The synthesis and studies towards the self-replication of bis(capped porphyrins)

Article abstract of DOI:10.1039/b211015f

Connecting two facially-protected porphyrins was expected to lead to an equal mixture of laterally-bridged doubly-protected bis-porphyrins; one in which the two porphyrin units were protected on the same face (syn) and one with the two porphyrin units protected on opposite faces (anti). Addition of a co-factor (bidentate ligand) was expected to lead predominantly to the syn-bis-porphyrin by a templated self-replication process. This concept was explored using Baldwin's capped porphyrin. Bis(capped porphyrins) were synthesised in several steps starting from zinc(II) capped porphyrin 2. Nitration of 2 followed by reduction and photo-oxidation yields a mixture of zinc(II) porphyrin-diones 7 and 8 that can be separated by HPLC. The condensation of 2 molar eq. of zin(II) porphyrin-7,8-dione 8 with 1,2,4,-5-benzenetetramine leads to the formation of a 1 : 1 mixture of syn- and anti-dizinc(II) bis(7,8-capped porphyrins), 11 and 12, respectively, that have almost identical spectroscopic properties. These two geometric isomers were distinguished by significant differences in their molecular recognition properties. Likewise the syn- and anti-dizinc(II) bis(2,3-capped porphyrins), 9 and 10, respectively, are synthesised from the related zinc(II) capped porphyrin-2,3-dione 7, and were also identified using molecular recognition studies. The molecular recognition properties of these bis(capped porphyrins) were utilised in studies of self-replicating porphyrin systems. The results show that tetraazaanthraceno-bis-porphyrins 9-12 can catalyse their own formation but self-replication was not observed. These results highlight the potential that these interesting hosts could have as templates in supramolecular chemistry, synthesis and catalysis.

Full text of DOI:10.1039/b211015f

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The synthesis and studies towards the self-replication of
bis(capped porphyrins)
Pall Thordarson,† Annie Marquis‡ and Maxwell J. Crossley*
School of Chemistry, The University of Sydney, NSW 2006, Australia.
E-mail: m.crossley@chem.usyd.edu.au; Fax: ϩ61 2 9351 3329; Tel: ϩ61 2 9351 2751
Received 11th November 2002, Accepted 20th February 2003
First published as an Advance Article on the web 6th March 2003
Connecting two facially-protected porphyrins was expected to lead to an equal mixture of laterally-bridged doubly-
protected bis-porphyrins; one in which the two porphyrin units were protected on the same face (syn) and one with
the two porphyrin units protected on opposite faces (anti). Addition of a co-factor (bidentate ligand) was expected
to lead predominantly to the syn-bis-porphyrin by a templated self-replication process. This concept was explored
using Baldwin’s capped porphyrin. Bis(capped porphyrins) were synthesised in several steps starting from zinc()
capped porphyrin 2. Nitration of 2 followed by reduction and photo-oxidation yields a mixture of zinc() porphyrin-
diones 7 and 8 that can be separated by HPLC. The condensation of 2 molar eq. of zinc() porphyrin-7,8-dione
8 with 1,2,4,5-benzenetetramine leads to the formation of a 1 : 1 mixture of syn- and anti-dizinc() bis(7,8-capped
porphyrins), 11 and 12, respectively, that have almost identical spectroscopic properties. These two geometric isomers
were distinguished by significant differences in their molecular recognition properties. Likewise the syn- and anti-
dizinc() bis(2,3-capped porphyrins), 9 and 10, respectively, are synthesised from the related zinc() capped
porphyrin-2,3-dione 7, and were also identified using molecular recognition studies. The molecular recognition
properties of these bis(capped porphyrins) were utilised in studies of self-replicating porphyrin systems. The results
show that tetraazaanthraceno-bis-porphyrins 9–12 can catalyse their own formation but self-replication was not
observed. These results highlight the potential that these interesting hosts could have as templates in supramolecular
chemistry, synthesis and catalysis.
and steric restrictions (e.g. a protecting group) around the
binding sites. Considering these features, we have designed
Introduction
The questions surrounding the origins of life remain among
and synthesised four different isomers of a rigid bis(capped
the most challenging questions within Science. Although there
porphyrin) host. These host molecules were designed for use in
are a number of conflicting theories a common point of most
studies of molecular recognition,18,19 self- and complementary-
of the credible ideas1 is that an important transition point
recognition and self-replication.
Our concept for a porphyrin-based self-replicating system
is based on the idea that a syn bis(capped porphyrin) could act
as a template for its own formation in the presence of a
co-factor while in the “background” reaction, in the absence of
co-factor, both the syn-isomer and the anti bis(capped por-
phyrin) would be formed in a 1 : 1 ratio (Fig. 1). Therefore,
between live and inanimate matter was when the first self-
replicating molecule arose from the pre-biotic soup. For this
reason, it is not surprising there have been a number of studies
of artificial self-replication in the laboratory to shed more
light on this important phenomenon. The first artificial self-
replicating system was reported in 1986 by von Kiedrowski,2
soon to be followed by other groups.3–13 Central to the design of
by looking at the final product distribution the extent of self-
any self-replicating system is complementarity between the
replication should be easily determined. This design should be
product (template) and the reagent from which the template
valid for any potentially self-replicating system based on a rigid
is formed. It is this complementarity that distinguishes self-
host and/or guest ligand-mediated recognition of the reactants
replication from other forms of autocatalysis or as Wintner
to the template (product) to give one geometric isomer instead
and Rebek pointed out: “self-replication is a special subset of
of two or more isomers in the absence of the ligand interaction.
autocatalytic reactions in which molecular recognition plays a
role”.14
Designing a system with molecular recognition properties
for applications such as self-replication, depends heavily on the
ability to synthesise well-defined host molecules. As any poten-
tial self-replicating molecule is made up of two or more smaller
sub-units, multi-site hosts (e.g., ditopic) are particularly inter-
esting in this respect. Additionally, multi-site hosts are of great
interest to researchers in supramolecular chemistry as they can
be utilised for such diverse applications as signal magnification
by allosteric interactions15 and templated synthesis.16,17 Some
of the desirable features of a successful multi-site host are a
certain rigidity (to keep the binding sites at a fixed distance)
† Present address: Department of Organic Chemistry, The University
of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
‡ Present address: Laboratoire de Chimie Supramoléculaire ISIS-
Université Louis Pasteur, 8 rue Gaspard Monge, F-67000 Strasbourg,
France.
Fig.
1
Schematic representation of a self-replicating porphyrin
system.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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The compounds developed in this study are derived from the
C2-capped porphyrin 1 which is encumbered on one face. This
compound, and related capped porphyrins, was developed by
Baldwin and co-workers in their studies of reversible oxygen
carriers.20,21 They showed that compounds like the C2-capped
porphyrin 1 could reversibly bind dioxygen and other small
molecules within the cavity when the porphyrin was chelated
with iron and the co-ordination site on the unencumbered face
is ligated.21–23
In studies by Baldwin and co-workers it was also shown that
capped porphyrins can easily be functionalised like ordinary
porphyrins, for instance to introduce a β-pyrrolic nitro or
amino functionality.24,25 In previous work by Crossley and co-
workers porphyrin-2,3-diones, obtained by the photo-oxidation
of 2-aminoporphyrins, have served as the main building block
for more elaborated porphyrin systems such as rigid, laterally-
bridged oligoporphyrins.26–28 Therefore the methodology to
synthesise a capped porphyrin-2,3-dione as the building block
for a bis(capped porphyrin) system was applied. Compared to
previous syntheses of bis- and oligomeric-porphyrins, capped
porphyrins provided two additional challenges. One related
to the sensitivity of the ester-functionality in the capping
superstructure to some reaction conditions that the simpler
porphyrin system can easily tolerate. The other was the
presence of two regioisomers of the substituted capped
porphyrin due to the presence of the capping aryl protons,
requiring separation of these at some stage in the synthetic
scheme. In addition, once the capped porphyrin-diones
were reacted to form bis(capped-porphyrins), two isomers,
the syn- and anti-isomers were formed and had to be separ-
ated. After overcoming these problems, a total of four
different bis(capped porphyrins), two pairs of syn- and
anti-isomers, were obtained. Some of their interesting
molecular recognition properties have been reported pre-
viously,18 here their synthesis and the studies towards the
possible self-replication of these bis(capped porphyrins) will
be discussed.
Scheme 1 Reagents and conditions: a, Zn(OAc)2ؒ2H2O in CH2Cl2–
MeOH, heat, 1 h; b, I2–AgNO2 in CH2Cl2–MeCN; c, NaBH4–Pd–C in
CH2Cl2–MeOH; d, Rose Bengal, O2, hν in CH2Cl2, chromatography
over silica.
