Novel Cofacial Porphyrin-Based Homo- and Heterotrimetallic Complexes of Transition Metals

Article abstract of DOI:10.1002/chem.202102376

We present a straightforward and generally applicable synthesis route for cofacially linked homo- and heterotrimetallic trisporphyin complexes. The protocol encompasses synthesising the first aryl-based, trans-o-phenylene trisporphyrin starting from pyrrole and benzaldehyde with an overall yield of 3.6 %. It also allows investigating the respective cis-isomer as the first conformationally restricted planar-chiral trisporphyrin. The free-base ligand was used in subsequent metalation reactions to afford the corresponding homotrimetallic Mn(III)-, Fe(III)-, Ni(II)-, Cu(II)-, Zn(II)- and Pd(II) complexes – additionally, a small adaptation of the protocol resulted in the defined Ni(II)Fe(III)Ni(II) complex in a total yield of 2.3 %. By monitoring Ni(II) insertion into the empty trimeric ligands, we affirmed that the outer porphyrin rings are filled before the internal ring. The molecular species were characterised by ¹H NMR, UV-Vis, photoluminescence, IR, MS, CID, and high-resolution IMS measurements.

Full text of DOI:10.1002/chem.202102376

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Chemistry—A European Journal
Novel Cofacial Porphyrin-Based Homo- and
Heterotrimetallic Complexes of Transition Metals
Christoph Schissler,[a] Erik K. Schneider,[b] Sergei Lebedkin,[c] Patrick Weis,[b]
Gereon Niedner-Schatteburg,[d] Manfred M. Kappes,[b, c] and Stefan Bräse*[a, e]
Abstract: We present a straightforward and generally appli-
cable synthesis route for cofacially linked homo- and
heterotrimetallic trisporphyin complexes. The protocol en-
compasses synthesising the first aryl-based, trans-o-
phenylene trisporphyrin starting from pyrrole and benzalde-
hyde with an overall yield of 3.6%. It also allows investigating
the respective cis-isomer as the first conformationally re-
stricted planar-chiral trisporphyrin. The free-base ligand was
used in subsequent metalation reactions to afford the
corresponding homotrimetallic Mn(III)-, Fe(III)-, Ni(II)-, Cu(II)-,
Zn(II)- and Pd(II) complexes – additionally, a small adaptation
of the protocol resulted in the defined Ni(II)Fe(III)Ni(II)
complex in a total yield of 2.3%. By monitoring Ni(II) insertion
into the empty trimeric ligands, we affirmed that the outer
porphyrin rings are filled before the internal ring. The
molecular species were characterised by 1H NMR, UV-Vis,
photoluminescence, IR, MS, CID, and high-resolution IMS
measurements.
Introduction
developed to investigate catalysts for photosynthetic charge
separation and transfer.[4,5] Apart from the special pair, one
needs to consider an aggregate consisting of at least two
additional porphyrins spatially coupled by appropriate pros-
thetic groups to simulate the charge separation processes
occurring in nature.[3] A detailed analysis requires tuning
distance, orientation and number of discrete chromophores in
the model aggregate.[4] For this, rigidly fixed geometry and
distance are critical – but often difficult to control in artificially
synthesised analogues.
Beyond catalysing charge transfer, the chromophore orien-
tation in oligomeric metalloporphyrins can also influence energy
transfer via corresponding changes to electronic structure and
overall photophysical properties. We have been interested in
how this can be mediated by cooperative interactions between
non-covalently bound porphyrin subunits (and the metal
centres contained in them) and have used mass spectrometry
(MS) -based methods to study the dependence of electronic
The enforced aggregation of various metal ions or prosthetic
groups often constitutes an essential instrument in biological
systems to arrange catalytically active sites.[1] X-ray analysis of
the bacterial photosynthetic reaction centre has shown just
how sophisticatedly nature has evolved the spatial arrangement
of the six interacting tetrapyrroles involved in photosynthesis.[2]
Among these six chromophores, the primary electron donor in
the bacterial and green plant photosynthetic reaction centre
consists of a dimeric porphyrinoid pigment, the so-called
’special pair‘. This has been studied extensively and is well
understood. Complete elucidation of the electron-transport
processes subsequent to light triggered charge separation
remains one of the fundamental open questions in
photosynthesis.[3] Inspired by the three-dimensional orientation
of bacterial photosynthetic reaction centres in Rhodopseudomo-
nas viridis, several porphyrin-based synthetic models have been
[a] C. Schissler, Prof. S. Bräse
[e] Prof. S. Bräse
Institute of Organic Chemistry
Institute of Biological and Chemical Systems – Functional Molecular
Systems (IBCS-FMS)
Karlsruhe Institute of Technology (KIT)
Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Ger-
many)
Karlsruhe Institute of Technology (KIT)
Fritz-Haber-Weg 6, 76131 Karlsruhe (Germany)
E-mail: braese@kit.edu
[b] E. K. Schneider, Dr. P. Weis, Prof. M. M. Kappes
Institute of Physical Chemistry
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/chem.202102376
Karlsruhe Institute of Technology (KIT)
Fritz-Haber-Weg 2, 76131 Karlsruhe (Germany)
This manuscript is part of a Special Issue “Cooperative effects in hetero-
metallic complexes”.
