Synthesis, characterization and coordination chemistry of dibenzofuran derivatives of 1,4,7,10-tetraazacyclododecane

Article abstract of DOI:10.1016/j.ica.2010.04.039

A 1,4-disubstituted dibenzofuran derivative of 1,4,7,10- tetraazacyclododecane (cyclen), L1, has been prepared by the direct reaction of cyclen and chloroacetyldibenzofuran and the mono-substituted derivative, L2, by reaction of chloroacetyldibenzofuran and 1,4,7-tris(t-butoxycarbonyl)-1,4,7,10- tetraazacyclododecane followed by deprotection with trifluoroacetic acid. The ligands were characterized by ¹H and ¹³C NMR spectroscopy, IR spectroscopy and mass spectrometry. The reaction of the 1,4-disubstituted dibenzofuran cyclen, L1, with Cu(ClO₄)₂·6H ₂O in methanol yielded crystals of [CuL1](ClO₄) ₂·MeOH·1/2H₂O that were suitable for single crystal structural analysis. The X-ray structure confirmed that the 1,4-disubstituted dibenzofuran cyclen had been formed. The copper(II) coordination sphere in the complex cation, [CuL1]²⁺, is occupied by four nitrogen atoms from the macrocycle and an amide oxygen donor from one dibenzofuran pendant group. As is typical for copper(II)-cyclen complexes, the Cu(II) centre sits above the plane of the macrocycle nitrogen towards the oxygen donor, in this case by 0.5 . Fluorescence emission studies indicate that coordination of the macrocycle to either copper(II) or zinc(II) results in a decrease in emission with respect to the emission of the pure ligand.

Full text of DOI:10.1016/j.ica.2010.04.039

Inorganica Chimica Acta 363 (2010) 2896–2904
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis, characterization and coordination chemistry of dibenzofuran
derivatives of 1,4,7,10-tetraazacyclododecane
a,b
a
a
b
a,*
T.K. Venkatachalam , Jose Barreto , Ute Kreher , David C. Reutens , Leone Spiccia
a
School of Chemistry, Monash University, Clayton, Victoria 3800, Australia
Centre for Advanced Imaging, The University of Queensland, St. Lucia, QLD 4072, Australia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A 1,4-disubstituted dibenzofuran derivative of 1,4,7,10-tetraazacyclododecane (cyclen), L1, has been pre-
pared by the direct reaction of cyclen and chloroacetyldibenzofuran and the mono-substituted derivative,
L2, by reaction of chloroacetyldibenzofuran and 1,4,7-tris(t-butoxycarbonyl)-1,4,7,10-tetraazacyclodode-
Received 5 February 2010
Received in revised form 22 April 2010
Accepted 25 April 2010
cane followed by deprotection with trifluoroacetic acid. The ligands were characterized by 1H and 13
C
Available online 11 May 2010
NMR spectroscopy, IR spectroscopy and mass spectrometry. The reaction of the 1,4-disubstituted diben-
zofuran cyclen, L1, with Cu(ClO O in methanol yielded crystals of [CuL1](ClO O that
4
)
2
ꢀ6H
2
4
)
2
ꢀMeOHꢀ1/2H
2
Dedicated to Animesh Chakravorty
were suitable for single crystal structural analysis. The X-ray structure confirmed that the 1,4-disubsti-
tuted dibenzofuran cyclen had been formed. The copper(II) coordination sphere in the complex cation,
CuL1] , is occupied by four nitrogen atoms from the macrocycle and an amide oxygen donor from
Keywords:
Macrocyclic ligands
Dibenzofuran derivatives
2
+
[
one dibenzofuran pendant group. As is typical for copper(II)–cyclen complexes, the Cu(II) centre sits
above the plane of the macrocycle nitrogen towards the oxygen donor, in this case by 0.5 Å. Fluorescence
emission studies indicate that coordination of the macrocycle to either copper(II) or zinc(II) results in a
decrease in emission with respect to the emission of the pure ligand.
1
,4,7,10-Tetraazacyclododecane
Coordination chemistry
Copper(II) complexes
X-ray structure
Ó 2010 Elsevier B.V. All rights reserved.
