Porphyrin-based molecular receptors for alkali metal cations: synthesis and chemical modification

Article abstract of DOI:10.1016/j.tetlet.2008.04.029

A synthetic approach leading to the meso-arylporphyrins containing a conformationally mobile polyether fragment on the benzene ring with a terminal pyridine ring has been developed, which opens the possibility for design of new porphyrin-based molecular receptors for detection and selective binding of alkali metal cations.

Full text of DOI:10.1016/j.tetlet.2008.04.029

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3752–3756
Porphyrin-based molecular receptors for alkali metal cations:
synthesis and chemical modification
Nugzar Zh. Mamardashvili *, Olga V. Maltseva, Yulia B. Ivanova, Galina M. Mamardashvili
Institute of Solution Chemistry, Russian Academy of Sciences, Akademicheskaya 1, Ivanovo 153045, Russia
Received 8 February 2008; revised 4 March 2008; accepted 4 April 2008
Available online 8 April 2008
Abstract
A synthetic approach leading to the meso-arylporphyrins containing a conformationally mobile polyether fragment on the benzene
ring with a terminal pyridine ring has been developed, which opens the possibility for design of newporphyrin-based molecular receptors
for detection and selective binding of alkali metal cations.
Ó 2008 Elsevier Ltd. All rights reserved.
Porphyrins occupy a unique place among numerous
macroheterocyclic compounds, which are able to form
self-organized supramolecular ensembles via multisite
binding.1–3 Their properties originate from the unusual
geometric and electronic structure of the tetrapyrrole chro-
mophore, which can act as a source of signal reflecting pro-
cesses occurring in the system under study.4–6 In recent
years, interest in porphyrin derivatives has increased con-
siderably due to their ability to participate in molecular
recognition, that is, in a selective binding process in which
a receptor interacts effectively only with molecules of a def-
inite type through intermolecular forces.7–9 In this connec-
tion, important results can be obtained by modification of
the porphyrin macrocycle with polyether fragments pos-
sessing intrinsic binding ability toward different substrates.
Combinations of porphyrin and polyether fragments
linked together through covalent bonds could give rise to
spatially preorganized three-dimensional structures, show-
ing an effective cation-assisted chirality induction.10,11
In our investigation, a synthetic approach leading to
meso-arylporphyrins containing a conformationally mobile
complexing polyether fragment on the benzene ring with a
terminal pyridine ring has been developed. The results of
the studies on the dependence of the spectral parameters
of the tetrapyrrole chromophore upon acid–base equilibria
and complex formation with alkali metal cations indicate
that the porphyrin derivatives can be used to construct
molecular devices possessing practically important
properties.
The reaction of 2-ethoxycarbonyl-3-butyl-4-methyl-
pyrrole (1) with 3-methoxybenzaldehyde (2) in ethanol in
the presence of HCl gave meso-(3-methoxyphenyl)-dipyrro-
lylmethane (3 ), which was easily converted into meso-
(3-hydroxyphenyl)-dipyrrolylmethane (4) by treatment
with BBr3. The reaction of 4 with polyethylene glycol bis-
(4-toluenesulfonates) 5, 6, and 3-hydroxypyridine (7) in
the presence of cesium carbonate in DMF–MeCN resulted
in the dipyrrolylmethanes (8, 9) having conformationally
mobile polyether fragments with a terminal pyridine group
at the meso-position. Alkaline hydrolysis and high temper-
ature decarboxylation of the 5,50-bis(ethoxycarbonyl)-di-
pyrrolylmethanes 8, 9 gave the intermediate 5,50-di-
unsubstituted dipyrrolylmethanes, acid-catalyzed conden-
sation of which with 5,50-diformyl-4,40-dibutyl-3,30-dim-
ethyldipyrrolylmethane (10) with subsequent oxidation of
the reaction mixture using tetrachloro-1,4-quinone resulted
in the porphyrin ligands 11, 12. The reaction of 11, 12 with
zinc(II) acetate in boiling DMF gave porphyrin metal com-
plexes 13, 14. The assumed structures of the dipyrrole and
tetrapyrrole compounds 3, 4, 8, 9, 11–14 were consistent
*
Corresponding author. Tel.: +7 4932 336990; fax: +7 4932 336237.
E-mail address: ngm@isc-ras.ru (N. Zh. Mamardashvili).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.029

