Synthesis of indaphyrins: meso-tetraarylsecochlorin-based porphyrinoids containing direct o-phenyl-to-beta-linkages.

Article abstract of DOI:10.1039/b401629g

The synthesis of indaphyrins, novel meso-tetraarylsecochlorin-derived chromophores incorporating o-phenyl-to-beta-linkages, is described. Oxidative diol cleavage of meso-tetraaryl-2,3-dihydroxy-2,3-chlorins results in the formation of a secochlorin bisaldehyde. Depending on the reaction conditions during the ring cleavage reaction, one or two of the aldehyde groups react with the adjacent o-phenyl positions, leading to an intramolecular electrophilic aromatic substitution of the o-phenyl proton, and the establishment of a direct o-phenyl-to-beta-linkage. The initially formed carbinol is spontaneously oxidized to the corresponding ketone. This modification forces the aryl groups into co-planarity with the macrocycle, allowing for interactions between the pi-electrons of the aryl groups, the ketone linkage, and those of the chromophore, resulting in a significant electronic modulation of the porphyrinic pi-system. The UV-vis spectroscopic properties of the free base, CuII, NiII, and ZnII indaphyrins are discussed.

Full text of DOI:10.1039/b401629g

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Synthesis of indaphyrins: meso-tetraarylsecochlorin-based
porphyrinoids containing direct o-phenyl-to-ꢀ-linkages
Jason R. McCarthy, Michael A. Hyland and Christian Brückner*
University of Connecticut, Department of Chemistry, Storrs, CT 06269-3060, U. S. A.
E-mail: c.bruckner@uconn.edu; Fax: ϩ860 486-2981; Tel: ϩ860 486-2743
Received 4th February 2004, Accepted 25th March 2004
First published as an Advance Article on the web 21st April 2004
The synthesis of indaphyrins, novel meso-tetraarylsecochlorin-derived chromophores incorporating o-phenyl-to-β-
linkages, is described. Oxidative diol cleavage of meso-tetraaryl-2,3-dihydroxy-2,3-chlorins results in the formation
of a secochlorin bisaldehyde. Depending on the reaction conditions during the ring cleavage reaction, one or two of
the aldehyde groups react with the adjacent o-phenyl positions, leading to an intramolecular electrophilic aromatic
substitution of the o-phenyl proton, and the establishment of a direct o-phenyl-to-β-linkage. The initially formed
carbinol is spontaneously oxidized to the corresponding ketone. This modification forces the aryl groups into
co-planarity with the macrocycle, allowing for interactions between the π-electrons of the aryl groups, the ketone
linkage, and those of the chromophore, resulting in a significant electronic modulation of the porphyrinic π-system.
The UV-vis spectroscopic properties of the free base, CuII, NiII, and ZnII indaphyrins are discussed.
Introduction
One of the main driving forces behind current synthetic por-
phyrin chemistry is the synthesis of chromophores with desig-
ned optical properties. The maximum wavelength of absorption
for porphyrins and many chlorins (β,βЈ-dihydroporphyrins) is
about 650 nm. However, porphyrinoid chromophores absorb-
ing and emitting in the red to infra-red region of the electro-
magnetic spectrum are of potential use in photodynamic
therapy (PDT),1 as well as in cell imaging and tagging appli-
cations.2 This is due to the so called ‘spectroscopic window’ of
biological systems, the range of light that is able to penetrate
tissue. Red and near-infra-red wavelengths penetrate tissue the
best.1 Light scattering in opaque biological media is also wave-
length dependent – longer wavelengths scatter less than shorter
ones.3 Chromophores with a broad absorption over the entire
visible range may also aid in the design of synthetic light
harvesting assemblies.4
Scheme 1 Synthesis of naphthoporphyrins 3M from meso-tetraphenyl-
porphyrins 1. Reaction conditions: i. 1. POCl3/DMF, 2. H2O; ii. TFA.
complex, was β-formylated under Vilsmeier–Haak conditions.
An attempt to demetallate the resulting β-formyl porphyrins
2M with TFA resulted in an intramolecular ring closure reac-
tion and formation of naphthoporphyrin 3M. The overall result
of the direct o-phenyl-to-β-linkages is a benzocyclohexenone
unit fused into the porphyrin macrocycle. The photophysical
consequences of this ring closure are exemplified by a 32 nm
bathochromically shifted Soret band for 3Cu (λSoret = 465 nm),
as compared to that of 2Cu (λSoret = 432 nm), and a 75% reduc-
tion of the extinction coefficient. The longest wavelength of
absorption is even 100 nm bathochromically shifted (λmax = 594
nm for 2Cu as compared to 694 nm for 3Cu). The utility of this
reaction was further explored by the groups of Callot and
Dolphin.13,14 Derivatives of 3 were designed to chelate to transi-
tion metals and were used in the construction of metal-linked
porphyrin-oligomers.13
If the general reaction depicted in Scheme 1 is performed on
the methoxyphenyl-substituted porphyrin 1M, the resulting
product is identified as the doubly-cyclized naphthoporphyrin
4H2 (Fig. 1).14 Besides the naphthoporphyrin linkage, a direct
o-phenyl-to-β-position linkage was established. This chromo-
phore is one example of a meso-arylporphyrin-derived chromo-
phore containing a five-membered ring between the aryl group
and the porphyrin ring. Most recently, Fox and Boyle intro-
duced the Pd(0)-catalyzed o-to-β-ring closure of o-iodinated
meso-arylporphyrins to establish such a fused five-membered
ring.15
Much of the research toward the goal of synthesizing red-
absorbing porphyrinoids has focused on the synthesis of
expanded and isomeric porphyrins,5 heteroporphyrins and
porphyrin-analogs containing non-pyrrolic heterocycles.6 The
majority of these chromophores were made from monopyrrolic
starting materials using a step-by-step approach.
An alterative synthesis of porphyrinoids relies upon the
modification of porphyrins.7-10 This method has a number of
advantages, especially when utilizing meso-tetraarylporphyrin 1
as the starting material: firstly, porphyrin 1 is readily available
with a wide range of meso-aryl substituents, allowing the
adjustment of the solubility and biodistribution properties
of meso-arylporphyrin-derived chromophores.11 Secondly, the
meso-aryl groups themselves can potentially be utilized in the
modulation of the porphyrinic chromophore. The aryl groups
in 1 are arranged essentially orthogonal to the plane of the
porphyrin. Hence, aryl-substituents have only a minor effect
on the optical properties of 1. However, the establishment
of a covalent linkage between the o-phenyl position and the
β–position of a porphyrin forces the aryl group into (idealized)
co-planarity with the macrocycle. As a result, the π-system of
the aryl group can interact with the porphyrinic π-system, lead-
ing to a significant modulation of the electronic properties of
the chromophore.
