A Bis-Triazacyclononane Tris-Pyridyl N9-Azacryptand “Beer Can” Receptor for Complexation of Alkali Metal and Lead(II) Cations

Article abstract of DOI:10.1002/chem.201801300

A new bis-triazacyclononane tris-pyridyl N₉-azacryptand ligand is prepared via a convenient one-pot [2+3] condensation reaction between triazacyclononane and 2,6-bis(bromomethyl) pyridine in the presence of M₂CO₃ (M=Li, Na, K). The proton, lithium, sodium, potassium and lead(II) complexes of the ligand are characterised in the solid state. Preliminary solution-phase competition experiments indicate that the cryptand ligand preferentially binds lead(II) in the presence of sodium, calcium, potassium and zinc cations in methanol solution.

Full text of DOI:10.1002/chem.201801300

A Journal of
Accepted Article
Title: A bis-triazacyclononane tris-pyridyl N9-azacryptand 'Beer Can'
receptor for complexation of alkali metal and lead(II) cations
Authors: Asha Brown, Thanthapatra Bunchuay, Christopher Crane,
Nicholas White, Amber Thompson, and Paul D. Beer
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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To be cited as: Chem. Eur. J. 10.1002/chem.201801300
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A bis-triazacyclononane tris-pyridyl N -azacryptand ‘Beer Can’
9
receptor for complexation of alkali metal and lead(II) cations
[a]
[a]
[a]
[b]
Asha Brown, Thanthapatra Bunchuay, Christopher G. Crane, Nicholas G. White, Amber L.
[a]
[a]
Thompson and Paul D. Beer*
Abstract: A new bis-triazacyclononane tris-pyridyl N
9
-azacryptand
Since the early work on metal cryptate complexes, numerous
cryptand host systems have been developed for metal cations, as
well as anions[16,17] and organic guest molecules.[18] The resulting
cryptate systems have found varied applications, for example as
phase transfer catalysts,[19] anion-exchange column stationary
phases,[20] ionophores in ion-selective electrodes,[21–23] inert
cations for the stabilisation of unusual alkalide[24,25], electride[26]
and homopolyatomic[27–29] anions, and components of higher
order rotaxane-based molecular muscles.[30] Cryptands have also
attracted interest as selective chelates for the detection and
sequestration of toxic heavy metal cations such as Pb(II), which
is a pernicious environmental pollutant as a consequence of the
historical widespread industrial use of lead in the production of
lead-acid batteries; paints, pigments and glazes; ammunitions;
plumbing pipes, solder and fixtures; herbal medicines; and leaded
fuels. Once ingested or inhaled by humans lead is known to
accumulate in soft tissues including the liver, kidneys and brain,
ligand is synthesised via a convenient one-pot [2 + 3] condensation
reaction between triazacyclononane and 2,6-bis(bromomethyl)
pyridine in the presence of M
sodium, potassium and lead(II) complexes of the ligand are
characterised in the solid state. preliminary solution-phase
2 3
CO (M = Na, K). The proton, lithium,
A
competition experiment indicates that the cryptand ligand
preferentially binds lead(II) in the presence of sodium, calcium,
potassium and zinc cations in methanol solution.
Introduction
Cryptands are a class of cage-like polycyclic host molecules, first
synthesised during the late 1960s, which played a central
historical role in the advent of supramolecular chemistry.[1] The
early diaza polyether cryptand ligands were shown to be capable
of binding spherical alkali metal and alkaline earth metal
cations[2,3] with unprecedented thermodynamic and kinetic
stabilities, and with unrivalled selectivities for complementary
sized metal cationic guests. The remarkable complexation
properties of cryptand ligands, collectively termed the ‘cryptate
effect’ are elegantly exemplified by Lehn’s prototypical
diazapolyoxa cryptand 222.[4,5] This receptor binds potassium
cations[6] selectively over sodium and rubidium,[7,8] with stability
constants which are several orders of magnitude greater than
those observed for macrocyclic ligands such as crown ethers and
the naturally occurring antibiotic valinomycin,[9] and with an
unusually slow kinetic rate of dissociation.[10] The high
thermodynamic stability of metal cryptate complexes is enthalpic
in origin, arising predominately from the high degree of
preorganisation and low degree of solvation of the cryptand
ligands;[11] the ligands’ stringent selectivity preferences have often
been attributed to size complementarity considerations[12] but
other factors such as ligand flexibility and the solvation enthalpy
and coordination preferences of the guest are also recognised to
have an important influence.[13–15]
where it can bind to the phosphate, thiol and amide groups of
nucleic acids,[31] proteins[32] and enzymes[33] with severe
toxicological effects, especially in young children.[34] Efforts to
control the industrial use of this toxic metal have led to declining
levels of lead in the environment, food and the human blood
stream over recent decades; however there is thought to be no
safe exposure threshold, with even low exposure levels
presenting a significant public health risk.[35] Selective chelate
forming compounds which can be used for the environmental
detection and extraction of lead, as well as in the diagnosis and
treatment of lead intoxication, are therefore highly attractive
targets.[36,37]
Herein we report the convenient one-pot synthesis of a new
9
bis-triazacyclononane tris-pyridyl N -azacryptand ligand which is
shown to encapsulate alkali metal and divalent lead cations. The
lithium, sodium, potassium and lead(II) complexes of the cryptand
ligand are characterised in solution and in the solid state.
