Diastereoselective assembly of pentanuclear circular helicates

Article abstract of DOI:10.1039/c1dt11414j

Reaction of a ligand which contains two N-donor and O-donor tridentate domains separated by a 1,3-phenylene spacer unit with Zn²⁺ ions results in a pentanuclear circular helicate [Zn₅(L)₅] ¹⁰⁺ and this structure

Full text of DOI:10.1039/c1dt11414j

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Self-Assembly in Inorganic Chemistry
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Metal ion directed self-assembly of sensors for ions, molecules and biomolecules
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Dalton Trans., 2011, DOI: 10.1039/C1DT10876J
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Self-assembly between dicarboxylate ions and a binuclear europium complex: formation of stable
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Dalton Trans., 2011, DOI: 10.1039/C1DT11103E
Structural and metallo selectivity in the assembly of [2 × 2] grid-type metallosupramolecular
species: Mechanisms and kinetic control
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PAPER
Diastereoselective assembly of pentanuclear circular helicates†
Oliver R. Clegg,a Rebecca V. Fennessy,a Lindsay P. Harding,a Craig. R. Rice,*a T. Riis-Johannessenb and
Nicholas C. Fletcherc
Received 26th July 2011, Accepted 7th October 2011
DOI: 10.1039/c1dt11414j
Reaction of a ligand which contains two N-donor and O-donor tridentate domains separated by a
1,3-phenylene spacer unit with Zn2+ ions results in a pentanuclear circular helicate [Zn5(L)5]10+ and this
structure persists in both the solid and solution state. The formation of this high nuclearity species is
governed by unfavourable steric interactions between the phenyl units which destabilize the simple
linear helicate. Incorporation of enantiopure units within the ligand strand controls the
diastereoselectivity with up to 80% d.e.
linear dimers with tetrahedral metal ions and trinuclear circular
Introduction
helicates with octahedral metal ions.10 Other reports have cited
Transition metal helicates arise from the reaction of a suitable
inter-strand CH ◊ ◊ ◊ p interactions as the principal driving force for
ligand L with a transition metal ion Mz+ giving, in the simplest
the preferential formation of high complexity cyclic assemblies
case, the dinuclear species [M2(L)2]2z+. This type of self-assembly is
generally well understood and there are now numerous examples
in the literature.1–7 Circular helicates are cyclic oligomers of
general formula [Mn(L)n]nz+ (n > 2) which retain the “over-
and-under” ligand motif requisite of helical chirality. However,
they are much less common and are more difficult to generate
compared with the linear helicates. This is in part due to the
fact that the requirements of the ligand strand are identical in
both cases, i.e. the ligand must simply be able to partition into
two different coordination domains each of which coordinates a
different metal ion. For a cyclic helicate to result, therefore, the
formation of the entropically favoured linear [M2(L)2]2z+ helicate
has to be prevented. This can be achieved by a number of methods.
One mechanism is by anion templation, wherein intramolecular
interactions between the metal complex and the anion result
in a high nuclearity species.8 For example, work reported by
Ward et al. demonstrated that a ligand with two bidentate
domains separated by a 1,8-naphthalenediyl spacer forms a simple
mononuclear species with Cu(CF3SO3), but in the presence of
tetrafluoroborate, a tetranuclear cyclic helicate [Cu4L4]4+ was
observed.9 Hannon, on the other hand, demonstrated that a
metal ion’s preference for different coordination geometries could
affect the self-assembly outcome. In this case a bis-bidentate
ligand containing a 1,3-bis(aminomethyl)phenyl spacer formed
over their dimeric counterparts.11
Destabilizing the linear helicate assembly can also result in
the formation of a circular helicate. Recently we have shown
that the ligand L (Fig. 1), which contains two tridentate binding
domains separated by a 1,3-phenylene spacer unit, reacts with
Cd2+ to give the simple linear helicate [Cd2(L)2]4+ whilst Zn2+
gives a pentanuclear circular helicate [Zn5(L)5]10+. This difference
is attributed to steric interactions between the two spacer units. In
the [Cd2(L)2]4+ complex the distance between the two phenyl rings
˚
is ca. 4.2 A and examination of the van der Waals radii reveals
marginal surplus space between these inward facing protons.
When smaller zinc ions are employed it is likely that any steric
and/or electrostatic repulsion between these protons would be
significantly emphasized in an isostructural di-zinc(II) helicate. As
a result of this destabilization an alternative pentanuclear circular
helicate [Zn5(L)5]10+ is formed.12
Fig. 1 Structure of the previously reported ligand L.
Another important aspect of helicates is that they can be
programmed to express certain structural features of higher-order
complexity. This is achieved by elaborating on the basic design
principles that govern helicate formation itself (i.e. careful consid-
eration of ligand topology and metal stereoelectronic preference),
and can entail: (i) directional control over ligand alignment, i.e.
head-to-tail vs. head-to-head helicates, (ii) selective incorporation
of different metal cations along the helical axis (i.e. heterometallic
assemblies) and (iii) selective incorporation of different ligand
aDepartment of Chemical and Biological Sciences University of Huddersfield,
Huddersfield, HD1 3DH, UK. E-mail: c.r.rice@hud.ac.uk; Fax: (+44) 148-
447-2182
bEPFL SB ISIC LCS BCH 3307 (Baˆtiment de chimie UNIL), CH-1015,
Lausanne, Switzerland
cSchool of Chemistry and Chemical Engineering, Queen’s University Belfast,
Belfast, BT9 5AG, UK
† CCDC reference number 836308. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1dt11414j
This journal is
The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 12381–12387 | 12381
©

strands within the helical array (i.e. heteroleptic assemblies). There
are numerous examples of this type of control for the simple linear
helicates2–5 and the formation of head-to-tail and heteroleptic
cyclic helicates has recently been reported.13 Since helicates are
intrinsically chiral, stereoselective control over their self-assembly
can also been achieved, usually by incorporation of enantiopure
units within the ligand framework (i.e. chiral auxiliaries). This
type of control has already been implemented in the self assembly
of both linear and circular helicates. However, although such
elements of higher order complexity have often been incorporated
into linear helicates, the analogous treatment of circular helicates
has been studied to a much lesser degree.14
In the following we discuss the preparation of a ligand system
that contains two tridentate binding domains comprised of two
N-donors and one O-donor separated by a 1,3-phenylene unit.