A small number of other chromophores with o-phenyl-to-β-
linkages are known. For instance, acid-catalyzed ring-closure of
2-vinylporphyrin generates naphthochlorin 5aM, which has a
λmax of 670 nm (for M = Ni).16 The mechanism of formation of
The validity of this approach was firstly demonstrated by
Henrick et al. using a serendipitously discovered reaction
(Scheme 1).12 meso-Tetraarylporphyrin 1, as its NiII or CuII
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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 4
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instance, reaction of 7aH2 under diol cleavage conditions
(NaIO4-silica gel) in the presence of EtOH produced morpho-
linochlorin 9aH2 incorporating a morpholine building block
(Scheme 2).20 The key intermediate in these syntheses was the
in situ reacted unstable secochlorin bisaldehyde intermediate
8H2. As its NiII complex 8Ni, the secochlorin can be isolated.8,9
Following up on our recent communication, we report here
on the use of 7, 8, and 9 in the synthesis of diphenylindaphyrins
10, novel secochlorin-based chromophores incorporating
o-phenyl-to-β-position linkages.10 We will describe different
routes toward the synthesis of these macrocycles as their free
base, CuII, NiII, and ZnII complexes. The optical properties of
these chromophores will be discussed. In so doing, we further
expand the class of meso-aryl-based porphyrinoid chromo-
phores containing o-phenyl-to-β-linkages, and introduce a
novel class of secochlorin-based chromophores with extremely
red-shifted optical spectra.
Fig. 1 Structures of precedent porphyrinoid chromophores contain-
ing o-phenyl-to-β-linkages.14,16,17
this chlorin-like chromophore is reminiscent of the formation
of naphthoporphyrins 3M. A fundamentally different fashion
of generating chromophores with co-planar meso-aryl groups
was described by Smith and co-workers. Bergman cyclization
of meso-tetraphenyl-2,3-dialkynylporphyrins afforded 6M, a
chromophore containing a [5]phenacene unit fused to the
porphyrin macrocycle.17 Again, the optical properties of 6M are
much altered as compared to those of porphyrins, with a much
bathochromically shifted λmax of 629 nm for 6Ni and of 684 nm
for the corresponding free base chromophore.
We have reported the utility of meso-tetraaryl-2,3-dihydroxy-
chlorins 7, made by OsO4-mediated dihydroxylations of the
corresponding porphyrins 1,8,18 in the synthesis of porphyrinoid
chromophores in which one of the pyrrolic units of a porphyrin
was formally replaced by a non-pyrrolic heterocycle.8,19,20 For
Results and discussion
Synthesis and characterization of indaphyrins
The nucleophile-induced intramolecular ring-closure reaction
of bisaldehyde 8Ni to form morpholinochlorin 9Ni is acid-
catalyzed using only traces of acid (Scheme 2).8,19,20 However,
when 8aNi was reacted with EtOH in the presence of too high
a concentration of acid or for an extended period of time,
one non-polar, deep green degradation product formed at the
expense of morpholinochlorin 9aNi. The high resolution mass
spectrum of this product indicated its composition to be
Scheme 2 Reaction conditions: i. NaIO4/silica gel, EtOH; ii. EtOH, TFA; iii. 10% TFA/CH2Cl2; iv. [O]; v. NaIO4/silica gel or PbIV(OAc)4; vi. TFA
vapors; vii. 2% TFA/CH2Cl2; viii. ZnII(OAc)2, 10% MeOH/CHCl3, ∆; ix. CuII(OAc)2, DMF, ∆.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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Fig. 2 A: Partial 1H,1H COSY (CDCl3, 400 MHz, r.t.) spectrum of 10aH2; B: Partial 1H NMR (CDCl3, 400 MHz, r.t.) spectrum of 12aH2. C: Full
13C NMR (CDCl3, 100 MHz, r.t.) spectrum of 10aH2. D: Full 13C NMR (CDCl3, 100 MHz, r.t.) spectrum of 12aH2.
C44H24N4NiO2 (m/z = 698.1262, Mϩ, FABϩ), i.e. formally
derived from 8aNi by loss of four hydrogens. This suggested
that EtOH was not involved in the transformation. Indeed, the
identical product was obtained as the major product when 8aNi
was reacted with TFA in the absence of an alcohol (80% yield,
5 × 10Ϫ5 mol scale). The UV-vis absorption spectrum of 10aNi
resembles that of a bathochromically shifted NiII chlorin, indi-
cating the presence of a porphyrinoid macrocycle, and exclud-
ing the presence of a linear oligopyrrolic product (see Fig. 3;
for a detailed discussion of the optical properties of this
region shows the correlation between the four signals, which
corresponds to a non-symmetrically 1,2-disubstituted phenyl
group. For reactions involving the meso-tolyl- or meso-(3,4,5-
trimethoxyphenyl)-substituted secochlorin bisaldehydes 8b and
8c, the proton signals in the phenyl region were correspondingly
simplified (10c, for instance, displays only two singlets in a 1 : 2
ratio in the phenyl region). Additional signals for the methyl-
and methoxy-groups were observed for these derivatives,
respectively.
This spectroscopic evidence suggests the presence of an
o-phenyl-to-β-position linkage. What, however, is its nature?
The mass spectrum suggests the presence of two carbonyl
groups.23 This implication is confirmed by the observation of a
νC᎐O at 1699 cmϪ1 in the IR spectrum of 10aH2. The 13C NMR
sp᎐ectrum of 10aH2 also provides clear evidence for the presence
of a carbonyl carbon (189.5 ppm, Fig. 2C). Thus, chromophore
10 was assigned the structure shown in Scheme 2. In this
macrocycle, a ketone functionality joins the o-phenyl position
with the α-position of a secochlorin chromophore, fusing
indanone moieties to a secochlorin backbone. Thus, we suggest
the trivial name ‘indaphyrin’ for this chromophore.
