Water-soluble porphyrin-phosphonate conjugates as potential photodynamic therapy photosensitizers

Article abstract of DOI:10.1142/S1088424615500789

Two novel water-soluble porphyrin-phosphonate conjugates were synthesized and characterized. Although both conjugates showed significant potential in photodynamic therapy, the variety of their structure induced the obvious differences in the binding manne

Full text of DOI:10.1142/S1088424615500789

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2015; 19: 1–7
DOI: 10.1142/S1088424615500789
Published at http://www.worldscinet.com/jpp/
Water-soluble porphyrin-phosphonate conjugates as
potential photodynamic therapy photosensitizers
Yunguo Lua‡, Zhihang Chenb‡, BingqiongYua, KunYan*a and Zaoying Li*a
a College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China
b Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Received 14 April 2015
Accepted 22 June 2015
ABSTRACT: Two novel water-soluble porphyrin-phosphonate conjugates were synthesized and
characterized. Although both conjugates showed significant potential in photodynamic therapy, the
variety of their structure induced the obvious differences in the binding manner with calf thymus DNA,
the cytotoxicity and the cellular sublocalization.
KEYWORDS: porphyrin-phosphonate conjugates, photodynamic therapy, photosensitizers, DNA.
human body. Meanwhile, its derivates have a variety of
INTRODUCTION
therapeutic benefits. Inositol-phosphonates analogs have
Photodynamic therapy (PDT) has been emerging as an
been reported to show good inhibition to non-small cell
effective modality for the selective treatment of cancers
lung cancer (NSCLC) cell growth together with less
and other diseases for many years [1, 2]. Due to the non-
toxicity against normal breast epithelial cell (MCF10A)
targeted distributions of the photosensitizers (PSs), which
[17]; anthracene-phosphonate conjugate (TEABP) was
lead to unwanted photodynamic effects in normal tissues
indicated as a selective anticancer agent in apoptosis
[3], PDT has been mostly limited to cure melanomas and
mediated cancer therapy for U937 cell [18]; phosphonate-
solid tumors like the bladder and the esophagus [4], which
functionalized nanoparticles provided a promising basis
occurred in externally accessible cavities. To overcome
for further development of biodegradable nanoparticles
these limitations, especially the undesirable side-effects,
with high intracellular uptake rates or for drug release in
PSs have been conjugated with some biological molecules,
a specific target cell [19].
such as carbohydrates [5, 6], monoclonal antibodies [7, 8],
Here we designed and synthesized two novel water-
peptides [9–11], oligo-nucleotides [12] and some other
soluble cationic porphyrin-phosphonate conjugates
natural products [13], to improve their biocompatibility,
(Chart 1), as potential photodynamic agents with high
selectivity, efficacy and stability.
Theporphyrintendtoaccumulateinneoplastictissueto
higher concentrations than in surrounding normal tissue,
therapy efficiency and biocompatibility.
and they might be photo-triggered to produce singlet-
state oxygen to cleave DNA and eventually damage the
tumor cells [14]. Therefore, porphyrin compounds have
RESULTS AND DISCUSSION
Preparation of porphyrin-phosphonate conjugates
attracted significant attention in cancer diagnosis and
treatment using photodynamic therapy(PDT) [15, 16].
Phosphonate, which is an important component of
cell membranes and nucleotides, widely exists in the
The water-soluble porphyrin P1, which was used
as the control compound in our bioactivity studies,
was synthesized as described in the literature [20]. The
syntheses of porphyrin-phosphonate conjugates P2 and P3
were carried out as shown in Scheme 1. In brief, compound
1, which was prepared as described in the literature,
was transfered to compound 2 with active hydroxyl by
boron tribromide. Then diethyl phosphorochloridate and
*Correspondence to: Kun Yan, email: kyan@whu.edu.cn;
Zaoying Li, email: zyliwuc@whu.edu.cn, tel: + 86 27-68752366,
fax: + 86 27-68754067
‡Equally contributing authors
Copyright © 2015 World Scientific Publishing Company