Reaction of this ligand strand with Zn2+ results in the formation
of a pentanuclear circular helicate wherein the zinc ions are oc-
tahedrally coordinated by four N-donor and two O-donor atoms.
Furthermore, incorporation of enantiopure amino acid esters on
the amide functional groups results in diastereoselective assembly
of a pentanuclear circular helicate with a d.e. of up to 80%.
DPX400. Mass spectra were obtained on a Bruker MicroTOF-q
LC mass spectrometer. Circular Dichroism and UV vis spectra
were recorded at a concentration of 2.5 ¥ 10-5 mol dm-3 in
acetonitrile at 298 K on a JASCO J-815. Extreme care should
be taken when using NaCN and it should only be used in a well
ventilated fume cupboard.
Synthesis of picolinamide derivative 1a. To a two necked round
bottom flask charged with picolinic acid (1.5 g, 0.012 mol),
anhydrous DCM was added and the reaction stirred under an
atmosphere of nitrogen at 0 ◦C. To this was then added oxalyl
chloride (2 M, 8.5 ml, 0.017 mol) and the solution left to stir
for 10 min. After this time triethylamine (2.4 g, 0.024 mol) was
slowly added and the reaction was left at room temperature for
3 h. The solvent was removed by rotary evaporation giving a black
◦
solid. This was re-dissolved in anhydrous DCM, stirred at 0 C
and triethylamine (1.9 g, 0.019 mol) and diethylamine (0.73 g,
0.010 mol) added and the reaction stirred at room temperature
for 2 h. The solution was then poured into NaHCO3 (aq) (30 ml)
then extracted with DCM (3 ¥ 50 ml), and the combined organic
layers dried (MgSO4) and evaporated. The crude product was
dissolved in ether (100 ml) and de-colourising charcoal (0.1 g)
added, filtration and removal of solvent gave the pure product as a
dark yellow oil. Yield = 0.6 g, 60%. 1H NMR (400 MHz, CDCl3):
dH = 8.59 (ddd, J = 4.8, 1.6, 1.0, 1H, Py), 7.78 (dt, J = 7.7, 1.7,
1H, Py), 7.58 (dt, J = 7.8, 1.0, 1H, Py), 7.33 (ddd, J = 7.6, 4.9,
1.2, 1H, Py), 3.58 (q, J = 7.2, 2H, –CH2CH3), 3.39 (q, J = 7.1,
2H, –CH2CH3), 1.28 (t, J = 7.1, 3H, –CH2CH3), 1.16 (t, J = 7.1
Hz, 3H, –CH2CH3). ESI-MS m/z 201.1 (M + Na+), HR ESI-MS
found 201.1002 C10H14N2NaO requires 201.0998 (error 2.03 ppm).
Experimental
Crystallographic data
Single crystal X-ray diffraction data were collected at 150(2) K
on a Bruker Apex Duo diffractometer equipped with a graphite
monochromated Mo(Ka) radiation source and a cold stream of
N2 gas. Crystal data for [Zn5(L1)5](CF3SO3)10·10 ¥ EtOAc·10 ¥
MeCN (C170H155F30N30O40 S20Zn5·10 ¥ EtOAc·10 ¥ MeCN): M =
¯
6090, Triclinic, P1, a = 20.3776(13), b = 21.5461(15), c = 28.7397(19)
Synthesis of picolinamide derivative 1b. This compound was
prepared in an identical manner to 1a, except glycine methyl ester
was used in place of diethylamine and the resulting compound
purified by column chromatography (Al2O3 5% MeOH in DCM).
3
˚
˚
A, a = 79.876(2), b = 85.013(2), g = 77.697(2), V = 12120.6(1) A ,
Z = 2; rc = 1.668 Mg m-3, F(000) = 6290; dimensions 0.5 ¥ 0.2
¥ 0.2 mm-3; m(Mo-Ka) = 0.71073 mm-1, T = 150 K. A total of
131 442 reflections were measured in the range 1.44 £ q £ 23.37◦
(hkl range indices: -22 £ h £ 22, -24 £ k £ 23, -31 £ l £ 32), 35 025
unique reflections (Rint = 0.0667). The structure was refined on F2
to Rw = 0.2819, R = 0.1032 (22 284 reflections with I > 2s(I)) and
GOF = 1.069 on F2 for 2360 refined parameters, 369 restraints.
