Copper(II) interaction with mono-, bis- and tris-ring N3O 2 macrocycles: Synthetic, X-ray, competitive membrane transport, and hypochromic shift studies

Article abstract of DOI:10.1021/ic801265y

New N-phenyl (L¹), azo-coupled (L²), and tri-linked (L³) substituted derivatives of a parent dibenzo-N₃O ₂ macrocycle, 1,12,15-triaza-3,4:9,10-dibenzo-5,8- dioxacycloheptadecane (L⁴), have

Full text of DOI:10.1021/ic801265y

Inorg. Chem. 2009, 48, 2770-2779
Copper(II) Interaction with Mono-, Bis- and Tris-Ring N3O2 Macrocycles:
Synthetic, X-ray, Competitive Membrane Transport, and Hypochromic
Shift Studies
Joobeom Seo,† Sunhong Park,† Shim Sung Lee,*,† Marina Fainerman-Melnikova,‡
and Leonard F. Lindoy*,‡
Department of Chemistry (BK21) and Research Institute of Natural Science, Gyeongsang National
UniVersity, Jinju 660-701, S. Korea, and Centre for HeaVy Metal Research, School of Chemistry,
F11, The UniVersity of Sydney, NSW 2006, Australia
Received July 7, 2008
New N-phenyl (L1), azo-coupled (L2), and tri-linked (L3) substituted derivatives of a parent dibenzo-N3O2 macrocycle,
1,12,15-triaza-3,4:9,10-dibenzo-5,8-dioxacycloheptadecane (L4), have been synthesized. Competitive seven-metal
transport studies across a bulk chloroform membrane employing an aqueous source phase containing equal molar
concentrations of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Ag(I), and Pb(II) as their nitrate salts have been performed
using both L1 and L3 as the ionophore, with the results discussed in terms of those obtained previously for related
mono-ring (L5) and di-linked (L6) macrocyclic systems. Sole transport selectivity for Cu(II) was observed in each
case. On a per macrocyclic cavity basis the tri-linked analogue L3 gave less efficient Cu(II) transport than its
monomeric or di-linked analogues. At least in part, this may reflect the tendency of tri-linked derivative L3 to form
a 2:1 complex (metal/ligand) with Cu(II) under the conditions employed; such a stoichiometry was demonstrated to
occur in acetonitrile using both spectrophotometric titration and Job plot procedures. The azo-coupled derivative
(L2) yields a red solution (λmax ) 495 nm, εmax ) 23000 M-1 cm-1) and undergoes significant hypochromic metal-
induced shifts (∆λmax ) 54-174 nm) on metal addition. Cu(II) induces the largest shift (∆λmax ) 174 nm),
corresponding to a color change from red to pale-yellow. The X-ray structures of red L2 · HNO3 together with its
Cu(II) complexes, [Cu(L2)NO3]NO3 ·CH2Cl2 (6) (pale-yellow) and [{Cu(L2)}2(µ-OH)2](ClO4)2 · 2CH2Cl2 ·2H2O (7) (dark-
red), are reported. The structural determinations have allowed insight into the structure-function relationships
governing the observed color variation between these species.
