Synthesis and characterization of 5-(4-carboxyphenylspermine)-10,15,20-triphenylporphyrin

Article abstract of DOI:10.1142/S1088424619501839

We synthetized and characterized a mono spermine porphyrin derivative by NMR, UV-vis and fluorescence spectroscopy. The photophysical properties and the protonation equilibria of 5-(4-carboxyphenylspermine)-10,15,20-triphenylporphyrin have been investigated, showing that porphyrin does not aggregate in acidic solutions, differently from what occurs as soon as the core of the porphyrin is deprotonated. These aggregation processes have been detected by the rising of new fluorescence band and a significant splitting of the Soret band.

Full text of DOI:10.1142/S1088424619501839

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2019; 23: 1–7
DOI: 10.1142/S1088424619501839
Published at https://www.worldscinet.com/jpp/
Synthesis and characterization of
5-(4-carboxyphenylspermine)-10,15,20-triphenylporphyrin
Chiara M.A. Gangemi, Rosalba Randazzo, Massimiliano Gaeta, Cosimo G. Fortuna,
Maria E. Fragalà, Roberto Purrello* and Alessandro D’Urso*◊
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Italy
Dedicated to Professor Roberto Paolesse on the occasion of his 60th birthday.
Received 3 November 2019
Accepted 11 November 2019
ABSTRACT: We synthetized and characterized a mono spermine porphyrin derivative by NMR,
UV-vis and fluorescence spectroscopy. The photophysical properties and the protonation equilibria
of 5-(4-carboxyphenylspermine)-10,15,20-triphenylporphyrin have been investigated, showing that
porphyrin does not aggregate in acidic solutions, differently from what occurs as soon as the core of
the porphyrin is deprotonated. These aggregation processes have been detected by the rising of new
fluorescence band and a significant splitting of the Soret band.
KEYWORDS: spermine porphyrin, self-assembly, synthesis, fluorescence spectroscopy, pK
determination.
biocompatible. Indeed, due to the great tendency of
INTRODUCTION
porphyrins to aggregate it is difficult to use them in
Porphyrins are widely studied for their unique
media with increasing lipophilicity. To overcome this
and fascinating optical and electronic properties. The
issue, the renowned ability of the polyamine transport
extensive electronic delocalization due to the aromatic
system of the cell which affords a selective accumulation
core leads these molecules to work as light-harvesting
of polyamine analogues in neoplastic tissues [16–19]
and energy- or electron-transfer systems in several
could be exploited. Indeed several porphyrin-poliamine-
biological processes, making these macrocycles essential
conjugated molecules have been reported in the literature
for life. By attempting to mimic these processes, one
with the aim to make porphyrin more biocompatible for
can obtain porphyrin-based systems useful in different
several applications ranging from boron delivery agents
applications ranging from sensing [1–2], to photocatalysis
for boron neutron capture therapy, to PDT and DNA
[3–5] and biology [6–7]. Although porphyrins are
cleavage [20–27].
mainly hydrophobic macrocycles, by exploiting their
In particular, very recently, our group developed a
extreme synthetic versatility it is possible to introduce
synthetic strategy to obtain a tetra-spermine porphyrin
peripherally charged substituents making them soluble in
derivative which showed interesting features in the
water [8–12]. As a consequence of the solvophobicity of
formation of supramolecular assemblies, depending on
the porphyrins, their application in biomedical fields, e.g.
the pH, solvent and the solution preparation method [28].
photodynamic therapy (PDT) is increased exponentially
We demonstrated that tetra-spermine porphyrin and its
[13–15]. With this purpose, synthetic efforts are
Zn(II) derivative show an interesting affinity towards
centered around making water-soluble porphyrins also
different structures of poly-nucleotides [29]. Indeed,
exploiting the ability of both Zn(II) porphyrin derivatives
to axially coordinate and spermine as a groove binder, we
◊ꢀSPP full member in good standing.
realized an inducer, stabilizer and probe for the Z form
of DNA [30]. Moreover, we studied also the stabilizer/
destabilizer effect of naked tetraspermine derivative
*Correspondence to: Prof. A. D’Urso, Viale Andrea Doria, 6,
tel.: +39-0957385095, fax: +39-095580138; email: adurso@
unict.it.