The zinc() capped porphyrin-diones 7 and 8 were then
condensed with 1,2,4,5-benzenetetramine26 to give the desired
bis(capped porphyrins). The porphyrin-dione 7 gave a 1 : 1
mixture of syn- and anti-dizinc() bis(2,3-capped porphyrins),
9 and 10, respectively and the porphyrin-dione 8 gave a 1 : 1
mixture of syn- and anti-dizinc() bis(7,8-capped porphyrins),
11 and 12, respectively (Scheme 2). Both reactions were con-
centration dependent and that some demetallation occurred
during the course of the reaction. As these compounds were
required as the dizinc() derivatives, the reaction mixture was
treated with zinc() acetate dihydrate after the initial workup.
The separation and characterisation of these two pairs of
syn- and anti-isomers [bis(2,3- and 7,8-capped porphyrins)] will
now be discussed separately.
Before the two isomers 11 and 12 were separated it was found
beneficial to run the mixture through a size-exclusion column.
This removed all the unreacted starting material resulting in the
isolation of a mixture of 11 and 12. The separation of 11 and 12
was achieved on either a silica column or by preparative HPLC,
the latter method being preferred. The spectroscopic properties
of the two fractions collected were so similar (albeit not ident-
ical) that initially they could not be unambiguously assigned to
the structures of 11 and 12. Assignment of the more polar and
the less polar fractions as 11 and 12, respectively, was achieved
by their molecular recognition properties towards a “molecular
ruler” ligand 1,12-diaminododecane.18 These findings were
reinforced by studies using several different ditopic ligands.19 It
should also be pointed out that the polarity difference and
order of elution of 11 and 12 on a silica column was not
unexpected. Previous work has shown that zinc() porphyrins
are generally more polar on silica than their free-base counter-
parts.28 This implies higher specificity for zinc() porphyrin
interactions towards silica. Based on this, a difference in polar-
ity on silica of 11 and 12 would be expected and could be used
for their tentative assignment as the geometry of the syn-isomer
11 leaves two zinc() molecules (binding sites) exposed to the
Results and discussion
Synthesis
The nitration of 2 following Baldwin’s method,24,25 gave as
expected two zinc() nitro-capped porphyrin regioisomers, 3
and 4. These were reduced24,25 to yield the unstable zinc()
amino-capped porphyrins, 5 and 6, which were photo-oxidised
to give the desired zinc() capped porphyrin-diones, 7 and 8
(Scheme 1). Two different approaches were explored for this
synthesis. In the first, the mixture of 3 and 4 was separated25
and the individual fractions of 3 and 4 were reduced and photo-
oxidised29 to the corresponding porphyrin-diones, 7 from 2 in
17% overall yield and 8 from 2 in 13% yield. Alternatively, the
mixture of 3 and 4 could be reduced and photo-oxidised to
give a 1 : 1 mixture of 7 and 8 which was then separated by
preparative HPLC. The overall yield by this method of 7 from 2
was 26% and that of 8 from 2 was 22%. The latter method
therefore became the method of choice. The difference in yields
between the two methods is due to the reduction and photo-
oxidation steps of 3 and 4 that always leads to some formation
of side-products that need to be removed. It is desirable there-
fore to couple the purification of the porphyrin-diones 7 and 8
with the necessary separation of the two regioisomers formed.
It should also be noted here that the synthesis of 7 and 8 from 3
and 4, respectively, confirmed the assignments of 3 and 4 by
Baldwin and co-workers.29 The two porphyrin-diones 7 and 8
differ in the 1H NMR spectrum as 7 has two chemically
unequivalent capping protons whilst these protons are chem-
ically equivalent in 8. Related compounds obtained by Baldwin
and DeBernardis and reported as 2,13-dioxoporphyrins were
clearly incorrectly assigned by them.24
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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Scheme 2 Reagents and conditions: a, pyridine, N2, heat.
same silica particle unlike the anti-isomer, hence making it more
to be a coincidence, at temperatures above and below 300 K,
tightly bound to the silica support.
two singlets were observed in the capping proton region for the
more polar fraction as expected.
The other pair of bis(capped porphyrins), 9 and 10, which
differ from 11 and 12 by being connected via the 2,3-position
(relative to the capping protons) while 11 and 12 are connected
by the 7,8-position, have some different properties to the
previous pair. The bis(capped porphyrins) 9 and 10 were
first purified by size-exclusion chromatography. Membrane
filtration through a cellulose membrane (0.5 µm), originally
designed to remove foreign particles from the solution prior to
injection on the preparative HPLC column, achieved partial
separation of the two isomers. A precipitate collected on the
membrane of the syringe was washed off with excess chloro-
form. Analytical TLC analysis showed the collected precipitate
to be an almost pure fraction of the less polar isomer. By
repeating the filtration process on this fraction, a pure sample
Development of self-replication methodology
To be able to study a self-replicating system as described above
(Fig. 1) several issues had first to be addressed. One was the
choice of ligand to template the formation of the syn bis-
(capped porphyrins). The molecular recognition studies carried
out on the bis(capped porphyrins) indicated that if a relatively
short bidentate ligand was chosen, a sandwich structure (the
key intermediate in Fig. 1) would result.18,19 Although their
complexation with dizinc() bis-porphyrins does generate
“sandwich” structures, the α,ω-diaminoalkane ligands were
ruled out from the self-replication studies as the primary
amines might well react with the porphyrin-diones. The promis-
ing results obtained from binding studies on the 4,4Ј-bipyridine
ligand 15 with the simpler bis-porphyrin 14 made it a good
candidate.19 The pyridine functionality was known not to cause
problems in reactions with a porphyrin-2,3-dione although the
rigidity of 15 might cause problems as some flexibility in the
proposed “sandwich” complex could be necessary. Therefore,
1,3-bis(4-pyridyl)propane 16 was also chosen as it contains a
flexible linker between the two pyridine functionalities.
It was also necessary to determine how to carry out these
reactions without using pyridine (that would otherwise block
all the binding sites). To do this, preliminary studies were
carried out on the simpler zinc() porphyrin-dione 13 and di-
zinc() bis-porphyrin26 14. Pyridine had served the dual roles of
solvent and base to liberate 1,2,4,5-benzenetetramine from its
tetrahydrochloride salt form in situ. The obvious approach was
to liberate and isolate the 1,2,4,5-benzenetetramine§ first and
to carry the condensation reaction out in a different solvent.
Liberated 1,2,4,5-benzenetetramine was immediately added
to a solution of the zinc() porphyrin-dione 13 in dichloro-
methane in the presence of molecular sieves. The solution was
stirred at room temperature for 7 days to give the dizinc()
1
of the less polar isomer was obtained, identical by H NMR
spectroscopy to samples of less polar fractions obtained later
by preparative HPLC. The filtrate obtained from the membrane
filtration was, however, always a mixture of the two isomers 9
and 10, with the more polar isomer in large excess. The mem-
brane filtration technique, therefore, relies on the low solubility
of the less polar isomer in chloroform. The filtrate was then
separated by preparative HPLC and two fractions were col-
lected. The spectroscopic properties of the two fractions were
almost identical with the result that they could not be assigned
to the structures of 9 and 10. As detailed elsewhere,19 molecular
recognition studies did later allow the unambiguous assignment
of the more polar and less polar fractions as 9 and 10, respect-
ively, again in agreement with their expected difference in polar-
ity on silica. The two compounds 9 and 10 showed some inter-
esting differences. The less polar fraction (later assigned as 10)
did not only have much lower solubility in common organic
solvents than the more polar fraction but, for reasons not
understood, repetitively failed to give satisfactory results from
microanalysis. Despite this all the other spectroscopic data were
in agreement with the expected structure of 10 (or 9). The more
polar fraction (later assigned as 9) showed only one singlet for
the capping protons at 300 K, not two as expected and shown
for the other isomer. Variable temperature studies showed this
§ Sensitive to moisture and oxygen.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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Table 1 Yields of bis-porphyrin 14 after 3 days from the reaction of
1,2,4,5-benzenetetramine tetrahydrochloride and porphyrin-dione 13 in
the presence of different bases (ligands)
Entry
Template
Base 1
Base 2
Et3N
Yield (%)
1
2
3
4
5
No
16
16
35
49
<5
19
11
Yesa
No
16
Yesa
No
None
None
a 0.5 Eq. of bis-porphyrin 14 was added (yields are then net yields).
Self-replication studies on bis(capped porphyrins)
Because of the solubility problems encountered with the anti-
dizinc() bis(2,3-C2-capped porphyrin) 10, as detailed above,
the focus in this work was on the syn- and anti-dizinc() bis-
(7,8-C2-capped porphyrins), 11 and 12.