Introduction
and the substituents on the ring have all been employed to
“tune” such ring systems for selective metal ion recognition.2
In an extension of these studies we now present a compara-
tive investigation of aspects of the complexation behavior
of the new cyclic derivatives L1, L2, and L3 toward selected
transition and post-transition metal ions. The results are
compared with those obtained previously3c from parallel
studies for the parent N3O2-macrocycle L4 and the related
substituted derivatives L5 and L6 (see Chart 1). Structure/
Related to the presence of a central cavity, macrocycles
have long been employed in investigations of metal ion
recognition.1 In this context, we have investigated the
selective behavior of a range of dibenzo-substituted, mixed
donor macrocyclic systems toward a range of transition and
post-transition metal ions.2,3 Such ligands have been dem-
onstrated to form complexes with a wide range of transition
and post-transition metal ions. In these studies systematic
variation of the macrocyclic ring size, the donor atom set,
(2) (a) Adam, K. R.; Antolovich, M.; Baldwin, D. S.; Brigden, L. G.;
Duckworth, P. A.; Lindoy, L. F.; Bashall, A.; McPartlin, M.; Tasker,
P. A. J. Chem. Soc., Dalton Trans. 1992, 1869. (b) Adam, K. R.;
Arshad, S. P. H.; Baldwin, D. S.; Duckworth, P. A.; Leong, A. J.;
Lindoy, L. F.; McCool, B. J.; McPartlin, M.; Tailor, B. A.; Tasker,
P. A. Inorg. Chem. 1994, 33, 1194. (c) Adam, K. R.; Baldwin, D. S.;
Duckworth, P. A.; Lindoy, L. F.; McPartlin, M.; Barshall, A.; Powell,
H. R.; Tasker, P. A. J. Chem. Soc., Dalton Trans. 1995, 1127.
* To whom correspondence should be addressed. E-mail: sslee@gnu.ac.kr
(S.S.L.), lindoy@chem.usyd.edu.au (L.F.L.).
†
Gyeongsang National University.
The University of Sydney.
‡
(1) Gloe, K. Macrocyclic Chemistry: Current Trends and Future; Springer:
Dordrecht, 2005.
2770 Inorganic Chemistry, Vol. 48, No. 7, 2009
10.1021/ic801265y CCC: $40.75  2009 American Chemical Society
Published on Web 03/09/2009

Complexation of Cu(II) with N3O2-Donor Macrocyclic Rings
Chart 1. Mono-, Bis-, and Tris-Ring N3O2 Macrocycles
cooled and then filtered. On addition of ice to the filtrate, an oil
separated, which was extracted into dichloromethane. The combined
organic phases were dried over anhydrous sodium sulfate and
evaporated to yield L1 as a yellow glassy solid (1.05 g. 50%). Mp:
59-61 °C, IR (KBr, cm-1): 3323(m), 2925(w), 1599(m), 1506(m),
1450(m), 1363(m), 1232(s), 1126(m), 1063(w), 937(w), 750(w).
function relationships underlying the metal induced color
changes of L2, obtained by attaching a chromophoric benzo-
azo substituent to the central amine group of the parent
macrocycle L4, are also discussed.
Experimental Section
1
MS (ESI): m/z ) 418.1 [(M+1)+, (C26H31N2O2+H)+], H NMR
General Procedures. NMR spectra were recorded on a Bruker
Avance 300 spectrometer (300 MHz) and mass spectra were
obtained on a JEOL JMS-700 spectrometer at the Central Labora-
tory of Gyeongsang National University. The UV-vis absorption
spectra were recorded with a Cary 5E (Varian) or a Scinco S-3100
spectrophotometer. Infrared spectra were measured with a Mattson
Genesis Series FT-IR spectrophotometer. Microanalyses were
performed by an Elemental Analysen Systeme Vario EL at the
KBSI (Daegu, S. Korea).
(300 MHz, CDCl3) δ 7.20-6.65 (m, 13H, aromatic H), 4.27 (s,
4H, CH2O), 3.98 (br, 2H, NH), 3.85 (s, 4H, ArCH2), 3.39 (t, J 5.3
Hz, 4H, NCH2), 2.74 (t, J 5.3 Hz, 4H, NCH2CH2). 13C-{1H} NMR
(75 MHz, CDCl3): 156.9, 148.7, 131.2, 129.0, 128.8, 127.7, 121.3,
118.7, 115.9, 112.2, 67.2, 53.0, 49.2, 46.6. Anal. Calcd for
C26H31N3O2: C, 74.79; H, 7.48; N, 10.06. Found: C, 74.98; H, 7.78;
N, 9.84%.