1
. Introduction
The ability of macrocycles to chelate strongly to particular
this case, cyclen was protected at three nitrogens using tert-
butoxycarbonyl groups and alkylation was then performed to
obtain exclusively the mono-alkylated product. Won and co-
workers [12] have also reported a number of mono-alkylated
cyclen compounds.
metal ions makes them attractive compounds for a plethora of
applications, including various biomedical applications. Biological
sensors, fluorescent sensors and neuroimaging agents have
emerged that utilise these macrocycles as metal binding agents
For our own part, we have been interested in cyclen derivatives
with appended redox and/or photoactive functionalities that can
be applied in the sensing of various biologically important mole-
cules, protein purification and RNA cleavage. Cyclen derivatives
have been developed which utilise changes in the fluorescent or
electrochemical response of appended pyrene or ferrocene units,
respectively, to sense thymine and derivatives of thymine that in-
[
1–5]. Many of these applications rely on the selective function-
alization of the macrocycle at specific positions within the
macrocyclic ring. The literature on this aspect is quite expansive
[
6–9] but the controlled modification of these ligands, as re-
quired for a particular application, still presents some challenges.
In the case of cyclen (1,4,7,10-tetraazacyclododecane), Massue
et al. [10] reported that mono-N-alkylation can be achieved using
an excess of the macrocycle in the reaction medium. Skwierawska
provided an alternative route for making both the mono- and
di-N-alkylated derivative of cyclen related compounds [11]. In
0
clude thymidine, thymidine polyphosphates and thymidilyl(3 –
0
5 )thymidine (TpT) [13–15]. Additionally the copper(II) complex
of a mono-ferrocenyl-cyclen derivative was found to exhibit an
uncommon binding mode for nitrate which led to interesting elec-
trochemical behaviour [16].
As part of the ongoing investigations into the coordination
chemistry and sensing application of N-functionalised derivatives
of cyclen, we report the synthesis and characterization of two
new cyclen derivatives incorporating either one or two photo-
active dibenzofuran pendant groups, L2 and L1 as shown below,
together with initial investigations of their copper(II) and zinc(II)
coordination chemistry.
*
Corresponding author. Fax: +61 3 9905 4526.
E-mail address: leone.spiccia@sci.monash.edu.au (L. Spiccia).
0
020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.04.039

T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
2897
MeO
N
ing a Pt counter electrode, an Ag/AgNO
AgNO
(GC) working electrode. Standard potentials were referenced to the
3
(acetonitrile, 10 mM
) reference electrode and a 3.06 mm diameter glassy-carbon
OMe
N
3
O
O
N
N
N
N
H
O
H
O
0/+
4 6
usual Fc couple in the presence of Bu NPF (0.1 M) as the sup-
porting electrolyte. These potential values are assumed to be inde-
pendent of the electrolyte and scan rate. Measurements were
H
H
ꢁ1
recorded over a scan-rate range of 0 to ꢁ1200 mV s at 20 °C in-
side a Faraday cage under a N atmosphere to minimize electro-
/H O interference, respectively.
L1
2
chemical noise and atmospheric O
2
2
OMe
N
H
H
2.4. Synthesis
O
N
N
H
O
2.4.1. Chloroacetylaminodibenzofuran
N
N
H
In a 250 mL round bottomed flask was placed 3-amino-2-meth-
oxydibenzofuran (4.26 g, 20 mmol) and 80 mL of anhydrous meth-
ylene chloride. The mixture was stirred at room temperature for
L2
3
0 min but the compound did not dissolve completely in this med-
ium. Using a dry syringe, 2 mL of freshly distilled triethylamine
was introduced into the flask and the contents were stirred for
additional 20 min resulting in a clear homogenous solution. Using
another dry syringe, chloroacetyl chloride (2.60 mL, 3.64 g,
2
. Experimental
2.1. Materials and methods
3
0 mmol) was added in aliquots where upon a vigorous exother-
mic reaction took place. After addition of this reagent was com-
plete, the mixture was allowed to stir at room temperature for
All chemicals were purchased from Sigma–Aldrich and used
without further purification. Unless otherwise stated, each reaction
was conducted under a nitrogen atmosphere. Column chromatog-
raphy was performed using silica gel (60 mesh) from Merck. The
solvent used for elution varied depending on the compound of
interest as detailed in Section 2.4 below. The synthesis of
2
days. The insoluble precipitate that formed in the reaction mix-
ture was filtered and dried. The filtrate was treated with 5 M
hydrochloric acid (2 ꢂ 20 mL), the organic layer separated from
the aqueous layer and subsequently washed with water
(
2 ꢂ 20 mL). The organic layer was dried over anhydrous sodium
1
,4,7-tris(t-butoxycarbonyl)-1,4,7,10-tetraazacyclododecane was
achieved following the method reported by Brandes et al. [17].
sulfate, filtered and the solvent removed in vacuo to yield a residue
which was triturated with ether. The insoluble material was fil-
tered under vacuum to furnish the required chloroacetyl derivative
of aminomethoxydibenzofuran. The combined precipitates were
dried in vacuum to obtain a light yellow solid. Yield: 4.90 g, 84%.