Continuing from the preliminary studies outlined above, the
zinc() C2-capped porphyrin-7,8-dione 8 and 1,2,4,5-benzene-
tetramine tetrahydrochloride were reacted together in chloro-
form in the presence of the 1,3-bis(4-pyridyl)propane 16 ligand.
Dizinc() bis(7,8-C2-capped porphyrins) were not observed in
the reaction mixture after 16 days.
In light of this result and the problems encountered earlier
with the liberation of 1,2,4,5-benzenetetramine tetrahydro-
chloride, the approach was modified. Instead of trying to use
the 1,2,4,5-benzenetetramine tetrahydrochloride together with
zinc() C2-capped porphyrin-7,8-dione 8, in the presence of the
ligand and an appropriate solvent, the process was separated
into two steps. First the zinc() C2-capped 6Ј,7Ј-diamino-
quinoxalino-porphyrin 17 was formed and then it was added to
a solution of 8 (in a 1 : 1 ratio) in the presence of the desired
ligands and templates.
Scheme 3
bis-porphyrin 14 in 11% yield (Scheme 3). These results were
not encouraging, so a different approach was desirable.
Using lithium hydroxide was also ruled out as a trial reaction
on the zinc() C2-capped porphyrin-7,8-dione 8 in chloroform
at room temperature failed to give the desired product and
showed that the ester groups of the starting material had been
completely hydrolysed by the base. This meant that a milder
method would be necessary to liberate the 1,2,4,5-benzene-
tetramine in situ. One option here would be to see if the ligands
15 and 16 themselves could be efficient as bases in liberating
the 1,2,4,5-benzenetetramine tetrahydrochloride. To test this,
the reaction between zinc() porphyrin-dione 13 and 1,2,4,5-
benzenetetramine tetrahydrochloride in chloroform was per-
formed in the presence of the ligand 16. The results were
compared to those obtained in the absence of the ligands
15 and 16, and also in the presence of the ligand with triethyl-
amine (Et3N) base (Table 1).
These results showed that the ligand 16 would act as the base
in the reaction to give 14 in considerably higher yields than in
the absence of a ligand (35% vs. 11%) that in turn were higher
than in the presence of Et3N and the ligand 16. No explanation
could be found for the latter observation. Interestingly, addition
of the template (product), dizinc() bis-porphyrin 14, seemed to
significantly increase the yield of 14. It appeared to either act as
a base, or to catalyse the reaction. These results hint that the
tetraazaanthracene-bridge in the structure of 14 could act as
a base to liberate 1,2,4,5-benzenetetramine in situ.
The zinc() C2-capped 6Ј,7Ј-diaminoquinoxalino-porphyrin
17 was synthesised by treating the zinc() C2-capped porphyrin-
7,8-dione 8 with excess 1,2,4,5-benzenetetramine tetrahydro-
chloride in refluxing pyridine for 20 h. As some demetallation
had occurred in removing the pyridine in the workup, the
mixture was remetallated with zinc() acetate dihydrate in
refluxing dichloromethane–methanol. The polar product was
then purified quickly by flash silica chromatography to give the
crude 17 product in 66% yield (Scheme 4).
The product 17 was unstable and therefore used quickly
without extensive purification. Characterisation by techniques
1
1
other than H NMR spectroscopy was not attempted. Its H
NMR spectrum showed the expected amine protons as a broad
peak around 2.8 ppm and the β-pyrrolic protons in the 8.7–8.9
ppm region with the expected pattern of a ABq system and a
singlet.
Once zinc() C2-capped 6Ј,7Ј-diaminoquinoxalino-porphyrin
17 was obtained, self-replication studies were performed. These
studies were conducted in a manner allowing comparison for
experiments under different conditions to be made with some
confidence using stock solutions of the main reagents in dry,
deacidified chloroform. The ligands used were 4,4Ј-bipyridine
15, 1,3-bis(4-pyridyl)propane 16 and pyridine. The appropriate
ligands and templates were mixed and diluted to a constant
volume and then stirred for several days while monitored by
analytical HPLC and 1H NMR spectroscopy. After 7 days, the
products were purified by size-exclusion chromatography and
analysed by 1H NMR spectroscopy. The products obtained
from the size-exclusion chromatography were not further
purified and the yields reported therefore only indicative.
Furthermore, it was noted that some of the anti-isomer 12 was
lost in the workup in preference to the syn-isomer 11. Based on
this observation, only the product distributions obtained from
analysing the reaction product (before size-exclusion chrom-
atography) are reported here. The templates used in these
These preliminary studies on the simple zinc() porphyrin-
dione 13 gave an indication of what could be expected in
self-replication studies on bis(C2-capped porphyrins). Particu-
larly, these studies highlighted the difficulties associated with
the liberation of the 1,2,4,5-benzenetetramine tetrahydrochlor-
ide. These results also showed that secondary unexpected
effects, such as the product acting as a base, might create
ambiguity in these studies.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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Table 2 Product distribution and crude yields (upper limit) for the reaction between 8 and 17 in the presence of various ligands and templates
Product after 7 daysa
HPLC
NMR
Ratio of 12/11 (anti/syn)
b
b
Entry
Ligand
Template
anti (%)
syn (%)
anti (%)
syn (%)
3 days
7 days
7 daysc
Yield (%)
1
2
3
4
5
6
7
8
9
None
None
Pyridine
Pyridine
15
None
14
None
None
None
None
None
75
73
25
27
78
72
60
74
86
68
94
82
85
83
70
22
28
40
26
14
32
6
18
15
17
30
3.3
3.3
3.0
2.7
38
28
47
31
36
38
53
15
71
36
54
1.5d
4.6
82
18
4.6
4.9d
2.1d
11.5d
5.3
16
16
16
14
84
92
84
73
16
8
16
27
10.1
32.3e
13.3
2.7e
16
12 (anti 7,8)
9 (syn 2,3)
11 (syn 7,8)
11.5e
5.3
4.3
8.1
10
11
16
16
2.7e
a The values for anti and syn refer to anti- and syn-bis(capped porphyrins), 12 and 11, respectively, as measured by HPLC or 1H NMR spectroscopy.
b Ratio of anti-/syn-bis(capped porphyrins), 12 : 11, formed measured by analytical HPLC. Data not corrected for amounts of template present.
c Ratio of anti-/syn-bis(capped porphyrins), 12 : 11, formed measured by 1H NMR and corrected for the amount of template present. d Ratio of anti-/
syn-bis(capped porphyrins), 12 : 11, formed measured by 1H NMR. e Note that the template is the same as one of the products.
Scheme 4
reactions were the anti- and syn-dizinc() bis(7,8-C2-capped
porphyrins), 12 and 11 as well as the syn dizinc() bis(2,3-C2-
capped porphyrin) 9 and dizinc() bis-porphyrin 14. The results
from these experiments are summarised in Table 2.
anti-isomer 12 than for the syn-isomer 11). Of the two options,
kinetic factors are more likely, as there are different product
distributions at different temperatures. To try to determine
the effect of temperature on the reactions, the reaction to form
11 and 12 was tested in pyridine at room temperature.
Unfortunately, no product was obtained so no direct com-
parison in pyridine was possible.
The reason the anti-isomer 12 might form faster (kinetically)
than the syn-isomer 11 at room temperature is likely to be some
steric hindrance between the two caps in the initial steps in one
of the pathways to the formation of the syn-isomer, which is
absent in the formation of the anti-isomer (Fig. 2).
At elevated temperatures, the thermal energy is enough to
overcome this kinetic barrier for the formation of the syn-
isomer 11, leading to the observed 1 : 1 product ratio. The
relatively small effects of the templates leading to an increase in
the relative amounts of anti-isomer 12 remain unexplained.
Studies towards self-replication at elevated temperatures are
currently in progress.
These results indicate that self-replication did not occur, at
least not according to the scenario outlined in Fig. 1. In every
reaction more of the anti dizinc() bis(7,8-C2-capped por-
phyrin) 12 was formed than the corresponding syn-isomer 11.
Even in reactions when no ligand was present (entries 1–2
in Table 2) or when pyridine was the ligand (entries 3–4 in
Table 2), the anti-isomer 12 was formed in 2 : 1 up to 5 : 1 ratio
to the syn-isomer 11. This indicates that under these conditions,
the assumption that the “background” reaction (Fig. 1) gives a
1 : 1 mixture of 12 and 11 is no longer valid. One trend observed
in these results (Table 2) is that the 12 : 11 ratio seems slightly
higher (i.e. more 12) in cases when a ligand or template is
present.
These results also indicate that the ratio of the anti-isomer 12
to the syn-isomer 11 is higher after 3 days than after 7 days
when a template and a ligand is present. Note that this also
suggests that the anti-isomer 12 is acting as the template but
according to the initial self-replication model (Fig. 1) the anti-
isomer 12 should not catalyse its own formation. Changing the
solvent from chloroform to toluene did not change the product
distribution greatly; the anti-isomer 12 was always formed in
preference to the syn-isomer 11 (results not shown).