N. Zh. Mamardashvili et al. / Tetrahedron Letters 49 (2008) 3752–3756
3753
1
with elemental analysis, electronic absorption, H NMR
and mass spectra data.
A study on the complex formation between compound
14 and K+ by spectrophotometric titration showed that
OCH3
CH3O
Bu
Me
CHO
Bu
Bu
Me
Me
2
H+, reflux
BBr3
EtOOC
COOEt
EtOOC
H
N
H
1
N
H
N
H
97 %
79 %
3
N
O)
n
X(CH2OCH2O)nY
OH
,
6
5
O
(
OH
Bu
Bu
Me
Me
Bu
Bu
Me
Me
N
7
BBr3
EtOOC
COOEt
EtOOC
COOEt
N
H
N
H
97 %
N
H
N
H
8 (66%), 9 (72 %)
4
Bu
Bu
Me
Me
N
O
O
O)
n
C
N
C
Bu
Bu
N
H
O
H
H
Me
Me
Me
(
H
N
N
M
10
N
N
Me
Bu
Bu
11 (24 %), 12 (19 %), 13 (86 %), 14 (71 %)
M = H2(11, 12), Zn (13,14); n = 4 (8, 11, 13), 5 (9, 12, 14)
The binding ability of porphyrins 13 and 14 toward
alkali metal cations (Li+, Na+, and K+) was studied in a
2:1 toluene–methanol mixture. Among the examined com-
pounds, only 14 was able to bind potassium cations with
the formation of complex 15 due to the geometric para-
meters of the polyether cavity. Conformational flexibility
of the polyether bridge enables the terminal pyridine ring
to approach the tetrapyrrole macrocycle, which is readily
complex 15 has a composition of 1:1. The titration curve
is characterized by one step (Fig. 1), which corresponds
to an isosbestic point in the electronic absorption spectra
(Fig. 2). Upfield shifts of signals of the protons in the pyr-
idine fragment (as compared to pyridine) were observed in
the 1H NMR spectrum of complex 15 (Dd = 4.5 and
1.1 ppm for a-H and b-H, respectively) in the concentra-
tion range corresponding to the inflection on the spectro-
photometric titration curve.
1
detected by the electronic absorption and H NMR spec-
tra. The donor–acceptor interaction between the pyridine
nitrogen atom and the zinc cation leads to a red shift of
the absorption band (up to 10 nm) in the UV–vis spectra,
and shielding of the pyridine fragment by the porphyrin
ring current induces upfield shifts of the signals of the pro-
tons of the pyridine ring, which reside in the vicinity of the
macrocycle.
The stability constant of complex 15 (Ks = 0.361 ꢀ
106 Mꢁ1) was calculated according to a standard procedure9
on the basis of spectrophotometric data obtained at two
wavelengths (descending and ascending) using formula 1:
ꢀ
ꢁ
½ZnPꢂKþꢃ
1
DAi;k DA0;k
1
2
Ks ¼
¼
:
ð1Þ
½ZnPꢃ½Kþꢃ ½Kþꢃ
DA0;k DAi;k
1
2
O
O
O
O
K
N
O
O)
n
Bu
Bu
Me
Bu
N
Bu
Me
K
O
O
Me
Me
(
N
N
Me
Me
N
Zn
N
Zn
N
N
N
N
Me
Me
Bu
Bu
Bu
Bu
14, n = 5
15

3754
N. Zh. Mamardashvili et al. / Tetrahedron Letters 49 (2008) 3752–3756
Fig. 1. Spectrophotometric titration curve of 14 with K+ intoluene–MeOH
(2:1) at the ascending wavelength (k = 415 nm, c (14) = 5.5 ꢀ 10ꢁ6 M) at
298 K.
Fig. 3. Spectrophotometric titration curve of 12 with H+ in the system 12-
HClO4–MeCN at 298 K.
is the absorption at a given wavelength and concentration.9
The error in the determination of Ks was 7–10%. No bind-
ing with Li+ or Na+ ions was observed.
With a view to design sterically preorganized complex-
ing cavities for selective binding of alkali metal cations,
we also examined the effect of acid–base equilibria on the
spectral parameters of the tetrapyrrole chromophore. Spec-
trophotometric–potentiometric titration of porphyrin 12
in the system 12-HClO4–MeCN showed that the process
can be represented by equilibria 2 and 3.
Fig. 2. Changes in the electronic absorption spectra of 14 (Soret band
region) upon addition of K+ from 0 to 10ꢁ3 M in toluene–MeOH (2:1) at
298 K (c (14) = 5.5 ꢀ 10ꢁ6 M).
Kb1
H2P þ Hþ ¢ H3Pþ;
ð2Þ
ð3Þ
Kb2
H3P þ Hþ ¢ H4P2þ
:
Here k1 is the descending wavelength, k2 is the ascending
wavelength, [K+] is the concentration of K+ ions, [ZnP]
is the concentration of zinc–porphyrin, DA0 is the maximal
variation of the absorption at a given wavelength, and DAi
The spectrophotometric titration curve of 12 with H+ is
characterized by two steps (Fig. 3), each corresponding to
a family of isosbestic points (Fig. 4). At the limiting values
Fig. 4. Changes in the UV–vis spectra of the 12-HClO4–MeCN system in the region of HClO4 concentration 10ꢁ14–10ꢁ10 M (a) and 10ꢁ10–10ꢁ7 M (b) at
298 K (c (12) = 1.51 ꢀ 10ꢁ5 M).