1
chromophore, see below). The H and 13C NMR spectra of
this compound are well resolved and indicate a porphyrinic
chromophore of two-fold symmetry. A carbonyl stretch at
1599 cmϪ1 is present in its IR spectrum. However, 10aNi is
unstable and decomposes in solution within 12 hours, providing
a red pigment with a spectroscopic signature suggesting a
ring-opened, linear oligopyrrolic structure.21
Fortunately, free base morpholinochlorin 9H2 proved to be
susceptible to an equivalent acid-induced reaction, producing
10aH2 in 30% isolated yield as a stable, non-polar, deep red
chromophore of the composition C44H27N4O2 (m/z = 643.2145,
MHϩ, FABϩ). Again, the pigment is formally derived from
secochlorin bisaldehyde 8H2 by loss of four hydrogens. The 1H
NMR spectrum of this product (10aH2) is shown in Fig. 2A.
This spectrum has features generally observed in two-fold
symmetric pyrrole-modified porphyrins such as 7, 8, and 9.8,19,20
The β-protons appear as two doublets (centred at 8.54 and 9.15
The inner NH protons in 10aH2 resonate in the 1H NMR at
1.49 ppm. The down-field shift (cf. to the corresponding signals
at Ϫ0.84 ppm for 7aH2) may indicate an unusual π-resonance
pattern which reduces the diatropic ring current of the por-
phyrinoid chromophore. Alternatively, this shift may indicate
a significant non-planarity of the chromophore. However,
models do not suggest an unusually large deviation from
planarity for 10aH2 (see below). The extinction coefficient for
the diphenylindaphyrin is also reduced as compared to diol
chlorin 7aH2, further supporting the notion of a perturbed
aromatic system. The unusual UV-vis properties of indaphyrins
are discussed below.
The mechanism of formation of indaphyrin 10 from
secochlorin 8 can be rationalized by an acid-catalyzed intra-
molecular electrophilic attack of the formyl groups onto the
adjacent o-phenyl positions, forming carbinol 11, which then
oxidizes spontaneously to the final product (Scheme 2). The
3
ppm, with the small J of 4.9 Hz characteristic of β-protons)
and a singlet (8.15 ppm) in an 1 : 1 : 1 intensity ratio. The phenyl
region of the 1H NMR spectrum is, however, unusual. The sig-
nals are split into two distinct sets (Fig. 2A). One broad peak
corresponds to the ten hydrogens of two phenyl groups. This
unresolved signal is similar to that observed for the phenyl
groups in many meso-phenylporphyrin derivatives. The second
set are four well resolved signals, corresponding to 2H each
(two doublet-of-doublets centred at 7.32 and 7.64 ppm, and two
doublets centred at 7.81 and 8.24 ppm, all with a coupling con-
stant of 7.7 Hz). The H,H–COSY spectrum of the aromatic
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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sensitivity of carbinols of this type towards air oxidation was
previously shown by Barloy and co-workers.14 In the decom-
position reactions of morpholinochlorins 9, the double acetal
group functions as a masked bisaldehyde which is liberated
under the acidic reaction conditions, and which reacts in situ.
This mechanism suggests a rational synthesis of the free base
chromophore 10H2, i.e. a synthesis not involving the initial
formation of morpholinochlorin 9H2. We have earlier shown
that bisaldehyde 8H2 is unstable but can be formed and reacted
in situ.20 Correspondingly, reaction of free base diol chlorins
7aH2 or 7bH2 under diol cleavage conditions (NaIO4/silica gel)
in the presence of acid (2% TFA/CH2Cl2) produces indaphyrin
10H2 in 44% isolated yield. This synthesis constitutes a greatly
improved procedure over the originally reported one.10 If, how-
ever, this reaction is performed using 7aH2 in a solvent contain-
ing only traces of TFA, a low polarity orange compound 12aH2
is isolated as the main product, and no indaphyrin 10 is formed.
The mass spectrum of 12aH2 specifies a composition of
C44H29N4O2 (m/z = 645.2334, MHϩ, FABϩ), i.e. formally
derived from secochlorin bisaldehyde 8aH2 by loss of only two
hydrogens. The 1H NMR spectrum of this compound is shown
in Fig. 2B. Clearly, the two-fold symmetry of the starting
material is lost (see e.g. the 6 doublets in the β-region, 8.0–9.1
ppm, 1H each). The phenyl region is convoluted, but the coup-
ling pattern corresponding to one 1,2–disubstituted phenyl
group can be distinguished: two doublets centred at 7.86 and
9.13 (J = 7.2 Hz) and two doublet-of-doublets centred at 7.32
and 7.66 ppm (J = 7.6 Hz). A singlet at 9.57 ppm suggests the
presence of an aldehyde moiety. Furthermore, the 13C NMR
and IR spectra indicate the presence of two different carbonyls
standard conditions (M(OAc)2, 10% MeOH/CHCl3 for M =
ZnII or DMF for M = CuII) proceeds smoothly. The deep red
color of the free base indaphyrin 10aH2 changes upon form-
ation of the CuII complex 10aCu to red–orange whereas the red
color of the ZnII complex 10aZn is very similar to that of the
free base. Insertion of nickel(II) using Ni(OAc)2 in hot pyridine
or DMF did not take place, instead, the free base indaphyrin
was recovered quantitatively. This finding is very unusual for
porphyrinoid macrocycles. In line with this finding, however,
the NiII diphenylindaphyrin 10aNi is also relatively unstable.
This may indicate that the insertion of NiII into indaphyrins
requires a significant conformational change. Molecular model-
ling studies (see below) provide some confirmation of this
assumption. The optical properties of the metalloindaphyrins
are discussed below.
UV-vis properties of indaphyrins
The combination of the steric and electronic effects caused by
the formation of indaphyrins is expected to have a profound
impact on the photophysical properties of these chromophores.
The formation of an o-aryl-to-β-position ketone linkage in
indaphyrins 10 and 12 forces one or two phenyl groups into
idealized co-planarity, and thus, conjugation with the macro-
cycle, expanding the porphyrinic π-system. Carbonyl function-
alities are also known to greatly influence the optical properties
of porphyrins.8,25,26 In indaphyrin 10, ketone bridges link both
the phenyl and chromophore π-systems, while in 12, one alde-
hyde functionality and one linking ketone functionality are in
conjugation with the porphyrinic chromophore. The o-aryl-to-
β-position linkage may also distort the secochlorin chromo-
phore from planarity. Any distortion of a porphyrinoid
chromophore from planarity has pronounced effects on its elec-
tronic structure, although the exact reasons for this effect are
currently being debated.27
(187.3 and 190.7 ppm, Fig. 2D, and νC᎐O = 1655 and 1710 cmϪ1).