The conclusion from these studies is that changing the
solvent and temperature from refluxing pyridine changes the
product distribution so that the syn- and anti-isomers 11 and 12
are no longer formed in a 1 : 1 ratio. These results are difficult
to explain but kinetic effects offer an explanation. Thermo-
dynamic effect cannot be ruled out either, as the products 11
and 12 are not necessarily equal in energy (∆Gformation) even
though they are structural isomers (force field calculations30
indicate that the heat of formation is 15 kJ molϪ1 lower for the
Conclusions
The synthesis of the four facially protected bis(capped
porphyrins) 9–12 based on our earlier methodology for the
synthesis of rigid, laterally-bridged bis-porphyrins has been
shown to proceed in a similar fashion to the simpler bis-
porphyrins (such as 14) if challenges with separation of all the
possible different stereoisomers are excluded. This demon-
strates the usefulness of this approach to multi-porphyrin
arrays. The bis(capped porphyrins) described here have already
been shown to have interesting molecular recognition proper-
ties.18,19 Studies described here to utilise these compounds as the
basis for a self-replicating porphyrin system were inconclusive.
These studies did indicate that these bis(capped porphyrins)
could act as catalysts for their own formation; however, whether
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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Fig. 2 The proposed key intermediate in the mechanism for the formation of anti- and syn-bis(capped porphyrins), 12 and 11, from 17 and 8
indicating the steric hindrance in the formation of 11. Note that the last step, aromatisation of the tetraazaanthracene-bridge (not shown), is the only
irreversible step and the two units can rotate freely around the hemiaminal-linkage.
they can truly act as templates or are capable of unequivocal
self-replication remains to be determined. While these systems
do not show signs of self-replication, other uses of the
bis(capped porphyrins) can be envisaged such as acting as co-
factors for other types of templated synthesis and templated
catalyses and as substrates for self- and complementary
recognition studies.
compared with the maximum of a simulated spectrum. Electro-
spray ionisation (ESI) mass spectra were recorded on a
ThermoQuest Finnigan LCQ Deca mass spectrometer. High
resolution fast atomic bombardment (HRFAB) mass spectra
were acquired at the Research School of Chemistry, Australian
National University. The HRFAB mass spectra were obtained
as an envelope of the isotope peaks of the molecular ion and
calibrated against an external CsI standard. For heavy mole-
cules (> 2000 amu) the mass of individual peaks in the envelope
were reported and compared to a simulated spectrum. Fourier
transform matrix assisted laser desorption ionisation time of
flight (FT-MALDI-TOF) were acquired at the School of
Chemistry, The University of New South Wales.
Column chromatography with flash silica was performed
using Merck silica gel 60, Type 9385 (230–400 mesh) with the
stated solvent systems. Analytical thin layer chromatography
(TLC) was performed on Merck silica gel 60 F254 precoated
sheets (0.2 mm) in the stated solvents. Preparative TLC plates
(1 mm thick) were prepared from a slurry of Merck silica gel 60,
Type 7747 in water according to instructions from the
manufacturer. Alumina refers to Merck aluminium oxide 90
active neutral I, Type 1077 (63–200 mesh). Class IV alumina
refers to the water content (10% water added).31 Analytical
alumina TLC was performed on Merck alumina 60 F254 pre-
coated sheets (0.2 mm) in the stated solvents. Size-exclusion
chromatography was conducted using gravity feed columns
containing BioBeads (S–X1 polystyrene based size-exclusion
particles) using toluene as the eluent. Analytical high perform-
ance liquid chromatography (HPLC) was performed with a
Waters 510EF pump, U6K injector and a 490E multiwave-
length detector (set at wavelengths 280 and 428 nm) controlled
by Millennium software. The column used was Zorbax RX-SIL
(4.6 mm id × 250 mm) eluting at a rate of 1.5 cm3 minϪ1 in the
stated solvent systems. Preparative HPLC was performed with
a Waters 510EF pump, U6K injector, a Waters 481 ultraviolet
detector (set at a wavelength of 280 nm) and a Waters
R403 refractive index detector. The columns used were
either a Whatman Partisil M20 10/50 (22 mm id × 50 mm) or
Zorbax RX-SIL (21.2 mm id × 25 mm, 7 µm particle size).
Experimental
General remarks
Melting points were recorded on a Reichert melting point stage
microscope and are uncorrected. Microanalyses were per-
formed by the Campbell Microanalytical Laboratory, The
University of Otago, New Zealand. Infrared spectra were
recorded on chloroform solutions with a Perkin-Elmer Model
1600 FT-IR spectrophotometer. Electronic absorption spectra
were recorded on a Cary 5E UV–vis spectrophotometer at
1
25 ЊC. H NMR spectra were recorded on a Bruker AC-200F
(200 MHz), a Bruker DRX-400 (400 MHz) or a Bruker DPX-
400 (400 MHz) spectrometer and signals are quoted in ppm
relative to tetramethylsilane (SiMe4, 1H and 13C = 0 ppm) or the
solvent residue peak (CDCl3; 1H = 7.26 and 13C = 77.16 ppm) as
the internal standard. Temperature was controlled by a Bruker
B-VT 2000 variable temperature unit. For spectra recorded at
temperatures other than 300 K either tetramethylsilane or a
residual “silicon grease” peak (1H = 0.07 ppm) were used as
internal references. 13C NMR spectra were acquired on either a
Bruker AC-200F (50 MHz) or a Bruker DPX-400 (100 MHz)
spectrometer as stated and are reported as the fully decoupled
spectra assigned with the aid of DEPT analysis.
Matrix assisted laser desorption ionisation time of flight
(MALDI-TOF) mass spectra were recorded on a VG TofSpec
spectrometer. For most porphyrins under study, no matrix was
required but when necessary α-cyano-4-hydroxycinnamic acid
was used as the matrix. Mass spectra were obtained as an
envelope of the isotope peaks of the molecular ion. The mass
corresponding to the envelope’s maximum is reported and was
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
1221

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The solvent systems used were as stated eluting at a rate of 13.5
cm3 minϪ1
for conversion from a mixture of 3 and 4)] contaminated with
.
porphyrin 2 (15%) as a dark brown–green–purple solid, mp >
1
Light petroleum refers to the fraction of bp 60–80 ЊC.
Chloroform and dichloromethane were typically distilled from
potassium carbonate prior to use as HPLC solvents. Other
chemicals were used as obtained from commercial sources.
The synthesis of [5,5Ј,10,10Ј,15,15Ј,20,20Ј-octakis(3,5-di-
tert-butylphenyl)-1Љ,4Љ,6Љ,9Љ-tetraazaanthraceno[2,3-b:2Ј,3Ј-e]-
bisporphyrinato]dizinc() 14 was carried out according to a
previously published procedure.26
300 ЊC. The H NMR spectrum showed a 1 : 1 mixture of 7
and 8.
A portion of the crude mixture of 7 and 8 (54 mg) was separ-
ated by preparative HPLC (dichloromethane–methanol; 100 :
0.5). Samples (25–30 mg) of the above mixture in chloroform
(1.0 cm3) were applied to the column. A less polar fraction (Rt =
16–21 min) and a more polar fraction (Rt = 30–54 min) was
collected.
The combined less polar fractions (which have a bronze hue)
yielded 8 (17.6 mg, 65% recovery of this isomer) as a brown–
red–purple solid, mp > 300 ЊC (Found: C, 64.2; H, 3.45; N, 4.7.