Di-Boc-Protected Macrocycle 1. Di-tert-butyl dicarbonate (2.36
g, 10.8 mmol) was added to a stirred solution of L1 (1.81 g, 4.33
mmol) in dichloromethane (100 mL). The solution was stirred at
room temperature for 30 min and then evaporated to give yellow
oil. Flash column chromatography on silica gel using 10% ethyl
acetate/n-hexane as the eluent led to the isolation of 1 as a white
solid (2.41 g, 90%). 1H NMR (300 MHz, CDCl3) δ 7.28-6.62 (m,
13H, aromatic H), 4.59 (s, 4H, CH2O), 4.42 (s, 4H, CH2O),
3.34-3.28 (br, 8H, NCH2CH2), 1.53 (s, 9H, t-Bu), 1.46 (s, 9H,
t-Bu). 13C-{1H} NMR (75 MHz, CDCl3): 156.4, 148.4, 129.3, 128.7,
128.4, 126.3, 121.5, 120.9, 116.16, 111.4, 110.9, 80.1, 67.3, 47.7,
43.8, 43.1, 28.5. HRMS (EI): Calcd for C36H47N3O6 (M+): 617.3465.
Found: 617.3470.
Ligand L1. 4-Phenyl-diethylenetriamine4 (0.90 g, 5.02 mmol)
in methanol (50 mL) was slowly added to a stirred solution of 1,4-
bis(2-formylphenyl)-1,4-dioxabutane5 (1.36 g, 5.03 mmol) in
methanol (200 mL). The solution was refluxed for 1 h, and then
sodium borohydride (0.57 g, 15.1 mmol) was slowly added to the
stirred solution. After the reaction had ceased, the solution was
(3) (a) Fenton, R. R.; Gauci, R.; Junk, P. C.; Lindoy, L. F.; Luckay, R. C.;
Meehan, G. V.; Price, J. R.; Turner, P.; Wei, G. J. Chem. Soc., Dalton
Trans. 2002, 2185. (b) Jin, Y.; Yoon, Il.; Seo, J.; Lee, J.-E.; Moon,
S.-T.; Kim, J.; Han, S. W.; Park, K.-M.; Lindoy, L. F.; Lee, S. S.
Dalton Trans. 2005, 788. (c) Fainerman-Melnikova, M.; Nezhadali,
A.; Rounaghi, G.; McMurtrie, J. C.; Kim, J.; Gloe, K.; Langer, M.;
Lee, S. S.; Lindoy, L. F.; Nishimura, T.; Park, K.-M.; Seo, J. Dalton
Trans. 2004, 122.
Di-Boc-Protected Marocycle 2. A diazonium salt of 4-nitro-
aniline (0.20 g, 1.44 mmol) was prepared by adding an aqueous
solution of sodium nitrite (0.13 g, 1.87 mmol) dropwise into a
homogeneous mixture of sulfuric acid (0.3 mL) and glacial acetic
(4) Ueda, T.; Kobayashi, S. Chem. Pharm. Bull. 1969, 17, 1720.
(5) Armstrong, L. G.; Grimsley, P. G.; Lindoy, L. F.; Lip, H. C.; Norris,
V. A.; Smith, R. J. Inorg. Chem. 1978, 17, 2350.
Inorganic Chemistry, Vol. 48, No. 7, 2009 2771

Seo et al.
acid (1 mL). The mixture was stirred at 0 °C for 5 min. The
diazonium salt solution was added dropwise to a solution of 1 (0.69
g, 1.12 mmol) in N,N-dimethylformamide at 0 °C. The solution
was stirred for 12 h at 0 °C. Dichloromethane (50 mL) and water
(50 mL) were added, and the organic layer was separated and dried
over anhydrous sodium sulfate. Removal of the organic solvent
under reduced pressure afforded a reddish oil. Flash column
chromatography on silica gel using 20% ethyl acetate/n-hexane as
the eluent led to the isolation of 2 as a pink solid (0.69 g, 80%).