2
Y. LU ET AL.
N
N
N
3
3
I
3
I
I
O
O
O
O
O
O
P
O
NH
N
NH
N
N
N
NH
N
P
O
(b) or (c)
R
O
N
N
N
HN
HN
HN
N
N
N
N
P1
P2
P3
Chart 1. Molecular structure of P1–P3
N
N
NH
N
NH
N
N
(a)
O
OH
N
N
HN
N
HN
N
N
1
2
I -
N
N
NH
N
NH
N
N
N
(d)
O
R
O
N
N
HN
HN
I -
N
N
I -
O
P
O
P
O
O
O
O
3: R =
4: R =
P2: R =
P3: R =
O
O
P
O
O
P
O
O
Scheme 1. Preparation of water-soluble porphyrin-phosphonate conjugates. Reagents and conditions: (a) BBr3, CH2Cl2, 0°C to rt,
overnight; (b) ClPO(OC2H5)2, K2CO3, DMF, 70°C, 8 h; (c) BrCH2CH2CH2PO(OCH3)2, K2CO3, DMF, 70°C, 8 h; (d) CH3I, DMF,
rt, overnight
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 2–7

WATER-SOLUBLE PORPHYRIN-PHOSPHONATE CONJUGATES AS POTENTIAL PHOTODYNAMIC THERAPY
3
dimethyl(3-bromopropyl)phosphonate [21, 22] coupled
fluorescence titration and CD spectrum (Figs 1–3). The
spectral measurements were performed at 25°C in buffer
solution (50 mM Tris-HCl, 100 mM NaCl, pH = 7.4).
The UV-vis absorption spectra of P1–P3 (3.0 mM) with
addition of CT DNA are shown in Fig. 1. With increasing
amounts of CT DNA (0–3.2 mM), the absorption spectra
of P1 and P3 showed the red shift of 10–11 nm and the
hypochromicities of 40–42%. However, further addition
of CT DNA (3.5–50.0 mM) led to the additional red shift
of 3–5 nm and the unexpected hyperchromicities of about
5%, which indicated that the binding model towards CT
DNA might have been changed from an intercalative
binding to a mixed binding model [23]. However, there
was no similar inflection point in the titration spectra of
P2, and the absorption spectra of P2 only showed a red
shift of 7 nm and a lower hypochromicity of 35%. The
lack of hyperchromicity at high DNA/P2 ratio indicates
that binding manner of P2 to DNA is different from the
binding manner of P1 and P3 to DNA, and the sterical
effect [24] is the main possible reason that causes this
difference.
with compound 2 in the presence of K2CO3 respectively
to afford porphyrin 3 and 4 in good yields. Finally, the
N-methylation of pyridine in porphyrin rings with excess
of methyl iodide in DMF resulted in desired cationic
conjugate P2 or P3 in high yields.
In vitro photocytotoxicity
The photocytotoxicities of P1–P3 against human
prostate cancer cell line PC3 and human breast cancer cell
line MDA-MB-231 were determined by the MTT assay.
The cells were incubated with medicines in dark for 12 h,
then replenished with fresh medium and irradiated
with lights (10 J/cm2) by mercury lamp. After another
24 h incubation in dark, cell viabilities are determined.
The cell viabilities are listed in Table 1, in which the
cytotoxicities were expressed as the drug concentration
that inhibits cell proliferation by 50% (IC50). As seen in
Table 1, all porphyrins were considered to be nontoxic in
the dark as the values of IC50 were larger than 100 mM.
With light irradiation, P1 and P3 exhibited similar
significant cytotoxicity against the cancer cells in the
nanomolar range. It is noteworthy that P2 had 6-fold less
cytotoxic effect than P1 and P3.
The results of fluorescence titration with CT DNA
for P1–P3 are shown in Fig. 2. The emission spectra
of cationic porphyrin conjugate P1–P3 (3.0 mM) were
recorded with increasing amounts of CT DNA (0–50 mM).
