A porphyrin molecule that generates, traps, stores, and releases singlet oxygen

Article abstract of DOI:10.1016/j.jphotochem.2013.03.003

Tetraphenylporphyrin (H2TPP), covalently linked to four 2-pyridone moieties was synthesized (II) and studied. This composite molecule, in combination with light and ground state oxygen, has the ability to generate, trap, store, and release singlet oxygen. The process can be operated reversibly without detectable decomposition or side reactions using light with wavelength greater than 500 nm. Oxidation of the target molecule, 2-chloroethyl ethyl sulfide (CEES), by singlet oxygen released from the endoperoxide of the porphyrin-2-pyridone molecule (I) is demonstrated. Spectroscopic and kinetic data do not reveal evidence of perturbation between the porphyrin and pyridone ring systems of II. The decomposition kinetics for the endoperoxide adduct I are first order with activation parameters ΔH? = 26.7 (kcal/mol) and ΔG? = 24.0 (kcal/mol). Experimental and computational studies of unattached N-benzyl-2-pyridone peroxide are reported and compared to the experimental data for I.

Full text of DOI:10.1016/j.jphotochem.2013.03.003

Journal of Photochemistry and Photobiology A: Chemistry 260 (2013) 9–13
Contents lists available at SciVerse ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
A porphyrin molecule that generates, traps, stores, and releases singlet oxygen
a
a
a
a
b
Chuchawin Changtong , Daniel W. Carney , Lan Luo , Christopher A. Zoto , John L. Lombardi ,
Robert E. Connors
a
a,∗
Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA
Ventana Research Corporation, Tucson, AZ 85713, USA
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Tetraphenylporphyrin (H2TPP), covalently linked to four 2-pyridone moieties was synthesized (II) and
studied. This composite molecule, in combination with light and ground state oxygen, has the abil-
ity to generate, trap, store, and release singlet oxygen. The process can be operated reversibly without
detectable decomposition or side reactions using light with wavelength greater than 500 nm. Oxidation of
the target molecule, 2-chloroethyl ethyl sulfide (CEES), by singlet oxygen released from the endoperoxide
of the porphyrin-2-pyridone molecule (I) is demonstrated. Spectroscopic and kinetic data do not reveal
evidence of perturbation between the porphyrin and pyridone ring systems of II. The decomposition
kinetics for the endoperoxide adduct I are first order with activation parameters ꢀH‡ = 26.7 (kcal/mol)
and ꢀG‡ = 24.0 (kcal/mol). Experimental and computational studies of unattached N-benzyl-2-pyridone
peroxide are reported and compared to the experimental data for I.
Received 1 February 2013
Received in revised form 7 March 2013
Accepted 10 March 2013
Available online 21 March 2013
Keywords:
Singlet oxygen
Photosensitizer
Porphyrin
©
2013 Elsevier B.V. All rights reserved.
1
. Introduction
1
3
−
O ( ꢀg) → O ( ꢁ g)
2
2
It is well known that the 1ꢀg excited state of oxygen, referred
to as singlet oxygen, shows chemical reactivity that differs sig-
1
M + O ( ꢀg) → Oxidized products
2
nificantly from that of ground state 3
ꢁ g molecular oxygen. This
−
has led to a range of applications for singlet oxygen that include
photodynamic therapy (PDT), water purification, novel chemical
synthesis, and chemical/biological decontamination [1,2]. Singlet
oxygen is commonly generated by the transfer of energy from a
Previous work has established that a number of organic ring
compounds are capable of reversibly trapping and storing singlet
oxygen with high efficiency by forming endoperoxides as oxida-
tion products [4]. These storage endoperoxides decompose to the
original molecule by releasing oxygen in the excited 1ꢀg state
which, as noted, has stronger oxidizing properties than O2 in its
triplet ground state [1]. Matsumoto et al. [5] has shown that a
series of N-substituted 2-pyridones form endoperoxides that yield
singlet oxygen in high yield upon thermal decomposition. The
photosensitizer dye to a 3
ꢁ g oxygen molecule. The process is ini-
−
tiated when light promotes the sensitizer to its first excited singlet
state which then undergoes intersystem crossing to populate the
lowest triplet state. Singlet oxygen is produced when the triplet
state of the sensitizer transfers energy to ground state oxygen.
Depending upon the solvent, singlet oxygen decays back to the
◦
first-order thermolysis reactions have ꢂ1/2 = 2–6 h at 40 C for the
−
6
−2
ground state with a half-life (ꢂ1/2) in the range of 10 –10 s. [3].
2-pyridones studied [5]. The work presented here describes the
preparation and several physical and chemical properties of a com-
posite molecule that has four 2-pyridone moieties that store singlet
oxygen bonded directly to a porphyrin photosensitizer dye. These
materials, under the action of light and oxygen, have the capacity
Other molecules (M) in solution may be oxidized if they react with
singlet oxygen before it deactivates to 3
summarized below.
ꢁ
−
g. These processes are
1
3
1
Sens + h␯ → Sens → Sens
to generate, trap, store, and release singlet oxygen (Fig. 1). H NMR
reveals that this cycle can be repeated a number of times with-
out detectable degradation or formation of side products. Unlike
conventional photosensitization methods to produce singlet oxy-
gen, the reversible storage capacity of these materials ensures
that singlet oxygen will continue to be generated for hours after
the excitation light source has been removed. Spectroscopic and
kinetic properties have been measured and theoretically modeled
for this novel compound. In addition, oxidation of the mustard gas
3
3
−
1
Sens + O ( ꢁ g) → Sens + O ( ꢀg)
2
2
∗ Corresponding author. Tel.: +1 508 831 5394.
E-mail address: rconnors@wpi.edu (R.E. Connors).
1
010-6030/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jphotochem.2013.03.003

