Synthesis and anion binding properties of 2,5-diamidothiophene polypyrrole Schiff base macrocycles

Article abstract of DOI:10.1021/ol052162b

(Chemical Equation Presented) Two easy-to-synthesize polypyrrolic 2,5-diamidothiophene Schiff base macrocycles are reported, along with their anion binding properties as determined via UV-vis spectroscopic titrations carried out in dichloroethane. There i

Full text of DOI:10.1021/ol052162b

ORGANIC
LETTERS
2005
Vol. 7, No. 23
5277-5280
Synthesis and Anion Binding Properties
of 2,5-Diamidothiophene Polypyrrole
Schiff Base Macrocycles
Jonathan L. Sessler,*,† Vladimir Roznyatovskiy,†,‡ G. Dan Pantos,†
Natalya E. Borisova,‡ Marina D. Reshetova,‡ Vincent M. Lynch,†
Victor N. Khrustalev,§ and Yuri A. Ustynyuk*,‡
Department of Chemistry and Biochemistry and Institute for Cellular and Molecular
Biology, UniVersity of Texas at Austin, 1 UniVersity Station A5300, Austin, Texas
78712-0165, Department of Chemistry, M. V. LomonosoV Moscow State UniVersity,
Leninskie Gory, 119899 Moscow, Russian Federation, and A. N. NesmeyanoV Institute
of Organoelement Compounds, 28 VaViloV str., 119991 Moscow, Russian Federation
sessler@mail.utexas.edu; ustynyuk@nmr.chem.msu.su
Received September 8, 2005
ABSTRACT
Two easy-to-synthesize polypyrrolic 2,5-diamidothiophene Schiff base macrocycles are reported, along with their anion binding properties as
determined via UV vis spectroscopic titrations carried out in dichloroethane. There is a striking difference between the interactions with
−
anions of the two macrocycles, a finding ascribed to differences in their rigidity. For example, the more flexible dipyrromethane-derived
macrocycle displays a 1.2:1 hydrogen sulfate versus nitrate selectivity, while its more rigid bipyrrole-derived congener shows a 7.4:1 selectivity
in favor to hydrogen sulfate.
The ubiquity of anions in nature makes an understanding of
biological anion-receptor interactions a topic of considerable
current interest.1 It is also inspiring the synthesis of synthetic
anion receptors, systems whose potential utility could span
the full spectrum of applications from separations and waste
remediation to biomedical analysis and therapy.2 Indeed, the
field of synthetic anion receptor chemistry is one of the
fastest growing disciplines within the general context of
supramolecular chemistry.3 One of the problems that has
attracted the attention of our groups6 and others4 is the design
of systems that effect the specific recognition of hydrogen
sulfate in nitrate-rich mixtures. The reason for this interest
is that such mixtures are surrogates for nuclear tank waste,
whose remediation is made difficult by the presence of small
† University of Texas at Austin.
‡ M. V. Lomonosov Moscow State University.
§ A. N. Nesmeyanov Institute of Organoelement Compounds.
(1) Bianchi, A.; Bowman-James K.; Garcia-Espan˜a, E. Supramolecular
Chemistry of Anions; Wiley-VCH: New York, 1997.
(2) (a) Fundamentals and Applications of Anion Separations; Moyer,
B. A., Singh, R. P., Eds.; Kluwer Academic/Plenum Publishers: New York,
2004. (b) Anion Sensing; Stibor, I., Ed.; Springer-Verlag: Berlin, 2005.
10.1021/ol052162b CCC: $30.25
© 2005 American Chemical Society
Published on Web 10/11/2005

amounts of sulfate.5 Recently, we reported the synthesis of
a 2,6-diamidopyridine-dipyrromethane hybrid macrocycle6
and several congeners based on bipyrole7 that displayed high
new agents display affinities for a broader range of anions.
They also differ in terms of selectivity. In particular, while
the pyridine-based macrocycles display a preference for
tetrahedral anions, the thiophene-based systems permit a
discrimination based on size rather than specific geometry.