The fluorescence intensities of P1–P3 all displayed
significant decreases around 665 nm with the addition of
CT DNA, indicating they adopt an outside binding or a
combination of intercalation and outside binding mode
Spectroscopic properties
The interaction of cationic porphyrins P1–P3 with calf
thymus DNA (CT DNA) was studied by UV-vis spectrum,
Table 1. Cytotoxicities (IC50, mM) of P1–P3 against PC3 and MDA-MB-231 cells (irradiation
energy: 10 J/cm2)
Porphyrins
PC3
MDA-MB-231
In dark
With light irradiation
In dark
With light irradiation
P1
P2
P3
>100
>100
>100
0.24 0.004
1.42 0.005
0.25 0.004
>100
>100
>100
0.30 0.004
2.06 0.003
0.31 0.005
Fig. 1. Absorbance spectra of P1–P3 (the concentrations of porphyrin are 3.0 mM, arrows indicate the change in intensity with
increasing of CT DNA concentrations)
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 3–7

4
Y. LU ET AL.
Fig. 2. Fluorescence spectra of P1–P3 (the concentrations of porphyrin are 3.0 mM, arrows indicate the change in intensity with
increasing of CT DNA concentrations)
Fig. 3. Induced CD spectra of P1–P3 (the concentrations of porphyrin are 10.0 mM, the ratio of [porphyrin]/[DNA base pair] running
from 0.2 to 0.05)
with CT DNA. The binding constant (K, M-1) values
P3 were higher than that of P2; therefore the higher
are 3.39 × 105, 3.18 × 105 and 3.71 × 105, respectively
cell up-takes were the possible main reason that causes
the higher cytotoxicity of P1 and P3. P2 and P3 both
showed almost uniform distribution in the entire cell, and
there was no obvious organelle specificity. Although the
obvious enrichment of P1 in cytoplasm could been seen,
there was no significant organelle specificity of P1 when
compared with other organelle specifical probe such as
mitochondrion, lysosome, Golgi, ER and endosome.
Compared with P2 and P3, P1 without phosphonate
had the higher positive charge density and smaller steric
hindrance. Therefore we considered that P1 was easy
to bind and aggregated with protein in cytoplasm, and
this stronger interactions with protein induced the non-
specific enrichment of P1 in cytoplasm.
for P1, P2 and P3 [25].
To further clarify the binding mode, the induced CD
spectra of the porphyrins were recorded in the presence
of CT DNA. As shown in Fig. 3, the strong negative
peaks of all conjugates centered at 452 nm indicated the
intercalation mode. The weak positive peaks centered
at 428 nm had appeared in the spectra of P1 and P3.
The strong positive peaks centered at 428 nm were
observed in the spectra of P2, which revealed that outside
binding also took a role in the interaction [26–28].
When porphyrin compounds interacted with CT DNA,
intercalation was dominant for P1 and P3, but outside
binding was dominant for P2 due to the steric effect.
Subcellular localization
EXPERIMENTAL
The confocal laser scan microscope was performed to
investigate the cell up-takes and localization of P1–P3 in
PC3 cells and MDA-MB-231 cells. All of the imaging
pictures were obtained with same instrument parameters
and the results are shown in Fig. 4. In both PC3 and
MDA-MB-231 cells, it is obvious that the fluorescence
intensities of P1 and P3 were stronger than that of the P2.
Because of the similar molar extinction and fluorescence
quantum yields. It indicated the cell up-takes of P1 and
Material and methods
Pyrrole, 4-pyridinecarboxaldehyde, 4-methoxybenzal-
dehyde, 1,3-dibromopropane, trimethyl phosphite and
triethyl phosphite were freshly redistilled before using.
