Synthesis and properties of Zn-porphyrin with bipyridine-terminated side chains: Large conformational change induced by metal complexation

Article abstract of DOI:10.1016/j.tetlet.2011.11.041

Zinc porphyrin (1) containing 2,2′-bipyridyl units at the peripheral ends of both conjugated and alkyl side chains was prepared. Upon addition of Fe(II), the three bipyridyl terminals at both ends bind to Fe(II)s to form 1:2 complex 1·2Fe. The formation o

Full text of DOI:10.1016/j.tetlet.2011.11.041

Tetrahedron Letters 53 (2012) 309–312
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and properties of Zn-porphyrin with bipyridine-terminated
side chains: large conformational change induced by metal complexation
⇑
⇑
Mutsumi Kato, Erika Hashimoto, Masatoshi Kozaki , Shuichi Suzuki, Keiji Okada
Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan
a r t i c l e i n f o
a b s t r a c t
Zinc porphyrin (1) containing 2,20-bipyridyl units at the peripheral ends of both conjugated and alkyl side
chains was prepared. Upon addition of Fe(II), the three bipyridyl terminals at both ends bind to Fe(II)s to
form 1:2 complex 1ꢀ2Fe. The formation of 1ꢀ2Fe induced a large conformational change in the alkyl side
chains and moderately affected the binding between the zinc porphyrin and an imidazole ligand. These
results show that this method is useful for the communication between the porphyrin functional site and
the remote metal-binding site.
Article history:
Received 13 September 2011
Revised 1 November 2011
Accepted 7 November 2011
Available online 15 November 2011
Keywords:
Porphyrin
Ó 2011 Elsevier Ltd. All rights reserved.
Bipyridine
Iron complex
Conformation
Phenylene–ethynylene
The molecules that can reversibly change their shape and con-
formation in response to an external stimulus are attracting broad
interest for the construction of intelligent catalysts1 and receptors2
as well as molecular-scale machines.3 One of the challenging tasks
for the construction of complex molecular systems is to transfer
stimuli-induced structural alteration at a receptor to a remote
functional site as a property change. Metalloporphyrins are very
popular and valuable functional units for the construction of artifi-
cial enzymes where substituents around the porphyrin ring play an
essential role in controlling both the catalytic and ligand-binding
properties of metalloporphyrins.4 The function or property change
in metalloporphyrins induced by a large geometrical change via an
external stimulus at a distant receptor has many potential applica-
tions. However, the modulation of the function or property in
metalloporphyrins by external stimuli received at the remote
receptor has not been achieved. While a natural enzyme employs
a complex and precise hydrogen-bonding network to transfer local
structural deformation over large distances, a much simpler
approach may be possible using the combination of a rigid conju-
gated chain and flexible non-conjugated chains. Here we propose a
relatively simple method for the communication between the
porphyrin functional site and the remote stimuli-receiving site.
We report the unique design, synthesis, and properties of the
metal-switchable system in which the addition of metal ions
altered the conformation of substituents around a zinc porphyrin
unit. This system is extensively applicable to arosteric regulations
of both ligand-binding and catalytic ability of porphyrins.
We designed zinc porphyrin 1 on the basis of previously re-
ported snowflake-shaped architectures.5 Zinc porphyrin 1 consists
of both flexible and rigid chains and a porphyrin core (Fig. 1). Both
the flexible and rigid chains are terminated with bipyridine units.
The addition of a metal ion (Mn+) results in the formation of a cou-
ple of [M(bpy)3]-type complexes at both the ends of molecule 1.
The rigid chains determine the distance and the relative orienta-
tion between the coordinated metal ion and the porphyrin core.
As a result, metal complexation induces a large conformational
change in the flexible chains and changes the conformation of sub-
stituents around the porphyrin core. This may modify several prop-
erties of metalloporphyrin units.
In this system, the alkyl chain length is quite important since it
affects both the stability of the [M(bpy)3]-type complexes and the
steric demand of the ligand-binding site in the porphyrin unit.
Molecular mechanics (MM) calculations were performed for the
model compounds with several alkyl chain lengths that suggested
that an undecamethylene chain (C11H22) is most suitable for the
formation of the stable metal complex (see below).6
A
metal-ion-responsive unit was prepared according to
Schemes 1 and 2. First, the deprotonation of 5-methyl-2,20-bipyri-
dine (2) with LDA and subsequent treatment with excess 1,
10-dibromodecane gave 5-(11-bromoundecyl)-2,20-bipyridine (3)
in a 52% yield.7 Bipyridine-terminated pinacol borate 5 was ob-
tained in a 74% yield by the condensation of bipyridine 3 and pina-
col borate 4. A bipyridine-terminated rigid chain 8 was prepared in
⇑
Corresponding authors. Tel.: +81 6 6605 2564; fax: +81 6 6605 2522 (M.K.); tel.:
+81 6 6605 2568; fax: +81 6 6605 2522 (K.O.).
E-mail addresses: kozaki@sci.osaka-cu.ac.jp (M. Kozaki), okadak@sci.osaka-
cu.ac.jp (K. Okada).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.041