C62H40N4O14Zn ϩ 0.5 CH2Cl2 requires C, 64.0; H, 3.5; N,
4.8%); νmax (CHCl3)/cmϪ1 2931, 2849, 1731, 1602, 1578, 1490,
1443, 1337, 1284 and 1243; λmax (CHCl3)/nm 416.5 (log ε 5.14),
493 (4.28), 613.5sh (3.51), 638.5sh (3.68) and 713.5 (3.75);
δH (400 MHz, CDCl3) 3.84 (2 H, ddd, J = 11.5, 6.1 and 2.2,
CH2), 4.06–4.45 (12 H, m, CH2), 4.64–4.72 (2 H, m, CH2), 5.81
(2 H, s, capping H), 7.24 (2 H, ddd, J 7.5, 7.4 and 0.8, Ar–H5),
7.31 (2 H, dd, J 8.0 and 0.9, Ar–H3), 7.35 (2 H, ddd, J 7.5, 7.4
and 0.8, Ar–H5), 7.42 (2 H, dd, J 8.4 and 0.8, Ar–H3), 7.46 (2 H,
dd, J 7.5 and 1.6, Ar–H6), 7.66 (2 H, ddd, J 8.4, 7.4 and 1.6,
Ar–H4), 7.72 (2 H, ddd, J 8.0, 7.4 and 1.7, Ar–H4), 7.80 (2 H,
dd, J 7.5 and 1.7, Ar–H6), 8.30 and 8.48 (4 H, ABq, J 4.7,
β-pyrrolic H-2, H-3, H-12 and H-13) and 8.40 (2 H, s, β-pyr-
rolic H-17 and H-18); δC (100 MHz, CDCl3) 62.68 (4 × CH2),
66.46 (2 × CH2), 68.20 (2 × CH2), 110.12 (2 × meso-C), 113.32
(2 × Ar–CH), 116.54 (2 × Ar–CH), 120.88 (2 × Ar–CH), 121.49
(2 × Ar–CH), 122.39 (2 × meso-C), 127.19 (2 × capping
Ar–CH), 129.47 (2 × Ar–CH), 130.13 (2 × Ar–CH), 130.19 (2 ×
β-pyrrolic CH), 131.19 (2 × β-pyrrolic CH), 131.30 (2 × Ar–C),
130.51 (2 × Ar–C), 131.82 (2 × α-pyrrolic C), 131.89 (2 ×
β-pyrrolic CH), 133.92 (2 × capping Ar–C), 135.27 (2 ×
Ar–CH), 135.59 (2 × Ar–CH), 138.17 (2 × capping Ar–C),
149.16 (2 × α-pyrrolic C), 150.44 (2 × α-pyrrolic C), 154.14
(2 × α-pyrrolic C), 157.36 (2 × Ar–C), 157.38 (2 × Ar–C),
Synthesis and separation of [2-nitro-5,10,15,20-[pyromellitoyl-
(tetrakis-o-oxyethoxyphenyl)]porphyrinato]zinc(II) 3 and
[7-nitro-5,10,15,20-[pyromellitoyl(tetrakis-o-oxyethoxy-
phenyl)]chlorinato]zinc(II) 4 mixture
Starting from C2-capped porphyrin20,21,32 1 the mixture of the
two isomeric zinc() nitro-C2-capped porphyrins 3 and 4 was
obtained in 94% yield following the method of Baldwin and
co-workers.20,21,24,25 The crude mixture of the two isomeric
zinc() nitro-C2-capped porphyrins 3 and 4 (260 mg) was separ-
ated by preparative HPLC (toluene–ethyl acetate; 17 : 3).25 The
combined less polar fractions were evaporated to give 4 (92 mg,
71% recovered of this isomer) which co-chromatographed with
an authentic sample and had an identical 1H NMR spectrum to
that reported in the literature.25 The combined more polar
fractions were evaporated to give 3 (100 mg, 77% recovered of
this isomer) which co-chromatographed with an authentic
sample and had an identical 1H NMR spectrum to that
reported in the literature.25
Synthesis and separation of [2,3-dioxo-5,10,15,20-[pyromellitoyl-
(tetrakis-o-oxyethoxyphenyl)]chlorinato]zinc(II) 7 and
[7,8-dioxo-5,10,15,20-[pyromellitoyl(tetrakis-o-oxyethoxy-
phenyl)]chlorinato]zinc(II) 8 mixture
Method 1. A mixture of 3 and 4 (389 mg, 0.340 mmol) was
dissolved in a mixture of dry dichloromethane (40 cm3) and dry
methanol (30 cm3) under an argon atmosphere in a round
bottom flask (100 cm3) shielded from light. The solution was
purged with argon for 20 min and then 10% palladium on
carbon (281 mg) was added. Sodium borohydride (305 mg, 8.06
mmol) was added in portions over 5 min. The reaction mixture
was stirred and monitored by TLC analysis (the product
appeared as a reddish spot just underneath the green starting
material). After 7 min, when all the starting material had been
consumed, the mixture was filtered through a small plug of
celite and the filtrate evaporated to dryness. The resultant solid
was dissolved in dichloromethane (100 cm3) and then washed
with water (100 cm3). The aqueous layer was extracted with
dichloromethane (2 × 30 cm3) and the combined organic layers
were dried over anhydrous sodium sulfate and filtered to yield
the crude mixture of 5 and 6. [This compound was unstable and
converted slowly to 7 and 8 upon standing. A reasonably pure
sample of the mixture of zinc() 2- and 7-amino-C2-capped
porphyrins 5 and 6 was obtained by column chromatography
over flash silica (dichloromethane–methanol; 100 : 1) to give a
dark green-purple solid, mp > 300 ЊC. νmax (CHCl3)/cmϪ1 3389,
3013, 2931, 2872, 1731, 1614w, 1578, 1490, 1443, 1378, 1337,
1320, 1284 and 1243; λmax (CHCl3)/nm 407.5sh (log ε 4.94), 423
(5.19), 473.5 (4.16), 553 (3.95), 603 (3.66) and 653 (3.52); m/z
(MALDI-TOF) 1114.3 (simulated maximum requires 1114.7).
The mixture of 5 and 6 was immediately diluted with di-
chloromethane (to 250 cm3) and photo-oxidised. The reaction
was monitored by TLC analysis. Rose Bengal (5 mg) was added
to the solution and after 1 h more Rose Bengal (5 mg) was
added. After 2.5 h, no starting material remained and the
solvent was removed under vacuum and the residue purified by
column chromatography over flash silica (dichloromethane–
methanol; 100 : 0.75). The main fraction yielded a mixture
(310 mg) of the products 7 and 8 [267 mg, 69% (yield calculated
163.52 (4 × C᎐O) and 188.03 (2 × β-pyrrolic C-7 and C-8); m/z
᎐
(FT-MALDI-TOF) 1129.36 (simulated maximum requires
1129.3); m/z (MALDI-TOF) 1129.9 (simulated maximum
requires 1129.3); m/z (ESI) 1151.0 (M(Zn64)ϩϩNaϩ requires
1151.2), 1130.0 (M(Zn66)ϩ requires 1130.2).
The combined more polar fractions (which have a brown
hue) yielded 7 (20.4 mg, 76% recovery of this isomer) as a
brown–green–purple solid, mp > 300 ЊC (Found: C, 65.7; H,
3.4; N, 5.05. C62H40N4O14Zn requires C, 65.9; H, 3.6; N, 5.0%);
νmax (CHCl3)/cmϪ1 2932, 2851, 1726, 1601, 1581, 1490, 1445,
1339, 1264 and 1244; λmax (CHCl3)/nm 417 (log ε 5.12), 501
(4.30), 605.5sh (3.34), 652.5sh (3.53) and 735 (3.76); δH (400
MHz, CDCl3) 3.85–3.93 (2 H, m, CH2), 4.08–4.45 (14 H, m,
CH2), 5.82 (1 H, s, capping H), 6.37 (1 H, s, capping H), 7.24
(2 H, ddd, J 7.6, 7.4 and 0.8, Ar–H5), 7.34 (2 H, ddd, J 7.6, 7.4
and 0.9, Ar–H5), 7.40 (2 H, dd, J 8.7 and 0.8, Ar–H3), 7.43 (2 H,
dd, J 8.8 and 0.9, Ar–H3), 7.47 (2 H, dd, J 7.4 and 1.6, Ar–H6),
7.67 (2 H, ddd, J 8.8, 7.4 and 1.8, Ar–H4), 7.72 (2 H, ddd, J 8.7,
7.4 and 1.6, Ar–H4), 7.74 (2 H, dd, J 7.6 and 1.8, Ar–H6), 8.26
and 8.45 (4 H, ABq, J 4.7, β-pyrrolic H-7, H-8, H-17 and H-18)
and 8.33 (2 H, s, β-pyrrolic H-12 and H-13); δC (100 MHz,
CDCl3) 62.80 (2 × CH2), 63.27 (CH2), 63.46 (CH2), 67.38
(2 × CH2), 68.46 (2 × CH2), 110.80 (2 × meso-C), 115.44 (2 ×
Ar–CH), 116.40 (2 × Ar–CH), 121.45 (2 × Ar–CH), 121.70
(2 × Ar–CH), 122.54 (2 × meso-C), 126.84 (capping Ar–CH),
127.51 (capping Ar–CH), 129.17 (2 × Ar–C), 129.76 (2 × Ar–
CH), 130.23 (2 × Ar–CH), 130.47 (2 × β-pyrrolic CH), 130.65
(2 × β-pyrrolic CH), 131.52 (2 × Ar–C), 132.02 (2 × α-pyrrolic
C), 132.70 (2 × β-pyrrolic CH), 133.44 (2 × capping Ar–C),
134.36 (2 × Ar–CH),135.70 (2 × Ar–CH), 137.90 (2 × capping
Ar–C), 149.30 (2 × α-pyrrolic C), 150.42 (2 × α-pyrrolic C),
154.39 (2 × α-pyrrolic C), 157.24 (2 × Ar–C), 157.35 (2 ×
Ar–C), 163.04 (2 × C᎐O), 163.89 (2 × C᎐O) and 188.77 (2 ×
᎐
᎐
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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β-pyrrolic C-2 and C-3); m/z (FT-MALDI-TOF) 1130.37
(simulated maximum requires 1129.3); m/z (MALDI-TOF)
1129.7 (simulated maximum requires 1129.3); m/z (ESI) 1130.9
(M(Zn66)ϩ requires 1130.2), 1128.7 and 1128.0 (M(Zn64)ϩ
requires 1128.2).
analysed by TLC and showed a major band of the less polar
fraction with minor contamination of the more polar fraction.