Copyright © 2019 World Scientific Publishing Company

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C. M.A. GANGEMI ET AL.
Scheme 1. General synthetic procedure to obtain the compound (1)
on both telomeric and aptamer sequences forming
G-quadruplex structures [31–32].
tri-BOC-spermine (2) was previously obtained after
differential protection/deprotection reactions of primary
and secondary amine groups in spermine [38–40]. The
mono-functionalized derivative 5-(4-carboxyphenyl-tri-
BOC-spermine)10,15,20-triphenylporphyrin (1a), was
then treated with trifluoroacetic acid in CH2Cl2 in order
to remove the BOC-protecting groups in the spermine
pendant and to obtain the corresponding trifluoracetic
salt H2MCPSpmTPP (1). Unfortunately, the presence
of only one hydrophilic spermine pendant does not
guarantee the complete solubility in water (directly from
solid at neutral pH) of our porphyrin derivative. However
it is perfectly soluble in DMSO, allowing us to prepare
stock solutions in DMSO and to perform characterization
in water solution of compound (1).
The possibility of introducing a variable number
of poly-amine pendants in the meso-position through
simple amidation reaction broadens the perspectives
to obtain a great variety of supramolecular structures
[33] useful for different purposes from biological to
material application fields. In the present work, we
designed, synthetized and characterized a new mono-
spermine tri-phenyl porphyrin derivative (Fig. 1). The
desired compound carrying one single spermine arm,
5-(4-carboxyphenylspermine)-10,15,20-triphenylpor-
phyrin H2MCPSpmTPP (1) (Scheme 1) was achieved
using a modified literature procedure [28].
RESULTS AND DISCUSSION
Spectroscopic measurements
Our porphyrin derivative was spectroscopically
characterized by UV-vis and fluorescence spectroscopy
techniques. In Fig. 1 the UV-vis absorption spectra of
(1) [1 mM] in water shows at pH = 1.5 a Soret band at
434 nm (black line), due to the core-protonated porphyrin
derivative, which is stable even after one hour. In
contrast, at pH = 6.9 we observe a Soret band at 414 nm
(Fig. 1, blue line) ascribed to the core non-protonated
derivative, which in just one hour starts to aggregate as
highlighted by the hypochromic effect of the Soret band
at 414 nm (Fig. 1, red dotted line). Upon performing a
Synthesis of 5-(4-carboxyphenylspermine)-
10,15,20-triphenylporphyrin (1)
The first step of the synthetic procedure consists in the
preparation of 5-(4-methoxycarbonylphenyl)-10,15,20-
triphenylporphyrin (1c), using a Lindsey’s method
[34–35]. Then, we remove the methyl protecting group
[36–37], and after activation in situ using HATU as a
couplingagentwiththefreecarboxylicgroupincompound
(1b), we attach the primary amine group of the pendant
forminganamidederivative(1a).Thepoly-aminependant
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SYNTHESIS AND CHARACTERIZATION OF 5-(4-CARBOXYPHENYLSPERMINE)-10,15,20-TRIPHENYLPORPHYRIN
3
Fig. 1. UV-vis absorption spectra of compound (1) 1 mM in
water at pH = 1.5 (black line); at pH = 7 fresh prepared (blue
line) and after 60 min (red dotted line)
Fig. 3. Plot of absorbance at 434 nm (black circle) and at
412 nm (red circle) and fluorescence emission at 675 nm (inset)
of 1 mM solution of (1) vs. pH values
form. The Soret band decreases in intensity up to pH 3,
suggesting that at this pH the deprotonation of the core
of (1) and the aggregation process start. As a result, the
second derivative of the Soret band after pH 3 shows
two absorption bands, one at ~400 nm and the second
at ~425 nm, suggesting a splitting of the non-protonated
band (414 nm, Fig. 2 inset). As proof of the inertness of
these aggregates, decreasing the pH with one single fast
addition of HCl up to 1.5 value, it was not able to restore
the initial absorbance at 434 nm (Fig. S14).
