Tris(2-aminoethyl)amine based tripodal urea receptors for oxalate: Encapsulation of staggered vs. planar conformers

Article abstract of DOI:10.1039/c3ob41071d

Simple tris(2-aminoethyl)amine (TREN) based tripodal urea receptors are investigated for the encapsulation of divalent oxalate (C₂O ₄^2-) in a semi-aqueous medium. A single crystal X-ray diffraction study shows that the receptor with 3-cyanophenyl functionality captures a staggered conformer whereas the 3-fluorophenyl functionalized receptor encapsulates a less stable planar conformer.

Full text of DOI:10.1039/c3ob41071d

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Tris(2-aminoethyl)amine based tripodal urea receptors
for oxalate: encapsulation of staggered vs. planar
conformers†
Cite this: Org. Biomol. Chem., 2013, 11,
4581
Received 28th March 2013,
Accepted 28th May 2013
Purnandhu Bose, Ranjan Dutta and Pradyut Ghosh*
DOI: 10.1039/c3ob41071d
www.rsc.org/obc
Simple tris(2-aminoethyl)amine (TREN) based tripodal urea recep- recently, a bis-amidocarbazolyl urea based receptor has been
tors are investigated for the encapsulation of divalent oxalate utilized for the recognition of dicarboxylate anions which also
(C2O42−) in a semi-aqueous medium. A single crystal X-ray diffrac- represents the rare example of solid state structural evidence
recognition by neutral urea receptors.10a The
2−
tion study shows that the receptor with 3-cyanophenyl functional- of C2O4
2−
ity captures a staggered conformer whereas the 3-fluorophenyl sensing of C2O4 via the indicator displacement assay tech-
functionalized receptor encapsulates
conformer.
a
less stable planar nique using a dicopper complex is also reported, where quite a
large binding constant value (∼105) is calculated in aqueous
media.10b,c TREN based tripodal ureas/thioureas are some of
The recognition and transportation of substrates containing
carboxylate functionalities are of great importance due to their
crucial role in the metabolism of cells.1 The recognition and
sensing of the simplest dicarboxylate anion, C2O42−, is very
useful in food chemistry and it is also an important nutrient
found in many plants.2 Insoluble calcium oxalate is a prime
the most popular and widely used classes of anion receptors in
recent times.11–35 These receptors have an interesting property
to form a capsular assembly that creates a microenvironment
for recognition of various anionic guests.29,32,34,35 Herein, two
closely related tripodal ureas L1 and L2 (Chart 1) are explored
2−
for C2O4
encapsulation in a semi-aqueous environment.
2−
constituent of renal stones.3 A high level of C2O4 in urine
Importantly, we have shown the trapping of a staggered confor-
may be indicative of renal failure, kidney lesions and pancrea-
tic insufficiency.4 Oxalate exists in two different conformers as
illustrated by single crystal X-ray crystallography, one of which
is a planar conformer with D2h molecular symmetry, while the
other one is a staggered conformer with approximate D2d sym-
2−
mer of C2O4 in the dimeric capsular aggregation (9.815 Å) of
L1, whereas a relatively bigger dimeric capsular assembly
2−
(10.823 Å) of L2 encapsulates the planar form of C2O4 by a
single crystal X-ray structural study.
To synthesize the C2O42− complexes we have carried out the
reaction between L1/L2 and TBAI (2 equiv.) with excess potass-
ium oxalate in a DMSO–H2O binary solvent system. Eventually,
metry.5 The calculated rotational energy barrier between the
D2h and D2d conformers of C2O4 is about 2–6 kcal mol−1 5,6
.
2−
2−
The staggered conformer is the stable form of C2O4 in solu-
2−
we were able to isolate C2O4 encapsulated capsular aggre-
tion. Surprisingly, a reverse pattern is observed in most of the
structural evidence.6 Only a few examples of the staggered
C2O42− conformer have been reported in the solid state.6,7,10a
Oxalate recognition by a macrobicyclic polyammonium
gates C1 and C2 of L1 and L2 in ∼75–80% yield after slow
evaporation of the 5% H2O–DMSO solvent mixture. C1 crystal-
ˉ
lizes in the triclinic crystal system with a P1 space group. The
asymmetric unit of C1 has two receptor units L1, two TBA
8
cryptand was first explored by Nelson et al. Delgado et al.
recently reported the recognition of dicarboxylates in the solu-
tion state by macrobicyclic polyammonium receptors.9 Very
Department of Inorganic Chemistry, Indian Association for the Cultivation of
Science, 2A & 2B Raja S C Mullick Road, Jadavpur, Kolkata-700032, India.