[c] Dr. S. Lebedkin, Prof. M. M. Kappes
Institute of Nanotechnology
© 2021 The Authors. Chemistry - A European Journal published by Wiley-
VCH GmbH. This is an open access article under the terms of the Creative
Commons Attribution Non-Commercial License, which permits use, dis-
tribution and reproduction in any medium, provided the original work is
properly cited and is not used for commercial purposes.
Karlsruhe Institute of Technology (KIT)
Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Ger-
many)
[d] Prof. G. Niedner-Schatteburg
Fachbereich Chemie und Forschungszentrum OPTIMAS
Technische Universität Kaiserslautern
67663 Kaiserslautern (Germany)
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structure on the shape of porphyrin dimers containing various
metal centres.[6–8] In the contexts of both charge and energy
transfer in more rigidly fixed geometries, we have begun a
systematic study of oligomeric metalloporphyrins covalently
linked by way of o-phenylene subunits and have recently
reported a general synthesis route accessing homo- and
heterometallic dimers. Here we present a related synthesis
route to access trimetallic trisporphyrins.
In 1982, Wasilewski et al. were the first to synthesise a
stacked porphyrin trimer comprising coproporphyrin I doubly-
linked via ester bridges. However, due to the C2h symmetry of
the monomeric porphyrin derivatives used, the resulting trimer
could only be obtained as an inseparable mixture containing
three diastereomers.[9] Later on, in the ’80s Hamilton et al. and
Seta et al. synthesised comparable rather flexible trimeric
Towards this goal, we have aimed in this study for o-
phenylene linked trisporphyrins as ligands for homo- and
heterotrimetallic complexes. We base our approach on our
previously reported synthetic protocol for bisporphyrins which
we have developed further to access homo- and heterometallic
cofacial trisporphyrin complexes in comparatively high yield.
We have analysed the molecular structures via NMR spectro-
scopy in combination with ion mobility spectrometry (IMS). In
addition, we report collision-induced dissociation (CID) MS
measurements, UV-Vis absorption as well as photoluminescence
spectroscopy. Finally, high-resolution MS has been used to
evaluate the potential of the prebuilt (free-base) trimeric ligand
for selective metal ion complexation from solution.
porphyrins as pigments doubly connected via amide bridges - Results and Discussion
both to mimic photosynthetic reaction centres and to synthe-
sise molecular wires.[1,2,10] Chang et al. modified this multistep,
linear-sequence strategy by instead utilising anthracenes as
rigid spacers to fix three porphyrins in a defined spatial
arrangement. For this, 1,8-anthracene dicarboxaldehydes were
used as precursors in a two-fold condensation reaction to afford
a triple-decker trisporphyrin.[11] Osuka et al. extended this
reaction procedure by synthesising 1,3-diphenoxypropane-
linked trisporphyrins and was then able to expand the substrate
scope to pentameric porphyrin stacks in cooperation with
Maruyama.[4,12]
The above-mentioned cofacial porphyrin subunits all have
at least a 4.94 Å clearance (anthracene case) between the
molecular planes.[11,13] This can be reduced by exchanging the
linker moiety. In the corresponding o-phenylene-bridged
porphyrin dimer case, the average inter-plane distance reduces
to 3.43 Å.[14] X-ray analysis confirms that the strong π-interaction
Homometallic complexes
We have developed a facile synthetic route towards the novel
o-phenylene-trisporphyrin (free base OBTP, 6H-OBTP) 3 as a
cofacial ligand system (Scheme 1) using pyrrole and benzalde-
hyde as starting materials. As previously reported by us for
bisporphyrins, we have used the well-established condensation
of two pyrroles 1 with paraformaldehyde to yield dipyrro-
methane 4 in 65% yield to begin the seven-step reaction
procedure.[17,18] 4 can be used to build up trans-substituted
porphyrin cores like 5,15-diphenylporphyrin (5) if benzaldehyde
is employed as the corresponding aldehyde.[19] The subsequent
nucleophilic phenylation with PhLi, described by Senge et al.
