Synthesis and Properties of Isoindoline Nitroxide-containing Porphyrins

Article abstract of DOI:10.1002/jhet.2928

Isoindoline nitroxide-containing porphyrins were synthesized by the reaction of 5-phenyldipyrromethane and 5-(4′-nitrophenyl)-dipyrromethane with 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl using the Lindsey method. These spin-labeled porphyrins were

Full text of DOI:10.1002/jhet.2928

Month 2017
Synthesis and Properties of Isoindoline Nitroxide‐containing Porphyrins
Fan Liu, Yan‐Chun Shen, Yao‐Hua Ouyang, Guo‐Ping Yan,*
Si Chen, Hui Liu, Yan‐Guang Wu, and Jiang‐Yu Wu
School of Material Science and Engineering, Wuhan Institute of Technology, Wuhan 430074, China
E‐mail: guopyan2006@163.com
*
Received January 22, 2017
DOI 10.1002/jhet.2928
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
Isoindoline nitroxide‐containing porphyrins were synthesized by the reaction of 5‐phenyldipyrromethane
and 5‐(4′‐nitrophenyl)‐dipyrromethane with 5‐formyl‐1,1,3,3‐tetramethylisoindolin‐2‐yloxyl using the
1
Lindsey method. These spin‐labeled porphyrins were further characterized by MS, UV, FTIR, H‐NMR,
cyclic voltammetry, electron paramagnetic resonance (EPR), and fluorescence spectroscopy. The
electrochemical assay demonstrated that these isoindoline nitroxides‐containing porphyrins had similar
electrochemical and redox properties as 5‐carboxy‐1,1,3,3‐tetramethylisoindolin‐2‐yloxyl. Electron
paramagnetic resonance test exhibited these porphyrins possessed the hyperfine splittings and characteristic
spectra of isoindoline nitroxides, with typical nitroxide g‐values and nitrogen isotropic hyperfine coupling
constants. Fluorescence spectroscopy revealed that these porphyrins indicated fluorescence suppression
characteristic of nitroxide–fluorophore systems. Moreover, their reduced isoindoline nitroxide‐containing
porphyrins eliminated the fluorescence suppression and displayed strong fluorescence. Thus, these
isoindoline nitroxide‐containing porphyrins may be considered as the potential fluorescent and EPR
probes.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
roles as spin probes in EPRI with adequate steady‐state
concentration or biological half‐life in vivo [4–6]
Electron paramagnetic resonance (EPR) is the most
effective method to detect exogenous paramagnetic
species in vivo, such as nitroxides. Currently, the low
frequency EPR imaging (EPRI) is receiving increased
attention to be an important new clinical tool for non‐
invasive three‐dimensional spatial mapping of tissue
oxygenation and potentially multidimensional imaging of
the spatial distribution of paramagnetic species in
biological tissues [1–3]. Moreover, EPRI can be used to
study on tumor hypoxia, tissue heterogenicity with respect
to oxygen and redox status, and vascular deficiencies
in vivo. Meanwhile, free radicals have played important
Most nitroxides have EPR lines that contain unresolved
proton hyperfine interactions, typically from the alkyl
environments surrounding the nitroxide moiety [7–9].
Tetramethyl isoindoline nitroxides can display superior
EPR linewidths, compared to other classes of nitroxides
[10–12]. 2,2,6,6‐Tetramethylpiperidine‐1‐yloxyl (TEMPO)