The washings were sonicated and then applied on the HPLC
column as above.
The less polar fractions were evaporated to give the anti-
isomer 10 (1.07 mg, 74% recovery of this isomer) as a brown–
purple solid, mp > 300 ЊC. νmax (CHCl3)/cmϪ1 3506, 2931, 2860,
1731, 1602, 1578, 1490, 1443, 1337, 1279 and 1243; λmax
(CHCl3)/nm 426 (log ε 5.39), 457 (5.24), 515.5sh (4.68), 548
(4.70), 604.5sh (4.08) and 678.5 (4.16); δH (600 MHz, CDCl3)
3.92–3.97 (8 H, m, CH2), 4.30–4.38 (8 H, m, CH2), 4.40–4.45
(4 H, m, CH2), 4.45–4.50 (4 H, m, CH2), 4.51–4.55 (4 H, m,
CH2), 4.60–4.65 (4 H, m, CH2), 5.59 (2 H, s, capping H), 5.62
(2 H, s, capping H), 7.41 (4 H, ddd, J 7.3, 7.2 and 0.8, Ar–H5 at
C10,15), 7.49 (4 H, ddd, J 7.7, 7.1 and 0.6, Ar–H5 at C5,20), 7.58
(4 H, dd, J 8.7 and 0.8, Ar–H3 at C10,15), 7.72 (4 H, dd, J 7.1 and
1.5, Ar–H6 at C5,20), 7.81 (4 H, ddd, J 8.7, 7.3 and 1.6, Ar–H4 at
C10,15), 7.85 (4 H, dd, J 7.2 and 1.6, Ar–H6 at C10,15), 7.87 (4 H,
dd, J 8.7 and 0.6, Ar–H3 at C5,20), 8.13 (4 H, ddd, J 8.7, 7.7 and
1.5, Ar–H4 at C5,20), 8.72 (4 H, s, β-pyrrolic H-12 and H-13),
8.84 (2 H, s, bridging H-5Љ and H-10Љ), 8.90 and 8.98 (8 H,
ABq, J 4.5, β-pyrrolic H-7, H-8, H-17 and H-18); m/z (LRFAB)
2326.6 (simulated maximum requires 2326.5); m/z (MALDI-
TOF) 2327.3 (simulated maximum requires 2326.5).
The more polar fractions were evaporated to give the syn-
isomer 9 (1.15 mg, 80% recovery of this isomer) as a red–purple
solid, mp > 300 ЊC (Found: C, 66.15; H, 3.65; N, 6.9.
C130H82N12O16Zn2 ϩ 0.5 CH2Cl2 requires C, 66.15; H, 3.5; N,
7.1%); νmax (CHCl3)/cmϪ1 3433, 2925, 2852, 1730, 1600, 1491,
1455, 1278 and 1237; λmax (CHCl3)/nm 427.5 (log ε 5.44), 459.5
(5.32), 495sh (4.58), 539.5 (4.71), 614sh (4.16), 678.5 (4.23) and
681 (4.23); δH (600 MHz, CDCl3) 3.92–3.98 (8 H, m, CH2),
4.29–4.37 (8 H, m, CH2), 4.45–4.55 (12 H, m, CH2), 4.60–4.64
(4 H, m, CH2), 5.61 (4 H, s, capping H), 7.41 (4 H, ddd, J 7.8,
7.1 and 0.9, Ar–H5 at C10,15), 7.49 (4 H, ddd, J 7.7, 7.1 and 0.9,
Ar–H5 at C5,20), 7.57 (4 H, dd, J 8.7 and 0.9, Ar–H3 at C10,15),
7.71 (4 H, dd, J 7.1 and 1.6, Ar–H6 at C5,20), 7.80 (4 H, ddd,
J 8.7, 7.8 and 1.6, Ar–H4 at C10,15), 7.85 (4 H, dd, J 7.1 and 1.6,
Ar–H6 at C10,15), 7.87 (4 H, dd, J 8.8 and 0.9, Ar–H3 at C5,20),
8.14 (4 H, ddd, J 8.8, 7.7 and 1.6, Ar–H4 at C5,20), 8.72 (2 H, s,
β-pyrrolic H-12 and H-13), 8.83 (2 H, s, bridging H-5Љ and
H-10Љ), 8.89 and 8.97 (8 H, ABq, J 4.4, β-pyrrolic H-7, H-8,
H-17 and H-18); m/z (HRFAB) Envelope (Mϩ requires):
2322.45/22% (2322.42/33%), 2323.45/48 (2323.418/50), 2324.47/
60 (2324.416/80), 2325.45/80 (2325.417/89), 2326.46/90
Method 2 for the synthesis of 8. Porphyrin 4 (62 mg, 0.054
mol) was reduced to give crude 6 using sodium borohydride
as in Method 1 and 6 was then immediately dissolved in
dichloromethane (300 cm3) and photo-oxidised. The reaction
was monitored by TLC analysis and after 3 h when no starting
material remained, the solvent was removed. The residue was
purified by two preparative TLC plates (20 cm × 20 cm × 1 mm)
using toluene–ethyl acetate (7 : 3) as the solvent system.
Dichloromethane–methanol (100 : 3) was used to extract the
compound from the silica. The main band yielded 8 [22 mg,
36% (yield calculated for conversion from 4)], which
co-chromatographed with and had identical spectroscopic
properties to the compound obtained by Method 1.
Method 2 for the synthesis of 7. Porphyrin 3 (18 mg,
0.016 mol) was reduced to give crude 5 using sodium
borohydride as in Method 1 and 5 was then immediately
dissolved in dichloromethane (300 cm3) and photo-oxidised.
The reaction was monitored by TLC analysis and after 4 h
when no starting material remained, the solvent was removed.
The residue was purified by column chromatography over flash
silica (ethyl acetate–toluene; 1 : 1) to yield zinc() C2-capped
porphyrin-2,3-dione 7 [8 mg, 45% (yield calculated for con-
version from 3)], which co-chromatographed with and had
identical spectroscopic properties to the compound 7 obtained
by Method 1.
Synthesis and separation of syn- and anti-[5,5Ј,10,10Ј,15,15Ј,-
20,20Ј-di[pyromellitoyl(tetrakis-o-oxyethoxyphenyl)]-1Љ,4Љ,6Љ,9Љ-
tetraazaanthraceno[2,3-b:2Ј,3Ј-e]bisporphyrinato]dizinc(II)
9 and 10
A flask containing a mixture of 7 (40 mg, 0.035 mmol) and
1,2,4,5-benzenetetramine tetrahydrochloride (6.8 mg, 0.024
mmol) under a nitrogen atmosphere was charged with dry
pyridine (10 cm3) which had previously been degassed with
nitrogen by cannula. The reaction was shielded from light and
the mixture heated at reflux for 3 days. The mixture was diluted
with toluene (70 cm3) and dichloromethane (20 cm3) and the
solvents removed. The crude residue was dissolved in toluene
(100 cm3) and the solvent removed again. Then the residue was
dissolved in dichloromethane (75 cm3), heated to reflux and a
solution of zinc() acetate dihydrate (17 mg, 0.077 mmol) in
methanol (15 cm3) was added. The mixture was heated at reflux
for 30 min. The solvents were removed and the residue was
dissolved in a mixture of dichloromethane–methanol (9 : 1) and
filtered through a plug of flash silica and the solvent removed.
The crude mixture was purified by column chromatography
over flash silica (chloroform changing to chloroform–methanol;
100 : 6) giving several fractions. The solvent was removed and
the fractions purified by BioBeads size-exclusion chromato-
graphy (2.5 cm id × 90 cm, toluene) to give a crude mixture of
syn and anti dizinc() bis(2,3-C2-capped porphyrins) 9 and
10 (29 mg, 70%) as a dark brown-purple solid, mp > 300 ЊC.
The 1H NMR spectrum showed a 1 : 1 mixture of 9 and 10 (see
below). m/z (MALDI-TOF) 2326.9 (simulated maximum
requires 2326.5).