The independent solutions method allows us to detect
the pKa value of the porphyrin core (Fig. 3). We prepared
different solutions of (1) at distinct pH values, diluting
with water the desired amount of the stock solution of
(1) (previously dissolved in DMSO), in order to reach a
1 mM concentration. Then UV-vis spectra were recorded
for each solution. At acidic pH, the absorption spectra
show only one band centered at 434 nm, in line with
what was reported in the continuous titration, confirming
the absence of any evidences of aggregation (Fig. S15).
Starting from pH 3, it is possible to note the well-defined
band at 412 nm, indicating the presence of the non-
protonated form of (1) (Fig. S15). Through the plot of
absorbances intensities at 434 nm and 412 nm vs. the
pH values Fig. 3, is possible to evidence the pKa value
for the inner core protonation process, which is around
pH ~3.
After pH 5, we detect aggregation processes, high-
lighted by the hypochromic effect and broadening of
the Soret band (Figs 4 and S14). As observed previously
in the continuous titration, in the independent solution
experiments the second derivatives of spectra at higher
pH (ranging from 5.5 and 8.5) show the presence of two
bands centered at ~400 nm and ~424 nm (inset, Fig. 4).
From pH 8.6 the band at 424 nm shifts to ~440 nm,
suggesting the formation of a new family of aggregates.
These aggregation processes hinder the possibility of
Fig. 2. UV-vis titration of compound (1) 1 mM in water
preliminary UV-vis characterization, we determined the
molar extinction coefficients both in DMSO and in water
at pH = 1.5 per HCl, obtaining respectively e418.5 nm
=
-1
-1
3.20 × 105 M-1 cm and e434 nm = 1.72 × 105 M-1 cm
(see Figs S12 and S13 in the Supporting information).
Taking into account the possible aggregation
phenomena, we studied the protonation equilibria and
aggregation both through slow titration increasing the
pH values and through independent solution methods.
In the first method, a solution of (1) [1 mM] at pH =
1.5 was slowly titrated, adding increasing amounts
of NaOH solution and recording the UV-vis spectra
at different pH (Fig. 2). The decreasing intensity of
the Soret band at 434 nm with increasing pH values,
without the appearance of a band at 414 nm, confirms the
possibility of aggregation, which should occur as soon as
deprotonation of the porphyrin core happens. Indeed, we
think that the positive charges of the spermine arm alone
are not sufficient to hold the porphyrin in its monomeric
.
.
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C. M.A. GANGEMI ET AL.
porphyrin UV spectra at pH 8.6 with different solvent
(Fig. S16).
To further investigate the behavior of our compound,
fluorescence, RLS and excitation experiments were
conducted. From the plot of fluorescence spectra
(Fig. S17) at 675 nm vs. pH values, we can confirm
the pKa of the porphyrin core which in this case also
is ~3 (inset Fig. 3). RLS spectra performed at different
pH also confirm the formation of aggregates from pH 6
which evolve into more structured aggregates at pH 9
as indicated by the intense band at 450 nm (Fig. S18).
From the comparison of fluorescence spectra at pH =
0.9, at pH = 6.3 with lex = 422 nm and lex = 412 nm
(Fig. 5) it is possible to note the presence of emission
band at 605 nm, detectable only at pH 6.3 with lex
=
Fig. 4. UV-vis absorption spectra of compound (1) 1 mM in
water at pH = 6.9 (black line); at pH = 7.2 (red line) and at pH =
8.6 (blue line). In the inset the second derivatives of the same
spectra are reported
422 nm. In order to investigate the origin of the
605 nm emission band, we recorded excitation spectra.