1H NMR (300 MHz, CDCl3) δ 8.33-6.80 (m, 16H, aromatic H),
4.62 (s, 2H, CH2O), 4.40 (s, 2H, CH2O), 4.40 (s, 4H, ArCH2),
3.46-3.34 (br, 8H, NCH2CH2), 1.53 (s, 9H, t-Bu), 1.50 (s, 9H,
t-Bu). 13C-{1H} NMR (75 MHz, CDCl3): 156.8, 156.6, 156.2, 152.6,
147.6, 144.0, 130.0, 129.0, 126.9, 126.2, 125.0, 122.8, 121.7, 111.8,
111.0, 67.8, 67.0, 48.6, 44.8, 42.9, 28.8. HRMS (EI): Calcd. for
C42H50N6O8 (M+): 766.3690. Found: 766.3694.
and 13C NMR spectra of this compound were observed. HRMS
(FAB): Calcd for C99H130N9O21 (M+H+): 1780.9381. Found:
1780.9281.
Triamide 5. The protected triamide 4 (1.18 g, 0.65 mmol) was
added to a stirred mixture of dichloromethane (30 mL) and
trifluoroacetic acid (30 mL). The reaction mixture was stirred at
room temperature for 2 h. After removal of the solvent in a rotary
evaporator, methanol was added and then evaporated again to
dryness. Aqueous sodium carbonate (15%, 50 mL) was added to
the residue, and this mixture was extracted with dichloromethane
three times. The combined organic phases were dried over
anhydrous sodium sulfate, and the solvent removed to yield triamide
5 as a pale yellow glassy solid (0.69 g, 90%). Mp: 112-115 °C,
IR (KBr, cm-1): 2932(m), 1624(s, νCdO), 1468(m), 1236(m),
1113(s), 933(w), 756(w). MS (ESI): m/z ) 1180.8 ([M+1]+,
1
[C69H81N9O9+H]+), H NMR (300 MHz, CDCl3): 7.41-6.88 (m,
Ligand L2. Protected intermediate 2 (0.69 g, 0.90 mmol) was
added to a stirred mixture of dichloromethane (30 mL) and
trifluoroacetic acid (30 mL) and stirring was continued at room
temperature for 2 h. The solvent was removed using a rotary
evaporator, methanol was added to the residue, and the resulting
solution again taken to dryness. This procedure was repeated three
times to remove any remaining trifluoroacetic acid. Aqueous sodium
carbonate (15%, 50 mL) was added to the residue, and the mixture
extracted with dichloromethane three times. The combined organic
phases were dried over anhydrous sodium sulfate and evaporated
27H, aromatic), 4.40 (s, 6 H, CH2O), 4,36 (s, 6H, CH2O), 3.85 (s,
6H, ArCH2), 3.73 (s, 6H, ArCH2), 3.56 (s, 6H, NCH2), 3.30 (s,
6H, NCH2), 2.88 (m, 6H, NHCH2CH2), 2.65 (m, 6H, NHCH2CH2).
13C-{1H} NMR 157.1, 135.8, 131.1, 129.8, 128.8, 128.5, 120.8,
111.2, 67.1, 54.8, 50.2, 48.5. Pronounced broadening and/or splitting
1
of signals in the H and 13C NMR spectra of this compound were
observed. HRMS (FAB): Calcd for C69H82N9O9 (M+H+): 1180.6236.
Found: 1180.6298.
Ligand L3. A solution of BH3 ·Me2S complex (2.0 M; 2.23 mL,
4.46 mmol) was added to triamide 5 (0.87 g, 0.73 mmol) in dry
THF (50 mL) at 60 °C. The reaction mixture was stirred until no
carbonyl absorption could be observed by IR spectroscopy (ca. 6 h).
Excess borane was destroyed by careful addition of methanol, and
the solvent was removed under reduced pressure. The residual white
powder was then refluxed in MeOH-H2O-conc.HCl (20:5:2, 27 mL)
for 1.5 h. The methanol was evaporated under reduced pressure,
and the aqueous residue basified with 10% aqueous sodium
hydroxide (100 mL). The basic solution was extracted with CH2Cl2
and then the combined organic extracts dried and evaporated to
yield L3 as a white glassy solid (0.74 g, 90%). IR (KBr, cm-1):
3310(m), 2924(m), 1450(m), 1238(m), 1109(s), 943(w), 752(w).