(2326.416/100),
2327.45/100
(2327.416/94),
2328.46/98
(2328.416/80), 2329.46/67 (2329.416/60), 2330.46/49 (2330.416/
40) and 2331.44/29 (2331.416/29); m/z (ESI) 2326.4 (simulated
maximum requires 2326.5); m/z (MALDI-TOF) 2326.7
(simulated maximum requires 2326.5).
Synthesis and separation of syn- and anti-[5,5Ј,10,10Ј,15,15Ј,-
20,20Ј-di[pyromellitoyl(tetrakis-o-oxyethoxyphenyl)]-1Љ,4Љ,6Љ,9Љ-
tetraazaanthraceno[7,8-b:7Ј,8Ј-e]bisporphyrinato]dizinc(II)
11 and 12
A flask containing a mixture of 8 (52 mg, 0.046 mmol) and
1,2,4,5-benzenetetramine tetrahydrochloride (9.2 mg, 0.032
mmol) under a nitrogen atmosphere was charged by cannula
with dry pyridine (10 cm3) which had previously been degassed
with nitrogen. The reaction was shielded from light and the
mixture heated at reflux for 2 days. The mixture was then
diluted with toluene (70 cm3) and dichloromethane (20 cm3)
and the solvents removed. The crude residue was dissolved in
toluene (50 cm3) and the solvent removed again. The residue
was dissolved in dichloromethane (50 cm3) and a solution of
zinc() acetate dihydrate (26 mg, 0.118 mmol) in methanol (15
cm3) was added and the mixture heated at reflux for 30 min. The
crude product obtained from evaporation of the solvent was
purified by BioBeads size-exclusion chromatography (2.5 cm id
A portion of the mixture of 9 and 10 (2.86 mg) was separated
by preparative HPLC (chloroform). The sample was dissolved
in chloroform (1 cm3) and prefiltered through a membrane filter
(Millipore, Type FH, 0.5 µm). The filtrate was applied to the
column. A less polar fraction (Rt = 3.7–4 min) and a more polar
fraction (Rt = 4–4.5 min) were collected. The precipitate col-
lected on the membrane was washed off with chloroform and
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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× 90 cm, toluene). The front-running main fraction was
collected. A considerable amount of material had precipitated
at the top of the BioBeads column. The top 5 cm of the
BioBeads was carefully removed and extracted with toluene
and chloroform. Filtration and evaporation of the solvent
yielded a solid which was purified by column chromatography
over flash silica (chloroform–methanol; 100 : 1). One main
fraction was collected. The crude residue was rechromato-
graphed over BioBeads size-exclusion chromatography (2.5 cm
id × 90 cm, toluene) and the main front-running band com-
bined with the previously obtained fraction to yield a crude
mixture of 11 and 12 (23 mg, 42%) as a dark brown–purple
solid, mp > 300 ЊC. The 1H NMR spectrum showed a 1:1
mixture of 11 and 12. m/z (MALDI-TOF) 2326.9 (simulated
maximum requires 2326.5).
78 (2329.416/60), 2330.36/58 (2330.416/40), 2331.36/29
(2331.416/29) and 2332.36/22 (2332.42/16); m/z (FT-MALDI-
TOF) 2327.86 (simulated maximum requires 2326.5); m/z
(MALDI-TOF) 2326.5 (simulated maximum requires 2326.5).
Synthesis of [2,3-dioxo-5,10,15,20-tetrakis(3,5-di-tert-
butylphenyl)chlorinato]zinc(II) 13
A mixture of 2,3-dioxo-5,10,15,20-tetrakis(3,5-di-tert-butyl-
phenyl)chlorin29 (317 mg, 0.290 mmol) and zinc() acetate
dihydrate (291 mg, 1.33 mmol) in dichloromethane (250 cm3)
and methanol (20 cm3) was heated at reflux for 3 h. The solvent
was removed and the residue purified by column chromato-
graphy over flash silica (dichloromethane–light petroleum; 1 : 2
changing to 1 : 1) to yield [2,3-dioxo-5,10,15,20-tetrakis(3,5-di-
tert-butylphenyl)chlorinato]zinc() (zinc() porphyrin-dione)
13 (270 mg, 80%) as a green–grey solid, mp > 300 ЊC. δH (400
MHz, CDCl3) 1.44 (36 H, s, t-butyl H), 1.48 (36 H, s, t-butyl H),
7.63 (4 H, d, J 1.8, Ar–Ho at C5,20), 7.69 (2 H, t, J 1.8, Ar–Hp at
C5,20), 7.73 (2 H, t, J 1.8, Ar–Hp at C10,15), 7.90 (4 H, d, J 1.8,
Ar–Ho at C10,15), 8.32 and 8.58 (4 H, ABq, J 4.7, β-pyrrolic H-7,
H-8, H-17 and H-18) and 8.50 (2 H, s, β-pyrrolic H-12 and
H-13); m/z (MALDI-TOF) 1159.3 (Mϩ requires 1157.0).
A portion of the mixture of 11 and 12 (20.3 mg) was separ-
ated by preparative HPLC (chloroform–dichloromethane;
1 : 1). Samples (2.5–3 mg) of the above mixture in chloroform
(1.0 cm3) were applied to the column. A less polar fraction
(Rt = 6–7 min) and a more polar fraction (Rt = 8–9 min)
was collected.
The less polar fractions were evaporated to give the anti-
isomer 12 (9.25 mg, 91% recovery of this isomer) as a brown–
purple solid, mp > 300 ЊC (Found: C, 63.1; H, 3.85; N, 6.2.
C130H82N12O16Zn2 ϩ 2 CH2Cl2 requires C, 63.5; H, 3.5; N,
6.7%); νmax (CHCl3)/cmϪ1 3600, 2931, 2861, 1731, 1602, 1578,
1490, 1443, 1337, 1279 and 1243; λmax (CHCl3)/nm 425.5 (log ε
5.36), 456 (5.23), 521sh (4.70), 538.5 (4.71), 624.5 (4.28) and 666
(4.32); δH (600 MHz, CDCl3) 3.82–3.86 (4 H, m, CH2),
3.91–3.98 (8 H, m, CH2), 4.28–4.37 (16 H, m, CH2), 4.46–4.50
(4 H, m, CH2), 5.69 (4 H, s, capping H), 7.43 (4 H, ddd, J 7.6,
7.1 and 0.9, Ar–H5 at C15,20), 7.54 (4 H, dd, J 8.7 and 0.9, Ar–H3
at C15,20), 7.61 (4 H, ddd, J 7.7, 7.0 and 0.8, Ar–H5 at C5,10), 7.66
(4 H, dd, J 8.7 and 0.8, Ar–H3 at C5,10), 7.81 (4 H, ddd, J 8.7, 7.6
and 1.5, Ar–H4 at C15,20), 7.92 (4 H, dd, J 7.0 and 1.6, Ar–H6 at
C5,10), 7.93 (4 H, dd, J 7.1 and 1.5, Ar–H6 at C15,20), 8.13 (4 H,
ddd, J 8.7, 7.7 and 1.6, Ar–H4 at C5,10), 8.75 (4 H, s, β-pyrrolic
H-17 and H-18), 8.84 (2 H, s, bridging H-5Љ and H-10Љ), 8.87
and 8.96 (8 H, ABq, J 4.4, β-pyrrolic H-2, H-3, H-12 and
H-13); m/z (HRFAB) Envelope (Mϩ requires): 2323.49/43%
Synthesis of {5,10,15,20-[pyromellitoyl(tetrakis-o-oxyethoxy-
phenyl)]-6Ј,7Ј-diaminoquinoxalino[7,8-b]porphyrinato}zinc(II)
17
A flask containing a mixture of zinc() C2-capped porphyrin-
7,8-dione 8 (20 mg, 0.018 mmol) and 1,2,4,5-benzenetetramine
tetrahydrochloride (31 mg, 0.11 mmol) under a nitrogen atmos-
phere was charged by cannula with dry pyridine (50 cm3) which
had previously been degassed with nitrogen. The reaction was
shielded from light and the mixture heated at reflux for 20 h.
The mixture was cooled and diluted with dichloromethane
(50 cm3) and water (250 cm3). The aqueous phase was extracted
with dichloromethane (2 × 25 cm3). The combined organic
extracts were washed with water (3 × 250 cm3), dried over
anhydrous sodium sulfate and evaporated to dryness. The resi-
due was dissolved in toluene (50 cm3) and the solvent removed
again. The residue was dissolved in dichloromethane (75 cm3)
and a solution of zinc() acetate dihydrate (16 mg, 0.073 mmol)
in methanol (20 cm3) was added and the mixture heated at
reflux for 1 h. The crude product obtained from evaporation of
the solvent was purified by column chromatography over flash
silica (dichloromethane–methanol; 100 : 0.8 changing to 100 : 4).