and 5‐carboxy‐1, 1, 3, 3‐tetramethylisoindolin‐2‐yloxyl
(CTMIO) are commonly used as the EPRI spin probes
[13]. However, they are low molecular weight
compounds and then have short retention time and
nonspecific distribution in tumors. An ideal method to
overcome these insufficiencies is to design and
©
2017 Wiley Periodicals, Inc.

F. Liu, Y.‐C. Shen, Y.‐H. Ouyang, G.‐P. Yan, S. Chen, H. Liu, Y.‐G. Wu, and J.‐Y. Wu
Vol 000
synthesize a nonionic, low‐toxicity, and tumor‐targeting
spin probe [14–16]
the receptor‐mediated endocytosis of low‐density
lipoproteins (LDL) because the tumor cells express high
levels of LDL receptors [21–24]
Some porphyrins and their metal complexes play
important roles in magnetic resonance imaging (MRI),
photodynamic therapy (PDT), anticancer drug, and
fluorescence imaging because of their preferential
selective uptake and retention by tumor tissues [17–20]
Meso‐tetrakis[4‐(carboxymethyleneoxy) phenyl] porphyrin
Spin‐labeled porphyrins have attracted much interest
since the early 1970s when Asakura et al. and Eaton
et al. reported the EPR spectroscopies of spin‐labeled
heme and spin‐labeled metalloporphyrins, respectively
[25,26]. Recently, spin‐labeled porphyrins have received
more and more attention to the potential molecular
magnetic materials and EPR probes in the study of
porphyrin excited states [27–38]
(
H T CPP) can accumulate in the Sarcoma 180 in mice
2 4
and in mammary tumors of Sprague–Dawley rats [21].
Meso‐tetrasulfonatophenyl porphyrin (TPPS) was found
to be highly concentrated in Walker carcinosarcoma [22].
Several other groups have made efforts towards the
synthesis of porphyrin‐antitumor drug conjugates and
studied on their tumor selectivity and antitumor activity
In this work, a series of isoindoline nitroxide‐containing
porphyrins were synthesized by the reaction between 5‐
phenyldipyrromethane, 5‐(4′‐nitrophenyl)dipyrromethane
and
5‐formyl‐1,1,3,3‐tetramethylisoindolin‐2‐yloxyl
[
23]. The uptake mechanism of porphyrins is most likely
(FTMIO) (Scheme 1). Subsequently, these porphyrins
were characterized by MS, UV, H‐NMR, and FTIR.
1
that porphyrins are incorporated into the tumor cells via
Scheme 1. Synthetic route of isoindoline nitroxide‐containing porphyrins.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis and Properties of Isoindoline Nitroxide‐containing Porphyrins
Their properties including cyclic voltammetry, EPR, and
fluorescence were also evaluated herein.
Figure 2 shows similar peaks for the oxidation and
reduction reactions in TMIOTPP, TMIONPBPP,
TMIOBNPPP, p‐BTMIOBPP, o‐BTMIOBPP, p‐BTMIONPPP,
o‐BTMIONPPP, and TTMIOPP solutions as CTMIO, which
demonstrated that isoindoline nitroxide‐containing
porphyrins possess similar electrochemical and redox
properties as CTMIO.
RESULTS AND DISCUSSION
Synthesis and characterization. Isoindoline nitroxide‐
containing porphyrins including TMIOTPP, TMIONPBPP,
TMIOBNPPP, p‐BTMIOBPP, o‐BTMIOBPP, p‐BTMIONPPP,
o‐BTMIONPPP, and TTMIOPP were synthesized by the
Electron paramagnetic resonance spectroscopy. Samples
were deoxygenated by bubbling argon through the
solution prior to analysis. X‐band EPR spectra were
recorded at room temperature for TMIOTPP, TMIONPBPP,
TMIOBNPPP, p‐BTMIOBPP, o‐BTMIOBPP, p‐BTMIONPPP,
o‐BTMIONPPP, and TTMIOPP solutions (Fig. 3). These
isoindoline nitroxide‐containing porphyrins exhibited the
characteristic EPR hyperfine splittings of tetramethyl
isoindoline nitroxides, typical nitroxide g‐value for a free
electron of approximately 2.006 and nitrogen isotropic
hyperfine coupling constants (a values, a and a , 293 K)
reaction
between
5‐phenyldipyrromethane,
5‐(4′‐
nitrophenyl)‐dipyrromethane and FTMIO using the
Lindsey method. The experimental data of FTIR, UV,
MS, H‐NMR, cyclic voltammetry, EPR, and fluorescence
provided the evidences for the formation of these
1
isoindoline nitroxide‐containing porphyrins. However,
1
good quality H‐NMR spectra could not be measured due
to the expected paramagnetic broadening that arises from
the presence of the nitroxide radicals. (The experimental
data were listed in the Supporting Information).
