) þ irradiation; lane 10: H2O2 (0.4 M);
lane 11: H2O2 (0.4 M) þ irradiation.
Figure 4. Supercoiled pBR322 plasmid DNA cleavage properties of ZnPc (7). Lane 1: DNA control;
lane 2: 7 (12.5 lM); lane 3: 7 (25 lM); lane 4: 7 (12.5 lM) þ irradiation; lane 5: 7 (25 lM) þ irradi-
ation; lane 6: 7 (12.5 lM) þ H2O2 (0.4 M); lane 7: 7 (25 lM) þ H2O2 (0.4 M); lane 8: 7 (12.5 lM) þ
H2O2 (0.4 M) þ irradiation; lane 9: 7 (25 lM) þ H2O2 (0.4 M) þ irradiation; lane 10: H2O2 (0.4 M);
lane 11: H2O2 (0.4 M) þ irradiation.
Figure 5. Supercoiled pBR322 plasmid DNA cleavage properties of MgPc (8). Lane 1: DNA control;
lane 2: 8 (12.5 lM); lane 3: 8 (25 lM); lane 4: 8 (12.5 lM) þ irradiation; lane 5: 5 (25 lM) þ irradi-
ation; lane 6: 8 (12.5 lM) þ H2O2 (0.4 M); lane 7: 8 (25 lM) þ H2O2 (0.4 M); lane 8: 8 (12.5 lM) þ
H2O2 (0.4 M) þ irradiation; lane 9: 8 (25 lM) þ H2O2 (0.4 M) þ irradiation; lane 10: H2O2 (0.4 M);
lane 11: H2O2 (0.4 M) þ irradiation.
3.4. DPPH radical scavenging assay
DPPH assay is one of the routinely and easy colorimetric methods to determine radical
scavenging potential of compounds [41]. The results of DPPH radical scavenging prop-
erties of 5–8 at 12.5, 25, 50 and 100 mM are depicted in Table 1. Gallic acid (GA) was
used as positive control. As shown in Table 1, 5 displayed the highest radical scaveng-
ing activities among the tested compounds at all concentrations. Compound 5 ranged
from 85.35 2.45% (12.5 mM) to 95.38 1.44% (100 mM). At 12.5 and 25 mM, 5 showed
higher antioxidant activity than GA as a positive control. The other compounds (6–8)

JOURNAL OF COORDINATION CHEMISTRY
11
Table 1. Radical-scavenging activity on DPPH radicals (%) of 5–8.
lM
5
6
7
8
GA
12.5
25
50
85.35 2.45
90.10 2.40
94.98 1.04
95.38 1.44
13.98 0.88
15.30 2.49
23.88 2.74
34.70 3.92
15.96 1.37
26.25 2.29
34.96 2.66
41.42 3.91
5.01 0.34
18.86 1.93
39.31 3.91
53.03 4.22
60.38 0.22
80.03 0.35
96.93 1.25
98.93 1.50
100
had moderate radical scavenging activities from 5.01 0.34% to 53.03 4.22%. Fadda
et al. reported that new Pcs carrying peripherally functionalized fused heterocyclic
compounds showed DPPH radical scavenging activities with IC50 values of
0.098–6.011 mM [42]. Aydın et al. reported that IC50 values of tetra-substituted Zn(II)
and Co(II) phthalocyanines bearing (4-(methylthio)phenylthio) were determined as
0.1 0.02 and 0.09 0.03 mg/mL [43].
4. Conclusion
Herein, we reported the synthesis processes and structural characterization of the new
non-peripheral tetra-substituted organo-soluble CoII (5), CuII (6), Zn(II) (7) and Mg(II) (8)
phthalocyanine complexes carrying four 4-methyl-N-(4-morpholinophenyl)benzenesul-
fonamide units. The structural characterization of the newly synthesized molecules
was elucidated by spectroscopic techniques comprising elemental analysis, MALDI-TOF
1
mass spectral data, FT-IR, H-NMR (for 2, 4, 7 and 8), UV-vis (for 5–8) and 13C-NMR (for
2, 4, 7 and 8). The hydrolytic, oxidative and photo DNA-cleavage effects of the prod-
ucts were investigated by agarose gel electrophoresis. Compound 7 indicated oxida-
tive photocleavage activity in the presence of H2O2, indicating the conversion of
supercoiled pBR322 plasmid DNA to nicked circular form (19.90%) and linear form
(4.40%). In addition, DPPH-radical scavenging percentages of the compounds were
determined using colorimetric methods and 5 displayed the highest radical scaveng-
ing activity among the tested compounds. The DPPH radical scavenging percentages
of 5 ranged from 85.35 2.45% (12.5 mM) to 95.38 1.44% (100 mM). Compounds 5–8
synthesized under the framework of this study are favorable for further research since
the broad range of pharmaceutical and biological activities of morpholine-
based compounds.
Disclosure statement
No potential conflict of interest was reported by the authors.
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