All reaction solvents were dried and purified according to
standard procedures. The 5-(4-methoxyphenyl)-10,15,20-
tri(pyridin-4-yl) porphyrin (1) was synthesized according
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 4–7

WATER-SOLUBLE PORPHYRIN-PHOSPHONATE CONJUGATES AS POTENTIAL PHOTODYNAMIC THERAPY
5
Fig. 4. Laser confocal fluorescence microscopy images of P1–P3 in (left) PC3 cells and (right) MDA-MB-231 cells (dosage: 5 mM;
incubation time: 6 h)
to literature method [20]. Diethyl phosphorochloridate
was synthesized according to the literature [21], and
dimethyl (3-bromopropyl)phosphonate was prepared
following the literature [22]. UV-visible spectra were
recorded on a Shimadzu 1601 spectrophotometer. Fluores-
cence spectra were recorded on PerkinElmer LS-55
fluorospectrophotometer. Proton NMR spectra were
measured using a Varian Mercury VX 300 spectrometer.
Elemental analysis was performed on VarioEL III. High
resolution electrospray ionization (ESI) mass spectra were
obtained on Voyager DE-STR.
5-(4-(Diethoxyl-phosphonoxy)phenyl)-10,15,20-
tri(4-pyridinyl)porphyrin (3). To a solution of 2
(400.0 mg, 0.062 mmol) and ClPO(OC2H5)2 (51.0 mg,
0.30 mmol) in 10 mL carefully dried DMF was added
K2CO3 (500.0 mg, 3.62 mmol), after stirring for 10 h at
80°C, the mixture was cooled to ambient temperature
and saturated brine (30 mL) was added. The mixture
was kept at 0°C overnight and purple solid was isolated
by suction filtration, washing with saturated brine, and
drying in vacuum. The product was then purified by
silica gel column chromatography with chloroform and
methanol (v/v, 50:1) as eluant. The second purple-red
band was collected. The solvents were removed under
reduced pressure, and the final products were obtained
by recrystallization from chloroform-petroleum ether.
Syntheses
5-(4-Hydroxyphenyl)-10,15,20-tri(4-pyridinyl)
porphyrin (2). The 5-(4-methoxyphenyl)-10,15,20-
tri(pyridine-4-yl) porphyrin 1 (100.0 mg, 0.15 mmol)
was dissolved in dried and degassed CH2Cl2 (25 mL).
The solution was stirred at -10°C and BBr3 (0.7 mL,
0.75 mmol) in 5 mL of CH2Cl2 was slowly added over
1 h. The bluish-green reaction mixture was allowed to
warm to room temperature and stirred overnight under
nitrogen. The mixture was quenched with methanol
(3 mL), cautiously poured into a mixture of ice and
saturated aqueous solution of NaHCO3 and stirred for
further 30 min. The resulting solid was isolated by suction
filtration, thoroughly washed with cold water and CHCl3,
and drying in vacuum afford product 2 as purple solid.
Yield 85%. 1H NMR (300 MHz; DMSO-d6): d, ppm 9.05
(d, J = 6.8 Hz, 6H), 8.78–8.93 (m, 8H), 8.14 (d, J = 6.6 Hz,
6H), 8.13 (d, J = 9.6 Hz, 2H), 7.32 (d, J = 9.6 Hz, 2H),
-2.75 (s, 2H). Anal. calcd. for C41H27N7O: C, 77.71; H,
4.29; N, 15.47%. Found C, 77.68; H, 4.25; N, 15.41.
1
Yield 42.0 mg (88%). H NMR (300 MHz; CDCl3): d,
ppm 9.05 (d, J = 3.0 Hz, 6H), 8.91 (d, J = 6.0 Hz, 2H),
8.84 (d, J = 6.0 Hz, 6H), 8.82 (d, J = 3.0 Hz, 2H), 8.17
(d, J = 6.0 Hz, 2H), 8.16 (d, J = 3.0 Hz, 6H), 7.64 (d, J =
6.0 Hz, 2H), 4.43 (m, 4H), 1.52 (t, J = 6.0 Hz, 6H), -2.91
(s, 2H). 31P NMR (CDCl3): d, ppm -6.07. Anal. calcd. for
C45H36N7O4P: C, 70.21; H, 4.71%; N, 12.74. Found C,
70.44; H, 4.55; N, 12.69.