310
M. Kato et al. / Tetrahedron Letters 53 (2012) 309–312
N3Et2
N
N
N
N
N
N
H
N
N
Br
Br
7
Pd(PPh3)2Cl2, CuI
THF, -Pr2EtN
rt, 1 day
i
Metal-
binding site
Rigid
chain
66%
(CH2)11
(CH2)11
I
Flexible
chain
6
R
N3Et2
O
O
Porpyrin core
(Ligand
binding site)
Br
Br
O
O
tBu
(CH2)11
(CH2)11
tBu
5
N
N
N
Pd(PPh3)4
Cs2CO3,
Zn
N
N
N
N
N
tBu
tBu
DMF, toluene
80 ºC, 4 days
72%
N
N
N
N
O
O
Flexible
chain
I2, toluene
19 h, 71%
9: R = N3Et2
10: R = I
8
(CH2)11
(CH2)11
Rigid
chain
Metal-
binding site
Scheme 2. Synthesis of 10.
tBu
tBu
N
N
N
N
N
N
10
N
N
N
O
O
O
Pd(PPh3)4, Cs2CO3
Figure 1. Chemical structure of porphyrin 1.
B
Zn
B
1
DMF, toluene
80 ºC, 4 days
O
N
N
N
N
N
54%
1.LDA
(CH2)11Br
2.Br(CH2)10Br
52%
tBu
tBu
2
3
O
11
O
HO
B
B
O
N
O
N
4
O
Scheme 3. Synthesis of 1.
(CH2)11
K2CO3, DMF
50 ºC, overnight
74%
5
intense
p–
p⁄ bands at 290 nm (bipyridine skeletons) and 370 nm
(rigid conjugated chains) in addition to the characteristic Soret band
absorption (440 nm) and Q-band absorption (550–630 nm) of the
zinc porphyrin skeleton. The addition of Fe(II) solution
(1.20 ꢁ 10ꢂ3 M) caused a spectral change with clear isosbestic
points. The characteristic metal–ligand charge transfer (MLCT)
absorption for a [Fe(II)(bpy)3]-type complex appeared at around
500 nm.13 The intensity of the absorption at 500 nm increased line-
arly up to a plateau value, which was brought at about 2 equiv of
Fe(II) (Fig. 2 inset). These results suggest the quantitative formation
of [Fe(II)(bpy)3]-type complexes at both ends of 1. The formation of
the 1:2 (1:Fe(II)) complex is further supported by a series of ion
peaks observed at m/z = 3433 ([1ꢀ2Fe + 3BF4]+), 1673 ([1ꢀ2Fe +
2BF4]2+), 1086 ([1ꢀ2Fe + 3BF4]3+), and 793 ([1ꢀ2Fe]4+) in ESI-MS
(Fig. 3).
Scheme 1. Synthesis of 5.
a 66% yield by the Sonogashira coupling reaction of triazene 68 and
5-ethynyl-2,20-bipyridine (7).9 The Suzuki–Miyaura coupling reac-
tion of pinacol borate 5 and the rigid chain 8 afforded triazene 9 in
a 72% yield. Triazene 9 was heated with iodine in toluene to give
aryl iodide 10 in a 71% yield.10
The Suzuki–Miyaura coupling reaction of 10 and 1111 afforded
zinc porphyrin 1 as a purple solid in a 54% yield (Scheme 3). Zinc
porphyrin 1 was soluble in various organic solvents such as chloro-
form and toluene and was unambiguously characterized by means
of NMR, MALDI-TOF mass spectroscopy, and elemental analysis.12
The complexation of zinc porphyrin 1 and Fe(II) in a toluene–ace-
tonitrile (1:1 v/v) solution was monitored by means of UV–vis spec-
tral measurement (Fig. 2). A solution of 1 (2 ꢁ 10ꢂ5 M) showed
The MM calculations suggest that the alkyl chains in 1 have
large conformational freedom since many conformers with similar
steric energy are found for 1.6 One of the typical structures is