N
1
2
(
Table 2), respectively. In contrast, CTMIO has the typical
nitroxide g‐value for a free electron of 2.00628 and aN
values (a and a ) of 14.57 and 14.48 G (293 K) under
the same conditions.
Evaluation of fluorescence suppression.
Fluorescence
1
2
spectra of isoindoline nitroxide‐containing porphyrins
and their diamagnetic hydroxylamine equivalents were
carried out on a deoxygenated solution in methanol
−
6
(
10 mol/L). The optimum excitation wavelength was
SUMMARY
determined to be 414–426 nm. Addition of excess
ascorbic acid to the solution of isoindoline nitroxide‐
containing porphyrins resulted in an increase in
fluorescence intensity with a maximum intensity reached
after 1 h. The further ascorbic acid was added; however,
no further change was observed, indicating that all
nitroxide groups (N―O·) had been reduced to
hydroxylamine groups (N―OH).
The fluorescence suppression was observed at the
fluorescence measurements between the nitroxides and
their diamagnetic hydroxylamine equivalents. Spin‐
labeled porphyrins and their related hydroxylamines had
two characteristic fluorescence emission peaks at
Isoindoline nitroxide‐containing porphyrins were
synthesized and evaluated as the potential fluorescence‐
suppressed spin probes. Compared with CTMIO, these
isoindoline nitroxide‐porphyrins possessed similar
electrochemical and redox properties, and the
characteristic EPR hyperfine splittings as well as superior
EPR linewidth and resistance to reduction. Moreover,
these porphyrins exhibited fluorescence suppression
characteristic of nitroxide–fluorophore systems. Their
reduced isoindoline nitroxide‐porphyrins eliminated the
fluorescence suppression and displayed the strong
fluorescence properties. Thus, these isoindoline nitroxide‐
porphyrins may be considered as the potential
fluorescence and EPR probes.
6
50–654 nm and 716–718 nm. In general, the
intensities of the hydroxylamine of spin‐labeled
porphyrins were 2.34–13.13 times greater than that of
the corresponding nitroxides (Fig. 1, Table 1). It
appears that the typical pathways for fluorescence
quenching in radical–fluorophore systems were effective
in spin‐labeled porphyrins.
EXPERIMENTAL
Instrumentation and reagents. The compounds were
characterized using a Voyager DE STR MALDI‐TOF‐
MS Laser Time‐of‐Flight Mass Spectrometer (Applied
Biosystems by Life Technologies Co., USA), a Varian
Mercury‐VX300 NMR spectrometer (Varian, Inc.
Corporate, Palo Alto, CA), a UV–Vis spectrophotometer
(UV‐2800 series, Unico, Shanghai, China), a Nicolet IS10
Fourier transform‐infrared (FT‐IR) spectrophotometer
(Thermo Fisher Scientific Inc., Madison, WI), and an
Electrochemical assay. The current–potential curves at
a potential sweep rate of 0.1 V/s are given in Figure 2. It
can be seen that two type reversible oxidation/reduction
reactions appear at −1.5–1.6 V in the current–potential
curve of CTMIO in the methanol solution. The reversible
oxidation/reduction reactions include the change between
nitroxide NO· and hydroxylamine N―OH and the
conversion from nitroxide NO· to nitroso‐onium ion.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

F. Liu, Y.‐C. Shen, Y.‐H. Ouyang, G.‐P. Yan, S. Chen, H. Liu, Y.‐G. Wu, and J.‐Y. Wu
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Figure 1. Fluorescence spectra obtained before and after addition of excess ascorbic acid to TMIOTPP, TMIONPBPP, TMIOBNPPP, p‐BTMIOBPP,
o‐BTMIOBPP, p‐BTMIONPPP, o‐BTMIONPPP, and TTMIOPP, respectively. [Color figure can be viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
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Synthesis and Properties of Isoindoline Nitroxide‐containing Porphyrins
Table 1
2.4 mg, 0.62%), 5‐(1′,1′,3′,3′‐tetramethylisoindolin‐2′‐yloxyl‐
Fluorescence measurement between isoindoline nitroxide‐labeled
5′‐yl)‐10,15‐bis (4′‐nitrophenyl)‐20‐phenylporphyrin (Band 8,
TMIOBNPPP, 2.7 mg, 0.66%), 5,15‐bis (1′,1′,3′,3′‐
tetramethylisoindolin‐2′‐yloxyl‐5′‐yl)‐10,20‐bisphenylporphyrin
(Band 9, p‐BTMIOBPP, 1.0 mg, 0.23%), 5,10‐bis (1′,1′,3′,3′‐
tetramethylisoindolin‐2′‐yloxyl‐5′‐yl)‐15,20‐bisphenylporphyrin
(Band 10, o‐BTMIOBPP, 2.3 mg, 0.54%), 5,15‐bis
(1′,1′,3′,3′‐tetramethylisoindolin‐2′‐yloxyl‐5′‐yl)‐10‐(4′‐
nitrophenyl)‐20‐phenyl‐porphyrin (Band 11, p‐BTMIONPPP,
porphyrins and their related hydroxylamines.