᎐
Thus, we assign it the structure of the meso-triphenyl-1-
formylindaphyrin 12aH2. This compound can be smoothly con-
verted to meso-diphenylindaphyrin 10aH2 by treatment with 2%
TFA in CH2Cl2.
In reactions using the trimethoxyphenyl-derived diols 7cH2
or bisaldehyde 8cNi, the ring-forming reaction proceeded much
faster (within minutes instead of hours) and using lower acid
concentrations (TFA vapours instead of the 2% TFA/CH2Cl2
used in the synthesis of 10aH2). This reflects the increased
susceptibility of the trimethoxyphenyl group toward electro-
philic aromatic substitution and, most likely, the subsequent
oxidation of the benzylic carbinol.
Fig. 3 shows the UV-vis absorption spectrum of [indaphyrin-
ato]NiII 10aNi in comparison to that of a number of related
[chlorinato]NiII complexes. The spectrum of 10aNi is metallo-
chlorin-like, albeit significantly bathochromically shifted (λSoret
= 446 nm, λmax = 635 nm) as compared to, for instance, the
spectrum of [diolchlorinato]NiII 7aNi (λSoret = 416 nm, λmax
=
612 nm)8. A comparison of the UV-vis spectra of 10aNi with
those of the largely planar [2,3-dioxochlorinato]NiII 13Ni25 and
the non-planar [diformylsecochlorinato]NiII 8aNi8,9 allows
some delineation of the steric and electronic influences operat-
ing in these chromophores. The two conjugated carbonyl
groups in 13Ni render its UV-vis spectrum broadened, and one
band emerges next to the Soret band. However, the position of
the Soret band of 13Ni is comparable to that of planar [diol-
chlorinato]NiII 7aNi. The spectrum of the extremely ruffled
[diformylsecochlorinato]NiII 8aNi, a chromophore also con-
taining two carbonyl groups at the β-positions, is also some-
We have recently demonstrated that AgII can serve as a
removable metal template in the diol cleavage reaction of diol
chlorins, and that the AgII secochlorin bisaldehyde 8aAg is isol-
able, albeit in low yields.22 When [diolchlorinato]AgII 7aAg is
subjected to the diol cleavage conditions (NaIO4/silica gel), fol-
lowed by addition of acid upon consumption of the starting
material, free base formyl indaphyrin 10aH2 is isolated in up to
20% yield. Thus, the use of templating metal to stabilize the
secochlorin bisaldehyde intermediate 8aAg provides here no
advantage over the use of the free base diol chlorin. Further, the
presence of this templating metal does not seem to affect the
course of the reaction as compared to the reactivity of the free
base diol chlorin.
Preliminary studies on the reactivity of indaphyrins have
been undertaken. We have previously demonstrated the hydro-
decarbonylation of secochlorin bisaldehyde 8aNi to the corre-
sponding chlorophin.9 However, reaction of formyl indaphyrin
12aH2 under the same decarbonylation conditions (Wilkinson’s
catalyst, PhCN, reflux for several h) leads only to the formation
of indaphyrin 10aH2. Evidently, the thermally induced ring
closure reaction is faster than decarbonylation. The ketone
moieties of 10aH2 are not susceptible to reduction by NaBH4,
likely owing to their stabilization through conjugation. Bonnett
and co-workers reported a similarly unreactive conjugated car-
bonyl group incorporated into a porphyrinoid chromophore.24
The susceptibility of the indaphyrins toward metallation
reactions was tested. Insertion of zinc(II) or copper(II) using
Fig. 3 Comparison of the normalized UV-vis absorption spectra of
[diolchlorinato]NiII 7aNi, [2,3-dioxochlorinato]NiII 13Ni (structure of
this chromophore is shown above), [diformylsecochlorinato]NiII 8Ni,
and [diphenylindaphyrinato]NiII 10aNi (all in CH2Cl2).
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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what broadened but, most significantly, much bathochromically
shifted as compared to that of dioxochlorin 13Ni. In that
respect, the spectra of 13Ni and 10aNi are, however, similar,
likely indicating that the [indaphyrinato]NiII complex is also
non-planar.
The fact that the co-planar aryl groups are in conjugation
with the porphyrinic π-system can be ascertained by comparing
the UV-vis spectra of the phenyl-, tolyl- and trimethoxyphenyl-
substituted derivatives. For instance, λmax of the free base
indaphyrins shifts from 810 nm for the phenyl derivative 10aH2,
to 812 nm for the tolyl-derivative 10bH2, and to 818 nm in the
trimethoxyphenyl-derivative 10cH2. This shift, albeit modest in
absolute terms, is an unusually large phenyl-substituent effect
for meso-tetraarylporphyrins.
Fig. 5 UV-vis absorption spectra of 10aCu (—), 10aNi (ؒ ؒ ؒ ؒ ؒ ؒ), and
10aZn (——). 10aNi normalized to ε = 50000 MϪ1cmϪ1.
.
Interestingly, the UV-vis spectra of naphtho-porphyrins and
-chlorins, as their NiII complexes, show characteristics similar
to that of the spectrum of [indaphyrinato]NiII 10aNi.12–14,16
Bonnett and coworkers have synthesized a [dioxosecochlorin-
ato]NiII complex with ketone moieties at its β-positions.24 The
UV-vis absorption spectrum of this macrocycle is very similar
to that of 10aNi (λSoret = 444 nm, λmax = 648 nm), which illus-
trates the general combined effect of the carbonyl moiety and
inferred non-planarity on the photophysical properties of
[secochlorinato]NiII chromophores.