The bis(2-aminophenyl)-thiophene-2,5-dicarboxamide 3
(Scheme 1) is the central precursor for the synthesis of
-
selectivity for HSO4- over NO3 . In an effort to understand
more completely the determinants of this selectivity, we have
sought to replace the central 2,6-diamidopyrridine moiety
by another known anion receptor subunit, namely, 2,5-
diamidothiophene.8 Such a substitution was expected to result
in a more flexible macrocyclic receptor and one that would
interact with a wider range of anions.9
Scheme 1. Synthesis of Precursor 3
We now wish to report the synthesis and anion binding
properties of the first members of this potentially large series
of receptors, as well as their anion binding properties. As
compared to the corresponding pyridine-based systems, these
(3) For recent reviews of work in the anion-binding field, please see:
(a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486-516. (b)
Martinez-Man˜ez, R.; Sanceno´n, F. Chem. ReV. 2003, 103, 4419-4476. Beer,
P. D.; Hayes, E. J. Coord. Chem. ReV. 2003, 240, 167-189. (c) Best, M.
D.; Tobey, S. L.; Anslyn, E. V. Coord. Chem. ReV. 2003, 240, 3-15. (d)
Sessler, J. L.; Camiolo, S.; Gale, P. A. Coord. Chem. ReV. 2003, 240, 17-
55. (e) Llinares, J. M.; Powell, D.; Bowman-James, K. Coord. Chem. ReV.
2003, 240, 57-75. (f) Bondy, C. R.; Loeb, S. J. Coord. Chem. ReV. 2003,
240, 77-99. (g) Choi, K.; Hamilton, A. D. Coord. Chem. ReV. 2003, 240,
101-110. (h) Wedge, T. J.; Hawthorne, M. F. Coord. Chem. ReV. 2003,
240, 111-128. (i) Lambert, T. N.; Smith, B. D. Coord. Chem. ReV. 2003,
240, 129-141. (j) Davis, A. P.; Joos, J.-B. Coord. Chem. ReV. 2003, 240,
143-156. (k) Hosseini, M. W. Coord. Chem. ReV. 2003, 240, 157-166.
(l) Gale, P. A. Coord. Chem. ReV. 2003, 240, 191-221. (m) Wiskur, S. L.;
Ait-Haddou, H.; Anslyn, E. V.; Lavigne, J. J. Acc. Chem. Res. 2001, 34,
963-972.
(4) (a) Beer, P. D.; Hesek, D.; Nam, K. C. Organometallics 1999, 18,
3933-3943. (b) Choi, K.; Hamilton, A. D. J. Am. Chem. Soc. 2001, 123,
2456-2457. (c) Hossain, Md. A.; Llinares, J. M.; Powell, D.; Bowman-
James, K. Inorg. Chem. 2001, 40, 2936-2937. (d) Kubik, S.; Kirchner, R.;
Nolting, D.; Seidel, J. J. Am. Chem. Soc. 2002, 124, 12752-12753. (e)
Ihm, H.; Yun, S.; Kim, H. G.; Kim, J. K.; Kim, K. S. Org. Lett. 2002, 4,
2897-2900. (f) Herges, R.; Dikmans, A.; Jana, U.; Ko¨hler, F.; Jones, P.
G.; Dix, I.; Fricke, T.; Ko¨nig, B. Eur. J. Org. Chem. 2002, 3004-3014.
(g) Lee, D. H.; Lee, H. Y.; Hong, J.-I. Tetrahedron Lett. 2002, 43, 7273-
7276. (h) Kang, S. O.; Oh, J. M.; Yang, Y. S.; Chun, J. C.; Jeon, S.; Nam,
K. C. Bull. Korean Chem. Soc. 2002, 23, 145-147. (i) Coles, S. J.; Denuault,
G.; Gale, P. A.; Horton, P. N.; Hursthouse, M. B.; Light, M. E.; Warriner,
C. N. Polyhedron 2003, 22, 699-709. (j) Kang, S. O.; Llinares, J. M.;
Powell, D.; VanderVelde, D.; Bowman-James, K. J. Am. Chem. Soc. 2003,
125, 10152-10153. (k) Tobey, S. L.; Anslyn, E. V. J. Am. Chem. Soc.