2
.2. Spectroscopic studies
1H and 13C NMR spectra were recorded on either 200, 300 or
ꢁ1
IR spectrum (cm ): 3369w, 3075w, 2937w, 2840w, 1662vs,
4
00 MHz (Bruker or Varian) spectrometers using either CDCl
3
or
1
1
8
4
610s, 1532vs, 1434vs, 1412s, 1400s, 1304s, 1281s, 1240s, 1217s,
d
6
-DMSO as solvent. Chemical shifts are reported as d values in
194s, 1167s, 1032s, 1014s, 986s, 961m, 931m, 918m, 878s,
parts per million (ppm). Splitting patterns were designated as fol-
lows: s = singlet, t = triplet, m = multiplet, br = broad. Fourier trans-
form infrared (FT-IR) spectra were recorded using KBr pellets on a
1
68s, 846m, 804m, 772s, 760s, 669s, 625m. H NMR (d6-DMSO,
00 MHz); d (ppm): 9.67 (s, 1H), 8.40 (s, 1H), 8.06–8.04 (d, 1H,
J = 8.0 Hz); 7.81–7.80 (d, 1H, J = 4.0 Hz), 7.63–7.61 (d, 1H,
ꢁ1
Perkin–Elmer 1600 FTIR spectrometer at a resolution of 4 cm
.
J = 8.0 Hz), 7.45–7.41 (m, 1H), 7.36–7.32 (m, 1H), 4.45 (s, 2H),
Mass spectra were obtained using a Micromass Platform II quadru-
pole mass spectrometer fitted with an electrospray source. Micro-
analyses were performed by the Campbell Microanalytical Service,
University of Otago, New Zealand. Electronic spectra were recorded
on a Cary 5G UV–Vis-NIR spectrophotometer in 1 cm quartz cells.
Fluorescence spectra were recorded on a Varian Cary Eclipse fluo-
rescence spectrophotometer using glass cuvettes supplied by the
manufacturer. The wavelength of excitation was set at 300 nm
and the fluorescence emission was measured in the 310–550 nm
region. The excitation and emission slit width were set to 5 and
13
3
1
1
6
.96 (s, 3H). C NMR (d -DMSO) d (ppm): 165.8, 156.8, 150.2,
46.9, 127.6, 127.5, 124.8, 123.6, 121.4, 119.7, 112.3, 104.6,
03.6, 57.4, 44.3. ESI MS (+ mode): 292 (M+1).
2.4.2. 1,4-Dibenzofuran substituted cyclen (L1)
The chloroacetyl derivative (0.72 g, 2.50 mmol) was placed in a
1
00 mL round bottomed flask, chloroform (40 mL) was added and
the contents stirred at room temperature for 20 min to dissolve
the material. Using a dry syringe, 0.5 mL of triethylamine was intro-
duced to the flask and the contents were stirred for a further 20 min.
A solution of cyclen (0.43 g, 2.50 mmol) dissolved in chloroform
1
0 mm, respectively. The fluorescence and the UV–Vis spectra
were measured at room temperature using acetonitrile as solvent.
Copper(II) and zinc(II) perchlorate salts were used the metal ion re-
agent. The titration was performed by adding known volumes of a
(
10 mL) was added and the solution refluxed for 5 days. After this
period, the solvent was removed under vacuum and the residue
was re-dissolved in 150 mL of chloroform and washed with
1
0
l
M solution of the metal salt in acetonitrile to 1 mL of a 10
solution of the ligand in acetonitrile. The total volume was kept as
mL by the addition of acetonitrile, as required. The final ligand
concentration was 3.33 M and metal concentration in the range
lM
2
ꢂ 50 mL of water. The organic layer was separated from the aque-
ous layer and dried over anhydrous sodium sulfate. Filtration and
rotary evaporation yielded a colourless foam (0.52 g). This crude
material was purified by column chromatography on silica gel using
a mixture of chloroform:methanol:methanolic ammonia (12:4:1)
as eluent. L1 was obtained as a colourless solid. Yield: 0.22 g, 26%.
3
l
0
–6.67
lM.
