Photophysical properties of gallium hydroxyl tetratolylporphyrin and 132-demethoxycarbonyl-(gallium hydroxyl)-methyl-pheophorbide a

Article abstract of DOI:10.1016/j.cplett.2005.10.131

Two metal tetrapyrroles containing gallium, gallium hydroxyl tetratolylporphyrin and 13²-demethoxycarbonyl-(gallium hydroxyl)-methyl pheophorbide a (Ga-(OH)-chlorin), were synthesized from their respective free bases using Ga(III)-acetylacetonate in a phenol melt. Their photophysical properties were investigated and the quantum yields of different monomolecular deactivation processes were determined. For Ga-(OH)-porphyrin S₂-fluorescence was observed and quantified. In contrast, for Ga-(OH)-chlorin no S₂-fluorescence was observed. Both compounds should be useful as efficient photosensitizers in photodynamic therapy.

Full text of DOI:10.1016/j.cplett.2005.10.131

Chemical Physics Letters 418 (2006) 355–358
www.elsevier.com/locate/cplett
Photophysical properties of gallium hydroxyl tetratolylporphyrin
and 132-demethoxycarbonyl-(gallium hydroxyl)–methyl-pheophorbide a
a
a
b
c
a,
*
Christian Litwinski , Sebastian Tannert , Aldo Jesorka , Martin Katterle , Beate Ro¨der
a
Humboldt University of Berlin, Institute of Physics, Newtonstrasse 15, D-12489 Berlin, Germany
Chalmers University of Technology, Department of Chemistry and Bioscience, Kemiva¨gen 10, SE-41296 Go¨teborg, Sweden
University of Potsdam, Institute of Biochemistry and Biology, Karl-Liebknecht-Str. 24–25, Bldg. 25, D-14476 Potsdam, Germany
b
c
Received 11 July 2005; in final form 27 October 2005
Available online 28 November 2005
Abstract
Two metal tetrapyrroles containing gallium, gallium hydroxyl tetratolylporphyrin and 132-demethoxycarbonyl-(gallium hydroxyl)–
methyl pheophorbide a (Ga-(OH)-chlorin), were synthesized from their respective free bases using Ga(III)-acetylacetonate in a phenol
melt. Their photophysical properties were investigated and the quantum yields of different monomolecular deactivation processes were
determined. For Ga-(OH)-porphyrin S2-fluorescence was observed and quantified. In contrast, for Ga-(OH)-chlorin no S2-fluorescence
was observed. Both compounds should be useful as efficient photosensitizers in photodynamic therapy.
ꢀ 2005 Elsevier B.V. All rights reserved.
1. Introduction
the porphyrin with gallium (III)-acetylacetonate in a phe-
nol melt [7].
Metal porphyrin derivatives are biologically important
chromophores with a macrocyclic-conjugated system of
p-electrons. The synthesis and photophysical characteriza-
tion of metal porphyrins and especially the diamagnetic
Ga-porphyrin-complexes were and still are a hot topic in
chemistry and optical spectroscopy [1–4]. Characteristic
and partly intense B and Q absorption bands in the near-
ultraviolet and visible regions, respectively, arise from the
(p ! p*) transitions of the electronic system of the porphy-
rin. In case of closed shell configuration of the central
metal, the outer-shell electrons give only a minor perturba-
tion [3,5].
Specifically, several reports on Ga-porphyrin-complexes
have appeared in the past, where both synthetic procedures
and photophysical studies were in the center of interest [1–
4]. Insertion of gallium into porphyrins has been achieved
by two different synthetic approaches in the past: reaction
of the free base with gallium (III)-salts, e.g. chloride, in ace-
tic acid [6] and by the solvent-free procedure by reacting
Interestingly, no photophysical studies on gallium chlo-
rins have been published to our knowledge, and prepara-
tive chemistry is largely unknown. Generally, synthetic
procedures and photophysical properties of free base chlo-
rins and of a large variety of metal chlorins, especially chlo-
rophyll a derivatives, have been studied extensively for
decades [8–15]. Related gallium containing species, how-
ever, do not seem to have gained much interest, even
though the additionally available axial position in gallium
centered tetrapyrroles could be particularly useful as a ver-
satile coupling site for the synthesis of novel donor–accep-
tor systems. Such novel dyads could be utilized in the
investigation of photoinduced energy or electron transfer.
Moreover, on the way towards 2nd and 3rd generation
photosensitizers for photodynamic therapy (PDT) [16],
besides a number of porphyrins, certain chlorins were con-
sidered as prospective photosensitizing molecules [17].
Their characteristic absorption spectra with bands in the
far red spectral region with large extinction coefficients
combined with high quantum yields for singlet oxygen gen-
eration [18] suggest their potential efficiency in photody-
namic activity.
*
Corresponding author. Fax: +49 30 20937666.
E-mail address: roeder@physik.hu-berlin.de (B. Ro¨der).
0009-2614/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.cplett.2005.10.131

356
C. Litwinski et al. / Chemical Physics Letters 418 (2006) 355–358
In 1971, Bajema et al. [19] first observed S2-fluorescence
under reduced pressure. The crude reaction mixture was
subjected to flash chromatography on silica to hydrolyze
the phenoxide, using THF/MeOH (9:1) as eluent. The
major blue–green band was collected and purified by chro-
matography on neutral aluminium oxide, eluting with chlo-
roform to give 110 mg (35%) as a blue–green solid.
of a porphyrin: zinc tetrabenzoporphyrin (zinc tetra-
phenylporphyrin) in octane and in argon matrices. Since
that time emission from higher excited states was observed
for a variety of diamagnetic metal porphyrins [3,5,19–24].
The large energy gap (Ga-(OH)-TTP: 6800 cmꢀ1) and the
parallel energy surfaces of S1 and S2 state retard the inter-
nal conversion between the two states. Therefore a greater
transition moment granted to S2 ! S0 transition yields
emission from the S2 state [5]. Ohno et al. investigated
the S2-fluorescence of different metal porphyrins and also
for a gallium porphyrin (Ga-Cl-TPP in benzene) [3].
The steady state S2-fluorescence can be used as a refer-
ence to determine the rates of photoinduced electron trans-
fer (PET) in, e.g., thin layers like Langmuir–Blodgett-films,
where the fluorescence intensity is very low and time
resolved measurements become impossible. Due to the fact
that only the S1 contributes to the PET, the ratio between
the intensities of S1- and S2-fluorescence can be considered
as measure of PET rates [25].
1H NMR (300 MHz, CDCl3): 9.14 (s, 1H, 10-H), 9.01 (s,
1H, 5-H), 8.39 (s, 1H, 20-H), 7.88 (dd, J3-1,3-2A = 17.7 Hz,
J3-1,3-2B = 11.3 Hz, 1H, 31-H), 6.14 (dd, J3-2A,3-2B = 1.7 Hz,
J3-2A,3-1 = 17.8 Hz, 1H, 32A-H), 6.04 (dd, J3-2B,3-2A
=
1.7 Hz, J3-2B,3-1 = 11.5 Hz, 1H, 32B-H), 4.82 (2d,
J = 19.7 Hz, 2H, 132-CH2), 4.40 (m, J17,18 = 1.9 Hz,
J18,18Me = 7.1 Hz, 1H, 18-H), 4.15 (m, 1H, 17-H), 3.48 (q,
J = 7.6 Hz, 2H, 82-CH2), 3.32 (s, 3H), 3.03 (t, J = 6.3 Hz,
2H, 172-CH2), 3.31 (s, 3H), 3.22 (s, 3H), 2.52 (m, 1H,
171A-H), 2.21 (m, 1H, 171B-H), 1.83 (d, J = 7.2 Hz, 3H,
18-Me), 1.55 (t, J = 7.6 Hz, 3H, 81-Me), 1.43 (m, 1H,
172A-H), 1.25 (m, 1H, 172B-H).
EI-MS: m/e: ber. fur C H GaN O : 633,4, gef.: 633,2
¨
34 35
4
4
(10%, M+), 616 (60%, M–OH).
In a comparative study we investigated the photophysi-
cal properties of Ga-(OH)-TTP and a novel semi synthetic
Ga-(OH)-chlorin derived from chlorophyll a, and evalu-
ated their suitability as either electron donor in electron
transfer systems or as efficient photosensitizer for PDT.
This study is expected to re-focus attention on gallium con-
taining tetrapyrroles and to stimulate further preparative-
synthetic and photophysical investigations.
2.2. Steady state absorption and fluorescence
Ground state absorption spectra were recorded at room
temperature using the commercial spectrophotometer Shi-
madzu UV160A. The emission spectra of the compounds
dissolved in toluene were taken at room temperature in a
1 cm · 1 cm optical quartz cell using a Ti:Sapphire-laser
(Mira 900, Coherent) for excitation at 400 nm and a poly-
chromator with a CCD matrix for detection (LOT-Oriel,
Instaspec IV). As reference for measurements of fluores-
cence quantum yield free base tetraphenylporphyrin
(H2TPP) in toluene (/fl = 0.11) [27] was used.
2. Materials and methods
2.1. Sample preparation and analysis
Tetratolylporphyrin, gallium acetylacetonate, phenol
and common laboratory solvents were obtained from
Sigma–Aldrich, Taufkirchen, Germany. 132-Demethoxy-
carbonyl methylpheophorbide a was obtained by extract-
ing and processing the blue–green algae Spirulina maxima
following a procedure of Smith et al. [26]. NMR-spectra
were recorded using a Bruker DRX-300 NMR spectrome-
ter (300 MHz for 1H). Mass analysis was performed with a
Finnigan MAT 90 spectrometer and UV/VIS spectra were
recorded on a Shimadzu 160A spectrometer.
Tetratolylporphyrin-hydroxy-gallium (III)-complex(1)
was synthesized according to the literature procedure by
Buchler and Puppe [7], starting from the TPP free base,
phenol and gallium (III)-acetylacetonate. The NMR and
mass spectroscopic data are in accordance with the litera-
ture reports of the first published synthesis of this com-
pound by Eaton et al.[6].
2.3. Time resolved fluorescence
Time resolved fluorescence measurements of the samples
dissolved in toluene were carried out by time-correlated-
single-photon-counting-technique (Becker & Hickl GmbH,
SPC 300) using frequency-doubled pulses of a Ti:Sapphire-
Laser (Coherent Mira 900, 350–460 nm, FWHM 120 fs)
for excitation. The response function of the system, mea-
sured with a fiber as scatter medium, had a FWHM of
about 60 ps. The setup was previously described in [28].
2.4. Singlet oxygen generation
Photosensitized generated singlet oxygen luminescence
(SOLM) of the molecules dissolved in toluene was mea-
sured time resolved at 1270 nm. A nanosecond Nd–YAG
laser (BMI) together with an OPO (BMI) was used to
excite the samples at 510 nm. The luminescence signal
was recorded using a germanium pin diode (Northcoast).
For calculation of the singlet oxygen quantum yield of both
samples H2TPP in toluene was used as reference
(/D = 0.68) [18]. The setup and details are described else-
where [29].
132-Demethoxycarbonyl methylpheophorbide a–hydroxy-
gallium (III)-complex(2). In modification of the above
procedure, 300 mg (0.35 mmol) 132-demethoxycarbonyl
methylpheophorbide a, 125 mg (0.35 mmol) Ga(III)-acetyl-
acetonate and 1 g phenol in a 10 ml flask under argon and
heated for 15 min at 140 ꢁC on a metal bath. Subsequently
the excess phenol was removed by Kugelrohr distillation

C. Litwinski et al. / Chemical Physics Letters 418 (2006) 355–358
357
3. Results and discussion
424 nm compared to the Ga-(OH)-chlorin 2, which has a
broad Soret-band with an extinction of 1 · 105 Mꢀ1 cmꢀ1
at 425 nm. Such absorption spectrum is typical for metal
porphyrins [10]. The absorption spectrum of Ga-Cl-TPP
which was investigated by Ohno et al. [3] had a similar
shape. Due to the D4,h-symmetry the absorption spectrum
of Ga-(OH)-TTP 1 has two Q-bands, as compared to the
chlorin spectrum with four Q-bands (Fig. 1). The ratio
between the intensity of the Soret-band and the Qy (0, 0)-
band of Ga-(OH)-chlorin 2 is two to one.
The S1-fluorescence spectra of both compounds con-
sisted of two main bands (Fig. 3). For chlorin 2 the fluores-
cence peak at 666 nm is 10 times more intense than the
peak at 725 nm. The opposite was found for the metal por-
phyrin, as the fluorescence intensity of the peak at 600 nm
is about three times less intense than the second peak at
653 nm. In addition, the fluorescence spectrum of Ga-
(OH)-TTP 1 shows a third fluorescence band at 426 nm,
caused by emission from the S2-state (see inset in Fig. 3).
The fluorescence spectrum of Ga-Cl-TPP published by
Ohno et al. shows a similar shape as the Ga-(OH)-TTP 1
including the S2-fluorescence [3].
The structures of Ga-(OH)-TTP 1 and Ga-(OH)-chlorin
2 are shown in Fig. 1. The OH-group of 2 can be positioned
either syn or anti to the 17-ester chain. Both isomers were
not separated, since significant differences in the photo-
physical properties of both isomers are not expected. The
absorption spectra of 1 and 2 are displayed in Fig. 2. Con-
cerning the latter compound, it is well known that dihydro-
genation of one of the peripheral cryptoolefinic double
bonds of the porphyrin system causes pronounced changes
in the electronic absorption spectrum. For both the chlorin
and the metal porphyrin, shape and position of the absorp-
tion bands are the typical ones for compounds of the
related class [1–5,8–10].
The reduced ring of a chlorin compared to the porphyrin
ring system causes the characteristic, intense far-red shift of
the Qy (0, 0)-band (660 nm) in the absorption spectrum of
Ga-(OH)-chlorin 2, which is typical for chlorophyll related
compounds [6]. Ga-(OH)-TTP 1 shows an intense and nar-
row Soret-band with an extinction of 4 · 105 Mꢀ1 cmꢀ1 at
The photophysical parameters determined for both
compounds are summarized in Table 1. Both compounds
have a single exponential fluorescence decay with compara-
ble lifetimes (Table 1). Otherwise, fluorescence quantum
1
2
1.0
0.8
0.6
0.4
0.2
0.0
S2-fluorescence
0.04
0.03
0.02
0.01
0.00
426 nm
400
420
440
460
wavelength [nm]
Fig. 1. Structural formulas of the investigated compounds: hydroxy
gallium (III)-porphyrin 1 and hydroxy gallium (III)-chlorin 2.
400
500
600
700
800
wavelength [nm]
400000
1
2
Fig. 3. Fluorescence spectra of Ga-(OH)-TTP 1 and Ga-(OH)-chlorin 2 in
toluene.
15000
300000
Table 1
10000
Photophysical parameters of Ga-(OH)-TTP 1 and Ga-(OH)-chlorin 2
200000
5000
Ga-(OH)-TTP 1
Ga-(OH)-chlorin 2
B-band (nm)
Q-bands (nm)
kem (nm)
424
425
0
480
520
560
600
640
553, 593
600, 653
426
2.4 · 107
2.47 · 108
2.43
518, 560, 610, 660
100000
0
wavelength [nm]
666, 725
–
7.7 · 107
1.99 · 108
2.87
S2-kem (nm)
kfl (sꢀ1
)
kISC (sꢀ1
sfl (ns)
)
300
400
500
600
700
800
wavelength [nm]
/
fl
0.06
0.22
/
0.60
0.60
0.57
0.57
ISC
Fig. 2. Absorption spectra of Ga-(OH)-TTP 1 and Ga-(OH)-chlorin 2 in
toluene.
/
D

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C. Litwinski et al. / Chemical Physics Letters 418 (2006) 355–358
yields (/fl) differ significantly with 0.22 for Ga-(OH)-chlo-
rin 2 and 0.06 for Ga-(OH)-TTP. Furthermore, the inter-
system crossing quantum yield (/ISC) is similar and high
with 0.57 for the chlorin and 0.60 for the porphyrin, respec-
tively. Because of similar fluorescence lifetimes and triplet
quantum yields, an additional depopulation process of
the S1-state occurring in the metal porphyrin can only
explain these results. For the investigated Ga-(OH)-TTP
1, a second deactivation process is the S2-fluorescence.
The ratio between the intensity of the S2- and the S1,0-fluo-
rescence (at 600 nm) is 1:89.
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The photophysical properties of both compounds make
them interesting for application as photosensitizers in
PDT and as electron donors in artificial photosystems.
Moreover the S2-fluorescence of the Ga-(OH)-TTP could
be used as strong measure of the efficiency of light induced
electron transfer in artificial photosystems. The Ga-(OH)-
chlorin has suitable absorption bands and extinction coeffi-
cients as well as a high singlet oxygen quantum yield to be
effectively utilized as photosensitizer in PDT. It might pos-
sibly be employed favorably in combination with ultrasonic
sound therapy, which is based on the unique sensitizing
properties of certain gallium containing compounds. Com-
pared to the porphyrin, the considerable bathochromic shift
of the Q absorption bands together with the stronger
absorption of the chlorin enables the use of light with longer
wavelengths, increasing the depth of tissue penetration, and
leading to more efficient tumor damage. Finally, the fifth
axial coordination site of gallium in these porphyrins and
chlorins make them potentially useful for functionalization
of the macrocycle with suitable moieties in order to obtain
more complex chromophor arrays, e.g., gallium containing
dyads for photoinduced electron transfer studies. Impor-
tantly, the axial approach bears the advantage that the mac-
rocycle preserves its electronic characteristics.
Acknowledgments
The authors thanks Mr. Wo¨hlecke for the technical
support.