2003, 125, 14807-14808. (l) Yang, Y. S.; Ko, S. W.; Song, I. H.; Ryu, B.
J.; Nam, K. C. Bull. Korean Chem. Soc. 2003, 24, 681-684. (m) Hossain,
A.; Liljegren, J. A.; Powell, D.; Bowman-James, K. Inorg. Chem. 2004,
43, 3751-3755. (n) Curiel, D.; Beer, P. D. Chem. Commun. 2005, 1909-
1911. (o) Kang, S. O.; Hossain, M. A.; Powell, D.; Bowman-James, K.
Chem. Commun. 2005, 328-330.
(5) Vienna, J. D.; Schweiger, M. J.; Smith, D. E.; Smith, H. D.; Crum,
J. V.; Peeler, D. K.; Reamer, I. A.; Musick C. A.; Tillotson, R. D. Report
PNNL-12234, Pacific Northwest National Laboratory, Richland, 1999. (b)
Crawford, C. I.; Ferrara, D. M.; Schumacher, R. F.; Bibler, N. E. Report
WSRC-MS-2002-00449, Westinghouse Savannah River Company, Aiken,
2002.
(6) (a) Sessler, J. L.; Katayev, E.; Pantos, G. D.; Ustynyuk, Yu. A. Chem.
Commun. 2004, 1276-1277. (b) Sessler, J. L.; Katayev, E.; Pantos, G. D.;
Scherbakov, P.; Reshetova, M. D.; Khrustalev, V. N.; Lynch, V. M.;
Ustynyuk, Yu. A. J. Am. Chem. Soc. 2005, 127, 11442-11446.
(7) Katayev, E.; Pantos, G. D.; Reshetova, M. D.; Khrustalev, V. N.;
Lynch, V. M.; Ustynyuk, Yu. A.; Sessler, J. L. Angew. Chem., Intl. Ed.
2005, in press.
(8) (a) Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Warriner, C. N.
Collect. Czech. Chem. Commmun. 2004, 69, 1301-1308. (b) Coles, S. J.;
Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Warriner, C. N. Supramol.
Chem. 2004, 16, 469-486.
(9) For studies of the anion binding properties of oligopyrroles analogous
to the pyrrolic building blocks used in this study, see: (a) El Drubi Vega,
I.; Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E. Chem.
Commun. 2003, 1696-1687. (b) El Drubi Vega, I.; Gale, P. A.; Hursthouse,
M. B.; Light, M. E. Org. Biomol. Chem. 2004, 2, 2935-2941. (c) Sessler,
J. L.; Eller, L. R.; Cho, W.-S.; Nicolaou, S.; Aguilar, A.; Lee, J. T.; Lynch,
V. M.; Magda, D. J. Angew. Chem., Int. Ed. 2005, 44, 5989-5992.
macrocycles 6 and 7 (Scheme 2). It was prepared using an
extension of the procedure introduced by Picard et al.10
Specifically, 2,5-thiophene dicarboxylic acid was converted
into the corresponding diacid dichloride, 1, by treatment with
SOCl2.8 Compound 1 was then condensed with 1,3-thiazo-
lidine-2-thione to give the diamide 2 in 74% yield. Reaction
of 2 with o-phenylenediamine in dichloromethane then
afforded compound 3 in 78% yield. In analogy to what was
done previously,6,7 precursor 3 was condensed with the
diformyldipyrromethane 4 in the presence of 2.5 equiv of
H2SO4 to give 6‚H2SO4 in 90% yield.11 In a similar manner,
macrocycle 7‚HCl was synthesized in 83% yield via the
condensation of 3 with diformylbipyrrole 5 in the presence
of 2.5 equiv of HCl. Both macrocycles were converted to
their respective “free base” forms by treating methylene
chloride solutions of the corresponding acid salts with
triethylamine. The overall yields for the deprotonation steps
were 81% and >99% for 6 and 7, respectively.