ꢁ1
2
.3. Electrochemical studies
IR spectrum (cm ): 3338m, 2929m, 2831m, 1685s, 1636w,
1
603m, 1517vs, 1468s, 1424s, 1348w, 1304w, 1280w, 1196s,
All voltammetric measurements were performed with a BAS
Epsilon potentiostat operated by BASi Epsilon-EC Software, version
.50.69_XP. A typical three-electrode cell was employed, compris-
1165s, 1132w, 1103w, 1062w, 1028m, 986w, 935w, 868m,
1
3
807m, 748s. H NMR (200 MHz)(CDCl ): d (ppm): 8.71 (bs, 2H),
1
8.27 (s, 2H), 7.49–7.46 (d, 2H, J = 6.0 Hz), 7.38–7.26 (m, 4H),

2
898
T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
7
.23–7.01 (t, 2H), 6.99 (s, 2H), 3.89 (s, 6H), 3.45 (s, 4H), 3.1–2.93
Table 1
Crystallographic data for C1.
13
(
m, 16H). C NMR (400 MHz) (CDCl
3
) d ppm: 169.3, 156.4, 150.2,
45.1, 126.4, 126.0, 124.1, 119.7, 118.8, 111.2, 104.0, 100.9, 59.8,
6.2, 55.2, 52.8, 46.6, 46.5, 45.8. ESI MS (+ mode): 679 (M+1).
1
5
Chemical formula
M (g mol
Crystal system
Space group
a (Å)
2 6 15.50
C39H46Cl CuN O
981.26
Monoclinic
C2/c
ꢁ
1
)
2.4.3. Mono-dibenzofuran substituted cyclen (L2)
38.125(8)
15.616(3)
15.280(3)
90
110.98(3)
90
8494(3)
8
1.535 Mg m
Chloroacetyldibenzofuran (1.16 g, 4.00 mmol) was placed in a
b (Å)
round bottomed flask, acetonitrile (40 mL) was added and the con-
tents were stirred to form a homogenous solution. Potassium io-
dide (0.60 g) was then added followed by anhydrous potassium
carbonate (3.00 g) and the mixture was stirred at room tempera-
c (Å)
a
(°)
b (°)
(°)
c
3
Volume (Å )
ture for 10 min prior to the addition of (t-boc)
3
cyclen (1.70 g,
Z
D
(g m 3
ꢁ
)
ꢁ3
3
.50 mmol) dissolved in acetonitrile (20 mL). The mixture was re-
c
h range (°)
1.42°–25.00°
fluxed for 4 days after which it was filtered to remove any insolu-
ble salts. The solvent was removed on a rotary evaporator to yield a
residue which was dissolved in methylene chloride (100 mL) and
washed in a separatory funnel with 3 M sodium hydroxide
Data collection method
Absorption corrections
Reflections collected
Unique reflections (Rint
Goodness-of-fit (GOF) on F
F(0 0 0)
Phi and omega scans
Multi-scan (SORTAV [18,19])
47 386
7476(0.1463)
1.008
4072
0.1463
0.0705, 0.1488
ꢁ0.395, 0.906
)
2
(
3 ꢂ 10 mL). The organic layer was separated from the aqueous
phase and dried over anhydrous sodium sulfate. Filtration and
evaporation of the solvent left a residue which was purified by col-
umn chromatography, using a 5% methanol in chloroform as elu-
R
R
int
a, wR b
1
2
[I > 2
r
(I)]
Largest difference peak and hole (e Åꢁ3)
3
ent. The (t-boc) cyclen dibenzofuran derivative was obtained as a
white solid (1.39 g) and was used directly in the next step.
a
R
1
=
R
||F
o
| ꢁ |F
c o
||/R|F |.
b
2
o
2
c
2
wðF Þ ꢃ1=2.
2
o
2
wR
2
¼ ½R
wðF ꢁ F Þ =
R
The white solid was placed in a 100 mL round bottomed flask
and methylene chloride (4 mL) was added followed by trifluoro-
acetic acid (1 mL) and the contents stirred for 24 h at room temper-
ature. The solvent was then removed to yield a dark coloured
residue which was dissolved in minimum quantity of distilled
water (1.5 mL). The pH of the solution was adjusted to 14 by add-
ing carefully sodium hydroxide pellets (five pellets, approximate
weight 0.2 g) and the resultant viscous oily mixture was extracted
with chloroform (3 ꢂ 20 mL). The chloroform solution was dried
over anhydrous sodium sulfate and filtered. Evaporation of the sol-
vent yielded a light yellow coloured viscous oil. Yield of L2: (0.56 g,
least squares using SHELX-97 software [20]. The program X-Seed
21] was used as an interface to the SHELX programs and to prepare
the figures. In the figures, the ellipsoids have been drawn at the
0% probability level unless stated otherwise and hydrogen bonds
[
5
are presented by dashed lines. Where applicable, # indicates sym-
metry-generated atoms. All hydrogen atoms were located in the
difference electron density map, placed at geometrically idealised
positions and constrained to ride on their parent atoms (C–H dis-
tances: 0.95–0.99 Å, N–H distances: 0.88, 0.93, Uiso(H) = 1.2). The
asymmetric unit contains the complex cation, one full perchlorate
anion (Cl1) and two half of a perchlorate anion (Cl2 and Cl3), a
methanol molecule and a disordered water molecule. The latter
are disordered over two positions about the twofold axis. Crystal
parameters and details of the data collection and refinement are
summarised in Table 1.