1
Yield = 42%. H NMR (400 MHz, CDCl3): dH = 8.60 (ddd, J =
4.8, 1.6, 0.9, 1H, Py), 8.49 (br s, 1H, –CONH), 8.19 (dt, J = 7.8,
1.0, 1H, Py), 7.86 (dt, J = 7.8, 1.7, 1H, Py), 7.46 (ddd, J = 7.6,
4.8, 1.2, 1H, Py), 4.29 (d, J = 5.7 Hz, 2H, –NHCH2CO2), 3.80 (s,
3H, –CO2CH3). ESI-MS m/z 217 (M + Na+), HR ESI-MS found
217.0590 C9H10N2NaO3 requires 217.0584 (error = 3.11 ppm).
-3
˚
Largest peak and hole 1.417 and -1.425 eA . A number of triflate
anions and terminal diethylamide fragments were refined with
geometric similarity restraints (SAME and SIMU). A remaining
four triflate anions were modelled using two-component disorder
models. Each component was treated as a rigid body (AFIX 9) and
population parameters for each component were refined against
a free variable. The unit cell contained large amounts of diffuse
electron density, presumably due to highly disordered interstitial
solvent. However, attempts at modelling this were unsuccessful
and the relevant scattering contributions were thus removed using
the SQUEEZE routine in PLATON. We further note that of the
ten expected triflate counter anions, only nine were resolved in the
electron density map, the tenth presumably being likewise highly
disordered. An estimated additional solvent/anion contents of
10 ¥ EtOAc, 10 ¥ MeCN and 1 ¥ OTf has therefore been included
in the moiety formula. CCDC 836308.†
Synthesis of picolinamide derivative 1c. This compound was
prepared in an identical manner to 1a, except L-valine methyl
ester was used in place of diethylamine. Yield = 37%. H NMR
1
(400 MHz, CDCl3): dH = 8.61 (ddd, J = 4.8, 1.6, 0.9, 1H, Py), 8.53
(br d, J = 8.9, 1H, –CONH), 8.19 (dt, J = 7.8, 1.0, 1H, Py), 7.86
(dt, J = 7.7, 1.7, 1H, Py), 7.45 (ddd, J = 7.6, 4.8, 1.2, 1H, Py),
4.75 (dd, J = 9.3, 5.2, 1H, –NHCH), 3.78 (s, 3H, –CO2CH3), 2.33
(m, 1H, –CH(CH3)2), 1.03 (d, J = 6.9, 3H, –CH(CH3)2), 1.02 (d,
J = 6.9 Hz, 3H, –CH(CH3)2). ESI-MS m/z 259 (M + Na+), HR
ESI-MS found 259.1051 C12H16N2NaO3 requires 259.1053 (error =
0.98 ppm).
Synthesis of picolinamide derivative 1d. This compound was
prepared in an identical manner to 1a, except L-phenylalanine
1
methyl ester was used in place of diethylamine. Yield = 54%. H
NMR (400 MHz, CDCl3): dH = 8.56 (ddd, J = 4.8, 1.6, 0.9, 1H,
Py), 8.50 (br d, J = 8.2, 1H, –CONH), 8.17 (dt, J = 7.8, 1.0, 1H,
Py), 7.85 (dt, J = 7.7, 1.7, 1H, Py), 7.44 (ddd, J = 7.6, 4.8, 1.2,
1H, Py), 7.31–7.20 (m, overlapping, 5H, Ph), 5.08 (dt, J = 8.4, 6.1,
General details
Chemicals were purchased and used without further purification.
1H NMR spectra were recorded on a 400 MHz Bruker Avance
12382 | Dalton Trans., 2011, 40, 12381–12387
This journal is
The Royal Society of Chemistry 2011
©

1H,–CHCH2Ph), 3.74 (s, 3H, –CO2CH3), 3.28 (dd, J = 13.8, 6.0,
1H, –CH2Ph), 3.23 (dd, J = 13.8, 6.2 Hz, 1H, –CH2Ph). ESI-MS
m/z 307 (M + Na+), HR ESI-MS found 307.1047 C16H16N2NaO3
requires 307.1053 (error = 1.95 ppm).
(0.1 g, 2.00 mmol) and the reaction stirred for 5 mins, during which
time a yellow oil was produced. Extraction into DCM (3 ¥ 30 ml),
followed by drying (MgSO4) and evaporation produced the nitrile
1
derivate 3a as a light purple solid (0.16 g, 77% yield). H NMR
(400 MHz, CDCl3): dH = 7.96 (t, J = 7.9, 1H, Py), 7.90 (dd, J = 8.0,
1.3, 1H, Py), 7.75 (dd, J = 7.9, 1.3, 1H, Py), 3.58 (q, J = 7.1, 2H,
–CH2CH3), 3.40 (q, J = 7.1, 2H, –CH2CH3), 1.29 (t, J = 7.1, 6H,
–CH2CH3), 1.32 (t, J = 7.1 Hz, 6H, –CH2CH3). ESI-MS m/z 226
(M + Na+), HR ESI-MS found 226.0951 C11H13NaN3O requires
226.0951 (error = 0.06 ppm).
Synthesis of picolinamide-N-oxide derivative 2a. To a solution
of 1a (0.3 g, 1.7 mmol) in DCM (25 ml) was added mCPBA (70%,
0.89 g. 3.7 mmol) and the solution stirred at room temperature.
The reaction was monitored by TLC and upon completion (~8 h)
the reaction was carefully evaporated (Caution: N-oxides are
potentially explosive). Purification by column chromatography
(2% methanol in DCM, Al2O3) gave the N-oxide 2a as a white
Synthesis of 6-cyanopicolinamide derivative 3b. This com-
pound was prepared in an identical manner to 3a, except 2b was
1
1
solid (0.3 g, 91% yield). H NMR (400 MHz, CDCl3): dH = H
NMR (400 MHz, CD3Cl3): dH = 8.32 (d, J = 6.2, 1H, Py), 7.35–
7.28 (m overlapping, 3H, Py), 3.65 (m, 1H, –CH2CH3), 3.54 (m,
1H, –CH2CH3), 3.20 (m, 2H, –CH2CH3), 1.29 (t, J = 7.2, 3H,
–CH2CH3), 1.13 (t, J = 7.2 Hz, 3H, –CH2CH3). ESI-MS m/z 217
(M + Na+), HR ESI-MS found 217.0958 C10H14N2NaO2 requires
217.0947 (error = 4.91 ppm).