Preliminary cation binding competition experiments indicate that
2+
+
the cryptand exclusively complexes Pb and Na in the presence
2+
2+
+
of Ca , Zn and K cations in methanol solution.
Results and Discussion
[
a]
b]
Dr A. Brown, Thanthapatra Bunchuay, Dr C. G. Crane, Dr. A. L.
Thompson, Prof. P. D. Beer, Department of Chemistry, University of
Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford,
OX1 3TA
The new cryptand ligand comprises two triazacyclononane
(
TACN) capping groups which are bridged by three pyridyl side-
arms to form a rigid cage-like structure in which each of the nine
nitrogen donor groups converges towards a central cation binding
cavity. The cryptand was synthesised via a one-pot [2 + 3]
condensation reaction between TACN and 2,6-bis(bromomethyl)
E-mail: paul.beer@chem.ox.ac.uk
[
Dr N. G. White, Research School of Chemistry, The Australian
National University, Canberra, ACT, Australia
Supporting information for this article is given via a link at the end of
the document
pyridine in the presence of M
2 3
CO (M = Li, Na, K) in refluxing
acetonitrile. Purification by column chromatography on neutral
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ions by electrospray mass spectrometry, the two
compounds are clearly distinguishable by
differences in their 1H NMR spectra. The 1
H
NMR spectrum of the minor product is
analogous to that of the product of the
potassium-templated reaction, suggesting
a
+
−,
helical sodium cryptate structure, [Na Ì 1] ·PF
6
in which the cation is centrally located within the
1
cavity (Figure 2(i)). The H NMR spectrum of the
major product reveals additional asymmetry
between the top and bottom of the molecule, with the methylene
and ethylene protons appearing as four and eight separate
signals respectively. Furthermore an extra proton signal is
observed at 10.2 ppm with an integral value of 1. The 2-D COSY
spectrum revealed through-bond coupling interactions between
this proton and the ethylene and methylene protons, suggesting
that the extra signal appears as a result of internal protonation of
one of the bridgehead nitrogen atoms (Figure 2(ii)). This
bridgehead nitrogen proton signal is consistently observed as a
Scheme 1. One-pot synthesis of the alkali metal cryptate complexes
+
−
[
M 1] ·PF
Ì
6
alumina followed by counteranion exchange afforded the alkali
metal cryptate products as their hexafluorophosphate salts
(
Scheme 1).
Potassium templated reaction. For the reaction performed in
the presence of K CO a single product was isolated in 20% yield.
The electrospray mass spectrum of this compound showed a
3
sharp singlet in the protic CD OD solvent, from which it is
2
3
apparent that the rate of the hydrogen–deuterium exchange
reaction is slower than the timescale of the NMR experiment.
Kinetically slow proton transfer rates are a characteristic feature
of azacryptand ligands which is thought to reflect the restricted
conformational dynamics of these cage-like structures.[38,39] The
major product was therefore assigned as the protonated sodium
]+ ion
−. The 1H NMR
single peak at m/z = 606.34, corresponding to the [M – PF
6
+
for the potassium cryptate complex [K Ì 1] ·PF
spectrum of this species in CD OD (Figure 1) reveals a
diastereotopic splitting of the methylene proton signals H and H ’,
along with the appearance of four separate signals corresponding
to the ethylene protons H , H ’, H and H ’, consistent with a
helical cryptate structure with overall D point group symmetry.
Variable temperature H NMR experiments in [D ]DMSO revealed
6
3
3
3
cryptate [Na Ì 1·H] ·2PF
6
−. The sodium cation presumably does
2
+
4
4
5
5
not interact with the protonated TACN group and is instead
displaced from the centre of the cryptand cavity towards the
neutral TACN group, forming a six-coordinate complex with the
three nitrogen atoms of this non-protonated TACN group and the
three pyridyl nitrogen atoms. This was later corroborated by solid
state structural characterisation of the complex (vide infra). The
ready protonation of the sodium cryptate structure presents a
possible indication that the size and topology of the ligand’s cavity
does not constitute an optimal coordination environment for the
sodium cation, which may prefer a lower coordination
3
1
6
that coalescence of the diastereotopic methylene signals is not
observed below 100 °C, suggesting a high kinetic barrier to
1
conformational interconversion (Figure S3, ESI). There is no H
NMR evidence of any additional asymmetry between the two
TACN capping groups or the three pyridyl side-arms, which is
consistent with an endo binding mode in which the potassium
cation resides centrally within the cryptand’s cavity.