1
0
C. Changtong et al. / Journal of Photochemistry and Photobiology A: Chemistry 260 (2013) 9–13
Fig. 1. Reversible generation, trap, and release of singlet oxygen by II.
simulant, 2-chloroethyl ethyl sulfide (CEES), by singlet oxygen
released in the dark from the sensitizer-storage molecule is demon-
strated.
values reported by Fukushima et al. [6]. The aldehyde precursor IV
was formed by reducing the nitrile group of ␣-bromo-p-tolunitrile
(V) with diisobutylaluminum hydride (DIBAL-H) in dry toluene,
followed by acid catalyzed hydrolysis [6].
2
. Materials
3. Methods
As depicted in Fig. 2, the 2-pyridone linked porphyrin
UV–vis absorption spectra were obtained with a Shimadzu
II was synthesized under anhydrous conditions by reacting
,10,15,20-tetrakis(␣-bromo-p-tolyl)porphyrin (III) for 4 h with 2-
UV2100U spectrometer. Fluorescence spectra were measured with
a Perkin-Elmer LS 50 B luminescence spectrometer outfitted with a
R928 phototube. Fluorescence quantum yields were determined
by the comparison method using the free base of 5,10,15,20-
5
hydroxypyridine (2-pyridone tautomer) in the presence of NaH in
refluxing THF. Solid remaining in the bottom of the reaction ves-
sel was filtered and washed with dichloromethane. The filtrate was
concentrated and a purple solid was recovered. The solid was ana-
tetraphenylporphyrin (H TPP) as the standard [9]. Fluorescence
2
lifetimes were measured with a Photon Technology International
TM-3 time resolved spectrometer with dye laser excitation. Pro-
1
lyzed by H NMR in DMSO-d6 and confirmed to be the pyridone
1
1
linked tetraphenylporphyrin. The H NMR spectrum of the pur-
ton H NMR spectra were recorded with a Bruker Avance 400 MHz
ple solid shows a broad singlet (2H) upfield at ı −2.81 which is
characteristic absorption by the porphyrin N H. The most down-
field singlet (8H) at ı 8.82 is assigned to the pyrrolic protons. Two
doublets at ı 7.68 (8H, d; J = 7.58 Hz) and ı 8.19 (8H, d; J = 7.58 Hz)
correspond to the ortho- and meta-phenyl ring protons of the por-
phyrin, respectively. Absorptions at ı 6.37 (t, 4 H; J = 6.82 Hz), 6.79
instrument using chloroform-d solvent. Endoperoxide moieties in
I were generated by irradiating chloroform-d solutions of II with
the output of a 150 W xenon arc lamp passed through a yellow cut-
off (500 nm) glass filter. Irradiations were performed with a fine
stream of O2 bubbling through the solutions. For the dark reaction
of CEES with singlet oxygen generated from the thermal degrada-
tion of I to form II, 15.7 mg of II was dissolved in chloroform-d and
irradiated in an NMR tube with bubbling oxygen until NMR spec-
tra indicated complete conversion of II to I. To this solution, 1.8 ␮L
of CEES was added under subdued room light. The solution was
then wrapped in aluminum foil to keep it from exposure to light.
The NMR spectrum was recorded immediately and it showed no
indication that any reaction of CEES had taken place.
(
d, 4 H; J = 9.09 Hz), 7.48 (t, 4 H; J = 9.09 Hz) and 7.63 (d, 4 H;
J = 6.82 Hz) are due to the pyridone ring protons. The singlet at
ı 5.54 (8H) which corresponds to the methylene protons on the
link between the phenyl group and the pyridone nitrogen is key
to establishing the final product. In porphyrin III the methylene
protons appear as a singlet at 4.85 ppm [6]. The downfield shift to
5
.54 ppm after coupling, with no residual signal at 4.85 ppm, indi-
cates that coupling occurs at all four tolyl sites of the porphyrin
5].
Porphyrin II was synthesized by condensing ␣-bromo-p-
Theoretical calculations were carried out using the Gaussian
09 program [8]. Solvent effects were included using the Self-
Consistent Reaction Field (SCRF) Polarizable Continuum Model
(PCM) options within the program.
[
tolualdehyde (IV) with pyrrole in the presence of amberlyst
ion-exchange catalyst in dry chloroform according to the method
of Lindsey et al. [7]. The aldehyde and pyrrole were allowed to react
for 5 h at room temperature before the oxidant, 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ), was added. After 40 min the reaction
mixture was filtered through a short column of neutral alumina. The
eluted solution was concentrated to yield a purple solid that was
characterized by a single TLC spot. 1H NMR signals agreed with the
4. Results and discussion
4.1. Spectroscopic properties
The UV–vis absorption spectrum of II in chloroform has charac-
teristic porphyrin Soret and Q-bands similar in position and relative