Fluorescence emission
Fluorescence
Sample solution
peak λem (nm)
suppression ratio
T
T
T
MIOTPP
MIONPBPP
MIOBNPPP
650, 718
651, 717
652, 717
652, 718
651, 718
654, 716
651, 718
653, 717
3.42, 3.84
4.54, 5.37
3.90, 4.46
4.54, 6.25
2.34, 2.47
4.56, 4.57
7.42, 5.57
13.13, 11.73
p‐BTMIOBPP
o‐BTMIOBPP
p‐BTMIONPPP
o‐BTMIONPPP
TTMIOPP
1
.8 mg, 0.41%), 5,10‐bis (1′,1′,3′,3′‐tetramethylisoindolin‐2′‐
yloxyl‐5′‐yl)‐15‐(4′‐nitrophenyl)‐20‐phenyl‐porphyrin (Band
2, o‐BTMIONPPP, 0.8 mg, 0.18%), 5,10,15‐tris (1′,1′,3′,3′‐
tetramethylisoindolin‐2′‐yloxyl‐5′‐yl)‐20‐phenylporphyrin
Band 13, TTMIOPP, 2.5 mg, 0.52%).
1
(
+
XT4‐100× microscopic melting point apparatus (Beijing
Electrooptics Science Factory, Beijing, China).
TPP (Band 1) [21,31]: MS found M + H m/z 615 (calc.
614 for C H N ). H NMR (CDCl ) δ: 8.88 (d, 2H,
1
44
30
4
3
All chemicals and solvents were of analytical grade. 5‐
β‐pyrrole), 8.225 (d, 4H, β‐pyrrole), 8.208 (d, 2H,
β‐pyrrole), 7.76 (m, 8H, ortho‐phenyl), 7.742, 7.208 (m,
Phenyldipyrromethane
[28],
5‐(4′‐nitrophenyl)
dipyrromethane [28], 5‐formyl‐1,1,3,3‐tetramethylisoin
dolin‐2‐yloxyl (FTMIO) [17], and 5‐carboxy‐1,1,3,3‐
tetramethylisoindolin‐2‐yloxyl (CTMIO) [17] were
synthesized by the methods cited in the literatures.
12H, meta/para phenyls), −2.79 (s, 2H, pyrrole NH); ν
max
(KBr)/cm− 2975, 2928 (C―H), 1597, 1557, and 1472
1
(C―C), 1374 and 1351 (N―O); UV–Vis [chloroform
(CHCl )] λ
417, 514, 549, 590, 645 nm.
3
max
+
Synthesis
of
isoindoline
nitroxide‐containing
NPTPP (Band 2) [22]: MS found M m/z 659.7 (calc. 659
1
porphyrins.