1
.31 mmol, 38%).
ꢁ1
IR spectrum (cm ): 3344m, 2929s, 2836s, 1682s, 1635m,
603m, 1515vs, 1468s, 1424s, 1356w, 1304m, 1280m, 1233m,
197m, 1166m, 1133w, 1083w, 1063w, 1031m, 1013w, 986w,
1
1
8
ꢁ1 1
68m, 807w, 749s cm
3
. H NMR (CDCl , 300 MHz); d ppm: 8.67
(
s, 1H), 7.81–7.78 (d, 1H, J = 9.0 Hz), 7.50–7.48 (d, 1H, J = 6.0 Hz),
7
2
1
1
4
.31–7.37 (m, 2H), 7.28–7.23 (m, 1H0, 3.98 (s, 3H), 3.29 (s, 2H),
.81–2.62 (m, 21H). C NMR (CDCl ); d ppm: 169.0, 156.5, 150.6,
3
45.2, 126.9, 126.0, 124.5, 122.3, 119.6, 118.5, 111.5, 103.5,
01.0, 61.3, 56.5, 52.6, 46.6, 45.8, 45.4, 45.0. ESI MS (+ mode):
26 (M+1).
13
3. Results and discussion
3.1. Synthesis and characterization
2
.4.4. [CuL1](ClO
A solution of Cu(ClO
methanol was added dropwise to a solution of L1 (0.052 g,
.12 mmol) in 10 mL methanol. The resulting dark blue solution
4
)
2
ꢀMeOHꢀ1/2H
2
O (C1)
The synthesis of 1,4-disubstituted dibenzofuran cyclen, L1, was
achieved following the synthetic route outlined in Scheme 1. Treat-
ment of the amino-methoxy substituted dibenzofuran with chloro-
4
)
2
ꢀ6H
2
O (0.045 g, 0.12 mmol) in 10 mL
0
2 2
acetyl chloride in CH Cl in the presence of a base gave the
was stirred at room temperature for 30 min. Slow evaporation of
this solution yielded dark blue single crystals suitable for X-ray
crystallography. Yield: 41 mg, 34%.
chloroacetyl substituted compound which was condensed with cy-
clen to yield the 1,4-bis(dibenzofuran) cyclen derivative. When
using this synthetic route we were unable to isolate any of the
mono-substituted cyclen derivative, L2, despite numerous at-
tempts at chromatographic separation.
An alternative synthetic route to prepare the monoalkylated
product was developed (Scheme 2) which involved the protection
of three of four secondary cyclen nitrogens with t-boc groups by
reaction with di-tert-butyl dicarbonate. Condensation of this com-
pound with the chloroacetyl substituted dibenzofuran yielded the
required tri-t-boc protected dibenzofuran cyclen derivative which,
following chromatographic purification, was treated with trifluoro-
acetic acid in methylene chloride to yield the required mono-alkyl-
ated compound as a viscous oil. Thus, the mono- and di-
substituted dibenzofuran cyclen derivatives were obtained using
two independent synthetic strategies.
ꢁ1
IR spectrum (cm ): 3281m, 1685m, 1647m, 1609m, 1530s,
1
7
8
474vs, 1449m, 1427m, 1194m 1115vs, 1084vs, 1029m, 858m,
38m, 624s. Anal. Calc. for C39
46
H N
6
Cl
2
CuO15.5: C, 47.7; H, 4.7; N,
.6. Found C, 46.7; H, 4.6; N, 8.6%.
2.5. Crystal and structure refinement data
X-ray crystallography data were obtained on a single crystal of
C1, mounted on thin glass fibre, using a Nonius Kappa CCD with
monochromated Mo K radiation (k = 0.71073 Å) at 123(2) K and
a
phi and/or omega scans. The absorptions have been corrected by
a semi-empirical approach using the SORTAV software [18,19]. The
structures were solved by direct method and refined by full matrix

T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
2899
OMe
OMe
NEt3
CH Cl
+
ClCH COCl
O
2
Cl
O
NH2
2
2
O
N
H
RT, 48 h
H
H
H
H
CHCl3
N
N
N
N
reflux/120 h
NEt3
OMe
MeO
N
O
N
H
O
N
N
N
H
O
O
N
H
H
L1
Scheme 1. Synthesis of L1.