1H NMR (300 MHz, CDCl3) 7.26-6.44 (m, 27H, aromatic H), 4.38
(s, 12H, CH2O), 3.79 (s, 12H, ArCH2NH), 3.41 (br, 6H, NH), 3.12
(s, 6H, NCH2Ar), 2.59 (m, 12H, NCH2CH2), 2.36 (m, 12H,
NHCH2CH2). 13C-{1H} NMR (75 MHz, CDCl3) 157.1, 136.6, 131.4,
129.8, 128.9, 127.9, 121.2, 111.8, 67.2, 52.5, 49.7, 45.7. Pronounced
broadening of signals in the 1H and 13C NMR spectra of this
compound was observed. HRMS (FAB): Calcd for C69H88O6N9
(M+H+) 1138.6858: Found: 1138.6855.
1
to yield L2 as a reddish glassy solid (0.46 g, 90%). MS (ESI): H
NMR (300 MHz, CDCl3) δ 8.33-6.62 (m, 16H, aromatic H), 4.31
(s, 4H, CH2O), 3.98 (s, 4H, ArCH2), 3.83 (br, 4H, NCH2), 2.98
(br, 4H, NCH2CH2), 2.53 (br, 2H, NH). 13C-{1H} NMR (75 MHz,
CDCl3): 157.3, 157.0, 148.0, 144.6, 142.4, 132.1, 130.0, 126.4,
125.1, 123.1, 122.6, 114.3, 112.4, 68.5, 52.0, 48.5, 46.4. HRMS
(EI): Calcd for C32H34N6O4 (M+): 566.2642. Found: 566.2630.
Di-Boc Protected Macrocycle 3. This was obtained by direct
Boc-protection of L4 followed by purification via column chroma-
tography as described previously.6
Boc-Protected Precursor 4. 1,3,5-Benzenetricarbonyl trichloride
(0.16 g, 0.60 mmol) in acetonitrile (40 mL) was added dropwise
to a refluxing suspension of 3 (1.12 g, 2.06 mmol) and potassium
carbonate (2.57 g, 18.50 mmol) in acetonitrile (150 mL). The
reaction mixture was then maintained at reflux for an additional
24 h with rapid stirring, allowed to cool to room temperature and
filtered. The filtrate was evaporated on a rotary evaporator, and
the residue was partitioned between water and dichloromethane.
The aqueous phase was separated and extracted with two further
portions of dichloromethane. The combined organic phases were
dried over anhydrous sodium sulfate, and the solution then
evaporated to dryness. Flash column chromatography on silica gel
using 70% ethyl acetate/n-hexane as the eluent led to the isolation
of 4 as a white solid (0.97 g. 92%). Mp: 135-138 °C, IR (KBr,
cm-1): 3065(m), 2974(m), 2932(s), 2877(m), 2359(w), 2335(w),
1693 (s, νCdO), 1644(m), 1597(w), 1486(m), 1455(m), 1413(m),
1365(m), 1241(w), 1158(m), 1126(w), 1051(m), 933(m), 888(w),
Synthesis of Cu(II) Complexes of L2. Toluene (0.4 mL) was
added to a dichloromethane solution (1.0 mL) of L2 (20 mg, 0.035
mmol); then the required Cu(II) salt (nitrate for 6 and perchlorate
for 7; 0.035 mmol) in methanol was layered on the toluene phase;
the (layered) mixture was allow to stand for 2 weeks during which
time crystalline complexes suitable for X-ray analysis formed at
the interface. Isolated yields were greater than 30%.
[Cu(L2)NO3]NO3 ·CH2Cl2 (6). Yellow crystals. IR (KBr, cm-1):
3421(m), 1601(s), 1514(m), 1452(m), 1385(s), 1339(s), 1244(m),
1132(m), 955(w), 858(w), 756(w). MS (FAB): m/z ) 691.25
([Cu(L2)NO3]+, [C32H34CuN7O7]+). HRMS (FAB): Calcd. for
C32H34CuN7O7 ([Cu(L2)NO3]+): 691.1816. Found: 691.1813.
