Fig. 2 Side and top views of a DFT calculated structure of the
dihydrogen phosphate complex of compound 3.
Fig. 1 Top and side views of the X-ray crystal structure of the
benzoate complex of compound 2. Non-acidic hydrogen atoms and
counter cations have been omitted for clarity.
between the hydrogen atoms in the 6-positions of the indole
with the oxygen of the urea may contribute to this stability.
A DFT calculation10 of the complex between compound 3
and dihydrogen phosphate (Fig. 2) showed the anion is bound
by four hydrogen bonds from the receptor (see ESI for more
detailsw). This may not represent the global minimum energy
structure.
benzoate anion is bound by four hydrogen bonds from the
receptor, two to each oxygen in the range Nꢃ ꢃ ꢃO
2.846(8)–2.907(8) A and bond angles N1–H1ꢃ ꢃ ꢃO3 1611;
N2–H2ꢃ ꢃ ꢃO3 1691; N3–H3ꢃ ꢃ ꢃO2 1761; N4–H4ꢃ ꢃ ꢃO2 1591.
In order to study the anion complexation properties of this
hydrogen bonding motif in a more polar solvent mixture,
compound 3 was synthesised (in an analogous fashion to
compound 2) in 50% yield, using commercially available
7-aminoindole. Again, proton NMR titration studies were
used to determine stability constants with various anions in
DMSO-d6–0.5% water and DMSO-d6–10% water and in all
cases similar affinities were observed to those found for
compound 2 (Table 2). However, in DMSO-d6–25% water,
precipitation of the anion complex only occurred upon addi-
tion of benzoate anions, allowing stability constants to be
determined for acetate and dihydrogen phosphate. Under
these polar conditions, it was found that compound 3 binds
dihydrogen phosphate with a stability constant of 160 Mꢀ1 vs.
20 Mꢀ1 for acetate. The high affinity for dihydrogen phos-
phate in this very polar and competitive solvent mixture is
remarkable for a neutral receptor. We presume the generally
high affinity for oxo-anions is due to the cleft-like conforma-
tion being the most stable in solution. Favourable interactions
The indole group is proving to be a highly effective moiety
for anion complexation in synthetic receptor systems. The
binding and encapsulation of oxo-anions is an area of increas-
ing importance.11 We have shown here that 1,3-diindolylureas
have a high affinity for oxo-anions and, in particular, dihy-
drogen phosphate in very polar solvent mixtures. The diindo-
lylurea skeleton is simple to make (in only one or two steps)
and functionalise and we are currently incorporating this
hydrogen bonding array into a variety of macrocyclic and
acyclic anion receptors. The results of these studies will be
reported in due course.
We would like to thank the EPSRC for a DTA studentship
(JRH) and for access to the crystallographic facilities at the
University of Southampton. CC would like to thank Regione
Sardegna for a Master & Back grant.
Notes and references
z Crystal data for compound 2ꢃtetrabutylammonium benzoate
C44H63N5O3, Mr = 709.99, T = 120(2) K, monoclinic space group
P21/c, a = 8.5824(3), b = 19.9254(9), c = 24.1820(10) A, b =
95.659(3)1, V = 4115.2(3) A3, rcalc = 1.146 g cmꢀ3, m = 0.072
mmꢀ1, Z = 4, reflections collected: 31 851, independent reflections:
7193 (Rint = 0.1307), final R indices [I 4 2sI]: R1 = 0.1469, wR2 =
0.3562, R indices (all data): R1 = 0.2215, wR2 = 0.4147.
Table 2 Stability constants (Mꢀ1) of compound 3 with a variety of
putative anionic guests (added as tetrabutylammonium salts) at 298 K
in (i) DMSO-d6–0.5% water, (ii) DMSO-d6–10% water and (iii)
DMSO-d6–25% water. In all cases binding fitted a 1 : 1 receptor :
anion stoichiometry model. Nd = not determineda
1. P. A. Gale, S. E. Garcıa-Garrido and J. Garric, Chem. Soc. Rev.,
´
2008, 37, 151–190; J. L. Sessler, P. A. Gale and W. S. Cho, Anion
Receptor Chemistry, (Monographs in Supramolecular Chemistry),
ed. J. F. Stoddart, Royal Society of Chemistry, Cambridge, 2006;
P. A. Gale and R. Quesada, Coord. Chem. Rev., 2006, 250,
3219–3244; F. P. Schmidtchen and M. Berger, Chem. Rev., 1997,
97, 1609–1646; P. A. Gale, Acc. Chem. Res., 2006, 39, 465–475;
P. A. Gale, Chem. Commun., 2005, 3761–3772; K. Bowman-
James, Acc. Chem. Res., 2005, 38, 671–678.
Anionic guest
Stability constant/Mꢀ1
(i)
(ii)
(iii)
Clꢀ
CH3CO2
128
17
774
521
Nd
20
4104
4104
4104
ꢀ
ꢀ
C6H5CꢀO2
Pptb
160
H2PO4
5170
2. K.-J. Chang, D. Moon, M. S. Lah and K.-S. Jeong, Angew.
Chem., Int. Ed., 2005, 44, 7926–7929; K.-J. Chang, M.-K. Chae,
C. Lee, J.-Y. Lee and K.-S. Jeong, Tetrahedron Lett., 2006, 47,
6385–6388; T. H. Kwon and K.-S. Jeong, Tetrahedron Lett., 2006,
a
b
Errors estimated to be no more than ꢁ10%. Precipitation occurred
upon addition of benzoate in 25% water.
ꢂc
This journal is The Royal Society of Chemistry 2008
3008 | Chem. Commun., 2008, 3007–3009