H
H
H
H
t-Boc
t-Boc
N
N
N
N
Boc O
N
N
N
N
2
2
CH Cl2
H
+
t-Boc
RT/48h
OMe
NH2
OMe
NEt3
ClCH COCl
O
2
Cl
O
CH
RT, 48 h
2
Cl
2
O
N
H
H
t-Boc
t-Boc
K CO , KI
2
3
N
N
N
ACN
N
Reflux
t-Boc
4
days
OMe
OMe
H
N
O
N
H
O
N
H
t-Boc
N
CF COOH
N
N
N
N
3
O
O
CH Cl2
2
L2
N
N
H
H
RT/18h
t-Boc
t-Boc
Scheme 2. Synthesis of L2.
All compounds were characterized by a combination of NMR
spectroscopy, mass spectrometry and IR spectroscopy. The IR spec-
trum of the final derivatives exhibited various diagnostic vibrations,
methylene signals were observed which were attributable to mac-
rocycle methylenes when two would be expected for the 1,7-di-
substituted derivative. As expected, the mono-substituted deriva-
tive also exhibits four macrocycle methylene signals and, for both
compounds, 13 signals due to the aromatic carbons of the dibenzo-
furan and the C@O of the amide linker were observed. ESI-MS pro-
vided further confirmation of the formation of the two ligands, viz.,
peaks were observed at 679 (M+1) for the di-substituted derivative
and at 426 (M+1) for the mono-substituted product.
The copper(II) complex of the disubstituted dibenzofuran–cy-
clen derivative was isolated by slow evaporation of a methanolic
solution of the L1 and copper(II) perchlorate. Elemental analysis
indicated that the complex has the composition [CuL1]-
ꢁ1
ꢁ1
e.g., ꢄ3340 cm (N–H stretches), 2800–3000 cm (C–H stretches),
ꢁ
1
ꢁ1
ꢄ1680 cm (C@O stretch) and 1400–1600 cm (various aromatic
1
ring vibrations). In the H NMR spectra of the two compounds, mea-
3
sured in CDCl , the expected resonances due to the aromatic pro-
tons of the furan group were observed in the 7–9 ppm region (see
Section 2). Signals due to the methylenes of the macrocyclic ring
were found in the 2.9–3.4 ppm region for the dibenzofuran deriva-
tive and 2.6–2.9 ppm region for the monobenzofuran derivative.
Singlets attributable to the methoxy group and methylene connect-
ing the benzofuran to the macrocycle were found in the 3.8–
4
.0 ppm and 3.30–3.5 ppm region, respectively. The number of
(ClO
4
)
2
ꢀMeOHꢀ1/2H
2
O. The infrared spectra showed the character-
1
3
ꢁ1
signals in the C NMR spectrum of the dibenzofuran derivative con-
firmed that the 1,4-disubstituted derivative was formed, e.g., four
istic bands for the ligand at 1685 cm (C@O stretch) and 1600–
1400 cm which correspond to various aromatic vibrations.
ꢁ1

2
900
T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
Fig. 1. Thermal ellipsoid plot of complex cation with atom-numbering scheme (drawn at 30% probability level). Hydrogen atoms, perchlorate anions and solvent molecules
are omitted for clarity.
and one disordered water molecule. The structure confirms the for-
mation of the 1,4-disubstituted cyclen derivative proposed on the
basis of the NMR studies. The Cu(II) centre is five-coordinate with
four nitrogen amines of the macrocycle and an oxygen atom, O25,
Table 2
Selected bond lengths (Å) and angles (°) for complex C1 (esd in parentheses).
Cu(1)–N(1)
Cu(1)–N(2)
Cu(1)–N(3)
Cu(1)–N(4)
Cu(1)–O(25)
2.014(5)
2.111(5)
2.010(5)
1.999(5)
2.127(4)
N(3)–Cu(1)–N(4)
N(1)–Cu(1)–O(25)
N(2)–Cu(1)–O(25)
N(3)–Cu(1)–O(25)
N(4)–Cu(1)–O(25)
O(10)–C(10)–C(9)
O(25)–C(25)–C(24)
N(1)–C(9)–C(10)
N(2)–C(24)–C(25)
86.4(2)
109.7(2)
80.14(16)
96.86(18)
128.3(2)
122.6(5)
121.3(5)
110.6(5)
111.0(5)
forming a distorted square-pyramidal environment (s = 0.02). The
average of the Cu–N bond lengths is 2.033 Å, which is as expected
for five coordinate copper(II)–cyclen complexes, with the Cu–Ntert
bonds being only slightly longer than the Cu–Nsec bonds. An amide
oxygen atom, O25, from one of the pendant arms binds in the axial
position of the copper(II) centre (Cu–O bond length of 2.127(4) Å).