[{Cu(L2)}2(µ-OH)2](ClO4)2 ·2CH2Cl2 ·2H2O (7). Red crystals.
IR (KBr, cm-1): 3566(m), 1601(s), 1522(m), 1454(m), 1336(s),
1245(m), 1105(s, νClO4), 858(w), 756(w), 624(w).
1
811(w), 752(w), 611(w), 552(w), 438(w). H NMR (300 MHz,
CDCl3): 7.24-6.89 (m, 27H, aromatic), 4.55 (br, 12H, CH2O), 4,35
(br, 12H, ArCH2), 3.75-3.13 (br, 24H, NCH2CH2), 1.60-1.26 (br,
54 H, C(CH3)3), 13C-{1H} NMR 170.9, 156.2, 128.3, 127.7, 126.4,
121.3, 110.9, 79.5, 67.1, 60.3, 48.9, 46.8, 45.0, 43.5, 28.4, 21.0,
1
14.2. Pronounced broadening and/or splitting of signals in the H
(6) (a) Chartres, J. D.; Groth, A. M.; Lindoy, L. F.; Lowe, M. P.; Meeham,
G. V. J. Chem. Soc., Perkin Trans. 1. 2000, 3444. (b) Park, K. J.;
Kim, J.-H.; Meehan, G. V.; Nishimura, T.; Lindoy, L. F.; Lee, S. S.;
Park, K.-M.; Yoon, I. Aust. J. Chem. 2002, 55, 773.
X-ray Crystallographic Analysis. Crystals of the respective
products were mounted on a Bruker SMART diffractometer
equipped with a graphite monochromated Mo KR (λ ) 0.71073
2772 Inorganic Chemistry, Vol. 48, No. 7, 2009

Complexation of Cu(II) with N3O2-Donor Macrocyclic Rings
Table 1. Crystal Data and Structural Refinement
L1 ·HNO3 ·HPF6 ·CH3OH·H2O
6
7
formula
M
C27H39F6N4O6.50
668.59
P
C33H34Cl2CuN8O10
837.12
C66H70Cl6Cu2N12O19
1675.12
T/K
173(2)
173(2)
173(2)
crystal system
space group
a/Å
b/Å
c/Å
monoclinic
C2/c
14.7378(8)
18.4875(10)
23.8503(13)
triclinic
P1
monoclinic
P21/n
15.1258(7)
15.6145(7)
16.5997(8)
j
8.2961(6)
12.8519(10)
17.9321(13)
77.861(2)
82.893(2)
78.241(2)
1823.4(2)
2
R/deg
ꢀ/deg
100.2780(10)
106.7310(10)
γ/deg
V/Å3
6394.1(6)
8
3754.6(3)
2
Z
µ(Mo KR)/mm-1
crystal size (mm)
absorption correction
reflections collected
independent reflections
goodness-of-fit on F2
final R1, wR2 [I > 2σ(I)]
(all data)
0.168
0.814
0.859
0.20 × 0.20 × 0.15
0.10 × 0.05 × 0.04
SADABS
11279
7756
1.073
0.10 × 0.10 × 0.05
SADABS
21079
7338
1.012
SADABS
20129
7504
1.086
0.1249, 0.3080
0.1757, 0.3422
0.0822, 0.2004
0.1887, 0.2648
0.0750, 0. 0.2020
0.1428, 0.2523
Table 2. Cu(II) Transport in Seven-Metal Competitive Transport
Experiments Across a Bulk Chloroform Membrane Employing L1 and
L3-L6 as Ionophores at 25 °Ca
Å) radiation source, and a CCD detector and 45 frames of two-
dimensional diffraction images were collected and processed to
deduce the cell parameters and orientation matrix. A total of 1271
frames of two-dimensional diffraction images were collected. The
frame data were processed to give structure factors by the program
SAINT.7 The intensity data were corrected for Lorentz and
polarization effects. Using the program SADABS,8 empirical
absorption corrections were also applied for compounds L1, L2, 1,
6, and 7. The structures were solved by a combination of direct
and difference Fourier methods provided by the program package
SHELXTL9 and refined using a full matrix least-squares against
F2 for all data. All the non-H atoms were refined anisotropically.