and the following monobromination with NBS, yielded the
bromo-porphyrin precursor 7 in an overall yield of 38%
(Scheme 2).[19,20] After introducing the bromo-substitution, the
linker moiety can be incorporated without a second mixed-
condensation reaction, as is normally the case in literature.[17]
Instead, we use a standard Suzuki–Miyaura cross-coupling
reaction with 2-formylphenyl-boronic acid as the coupling
counterpart (Scheme 3).
°
of the chromophores can compensate for the 60 bite angle of
the o-phenylene-linker and yield a cofacial arrangement.[10]
In 1992 Osuka et al. developed a step-by-step approach,
starting with a cross-condensation reaction, which converts a
formyl-substituted porphyrin and a monoprotected phthalde-
hyde to a dimeric porphyrin. This was deprotected and utilised
in a second cross-condensation reaction to yield the Z-shaped
trisporphyrin.[15]
A complementary synthetic pathway was
developed by Therien et al., who transformed the zinc(II)
complex of a linear ethynyl-linked alkyl-porphyrin trimer by
applying a two-fold transition-metal-mediated [2+2+2] cyclo-
addition to yield a Z-shaped trimer.[16] To our knowledge, there
have been no further synthetic method developments towards
cofacially stacked porphyrin trimers since then.
Both pioneering approaches, however, have shortcomings.
The procedure of Osuka et al. uses rather expensive bis(3-ethyl-
4-methyl-1H-pyrrol-2-yl)methane as the basis for all condensa-
tion reactions.[14] Additionally, this synthetic approach constrains
the fine-tuning of distances because it only allows meso-
connected porphyrin subunits and restricts the incorporation of
residues.[17] Similarly, the synthesis route developed by Therien
et al. is not easily applicable to a wide range of different
Scheme 1. Targeted structures: 3: o-phenylene-trisporphyrin (6H-OBTP). The
porphyrin-based cofacial ligand systems are connected via a phenyl back-
bone and allows for three-fold coordination of various metal ions.
transition metals
–
in particular, not for heterometallic
complexes.[16]
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Scheme 2. Synthesis of brominated precursors: a) formaldehyde, InCl3,
°
NaOH, 55 C, 3 h, 65%; b) benzaldehyde, TFA, DDQ 4 h, 63%; c) PhLi, DDQ,
°
°
THF, 0 C!r.t., 30 min, 95%; d) NBS, CH2Cl2, 0 C!r.t., 3 h, 97%.
Scheme 4. Condensation reaction of two dipyrromethane-containing por-
phyrins with benzaldehyde yielding two possible isomers of trimeric
porphyrin stacks: trans-isomer 3 and cis-isomer 10. a) benzaldehyde (7.22
equiv.), TFA (8.46 equiv.), DDQ (2.10 equiv.), NEt3, CH2Cl2, r.t. 26.5 h, 13%; b)
benzaldehyde (2.00 equiv.), BF3 ·OEt2 (2.00 equiv.), DDQ (2.44 equiv.), NEt3,
CH2Cl2, r.t. 19 h, 1.9%
Scheme 3. Synthesis of the monomeric porphyrin covalently linked to the
phenyl backbone 8 and the subsequent condensation reaction to 9 bearing
dipyrromethane as part of the future internal diphenyl-porphyrin. a) 2-
°
this condensation reaction. Subsequent IMS of the singly
protonated trimers proved the identity and additional presence
of the cis-isomer. From the integrated mobilograms, we could
determine the trans:cis ratio to be 25:1 with TFA and 21:(8+1)
with BF3 ·OEt2 as catalyst (see IMS section for details). By
contrast, the 1H NMR spectra show the ratio of the neutral
molecules to be 50:1 or 5:1, respectively. The IMS data
overestimate the cis-/trans- ratio probably due to the higher
basicity of the cis-isomer and, therefore, higher ionizability via
protonation. Cis-o-phenylene-trisporphyrin is the first conforma-
tionally restricted planar chiral porphyrin trimer reported in the
literature, and its formation can be enhanced by choosing
BF3 ·OEt2 as a catalyst. DFT calculations show an energy gap of
only 0.14 eV between the trans- and the cis isomer underlining
that the isomeric ratio of the condensation reaction is kinetically
controlled (see DFT calculation (Supporting Information) for
details). Since the TFA catalysed reaction showed less scram-
bling whereas the overall yield (13%) is superior, we optimised
the reaction procedure by consequently adding the minimum
amount of benzaldehyde necessary to see a conversion while
retaining a rather high concentration of the acid in previously
degassed CH2Cl2. trans-6H-OBTP contains a two-fold axis as a
symmetry element which leads to rather simple NMR spectra.