The four nitrogen atoms form the base of the pyramid and the
N(1)–Cu(1)–N(2)
N(1)–Cu(1)–N(3)
N(2)–Cu(1)–N(3)
N(1)–Cu(1)–N(4)
N(2)–Cu(1)–N(4)
85.92(19)
150.4(2)
85.9(2)
87.2(2)
151.3(2)
Cu(II) centre lies 0.513 Å above this N
been found for other Cu(II)–cyclen structures [22–24]. Within the
molecule intramolecular stacking interaction are observed be-
4
-plane. Similar values have
p–p
3.2. Crystal structure
tween the dibenzofuran pendant arms and the molecules are
aligned in head-to-tail arrangement (Fig. 2).
The molecular structure of the cationic copper(II) complex is
The crystal structure displays one-dimensional chains resulting
from hydrogen bonding interactions between perchlorate anions
(Cl2) and amine-protons, N3 and N4, of the macrocyclic ring (see
Fig. 1). There are several other intermolecular hydrogen bonding
shown in Fig. 1, while Table 2 summarises a selection of bond
lengths and angles. The crystal structure also contains two non-
coordinated perchlorate anions, one methanol solvent molecule
Fig. 2. Stick representation of head-to-tail arrangement of the molecules in C1 and intramolecular p–p stacking interactions with distances between pendant arms.

T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
2901
Fig. 3. Hydrogen bond interactions between perchlorate anions and cyclen-amine protons resulting in one dimensional chains.
3.3. Visible spectra and fluorescence measurements
Table 3
Hydrogen bonds for compound C1 (Å and °).
The visible spectra of the copper complexes for L1 and L2 shows
a maximum absorption band at 610 nm (e = 193 M cm ) and
D–Hꢀ ꢀ ꢀA
d(D–H)
d(Hꢀ ꢀ ꢀA)
d(Dꢀ ꢀ ꢀA)
\(DHA)
ꢁ1
ꢁ1
ꢁ
1
ꢁ1
N(3)–H(3)ꢀ ꢀ ꢀO(5) #1
N(3)–H(3)ꢀ ꢀ ꢀO(7) #1
N(3)–H(3)ꢀ ꢀ ꢀO(8)
0.93
0.93
0.93
0.93
0.93
0.93
0.88
0.88
0.84
2.06
2.18
2.45
2.17
2.34
2.59
2.41
2.16
2.14
2.892(10)
2.949(11)
3.343(12)
2.897(10)
3.223(11)
3.107(6)
3.105(6)
2.988(6)
2.944(6)
147.5
139.5
160.7
134.4
158.2
115.7
136.0
155.5
159.9
590 nm (
istics are typical for copper(II) complexes of cyclen derivatives
16]. A titration of a solution of the ligand (L1 and L2) with a
e = 273 M cm ), respectively. These spectral character-
[
N(4)–H(4)ꢀ ꢀ ꢀO(6) #2
N(4)–H(4)ꢀ ꢀ ꢀO(8) #3
N(4)–H(4)ꢀ ꢀ ꢀO(10)
N(5)–H(5)ꢀ ꢀ ꢀO(1)
2
+
Cu solution to a maximum of two equivalents of the metal ion re-
sulted in systematic changes in spectra (Figs. S1 and S2, Supporting
Information) which were complete when 1 equivalent of Cu2+ had
been added.
N(6)–H(6)ꢀ ꢀ ꢀO(60)
O(60)–H(60)ꢀ ꢀ ꢀO(2)
Initial fluorescence emission studies, conducted for the free li-
gands, revealed that both ligands have an emission maximum at
60 nm. The emission spectrum of L1 also shows a shoulder at
Symmetry transformations used to generate equivalent atoms: #1 x, y + 1, z; #2 x,
y, z ꢁ 1/2 #3 ꢁx + 1, ꢁy, ꢁz + 1.