A solution of 5‐phenyldipyrromethane
for C H N O ); H NMR (CDCl ) δ: 8.86 (d, 2H,
44
29
5
2
3
(
111.1 mg, 0.5 mmol, 1 equiv.), 5‐(4′‐nitrophenyl)
dipyrromethane (133.1 mg, 0.5 mmol, 1 equiv.), and 5‐
formyl‐1,1,3,3‐tetramethylisoindolin‐2‐yloxyl (FTMIO,
20 mg, 1.01 mmol, 2 equiv.) in freshly distilled
β‐pyrrole), 8.74 (d, 4H, β‐pyrrole), 8.64 (d, 2H, β‐
pyrrole), 8.41 (d, 2H, nitrophenyl), 8.22 (d, 2H,
nitrophenyl), 7.77 (m, 6H, ortho‐phenyl), 7.25 (m, 9H,
meta/para phenyls), −2.79 (s, 2H, pyrrole NH); UV–Vis
2
dichloromethane (DCM, 100 mL) was purged with argon
for 15 min. Boron trifluoride etherate (BF ·O(Et) ,
0
[chloroform (CHCl )] λ
418, 516, 550, 591, 645 nm.
max
3
+
3
2
BNPBPP (Band 3) [22]: MS found M + H m/z 705.9
1
.133 mL of 2.5 M stock solution in DCM, 0.0825 mmol/
(calc. 704 for C H N O ); H NMR (CDCl ) δ: 8.86
44
28
6
4
3
L) was then added, and the mixture was stirred at room
temperature under argon shielded from light. The mixture
(d, 2H, β‐pyrrole), 8.74 (d, 4H, β‐pyrrole), 8.64 (d, 2H,
β‐pyrrole), 8.41 (d, 4H, nitrophenyl), 8.22 (d, 4H,
nitrophenyl), 7.77 (m, 4H, ortho‐phenyl), 7.25 (m, 6H,
meta/para phenyls), −2.79 (s, 2H, pyrrole NH); UV–Vis
was stirred for
1
h, and then 2,3‐dichloro‐4,5‐
dicyanobenzoquinone (DDQ, 0.175 g, 0.075 mmol) was
added. The mixture was stirred for an additional 1 h,
and subsequently the solvent was removed under
reduced pressure. Column chromatography (length:
[chloroform (CHCl )] λ
420, 516, 552, 593, 654 nm.
max
3
+
TNPPP (Band 4) [22]: MS found M + H m/z 750.4 (calc.
1
749 for C H N O ); H NMR (CDCl ) δ: 8.86 (d, 2H,
44
27
7
6
3
6
2
0 cm, external diameter: 2.55 cm outer diameter:
β‐pyrrole), 8.74 (d, 4H, β‐pyrrole), 8.64 (d, 2H, β‐
pyrrole), 8.41 (d, 6H, nitrophenyl), 8.22 (d, 6H,
nitrophenyl), 7.77 (m, 2H, ortho‐phenyl), 7.25 (m, 3H,
meta/para phenyls), −2.79 (s, 2H, pyrrole NH); UV–Vis
.7 cm; chromatography silica gel SiO : 230–400 mesh
2
(60A), The first eluent: DCM/n‐hexane, v/v: 3/1; the
second eluent: ethyl acetate/DCM/n‐hexane, v/v: 1/3/4)
gave a series of porphyrins as follows: 5,10,15,20‐
tetraphenylporphyrin (Band 1, TPP, 4.2 mg, 1.37%),
[chloroform (CHCl )] λ
422, 514, 552, 590, 645 nm.
3
max
+
TNPP (Band 5) [22]: MS found M + H m/z 795.5 (calc.
1
5
2
1
0
‐(4′‐nitrophenyl)‐10,15,20‐trisphenylporphyrin
(Band
794 for C H N O ); H NMR (CDCl ) δ: 8.86 (d, 2H,
44
26
8
8
3
, NPTPP, 3.1 mg, 0.94%), 5,15‐bis(4′‐nitrophenyl)‐
0,20‐bisphenylporphyrin (Band 3, BNPBPP, 2.5 mg,
.71%), 5,10,15‐tris(4′‐nitrophenyl)‐20‐phenylporphyrin
β‐pyrrole), 8.74 (d, 4H, β‐pyrrole), 8.64 (d, 2H, β‐
pyrrole), 8.41 (d, 8H, nitrophenyl), 8.22 (d, 8H,
nitrophenyl), −2.79 (s, 2H, pyrrole NH); UV–Vis
(
Band 4, TNPPP, 1.1 mg, 0.29%), 5,10,15,20‐tetra(4′‐
nitrophenyl)porphyrin (Band 5, TNPP, 4.6 mg, 1.2%),
‐(1′,1′,3′,3′‐tetramethylisoindolin‐2′‐yloxyl‐5′‐yl)‐10,15,20‐
trisphenylporphyrin (Band 6, TMIOTPP, 9.2 mg, 2.53%),
‐(1′,1′,3′,3′‐tetramethylisoindolin‐2′‐yloxyl‐5′‐yl)‐15‐(4′‐
[chloroform (CHCl )] λ
418, 515, 554, 593, 644 nm.