1
used instead of 2a. Yield = 76%. H NMR (400 MHz, CDCl3):
dH = 8.43 (dd, J = 8.9, 1.0, 1H, Py), 8.28 (br s, 1H, –CONH), 8.06
(t, J = 7.9, 1H, Py), 7.87 (dd, J = 7.9, 1.0, 1H, Py), 4.30 (d, J =
5.8, 2H, –NHCH2CO2), 3.82 (s, 3H, –CO2CH3). ESI-MS m/z 242
(M + Na+), HR ESI-MS found 242.0529 C10H9N3NaO3 requires
242.0536 (error = 2.80 ppm).
Synthesis of picolinamide-N-oxide derivative 2b. This com-
pound was prepared in an identical manner to 2a, except 1b was
used instead of 1a. Yield = 85%. 1H NMR (400 MHz, CDCl3): dH =
11.72 (br s, 1H, –CONH), 8.43 (dd, J = 7.8, 2.3, 1H, Py), 8.29 (dd,
J = 6.4, 1.2, 1H, Py), 7.47 (dt, J = 7.7, 1.3, 1H, Py), 7.42 (dt, J =
6.4, 2.3, 1H, Py), 4.29 (d, J = 5.6 Hz, 2H, –NHCH2CO2), 3.80 (s,
3H, –CO2CH3). ESI-MS m/z 233 (M + Na+), HR ESI-MS found
233.0538 C9H10N2NaO4 requires 233.0533 (error = 2.25 ppm).
Synthesis of 6-cyanopicolinamide derivative 3c. This com-
pound was prepared in an identical manner to 3a, except 2c was
used instead of 2a. Yield = 77%. H NMR (400 MHz, CDCl3):
dH = 8.42 (dd, J = 8.0, 1.1, 1H, Py), 8.25 (br d, J = 8.9, 1H,
–CONH), 8.05 (t, J = 7.9, 1H, Py), 7.87 (dd, J = 7.7, 1.1, 1H, Py),
4.73 (dd, J = 9.2, 5.1, 1H, –NHCH), 3.97 (s, 3H, –CO2CH3), 2.34
(m, 1H, –CH(CH3)2), 1.04 (d, J = 1.7, 3H, –CH(CH3)2), 1.03 (d,
J = 1.7 Hz, 3H, –CH(CH3)2). ESI-MS m/z 284 (M + Na+), HR
ESI-MS found 284.1017 C13H15N3NaO3 requires 284.1006 (error =
3.96 ppm).
1
Synthesis of picolinamide-N-oxide derivative 2c. This com-
pound was prepared in an identical manner to 2a, except 1c was
1
used instead of 1a. Yield = 88%. H NMR (400 MHz, CDCl3):
Synthesis of 6-cyanopicolinamide derivative 3d. This com-
pound was prepared in an identical manner to 3a, except 2d was
dH = 11.82 (br d, J = 7.9, 1H, –CONH), 8.42 (dd, J = 7.9, 2.2, 1H,
Py), 8.28 (dd, J = 6.3, 0.9, 1H, Py), 7.47 (dt, J = 7.8, 1.0, 1H, Py),
7.42 (dt, J = 6.4, 2.3, 1H, Py), 4.70 (dd, J = 8.0, 4.9, 1H, –NHCH),
3.77 (s, 3H, –CO2CH3), 2.36 (m, 1H, –CH(CH3)2), 1.05 (d, J = 6.8,
3H, –CH(CH3)2), 1.04 (d, J = 6.9 Hz, 3H, –CH(CH3)2). ESI-MS
m/z 275 (M + Na+), HR ESI-MS found 275.1008 C12H16N2NaO4
requires 275.1002 (error = 2.24 ppm).
1
used instead of 2a. Yield = 74%. H NMR (400 MHz, CDCl3):
dH = 8.38 (dd, J = 8.0, 1.1, 1H, Py), 8.22 (br d, J = 8.2, 1H,
–CONH), 8.03 (t, J = 7.9, 1H, Py), 7.84 (dd, J = 7.8, 1.1, 1H,
Py), 7.35–7.19 (m, overlapping, 5H, Ph), 5.05 (dt, J = 8.3, 5.9,
1H, –CHCH2Ph), 3.77 (s, 3H, –CO2CH3), 3.29 (dd, J = 13.9, 5.9,
1H, –CH2Ph), 3.23 (dd, J = 13.9, 5.8 Hz, 1H, –CH2Ph). ESI-MS
m/z 332 (M + Na+), HR ESI-MS found 332.0991 C17H15N3NaO3
requires 332.1006 (error = 4.35 ppm).