HOD
CD
2
HOD
H
5H
4
'
4
+
H
H
number and shorter Na —NTACN distances than can be
5
'
N N N
H2
H
3
,H
3
'
achieved in the symmetrical nonacoordinate complex.
H
1
NNK+
N
H
2
H
H
3
Lithium templated reaction. Substitution of K
2 3
CO or
N
NN
3
'
Na CO for Li CO in the cryptand forming reaction was
2
3
2
3
H
1
H
4
, H
4
', H
5
, H
5
'
observed to have a detrimental effect on the cryptate yield.
Although small quantities of the protonated and non-
2
+
−
protonated lithium cryptates [Li
Ì
1×H] ·2X
and
+
−
[
Li 1] ·X were detected during analysis of the crude
Ì
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0
product mixture, we were unable to isolate pure samples
of these minor products owing to their very low yields of
Chemical Shift (ppm)
Figure 1. 1H NMR spectrum (500 MHz; CD
formation and suspected interconversion during chromatography.
This was taken as evidence that lithium is an inferior template for
the formation of the cryptand ligand as a result of poor
complementarity between the small, hard lithium cation and the
cryptand’s cavity. In spite of this, X-ray quality crystals of the
3
OD; 298 K) of the potassium
+
−.
cryptate complex [K
Ì
1] ·PF
6
Sodium templated reaction. In contrast, when the reaction was
carried out using Na CO in place of K CO the formation of two
separate products was apparent from analysis of the crude 1
2
3
2
3
2+
−
H
protonated complex [Li 1×H] ·2Cl were grown from a solution
Ì
NMR spectrum. After chromatographic purification each of these
products were isolated in yields of 20% and 5% respectively.
While both products were observed as [1 + Na] and [1 + Na]2+
containing a mixture of products isolated from the lithium
templated reaction, which allowed this complex to be
characterised in the solid state (vide infra).
+
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bridgehead nitrogen atoms in each TACN capping group.
The large twist angle between these capping groups
(
j = 47(2)°; see Figure 7c) helps to minimise electrostatic
repulsions between the two cationic ammonium groups.
The bromide counteranions are presumably too large to
penetrate the cavity and are instead located externally,
where they participate in a series of C-H—Br− short
2
contacts with the CH groups of the cryptand ligand and
the dichloromethane solvent molecules.
+
−. The potassium cryptate [K
+
−
[
K
Ì
1] ·PF
6
Ì
1] ·PF
6
was
similarly observed to crystallise as a racemate in the
monoclinic space group P2 /c. The asymmetric unit
1
contains two crystallographically independent potassium
cryptate complexes which have inverted helicities but
otherwise appear to show minimal structural variations.
Measurements have been taken from just one of the two
complexes, since the other was found to incorporate
1
significantly more disorder. In agreement with the H NMR
spectral assignment of the potassium cryptate, the metal
cation is centrally located within the cavity, residing just
0
.002 Å above the plane of the three Npy nitrogen donor
atoms and forming an almost linear 178° angle with the
centroids of the two TACN groups (Figure 4a). The cation
can be seen to interact with the full complement of nine
nitrogen donor atoms in a distorted tricapped trigonal
+
prismatic coordination geometry. The K —NTACN distances
+
(
(
2.855(4)–2.933(4) Å; mean = 2.895 Å) and K —Npy distances
Figure 2. 1H NMR characterisation (500 MHz; CD
OD; 298 K) of the sodium
3
2.710(3)–2.738(3) Å; mean = 2.725 Å) are 5-13% smaller than
cryptate complexes: (i) comparative 1-D spectra of the symmetrical complex
+
−
2+
−
[
Na
Ì
1] ·PF
6
(top) and monoprotonated complex [Na
Ì
1×H] ·2PF
6
(bottom)
the sum of the ionic and van der Waals radii of nine-coordinate
potassium and nitrogen (3.10 Å).[42,43] Assuming that the enthalpic
and (ii) section of the 2-D COSY spectrum of the monoprotonated complex
Ì
Na 1×H] ·2PF .
2
+
−
6
[
gain is maximised when the cation—donor atom distances are
approximately equal to the sum of their ionic and van der Waals
+
radii, the short K —Npy distances suggest that the volume of the
Solid state characterisation of alkali metal
cryptate complexes
cryptand’s cavity may be slightly too small to accommodate the
+
K cation without some unfavourable overlap of electron clouds.