M. Kato et al. / Tetrahedron Letters 53 (2012) 309–312
311
3
2.5
2
0.35
0.3
0.25
0.2
0.15
0.1
0.05
0
0
0.5
1
1.5
2
2.5
3
1.5
1
Equivalent (Fe(II) / 1)
3425 3430 3435 3440 3445
m / z
0.5
0
300
400
500
600
700
Wavelength / nm
700
1400 2100 2800 3500
m / z
Figure 2. UV–vis spectra resulting form the titration of
1
(2 ꢁ 10ꢂ5 M) with
Fe(BF4)2ꢀH2O in a toluene–acetonitrile (1:1 v/v) solution (1.20 ꢁ 10ꢂ3 M). The inset
shows the change in the absorbance of MLCT band at 500 nm as a function of
Fe(II):1 concentration.
Figure 3. ESI-MS of 1ꢀ2Fe and expanded MS spectra (inset).
shown in Figure 4(a). In contrast, the formation of 1ꢀ2Fe resulted in
shifting of the alkyl chains close to the rigid chains as illustrated as
a typical structure in Figure 4(b). These results indicate that the
formation of 1ꢀ2Fe dramatically reduces the conformational free-
dom of flexible alky chains and changes the steric congestion of
the porphyrin core.
The large conformational change of the alkyl chains may affect
the steric demand around the ligand-binding site in 1. This effect
can be investigated by the addition of axial ligands with different
bulkiness. We selected imidazole and its derivatives 12 and 13 as
axial ligands for this purpose and compared the ligand-binding con-
stants for zinc coordination before and after metal complexation.
Compound 13 is expected to exhibit the largest steric interaction
with the alkyl chains, whereas imidazole is expected to show the
least effect. First, UV–vis titration was carried out by addition of
the solution of 13 to the toluene–acetonitrile (1:1 v/v) solution of
1 (2 ꢁ 10ꢂ5 M) (Fig. 5). Upon adding 13, the porphyrin Q-band of 1
was red-shifted that was attributable to the axial coordination
of 13 to a zinc atom in 1.4c,14 The selective formation of 1:1
complexes of zinc porphyrins and an imidazole derivatives is
well-established.15 The binding constant K1ꢀ13 was determined to
be (2.5 0.2) ꢁ 104 Mꢂ1, from the curve fitting calculations, for
the change in the absorbance at 613 nm (Fig. 5(b)). Similar UV–
vis titration using the toluene–acetonitrile (1:1 v/v) solution of 1
Figure 4. Stable conformers of 1 before (a) and after (b) the addition of Fe(II).