Noteworthy, the excitation spectrum at lem = 605 nm
shows a Soret band centered at 420 nm, ascribed to non-
protonated aggregated species. This emission is, in fact,
undetectable at the same pH when the fluorescence is
recorded with lex = 412 nm (Fig. 5a blue line).
determining the pKa values of the poly-amine pendant,
even if, from the graph reporting the intensity of
absorbances at 412 nm vs. the pH values (Fig. 3), three
steps at around pH 5.5, 6.5 and 9 might be ascribed to the
pKa values of the spermine arm. In order to validate our
hypothesis about the pendant pKa values, we performed
simulation through the MoKa program [41–43]. The pKa
values of the poly-amine pendant result at around ~7 and
~8 for the inner secondary amine groups and ~10 for the
primary ones. These results are in line with what was
observed in the experimental data, which are slightly
shifted due to aggregation processes. Noteworthy, in
the presence of 10% of DMSO it is possible to reduce
the aggregation process as indicated by comparison of
EXPERIMENTAL
General
All chemicals were purchased from Sigma–Aldrich as
reagent grade and were used without further purification.
Ultra-pure water (18.2 MW.cm) was obtained from the
Elga Purelab Flex system by Veolia. NMR experiments
were carried out at 27°C on a Varian UNITY Inova
500MHz spectrometer (1H at 499.88 MHz, 13C NMR at
125.7 MHz) equipped with a pulse field gradient module
Fig. 5. (a) Fluorescence spectra of (1) 1 mM at pH = 0.9 (lex = 422 nm; black line) and at pH = 6.3 (lex = 422 nm; red line and
lex = 412 nm blue line). (b) Excitation spectra of (1) 1 mM at pH = 0.9 (lem = 675 nm; black line) and at pH = 6.3 (lem = 605 nm;
red line and lem = 650 nm blue line).
Copyright © 2019 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2019; 23: 4–7

SYNTHESIS AND CHARACTERIZATION OF 5-(4-CARBOXYPHENYLSPERMINE)-10,15,20-TRIPHENYLPORPHYRIN
5
(Z axis) and a tunable 5 mm Varian inverse detection
probe (ID-PFG). ESI mass spectra were acquired on a
API 2000TM AB Sciex system using MeOH (positive
ion mode). A JASCO V-560 UV-vis spectrophotometer
equipped with a 1 cm path-length cell was used for
UV-vis measurements. Luminescence measurements
were carried out using a Cary Eclipse fluorescence
spectrophotometer with different excitation wavelength
and a 0.5 nm resolution, at room temperature. The
emission was recorded at 90° with respect to the exciting
line beam using 5/5 nm slit-widths for all measurements.
100% to CHCl3/EtOH 98:2) to give desired compound
1a. Yield 36.5 mg (28%). UV-vis (CH3OH) lmax, nm
(log e) 413 (5.57), 512 (4.29), 548 (4.00), 590 (3.81), 645
(3.60). 1H NMR (500 MHz; Acetone-d6) dH, ppm 8.87 (br
s, 8H), 8.31–8.29 (dd, 4H), 8.24 (m, 6H), 7.82 (m, 9H),
5.95 (br s, 1H), 3.60–3.40 (br m, 4H), 3.35–3.22 (m, 6H),
3.08 (m, 2H), 1.93 (m br, 2H), 1.71 (m br, 2H), 1.60 (m
br, 4H), 1.51 (s, 9H), 1.47 (s, 9H), 1.39 (s, 9H), -2.72
(s, 2H). 13C NMR (125MHz; Acetone-d6) dC, ppm 166.0,
155.7, 150.1, 149.6, 146.2, 144.7, 143.3, 141.9, 134.5,
134.3, 131.7, 131.6, 131.6, 131.3, 127.9, 127.4, 126.8,
126.5, 125.6, 125.2, 120.72, 120.4, 120.3, 119.2, 78.5,
77.5, 46.7, 44.2, 37.5, 27.8, 27.8. ESI-MS: m/z 1143.87
[M +ꢀH]+.