Notably, are the downfield shifted NH protons occurring at
À 3.79 ppm as a broad signal for the outer four NH protons and
at À 4.20 ppm as a comparatively sharp singlet for the two inner
NH protons. In conclusion, our novel synthetic route presents
the synthesis of 5,15-bis(2-(10,15,20)-triphenylporphyrinylphen-
yl)-10,20-diphenylporphyrin (3) the first aryl-based trimeric
porphyrin stack, which can be synthesised starting with pyrrole
and benzaldehyde over 7 steps in an overall yield of 3.6%.
Next, the as-synthesised free-base ligand with the trans/cis
ratio of 98:2 was triply metallated with six different transition
metals (Scheme 5), and the resulting metal complexes, bearing
the same trans/cis ratio were systematically analysed with UV-
Vis, IR-spectroscopy, MS and IMS. For the metal coordination,
we observed that reaction times needed to be only slightly
formylphenyl-boronic acid, Pd(PPh3)4, K3PO4, THF, 80 C, 14 h, 78%; b)
pyrrole, TFA, NEt3, r.t., 4 h 93%.
Rather than reacting the aldehyde functionalities by mixed
condensation to obtain the respective o-phenylene-bisporphyr-
in, as previously reported by us, we have instead converted
them to a porphyrin-bearing dipyrromethane 9. First, we
attempted Bein’s strategy, which has been employed to
synthesise di(1H-pyrrole-2-yl)methane (4) using InCl3 as Lewis-
acid and NaOH as a neutralising agent. We could detect the
desired product via MS but only as a side product besides the
oxidised dipyrromethane. In the second attempt, we explored
TFA as a catalyst alongside NEt3 as a base - a procedure closer
to commonly used conditions in porphyrin chemistry. After 4 h
stirring at room temperature and continuously adding TFA, we
obtained the 5-(2-(di(1H-pyrrol-2-yl)methyl)phenyl)-10,15,20-tri-
phenylporphyrin (9) in 93% isolated yield after performing
flash-chromatography on silica gel and eluting with toluene.
The corresponding NMR spectra were recorded in toluene-d8 to
avoid oxidation and show the nine dipyrromethane protons in
the expected region of 4.98–6.30 ppm.
Additionally, the porphyrin NH signals experience a down-
field shift to À 2.19 ppm due to additional deshielding from the
pyrrole subunits. This robust procedure provides monomeric
porphyrin precursors in an excellent total yield of 28% via 6
steps. The dipyrromethane subunit now takes part in an acid-
catalysed concluding condensation with benzaldehyde in a
ratio of 1:1, as represented in Scheme 4. Surprisingly we
noticed by-product 10 in approaches a) and b), which could not
be separated from 3 even after four consecutive flash column
chromatography passes on silica gel eluting with differing
solvents.