N. Zh. Mamardashvili et al. / Tetrahedron Letters 49 (2008) 3752–3756
3755
of the examined acidity range, we observed absorption
spectra of individual neutral porphyrin 12 [H2P, kmax, nm
(loge): 496 (4.17), 528 (4.01), 565 (3.87), 618 (3.74)] and
its mono- [H3P+, kmax, nm (loge): 499 (3.91), 530 (3.95),
of tetrapyrrole compounds as selective receptors for extrac-
tion and membrane transfer processes and supersensitive
switches for data storage could be considerably extended.
The selectivity and high sensitivity of porphyrins to low-
energy effects provide the possibility for controlling chem-
ical processes involving these compounds.
559 (3.95), 599 (3.57), 618 (3.45)] and di- [H4P2+, kmax
,
nm (loge): 547 (4.45), 588 (3.94)] cations. The equilibrium
constants calculated according to a standard procedure12
were logKb1 = 11.58 0.01 (Eq. 2) and logKb2 = 8.77
0.01 (Eq. 3).
The constants Kb1 and Kb2 were calculated, and their
accuracy was estimated from two parallel measurements
using the SigmaPlot program by fitting the parameters in
Eq. 4, which relates absorption to the pH of solutions of
dibasic acids:13
Zinc(II) 2,8,12,18-tetrabutyl-3,7,13,17-tetramethyl-5-{3-
[11-(pyridin-3-yloxy)-3,6,9-trioxaundecyloxy]phenyl}-por-
phyrin: 13. To a solution of porphyrin (13): (30 mg) in
70 ml of DMF, excess zinc(II) acetate (molar ratio 1:10)
was added. The solution was heated for 30 min at the boil-
ing point, cooled, and diluted with an equal volume of
water. The residue was filtered, dried, and subjected to
chromatography over aluminum oxide using methylene
chloride–hexane (1:1) as eluent. A red-brown band was col-
lected and the solvent was evaporated. Recrystallization of
the residue from CH2Cl2–MeOH (1:1) yielded 15 as purple
needles (30.10 mg, 86%), mp 136 °C. Analytical data: Rf
0.63 (Al2O3, CH2Cl2–C6H14, 1:2). UV–vis (toluene): kmax
AH P þ 10pHKb1A
þ 102pHKb1Kb2A
þ 102pHKb1Kb2
þ
H4P2þ
H3P
b1
2
Ac ¼
:
ð4Þ
pH
1 þ 10
K
Here, Ac is the current absorption of H2P solution at an
þ
analytical wavelength, and AH P; A
, and AH P are
H4P2þ
1
2
3
in nm, (loge): 409.1 (5.03), 539.1 (4.22), 574.1 (3.79). H
the absorptions of solutions of individual H2P, H4P2+
,
NMR (300 MHz, CDCl3): 10.03 (s, 2H, meso-H), 9.92 (s,
1H, meso-H), 7.91 (d, J = 7.8 Hz, 1H, 6-H.), 7.81 (s, 1H,
2-H), 7.75 (d, J = 7.8 Hz, 1H, 40-H), 7.65 (t, J = 8.5 Hz,
1H, 50-H), 7.53 (t, J = 8.5 Hz, 1H, 5-H), 7.49 (m, 2H, 20-
H, 60-H), 7.29 (m, 1H, 4-H), 3.79 (t, J = 7.2 Hz, 8H,
CH2CH2CH2CH3), 3.24 (m, 16H, OCH2CH2O), 2.39 (m,
8H, CH2CH2CH2CH3), 1.47 (m, 8H, CH2CH2CH2CH3),
1.20 (s, 6H, CH3), 1.17 (s, 6H, CH3), 1.05 (t, J = 7.2 Hz,
12H, CH2CH2CH2CH3). FAB+ MS: [m/z (rel. intens.
%)]: 999.39 ( M+1, calcd: 998.41, 71%). Calcd for
C59H75N5O5Zn: C, 70.94; H, 7.51; N, 7.01. Found: C,
70.90; H, 7.49; N, 6.97.
and H3P+ species with an analytical concentration (c0).
The titration curve shown in Figure 3 has a stepwise shape
since the difference between the first and second proton-
ation constants is about three orders of value.13
Due to the binding of K+ by the –(OCH2CH2)n– com-
plexing site of 12, the conformation of the polyether chain
changes in such a way that the pyridine and tetrapyrrole
fragments in the resulting complex 16 become spatially
close and the pyridine nitrogen atom interacts with the
hydrogen atoms in the coordination site of the protonated
tetrapyrrole macrocycle. It should be noted that only
H4P2+ generates 16. Such self-organization seems to be
fairly promising from the viewpoint of the design of supra-
molecular receptors for alkali metal cations. It provides a
means for optimization of the geometric parameters of a
receptor cavity to match the substrate parameters.
Our results indicate that porphyrins containing poly-
ether moieties can be used for the design of new molecular
receptors for alkali metal cations. Such receptors are more
advantageous than the traditionally used crown ethers due
to the presence of a tetrapyrrole chromophore which
makes it possible to apply spectrophotometric methods
intrinsic to the chemistry of porphyrins while studying
complex formation processes. As a result, the application
Acknowledgment
We are indebted to the Russian Foundation for Basic
Research for financial support (Project No. 08-03-97501-
r_centre_a).
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2008.04.
029.
O
O
O
O
K+
N
O
O)
n
Bu
Bu
Bu
Bu
K+
Bu
Bu
Bu
N
O
, 2H+
Me
Me
O
Me
Me
(
N
N
Me
Me
N
+
Me
Me
H
HN
N
H
H
N
H +
N
H
N
Bu
12, n = 5
16