In comparison to the diprotonated free ligand, the cryptand
+
−, [Na
+
−
2+
−
The complexes [K
Ì
1] ·PF
1×H] ·2Cl were characterised by X-ray crystallography in
the solid state and their structures compared with that of the
6
Ì Ì
1] ·Cl , [Na 1×H] ·2Cl and
3
ligand is contracted along the C axis and expanded in the
2
+
−
[
Li
Ì
perpendicular plane in order to optimally accommodate the
potassium cation: this can be seen from the smaller TACN
centroid–to–centroid distance (4.66 Å), and greater Npy–Npy
distances (4.654(4)–4.780(5) Å; mean = 4.72 Å) compared to
2
+
− [40,41]
diprotonated free ligand, [H
2
·1] ·2Br .
Diprotonated free ligand. The solid state structure of the
2
+
−
2
those observed in the structure of [H ·1] ·2Br . There is a
2
+
−
diprotonated free ligand [H
2
·1] ·2Br (Figure 3) confirms that the
symmetric helical conformation, as
corresponding increase in the magnitude of the mean TACN
ligand skeleton adopts a D
3
NCCN torsion angle, Y, but the twist angle, j, is comparable in
1
suggested by the solution H NMR spectra of the cryptate
2
+
−
1]+ ·PF
−
the structures of [H
2
·1] ·2Br and [K
Ì
6
(Figure 7 and
+
−
and [Na 1] ·PF
Ì
6
−. The two TACN
+
complexes [K
Ì
1] ·PF
6
Table 1).
capping groups are staggered with respect to each other and the
pyridyl side-arms are twisted by 46–49° in the same sense with
respect to the planes defined by the three nitrogen atoms in each
TACN capping group. Despite possessing this conformational
chirality, the ligand crystallised as a racemate in the monoclinic
+
−
+
−
[
Na
Ì
1] ·Cl . The cryptate complex [Na
Ì
1] ·Cl crystallised in
the centrosymmetric space group P 1 . The asymmetric unit
contains two sodium cryptate complexes which are structurally
almost identical. In each complex the sodium cation is centrally
located within the cryptand cavity (Figure 4b), lying in the plane
defined by the three pyridyl nitrogen atoms and intersecting the
1
non-chiral space group P2 /c. All of the nitrogen atoms adopt an
endo conformation with their lone pairs converging towards the
spheroidal cryptand cavity. The TACN NCCN torsion angles,
Y (Figure 7d), are in the range 42.9(5)–49.0(6)°, which indicates
a relatively strain-free staggered synclinal conformation about the
C¾C bonds. A proton can be seen to reside on one of the
3
C axis which connects the centroids of the three nitrogen atoms
+
in each TACN capping group (ꢀcentroid–Na –centroid: 179.4°
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sufficient quality for discussion here, it is nevertheless apparent
that the coordination environment of the sodium cation in this
+
−
[
Na Ì 1] ·CF
3 3
SO structure does not significantly differ from that
+
−
observed in the structure [Na
Ì
1] ·Cl (section S4, ESI).
2
+
−
[
Na
Ì
1·H] ·2Cl . The solid state structure of the protonated
2
+
−
sodium complex [Na
Ì
1·H] ·2Cl is in the space group Fdd2.
The asymmetric unit contains one cryptate complex in which the
sodium cation is significantly displaced from the centre of the
cryptand cavity towards one of the two TACN groups, residing
0
.58 Å above the plane described by the three pyridyl nitrogen
atoms (Figure 4c). The cation’s coordination environment can be
regarded as an irregular six-coordinate polyhedron comprising
+
the three Npy donors (Na —Npy distances: 2.461(3)–2.550(3) Å;
mean = 2.51 Å) and the three nitrogen donors from the more
+
proximal of the two TACN groups (Na —NTACN distances:
+
2
.478(3)–2.485(3) Å; mean = 2.48 Å). The three shorter Na —
+
N
TACN are noticeably shorter than the Na —NTACN distances
+
−
+
observed in the complex [Na
Ì
1] ·Cl , while the three Na —Npy
+
distances are roughly comparable. The longer Na —NTACN
distances (3.405(3)–3.525(3) Å; mean = 3.48 Å) are significantly
beyond the sum of the van der Waals and ionic radii for nitrogen
and nine-coordinate sodium (2.79 Å),[42,43] suggesting that the
more distant TACN group does not participate in any coordinative
interactions with the cation. The asymmetric location of the cation
2
+
−
is fully consistent with the protonated structure [Na
Ì
1·H] ·2X
which was assigned from the solution NMR data. The Fourier
difference map revealed a convincing peak for the electron
density associated with the presence of a proton on one of the
three nitrogen atoms of the more distant, non-coordinating TACN
group. In addition, the presence of electron density corresponding
to two chloride counteranions per cryptate complex in the solid
state structure provides further indirect evidence of N protonation
of the ligand on the basis of charge balance considerations.