All hydrogen atoms were included in calculated positions with
isotropic thermal parameters 1.2 times those of attached atoms.
Crystallographic data for L1, 6, and 7 are summarized in Table 1.
Bulk Membrane Transport. Bulk membrane transport (water/
chloroform/water) experiments employed a “concentric cell” in
which the aqueous source phase (10 mL) and receiving phase (30
mL) were separated by a chloroform phase (50 mL). Details of the
cell design have been reported.10 The concentrations of the ligands
in the chloroform phase were set at 1.0 × 10-3 M to enable direct
comparison of the results with those for L4 and L5 given in previous
reports3c,11 (see Supporting Information, Figure S1). In each case
hexadecanoic acid (4 × 10-3 M) was also present in the chloroform
phase. A major role of the latter is to aid the transport process by
providing a lipophilic counterion in the organic phase (after proton
loss to the aqueous source phase) for charge neutralization of the
metal cation being transported; in this manner the need for uptake
of lipophobic nitrate anions into the organic phase is avoided. For
each experiment both aqueous phases and the chloroform phase
were stirred separately at 10 revolutions min-1; the cell was enclosed
b c
,
ionophore
CuII
d
e
L4 (mono-)
L1 (mono-)
L5 (mono-)
L6 (di-)
18.8
1.8
4.8e
12.7
10.2
L3 (tri-)
a Within experimental error, sole transport of Cu(II) into the receiving
phase was observed for each ionophore. Each value represents the mean
obtained from duplicate experiments and are × 10-6. The units are mol/24
h; values less than ∼1.5 × 10-6 are within experimental error of zero and
have been ignored in the present study; the quoted mean values are (8%
or lower. b The concentration of ligand in the organic phase was 1.00 ×
10-3 M. c In the seven-metal mixture (source phase), the concentration of
each metal was 1.00 × 10-2 M. d Values from ref 11. e Values from ref 3c.
by a water jacket and thermostatted at 25 °C. In each case the
aqueous source phase (buffered at pH 4.9 ( 0.1; 6.95 mL of 2 M
sodium acetate solution and 3.05 mL of 2 M acetic acid made up
to 100 mL) contained a mixture of Co(II), Ni(II), Cu(II), Zn(II),
Cd(II), Ag(I), and Pb(II) nitrates, each at a concentration of 10-2
M. The receiving phase was buffered at pH 3.0 (56.6 mL of 1 M
formic acid and 10.0 mL of 1 M sodium hydroxide made up to
100 mL) (Supporting Information, Figure S2). All transport runs
were terminated after 24 h, and atomic absorption spectroscopy
was used to determine the amount of metal ion transported over
this period. The transport fluxes are in mol/24 h and represent mean
values measured over 24 h; values in the range 1.5-2.0 × 10-6
are of higher uncertainty, and values less than this are within
experimental error of zero; the latter have been ignored in the
present study. The results are summarized in Table 2.
Results and Discussion
(7) SMART, SAINT and XPREP: Area detector control and data integra-
tion and reduction software, Ver. 5.0; Bruker Analytical X-ray
Instruments Inc.: Madison, WI, 1998.
Macrocycle Synthesis. The new phenyl-substituted mac-
rocycle L1 was obtained directly in 50% yield from reaction
of 4-phenyl-diethylenetriamine with 1,4-bis(2-formyl)1,4-
dioxabutane in methanol followed by sodium borohydride
reduction. Synthesis of 4-nitroazobenzene derivative involved
three steps starting from L1 as shown in Scheme 1, with
each step proceeding smoothly in reasonable yield. The
synthesis of L1 was carried out by the well established
procedure involving double Schiff base condensation in
(8) Sheldrick, G. M. SADABS: Empirical absorption and correction
software. University of Go¨ttingen, Institu¨t fu¨r Anorganische Chemie
der Universita¨t, Tammanstrasse 4, D-3400 Go¨ttingen, Germany, 1998.