ꢁ
3
ca. 390 nm indicating that emission could be taking place from
2
+
two excited states. Addition of Cu solutions to each ligand re-
sulted in the quenching of the fluorescence until no further change
is observed, typically when the copper to ligand ratio is higher than
interactions, e.g., between the perchlorate anion Cl1 and the meth-
anol molecule [O(60)–H(60)ꢀ ꢀ ꢀO(2), 2.944(6) Å] or the nitrogen
atom N6 of the pendant arm and the methanol molecule [N(6)–
H(6)ꢀ ꢀ ꢀO(60), 2.988(6) Å] (Fig. 3 and Table 3). However, these inter-
actions are not involved in the formation of the 1D chains and
probably only stabilise the crystal structure. When the crystal
packing is viewed along the c-axis, channels are evident which
accommodate perchlorate anions Cl2 and Cl3. The perchlorate an-
ion, Cl1, and the methanol solvent molecules are situated in the
interstitial crystal space on the outside of the channels (Fig. 4).
1
:1 (Figs. 5 and 7). Such a decrease in the fluorescence emission of-
2+
ten accompanies the coordination of Cu ions to metal binding
sites within the fluorophore [1–3]. The fact that the addition of
one equivalent of Cu almost completely quenched the fluores-
2+
cence of both L1 and L2 is in agreement to the UV–Vis spectral
titration which indicated no further changes in spectrum when
the M:L ratio was increased above 1:1. The addition of zinc(II) per-
chlorate solution was also found to decrease the fluorescence
Fig. 4. Crystal packing viewed down the c-axis showing the channels that accommodate the perchlorate anions.

2
902
T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
Fig. 5. Quenching of the fluorescence emission of L1 (3.33
l
M) on addition of Cu2+ in CH
3
CN.
3
Fig. 6. Quenching of the fluorescence emission of L1 (3.33 l CN.
M) on addition of Zn2+ in CH
3
Fig. 7. Quenching of the fluorescence emission of L2 (3.33 l CN.
M) on addition of Cu2+ in CH

T.K. Venkatachalam et al. / Inorganica Chimica Acta 363 (2010) 2896–2904
2903
3
Fig. 8. Quenching of the fluorescence emission of L2 (3.33 l CN.
M) on addition of Zn2+ in CH
emission intensity of the two ligands (Figs. 6 and 8) but, in this
case, the fluorescence was not completely quenched. This observa-
tion is very surprising as the addition of Zn2 ions has been found
to enhance the emission of a wide variety of fluorophores [3,7].
One possibility is that the binding of the oxygen from the amide
4. Conclusion
+
Two new dibenzofuran derivatives of cyclen have been pre-
pared and characterized; a mono-functionalized derivative L2
and a 1,4-dibenzofurancyclen derivative L1. The copper(II) com-
plex of L1 confirmed that the 1,4-disubstituted derivative had been
obtained instead of the 1,7-disubstituted product and revealed that
the copper(II) centre is arranged in a square pyramidal geometry
occupied by the four nitrogen donors from the macrocycle and
an amide oxygen from one dibenzofuran pendant group. A fluores-
cence emission study revealed that the emission intensity of both
group (as observed in the crystal structure of [CuL1](ClO
4
)
2
ꢀ
2
MeOHꢀ1/2H O) could be responsible for total or partially quench-
ing the fluorescence. As described by Ryan and Weber [25],
quenching of fluorescence of a ligand by titration with a metal
can be described with the non-linear equation:
h
2
+
2+
I ¼ ððIML ꢁ 100Þ=ð2KC
L
ÞÞ ðKC
L
þ KC
M
þ 1Þ
ligands is quenched by the addition of either Cu or Zn . The
changes in the emission spectra and UV–Vis spectra were consis-
tent with the formation of a 1:1 ML complex.
rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
i
2
2
ꢁ
ðKC
L
þ KC
M
þ 1Þ ꢁ 4K C
L
C
M
þ 100
Acknowledgement
where I = overall measured fluorescence intensity,
ML = fluorescence intensity of the bound ligand,
I
This research was funded in part by the National Health and
Medical Research Council through Program Grant 400121 (DCR).
C
C
M
= total metal ion concentration,
= total ligand concentration,
L
K = conditional stability constant for the reaction.
Appendix A. Supplementary material
Thus IML then represent a limiting value below which the fluo-
rescence will not decrease due to the addition of metal anion. In
the case of zinc(II) complexes of L1 and L2 the value IML is bigger
than for the copper(II) complexes of the same ligands as can be
seen in Figs. 5–8. This suggests that the zinc(II) complexes are fluo-
rescent but their emission intensity is lower than that of the ligand.
Nevertheless, these preliminary fluorescence studies indicate that
dibenzofuran–cyclen derivatives could prove to be useful fluores-
cence sensors.
CCDC 764952 contains the supplementary crystallographic data
for C1. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via http://www.ccdc.cam.a-
c.uk/data_request/cif. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.ica.2010.04.039.
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