E-mail: icpg@iacs.res.in; Fax: (+91) 33-2473-2805
†Electronic supplementary information (ESI) available: Synthesis and character-
ization of L2, C1 and C2, details of 1H NMR titration including a Job’s plot and
stack plots of the 1H NMR, details of the X-ray structure determination, X-ray
crystal structures, hydrogen bonding parameters and scatter plots of C1 and C2.
CCDC 914147 (C1) and 914149 (C2). For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c3ob41071d
Chart 1 Chemical structures of L1 and L2.
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Fig. 1 (a) Ball–stick representation of capsular aggregate C1 showing encapsu-
lated C2O42− via twelve N–H⋯O interactions in the dimeric capsular assembly of
L1; (b) view of the O–C–C–O dihedral angle of the encapsulated staggered
Fig. 2 (a) Ball–stick representation of capsular aggregate C2 showing encapsu-
lated C2O42− via twelve N–H⋯O interactions in the dimeric capsular assembly of
L2; (b) view of the O–C–C–O dihedral angle of the encapsulated planar C2O4
2−
2−
C2O4 conformer in C1 (all the non-acidic hydrogen atoms and TBA counter
cations are omitted for clarity).
conformer in C2 (all the non-acidic hydrogen atoms and TBA counter cations
are omitted for clarity).
counter cations and one C2O42−. In C1 two molecules of L1
form a cavity that engulfs a staggered form of C2O4 at its
2−
2−
Table 1 C–C bond length and torsion angles of C2O4 in capsular aggregates
C1 and C2 and in K2C2O4
centre via hydrogen bonding interactions with six urea NH
protons. There are a total of twelve hydrogen bonding inter-
actions between twelve NH units of two L1 and four O atoms
of C2O42−. All four O atoms of C2O42−, namely O7, O8, O9 and
O10, accept three N–H⋯O hydrogen bonds each. From the
scatter plot diagram it is clear that all the twelve hydrogen
bonding interactions fall in the strong hydrogen bonding
region (i.e. dH⋯O < 2.5 Å and dN⋯O < 3.2 Å) (Fig. 1, Fig. 8S and
C–C bond
distance (Å)
Torsion
angle (°)
Apical N⋯N
distance (Å)
Compounds
C1
C2
K2C2O4
1.501
1.576
1.595
68.81
0.12
0.00
9.815
10.823
—
Table 2S in the ESI†). Receptors L1 and L2 differ only in the lower than the normal C–C single bond length. In contrast, the
2−
attached electron withdrawing functionality at the meta posi- trapped C2O4 in C2 shows almost planar conformation with
tion. C2 obtained from L2 crystallizes in the monoclinic crystal an O–C–C–O dihedral angle of 0.12° (Table 1). The C–C bond
2−
2−
system with a P21/c space group. In the case of C2, C2O4 is length in C2O4 is found to be 1.576 Å, which indicates the
2−
perfectly encapsulated by two receptor units via a dimeric cap- single bond characteristic nature of C2O4 compared to other
sular assembly like C1. Unlike C1, the asymmetric unit of C2 staggered conformers. Thus, by simply tuning substituents
2−
consists of one L2, a half unit of C2O4 and one TBA counter from –CN to –F, discrimination between different conformers
2−
cation. C2 is centrosymmetric in nature as required by the (staggered and planar) of C2O4 is achieved in the solid state
space group symmetry, having one inversion centre (i) passing inside the dimeric capsular assembly of the receptors.
through the centre of encapsulated C2O42−. In C2 the C2O42− is
The solution state binding properties of L1 and L2 with
2−
2−
1
in the special position. There are eight C2O4 present at the C2O4 are investigated by H NMR titration in a D2O–DMSO-
2−
eight corners of the unit cell and two C2O4 situated at the d6 solvent system at 298 K in the presence of potassium
two opposite faces of the unit cell (Fig. 9S in the ESI†). There oxalate. In a typical NMR titration experiment, a standard solu-
2−
are twelve hydrogen bonds which are involved in binding the tion of C2O4 is prepared in D2O–DMSO-d6 (1.1 : 1, v/v) and
2−
C2O4 deep inside the capsular cavity. The oxygen atoms of titrated into a solution of the respective receptor in a D2O–
C2O42−, namely O4 and O5, accept three N–H⋯O hydrogen DMSO-d6 (1 : 9, v/v) solvent mixture. To maintain a similar
bonds each. All the N–H⋯O hydrogen bonding parameters fall solvent system throughout the titration, we have prepared a
in the strong hydrogen bonding regime (Fig. 2, Fig. 10S and stock solution of the receptor in D2O–DMSO-d6 (1 : 9, v/v).
2−
Table 3S, ESI†).
However, the lower solubility of potassium C2O4 in pure
The capsular size of C1 and C2 varies substantially. The DMSO-d6 or even in DMSO-d6–D2O (1 : 1) prevents us from
capsular size of C1 is determined as 9.815 Å from the apical maintaining an exactly similar solvent system during titration.