The unusual UV-vis spectrum of free base diphenyl-
indaphyrin 10aH2 is shown in Fig. 4. It is dissimilar to a regular
chlorin spectrum. It features a broad “double-Soret” band
(λSoret = 419, 554 nm), and an absorption into the NIR region
of the spectrum (λmax = 812 nm). As well, the extinction
coefficients for 10aH2 are reduced by ∼75%, as compared to
those measured for diol chlorin 7aH2.
radii of CuII and ZnII are significantly larger (0.71 Å and 0.74
Å, respectively).28 The central cavity of porphyrins is a little too
large to perfectly fit NiII. Thus, the central metal pulls the co-
ordinating nitrogens inward, leading to a ruffling of the por-
phyrin ring, whereby the structural rigidity of the macrocycle
limits the degree of ruffling. This effect of NiII on the conform-
ation of porphyrins is well described.9,29–31 Secochlorins, by
virtue of their ring cleavage and inherent compromised struc-
tural stability, are particularly susceptible to a NiII-induced
ruffling.9 The ruffling leads to a contraction of the central core
and the achievement of ideal Ni–N bond distances. We, there-
fore, also assume the [indaphyrinato]NiII complexes to be sig-
nificantly ruffled. On the other hand, the larger ions, CuII and
ZnII, do not induce any ruffling of porphyrins and, by analogy,
in the indaphyrins described here.
Molecular modelling of indaphyrins
We did not succeed in growing crystals suitable for single crystal
X-ray diffractometry studies for any of the indaphyrins. None
of the derivatives have shown a propensity to form well-defined
crystals. In fact, indaphyrins are remarkably well soluble in a
wide range of solvents.
In the absence of X-ray diffractometry results, we had to rely
upon molecular modelling studies to ascertain the possible con-
formations of the indaphyrins.32 Fig. 6 shows energy-minimized
models of the chromophores 10aH2, 12aH2, and 10aNi. The
two free base chromophores are expected to be slightly ruffled
(root mean square deviation from planarity (rms) of C20N4 core
Fig. 4 UV-vis absorption spectra of 10aH2 (—), and 12aH2 (ؒ ؒ ؒ ؒ ؒ ؒ).
In contrast, the UV-vis absorption spectrum of the formyl
indaphyrin 12aH2 features a single Soret band, (λSoret = 425 nm,
Fig. 4) but its absorption also ranges almost up to 800 nm
(λmax = 792 nm). The differences between the spectra of 10aH2
and 12aH2 illustrate the effect of the conversion of one formyl
group into an indaphyrin-type linkage, and the concomitant
electronic and conformational changes this modification
causes.
The UV-vis absorption spectra of the CuII and ZnII com-
plexes of 10aH2 are presented in Fig. 5. Similar to the spectrum
of 10aH2, the spectrum of the ZnII diphenylindaphyrin 10aZn
features a broad “double-Soret” band. The most intense
absorption band was at 566 nm (log ε = 4.70). The Soret band
of the CuII derivative 10aCu is very broad. It seems likely that
the two bands of the “double-Soret” feature of the free base
chromophore overlap. As expected, all metalloindaphyrin
spectra show a reduced number of side bands as compared to
the spectrum of the free base. Remarkably, the [indaphyrin-
ato]NiII spectrum is unlike that of the CuII complex. We interpret
this as further indication that the NiII complexes possess differ-
ent conformations.
Fig. 6 Molecular models of 1-formyl indaphyrin 12aH2 and diphenyl-
indaphyrins 10aH2 and 10aNi. Non-participating phenyl groups
included in the calculations but here removed for clarity. MM3 basis
set, Ni–N bond distances locked to 1.9 Å, the inferred ‘ideal’ bond
distance for square planar NiII–N bonds of this type.9
The NiII ion is relatively small (the effective ionic radius of
NiII in a square planar complex is 0.63 Å) whereas the ionic
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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of 10aH2: 0.36 Å, and of 12aH2: 0.39 Å). The ruffling appears
to be mainly caused by the steric interaction between the two
carbonyl functionalities (O–O distance 2.58 Å). The indaphyrin
linkage itself appears to cause only a minor distortion of the
macrocycle, if any, while the interactions between the oЈ-phenyl
proton with the protons of the β-pyrrolic units adjacent to the
cleaved pyrrole are likely the origins of non-planarity. The
molecular modelling studies of 4H2 performed by Barloy et al.
also show a chromophore which has a deviation from planarity
comparable to that of 10aH2.14 The main difference between the
two models is that they have different deformation modes (due
to the presence, or lack of, a β,βЈ-bond). As predicted based on
the optical properties of the NiII-complexes of indaphyrins, the
ruffling of the free bases is dramatically enhanced in the
presence of the central metal NiII (rms of C20N4 core of 10aNi:
0.63 Å). This observation is analogous to observations in other
[secochlorinato]NiII-derived complexes, in particular when
comparing the conformation of free base morpholinochlorin
9H2 (rms of C20N4 core 0.03 Å)20 and its NiII complex 9Ni (rms
of C20N4 core 0.55 Å)9. The extreme distortion of the C20N4
core highlights the response of the ring-fused indaphyrin
macrocycle toward a ruffling distortion and likely contributes
to the unusual instability of this complex. The degree of
distortion may be the upper limit at which [secochlorinato]NiII-
derivatives can be distorted from planarity.
meso-Diphenylindaphyrin (10aH2). Method A. NaIO4 hetero-
genized on silica gel (1.0 g) and 7aH2 (126 mg, 1.94 × 10Ϫ1
mmol) are combined in a flask. To this was added 2% TFA/
CH2Cl2 (40 mL). The solution was stirred for 10 h, after which
time Et3N (5 mL) was slowly added. The solution was filtered to
remove the silica gel, and the filter cake washed with CH2Cl2
until the filtrate was colorless. The filtrate was washed twice
with aq. NaHCO3, and once with H2O. The solution was dried
(anhydr MgSO4), filtered, and evaporated to dryness in vacuo.
10aH2 was purified by flash chromatography (CH2Cl2 : pet.
ether 30–60, 2 : 1, silica gel), and recovered as a microcrystalline
powder by slow solvent exchange with MeOH (yield: 44%, 55
mg).
Method B. A slurry of acidified silica gel (silica gel wetted
with conc. HCl and air dried, ∼500 mg) in CHCl3 (10 mL
amylene-stabilized) containing morpholinochlorin 9H2 (125
mg) was allowed to react for 12 h. The filtered solution was
subjected to preparative TLC chromatography to provide
10aH2 in 30% yield (33 mg).
Method C. Under an atmosphere of N2, silica gel-
heterogenized NaIO4 (2.0 g) was added to a stirring solution
of 7aAg (84 mg, 1.1 × 10Ϫ1 mmol) in CH2Cl2 (15 mL). The
reaction proceeded until the starting material was consumed
(∼15 min), at which point TFA (0.5 mL) was added to the reac-
tion mixture, which then was allowed to stir for an additional
10 min. The solution was filtered to remove the silica gel. The
volume of the solution was reduced to ∼5 ml and loaded onto a
flash chromatography column (CH2Cl2/pet ether 30–60, 2 : 1).