Figure 3. Solid state structure of the diprotonated free ligand [H
2
·1]2+·2Br . For
−
clarity, solvent molecules, non-polar hydrogen atoms and the two bromide
counteranions have been omitted.
2
+
−
[ 1·H] ·2Cl . X-ray quality crystals of the protonated lithium
Ì
Li
2
+
−
complex [Li
Ì
1·H] ·2Cl were obtained from a mixed solution
containing both the protonated and non-protonated complexes.
The data are of relatively low quality but it was possible to
unambiguously determine the structure of the complex, which is
and 179.7°). This allows the each cation to interact with the nine
available nitrogen donor atoms in a distorted tricapped trigonal
prismatic geometry, analogous to that observed in the structure of
2
+
−
+
−
+
similar to that of the protonated sodium complex [Na
Ì
1·H] ·2Cl .
the potassium complex [K
Ì
6
1] ·PF . The Na —NTACN distances
2
+
−
The [Li
Ì
1·H] ·2Cl structure likewise crystallises in the
fall in the range 2.820(2)–2.869(2) Å (mean = 2.84 Å) and are
orthorhombic space group Fdd2 and the asymmetric unit contains
half of a cryptate complex; this is related to the other half by a
rotation about the crystallographic two-fold axis, which coincides
comparable to the sum of the van der Waals and ionic radii for
nitrogen and nonacoordinate Na+ (2.79 Å).[42,43], whereas shorter
+
Na —Npy distances of 2.576(2)–2.611(2) Å (mean = 2.59 Å) are
2
with one of the C axes of the cryptand ligand. The structure
observed. The TACN centroid-centroid distances (4.54 Å and
contains substantial disorder and it was therefore necessary to
use two positions of equal occupancy to model the majority of the
atoms in the cryptand ligand, and four positions for the chloride
counteranions. The position of the lithium cation is significantly
offset from the centre of the cage towards one of the two TACN
capping groups, with a distance of 0.94 Å between the cation and
the mean plane of the pyridyl nitrogen atoms (Figure 4d). The
cation’s coordination sphere can therefore be regarded as a
highly distorted six-coordinate octahedron comprising the three
4
.57 Å) reveal that the ligand is compressed along the C
3
axis
2
+
−
compared to both the diprotonated free ligand [H
2
1] ·2Br and
−. It can be seen from the
+
the potassium complex [K
Ì
1] ·PF
6
N
py—Npy distances (4.468(4)–4.517(3) Å; mean = 4.49 Å) that this
compression is accompanied by an expansion in the
perpendicular plane compared to the diprotonated free ligand
2
+
−
2
[H ·1] ·2Br , but the degree of expansion is smaller than that
+
−
observed in the structure of the potassium complex [K
Ì
1] ·PF
6
(
Table 1). An additional solid state structure of the complex
+
+
−
pyridyl nitrogen atoms (mean Li —Npy distance: 2.39 Å) and the
[
3 3
Na Ì 1] ·CF SO was also obtained. While the data are not of
three nitrogen atoms of the more proximal TACN group (mean
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+
6
1] ·PF 1] ·Cl , c) [Na
−, b) [Na 1·H]2+·2Cl− and d)
Ì Ì Ì
+
−
Figure 4. Solid state structures of the potassium, sodium and lithium cryptate structures: a) [K
1·H]2+·2Cl . For clarity, solvent molecules, counteranions and non-polar hydrogen atoms have been omitted; only one of the two independent complexes found
−
[
Li
Ì
+
−
+
−
within the asymmetric units for the [Na
the cryptand ligand is shown for the [Li
Ì
Ì
1] ·Cl and [K
Ì
1] ·Cl structures are shown; and only one of the partially occupied positions used to model each atom in
1·H]2+·2Cl structure.