Synthesis of picolinamide-N-oxide derivative 2d. This com-
pound was prepared in an identical manner to 2a, except 1d was
1
used instead of 1a. Yield = 80%. H NMR (400 MHz, CDCl3):
Synthesis of picolinamide-6-thioamide derivative 4a. To a solu-
tion of the nitrile derivative3a (0.1 g, 0.49 mmol) in ethanol (20 ml),
triethylamine (1.0 g, 9.9 mmol) was added and H2S was slowly
bubbled through the solution which turned yellow after a few
minutes, the solution was then left to stand at room temperature
for 48 h during which a precipitate was produced. Filtration gave
dH = 11.75 (br d, J = 5.5, 1H, –CONH), 8.38 (dd, J = 7.9, 2.3, 1H,
Py), 8.25 (dd, J = 6.3, 1.2 1H, Py), 7.44 (dt, J = 7.6, 1.4, 1H, Py),
7.39 (dt, J = 6.3, 2.4, 1H, Py), 7.34–7.23 (m, overlapping, 5H, Ph),
5.00 (dt, J = 7.5, 5.5, 1H,–CHCH2Ph), 3.74 (s, 3H, –CO2CH3),
3.28 (dd, J = 13.9, 5.5, 1H, –CH2Ph), 3.19 (dd, J = 13.9, 7.6 Hz,
1H, –CH2Ph). ESI-MS m/z 323 (M + Na+), HR ESI-MS found
323.1013 C16H16N2NaO4 requires 323.1002 (error = 3.32 ppm).
1
the thioamide 4a as a light yellow powder (0.9 g, 78% yield). H
NMR (400 MHz, CDCl3): dH = 9.31 (br s, 1H, –NH2), 8.76 (dd, J =
7.8, 1.0, 1H, Py), 7.96 (t, J = 7.8, 1H, Py), 7.71 (dd, J = 7.8, 1.0, 1H,
Py), 7.67 (br s, 1H, –NH2), 3.60 (q, J = 7.1, 2H, –CH2CH3), 3.30
(q, J = 7.1, 2H, –CH2CH3), 1.30 (t, J = 7.1, 3H, –CH2CH3), 1.18
(t, J = 7.1 Hz, 3H, –CH2CH3). ESI-MS m/z 260.1 (M + Na+),
HR ESI-MS found 260.0820 C11H15N3NaOS requires 260.0828
(error = 2.92 ppm).
Synthesis of 6-cyanopicolinamide derivative 3a. To a 50 ml
round bottom flask containing 2a (0.2 g, 1.00 mmol) was added
dimethyl sulfate (3 ml) and the reaction was placed under nitrogen
and heated at 60 ◦C for 24 h with stirring. The reaction was allowed
to cool to room temperature then ether (25 ml) was added and left
to stir for 1 h. The reaction was allowed to settle for 12 h. The
ether was decanted off and the remaining oil was washed with
ether and decanted again and any remaining solvent removed by
rotary evaporation. Distilled water was added (10 ml) and the
solution neutralised with NaHCO3, to this was then added NaCN
Synthesis of picolinamide-6-thioamide derivative 4b. This com-
pound was prepared in an identical manner to 4a, except 3b was
used instead of 3a. Yield = 92%. 1H NMR (400 MHz, CDCl3): dH =
9.08 (br s, 1H, –NH2), 8.89 (dd, J = 7.9, 1.0, 1H, Py), 8.39 (dd,
This journal is
The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 12381–12387 | 12383
©

J = 7.9, 1.0, 1H, Py), 8.12 (br s, 1H, –CONH), 8.04 (t, J = 7.9, 1H,
Py), 7.71 (brs, 1H, –NH2), 4.31 (d, J = 5.4 Hz, 2H, –NHCH2CO2),
3.84 (s, 3H, –CO2CH3). ESI-MS m/z 253 (M + H+), HR ESI-
MS found 253.0510 C10H11N3O3S requires 253.0516 (error = 2.37
ppm).
–CH(CH3)2), 1.09 (d, J = 1.5 Hz, 6H, –CH(CH3)2). ESI-MS m/z
735 (M + Na+), HR ESI-MS found 735.2027 C36H36N6NaO6S2
requires 735.2030 (error = 0.39 ppm).
Synthesis of L4. This compound was prepared in an identical
manner to L1, except 4d was used instead of 4a. Yield = 67%. 1H
NMR (400 MHz, CDCl3): dH = 8.62 (t, J = 1.6, 1H, Ph), 8.53
(dd, J = 7.8, 1.0, 2H, Py), 8.47 (br d, J = 8.0, 2H, –CONH),
8.23 (dd, J = 7.8, 1.0, 2H, Py), 8.05 (t, J = 7.8, 2H, Py), 8.04
(dd, J = 7.7, 1.6, 2H, Ph), 7.78 (s, 2H, tz), 7.59 (t, J = 7.7, 1H,
Ph), 7.38–7.29 (m, overlapping, 10H, Ph), 5.09 (dt, J = 8.0, 5.9,
2H, –CHCH2Ph), 3.80 (s, 6H, –CO2CH3), 3.32 (d, J = 5.9 Hz,
4H, –CH2Ph). ESI-MS m/z 831 (M + Na+), HR ESI-MS found
831.2029 C44H36N6NaO6S2 requires 831.2030 (error = 0.10 ppm).
Synthesis of [Zn5(L1)5](CF3SO3)10. To a suspension of L1 (0.05
g, 0.08 mmol) in MeCN (1 ml) was added Zn(CF3SO3)2 (0.03 g,
0.08 mmol) and the suspension sonicated until all the ligand had
dissolved. Ethyl acetate was then slowly allowed to diffuse into the
solution giving colourless crystals, which were filtered and dried
under vacuum (0.04 g, 50%). NMR and mass spectroscopy data
are discussed in the text. Found: C, 42.9; H, 3.7; N, 12.2%. Calcu-
lated for C170H160N30F30O40S20Zn5: C, 42.5; H, 3.4; N, 11.9%. All
the other circular helicates using ligands L2–L4 were synthesised in
an identical manner. [Zn5(L2)5](CF3SO3)10 (yield = 45%) Found: C,
39.3; H, 2.7; N, 11.9%. Calculated for C160H120N30O60S20F30Zn5: C,
38.7; H, 2.4; N, 11.5%. [Zn5(L3)5](CF3SO3)10 (yield = 50%) Found:
C, 42.6; H, 3.8; N, 7.4%. Calculated for C190H180N30O60S20F30Zn5:
C, 42.4; H, 3.4; N, 7.8%. [Zn5(L4)5](CF3SO3)10 (yield = 55%) Found:
C, 47.5; H, 3.2; N, 10.1%. Calculated for C230H180N30O60S20F30Zn5:
C, 47.1; H, 3.1; N, 9.7%.