C. Changtong et al. / Journal of Photochemistry and Photobiology A: Chemistry 260 (2013) 9–13
11
Fig. 2. Reaction scheme for the preparation of II.
band is assigned to absorption by the 2-pyridone moieties in II.
The fluorescence and excitation spectra of II in chloroform are also
similar to those of H TPP. Photophysical properties of II were also
2
measured. The fluorescence quantum yield of II in chloroform was
determined to be 0.11, which is identical to the value that has been
reported for H TPP [9]. Fluorescence lifetimes in degassed chlo-
2
roform were measured in our laboratory to be 9.66 ± 0.13 ns for
II and 9.93 ± 0.08 ns for H TPP. Thus, the electronic spectral and
2
photophysical properties fail to reveal any significant ␲–␲ pertur-
bation between the porphyrin and 2-pyridone ring systems. The
methylene spacer appears to be effective in isolating the two units.
4.2. Cyclic irradiation of I in the presence of oxygen
A solution of II in chloroform was irradiated for 20 min in the
Fig. 3. UV–vis absorption spectra of II and of H2TPP in chloroform. The star indi-
cates the 296 nm band assigned to absorption by the 2-pyridone moieties in II. For
comparison, the inset shows the absorption spectrum of N-benzyl-2-pyridone.
presence of a fine stream of O2 gas at ambient temperature. A
comparison of 1H NMR spectra before and after irradiation indi-
cates approximately 90% consumption of the pyridone moieties
accompanied by the formation of new proton signals. By compar-
ison with the known 1H NMR spectrum of the endoperoxide of
N-benzyl-2-pyridone [5], the new signals that arise after irradiation
are attributed to formation of the corresponding endoperoxides
intensity to those of H TPP (Fig. 3). The absorption spectrum of II
2
also exhibits an absorption band in the UV region with a maximum
at 296 nm. Because of its similarity to the absorption spectrum of
N-benzyl-2-pyridone in chloroform (see inset, Fig. 3), the 296 nm
Table 1
Experimental and computed activation parameters for the decomposition of endoperoxides I and N-benzyl-2-pyridone.
‡
‡
Reaction
Method
ꢀH (kcal/mol)
ꢀG (kcal/mol)
A.
B.
NMR
NMR
26.7
26.3
21.6
24.0
24.2
22.1
*
DFT (B3LYP/6-311 + G )
1
A.
B.
I → II + O2