−
+
Li —NTACN distance: 2.23 Å). The comparatively large mean
distance between the lithium cation and the more distant set of
TACN nitrogen atoms (3.78 Å) suggests that the metal cation is
exclusive provision of nitrogen donor groups should help to confer
selectivity for Pb(II) over harder alkali metal cations; furthermore
Pb(II) is known to form complexes with high coordination numbers
not involved in any coordinative interactions with this TACN group. of up to 10, and has been previously documented to bind to
It therefore appears, by analogy with the structure of the [Na
Ì
1·
various azacryptand hosts[44–48] as well as to macrocyclic ligands
incorporating TACN[49–52] and pyridyl[50,52–56] donor groups. In
order to test the ligand’s capacity for lead encapsulation the
2
+
−
H] ·2Cl complex, that the more distant TACN group is
protonated. Although the data are not of sufficient quality for the
+
+
−
NH proton electron density to be unequivocally identified in the
potassium cryptate complex [K
presence of a threefold excess of Pb(NO
monitoring of the reaction by electrospray mass spectrometry, the
Ì
1] ·PF
6
was heated in the
difference maps, its presence is supported by the offset position
of the lithium cation, in combination with the presence of electron
density equating to two chloride anions per cryptate complex in
the unit cell. The ligand appears to be stretched in the direction of
3
)
2
in CH CN. During
3
the C
cation and the cationic ammonium group; as a result it displays
the largest TACN centroid–to–centroid distances, smallest Npy
py distances and second smallest twist angle between TACN
capping groups of all the metal cryptate complexes (Table 1).
3
axis in order to maximise the distance between the lithium
—
N
Lead (II) complexation. We reasoned that the azacryptand 1
may hold potential as a complementary host for the toxic divalent
lead cation based on the following considerations: the ionic radius
1]2+·2PF −
6
.
Scheme 2. Synthesis of the lead cryptate complex [Pb
Ì
+
+ [42]
of the Pb(II) cation lies in between those of Na and K , while
Pb(II) also benefits from a higher divalent charge; the ligand’s
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+
previously been structurally characterised,[44,47,48,58,59] to the best
of our knowledge this is the first example of a nonacoordinate
[
1 + K] molecular ion (m/z = 606) gradually disappeared and was
replaced by a new peak centred at m/z = 388 corresponding to
the [1 + Pb] ion, suggesting that the Pb2+ cation slowly displaces
2
+
Pb(II) N
lead cryptate were grown from a sample prepared by treatment of
the potassium cryptate with excess Pb(OAc) , followed by
azacryptand complex. X-ray quality single crystals of the
9
+
the K cation from the cryptand’s cavity, with the transmetallation
reaction reaching completion within 48 hours. After counteranion
exchange using Amberlite ion-exchange resin the lead cryptate
2
counteranion exchange using Amberlite IRA400 ion exchange
resin, which was expected to yield the product as a chloride salt,
2
+
−
complex [Pb
Ì
6
1] ·2PF was isolated in 65% yield (Scheme 2).
2
+
−
[
Pb 1] ·2Cl . Upon solving the structure the lead cryptate was
Ì
instead found to have crystallised with a disordered complex
counteranion. The counteranion was successfully modelled as a
mixture of [PbCl
]2— and [PbCl AcO]2—, both occupying the same
4 3
crystallographic site with fractional occupancies of 0.38 and 0.62
respectively. However, we note that this is a tentative assignment
and there remains some ambiguity about the identities of the
unusual counteranions in this structure (see Section, S4, ESI for
more details). Some positional disorder was identified in the
structure of the cryptate complex, and this was accordingly
modelled using two discrete positions for all of the atoms in the
ligand. The measurements discussed here are taken solely from
the major component of the model for the disordered cryptand
ligand, which has a refined partial occupancy of 0.84. The cryptate
structure reveals a symmetrically located Pb(II) cation which is co-
planar with the three pyridyl nitrogen donors and co-linear with the
two TACN centroids (distance between cation and plane: 0.015 Å;
2
+
∠
centroid–Pb –centroid: 179.7°), indicating
a
holodirected
Figure 5. Comparative 1H NMR spectra (500 MHz; CD
cryptate complex [Pb Ì 1]2+·2PF −
(top) and potassium cryptate complex
(bottom). *The observation of a double water peak is attributed to
the presence of both H O and HOD.
geometry with no evidence of any stereochemical lone pair
3
OD; 298 K) of the lead
2+
6
activity. The Pb —Npy (2.692(7)–2.732(6) Å; mean = 2.72 Å) and
+
−
[
K Ì 1] ·PF
6
2+
Pb —NTACN distances (2.751(9)–2.821(10) Å; mean = 2.77 Å)
2
are 3–8% shorter than the sum of the ionic and van der Waals
radii of nonacoordinate lead(II) and nitrogen (2.90 Å).[42,43] The
TACN centroid-to-centroid distance (4.39 Å) is the shortest of
those observed in any of the five cryptate structures discussed
here while the relatively large Npy—Npy distances (4.665(10)–
1
The H NMR spectrum of this lead cryptate is compared with that
of the potassium cryptate in Figure 5. Significant downfield shifts
2
in the aromatic pyridyl and methylene CH proton signals occur
4
.783(10) Å; mean = 4.71 Å) are comparable to those observed
upon displacement of K by the divalent Pb2+ cation. In addition
satellites of the methylene proton signals are observed in the
spectrum of the lead complex as a result of scalar coupling
interactions between the 1H
+
in the structure of the potassium cryptate complex.