3
max
+
TMIOTPP (Band 6): MS found M + H 727.44 (calc. 726
1
5
for C H N O); H NMR (CDCl , δ, ppm): 8.9–8.8 (br,
50
40
5
3
8H, β‐pyrrole), 8.2 (m, 8H, ortho phenyl), 8.0 (br, 1H,
meta phenyl), 7.8–7.7 (br, m, 9H, meta/para triphenyl),
1.4 (s, 12H, CH ), −2.75 (s, 2H, pyrrole NH); ν
5
nitrophenyl)‐10,20‐bisphenylporphyrin (Band 7, TMIONPBPP,
3
max
Journal of Heterocyclic Chemistry
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F. Liu, Y.‐C. Shen, Y.‐H. Ouyang, G.‐P. Yan, S. Chen, H. Liu, Y.‐G. Wu, and J.‐Y. Wu
Vol 000
Figure 2. Current–potential curves of the solutions of TMIOTPP, TMIONPBPP, TMIOBNPPP, p‐BTMIOBPP, o‐BTMIOBPP, p‐BTMIONPPP, o‐BTMIONPPP,
and TTMIOPP, respectively.
Journal of Heterocyclic Chemistry
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Synthesis and Properties of Isoindoline Nitroxide‐containing Porphyrins
Figure 3. EPR spectra of TMIOTPP, TMIONPBPP, TMIOBNPPP, p‐BTMIOBPP, o‐BTMIOBPP, p‐BTMIONPPP, o‐BTMIONPPP, and TTMIOPP in DCM at
room temperature.
Journal of Heterocyclic Chemistry
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F. Liu, Y.‐C. Shen, Y.‐H. Ouyang, G.‐P. Yan, S. Chen, H. Liu, Y.‐G. Wu, and J.‐Y. Wu
Vol 000
Table 2
8
.31 (br, 8H, β‐pyrrole), 8.0 (m, 8H, ortho phenyl), 7.2
Characteristic EPR data of isoindoline nitroxide‐containing porphyrins.
(d, 2H, nitrophenyl), 6.8 (br, 2H, meta phenyl), 6.3 (m,
3
2
H, meta/para phenyls), 1.6–0.8 (s, 24H, CH ), −2.75 (s,
3
a
N
values (G)
H, pyrrole NH); νmax(KBr)/cm− 2962, 2921, 2850
1
Sample solution
CTMIO
g‐value
a
1
a
2
(C―H), 1630, 1401 (C―C), 1384, 1261, and 1094
2.00628
2.00618
2.00653
2.00645
2.00646
2.00650
2.00650
2.00648
2.00645
14.57
14.43
14.37
14.57
14.57
14.67
14.57
14.57
14.67
14.48
14.44
14.57
14.67
14.77
14.57
14.67
14.77
14.57
(N―O), 1020 (C―N); UV–Vis [chloroform (CHCl3)]
λmax 420, 515, 550, 590, 646 nm.
o‐BTMIONPPP (Band 12): MS found M + H 884.79
T
T
T
MIOTPP
MIONPBPP
MIOBNPPP
+
1
(calc. 883 for C H N O ); H NMR (CDCl , δ, ppm):
p‐BTMIOBPP
o‐BTMIOBPP
p‐BTMIONPPP
o‐BTMIONPPP
TTMIOPP
56 49
7
4
3
8.8 (br, 8H, β‐pyrrole), 8.28 (m, 8H, ortho phenyl), 8.0
d, 2H, nitrophenyl), 7.7 (br, 2H, meta phenyl), 7.5 (m,
(
3
2
1
H, meta/para phenyls), 1.6–0.8 (s, 24H, CH ), −2.75 (s,
3
H, pyrrole NH); νmax(KBr)/cm− 2962, 2923 (C―H),
1
634, 1399 (C―C), 1384, 1261, and 1091 (N―O), 1021
(
5
C―N);UV–Vis [chloroform (CHCl )] λ
420, 516,
max
3
1
(
1
[
KBr)/cm− 2963, 2923 (C―H), 1631 and 1400 (C―C),
51, 591, 647 nm.
