(cis)-5,10,15,20-Tetrakis[2-(arylurea)phenyl]porphyrins: Novel neutral ligands for remarkably selective and exceptionally strong chloride anion complexation in (CD3)2SO

Article abstract of DOI:10.1039/a702389h

Urea appended free-base porphyrins 2-4 bind strongly (K > 10⁵ dm³ mol^-1) to spherical Cl^- in (CD₃)₂SO and exhibit significant binding selectivity since they complex with Cl^- to a

Full text of DOI:10.1039/a702389h

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(cis)-5,10,15,20-Tetrakis[2-(arylurea)phenyl]porphyrins: novel neutral ligands
for remarkably selective and exceptionally strong chloride anion complexation
in (CD3)2SO
Raymond C. Jagessar and Dennis H. Burns*
Department of Chemistry, Wichita State University Wichita, Kansas 67260-0051, USA
Urea appended free-base porphyrins 2–4 bind strongly (K >
105 dm3 mol21) to spherical Cl2 in (CD3)2SO and exhibit
significant binding selectivity since they complex with Cl2 to
a much greater extent (103–102 :1) than with the trigonal
NO32 and tetrahedral H2PO42 anions.
of 3 and 4, as well as the porphyrin’s ability to bind metals in its
core, allow for the moderation of the strength and selectivity of
anion binding for the supramolecule.
These receptors are the first example of a class of neutral,
free-base porphyrins† able to act as very selective anion
receptors, with 2–4 binding Cl2 greater than 1000:1 compared
2
2
The importance of anion binding and transport in chemical and
biochemical processes has been the impetus for the design and
fabrication of supramolecular anion receptors.1 We have begun
a project to prepare neutral anion receptors that exhibit selective
anion binding, ultimately for the development of sensors and
transport mimics that function in an aqueous environment.
Here, we report the synthesis (Scheme 1) of our initial receptors
2–7, superstructured porphyrins functionalized with urea moie-
ties. Owing to the different pocket size and orientation of urea
groups on the porphyrin scaffolding, it was anticipated that 2–4
would exhibit different aptitudes and selectivities for anion
complexation than those seen with the previously prepared urea
appended receptors.2–6 Furthermore, the addition of electroneg-
ative substituents (Cl, F) to the para position of the phenyl rings
to NO3 or 280:1 compared to H2PO4 (vide infra) (Cl2
receptors are biologically relevant, for Cl2 ion channels are
involved in the facilitated exchange of Cl2 for HCO32 anions in
erythrocytes, and, when not functioning properly, have been
implicated in the genetic disease cystic fibrosis7). For compar-
ison, the expanded porphyrin receptors can bind anions only
when protonated, and thus exhibit modest anion selectivity due
to nondirectional coulombic interactions3 (for example, sap-
2
phyrin binds H2PO4 and F2 ions with similar binding
constants in methanol1f). Cobaltocene and ferrocene appended
porphyrins have recently been reported.8 The former is another
example of a positively charged anion receptor, whereas the
neutral ferrocene appended porphyrins do not bind anions
unless metallated; both systems show little anion selectivity (no
better than 4:1 binding selectivity between halides, nitrate and
sulfate ions).
H2N
Porphyrins 2–4 were synthesized (Scheme 1) by the addition
of 4 equiv. of the requisite isocyanate (8–10) to the cis isomer
of H2TAPP9,10 1 in CHCl3 at room temp. and were obtained in
yields of 70–85% after purification by silica-gel column
chromatography and subsequent recrystallization from
CH2Cl2–C6H14. The Zn complexes 5–7 were synthesized by
stirring the free-base ligands with excess Zn(OAc)2·2H2O in
CH2Cl2–MeOH (2:1, v/v) and were obtained in 90–95% yield.
The model tetraphenylporphyrin was prepared using standard
literature procedure.11 The 1H NMR spectra of 2–4 recorded in
(CD3)2SO at ambient temperature revealed a singlet resonance
for the b-pyrrole protons, indicative of the cis conformation of
the molecules. In all cases, the urea NH protons were observed
as two broad singlets, the one at high field presumably due to
those in close proximity to the porphyrin ring, resulting from the
shielding effect of the macrocycle. The proposed structures 2–4
were corroborated by HRFABMS.
NH2
NH2
N
N
H H
N
N
H2N
1
i
R
R
R
R
HN
UV–VIS spectral anion titration revealed anion binding
through perturbation of the Soret and visible bands of 2–4 when
C
O
NH
HN
+
the anions Cl2, NO32 and H2PO42 were added as their NBu4
HN
O
2
salts. Addition of NO3 and Cl2 anions produced a hypso-
C
O
NH
O
NH
NH
chromic shift with concomitant decrease in intensity of the
Soret band after the addition of 1 equiv. of anion. Further
addition of anion resulted in an increase in intensity (Fig. 1).
C
N
N
M
N
N
2
Titration of porphyrins 2–4 with H2PO4 produced a hypso-
NH
chromic shift of the Soret band followed by a bathochromic
shift and an increase in absorbance with the addition of > 1
equiv. of anion. Furthermore, with porphyrins 3 and 4, a
broadened Soret band with the appearance of a shoulder was
observed (Fig. 1). Changes in the Soret band combined with
shifts of the porphyrin NH protons (vide infra) upon titration
with the anions strongly suggests that the anions were bound
within the porphyrin–urea pocket.
2–4
2–4, M = 2H
5–7, M = Zn
Scheme 1: Reagents and conditions: i, p-RC6H4NCO, CHCl3, room temp.;
R = H (2, 5, 8), Cl (3, 6, 9) or F (4, 7, 10)
Chem. Commun., 1997
1685