and 207Pb (I = ½; 22%
abundance) nuclei. Similarly,
satellites of the signals for the
methylene and pyridyl carbon
atoms area observed in the
13C
NMR spectrum (Figure
S13, ESI). There is no
apparent desymmetrisation of
the 1H NMR spectrum upon
2
+
complexation
suggesting
of
Pb ,
a
spherically
charge
symmetrical
distribution around the cation,
with no stereochemical activity
2
from the 6s lone electron pair,
as might be expected in a nonacoordinate Pb2+ complex.[57]
Figure 6. Orthogonal views of the solid state structure of the the lead cryptate
complex [Pb
been omitted.
Ì
1]2+·X2−. For clarity, hydrogen atoms and counteranions have
The lead complex was also characterised in the solid state
(
.
Figure 6). While a number of lead cryptate complexes have
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Chemistry - A European Journal
10.1002/chem.201801300
FULL PAPER
Figure 7. Parameters used to evaluate the distortions in the cryptand host conformation which occur in the presence of different cations: a) TACN centroid-to-
centroid distance, b) Npy—Npy distances, c) twist angle, j, between the two TACN capping groups and d) TACN NCCN torsion angle, Y.
-
1×H]2+·2Cl , [Na
−
+
−
Table 1. Selected distances and angles from the solid state structures of the proton and metal cryptate complexes [H
2
1]2+·2Br , [Li
Ì
Ì
1] ·Cl ,
1×H]2+·2Cl , [K
−
Ì
1] ·PF
+
−, and [Pb
Ì
1]2+·X2− (X2− = 38% PbCl
2—
62% PbCl
3
AcO2—).[a]
[Na
2.57
[
Na
Ì
6
4
,
+
+
−[b]
+
1] ·Cl−
1×H] ·Cl−
+
+
−[c]
Ì
1]2+·X2−[d]
[H
2
1] ·2Br−
[Li
Ì
1×H] ·Cl
[Na
Ì
Ì
[K
Ì
1] ·Cl
[Pb
R(M ) + RvdW(N) (Å)[e]
+
—
—
2.14
2.79
3.10
2.90
M—Npy distances (Å)
2.35(2)–2.42(2)
mean: 2.39(0.03)
2.576(2)–2.611(2)
mean: 2.59(0.01)
2.461(3) –2.550(3)
mean: 2.51(0.05)
2.710(3)–2.738(3)
mean: 2.73(0.01)
2.692(6) –2.732(6)
mean: 2.72(0.02)
2.14(2)–2.26(3)[g]
mean: 2.23(0.10)[g]
2.820(2)–2.869(2)
mean: 2.84(0.02)
2.478(3)–2.485(3)
mean: 2.48(0.00)
[g]
2.879(4)–2.933(4)
mean: 2.90(0.02)
2.751(9)–2.821(10)
mean: 2.77(0.03)
M—NTACN distances
(
—
Å)[f]
[g]
3
.62(2)–3.87(3)[h]
3.405(3)–3.525(3)
[h]
[h]
mean: 3.78(0.13)[
h]
mean: 3.48(0.06)
4.89
TACN centroid–
centroid distance (Å)[f]
5.21
4.91[i]
4.57[j]
4.54
4.66
4.39
5.04
Mean Npy—Npy
distance (Å)[
4.02(0.06)
3.81(0.24)
4.49(0.02)
4.22(0.05)
4.72(0.06)
4.71(0.07)
f],[k]
Twist angle, j (°)[f],[k]
47(2)
48(2)
44(1)
40(2)
41(1)
38(1)
Mean TACN NCCN
torsion angle, Y (°)
46.2(2.1)
—
50.9(0.6)
49.8(1.6) )[g]
52.7(1.7)
54.8(1.9)
[f],[k]
4
5.7(2.7)[h]
[
a] Where individual values are reported, estimated standard errors are given in parentheses. Where mean values are reported, the standard deviation is given
in parentheses. [b] The diffraction data for the crystal structure of the protonated lithium cryptate, [Li
Ì
1×H]2+·2Cl− are not of sufficient quality to support a detailed
analysis of bond lengths and angles, but ranges and mean values are provided. Measurements have been taken from both equally occupied components of the
disorder model. The variance in the measured values of the NCCN torsion angles is deemed to be too large for meaningful analysis so this parameter is not
+
included in the table. [c] All measurements for the structure of the potassium cryptate [K
Ì
1] ·PF
6
are taken from just one of the two crystallographically
independent complexes contained within the asymmetric unit, since the other was found to contain significantly more disorder. [d] The positional disorder in the
structure of the lead chelate [Pb
1]2+·X2— was modelled using two discrete, fractionally occupied positions for all of the atoms in the ligand. Measurements are
taken solely from the higher occupancy position, which has a refined partial occupancy of 84%. [e] The sum of the ionic and van der Waals radii of the metal
Ì
cation and nitrogen.[42,43] The values for the ionic radii are based on a coordination number of 9 for the [K
Ì
1] ·PF
+
−, [Na 1]2+·X2— structures,
Ì Ì
1] ·Cl and [Pb
+
−
6
1×H]2+·2Cl and [Li 1×H]2+·2Cl structures. [f] TACN centroid–centroid, Npy–Npy distances, twist angle, j, between
−
−
and a coordination number of 6 for the [Na