5-(4-(Dimethoxy-phosphoryl-propyl-oxo-lphenyl)-
10,15,20-tri(4-pyridinyl)porphyrin (4). Compound
4 was prepared from porphyrin 2 (40.0 mg, 0.062
mmol) and Br(CH2)3PO(OCH3)2 (70.0 mg, 0.30 mmol)
according to the method described above. Yield 41.0 mg
(84%). 1H NMR (300 MHz; CDCl3): d, ppm 9.06 (d, J =
3.0 Hz, 6H), 8.96 (d, J = 6.0 Hz, 2H), 8.85 (d, J = 6.0 Hz,
6H), 8.17 (d, J = 6.0 Hz, 2H), 8.03 (d, J = 3.0 Hz, 6H),
7.60 (d, J = 6.0 Hz, 2H), 4.37 (d, J = 9.9 Hz, 2H), 3.86 (d,
J = 9.6 Hz, 6H), 2.25–2.29 (m, 2H), 1.30 (t, J = 8.4 Hz,
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 5–7

6
Y. LU ET AL.
2H), -2.87 (s, 2H). HRMS (MALDI-TOF): m/z 784.1451
(calcd. for [M + H]+ 784.2800).
was running from 0.2 to 0.05. Baseline was corrected
using the same buffer before scanning the samples. The
spectra were recorded in 3 mM Tris–HCl, 6 mM NaCl
(pH 7.4).
(5-(4-Methoxyl-phenyl)-10,15,20-tri(4-N-methyl-
pyridy)porphyrintriiodide(P1). Amixtureofporphyrin
1 and methyl iodide were stirred at room temperature in
dry DMF overnight. Then the solvent and the excess of
methyl iodide were removed under vacuum. The residue
was dissolved in DMF and precipitated with CHCl3 to
yield the cationic porphyrin P1 in quantitative yields. 1H
NMR (400 MHz; DMSO-d6): d, ppm 9.07 (d, J = 7.0 Hz,
6H), 8.81–8.92 (m, 8H), 8.16 (d, J = 7.0 Hz, 6H), 8.10
(d, J = 10.0 Hz, 2H), 7.30 (d, J = 10.0 Hz, 2H), 4.86 (s,
9H), 4.11 (s, 3H), -2.78 (s, 2H). UV-vis (H2O): lmax, nm
(e) 425 (135000); 520 (7390); 562 (4000); 585 (3760).
5-(4-(Diethoxyl-phosphonoxy)phenyl)-10,15,20-tri-
(4-N-methylpyridy)porphyrin triiodide (P2). Cationic
porphyrin-phosphonate P2 was synthesized from com-
Cell viability assays
Cell lines (PC3, human prostate cancer cell line;
MDA-MB-231,humanbreastcancercellline)weregrown
according to media component mixtures, designated by
American Type Culture Collection in RPMI-1640 with
10% fetal calf serum in a 5% CO2 humidity incubator at
37°C. The cells were seeded in 96-well plate at a density
of 4 × 103 and incubated for 24 h before treatment. The
cells were incubated with medicines in dark for 12 h,
then replenished with fresh medium and irradiated with
lights (10 J/cm2) by mercury lamp. After further 24 h
incubation in dark, cell viabilities were determined by
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) reduction assay. Optical density (OD) of
dissolved formazan crystal was measured using a 96-well
plate reader (Tecan Infinit F200) at 570 and 690 nm.
1
pound 3 according to the method described above. H
NMR (300 MHz; DMSO-d6): d, ppm 9.48 (d, J = 3.0 Hz,
6H), 9.16 (d, J = 6.0 Hz, 4H), 9.06 (d, J = 6.0 Hz, 4H),
8.97 (d, J = 3.0 Hz, 6H), 8.10 (d, J = 3.0 Hz, 2H), 7.64 (d,
J = 3.0 Hz, 2H), 4.73 (s, 9H), 4.01–4.11 (m, 4H), 1.25 (t,
J = 6.0 Hz, 6H), -2.91 (s, 2H). UV-vis (H2O): lmax, nm (e)
425 (89100); 520 (5900); 560 (3820); 583 (2860). HRMS
(MALDI-TOF): m/z 814.1415 (calcd. for [M]+ 814.3300).