Synthesis of 5-(4-carboxyphenylspermine)-
10,15,20-triphenylporphyrin (1) (H2MCPPSpm1) (1)
Synthesis of 5-(4-carboxyphenylspermine)-10,15,20-
triphenylporphyrin (1). To a solution of 5-(4-carboxy-
phenyl-tri-BOC-spermine)-10,15,20-triphenylporphyrin
1a (20.6 mg, 0.018 mmol) in CH2Cl2 (3 mL) was added
40 µL of TFA (0.52 mmol). After about 8 h, were added
another 60 µL of TFA and 4 mL of CH2Cl2 and allowed
to react overnight. After about 24 h the solvent was
removed in vacuum to obtain the desired product 1 as
Synthesis of 5-(4-methoxycarbonylphenyl)-10,15,20-
triphenyl-21,23h-porphyrin (1c). To a solution of pyrrole
(2.52 mL, 36 mmol), in CHCl3 (500 mL) benzaldehyde
(3.64 mL, 36 mmol) and methyl-p-formylbenzoate
(985.0 mg, 6 mmol) were added and purged with
nitrogen (1 h) in the dark. Then boron trifluoride etherate
(0.69 mL, 5.4 mmol) was added and the reaction was
allowed to stir at room temperature. After one h, DDQ
(8.14 g, 36 mmol) was added and stirred for 16 h. The
reaction mixture was concentrated in vacuum and was
purified by double column chromatography (CH2Cl2) to
1
trifluoracetic acid salt yield 20.3 mg (95%). H NMR
(500 MHz; CD3OD) dH, ppm 8.87 (m, 8H), 8.71 (d,
J = 8.0 Hz, 2H), 8.60 (m, 6H), 8.53 (d, J = 8.0, 2H), 3.74
(t, J = 6.5 Hz, 2H), 3.27 (t, J = 7.0 Hz, 2H), 3.18 (m, 6H),
3.08 (t, J = 7.5 Hz, 2H), 2.20 (m, 2H), 2.12 (m, 2H), 1.92
(m,4H). 13C NMR (125 MHz; CD3OD) dC, ppm 169.3,
150.1, 143.7, 143.3, 140.4, 136.4, 134.3, 132.6, 131.3,
130.5, 129.6, 129.3, 129.1, 128.1, 127.0, 126.4, 126.0,
122.3, 122.1, 120.2, 46.9, 45.3, 44.5, 36.4, 29.3, 29.0,
26.5, 23.9, 23.0, 22.9. ESI-MS: m/z 843.73 [M + H]+.
1
give a solid purple powder 1c, yield 135.7 mg (3%). H
NMR (500 MHz; CDCl3): dH, ppm 8.88 (m, 6H), 8.80
(d, J = 5.0 Hz, 2H), 8.45 (d, J = 8.0 Hz, 2H), 8.32 (d, J =
8.0, 2H), 8.23 (d, J = 7.0 Hz, 6H), 7.78 (m, 9H), 4.12
(s, 3H), -2.76 (2H).
Synthesis of 5-(4-carboxyphenyl)-10,15,20-triphe-
nylporphyrin (1b). To a suspension of 1c (77.5 mg,
0.12 mmol) in EtOH (5 mL) was added a solution of
KOH (2N, 10 mL) and the suspension was refluxed for
24 h. Cooled to room temperature, the reaction mixture
was acidified with HClacq up to a pH ≈ 5. The compound
is extracted with ethyl acetate (3 × 20 mL). The organic
phase was collected and dried with anhydrous Na2SO4.