Synthesis of picolinamide-6-thioamide derivative 4c. This com-
pound was prepared in an identical manner to 4a, except 3c was
used instead of 3a. Yield = 60%.1H NMR (400 MHz, CDCl3): dH
=
9.06 (br s, 1H, –NH2), 8.88 (dd, J = 7.9, 1.1, 1H, Py), 8.38 (dd,
J = 7.8, 1.1, 1H, Py), 8.16 (br d, J = 8.8, 1H, –CONH), 8.04 (t,
J = 7.8, 1H, Py), 7.76 (br s, 1H, –NH2), 4.77 (dd, J = 8.8, 5.0,
1H, –NHCH), 3.81 (s, 3H, –CO2CH3), 2.34 (m, 1H, –CH(CH3)2),
1.03 (d, J = 7.0 Hz, 3H, –CH(CH3)2), 1.02 (d, J = 7.0 Hz, 3H,
–CH(CH3)2). ESI-MS m/z 318 (M + Na+), HR ESI-MS found
318.0893 C13H17N3NaO3S requires 318.0883 (error = 3.21 ppm).
Synthesis of picolinamide-6-thioamide derivative 4d. This com-
pound was prepared in an identical manner to 4a, except 3d was
used instead of 3a. Yield = 87%. 1H NMR (400 MHz, CDCl3): dH =
8.86 (dd, J = 7.8, 1.1, 1H, Py), 8.75 (br s, 1H, –NH2), 8.36 (dd,
J = 7.8, 1.1, 1H, Py), 8.03 (t, J = 7.8, 1H, Py), 7.99 (br d, J = 8.2,
1H, –CONH), 7.53 (br s, 1H, –NH2), 7.26–7.10 (m, overlapping,
5H, Ph), 5.10 (dt, J = 8.1, 5.2, 1H, –CHCH2Ph), 3.80 (s, 3H, –
CO2CH3), 3.34 (dd, J = 13.8, 5.2, 1H, –CH2Ph), 3.27 (dd, J = 13.8,
5.2 Hz, 1H, –CH2Ph). ESI-MS m/z 366 (M + Na+), HR ESI-MS
found 366.0870 C17H17N3NaO3S requires 366.0883 (error = 3.41
ppm).
Synthesis of L1. To a solution of 1,3-(a-dibromoacetyl) ben-
zene (0.05 g, 0.16 mmol) in ethanol (25 ml) was added the
thioamide 4a (0.08 g, 0.34 mmol) and the reaction refluxed for
3 h. On cooling a white precipitate formed, which was isolated by
filtration, followed by washing with EtOH (2 ¥ 2 ml) and Et2O
Results and discussion
(2 ¥ 2 ml). (0.064 g, 67% yield). 1H NMR (400 MHz, CDCl3): dH
=
Ligand synthesis
8.60 (t, J = 1.6, 1H, Ph), 8.42 (dd, J = 7.8, 1.0, 2H, Py), 8.02 (dd,
J = 7.7, 1.6, 2H, Ph), 7.95 (t, J = 7.8, 2H, Py), 7.75 (dd, J = 7.8, 1.0,
2H, Py), 7.74 (s, 2H, tz), 7.58 (t, J = 7.7, 1H, Ph), 3.63 (q, J = 7.1,
4H, –CH2CH3), 3.51 (q, J = 7.0, 4H, –CH2CH3), 1.38 (t, J = 7.0,
6H, –CH2CH3), 1.32 (t, J = 7.0 Hz, 6H, –CH2CH3). ESI-MS m/z
619 (M + Na+), HR ESI-MS found 619.1932 C32H32N6NaO2S2
requires 619.1920 (error = 1.88 ppm).
Ligands L1–L4 were all synthesised in an analogous fashion as out-
lined in Scheme 1. Activation of picolinic acid with oxalyl chloride
and reaction with either diethylamine or an amino acid ester gave
the amides 1a–d and reaction with mCPBA gave the corresponding
N-oxides 2a–d. Methylation with dimethyl sulphate and reaction
with sodium cyanide gave the 6-cyanopicolinamide species 3a–d.
Reaction with hydrogen sulphide then gave the thioamides 4a–d
which after reaction with 1,3-di(a-bromoacetyl)benzene gave the
potentially hexadentate ligands L1–L4. In all cases the ligands and
their precursors were characterized by 1H NMR, ESI-MS and HR
ESI-MS.