5-(4-(Dimethoxy-phosphoryl-propyl-oxo-lphenyl)-
10,15,20-tri(4-N-methylpyridy)porphyrin triiodide
(P3). Cationic porphyrin-phosphonate P3 was synthe-
sized from 4 according to the method described above.
1H NMR (300 MHz, DMSO-d6): d, ppm 9.48 (d, J =
3.0 Hz, 6H), 9.18 (d, J = 6.0 Hz, 4H), 9.08 (d, J =
6.0 Hz, 4H), 8.96 (d, J = 3.0 Hz, 6H), 8.14 (d, J = 6.0 Hz,
2H), 7.43 (d, J = 6.0 Hz, 2H), 4.72 (s, 9H), 4.35 (d, J =
9.9 Hz, 2H), 3.72 (d, J = 9.6 Hz, 6H), 3.58–5.62 (m, 2H),
2.12–2.15 (m, 2H), -2.87 (s, 2H). UV-vis (H2O): lmax, nm
(e) 425 (115000); 523 (10800); 560 (9390); 583 (9030).
HRMS (MALDI-TOF): m/z 829.1630 (calcd. for [M]+
828.3400).
Subcellular localization by fluorescence microscopy
Cells were plated in a 4-wells chamber silde, and
grown for 24 h. The cells were then incubated with 1 mM
porphyrins in complete medium for another 6 h. Cells
were washed with PBS three times, then were fixed with
5% formaldehyde PBS solution. DAPI was applied to
stain the cell nuclei. The confocal laser fluorescence
microscope Zeiss LSM 510 META (Carl Zeiss, Inc.
Oberkochen, Germany) was used to image the cells at
a resolution of 1024 × 1024 pixels. Porphyrin and DAPI
fluorescence images were obtained using lex = 405 nm
and lem = 680 nm, and lex = 405 nm and lem = 420–480 nm
filter sets respectively.
CONCLUSION
UV-vis and fluorescence titration spectroscopy
Two water-soluble porphyrin-phosphonate conjugates
P2 and P3 were prepared. Amongst them, P3 showed
similar bioactivities compared with the control porphyrin
P1. The spectroscopic studies (UV-vis and CD titrations)
suggested that P3 could intercalate into DNA, which
resulted in higher cell up-takes and lower IC50 values
against PC3 and MDA-MB-231 cancer cells. On the
contrary, theconjugateP2preferredtooutsidebindingdue
to the steric effect, which resulted in obvious differences
in the cytotoxicity and the cellular sublocalization.
Interactions between cationic porphyrins and calf
thymus DNA (ct DNA) were tested by UV-vis spectrum
and fluorescence spectrum. ct DNA (Invitrogen) was
dissolved in a buffer (pH = 7.4, 50 mM Tris-HCl, 100
mM NaCl). Initially, visible absorption and fluorescence
spectrum of each porphyrin-phosphonate conjugate was
measured at a concentration of 3.0 × 10-6 M. Then ct
DNA was added to each compound [porphyrin]/[DNA
base pair] ratio running from 3.0 to 0.2.
Circular dichroism (CD) studies
Acknowledgements
The spectral bandwidth was 2 nm, and the cell length
was 1 cm. ct DNA was added to the porphyrins (1.0 × 10-6
M), and after an incubation period of 15 min, the samples
were scanned in the visible region. R value, ratio of
concentration of the porphyrin to concentration of DNA,
The study was supported by National Natural Science
Foundation (NNSF) of China (Grant No. 21401144) and
Nature Science Foundation of Hubei Province, China
(Grant No. 2013CFB236).
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 6–7

WATER-SOLUBLE PORPHYRIN-PHOSPHONATE CONJUGATES AS POTENTIAL PHOTODYNAMIC THERAPY
7
14. Giri U, Iqbal M and Athar M. Carcinogenesis 1996;
REFERENCES
17: 2023–2028.
1. Detty MR, Gibson SL and Wagner SJ. J. Med.
Chem. 2004; 47: 3897–3915.