10aH2 was isolated in 20% yield (14 mg). Rf (silica–CH2Cl2):
0.67; UV-vis (CH2Cl2) λmax (log ε): 419 (4.65), 554 (4.61), 639
(4.05), 730 (3.62), 812 (3.29) nm; 1H NMR (400 MHz, CDCl3,
δ): 1.49 (br s, 1H, exchangeable with D2O), 7.32 (t, J = 7.6 Hz,
1H), 7.64 (t, J = 7.7 Hz, 1H), 7.71 (br s, 5H), 7.81 (d, J = 7.7 Hz,
1H), 8.14 (s, 1H), 8.24 (d, J = 7.7 Hz, 1H), 8.54 (d, J = 4.9 Hz,
1H), 9.15 (d, J = 4.9 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3, δ): 116.7, 122.7, 123.7, 124.2, 125.5, 127.1, 128.1, 128.5,
129.4, 130.3, 133.6, 134.1, 134.4, 135.7, 136.2, 140.3, 144.3,
The indaphyrins were computed to be ruffled, i.e. they are of
idealized C2–symmetry, they are chiral. We can, at this point,
not reliably estimate the barrier of inversion of the two free
base enantiomers of 10 but estimate 10aNi to be conform-
ationally rigid. Thus, racemic resolution of this macrocycle
may be possible, as was shown for [morpholinochlorinato]NiII
complexes.33
Conclusions
In conclusion, we have demonstrated the synthesis of a novel
class of secochlorin-based chromophores containing direct
o-phenyl-to-β-linkages, establishing an indanone unit fused into
the porphyrin macrocycle. The indaphyrins are, due to their
long-wavelength absorption properties, potentially useful in
photomedicine.
147.9, 155.6, 189.5 ppm; IR (KBr) ν = 1699 cmϪ1 (C᎐O); ϩESI-
᎐
MS (70 V, CH3CN) m/z = 643 (MHϩ); HR-MS (FABϩ of
MHϩ, PEG) calcd for C44H27O2N4: 643.2134, found: 643.2145.
Experimental
[meso-Diphenylindaphyrinato]Ni(II) (10aNi). A solution of
8aNi (29 mg, 4.1 × 10Ϫ2 mmol) in CHCl3 (10 mL amylene-
stabilized) was treated with TFA vapours obtained from the
headspace of a bottle of 10% TFA/CH2Cl2, and administered
by pipette. After all the starting material was consumed
(∼15 min, TLC control), the reaction mixture was filtered
through a plug of basic alumina. The resulting mixture was
separated by preparative TLC chromatography to provide
10aNi in 80% yield (23 mg). UV-vis (CH2Cl2) λmax (rel. inten-
sity): 446 (1.00), 635 (0.20) nm; 1H NMR (400 MHz, CDCl3, δ):
7.36-7.39 (t, J = 7. 3 Hz, 1H), 7.52-7.56 (t, 7.24 Hz, 1H), 7.65 (br
s, 3H), 7.84 (d, J = 7.3 Hz, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.09 (s,
1H), 8.21 (d, J = 7.64 Hz, 1H), 8.50 (d, J = 4.84 Hz, 1H), 8.9 (d,
J = 4.9 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3, δ): 110.7,
122.6, 124.9, 125.1, 125.3, 126.7, 127.9, 129.8, 130.2, 132.9,
134.9, 139.2, 139.8, 141.5, 141.8, 142.9, 148.5, 206.9 ppm; IR
General
All solvents and reagents used were reagent grade or better and
were used as received. The analytical TLC plates were Silicycle
ultra pure silica gel 60 (aluminum backed, 250 µm); preparative
TLC plates (500 µm silica gel on glass) and the flash column
silica gel (standard grade, 60 Å, 32–63 µm) used were pro-
vided by Sorbent Technologies, Atlanta, GA. 1H and 13C NMR
spectra were recorded on a Bruker DRX400 at ambient tem-
peratures and were referenced to residual solvent peaks. UV-vis
spectra were recorded on a Cary 50 spectrophotometer and IR
spectra on a Perkin-Elmer Model 834 FT-IR spectrometer. ESI
mass spectra were recorded on a Micromass Quattro II. High
resolution FAB mass spectra were provided by the Mass
Spectrometry Facility, Department of Chemistry and Bio-
chemistry, University of Notre-Dame (Bill Boggess). Elemental
analyses were provided by Numega Resonance Labs Inc., San
Diego, CA. Compounds 7aH2, 7bH2, and 7cH2 were prepared
according to the literature procedures.8,34
(KBr) ν: 1599 cmϪ1 (C᎐O); HR-MS (FABϩ of Mϩ, PEG) m/z:
᎐
calcd for C44H24N4NiO2: 698.1253, found: 698.1262.
[meso-Diphenylindaphyrinato]Cu(II) (10aCu). To a solution
of 10aH2 (20.5 mg, 3.19 × 10Ϫ2 mmol) in DMF was added
Cu(OAc)2ؒH2O (9.5 mg, 1.5 eq). The solution was heated to
reflux and the reaction progress monitored by TLC. Upon con-
sumption of the starting material, the solution was evaporated
to dryness in vacuo. The residue was re-dissolved in CH2Cl2,
and crystallized by slow solvent exchange with MeOH to yield
10aCu as a black microcrystalline powder in quantitative yield
Preparation of silica gel-supported NaIO4 35. NaIO4 (2.57 g,
12 mmol) was dissolved in hot water (5 mL, ∼70 ЊC) in a 25 mL
round-bottom flask. To the hot solution was added silica gel
(10 grams, 40 µ flash grade) under vigorous swirling and
shaking. The resulting product was dried in an open vessel at
50 ЊC for 12 h, resulting in a free flowing powder.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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(20 mg). Rf (silica–CH2Cl2): 0.59; UV-vis (CH2Cl2) λmax (log ε):
433 (4.48), 462 (4.51), 496 (4.51), 513 (4.51), 667 (3.98), 716 (sh)
nm; IR (KBr) ν: 1709 cmϪ1 (C᎐O); ϩESI-MS (70 V, CH CN)
consumption of the starting material (∼20 min), the solution
was neutralized with Et3N (1.0 mL), washed twice with conc
NaHCO3, once with H2O, and dried (anhydr MgSO4). The
solution was evaporated to dryness in vacuo. 10cH2 was purified
by flash chromatography (1% MeOH/CH2Cl2) and crystallized
by slow solvent exchange into MeOH to yield of 10cH2 in 60%
yield (12 mg, 1.1 × 10Ϫ2 mmol). Rf (silica–2.5% MeOH/
CH2Cl2): 0.24; UV-vis (CH2Cl2) λmax (log ε): 424 (4.58), 529 (sh),
᎐
3
m/z = 703 (Mϩ); HR-MS (FABϩ of Mϩ, PEG) calcd for
C44H24N4O2Cu: 704.1274, found: 704.1296.