2−
nitrogen distances, whereas the capsular size is relatively Further during titration, after addition of 2 equiv. of C2O4
,
higher for C2 (10.823 Å). Further insight into the geometry of slight precipitation is observed in the NMR tube. In each case,
2−
the trapped C2O4 reveals their conformational differences. a gradual downfield shift of NHa/b protons and an upfield shift
The central C–C bond length and dihedral angle differ upon of CHc/d protons are observed upon addition of a guest
moving from smaller to bigger capsular aggregates. In the case aliquot. All the titration curves give the best fit for the 1 : 1
of C1, the cavity of the dimeric assembly encapsulates the stag- binding model for receptors L1 and L2 to C2O42− in agreement
2−
gered conformer of C2O4 where the O–C–C–O dihedral angle with the Job’s plot indicating an optimum Δδ at around 0.5 =
is 68.8° (Table 1). The central C–C (C61–C62) bond length [L]/([L] + [C2O42−]), and the association constant values are cal-
around the staggered C2O42− in C1 is 1.501 Å, which is slightly culated using WINEQNMR software.
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competitive crystallization. When a mixture of the sodium
salts of the above-mentioned anions and oxalate is added to a
5% H2O–DMSO solution of L1 and allowed to crystallize, crys-
tals of C1 are isolated, which are confirmed by single crystal
X-ray diffraction analysis.
In conclusion, we have investigated the binding studies of
2−
the organic dicarboxylate anion C2O4 by two closely related
TREN based neutral tripodal urea receptors. Solid state struc-
tural evidence reveals the trapping of two possible conformers
2−
of C2O4 in the cavity of dimeric capsular assemblies of the
Fig. 3 (a) Partial 1H NMR (300 MHz) spectral changes of L1 in D2O–DMSO-d6
(1 : 9, v/v) with added standard K2C2O4 solution in D2O–DMSO-d6 (1.1 : 1, v/v)
(298 K) ([L1]0 = 4.94 mM). Ratio of concentration [C2O42−]/[L1]: (i) 0, (ii) 0.129,
(iii) 0.258, (iv) 0.387, (v) 0.517, (vi) 0.646, (vii) 0.775, (viii) 0.904, (ix) 1.033, (x)
1.162, (xi) 1.421, (xii) 1.938, (xiii) 2.584 and (xiv) 2.971; (b) Job’s plot for L1 with
K2C2O4 in D2O–DMSO-d6 (1.1 : 1, v/v) ([L1] is varied from 4.94 to 3.61 mM by
the addition of aliquots of 39.91 mM K2C2O4) (‘*’ indicates the DMSO-d6
solvent peak).
2
receptors. Conformational insight into the encapsulated C2O4
− shows rare evidence of staggered conformer encapsulation in
the solid state. Appreciable variation of capsular dimension is
also observed depending upon the encapsulated guest confor-
2−
mation. The staggered conformer of C2O4 acts as a template
for the formation of smaller capsular assemblies, whereas
bigger assemblies are driven by planar conformers.
P. G. thanks the Department of Science and Technology for
financial support through a Swarnajayanti Fellowship. P. B.
acknowledges DST, India for a fellowship. R. D. acknowledges
CSIR, India for a SRF. Single crystal X-ray diffraction data were
collected at the DST funded National Single Crystal X-ray Diffr-
action Facility at the Department of Inorganic Chemistry, IACS
and the DBT-funded CEIB program (project no. BT/01/CEIB/
11/V/13) awarded to the Department of Organic Chemistry,
IACS, Kolkata.
One such representative titration experiment between L1
and C2O42− is described in Fig. 3. The upfield shift of CHc and
CHd protons is monitored upon gradual addition of a guest
solution. Job’s plot analysis shows the presence of minima at
[L1]/([L1] + [C2O42−]) ≈ 0.5, which indicates 1 : 1 host–guest
association in solution for L1 (Fig. 3, Fig. 11S–13S in the ESI†).
Fig. 14S–16S in the ESI† describes the NMR titration profile
along with a Job’s plot for the titration of L2 with C2O42−. The
association constant (log K) and the corresponding free energy
2−
change (ΔG) values for C2O4 binding with L1 and L2 are cal-
culated and tabulated in Table 2. This stoichiometric discre-
pancy between solid and solution state binding properties is
common for this type of tripodal urea/thiourea receptor.29,35
From NMR titration experiment data the 3-cyanophenyl substi-
tuted urea L1 shows slightly higher binding affinity towards
Notes and references
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Host
log Ka
ΔG (kcal mol−1
)
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L2
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4.29
−6.62
−5.89
a Error range < 15%.
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