The solvent was removed in vacuum obtaining desired
product 1b as a violet powder. Yield 75.7 mg (95%). 1H
NMR (500 MHz; Acetone-d6) dH, ppm 8.90–8.91 (m,
8H), 8.52 (d, J = 8.0 Hz, 2H), 8.43 (d, J = 8.0 Hz, 2H),
8.28 (m, 6H), 7.86 (m, 9H).
Synthesisof5-(4-carboxyphenyl-tri-BOC-spermine)-
10,15,20-triphenylporphyrin (1a). To a solution of
compound 1b (75.7 mg, 0.115 mmol) in DMFdry (1 mL),
under nitrogen atmosphere and at room temperature,
HATU (50.7 mg, 0.133 mmol) in DMFdry (1 mL) was
added dropwise and stirred for 20 min. Then to the
reaction mixture a solution of tri-BOC-Spm (57.8 mg,
0.115 mmol) in DMFdry (500 µL) was added. After
40 min N,N-diisopropylethylamine (20 mL, 0.115 mmol)
was added to reaction mixture and it was stirred at room
temperature under nitrogen atmosphere for 54 h. Then
H2O was added and the precipitate was dried and after
purified by double chromatographic column (from CHCl3
Spectroscopic measurements
Stock solutions of compound (1) in DMSO ~mM
concentrations were obtained by dissolving the purple
solid directly in dry DMSO. For continuous titration we
diluted the calculated amount of stock solution in DMSO
to obtain a 1 mM working solution, at ~pH 1. Then, every
10 min we added small amounts of NaOH to increase
the pH of the solution and we recorded the spectrum. To
prepare independent solutions, we diluted into aqueous
solutions at different pH, obtained using HCl and/or
NaOH solution, the needed amount of porphyrin stock
solution to achieve 1 mM concentration.After preparation
of the samples we waited 10 min before recording the
spectra. All experiments were conducted by using 1cm
four face plastic cuvettes in order to avoid the porphyrin
sticking on the cuvette walls.
CONCLUSION
In conclusion, an interesting and simple synthetic
strategy was used to obtain a single spermine pendant
porphyrin derivative with good solubility in water
after dissolving it in a DMSO stock solution. The
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C. M.A. GANGEMI ET AL.
derivative was spectroscopically characterized and
showed fascinating behavior in water at different pH.
The presence of a single spermine pendant gave us the
opportunity to exploit the well-known capability of poly-
amine to interact with biological targets without giving
up on the hydrophobic features of the porphyrin core.
Thus, combining these properties it is possible to use this
compound both as single molecules and as aggregates for
further studies towards different applications in material
or biological fields.
8. Kadish KM, Smith KM and Guilard R. (Eds).
Handbook of Porphyrin Science: With Applications
to Chemistry, Physics, Materials Science, Engi-
neering, Biology And Medicine, Vols. 26–30, World
Scientific Publishing Co. Pte. Ltd., Singapore,
Singapore, 2013.
9. Vicente GHM and Smith KM. Curr. Org. Synth.
2014; 11: 13–28.
10. Lammer AD, Cook ME and Sessler JL. J. Porphy-
rins Phthalocyanines 2015; 19: 398–403.
11. Kadish KM, Smith KM and Guilard R. (Eds). The
Porphyrin Handbook: Inorganic, Organometal-
lic and Coordination Chemistry, Vol. 3 Academic
Press: San Diego, CA, 2000.
12. Mandal AK, Sahin T, Liu M, Lindsey JS, Bocian
DF and Holten D. New J. Chem. 2016; 40:
9648–9656.
13 (a) O’Connor AE, Gallagher WM and Byrne AT.
Photochem. Photobiol. 2009; 85: 1053–1074. (b)
Garcia-Sampedro A, Tabero A, Mahamed I and
Acedo P. J. Porphyrins Phthalocyanines 2019; 23:
11–27. (c) Frochot C and Mordon S. J. Porphyrins
Phthalocyanines 2019 23: 347–357.