15. Dougherty TJ, Gomer CJ, Henderson BW, Jori G,
Kessel D, Korbelik M, Moan J and Peng Q. J. Natl
Cancer Inst. 1998; 90: 889–905.
16. Ali H and van Lier JE. Chem. Rev. 1999; 99:
2379–2450.
17. Song FB, Zhang J, Cui QB, Wang T, Chen WB,
Li LY and Xi Z. Tetrahedron Lett. 2012; 53:
1102–1104.
18. Pramanik M, Chatterjee N, Das S, Das Saha K and
BhaumikA. Chem. Commun. 2013; 49: 9461–9463.
19. Tautzenberger A, Lorenz S, Kreja L, Zeller A,
Musyanovych A, Schrezenmeier H, Landfester K,
Mailander V and Ignatius A. Biomaterials 2010; 31:
2064–2071.
20. Gianferrara T, Giust D, Bratsos I and Alessio E.
Tetrahedron 2007; 63: 5006–5013.
21. Poshkus AC and Herweh JE. J. Am. Chem. Soc.
1957; 79: 6127–6129.
22. Hewitt DG and Teese MW. Aust. J. Chem. 1984; 37:
205–210.
23. Sari MA, Battioni JP, Dupre D, Mansuy D and
Lepecq JB. Biochemistry 1990; 29: 4205–4215.
24. Kubat P, Lang K, Kral V and Anzenbacher P.
J. Phys. Chem. B 2002; 106: 6784–6792.
25. LePecq JB and Paoletti C. J. Mol. Biol. 1967; 27:
87–106.
26. Pasternack RF, Gibbs EJ and Villafranca JJ.
Biochemistry 1983; 22: 2406–2414.
27. Carvlin MJ, Mark E, Fiel R and Howard JC. Nucleic
Acids Res. 1983; 11: 6141–6154.
2. Schmitt F and Juillerat–Jeanneret L. Anti Cancer
Agents in Med. Chem. 2012; 12: 500–525.
3. Pereira PMR, Carvalho JJ, Silva S, Cavaleiro JAS,
Schneider RJ, Fernandes R and Tome JPC. Org.
Biomol. Chem. 2014; 12: 1804–1811.
4. Agostinis P, Berg K, Cengel KA, Foster TH,
Girotti AW, Gollnick SO, Hahn SM, Hamblin
MR, Juzeniene A, Kessel D, Korbelik M, Moan J,
Mroz P, Nowis D, Piette J, Wilson BC and Golab J.
CA Cancer J. Clin. 2011; 61: 250–281.
5. Borbas KE, Mroz P, Hamblin MR and Lindsey JS.
Bioconjugate Chem. 2006; 17: 638–653.
6. Wirth T. Angew. Chem. Int. Ed. 2005; 44:
3656–3665.
7. Endo M, Shiroyama T, Fujitsuka M and Majima T.
J. Org. Chem. 2005; 70: 7468–7472.
8. Li J, Wei YL, Guo LM, Zhang CH, Jiao Y, Shuang
SM and Dong C. Talanta 2008; 76: 34–39.
9. Kralova J, Kejik Z, Briza T, Pouckova P, Kral A,
Martasek P and Kral V. J. Med. Chem. 2010; 53:
128–138.
10. Sibrian-Vazquez M, Jensen TJ and Vicente MGH.
J. Med. Chem. 2008; 51: 2915–2923.
11. Yuasa M, Oyaizu K, Horiuchi A, Ogata A, Hatsugai
T, Yamaguchi A and Kawakami H. Mol. Pharm.
2004; 1: 387–389.
12. Sol V, Chaleix V, Granet R and Krausz P. Tetrahedron
2008; 64: 364–371.
13. Kumar D, Mishra BA, Shekar KPC, Kumar A,
Akamatsu K, Kurihara R and Ito T. Org. Biomol.
Chem. 2013; 11: 6675–6679.
28. Carvlin MJ and Fiel RJ. Nucleic Acids Res. 1983;
11: 6121–6139.
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 7–7