3756
N. Zh. Mamardashvili et al. / Tetrahedron Letters 49 (2008) 3752–3756
7. Anderson, H. L.; Anderson, S.; Sanders, J. K. M. J. Chem. Soc.,
References and notes
Perkin Trans. 1 1995, 2231.
8. Jokic, D.; Asfari, Z.; Weiss, J. Org. Lett. 2002, 4, 2129.
9. Hunter, C. A.; Meah, M. N.; Sanders, J. K. M. J. Am. Chem. Soc.
1990, 112, 5773.
10. Kubo, Y.; Ishii, Y.; Yoshizawa, T.; Tokita, S. Chem. Commun. 2004,
1394.
11. Kubo, Y.; Ohno, T.; Yamanaka, J.; Tokita, S.; Iida, T.; Ishimaru, Y.
J. Am. Chem. Soc. 2001, 123, 12700.
12. Sheinin, V. B.; Ivanova, Yu. B.; Chizhova, N. V. Russ. J. Neorg.
Khim. 2004, 49, 112.
1. Koifman, O. I.; Mamardashvili, N. Zh.; Antipin, I. S. Synthetic
Receptors Based on Porphyrins and Their Conjugates with Calix-
[4]arenes; Nauka: Moscow, 2006; p 246.
2. Mamardashvili, N. Zh.; Koifman, O. I. Russ. J. Org. Chem. 2005, 41,
787.
3. Mamardashvili, N. Zh.; Golubchikov, O. A. Russ. J. Usp. Khim. 2000,
69, 337.
4. Wylie, R. S.; Levy, E. G.; Sanders, J. K. M. Chem. Commun. 1997, 1611.
5. Anderson, H. L.; Hunter, C. A.; Meah, M. N.; Sanders, J. K. M. J.
Am. Chem. Soc. 1990, 112, 5780.
13. Bernshtein, I. Ya.; Kaminskii, Yu. L. Spectrophotometric Analysis in
Organic Chemistry; Khimiya: Leningrad, 1986; p 200.
6. Pukhovskaya, S. G.; Guseva, L. Zh.; Kuvshinova, E. M.; Mamar-
dashvili, N. Zh.; Golubchikov, O. A. Russ. J. Koord. Khim. 1998, 29,
851.