14. (a) Patel NJ, Chen Y, Joshi P, Pera P, Baumann
H, Missert JR, Ohkubo K, Fukuzumi S, Nani
RR, Schnermann MJ, Chen P, Zhu J, Kadish KM
and Pandey RK. Bioconjugate Chem. 2016; 27:
667–680. (b) Aggarwal A, Samaroo D, Jovanovic
IR, Singh S, Tuz MP and Mackiewicz MR. J.
Porphyrins Phthalocyanines 2019; 23: 729–765.
(c) Glowacka-Sobotta A, Wrotynski M, Kryjew-
ski M, Sobotta L and Mielcarek J. J. Porphyrins
Phthalocyanines 2019; 23: 1–10.
Acknowledgments
This research was funded by University of Catania,
Department of Chemical Sciences (Piano per la Ricerca
2016-2018–Linea Intervento 2) and by Italian Ministero
della Istruzione, dell’Università e della Ricerca (MIUR)
PRIN Prot. 2017YJMPZN.
Supporting information
Synthetic scheme and spectral data (Figs S1–S18)
are given in the supplementary material. This material
is available free of charge via the Internet at http://www.
worldscinet.com/jpp/jpp.shtml.
REFERENCES
1. Paolesse R, Nardis S, Monti D, Stefanelli M and Di
Natale C. Chem. Rev. 2017; 22: 2517–2583.
2. Paolesse R, Monti D, Nardis S and Di Natale C.
In Handbook of Porphyrin Science World Scientific
Publishing Co. Pte. Ltd.: Singapore, 2011; Vol. 12,
pp. 121–225.
15. Rajora MA, Louac JWH and Zheng G. Chem. Soc.
Rev. 2017; 46: 6433–6469.
16. Cullis PM, Green RE, Merson-Davies L and Travis
N. Chem. Biol. 1999; 6: 717–729.
17. Carlisle DL, Devereux WL, Hacker A, Woster
PM and Casero RA Jr. Clin. Cancer Res. 2002; 8:
2684–2689.
18. Wang C, Delcros JG, Biggerstaff J and Phanstiel O,
IV. J. Med. Chem. 2003; 46: 2663–2671.
3. Ladomenou K, Natali M, Iengo E, Charalampidis
G, Scandola F and Coutsolelos AG. Coord. Chem.
Rev. 2015; 304–305: 38–54.
4. Wang Z, Medforth CJ and Shelnutt JA. J. Am.
Chem. Soc. 2004; 126: 16720–16721.
5. Fateeva A, Chater PA, Ireland CP, Tahir AA,
Khimyak YZ, Wiper PV, Darwent JR and
Rosseinsky MJ. Angew. Chem., Int. Ed. Engl. 2012;
51: 7440–7444.
19. Wang C, Delcros JG, Biggerstaff J and Phanstiel O,
IV. J. Med. Chem. 2003; 46: 2672–2682.
20. Dinesh NVS, Bhupathiraju K and Vicente MGH.
Bioorg. Med. Chem. 2013; 21: 485–495.
21. Lamarche F, Sol V, Huang Y-M, Granet R, Guillo-
ton M and Krausz P. J. Porphyrins Phthalocyanines
2002; 6: 130–134.
22. JakobsA, Bernadou J and Meunier B. J. Org. Chem.
1997; 62: 3505–3510.
6. (a) Imran M, Ramzan M, Kaleem Qureshi A, Khan
MA and Tariq M. Biosensors 2018; 8: 95. (b) Taw-
fik EH, Fadda AA, Soliman NN, Abou-Zeid L and
Negm A. J. Porphyrins Phthalocyanines 2019; 23:
251–259. (c) Bruce G, Samperi M, Amabilino DB,
Duch M, Plaza JA and Pérez-Garcìa L. J. Porphy-
rins Phthalocyanines 2019; 23: 223–233. (d) Sanad
MH, Farag AB and Saleh GM. Radiochemistry
2019; 61: 347–351.