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(a)
(d)
determined by UV–VIS spectrophotometry, showed the stoi-
chiometry of binding was 1:1. The binding affinity of 2–4 for
NO32 was even weaker (Table 1).‡ The noteworthy selectivity
in the binding of Cl2 with 2–4 was presumably due to a less
(e)
(d)
0.3
0.2
0.1
0.0
2.0
(a)
(c)
(c)
(b)
(b)
1.5
1.0
0.5
0.0
2
complementary fit of the trigonal NO32 or tetrahedral H2PO4
than that of spherical Cl2 within the urea binding pocket of the
free-base porphyrins. Under analogous titration conditions,
tetraphenylporphyrin exhibited negligible perturbation in its 1H
NMR and UV–VIS spectra, indicating the changes observed
with ligands 2–4 were truly caused by anion binding.
Future investigations will examine solvent systems where the
association constants of 2–4 for the complexation of Cl2 and
other spherical anions are of the proper magnitude (i.e. < 105)13
to allow for an accurate determination of their binding
constants, and therefore the determination of possible selec-
tivity trends with the different porphyrins. Future experiments
will also examine if metallated receptors 5–7 will bind anions
with the same selectivity trends as those observed with the free-
base porphyrins.
450
λ / nm
400
410
420
430
440
400
420
440
460
Fig. 1 UV–VIS spectra of porphyrins 3 and 4 demonstrating the change in
the Soret bands upon titration with anions in CH2Cl2. (Left) porphyrin 4
titrated with NBu4Cl in mol equiv.: (a) 0, (b) 1, (c) 2, (d) 5, (e) 10. (Right)
porphyrin 3 titrated with NBu4H2PO4 in mol equiv.: (a) 0, (b) 1, (c) 2, (d)
10.
Quantification of the association constants of neutral hosts
2–4 was accomplished by following the titrations of the anions
by 1H NMR in the strongly solvating solvent (CD3)2SO. In all
cases, proton shifts were observed for the receptor porphyrin-
phenyl, b-pyrrole, porphyrin NH, and urea-phenyl protons.
Larger shifts were observed for the urea NH protons, with the
downfield urea proton the most perturbed. The larger shift of the
urea NH proton was indicative of its essential role in the anion
recognition process.2,4 The association constants of 2–4 in
(CD3)2SO determined from their binding curves (Fig. 2) for the
complexation of Cl2 ion were calculated12 to be > 105 dm3
mol21 (Table 1),13 so it was impossible to judge any selectivity
in binding that might be occurring for these anions between the
different porphyrins. However, binding constants for Cl2 > 105
dm3 mol21 are significantly larger than those that have been
previously reported for urea functionalized anion receptors.1–6
The very strong binding of Cl2 ion allowed the mole ratio
method14 to be used in the determination of the binding
stoichiometry, which was found to be 1:1 for the three
porphyrins.
We thank Dr Todd Williams for obtaining the FAB mass
spectra. This research was supported by the National Science
Foundation (EPS-9550487).
Footnotes and References
* E-mail: burns@wsuhub.uc.twsu.edu
† Neutral meso-octaethylporphyrinogens have been shown to bind se-
lectively to F2 in CD2Cl2.1a However, the lack of macrocyclic aromaticity
(i.e., little useful UV–VIS, fluorescence, or electrochemical information)
makes this system less attractive for sensor development.
2
‡ Although the complexation stoichiometries for porphyrins 2–4 and NO3