1
2
C. Changtong et al. / Journal of Photochemistry and Photobiology A: Chemistry 260 (2013) 9–13
0
o
2
5 C
o
3
0 C
-0.5
o
3
5 C
o
4
4
0 C
-1
o
5 C
-1.5
-2
o
5
0 C
-2.5
0
2000
4000
6000
8000
10000
Time (s)
Fig. 5. Kinetics of endoperoxide decomposition were measured by monitoring the
1
decay of the H-NMR signal of I as a function of time at several fixed temperatures
◦
between 25 and 50 C. The linearity of the first-order plots demonstrates that the
decay data follow first-order kinetics throughout.
-13
Fig. 4. 1H NMR spectra showing the reversible cycling between II and I. The out-of-
phase growth and reduction of NMR peaks assigned to compound II (5.54 ppm) and
compound I (5.97 ppm) after cycles of irradiation and heating is clearly evident.
-14
-15
±
=
26.7 ± 0.5 Kcal/mol
±
S
=9.1 ± 1.0 cal/mol
derived from oxidation of the pyridone moieties in II by singlet
◦
oxygen. Heating the solution to 40 C after irradiating them and
maintaining the temperature there for 20 min resulted in a reduc-
tion of the signals from the endoperoxide moieties and a recovery of
signals from the pyridone moieties. The irradiation-heating exper-
iment was repeated for three cycles. The NMR overlay spectra in
Fig. 4 demonstrate reversible trapping and releasing of singlet oxy-
gen throughout these cycles without detectable decomposition or
side reactions.
-16
Kinetics of endoperoxide decomposition were measured by
monitoring the decay of the endoperoxide NMR signal as a func-
tion of time at several fixed temperatures between 25 and 50 C.
-17
3
◦
-3
-3
-3
-3
-3
.00x10
3.10x10
3.20x10
/T (K-1
3.30x10
3.40x10
The decay data followed first-order kinetics throughout, as shown
in Fig. 5. Thermodynamic activation parameters for the thermolysis
reaction were determined from an Eyring plot (Fig. 6) of the kinetic
data. It is seen from Table 1 that the values obtained are close to
values we measured for the related model compound, N-benzyl-
1
)
Fig. 6. Eyring plot of rate constants derived from the data presented in Fig. 5.
2
-pyridone, under identical conditions. Just as the spectroscopic
and photophysical properties associated with the porphyrin moiety
are not perturbed by the presence of the pyridone ring, the kinetic
properties of the endoperoxide decomposition are not significantly
altered by the presence of the porphyrin ring.
hours at room temperature. The NMR spectrum was rerecorded
and no change was apparent. After heating the solution to 40 C and
◦
holding at this temperature for 10 min, all done in the dark, clear
evidence of the buildup of CEES degradation products [2] are seen
in the 1H NMR spectrum, shown (in part) Fig. 7. This preliminary
study of a dark reaction of I will be followed up by more extensive
studies in the future. However, it does demonstrate the potential
for molecules that generate, trap, store, and release singlet oxygen
to be used in various applications.
4.3. Dark reaction of CEES with singlet oxygen generated from
thermal decomposition of I
A solution of CEES and I in chloroform-d prepared as described
in the Methods section was allowed to sit in the dark for several

C. Changtong et al. / Journal of Photochemistry and Photobiology A: Chemistry 260 (2013) 9–13
13
5. Conclusion
A new molecule, II, that has H TPP linked with four 2-pyridone
2
moieties has been synthesized and shown to reversibly generate,
trap, store, and release singlet oxygen. The use of this material as
a source of singlet oxygen in the absence of light has been demon-
strated by the dark oxidation of CEES. Kinetic data for the decay
of the endoperoxide adduct, I, show first-order behavior between
◦ ◦
2
5 C and 50 C. Further applications of this and related materials
are in progress.
Acknowledgements
This work was supported by the U.S. Department of Defense
under Army contracts W911NF-04-C-0081 and W911NF-07-D-
0
001 as well as by Air Force contracts W911QY-10C-0181 and
Fig. 7. NMR spectra of CEES and oxidized products formed by the reaction of CEES
with singlet oxygen released by I.
W911QY-10-C-018. Dr. Joseph Wander from the Airbase Technolo-
gies Division (AFRL/RXQ) of the U.S. Air Force Research Laboratory
is thanked for his technical insight provided during numerous dis-
cussions. In addition, we appreciate Dr. Heidi Schreuder-Gibson
of the U.S. Army Natick Soldier RDE Center for her interest and
stimulating conversations throughout this effort.
4.4. Computations
Wasserman et al. [10] have demonstrated that calculations
carried out at the B3LYP/6-311 + G* level of theory provides a
reasonable approach for studying the energetics of the decom-
position of endoperoxides of substituted naphthalenes to yield
singlet oxygen and the parent naphthalene. Under the assumption
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energy structures were confirmed by obtaining all positive fre-
quencies for the calculated normal modes of vibration. Zero-point
energy corrections were applied to the computed energies. The
transition state structure associated with the decomposition of
the endoperoxide to N-benzyl-2-pyridone and singlet oxygen was
characterized by one negative vibration that corresponds to oscil-
lation between the reactant and product side of the reaction
coordinate. Following Wasserman et al. [10], the energy of singlet
oxygen was estimated to be −150.32792 H. As shown in Table 1, the
agreement between the experimental activation parameters and
the DFT calculated values is reasonable and typical for this approach
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