[meso-Diphenylindaphyrinato]Zn(II) (10aZn). To a solution
of 10aH2 (26.2 mg, 4.0 × 10Ϫ2 mmol) in 10% MeOH–CHCl3
was added Zn(OAc)2 (13.3 mg, 6.07 × 10Ϫ2 mmol, 1.5 eq). The
reaction solution was heated to reflux for ∼30 min. Progress of
the reaction was monitored by UV-vis. Upon consumption of
the starting material, the solution was evaporated to dryness
in vacuo, the residue re-dissolved in CH2Cl2, and crystallized by
slow solvent exchange with ligroine to yield 10aZn as a black
precipitate in quantitative yields (26 mg). Rf (silica–CH2Cl2/1%
MeOH): 0.38; UV-vis (DMF) λmax (log ε): 425 (4.57), 446 (4.55),
1
560 (4.48), 641 (4.00), 692 (sh), 736 (sh), 810 (3.46) nm; H
NMR (400 MHz, CDCl3, δ): 1.44 (s, 2H), 3.75–4.40 (m, 36H),
7.52 (s, 2H), 8.23 (s, 2H), 8.59 (d, J = 4.8 Hz, 2H), 8.99 (d,
J = 4.6 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3, δ): 45.5,
56.3, 56.6, 61.2, 61.6, 62.5, 104.5, 111.6, 113.1, 115.5, 122.4,
123.8, 130.0, 133.6, 133.9, 135.7, 135.9, 138.0, 141.9, 145.0,
145.7, 151.8, 154.7, 155.1, 159.7, 186.6 ppm; IR (KBr) ν: 1696
cmϪ1 (C᎐O); LR-ESI-MS (30 V, CH CN) m/z = 1003 (MHϩ);
᎐
3
1
535 (sh), 566 (4.70), 695 (4.07), 747 (sh) nm; H NMR (400
HR-MS (FABϩ of MHϩ, PEG) calcd for C56H51N4O14:
MHz, DMF-d7, δ): 7.35 (m, 2H), 7.74 (m, 12H), 8.16 (s, 2H),
8.50 (d, J = 4.6 Hz, 2H), 8.54 (d, J = 7.8 Hz, 2H), 9.37 (d, J = 4.6
Hz, 2H) ppm; 13C NMR (100 MHz, DMF-d7, δ): 125.1, 125.1,
126.6, 126.9, 127.7, 128.4, 128.6, 131.6, 131.8, 134.1, 135.8,
136.8, 142.1, 147.6, 149.2, 151.1, 190.3 ppm; IR (KBr) ν: 1702
cmϪ1 (C᎐O); ϩESI-MS (60 V, CH CN) m/z = 704 (Mϩ);
1003.3402, found: 1003.3401.
meso-Ditolyl-4Ј-methylindaphyrin (10bH2). Prepared in 40%
yield (8 mg, 1.2 × 10Ϫ2 mmol) according to the procedure for
10aH2, using 7bH2 (21 mg, 3.0 × 10Ϫ2 mmol scale). Rf (silica–
CH2Cl2): 0.78; UV-vis (CH2Cl2) λmax (log ε): 364 (4.52), 420
(4.66), 498 (sh), 524 (sh), 560 (4.58), 644 (4.09), 741 (sh), 818
(3.31) nm; 1H NMR (400 MHz, CDCl3, δ): 1.43 (br s, 2H), 2.43
(s, 6H), 2.64 (s, 6H), 7.41 (d, J = 7.6 Hz, 2H), 7.48 (br s, 4H),
7.61 (s, 2H), 8.11 (d, J = 7.8 Hz, 2H), 8.14 (s, 2H), 8.52 (d,
J = 4.8 Hz, 2H), 9.10 (d, J = 5.0 Hz, 2H) ppm; 13C NMR (100
MHz, CDCl3, δ): 21.2, 21.4, 122.6, 123.5, 123.8, 126.1, 127.9,
129.8, 130.0, 133.6, 134.0, 134.1, 136.2, 136.4, 137.5, 137.8,
138.6, 144.8, 145.4, 155.8, 189.8 ppm; IR (KBr) ν: 1703 cmϪ1
(C᎐O); LR-ESI-MS (30 V, CH CN) m/z = 699 (MHϩ); HR-MS
᎐
3
HR-MS (FABϩ of Mϩ, PEG) calcd for C44H24N4O2Zn:
705.1269, found: 705.1295.
meso-Triphenyl-1-formylindaphyrin (12aH2). To a stirring
solution of 7aH2 (107 mg, 1.65 × 10Ϫ1 mmol) in CH2Cl2
(50 mL) were added NaIO4 heterogenized on silica gel (1 g),
followed by TFA vapors administered by pipette from the head-
space of a bottle of 10% TFA/CH2Cl2. The reaction was
allowed to proceed until the starting material had been con-
sumed (tlc control, ∼ 20 min), at which point Et3N (1 mL) was
added. The resulting solution was filtered to remove the silica
gel, washed twice with conc NaHCO3, once with H2O, dried
(anhydr MgSO4), and evaporated to dryness in vacuo. 12aH2
was purified by flash chromatography (silica gel, CHCl3). The
main fraction was evaporated to dryness, re-dissolved in
CH2Cl2, and crystallized by slow solvent exchange with MeOH.