Synthesis of L2. This compound was prepared in an identical
manner to L1, except 4b was used instead of 4a. Yield = 66%.1H
NMR (400 MHz, CDCl3): dH = 8.62 (t, J = 1.6, 1H, Ph), 8.55 (dd,
J = 7.7, 1.0, 2H, Py), 8.51 (br t, J = 5.4, 2H, –CONH), 8.26 (dd, J =
7.7, 1.0, 2H, Py), 8.05 (m, overlapping, 4H, Py/Ph), 7.79 (s, 2H, tz),
7.59 (t, J = 7.8, 1H, Ph), 4.36 (d, J = 5.4 Hz, 4H, –CH2–), 3.86 (s,
6H, –CO2CH3). ESI-MS m/z 629 (M + H+), HR ESI-MS found
629.1282 C30H25N6O6S2 requires 629.1272 (error = 1.74 ppm).
Coordination chemistry
Reaction of L1 with Zn(CF3SO3)2 in MeCN gave a colourless
solution from which were deposited colourless crystals upon
slow diffusion of ethyl acetate. Analysis by ESI-MS gave an
Synthesis of L3. This compound was prepared in an identical
manner to L1, except 4c was used instead of 4a and the resulting
ligand purified by column chromatography (Al2O3 1% MeOH in
DCM). Yield = 42%. 1H NMR (400 MHz, CDCl3): dH = 8.63 (t,
J = 1.0, 1H, Ph), 8.59 (br d, J = 8.9, 2H, –CONH), 8.54 (dd, J =
7.8, 1.0, 2H, Ph), 8.24 (dd, J = 7.6, 1.0, 2H, Py), 8.05 (t, J = 7.6,
2H, Py), 8.04 (dd, J = 7.6, 1.0, 2H, Py), 7.78 (s, 2H, tz), 7.60 (t,
J = 7.8, 1H, Ph), 4.78 (dd, J = 8.9, 4.7, 2H, –NHCH), 3.83 (s,
6H, –CO2CH3), 2.41 (m, 2H, –CH(CH3)2), 1.11 (d, J = 1.6, 6H,
2+
ion at m/z 2251 corresponding to {[Zn5(L1)5](CF3SO3)8} , also
present were ions at m/z 2731 and 1771 corresponding to
+
2+
{[Zn3(L1)3](CF3SO3)5} and {[Zn4(L1)4](CF3SO3)6} respectively.
Peaks corresponding to smaller di-/mononuclear species were
also present but these are likely due to fragmentation of the
parent pentanuclear species, as has been reported previously.13
Conformation of the formation of the [Zn5(L1)5]10+ pentanuclear
species was obtained by X-ray analysis (Fig. 2). In the solid state
12384 | Dalton Trans., 2011, 40, 12381–12387
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Scheme 1 Synthesis of ligands L1–L4. Reagents and conditions a)
C2O2Cl2, Et3N, DCM 0 ◦C; b) RR¢NH, Et3N, DCM, RT; c) mCPBA,
DCM, RT; d) (MeO)2SO2, 60 ◦C; e) NaHCO3, NaCN, H2O RT; f) H2S,
Et3N, EtOH, RT; g) 3-di(a-bromoacetyl)benzene, EtOH, reflux.
the ligand partitions into two tridentate donor units separated
by the 1,3-phenylene unit. All five Zn2+ ions are six-coordinate,
arising from the coordination of two tridentate N,N,O-donor
˚
˚
units (Zn–N: 2.028(7)–2.262(7) A; Zn–O 2.105(6)–2.203(6) A).
The 1,3-phenylene spacers bridge each of the tridentate domains in
an “over-and-under” conformation, giving rise to a helical cyclic
oligomer as opposed to a “face-to-face” array associated with
more grid-like architectures.
The one-dimensional 1H NMR spectrum of a CD3NO2 solution
of [Zn5(L1)5](CF3SO3)10 shows the expected 9 resonances for
a complex of D5 symmetry (Fig. 3a). Of the seven aromatic
signals, four corresponding to the pyridyl and thiazole protons
are present between 7.0 and 8.4 ppm. The three protons on
the bridging phenylene unit, however, resonate at much lower
frequency (7.0–5.8 ppm). This has been observed previously in
related circular helicates and it is attributed to the close proximity
of the central phenylene rings to the pyridyl-thiazole domains
˚
(average centroid ◊ ◊ ◊ centroid distance of 3.87 A). The phenylene
Fig. 2 (a) X-ray crystal structure of the complex cation [Zn5(L1)5]10+
Ellipsoids are shown at a 30% probability level. (b) Space-filling picture of
[Zn5(L1)5]10+ showing atoms with their van der Waals radii.
.
protons in [Zn5(L1)5]10+ are thus exposed to the shielding ring
currents produced by the aromatic heterocycles on adjacent ligand
strands, hence the unusually low chemical shifts. Indeed, this
phenomenon is a useful diagnostic tool for the confirmation of
helical wrapping in both linear and circular helicates.
which are between 7.0–6.0 ppm, confirming the formation of
a helical structure. Indeed, the spectrum is remarkably similar
to [Zn5(L1)5](CF3SO3)10 and this, coupled with the ESI-MS
results, indicates that the glycine derivative forms an analogous
pentanuclear species [Zn5(L2)5](CF3SO3)10. The presence of the
broad triplet at 9.4 ppm corresponding to the amide –NH suggests
that the ligand has not deprotonated, as is sometimes observed
with coordination of primary amides to metal ions.
Ligands L3 and L4 feature the same ligand scaffold of
L1, but the terminal amide groups have been functionalized
with enantiopure valine and phenylalanine units, respectively.
Reaction with Zn(CF3SO3)2 in MeCN gives, in each case, a
Having established that the L1 ligand system gives rise to
circular helicates, we decided to incorporate peripheral amino
acid esters in attempt to control the enantio-selectivity of the
chiral helicate assembly. Reaction of the glycine-containing ligand
L2 with Zn(CF3SO3)2 in CD3NO2 gave a colourless solution for
which the ESI-MS showed a signal at m/z 2330 corresponding
to {[Zn5(L1)5](CF3SO3)8} . The 1H NMR spectrum showed a
2+
total of seven aromatic signals, two aliphatic signals and a signal
corresponding to the amide –NH (Fig. 3b). Again, the most
informative signals are those due to the central phenylene spacer,
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Fig. 3 Aromatic region of the 1H-NMR spectra of a) [Zn5(L1)5]10+
(CD3NO2), b) Zn5(L2)5]10+(CD3NO2), c) Zn5(L3)5]10+(CD3NO2), and d)
Zn5(L4)5]10+ (CD3CN):
= selected peaks corresponding to the minor
᭺
diastereoisomer.
colourless solution for which ESI-MS shows peaks for the
usual adducts of the corresponding pentanuclear complex cations
Fig. 4 The CD spectra of (a) ligands L3 (red) and L5 (blue) and (b) the
resulting complexes on the addition of one equivalent of Zn2+ in acetonitrile
at 298 K at a concentration of 2.5 ¥ 10-5 mol dm-3.