have yet to determined by Job’s method,14 the calculated errors for the
binding constants were small only when a 1:1 binding isotherm was
utilized.
1 For reviews, see (a) R. M. Izatt, K. Pawlak and J. S. Bradshaw, Chem.
Rev., 1995, 95, 2529; (b) B. Dietrich, Pure Appl. Chem., 1993, 65, 1457.
For more recent examples (but by no means a comprehensive list), see
(c) K. Kavallieratos, S. R. de Gala, D. J. Austin and R. H.. Crabtree,
J. Am. Chem. Soc., 1997, 119, 2325; (d) A. P. Davis, J. J. Perry and
R. P. Williams, J. Am. Chem. Soc., 1997, 119, 1793; (e) M. Berger and
F. P. Schmidtchen, J. Am. Chem. Soc., 1996, 118, 8947; (f) V. Kra´l,
H. Furuta, K. Schreder, V. Lynch and J. L. Sessler, J. Am. Chem. Soc.,
1996, 118, 1595; (g) P. A. Gale, J. L. Sessler, V. Kra´l and V. Lynch,
J. Am. Chem. Soc., 1996, 118, 5140.
2 J. Scheerder, J. F. J. Engbersen, A. Casnati, R. Ungaro and D. N.
Reinhoudt, J. Org. Chem., 1995, 60, 6448.
3 P. Bu¨hlmann, S. Nishizawa, K. P. Xiao and Y. Umezawa, Tetrahedron,
1997, 53, 1647.
4 J. Scheerder, M. Fochi, J. F. J. Engbersen and D. N. Reinhoudt, J. Org.
Chem., 1994, 59, 7815.
5 E. Fan, S. A. Van Arman, S. Kincaid and A. D. Hamilton, J. Am. Chem.
Soc., 1993, 115, 369.
0.4
0.3
0.2
0.1
0.0
5
7
0
1
2
3
4
6
Mol. equiv. anion
2
6 B. C. Hamann, N. R. Branda and J. Rebek, Tetrahedron Lett., 1993, 34,
6837.
Fig. 2 Binding curves for porphyrin 4 and Cl2 (2), H2PO42 (5) and NO3
(“) ions in (CD3)2SO
7 L. Stryer, Biochemistry, W. H. Freeman, New York, 1988, pp. 963–964;
J. W. Hanrahan, J. A. Tabcharani, F. Becq, C. J. Mathews, O.
Augustinas, T. J. Jensen, X.-B. Chang and J. R. Riordan, in Ion
Channels and Genetic Diseases, ed. D. C. Dawson and R. A. Frizzel,
Rockefeller University Press, New York, 1995.
8 P. D. Beer, M. G. B. Drew, D. Hesek and R. Jagessar, J. Chem. Soc.,
Chem. Commun., 1995, 1187; P. D. Beer, Chem. Commun., 1996, 689;
P. D. Beer, M. G. B. Drew and R. Jagessar, J. Chem. Soc., Dalton
Trans., 1997, 881.
9 T. N. Sorrell, Inorg. Synth., 1980, 20, 163.
10 J. S. Lindsey, J. Org. Chem., 1980, 45, 5215.
11 A. D. Adler, F. R. Longo, J. D. Finarelli, J. Goldmacher, J. Assour and
L. Korsakoff, J. Org. Chem., 1967, 32, 476.
The association constants of 2–4 in (CD3)2SO for the binding
of H2PO42 ion were 400, 300, and 1400 dm3 mol21 (Table 1),
respectively. Thus, there seemed to be some small selectivity
between the p-fluorophenylurea porphyrin 4 and the other two
porphyrins in their affinity for H2PO42. Presumably, the very
electronegative p-F substituent produced a large enough
increase in the acidity of the urea protons to strengthen their
hydrogen bonding with the anion electrostatic field. Both Job’s
method of continuous variations14 and the mole ratio method,14
Table 1 Binding constants (K/dm3 mol21) for porphyrins 2–4 and Cl2,
12 The computer program EQNMR was used to calculate binding
constants: M. J. Hynes, J. Chem. Soc., Dalton Trans., 1993, 311.
13 Binding constants greater than 105 dm3 mol21 cannot be determined
accurately: T. Wang, J. S. Bradshaw and R. M. Izatt, J. Heterocycl.
Chem., 1994, 31, 1097.
NO32 and H2PO42 anions in (CD3)2SO
Porphyrin Cl2
NO3
H2PO4
2
2
2
3
4
> 105
> 105
> 105
90
60
55
400
300
1400
14 K. A. Connors, Binding Constants, Wiley, New York, 1987, pp. 24–
28.
Received in Columbia, MO, USA; 8th April 1997; 7/02389H
1686
Chem. Commun., 1997