312
M. Kato et al. / Tetrahedron Letters 53 (2012) 309–312
0.6
0.5
0.4
0.3
0.2
0.1
0
a
N
N
N
N
O
O
13
12
In conclusion, we designed and synthesized zinc porphyrin that
has a couple of metal-ion-responsive units. The formation of [Fe(II)
(bpy)3]-type complexes induced a large conformational change in
alkyl chains. A weak communication between the metal-binding
site and the distant ligand-binding site through bridging alkyl
chains was observed by using the relatively large axial ligand 13.
Finding tight communications in artificial arosteric system with
porphyrins is currently underway.
500
550
600
650
wavelength / nm
Acknowledgments
0.5
0.45
0.4
b
This work was partially supported by Grants (Nos. 23350022
and 22350066) from JSPS.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.11.041.
0.35
0.3
References and notes
1. Nabeshima, T. Bull. Chem. Soc. Jpn. 2010, 83, 969–991.
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2. Yoon, H. J.; Kuwabara, J.; Kim, J.-H.; Mirkin, C. A. Science 2010, 330, 66–69.
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4. (a) Che, C.-M.; Huang, J.-S. Chem. Commun. 2009, 3996–4015; (b) Collman, J. P.;
Boulatov, R.; Sunderland, C. J.; Fu, L. Chem. Rev. 2004, 104, 561–588; (c) Suslick,
K. In Porphyrin Handbook; Kadaish, K. M., Smith, K. M., Guliard, R., Eds.;
Academic Press, 2000; Vol. 4, pp 41–63.
5. (a) Kozaki, M.; Okada, K. Org. Lett. 2004, 6, 485–488; (b) Kozaki, M.; Akita, K.;
Okada, K. Org. Lett. 2007, 9, 1509–1512; (c) Kozaki, M.; Akita, K.; Suzuki, S.;
Okada, K. Org. Lett. 2007, 9, 3315–3318; (d) Kozaki, M.; Tujimura, H.; Suzuki, S.;
Okada, K. Tetrahedron Lett. 2008, 49, 2931–2934; (e) Kozaki, M.; Akita, K.;
Okada, K.; Islam, D.-M. S.; Ito, O. Bull. Chem. Soc. Jpn. 2010, 83, 1223–1237.
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Spencer, N.; Stoddart, J. F.; Wenger, S. Chem. Eur. J. 1998, 4, 2413–2422.
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0
0.0005 0.001 0.0015 0.002 0.0025 0.003
[13] / [1]
Figure 5. (a) UV–vis spectra resulting form the titration of 1 (2 ꢁ 10ꢂ5 M) with 13
in a toluene–acetonitrile (1:1 v/v) solution. (b) The change in the absorbance of Q-
band at 630 nm as a function of 13:1 concentration. The solid line is a theoretical
binding curve obtained by curve fitting calculations.
(2 ꢁ 10ꢂ5 M) containing 2 equiv of Fe(II) gave the binding constant
K(1ꢀ2Fe)ꢀ13 = (3.1 0.2) ꢁ 104 Mꢂ1 (Fig. S2). These results suggest that
the formation of the [Fe(II)(bpy)3]-type complexes slightly
increases the stability of the coordination of the largest ligand 13
to zinc porphyrin 1. Namely, the structural change at the metal
binding site was successively transferred to the distant ligand
binding site by bridging alkyl chains. Then, the toluene–acetonitrile
(1:1 v/v) solution of 1 (2 ꢁ 10ꢂ5 M) was titrated using the solution
(3.0 ꢁ 10ꢂ2 M) of imidazole or 12. The addition of imidazole or 12
resulted in the red-shift of the porphyrin Q-band of 1 to show the
formation of 1ꢀimidazole or 1ꢀ12, respectively. The Fe(II)-free bind-
ing constants were determined to be K1ꢀimidazole = (1.4 0.1) ꢁ
104 Mꢂ1 and K1ꢀ12 = (3.6 0.3) ꢁ 104 Mꢂ1 from the curve fitting cal-
culations. The similar UV–vis titration using the toluene–acetoni-
trile (1:1 v/v) solution of 1 (2 ꢁ 10ꢂ5 M) containing 2 equiv of
Fe(II) gave the binding constant K(1ꢀ2Fe)ꢀimidazole = (1.5 0.1) ꢁ 104
11. (a) Hyslop, A. G.; Kellett, M. A.; Iovine, P. M.; Therien, M. J. J. Am. Chem. Soc.
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Jung, T. A.; Diederich, F. Chem. Eur. J. 2009, 15, 11139–11150.
12. Fluorescence spectra of
1
and 1ꢀ2Fe were measured in degassed solvent
(toluene–acetonitrile (1:1 v/v)) (Fig. S8). The excitation of 1 at 575 nm (Q band)
gave characteristic fluorescence spectra for the zinc porphyrin unit
(kEMꢂmax = 617 and 667 nm). The excitation of 1ꢀ2Fe at 575 nm where both
the porphyrin and the [Fe(II)(bpy)3]-unit have absorption (e1ꢀ2Fe:2e9ꢀFe = 1:0.4)
also showed the characteristic fluorescence spectra for zinc porphyrin but with
considerably lower intensity (95% quenching) probably due to the electron
transfer from porphyrin to the [Fe(II)(bpy)3]-unit.
Mꢂ1 and K(1ꢀ2Fe)ꢀ12 = (4.0 0.4) ꢁ 104 Mꢂ1
.
13. (a) Nabeshima, T.; Yoshihira, Y.; Saiki, T.; Akine, S.; Horn, E. J. Am. Chem. Soc.
2003, 125, 28–29; (b) Nabeshima, T.; Tanaka, Y.; Saiki, T.; Akine, S.; Ikeda, C.;
Sato, S. Tetrahedron Lett. 2006, 47, 3541–3544.
14. The negligible decrease in intensity of the MLCT band (500 nm) was observed
by the addition of less than 300 equiv of imidazole to a toluene–acetonitrile
(1:1 v/v) solution of the Fe(II) complex 9ꢀFe. Less than 200 equiv of the ligands
was used for the titration experiments.
15. Sanders, J. K. M.; Bampos, N.; C-Watson, Z.; Darling, S. L.; Hawley, J. C.; Kim, H.-
J.; Mak, C. C.; Webb, S. J. In Porphyrin Handbook; Kadaish, K. M., Smith, K. M.,
Guliard, R., Eds.; Academic Press, 2000; Vol. 3, pp 1–48.
These results suggest that the formation of the [Fe(II)(bpy)3]-
type complexes shows negligible effect on the axial complexation
for imidazole and ligand 12: the binding constants are almost iden-
tical for these complexes within experimental errors. However,
there is small but clear difference on the binding constants, K1ꢀ13
[(2.5 0.2) ꢁ 104 Mꢂ1] and K(1ꢀ2Fe)ꢀ13 [(3.1 0.2) ꢁ 104 Mꢂ1], sug-
gesting a small positive arosteric effect on the axial ligand binding
by the [Fe(II)(bpy)3]-type coordination.