Ì Ì
TACN capping groups and TACN NCCN torsion angle, Y, are defined in Figure 7. [g] Measured values refer to the more proximal TACN group which is
coordinated to the metal cation. [h] Measured values refer to the more distant, protonated TACN group which is not coordinated to the metal cation. [i] Two
separate values are reported: one from each equally occupied component of the disorder model. [j] Two separate values are reported because Z’ = 2. [k] It is
possible to measure three values for the twist angle, j, and Npy—Npy distances, and six values for the TACN NCCN torsion angle, Y, per cryptand ligand. The
mean values are reported in the Table 1, with standard deviations given in parentheses.
Preliminary Competition experiments. In order to obtain a
qualitative estimate of the relative affinity of the cryptand 1 for Pb2+
heated at reflux in the presence of one molar equivalent of
Pb(NO , Ca(ClO , Zn(ClO and NaClO . After three days,
3
)
2
4
)
2
4
)
2
4
compared to other cations
a
competition experiment was
analysis of the product distribution by electrospray mass
undertaken. Na , K , Zn and Ca2+ cations were identified as
potentially important competitors whose concentrations may
typically exceed those of Pb2+ during environmental and
biomedical applications of lead(II) chelation processes. A 2 mM
+
+
2+
spectrometry revealed three [1 + Pb]2+ and [1 + Pb + X]+
(X = ClO -, PF -
) ions associated with the lead(II) cryptate
4 6
+
complex, along with a [1 + Na] ion. In contrast, the potassium,
calcium and zinc complexes of the cryptand ligand were not
detected (Figure 8). This provides a provisional indication that the
+
−
solution of the potassium complex [K
Ì
6 3
1] ·PF in CD OD was
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Chemistry - A European Journal
10.1002/chem.201801300
FULL PAPER
cryptand’s affinity for lead(II) compares favourably with those for Acknowledgements
potassium, calcium and zinc(II) cations, although it should be
noted that mass spectrometry is not a quantitative analysis
technique. The room temperature 1H NMR spectrum of the
reaction mixture was also recorded at the end-point of the reaction
in order to quantify the relative concentrations of the lead(II) and
We thank the European Research Council for funding under the
European Union’s 7th Framework programme (FP7/2007–2013),
ERC advanced grant agreement number 267426. TB thanks the
Development and Promotion Science and Technology Talent
Project (DPST), Thailand for funding. We also thank Diamond
Lightsource for an award of beamtime on I19 (MT13639) and Drs
David Allan, Mark Warren, Harriott Nowell, and Sarah Barnett for
technical support
sodium cryptate complexes, which each give rise to
a
1
3
characteristic set of H NMR signals in CD OD. Analysis of the
integral ratios revealed that the lead(II) cryptate complex is the
major product of the competition experiment, while complexes of
all other metal cations, including sodium, are only present as
baseline impurities (Figure S15, supporting information).[60] Two
additional minor sets of peak are observed in the spectrum. These
peaks are assigned to protonated forms of the free ligand, which
are estimated to make up ~13% of the total product distribution.[61]
The cryptand therefore appears to show a selectivity preference
for complexation of divalent lead cations in the presence of a
range of other mono- and di-cations.
Keywords: cryptands • metal cation recognition • template-
directed assembly • host–guest chemistry • supramolecular
chemistry
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
A new N
9
-azacryptand ‘Beer Can’
Asha Brown, Thanthapatra Bunchuay,
Christopher G. Crane, Nicholas G.
White, Amber L. Thompson, Paul D.
Beer*
receptor for metal cations is prepared
by a convenient one-pot [2 + 3]
condensation reaction which is
templated by alkali metal cations.
Page No. – Page No.
A bis-triazacyclononane tris-pyridyl
9
N -azacryptand ‘Beer Can’ receptor
for complexation of alkali metal and
Pb(II) cations
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