+
384, 1260, and 1091 (N―O), 1020 (C―N); UV–Vis
chloroform (CHCl )] λ 421, 514, 551, 590, 647 nm.
TMIONPBPP (Band 7): MS found M + H m/z 772.85
calc. 771 for C H N O ); H NMR (CDCl , δ, ppm):
.04–8.8 (br, 8H, β‐pyrrole), 8.37 (m, 8H, ortho phenyl),
.18 (d, 2H, nitrophenyl), 7.93 (br, 1H, meta phenyl),
.36 (m, 6H, meta/para phenyls), 1.4 (s, 12H, CH ),
2.75 (s, 2H, pyrrole NH); νmax (KBr)/cm 2963, 2923,
TTMIOPP (Band 13): MS found M + H 951.93 (calc. 950
for C H N O ); H NMR (CDCl , δ, ppm): 8.6 (br, 8H,
β‐pyrrole), 8.3 (m, 8H, ortho phenyl), 7.8 (br, 3H, meta
phenyl), 7.3 (m, 3H, meta/para phenyls), 1.6–0.8 (s, 36H,
CH ), −2.75 (s, 2H, pyrrole NH); νmax(KBr)/cm 2963,
1
3
max
62
60
7
3
3
+
1
50 39 6 3 3
(
−1
9
8
7
−
2
1
3
2
924, 2852 (C―H), 1630, 1401 (C―C), 1384, 1261, and
1094 (N―O), 1021 (C―N); UV–Vis [chloroform
(CHCl )] λ 419, 515, 549, 590, 645 nm.
3
−1
3
max
852 (C―H), 1646 and 1401 (C―C), 1384, 1261, and
094 (N―O), 1020 (C―N); UV–Vis [chloroform
Fluorescence spectroscopy. Fluorescence spectra were
recorded on Varian Cary Eclipse fluorescence
spectrophotometer (Varian, Inc. Corporate, Palo Alto, CA,
a
(
CHCl )] λ
418, 516, 552, 591, 646 nm.
max
3
+
TMIOBNPPP (Band 8): MS found M + H m/z 817.47
calc. 816 for C H N O ); H NMR (CDCl , δ, ppm):
.6 (br, 8H, β‐pyrrole), 7.66 (m, 8H, ortho phenyl), 7.39
d, 4H, nitrophenyl), 7.38 (br, 1H, meta phenyl), 7.3 (m,
H, meta/para phenyls), 1.4 (s, 12H, CH ), −2.75 (s, 2H,
pyrrole NH); νmax (KBr)/cm 2963, 2853 (C―H), 1645,
−6
1
50 38 7 5 3
United States of America). All solutions (10 mol/L) for
(
8
(
3
fluorescence spectroscopy were prepared in HPLC grade
methanol and deoxygenated with argon prior to use.
Isoindoline nitroxide‐containing porphyrins had to be first
3
−1
dissolved in a minimum volume of CHCl and then diluted
3
with methanol to the desired concentration. A deoxygenated
and saturated solution of ascorbic acid in methanol was
prepared for experiments. Fluorescence suppression
experiments were performed by adding and mixing excess
ascorbic acid (~50 μL of the saturated solution) to the
deoxygenated nitroxide sample at t = 0. Spectra were
recorded automatically every 2 min over a 1‐h period.
1
1
5
609, and 1412 (C―C), 1384, 1261, and 1026 (N―O),
020 (C―N); UV–Vis [chloroform (CHCl )] λmax 421,
3
14, 549, 589, 641 nm.
+
p‐BTMIOBPP (Band 9): MS found M + H 840.01 (calc.