The main fraction yielded crude {5,10,15,20-[pyromellitoyl-
(tetrakis-o-oxyethoxyphenyl)]-6Ј,7Ј-diaminoquinoxalino-
[7,8-b]porphyrinato}zinc() [zinc() C2-capped 6Ј,7Ј-diamino-
quinoxalino-porphyrin] 17 (14 mg, 66%) as a dark purple
solid, mp > 300 ЊC. δH (400 MHz, CDCl3) 2.60–3.00 (4 H,
br s, NH2 protons), 3.76–3.85 (4 H, m, CH2), 3.86–3.96
(4 H, m, CH2), 4.25–4.41 (8 H, m, CH2), 4.44–4.56 (4 H, m,
CH2), 5.57 (2 H, s, capping H), 6.51 (2 H, s, quinoxalino H),
7.36 (2 H, dd, J 7.6 and 1, Ar–H), 7.39–7.46 (2 H, m, Ar–H),
7.55 (2 H, dd, J 8.3 and 1.0, Ar–H), 7.70 (2 H, dd, J 6.9 and 1.0,
Ar–H), 7.72–7.83 (6 H, m, Ar–H), 8.74 (2 H, s, β-pyrrolic H-17
and H-18), 8.77 and 8.82 (4 H, ABq, J 4.6, β-pyrrolic H-2, H-3,
H-12 and H-13).
(2323.418/50%),
(2325.417/89),
2324.49/50
2326.49/90
(2324.416/80),
(2326.416/100),
2325.44/52
2327.49/100
(2327.416/94), 2328.52/76 (2328.416/80), 2329.49/64 (2329.416/
60), 2330.48/38 (2330.416/40) and 2331.53/32 (2331.416/29);
m/z (FT-MALDI-TOF) 2327.85 (simulated maximum requires
2326.5); m/z (MALDI-TOF) 2326.3 (simulated maximum
requires 2326.5).
The more polar fractions were evaporated to give the syn-
isomer 11 (10.0 mg, 98% recovery of this isomer) as a red–
purple solid, mp > 300 ЊC (Found: C, 65.9; H, 3.9; N, 6.9.
C130H82N12O16Zn2 ϩ 0.5 CHCl3 requires C, 65.7; H, 3.5; N,
7.1%); νmax (CHCl3)/cmϪ1 3601, 2954, 2931, 2872, 1731, 1602,
1578, 1490, 1443, 1337, 1284 and 1243; λmax (CHCl3)/nm 425.5
(log ε 5.52), 455.5 (5.40), 511.5sh (4.74), 533.5 (4.77), 624sh
(4.16) and 666 (4.28); δH (600 MHz, CDCl3) 3.86–3.91 (4 H, m,
CH2), 3.95–4.00 (4 H, m, CH2), 4.17–4.24 (4 H, m, CH2), 4.30–
4.35 (4 H, m, CH2), 4.37–4.48 (8 H, m, CH2), 4.48–4.54 (4 H, m,
CH2), 5.70 (4 H, s, capping H), 7.43 (4 H, ddd, J 7.7, 7.1 and
1.0, Ar–H5 at C15,20), 7.54 (4 H, ddd, J 7.7, 7.1 and 0.9, Ar–H5 at
C5,10), 7.55 (4 H, dd, J 8.8 and 1.0, Ar–H3 at C15,20), 7.73 (4 H,
dd, J 8.8 and 0.9, Ar–H3 at C5,10), 7.81 (4 H, ddd, J 8.8, 7.7 and
1.6, Ar–H4 at C15,20), 7.83 (4 H, dd, J 7.1 and 1.6, Ar–H6 at
C5,10), 7.92 (4 H, dd, J 7.1 and 1.6, Ar–H6 at H15,20), 8.11 (4 H,
ddd, J 8.8, 7.7 and 1.6, Ar–H4 at C5,10), 8.75 (4 H, s, β-pyrrolic
H-17 and H-18), 8.81 (2 H, s, bridging H-5Љ and H-10Љ), 8.87
and 8.96 (8 H, ABq, J 4.4, β-pyrrolic H-2, H-3, H-12 and
H-13); m/z (HRFAB) Envelope (Mϩ requires): 2322.37/24%
(2322.42/33%), 2323.36/50 (2323.418/50), 2324.38/72 (2324.416/
80), 2325.37/86 (2325.417/89), 2326.37/98 (2326.416/100),
2327.37/100 (2327.416/94), 2328.36/89 (2328.416/80), 2329.37/
Exemplary procedure for self-replication studies
The chloroform used in this experiment had been dried and
deacidified by filtering the solvent through a plug of alumina
and then purged with argon for at least 10 min. Zinc() C2-
capped porphyrin-7,8-dione 8 (13.4 mg, 0.0118 mmol) and
zinc() C2-capped 6Ј,7Ј-diaminoquinoxalino-porphyrin 17 (14.4
mg, 0.0117 mmol) were dissolved in chloroform (7.0 cm3). A
portion (1 cm3) of the stock solution was then added to seven
small (5–10 cm3) round-bottom flasks labelled no. 1–7. A
solution of 1,3-bis(4-pyridyl)propane 16 (8.9 mg, 0.0449 mmol)
in chloroform (1.02 cm3) was prepared and aliquots (0.038 cm3,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
1224

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3 T. Tjivikua, P. Ballester and J. Rebek Jr., J. Am. Chem. Soc., 1990,
112, 1249–1250.
0.0017 mmol) were added to flasks no. 1, 2, 3 and 5. A solution
of pyridine (0.007 cm3, 0.0865 mmol) in chloroform (1.00 cm3)
was prepared and a portion of that solution (0.020 cm3, 0.0017
mmol) was added to flask no. 4. anti Dizinc() bis(7,8-C2-
capped porphyrin) 12 (0.9 mg, 0.0004 mmol) was then added
to flask no. 1. syn Dizinc() bis(2,3-C2-capped porphyrin) 9
(0.99 mg, 0.0004 mmol) was added to flask no. 2. syn Dizinc()
bis(7,8-C2-capped porphyrin 11 (1.0 mg, 0.0004 mmol) was
added to flask no. 3. To flasks no. 5 and 6, dizinc() bis-por-
phyrin 14 (0.9 mg, 0.0004 mmol) was added to each flask. After
all the reagents had been added, chloroform was added to each
flask so that the total volume was close to 1.2 cm3. Argon was
briefly blown over the solution and the flasks then stoppered
with a septum and the solutions stirred in the dark. After 3
days, a 0.005 cm3 aliquot was removed from each flask by a
syringe and analysed by analytical HPLC (dichloromethane–
methanol; 100 : 0.65). After 7 days, dichloromethane (20 cm3)
was added to each flask and a small aliquot (ca. 0.01 cm3) of
that solution analysed by analytical HPLC column as above.
Each reaction mixture (no. 1–7) was then washed with aqueous
hydrochloric acid (0.001 M, 30 cm3), water (30 cm3), dried over
anhydrous sodium sulfate and evaporated to dryness. The crude
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1
residues were analysed by H NMR spectroscopy. Each crude
product mixture was then purified by BioBeads size-exclusion
chromatography (1.5 cm id × 35 cm, toluene) to give two main
fractions. The first main fraction, consisted mostly of the
bis-porphyrin templates and products; anti dizinc() bis(7,8-C2-
capped porphyrin) 12, syn dizinc() bis(7,8-C2-capped por-
phyrin 11, syn dizinc() bis(2,3-C2-capped porphyrin) 9 and
dizinc() bis-porphyrin 14 which were then analysed as above
22 J. Almog, J. E. Baldwin and J. Huff, J. Am. Chem. Soc., 1975, 97,
1
227–228.
by analytical HPLC and H NMR spectroscopy to determine
their ratios. The second fraction was also analysed by 1H NMR
and consisted mostly of unreacted starting materials (mono-
mers) 8 and 17.
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F. Basolo, J. Am. Chem. Soc., 1982, 104, 2101–2109.
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Acknowledgements
We thank the Australian Research Council for financial support
for this project and a scholarship to P.T. We would also like to
thank Dr Ming Xie and Dr Ian Luck for assistance with NMR
work, Dr Kelvin Picker for assistance with HPLC and Miss
Efstathia Kyriakopoulos for MALDI measurements.
30 Hyperchem 6.0, Hypercube Inc., Gainesville, FL, 2000.
31 A. I. Vogel, in Vogel’s Handbook of Practical Organic Chemistry,
ed. B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatcher,
Longman Scientific, London, 1989, pp. 199–208.
32 M. J. Crossley, P. Thordarson, J. P. Bannerman and P. J. Maynard,
J. Porphyrins Phthalocyanines, 1998, 2, 511–516.
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 1 6 – 1 2 2 5
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