Additionally, mass spectrometry alone did not help to solve
the corresponding molecular structure since the 3 and 10 are
isomers. Since we additionally obtained o-phenylene-bispor-
phyrin in traces, it became clear that scrambling plays a role in
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monoxide dehydrogenase active site analogue. To circumvent
potential oxidation of the porphyrin-dipyrromethane 9, the
Ni(II) cation was inserted after the Suzuki-Miyaura cross-
coupling reaction in the monomeric formyl-phenyl-porphyrin 8
°
by treatment with Ni(OAc)2 ×4 H2O at 100 C for 18.5 h in 93%
yield (Scheme 6). The conversion of the aldehyde functionality
to the dipyrromethane-containing Ni(II)porphyrin 18 was con-
ducted as described for the free-base analogue by doubling the
reaction time resulting in a yield of 84%. Apart from the missing
porphyrinic NH protons and slightly increased coupling con-
3
stants (from J=4.7 Hz to 4.9 Hz), Ni(II) coordination leads to
the sharpening of the signals arising from the dipyrromethane
1
subunit in the H NMR spectrum. A possible interpretation is
that Ni(II) complexation prevents intramolecular hydrogen
bonding, which would otherwise occur in the free-base
analogue 9. In a subsequently performed condensation reac-
tion, similar to Scheme 5 but with reduced reaction time, the
2Ni-2H-OBTP, 19, can be obtained in 14% yield. To isolate the
2Ni-2H-OBTP species, a tedious work-up comprising three
consecutive flash-column chromatographic cycles with differing
solvents was necessary. The ring currents of the two adjacent
porphyrins arranging in a sandwich-like structure lead to a
significant up-field shift of the NH protons of the interior
porphyrin ring to À 5.01 ppm. This indicates a significant change
in the electronic nature of this molecular subunit in comparison
to the free-base porphyrin contained in the Ni-2H-o-phenylene-
bisporphyrin - as reported earlier by our consortium.[17]
Scheme 5. Cofacial porphyrin-based homotrimetallic complexes a) (11) *Mn-
°
°
(III): MnCl2, DMF, 150 C, 3 h, 86%; (12) **Fe(III): FeBr2, HCl, DMF, 140 C, 3 h,
°
89%; (13) Ni(II): Ni(OAc)2 ×4 H2O, CHCl3/MeOH, 100 C, 17 h; 95%; (14) Cu(II):
°
Cu(OAc)2, CHCl3/MeOH, 80 C, 3 h, 65%; (15) Zn(II): Zn(OAc)2, CHCl3/MeOH,
°
r.t., 2 h, 86%; (16) Pd(II): Pd(OAc)2, CHCl3/MeOH, 80 C, 2 h, 84%; * 3Ni-, 3Cu-,
3Zn- and 3Pd-OBTP have been detected as monocations by MS, whereas
3Fe-OBTP has been detected with adducts of O and Cl. The Mn-trimer was
observed with mainly two attached chlorides.
extended relative to our previous dimer work to obtain
complete three-fold complexation.[17] Exceptionally this does
not hold for the 3Ni-OBTP 13 complex since we observed
°
degradation while stirring in DMF at 100 C.
This observation also led us to look more closely at the
reaction process leading to three-fold Ni(II) complexation of the
empty trisporphyrin ligand. Indeed, the reaction time depend-
Additionally, we measured the CID spectra of two differently
synthesised [2Ni-3H-OBTP]+ complexes. In the first approach,
the ligand was only partially filled with Ni(II) by sampling at
50% of the reaction time required for complete filling with
three metals. In the second approach, the Ni(II)porphyrin 18
(see below) was coupled to form a trimer. The CID-spectra have
been measured using a Bruker timsTOF system which couples
high-resolution ion mobility spectrometry with mass spectrom-
etry (IMS-MS). The fragment spectra of both samples look
almost identical and can be found in the Supporting Informa-
tion.
They do not show fragments corresponding to protonated
free-base monomers. Instead, nickelated monomers, as well as
1.5-mers containing one nickel atom and residues of a second
porphyrin ring, are observed as main products. This and the
similarities between the two sets of CID-spectra allow us to
conclude that both approaches lead to the same main product:
Ni has inserted into each of the two outer porphyrins
exclusively. We, therefore, agree with Osuka et al., who
postulated in 1991 that the outer porphyrin subunits were
metalated first.[14]
Scheme 6. Synthetic route towards an extended artificial carbon monoxide
dehydrogenase active site analogue (20) as proof of principle reaction for
several trimeric heterometallic porphyrin complexes. a) Ni(OAc)2 ×4 H2O,
Heterometallic complexes
°
CHCl3, MeOH, 100 C, 18.5 h, 93% b) pyrrole, TFA, NEt3, r.t., 8 h, 84%, c)
benzaldehyde (2,16 equiv.), TFA (3.69 equiv.), NEt3, CH2Cl2, r.t., 3 h, 14%, d)
As a proof of principle, to realise porphyrin-based-transition-
metal-containing trimeric heterometallic complexes, we specifi-
cally built a trisporphyrin containing two Ni(II) and one Fe(III)
centre – which may also be thought of as an extended carbon
°
FeBr2, DMF, 150 C, 2 h, 94%. (Ligand L cannot be determined precisely as in
MS we could assign adducts with several oxygens as dominant counter
ions).
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