Proof for the proposed structures of macrocycles 6 and 7
came from single-crystal X-ray diffraction analyses carried
out using their neutral forms. On this basis it was determined
that compound 6 adopts a conformation in the solid state in
which the two phenyl groups in the â-positions of the
thiophene are held above the effective macrocyclic cavity.
Presumably as a consequence, the sulfur atom of the
thiophene is forced to point out from the central macrocyclic
core. The presence of several solvent molecules (acetone)
is also seen in this structure. One of these is bound within
the central cavity of the macrocycle via an N4H-O3 (2.92
Å, 175°) hydrogen bond from one of the pyrrole rings, as
well as a weak C37H-O3 (3.33 Å, 141°) hydrogen bond
from one of the â-phenyl rings of the thiophene. A second
bound acetone molecule is coordinated via a hydrogen bond
(10) Picard, C.; Arnaud, N.; Tisne`s, P. Synthesis 2001, 1471-1478.
(11) Efforts to prepare an analogue of 6 lacking the â-phenyl substituents
were stymied by a lack of solubility.
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Org. Lett., Vol. 7, No. 23, 2005

Scheme 2. Synthesis of Macrocycles 6 and 7
involving the other pyrrole moiety (i.e., N3H-O4 ) 3.18
Macrocycles 6 and 7 were investigated as potential anion
binding agents. Toward this end, their interactions with
various tetrabutylammonium salts were studied via UV-
vis spectrophotometric titrations. For reasons of solubility,
involving both the anion salts and the macrocycles them-
selves, these studies were conducted in dichloroethane.
Binding stoichiometries were determined using Job plots.
Table 1 summarizes the associated findings.
Å, 127°). Finally, a third acetone molecule is coordinated
through two weak C22H-O5 (3.57 Å, 168°) and C24H-
O5 (3.59 Å, 135°) hydrogen bonds involving the imine CH
and an o-phenylene CH proton. In addition to these effects,
the structure reveals that both amide NH protons are
hydrogen bound to the Schiff base nitrogen atoms N1H-
N2 (2.68 Å, 111°) and N6H-N5 (2.66 Å, 113°). The X-ray
structure of 7 provides support for the notion that it contains
a framework more rigid than that of 6. In this case, the
bipyrrole unit forces the macrocycle to adopt an “all-in”
structure, wherein all of the N and S atoms point in toward
the center of the ring. There are two internal hydrogen bonds
in this structure, between the amide NHs and the Schiff base
nitrogen atoms: N1H-N2 (2.66 Å, 109°) and N6H-N5
(2.72 Å, 97°). Also to be noted is the twist (dihedral angle
) 53°) present in the bipyrrole moiety. This twisting could
reflect unfavorable steric interactions between the 4,4′-methyl
groups but mostly likely is due to presence of intramolecular
hydrogen bonding interactions involving the pyrrole NH
protons and the amide carbonyl oxygen atom of another
molecule. A second X-ray structure of 7 was solved from
single crystals obtained via slow evaporation of a methylene
chloride-acetone mixture. In this case, macrocycle 7 exists
in the form of a solvent-bridged dimer in the solid state (cf.
Supporting Information).
A quick inspection of this table reveals that, as a general
rule, macrocycle 6 displays a higher affinity for the various
test anions studied than does 7. There are two notable
exceptions, namely, bromide and acetate anion. In the case
of these two anions, the association constants were found to
be very similar (e.g., for acetate, Ka ) 3200 ( 600 and 3600
( 300 M-1 for 6 and 7, respectively). In attempting to
rationalize these findings, it is useful to note that macrocycle
6 displays the strongest interaction with hydrogen sulfate,
chloride, and nitrate anions, followed by dihydrogenphos-
phate, bromide, and acetate, respectively.