2+
(e.g. m/z 2541 for {[Zn5(L3)5](CF3SO3)8} and m/z 2781 for
2+
{[Zn5(L4)5](CF3SO3)8} ). The main features in the 1H NMR
spectra (Fig. 3c,d) are likewise consistent with the formation of
pentanuclear circular helicates, with the characteristic phenylene
protons appearing at significantly lower frequency than the other
aromatic protons. In both cases, however, a subset of low-intensity
peaks is also observed. It is unlikely that these signals correspond
to different nuclearity species, e.g. [M6L6}12+ or [M4L4]8+, as signals
for these generally appear at substantially different frequencies
(Dd > 0.2 ppm). They can therefore be assigned with confidence
to the corresponding minor diastereoisomers.15 Integration of
the two sets of peaks for [Zn5(L3)5]10+ suggests that the two
diastereoisomers are present in a ca. 9 : 1 ratio. This demonstrates
that the optically pure unit controls the self-assembly process and
that one isomer is formed in ca. 80% d.e. For [Zn5(L4)5]10+ the
process is less selective with d.e. of ~ 70%.
with a dihedral angle between the two chromophores of 70.8◦,
and the two chromophores at an angle of 59.8◦ relative to
the perpendicular between them, then the resulting dominant
complex can tentatively be assigned as having a D metal centred
configuration, and an overall M helicity as shown in Fig. 2b.
However extreme caution should be placed on this assignment
given that the metal centred exciton couplings will invariably be
cancelled out by additional couplings in the structure as previously
reported by Telfer and co-workers.18 In this particular case, it
is observed in the structural analysis of [Zn5L1 ]10+ that inter-
5
ligand phenyl-thiazole contacts possess the opposite sense of
˚
handedness with a separation of only 4.0 to 5.0 A, whilst the
˚
metal centred chromophores are longer (4.5–5.5 A). Given that
the strength of the observed exciton coupling being related by an
inverse r3 relationship these interactions can not be ignored,16 with
the possibility that these conflicting bis-ignate interactions could
account for the surprisingly low observed Cotton effect, and could
even lead to the mis-assignment of the overall helicity.
The CD spectra of ligands L3 and the opposite diasteroisomer
derived from D-valine L5 (Fig. 4a)16 shows a very weak, equal and
opposite bi-signate Cotton effect relating to the higher energy p–p*
transitions. These probably arise from a degree of exciton coupling
between the two halves of the ligand. On the introduction of Zn2+
to the solution, there is a considerable change to the observed
CD spectrum (Fig. 4b), with the growth of a second signal around
355 nm, although the intensity of the signals does not dramatically
increase, as had initially been anticipated. Similarly, the UV/vis
absorption spectrum also shows a considerable change with the
large absorption at 264 nm reducing in intensity and significantly
broadening. This is an indication of a strong exciton coupling
Conclusion
We have shown that a ligand which contains both N-donor and
O-donor domains and a 1,3-phenylene spacer unit forms pentanu-
clear circular helicates upon reaction with Zn2+ ions and this struc-
ture persists in both the solid and solution state. The formation
of this high nuclearity species is governed by unfavourable steric
interactions between the phenyl units which destabilize the similar
linear helicate. Incorporation of enantiopure units within the
ligand strand controls the diastereoselectivity with up to 80% d.e.
assuming the complex is adopting a similar configuration to that
16
demonstrated in the solid-state structure of [Zn5(L1)5]10+
.
In principle it should be possible to tentatively assign an
overall sense of handedness to the dominant isomer using an
exciton theoretical analysis.17 The 330 nm absorption is assumed
to relate to the p–p* transitions of the pyridyl-thiazole group.
The complex derived from L3 demonstrates a negative signal at
the lowest energy transitions in the CD spectrum in this region.
Assuming a similar structure is adopted to that of ligand L1,
Notes and references
1 J.-M. Lehn, Supramolecular Chemistry, VCH, Weinheim, 1995J. W.
Steed, J. L. Atwood, Supramolecular Chemistry, John Wiley and Sons,
Chichester, 2000.
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6 For examples of metallo-helicates see: S. P. Argent, H. Adams, L. P.
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15 We have found that the chemical shift of the central phenylene unit is
very susceptible to a change in the nuclearity of the circular helicate and
lower nuclearity species (e.g. [M4L4]8+ compared with [M5L5]10+) tend
to have a higher chemical shift compared to the pentanuclear species;
the difference in chemical shift is also quite pronounced (>0.3 ppm),
C.R. Rice, unpublished results.
16 The (R,R)-enantiomer of L3 (giving L5) was prepared in an identical
manner to the (S,S)-enantiomer of L3 apart from D-valine was used in
the initial synthetic procedure. To all intents and purposes the NMR,
ESI-MS data and yields of L5 were identical to that of L3.
17 M. Ziegler and A. von Zelewsky, Coord. Chem. Rev., 1998, 177, 257–
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©