23. Sol V, Lamarche F, Enache M, Garcia G, Granet R,
Guilloton M, Blais JC and Krausza P. Bioorg. Med.
Chem. 2006; 14: 1364–1377.
24. Garcia G, Sarrazy V, Sol V, LeMorvan C, Graneta
R, Alves S and Krausz P. Bioorg. Med. Chem. 2009;
17: 767–776.
7. Kadish KM, Smith KM and Guilard R. (Eds).
Handbook of Porphyrin Science with Applications
to Chemistry, Physics, Materials Science, Engi-
neering, Biology and Medicine: Vol. 33, Applica-
tions-Part II. World Scientific Publishing Co. Pte.
Ltd.: Singapore, 2014.
Copyright © 2019 World Scientific Publishing Company
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7
25. Sessler JL, Andrievsky A, Sansom PI, Král V and
Iverson BL. Bioorg. Med. Chem. Lett. 1997; 7:
1433–1436.
26. Sasaki H and Sasaki S. Chem. Commun. 2013; 49:
9024–9026.
27. Hahn F, Schmitz K, Balaban TS, Bräse S and
Schepers U. ChemMedChem 2008; 3: 1185–1188.
28. Gangemi CMA, Randazzo R, Fragalà ME, Toma-
selli GA, Ballistreri FP, Pappalardo A, Toscano RM,
Trusso Sfrazzetto G, Purrello R and D’Urso A. New
J. Chem. 2015; 39: 6722–6725.
29. Gangemi CMA; D’Agostino B, Randazzo R, Gaeta
M, Fragalà ME, Purrello R and D’Urso A. J. Por-
phyrins Phthalocyanines 2018; 22: 581–587.
30. Gangemi CMA, D’Urso A, Tomaselli GA, Berova
N and Purrello R. J. Inorg. Biochem. 2017; 173:
141–143.
34. Brewer A, Siligardi G, Neylond C and Stulz E. Org.
Biomol. Chem. 2011; 9: 777–782.
35. Lindsey JS, Hsu HC and Schreiman IC. Tetrahe-
dron Lett. 1986; 27: 4969–4970.
36. Matile S, Berova N, Nakanishi K, Fleischhauer
J and Woody RW. J. Am. Chem. Soc. 1996; 118:
5198–5206.
37. Balaz M, Holmes AE, Benedetti M, Proni G
and Berova N. Bioorg. Med. Chem. 2005; 13:
2413–2421.
38. Geall AJ and Blagbrough IS. Tetrahedron 2000; 56:
2449–2460.
39. Blagbrough IS and Geall AJ. Tetrahedron Lett.
1998; 39: 439–442.
40. Sunil AD and Dutta A. U.S. Pat. Appl. Publ., 2007,
US2007/0197658A1.
41. MoKa3.0.https://www.moldiscovery.com/software/
moka/.
31. D’Urso A, Randazzo R, Rizzo V, Gangemi CMA,
Romanucci V, Zarrelli A, Tomaselli G, Milardi D,
Borbone N, Purrello R, Piccialli G, Di Fabio G and
Oliviero G. Phys. Chem. Chem. Phys. 2017; 19:
17404–17410.
42. Milletti F, Storchi L, Sforna G and Cruciani G.
J. Chem. Inf. Model. 2007; 47: 2172–2181.
43. Cruciani G, Milletti F, Storchi L, Sforna G and
Goracci L. Chem. Biodivers. 2009; 6: 1812–1821.
32. Sabharwal NC, Chen J, Lee JH, Gangemi CMA,
D’Urso A and Yatsunyk LA. Int. J. Mol. Sci. 2018;
19: 3686.
33. Tuccitto N, Trusso Sfrazzetto G, Gangemi CMA,
Ballistreri FP, Toscano RM, Tomaselli GA, Pappa-
lardo A and Marletta G. Chem. Commun. 2016; 52:
11681–11684.
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