Yield 60% yield (64 mg). Rf (silica–CH2Cl2): 0.69; UV-vis
(CH2Cl2) λmax (log ε): 425 (4.86), 468 (sh), 541 (sh), 618 (3.95),
678 (3.98), 792 (3.59) nm; 1H NMR (400 MHz, CDCl3, δ): 1.90
(br s, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.58
(t, J = 7.1 Hz, 2H), 7.66 (t, J = 7.6 Hz, 1H), 7.73 (br s, 7H), 7.86
(d, J = 7.2 Hz, 1H), 7.90 (t, J = 7.4 Hz, 2H), 8.08 (d, J = 4.6 Hz,
1H), 8.16 (m, 3H), 8.27 (d, J = 4.6 Hz, 1H), 8.53 (d, J = 5.0 Hz,
1H), 9.09 (d, J = 5.0 Hz, 1H), 9.13 (d, J = 7.2 Hz, 1H), 9.57 (s,
1H) ppm; 13C NMR (100 MHz, CDCl3, δ): 112.2, 124.2, 124.2,
125.7, 125.9, 127.4, 127.6, 128.3, 128.4, 128.4, 129.2, 131.9,
133.2, 133.8, 135.0, 136.6, 137.2, 139.3, 140.3, 143.2, 149.6,
᎐
3
(FABϩ of MHϩ, PEG) calcd for C48H35N4O2: 699.2760, found:
699.2786.
[meso-Ditolyl-4Ј-methylindaphyrinato]NiII (10bNi). Prepared
in 80% yield (43 mg, 5.7 × 10Ϫ2 mmol) according to the pro-
cedure for 10aNi using 8bNi (54 mg, 7.1 × 10Ϫ2 mmol scale) as
starting material. Rf (silica–CH2Cl2/0.5% MeOH): 0.88; UV-vis
(CHCl3) λmax (rel. intensity): 431 (1.00), 640 (0.20) nm; 1H
NMR (400 MHz, CDCl3, δ): 7.36 (d, J = 7.2 Hz, 2H), 7.52 (br s,
6H), 7.67 (s, 2H), 8.12 (s, 2H), 8.13 (d, with overlapping signal,
2H), 8.51 (d, J = 4.6 Hz, 2H), 8.92 (d, J = 4.9 Hz, 2H) ppm; HR-
MS (FABϩ of Mϩ, PEG) calcd for C48H32N4NiO2: 754.19,
found: 772.94 (Mϩ ϩ H2O).
meso-Tritolyl-1-formyl-(4Ј-methyl)indaphyrin (12bH2). Pre-
pared in 50% yield (8 mg, 1,1 × 10Ϫ2 mmol) according to the
procedure for 12aH2, using 7bH2 (17 mg, 2.4 × 10Ϫ2 mmol scale)
as starting material. Rf (silica–CH2Cl2): 0.70; UV-vis (CH2Cl2)
λmax (log ε): 427 (4.71), 470 (sh), 550 (sh), 626 (3.83), 682 (3.91),
795 (3.42) nm; 1H NMR (400 MHz, CDCl3, δ): 1.96 (br s, 2H),
2.43 (s, 3H), 2.62 (m, 9H), 7.45 (m, 8H), 7.68 (m, 2H), 7.82 (br s,
2H), 8.02 (d, J = 7.8, 1H), 8.08 (d, J = 4.6, 1H), 8.14 (d, J = 4.6,
1H), 8.17 (d, J = 4.6, 1H), 8.26 (d, J = 4.6, 1H), 8.51 (d, J = 5.0,
1H), 8.99 (d, J = 7.4, 1H), 9.03 (d, J = 5.0, 1H), 9.51 (s, 1H)
ppm; 13C NMR (100 MHz, CDCl3, δ): 21.6, 21.9, 22.0, 30.2,
112.5, 124.2, 124.3, 125.8, 126.6, 127.3, 127.3, 128.3, 128.4,
131.8, 133.2, 133.9, 135.1, 136.0, 137.4, 138.1, 138.4, 138.6,
139.4, 143.6, 147.4, 154.1, 158.1, 187.6, 191.0 ppm; IR (KBr) ν:
1711 (C᎐O), 1662 cmϪ1 (C᎐O); LR-ESI-MS (30 V, CH CN) m/z
153.9, 157.7, 187.3, 190.7 ppm; IR (KBr) ν: 1655 (C᎐O), 1710
᎐
cmϪ1 (C᎐O); LR-ESI-MS (30 V, CH CN) m/z = 645 (MHϩ);
᎐
3
HR-MS (FABϩ of MHϩ, PEG) calcd for C44H29N4O2:
645.2291, found: 645.2334.
[meso-Di(3,4,5-trimethoxyphenyl)-3Ј,4Ј,5Ј-methoxyindaphy-
rinato]Ni(II) (10cNi). Prepared in 85% yield (36 mg, 3.5 × 10Ϫ2
mmol) according to the procedure for 10aNi, using 8cNi
(43 mg, 4.1 × 10Ϫ2 mmol scale) as starting material. Rf (silica –
5% MeOH/CH2Cl2): 0.83; UV-vis (CHCl3) λmax (rel. intensity):
460 (1.00), 651 (0.35) nm; 1H NMR (400 MHz, CDCl3, δ): 3.84-
4.23 (m, 36H), 6.7 (br s), 7.54 (s, 2H), 8.17 (s, 2H), 8.57 (br s),
8.60 (d, J = 8.0 Hz, 2H), 8.85 (d, J = 8.0 Hz, 2H) ppm.
᎐
᎐
3
= 701 (MHϩ); HR-MS (FABϩ of MHϩ, PEG) calcd for
C48H37N4O2: 701.2917, found: 701.2878.
meso-Di(3,4,5-trimethoxyphenyl)-3Ј,4Ј,5Ј-methoxyindaphyrin
(10cH2). To a stirring solution of meso-tetra(3,4,5-trimethoxy-
phenyl)-2,3-dihydroxychlorin 7cH2 (25 mg, 2.5 × 10Ϫ2 mmol) in
CH2Cl2 (10 mL) were added, by pipette, TFA vapours from
the headspace of a bottle containing 10%TFA/CH2Cl2. To this
was added NaIO4 heterogenized on silica gel (0.25 g). Upon
Acknowledgements
We thank the donors of the Petroleum Research Fund (PRF),
administered by the American Chemical Society (ACS), and the
University of Connecticut Research Foundation for support of
this work.
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17 (a) H. Aihara, L. Jaquinod, D. J. Nurco and K. M. Smith,
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O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 8 4 – 1 4 9 1
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