1
56 50 6 2 3
8
38 for C H N O ); H NMR (CDCl , δ, ppm): 8.94
(
2
br, 8H, β‐pyrrole), 8.63 (m, 8H, ortho phenyl), 8.26 (br,
H, meta phenyl), 7.80 (m, 6H, meta/para phenyls), 1.3
s, 24H, CH ), −2.75 (s, 2H, pyrrole NH); νmax(KBr)/cm
962, 2923, 2851 (C―H), 1661, 1646, 1399 (C―C),
384, 1261, and 1095 (N―O), 1021 (C―N); UV–Vis
CHCl ) λ 418, 515, 550, 591, 647 nm.
(
Electrochemical experiments.
The electrochemical
3
−
1
2
examinations were performed in a one‐compartment, three
electrode cell with the use of a CHI660C potentiostat
(Shanghai Chenghua, Shanghai, China) under the control
of a computer at room temperature. Electrochemical
behaviors were investigated with a platinum disc electrode
1
(
3
max
+
o‐BTMIOBPP (Band 10): MS found M + H 840.16 (calc.
1
56 50 6 2 3
8
8
2
0
38 for C H N O ); H NMR (CDCl , δ, ppm): 8.91 (br,
H, β‐pyrrole), 8.63 (m, 8H, ortho phenyl), 8.2–8.0 (br,
H, meta phenyl), 7.8 (m, 6H, meta/para phenyls), 1.8–
(1.96 × 10− cm ) that was polished and cleaned before each
experiment. An Ag/AgCl (0.1 mol/L KCl) electrode was
used as the reference electrode, and a platinum wire was
used as the counter electrode. The solution in acetonitrile
(1 mmol/L) was de‐gassed by the bubbling of dry argon
before each electrochemical experiment, and a slight argon
overpressure was maintained during the experiment. The
platinum disc was dried and then put into a sample solution
3
2
.9 (s, 24H, CH ), −2.75 (s, 2H, pyrrole NH); νmax(KBr)/
3
−
1
cm 2923, 2853 (C―H), 1631, 1400 (C―C), 1384,
1
261, and 1094 (N―O), 1021 (C―N); UV–Vis (CHCl3)
λmax 418, 515, 550, 592, 647 nm.
p‐BTMIONPPP (Band 11): MS found M + H 884.95
+
1
(calc. 883 for C H N O ); H NMR (CDCl , δ, ppm):
56 49 7 4 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis and Properties of Isoindoline Nitroxide‐containing Porphyrins
of acetonitrile with 0.1 mol/L TBAF to obtain the cyclic
voltammograms with a potential sweep rate of 0.1 V/s at
room temperature.
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Electron paramagnetic resonance spectroscopy. Samples
for EPR studies were prepared at concentrations of
7
≤
0.5 mM to eliminate intermolecular effects. Samples were
[
deoxygenated by bubbling argon or nitrogen through the
solution prior to analysis. X‐band EPR spectra were
recorded at room temperature for isoindoline nitroxide‐
containing porphyrin solutions in dichloromethane on a
Brucker EPR A300. A double Gunn diode X‐band (9 GHz)
microwave bridge and standard X‐band rectangular TE102
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isotropic hyperfine coupling constants (aN value) and g
value for a free electron are quoted within the spectroscopic
description given with each nitroxide synthesis.
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1
[
Acknowledgments. This work was supported by the National
Natural Science Foundation of China (Grant No. 51373128,
[
Natl Acad Sci U S A 1971, 68, 861.
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Eaton, S. S. J Am Chem Soc 1995, 117, 2049.
5
1173140), the Key National Research and Development
Program (2016YFB1101302), Wuhan Science and Technology
Innovation Team of Hi‐tech Industrial Project (Grant No.
[27] Shultz, D. A.; Gwaltney, K. P.; Lee, H. J Org Chem 1998,
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015070504020217), and Innovative Talents Project of Yellow
[
Crane Talents Plan of Wuhan City, Hubei Province, China.
[
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SUPPORTING INFORMATION
[
Additional Supporting Information may be found online
in the supporting information tab for this article.
[
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet