Synthesis and studies of a super-structured porphyrin derivative - A potential building block for CcO mimic models

Article abstract of DOI:10.1002/ejoc.200801122

A novel porphyrin complex that contains an Fe porphyrin linked to a tridentate ligand where a Cu ion could be coordinated was synthesized. The molecule also incorporated a tyrosine mimic attached to the porphyrin ring via a urea bond and was fully charact

Full text of DOI:10.1002/ejoc.200801122

FULL PAPER
DOI: 10.1002/ejoc.200801122
Synthesis and Studies of a Super-Structured Porphyrin Derivative –
A Potential Building Block for CcO Mimic Models
Georgios Charalambidis,[a] Kalliopi Ladomenou,[a] Bernard Boitrel,[b] and
Athanassios G. Coutsolelos*[a]
Keywords: Mimic models / Porphyrinoids / Enzyme models / Metalloenzymes / Oxidase / Dioxygen / Copper / Iron
A novel porphyrin complex that contains an Fe porphyrin
linked to a tridentate ligand where a Cu ion could be coordi-
nated was synthesized. The molecule also incorporated a ty-
rosine mimic attached to the porphyrin ring via a urea bond
and was fully characterized. We studied the action of di-
oxygen on several porphyrin derivatives electrochemically
with a rotating ring-disk electrode.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
heme a3, the oxy form reacts with CuIB to give FeIIIa3–O–
O–CuII, where the bound oxygen is already in the peroxy
state. The protonation of this bridging peroxy ligand is ex-
pected to induce heterolytic O–O cleavage. Several points
have not yet been clarified including the participation of
CuB in the oxygen activation reaction, the Tyr role and the
characterization of transient species. Thus, the synthesis,
characterization and studies of promising mimetic models
and their evaluation toward molecular oxygen reduction are
extremely challenging. Such studies have already been inves-
tigated by Karlin et al. with models bearing either a Tyr244
mimic or not. However, in such models, the triaza com-
pound was attached only by one linker on the porphyrin.[8,9]
In the present study, the Cu coordination sphere is attached
to the heme via three urea bonds.
Introduction
Cytochrome c oxidase (CcO), a membrane-bound metal-
loenzyme, is a member of the heme-Cu terminal oxidase
superfamily. It is involved in the respiratory chains of mito-
chondria and aerobic bacteria and catalyzes the 4e–/4H+
reduction of O2 to H2O.[1,2] The three-dimensional struc-
tures of CcOs from Paracoccus denitricans[3,4] and bovine
heart[5–7] have recently been determined by X-ray diffrac-
tion. Their oxygen metabolic sites consist of three major
components: heme, a Cu atom, and one tyrosine (Tyr)
molecule. The three-dimensional structures of CcOs dem-
onstrate that, as previously surmised from indirect evidence,
the “distal” O2-binding/activating site is composed of a
myoglobin-type Fe center (heme a3) and a Cu atom (CuB)
with three histidine (His) ligands (Figure 1). CuB is located
about 4.5 Å from heme a3 and 1 Å away from the normal
axis of the heme iron position. One of the three His residues
coordinating to CuB is covalently cross-linked to a Tyr
through the ε-nitrogen of His240 and C-6 of Tyr244 (the
residue number is based on the bovine enzyme). The hy-
droxy group of the Tyr residue is within hydrogen–bonding
distance of the dioxygen molecule bound to heme a3. The
arrangement of the active site residues has led to two dif-
ferent proposals for oxygen activation: (1) the oxy interme-
diate is protonated with the concomitant reduction of the
complex by an electron from heme a3 to give FeIIIa3–O–O–
H[2] or (2) without protonation and electron-transfer from
Figure 1. CcO-active center.
[a] Department of Chemistry, University of Crete, Laboratory of
Bioinorganic Chemistry,
Voutes Campus, P. O. Box 2208, 71003 Heraklion, Crete, Greece
Fax: +30-2810545001
E-mail: coutsole@chemistry.uoc.gr
Results and Discussion
[b] Sciences Chimiques de Rennes, UMR CNRS 6226, ICMV,
35042 Rennes, Cedex, France
The porphyrin ring that constitutes the basic structural
unit of the mimic derivative 1 is the 5,10,15,20-tetrakis(2-
Supporting information for this article is available on the
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aminophenyl)porphyrin 3 (TAPP, Scheme 1). This particu- amino groups of porphyrin 3 were transformed to isocyano
lar porphyrin ring has been used for the synthesis of many groups. We did not isolate the isocyano intermediate but
biomimetic models owing to its easy preparation protocol reacted immediately with the three amino groups of 4 lead-
as well as the possibility of anchoring various substitutes to ing to the formation of porphyrin 5. The presence of tri-
the four amino groups. Extensive studies with regard to the ethylamine was essential for the neutralization of the HCl
separation, the interconversion and characterization of the produced during the reaction. In order to avoid the connec-
four atropisomers of TAPP have been realized. For the syn- tion of one molecule of 4 with two different molecules of
thesis of model 1, we used the α,α,α,α atropisomer of 3. In porphyrin, we added reagents simultaneously and slowly.
order to increase the proportion of the latter in the mixture, The next step consisted in the attachment of the Tyr mimic
was used the method that consisted of refluxing the mixture moiety. We used 2-methoxyphenylamine to mimic the phe-
of TAPP atropisomers with silica gel (SiO2) in toluene.[10] nol of the Tyr. To porphyrin 5 we added triphosgene in the
With this procedure, 68% of the porphyrin was converted presence of triethylamine, and the isocyano intermediate
into the α,α,α,α isomer, and this yield can be improved by that was formed reacted with 2-methoxybenzylamine, giv-
reprocessing the remaining mixture of atropisomers.
ing porphyrin 6 in a satisfactory yield (51%). We completed
The host location (or substrate), in which the Cu will the synthesis of model 1 with the deprotection of the hy-
be coordinated, was N1-benzyl-N2,N2-bis[2-(benzylamino)- droxy group. We added an excess of boron tribromide
ethyl]ethane-1,2-diamine (4). This substrate was prepared (BBr3) to a solution of porphyrin 6, leading to the forma-
by a reaction between N1,N1-bis(2-aminoethyl)ethane-1,2- tion of model 1. We characterized all the aforementioned
diamine (tren) and benzaldehyde in the presence of sodium derivatives (before the addition of any metal ion) by means
1
borohydrate (NaBH4).[11] Tren could also be used for the of H and 13C NMR spectroscopy.
direct coordination of Cu. However, in our efforts to couple
In the next stage, we performed the metalation reactions
tren with porphyrin 3, we observed the formation of many of both final derivatives 1 and 6. For the metalation reac-
by-products. The formation of by-products was presumably tions of the porphyrin core, we used Fe bromide under an-
due to the increased reactivity of the primary aliphatic aerobic conditions in a glove box.[13] We observed a signifi-
amines of tren. Unlike in tren, the three secondary amines cant change in the color of the solution from purple to
in 4 react slowly. By this procedure, the reaction between 4 orange during the reaction, which is characteristic of the
and porphyrin 3 affords mainly the desired product 5.
ferrous porphyrins. After completion of the reaction, and
The following reactions for the synthesis of 1 are pre- because column chromatography under anaerobic condi-
sented in Scheme 1. Initially, we performed the connection tions is laborious, we exposed the solution to the atmo-
of 4 with porphyrin 3 via three urea bonds using the sphere, and the Fe was immediately oxidized from the +2
method of Collman et al.[12] For this purpose, we added to to the more stable +3 oxidation state. During the oxidation
porphyrin 3 a suitable quantity of triphosgene in the pres- of the Fe porphyrins by oxygen from the atmosphere, the
ence of triethylamine. In this procedure, three of the four formation of various oxygenated derivatives was possible
Scheme 1. Synthesis of ligand 1 bearing a phenyl group.
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Super-Structured Porphyrin Derivative
including oxo (Fe–OH) and peroxo (Fe–O–O) moieties. The Cu both on the final model and its analogue with a pro-
µ-oxo dimer (Fe–O–Fe) and the µ-peroxo dimer (Fe–O–O– tected hydroxy group. We performed the metalation reac-
Fe) also occurred. When the above-mentioned species were tions using a CuII salt.[14] To a solution of the porphyrin
present together, they were difficult to separate. For this derivatives in MeCN/ethanol, we added an eqimolar quan-
reason, we performed extractions with dilute HCl.[14] Under tity of [Cu(CO2CH3)2] in MeCN. We heated the mixture
these conditions, we observed the exchange of the axial li- at 55 °C for 5 min and isolated the desired derivative by
gand of Fe as well as the splitting of the dimer units. Thus, precipitation with pentane. The final derivatives are de-
we obtained exclusively monomeric species in which the Fe picted in Figure 2. The metalated Cu-Fe porphyrin deriva-
was pentacoordinate and had an axial Cl ligand. The struc- tives obtained by the above-described procedure could not
tures of the synthesized Fe-only and Fe-Cu complexes as be submitted to further purification because the weak coor-
well as their phenol-protected analogues are presented in dination of the Cu ion did not survive column chromatog-
Figure 2. For the metalation reaction, we used a 10-fold raphy. In this case also, we could not fully characterize the
excess of Fe dibromide. Under these conditions, the Fe product by NMR spectroscopy due to the presence of Fe,
could also coordinate to the location intended to host Cu. which was still paramagnetic. Again, HRMS contributed to
However, since we performed the extractions with dilute the identification of the formed complexes, and the results
aqueous HCl, the nitrogen atoms of the Cu coordination were in full agreement with the target structures.
site were protonated, leading to Fe liberation from that
In model 1, the host molecule for Cu binding (4) was
coupled with the porphyrin ring via three urea bonds. This
type of link is expected to form a rigid ligand, as the tren
residue is firmly held above the porphyrin. This conforma-
site.[15]
1
tion was supported by H NMR spectroscopy, as several
protons from 4 exhibited negative chemical shifts, indicating
that they were shielded by the macrocycle. However, the
phenyl ring that mimics the Tyr part of the enzyme is linked
to the porphyrin entity by only one urea bond and is still
somewhat mobile.
Many recrystallization efforts for derivatives 1, 5, and 6
have not provided the expected single crystals. The lack of
1
any crystal data set as well the poorly resolved H NMR
spectra of 1Fe and 1FeCu due to the presence of the para-
magnetic metal ion(s) drove us to a detailed study of deriva-
tives 1 and 6, as well as the synthesis of 8 (Scheme 2). A
comparison of the 1H and 13C NMR spectroscopic data
for derivatives 1 and 6 helped us to assign each peak to a
corresponding proton. For 6, we found the methoxy group
at δ = 3.70 ppm, but the OH group of 1 was difficult to
identify. In contrast, all the other signals of the OCH3/OH-
containing phenyl ring were clearly assigned. This is why
we used 8 as a probe to investigate the conformation of the
aromatic picket of 1.
Figure 2. The metalated complexes with or without the protected
phenol group. (The Cu counter anions are not represented).
We confirmed the incorporation of Fe into the porphyrin
ring by UV/Vis spectroscopy.[16] The Soret band of the por-
phyrin ring shifted to shorter wavelengths, which is charac-
teristic of the binding of Fe with the four pyrrolic nitrogens.
Moreover, we observed fewer Q bands as well as a decrease
of the absorption coefficient (ε).
Due to the electronic configuration ([Ar] 3d5) of the Fe,
it possesses unpaired electrons in both high-spin and low-
spin complexes. Consequently, the proton signals in the H
1
Scheme 2. Synthesis of 8 for the NMR comparison study.
Thus, we synthesized derivative 8 as a reference com-
NMR spectrum were spread from 80 ppm down to
–10 ppm, giving broad peaks that were difficult to assign.[17]
High-resolution mass spectrometry (HRMS) aided in the pound for the picket of porphyrin 1. The synthetic pathway
identification of the derivatives. is described in Scheme 2. Aniline reacted first with triphos-
In order to complete the formation of a synthetic ana- gene in the presence of triethylamine to give rise to the iso-
logue of CcO, we performed the metalation reaction with cyano intermediate. The addition of 2-methoxyphenylamine
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followed. We stirred the mixture for 1 h, at which time de- electrode. Indeed, there is no direct way to observe how the
rivative 7 formed. The next step involved the deprotection catalyst evolves during the catalytic process.
of the hydroxy group, which we achieved by the addition of
In order to carry out the electrochemical experiments, we
boron tribromide to obtain derivative 8.
adsorbed the molecules on the disk electrode, which was a
Obviously, the phenolic proton would be a good probe section of a highly ordered graphite rod, with the planes of
candidate but is not reliable as it is mobile, exchangeable graphite being perpendicular to the surface of the electrode
and its resonance frequency is temperature-dependent. On (edge-plane graphite electrode, EPGE). We scanned the po-
the other hand, the chemical shifts of the other phenyl ring tential of this modified graphite electrode from high to
protons such are indicative of their location in the shielding lower values so as to record the voltammogram for the re-
ring current of the macrocycle. From the values presented duction of O2. The graphite electrode was surrounded by a
on Table 1 we observe that chemical shifts of these protons platinum ring electrode, the potential of which we set at a
in 1 were smaller than those of the reference 8, indicating fixed value (1.0 V) such that the H2O2 eventually produced
that those protons were located above the porphyrin ring at the disk was oxidized to O2.
current. In addition, the most heavily shifted proton is H-4
Figure 3 depicts the catalytic studies for the various com-
(see Scheme 1 for the location), which is ortho to the hy- plexes elaborated from ligand 1. First, we studied complex
droxy group. This observation favors an orientation of the 1Fe without Cu. In this case (Figure 3, curve a), the re-
phenyl ring with the hydroxy group pointed oriented to- duction of dioxygen started at 0.05 V versus SCE. From the
ward the center of the molecule. Thus, in model 1, the host comparison with the 2e– reduction wave on a bare EPGE,
ligand for the Cu ion as well the phenyl ring most likely the number of electrons exchanged per O2 molecule was 3.2.
adopts a favorable conformation for the catalyzed reduction H2O2 is detected through its oxidation, as soon as O2 is
of dioxygen.
reduced, from the current increase at the platinum electrode
encompassing the graphite disk. This means that the 2e–
and 4e– reduction mechanisms occur simultaneously. From
the study of model 1FeCu (Figure 3, curve b), we observed
that the presence of Cu ion did not seem to affect the cata-
lytic ability of the complex. The number of the necessary
electrons for the reduction process as well the potential did
not significantly differ. We observed the most important
change in the current on the platinum electrode (ring).
However, this was attributed to the poisoning of the elec-
Table 1. Comparative chemical shifts of the phenol protons for 1
and 8.[a]
Entry
H-1
6.98
7.19
H-2
6.71
6.97
H-3
6.79
7.09
H-4
6.41
6.92
1
2
3
1
8
∆ppm
–0.21
–0.26
–0.30
–0.51
[a] In CDCl3.
We could not fully characterize the metalated com- trode from the catalyst molecules. The presence of catalyst
pounds by NMR spectroscopy due to the presence of the molecules on the surface of the electrode led to measure-
Fe, which is paramagnetic. However, from the chemical ment errors, as the observed current resulted not only from
shift of the pyrrole protons we determined the spin and the the reduction of H2O2 produced at the disk but also from
1
oxidation state of the Fe ion. In the H NMR spectra of the reduction of catalyst molecules. Models 1FeCu and 1Fe
the metalated compounds 6Fe, 6FeCu, 1Fe, and 1FeCu, the
chemical shift of the pyrrole protons was about 80 ppm.
This value is characteristic of oxidized high-spin Fe-porphy-
rins. Therefore, we concluded that in all the synthesized
models, the Fe was at the +3 oxidation state having an over-
all spin S = 5/2.
Finally, we evaluated these derivatives as promising en-
zyme mimics electrochemically with a rotating ring disk
electrode (RRDE) in the presence of molecular oxygen. Our
purpose was to compare the catalytic activity of the newly
synthesized compounds. The primary goal of this investiga-
tion was to shed light on the role of the hydroxy group
delivered by one picket in the meso position of the porphy-
rin. More precisely, we wanted to know if its presence was
essential for the 4e– reduction of dioxygen to water. On the
one hand, the main advantage of this technique is its ability
to detect H2O2 by a ring current at the anode (made of a
platinum ring). It is important to note that the H2O2 de-
tected at the anode was produced by the reduction of di-
oxygen at the cathode (composed of a graphite disk) and
had migrated dramatically. On the other hand, a disadvan-
tage of this technique consists in the irreversible adsorption
of the catalyst (the synthetic model) on the surface of the ring current).
Figure 3. RRDE voltammograms (a: 1Fe, b: 1FeCu, c and d: 2nd
scan for 1Fe and 1FeCu, respectively; bottom: disk current, top:
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Super-Structured Porphyrin Derivative
solution in CH2Cl2, 0.25 mL, 0.25 mmol). The mixture was stirred
at –78 °C for 30 min and at 0 °C for 1 h. The reaction was quenched
with MeOH (5 mL) and stirred for 10 min at 0 °C. The mixture
was washed with saturated aqueous NaHCO3 (2ϫ20 mL), water
(2ϫ20 mL), and dried, and the solvent was evaporated under re-
duced pressure. The crude material was purified by column
chromatography (10% MeOH in CH2Cl2) to give 1 as a purple
solid (22 mg, 89%). H NMR (500 MHz, CDCl3): δ = 8.97 (m, 2
H), 8.89 (d, J = 4.5 Hz, 2 H), 8.82 (s, 4 H), 8.54 (m, 2 H), 8.33 (d,
J = 8.5 Hz, 1 H), 8.06 (m, 1 H), 7.83 (m, 7 H), 7.76 (m, 2 H), 7.69
were unstable and decomposed quickly after two successive
scans. We also noticed a significant decrease in the current
for the graphite electrode (disk, Figure 3, curves c and d)
after the second scan, which we attributed to the decrease
of the catalyst concentration on the surface of the electrode.
This obstacle prevented us from further processing our
analysis.
1
Thus, we observed a higher selectivity for model 1 than
for the other models in the 4e– reduction of molecular oxy-
gen to H2O. For this reason, we performed further studies (m, 1 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H), 7.06
(m, 4 H), 6.98 (m, 7 H), 6.86 (m, 6 H), 6.79 (t, J = 7.5 Hz, 1 H),
6.71 (d, J = 7.5 Hz, 1 H), 6.41 (br. s, 4 H), 6.18 (br. s, 1 H), 4.67
(br. s, 2 H), 3.82 (s, 4 H), 2.99 (br. s, 2 H), 1.67 (m, 2 H), 0.99 (m,
2 H), 0.58 (br. s, 2 H), –1.42 (br. s, 2 H), –2.41 (s, 2 H), –2.57 (m,
2 H) ppm. Rf (CH2Cl2/MeOH, 9:1) = 0.41. HRMS (ES+): calcd.
for C81H70N13O5 [M + H]+ 1304.5623; found 1304.5631. UV/Vis
(CH2Cl2): λ (ε) = 422 (260.2), 516 (13.8), 549 (3.2), 588 (4.0), 646
(1.3) nm.
on the derivative in which a methyl group protects the hy-
droxy function. The difference between the results with 1
and 6 should provide evidence for the role of the proximal
Tyr mimic in our derivatives. Actually, with 6 absorbed on
the surface of the electrode, the results were consistent with
those from model 1, and we observed no difference. Conse-
quently, the hydroxy group of these derivatives did not seem
to participate in the reduction of dioxygen, as their catalytic
activity and their stability remained unchanged when the
hydroxy group was protected.
Tris(2-benzylaminoethyl)amine
(4):
Benzaldehyde
(1.7 mL,
16.5 mmol) was added dropwise to a solution of tris(2-aminoethyl)-
amine (0.75 mL, 5 mmol) in dry MeOH (5 mL) at room temp. The
resulting yellow solution was stirred for 1 h and then cooled in an
ice bath. NaBH4 (0.7 g, 19 mmol) was added portionwise, and the
mixture was stirred for an additional 2 h at room temp. The reac-
tion mixture was then diluted with water (10 mL) and extracted
with diethyl ether (3ϫ5 mL). The combined organic extracts were
washed with aqueous HCl (1 , 2ϫ20 mL). The combined aqueous
layers were extracted with diethyl ether (2ϫ5 mL), and then made
basic with solid K2CO3 to a pH Ͼ 10. The basic aqueous layer was
extracted with diethyl ether (3ϫ5 mL), and the combined organic
layers were dried and concentrated to give a pale yellow oil (1.67 g,
Conclusions
In conclusion, we tested the investigated molecules for
their ability to reduce dioxygen in water on graphite elec-
trodes in contact with an aqueous medium. Under these
very specific conditions, although we observed a significant
proportion of the 4e– process, we found no clear influence
of the hydroxy group of our model molecules on the pro-
portion of the 4e– versus 2e– reduction of dioxygen. This
lack of difference could come from the models themselves,
in which the orientation of the hydroxy group might not be
properly controlled. Further investigations of new deriva-
tives as building blocks for efficient molecular models for
CcO are needed. The complexity of the system requires very
flexible and well-designed molecules in order to take into
account all the involved parameters that could play a role
in the catalytic activity.
1
80%). H NMR (500 MHz, CDCl3): δ = 7.25 (m, 15 H), 3.73 (s, 6
H), 2.66 (t, J = 6 Hz, 6 H), 2.57 (t, J = 6 Hz, 6 H), 1.84 (br. s, 3
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 140.5 (C), 128.4 (CH),
128.1 (CH), 126.8 (CH), 54.5 (CH2), 54.0 (CH2), 47.2 (CH2) ppm.
Rf (CH2Cl2/MeOH, 9:1) = 0.31.
Porphyrin 5:
A mixture of tetraminoporphyrin 3 (67 mg,
0.10 mmol) and triethylamine (0.22 mL, 1.6 mmol) in dry CH2Cl2
(20 mL) was stirred for 1 h under argon at room temp. In another
flask, tris(2-benzylamino ethyl)amine (4, 42 mg, 0.10 mmol) was
dissolved in dry CH2Cl2 (20 mL) under argon. The two solutions
were added simultaneous and slowly to a third flask, which con-
tained dry CH2Cl2 (20 mL). The addition was competed in 1 h, and
the resulting solution was stirred at room temp. for an additional
16 h. The reaction was monitored by thin-layer chromatography
(4% MeOH in CH2Cl2). The residue was purified by column
chromatography, and the desired porphyrin 5 was eluted with 6%
ethyl acetate in CH2Cl2 to give a purple solid (73 mg, 63%). 1H
NMR (500 MHz, CDCl3): δ = 8.90 (d, J = 4.5 Hz, 4 H), 8.84 (d,
J = 4.5 Hz, 2 H), 8.78 (m, 2 H), 8.54 (d, J = 7 Hz, 2 H), 8.40 (d,
J = 8 Hz, 1 H), 7.81 (m, 6 H), 7.68 (t, J = 7.5 Hz, 2 H), 7.61 (t, J
= 7.5 Hz, 1 H), 7.55 (d, J = 7 Hz, 1 H), 7.41 (t, J = 7.5 Hz, 1 H),
7.17 (d, J = 7.5 Hz, 1 H), 7.12 (t, J = 7.5 Hz, 1 H), 7.00 (m, 5 H),
6.88 (m, 10 H), 6.42 (s, 2 H), 6.20 (s, 1 H), 4.90 (br. s, 2 H), 3.96
(s, 4 H), 3.57 (s, 2 H), 1.68 (m, 2 H), 1.21 (m, 4 H), 0.56 (m, 2 H),
–1.12 (m, 2 H), –2.33 (m, 2 H), –2.50 (s, 2 H) ppm. Rf (CH2Cl2/
EtOAc, 95:5) = 0.39. MS (EI): m/z = 1169.3 [M + H]+, (100%) for
C74H65N12O3. C74H64N12O3 (1169.38): calcd. C 76.01, H 5.52, N
14.37; found C 76.17, H 5.35, N 14.28. UV/Vis (CH2Cl2): λ (ε) =
422 (264.6), 516 (14.7), 549 (3.2), 588 (4.3), 646 (1.4) nm.
Experimental Section
General: 1H and 13C NMR spectra were recorded, unless otherwise
specified, as deuterochloroform solutions using the solvent peak as
an internal standard with a Bruker AMX-500 MHz spectrometer.
UV/Vis spectra were recorded with a Shimadzu Multispec-1501 in-
strument. All electrospray mass spectrometric experiments were
performed with an LCQ Advantage (ThermoElectron, San Jose,
CA) mass spectrometer. HRMS was performed with a MS/MS
ZABSpec TOF spectrometer at the University of Rennes I
(C.R.M.P.O.). Thin-layer chromatography was preformed on silica
gel 60 F254 plates. Chromatography refers to flash chromatography
and was carried out on SiO2 (silica gel 60, SDS, 70–230 mesh
ASTM). All dry solvents were dried by the appropriate technique.
Organic extracts were dried with magnesium sulfate unless indi-
cated otherwise. The evaporation of the solvents was accomplished
with a rotary evaporator.
Porphyrin 1: To a solution of porphyrin 6 (25 mg, 0.02 mmol) in
dry CH2Cl2 (20 mL), cooled to –78 °C, was introduced BBr3 (1.0 
Porphyrin 6: A mixture of porphyrin 5 (25 mg, 0.02 mmol), triethyl-
amine (6 µL, 0.04 mmol), and triphosgene (6 mg, 0.02 mmol) in dry
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CH2Cl2 (30 mL) was stirred for 1 h under argon at room temp. 2-
Methoxybenzylamine (5 mg, 0.04 mmol) was then added, and the
stirring was continued overnight. The resulting mixture was puri-
fied by column chromatography (10% ethyl acetate in CH2Cl2) to
give 6 as a purple solid (14 mg, 51%). 1H NMR (500 MHz,
CDCl3): δ = 8.91 (m, 2 H), 8.86 (d, J = 4.5 Hz, 2 H), 8.79 (s, 4 H),
8.55 (d, J = 6.5 Hz, 2 H), 8.35 (d, J = 8.5 Hz, 1 H), 8.10 (br. s, 1
H), 8.00 (d, J = 7 Hz, 1 H), 7.90 (m, 3 H), 7.82 (m, 4 H), 7.67 (t,
J = 7.5 Hz, 2 H), 7.60 (t, J = 7.5 Hz, 1 H), 7.45 (m, 2 H), 7.09 (br.
s, 1 H), 6.93 (m, 9 H), 6.82 (m, 7 H), 6.64 (d, J = 7 Hz, 1 H), 6.57
(t, J = 7.5 Hz, 1 H), 6.46 (br. s, 3 H), 5.91 (br. s, 1 H), 4.77 (br. s,
2 H), 3.91 (s, 4 H), 3.61 (s, 3 H), 2.98 (br. s, 2 H), 1.52 (m, 2 H),
0.98 (m, 2 H), 0.67 (br. s, 2 H), –1.42 (m, 2 H), –2.50 (s, 2 H), –2.60 [2]
(br. s, 2 H, H-13) ppm. Rf (CH2Cl2/EtOAc, 9:1) = 0.38. MS (EI):
m/z = 1318.7 [M + H]+, (100%) for C82H72N13O5. C82H71N13O5
(1318.53): calcd. C 74.70, H 5.43, N 13.81; found C 74.80, H 5.35,
Supporting Information (see also the footnote on the first page of
this article): H NMR spectra for all new compounds.
1
Acknowledgments
Pythagoras I and Heraklitos programmes from the Greek Ministry
have financially supported this work.
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Received: November 12, 2008
Porphyrin 6Fe: Under an inert atmosphere, porphyrin 6 (30 mg,
0.025 mmol) and Fe(II) bromide (54 mg, 0.25 mmol) were added
to a Schlenk flask. The addition of deoxygenated THF (6 mL) gave
a red solution. The mixture was stirred overnight at 55 °C and then
opened to the air and cooled to room temp. The solvent was then
removed under vacuum, and the resulting powder was dissolved in
CHCl3 (20 mL) and washed with HCl (2 , 1ϫ25 mL) and satu-
rated NaHCO3, dried, filtered, and concentrated under vacuum.
The resulting crude product was purified by chromatography (0–
6% MeOH in chloroform). The product was eluted at 2% MeOH
in chloroform to give 6Fe as a brown-purple solid (29 mg, 84%).
[8]
[9]
Rf (CH2Cl2/MeOH, 9:1)
=
0.40. HRMS (ES+): calcd. for
C82H69FeN13O5 [M – Cl]+ 1371.4894; found 1371.4899. UV/Vis
(CH2Cl2): λ (ε) = 417 (74.0) nm.
Porphyrin 1Fe: The insertion of the iron was carried out according
to the procedure described for 6Fe. Rf (CH2Cl2/MeOH, 9:1) = 0.37.
HRMS (ES+): calcd. for C81H67FeN13O5 [M – Cl]+ 1357.4738;
found 1357.4743. UV/Vis (CH2Cl2): λ (ε) = 417 (75.3) nm.
[10]
[11]
Porphyrin 6FeCu: To a solution of porphyrin 6Fe (7 mg, 5.5 µmol)
in MeCN (4 mL) was added Cu acetate [6.0 µmol, from a standard
solution of 50 mg of Cu(CH3COO)2 in 25 mL of MeCN], and the
mixture was stirred at 60 °C for 10 min. The solvent was then re-
moved under vacuum, and the resulting solid was dissolved in
CHCl3. Upon the addition of pentane, the complex precipitated.
The solid was filtered and washed with pentane, giving 6FeCu as a
brown-purple solid (7.5 mg, 97%). Rf (CH2Cl2/MeOH, 9:1) = 0.40.
HRMS (ES+): calcd. for C82H69CuFeN13O5 [M – Cl]+ 1434.4190;
found 1434.4181. UV/Vis (CH2Cl2): λ (ε) = 417 (60.9) nm.
[12]
[13]
[14]
[15]
[16]
Porphyrin 1FeCu: The insertion of copper was performed according
to the procedure described for 6FeCu. Rf (CH2Cl2/MeOH, 9:1) =
0.37. HRMS (ES+): calcd. for C81H67CuFeN13O5 [M – Cl]+
1420.4034; found 1420.4049. UV/Vis (CH2Cl2): λ (ε) = 417 (61.3)
nm.
[17]
Published Online: January 28, 2009
1268
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1263–1268