This selectivity, as well as the generally higher affinity
this system displays relative to that of 7, is ascribed to its
greater inherent flexibility. This flexibility allows it to interact
with anions of very different geometry, such as hydrogen
Table 1. Affinity Constants (M-1) for Binding of Anions by
Receptors 6 and 7 As Determined from UV-vis Spectroscopic
Titrationsd
anion
6
7
anion volume (Å3)b
Cl-
16 600 ( 900
7 100 ( 1000
3 200 ( 600
15 400 ( 2100
18 900 ( 1000
9 500 ( 400
3 300 ( 300
7 100 ( 900
3 600 ( 300
1 000 ( 300
7 400 ( 800
c
24.8
31.5
17.8
24.0
28.7
33.5
Br-
AcO-
NO3
HSO4
H2PO4
-
-
-
a The R2 values for the curves fits used to determine the affinity constants
Figure 1. ORTEP-POVray rendered view of 6 showing three
bound acetone molecules. Most hydrogen atoms have been removed
for clarity. Thermal ellipsoids are scaled to the 50% probability
level.
range between 0.989 and 0.998. b From ref 8. c No clean fit to the binding
d
profile could be made. Titrations were carried out in C2H4Cl2 at 23 °C.
The anions were studied in the form of their tetrabutylammonium salts.
Binding stoichiometries are 1:1 unless otherwise noted.
Org. Lett., Vol. 7, No. 23, 2005
5279

tions are considered consistent with the fact macrocycle 7
contains a core that is large and fairly rigid, as inferred from
the X-ray structural analysis. In other words, receptor 7, in
contrast to 6, possesses a well-defined cavity that cannot
change its size easily to interact with anions of higher charge
density and smaller dimensions. In conclusion, two thiophene-
containing polypyrrolic Schiff base macrocycles have been
prepared. To the best of our knowledge they are the first
members of a potentially large class of easy-to-synthesize
anion receptors. Studies of the anion binding behavior of
these systems revealed a dramatic difference between the
more flexible macrocycle (6) and an otherwise similar rigid
analogue, 7. This work thus serves to highlight further how
subtle changes in design can be translated into useful
differences in anion selectivity.
Acknowledgment. This project was supported by the
U.S. Department of Energy, Office of Science (grant no. DE-
FG02-04ER63741 to J.L.S.), and by the Russian Foundation
for Basic Research and Program of Basic Research in
Chemistry of the Russian Academy of Sciences (grant nos.
05-03-08017 and 05-03-32684 to Y.A.U.), and is part of an
ongoing collaboration involving the Sessler research group
at The University of Texas at Austin and those of Dr. Bruce
Moyer at The Oak Ridge National Laboratory and Prof.
Kristin Bowman-James at the University of Kansas.
Figure 2. ORTEP-POVray rendered view of 7. Most hydrogen
atoms have been removed for clarity. Thermal ellipsoids are scaled
to the 50% probability level.
sulfate (tetrahedral), nitrate (trigonal planar), and chloride
(spherical), while showing, naturally, a preference for those
it can best accommodate. A comparison of the anion affinities
with anion volume12 leads to the conclusion that macrocycle
6 favors anions with volumes ranging between 24.0 and 28.7
Å3. In contrast, macrocycle 7 interacts most strongly with
the larger anions considered in this study. For instance, the
ca. 2:1 selectivity for chloride over bromide seen in the case
of 6, is essentially reversed in the case of 7. Such observa-
Supporting Information Available: General methods
and materials, synthetic experimental, representative Job
plots, UV-vis titrations, corresponding binding isotherms,
details of affinity constant determinations, and X-ray crystal-
lographic information including CIF files. This material is
available free of charge via the Internet at http://pubs.acs.org.
(12) Marcus, Y.; Jenkins, H. D. B.; Glasser, L. J. Chem Soc., Dalton
Trans. 2002, 3795-3798.
OL052162B
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Org. Lett., Vol. 7, No. 23, 2005