(9) Sheldrick, G. M. SHELXTL: Programs for crystal structure analysis,
Ver. 5.16; University of Go¨ttingen, Institu¨t fu¨r Anorganische Chemie
der Universita¨t: Tammanstrasse 4, D-3400 Go¨ttingen, Germany, 1998.
(10) Chia, P. S. K.; Lindoy, L. F.; Walker, G. W.; Everett, G. W. Pure
Appl. Chem. 1993, 65, 521.
(11) Kim, J.; Leong, A. J.; Lindoy, L. F.; Kim, J.; Nachbaur, J.; Nezhadali,
A.; Rounaghi, G.; Wei, G. J. Chem. Soc., Dalton Trans. 2000, 3453.
Inorganic Chemistry, Vol. 48, No. 7, 2009 2773

Seo et al.
Scheme 1. Synthesis of L1 and L2
Scheme 2. Synthesis of L3
methanol followed by sodium borohydride reduction. N-
protection by Boc of the two secondary amines of L1 to yield
1 was then carried out. The di-Boc-protected azo-macrocycle
2 was obtained via exclusive azo formation at the para-
position of pendant phenyl group of 1 by reaction with
4-nitroaniline under acidic conditions. Removal of the Boc
groups of 2 by treatment with trifluoroacetic acid gave the
desired azo-coupled derivative L2.
the triamide 5 followed by reduction (BH3 · SMe2/THF)
afforded L3 in 90% yield.
Membrane Transport. Competitive mixed-metal trans-
port experiments have been carried out using a bulk
chloroform membrane incorporating L1 and L3 as ionophores.
In each case the aqueous source phase contained equimolar
concentrations of the nitrate salts of Co(II), Ni(II), Cu(II),
Zn(II), Cd(II), Ag(I), and Pb(II) (each at 10-2 M) buffered
at pH 4.9. The aqueous receiving phase was buffered at pH
3.0. The conditions employed were identical to those used
previously for studies incorporating L4, L5, and L6 as the
ionophores.3c,11 The ionophore concentration in the organic
phase in each case was 1.00 × 10-3 M. Overall, the transport
fluxes for Cu(II) were found to fall in the order L4 (18.8 ×
10-6)11 > L6 (12.7 × 10-6)3c > L3 (10.2 × 10-6) > L5 (4.8
× 10-6)3c > L1 (1.8 × 10-6), where the values in parentheses
are the transport fluxes in units of mol/24 h. No evidence
The synthesis of L3 is summarized in Scheme 2. The
symmetric di-Boc protected derivative 3 was prepared as
described previously.6,12 Reaction of slightly more than 3
equiv of 3 with 1,3,5-benzenetricarbonyl trichloride in
acetonitrile in the presence of potassium carbonate afforded
the tri-linked, N-protected macrocyclic species 4 in 92%
yield. Deprotection (using trifluoroacetic acid) of 4 to give
(12) Smith, R. M.; Martell, A. E. Critical Stability Constants; Plenum: New
York, 1975; Vol. 2, amines.
2774 Inorganic Chemistry, Vol. 48, No. 7, 2009

Complexation of Cu(II) with N3O2-Donor Macrocyclic Rings
Figure 1. Comparison of the transport rate of Cu(II) for the macrocycles shown. The chloroform phase contained macrocycle at a concentration of 1.0 ×
10-3 M and hexadecanoic acid at 4.0 × 10-3 M (see text). The aqueous source phase was buffered at pH 4.9 and contained a mixture of Co(II), Ni(II),
Cu(II), Zn(II), Cd(II), Ag(I), and Pb(II) nitrates, each at 1.0 × 10-2 M; (a) the effect of the substituents on the monomeric macrocycles and (b) transport
compared on a per-macrocyclic cavity basis on passing from the monomeric (L5), bis-macrocycle (L6) to the tris-macrocycle (L3).
Figure 2. (a) UV-vis titration of L3 (4.0 × 10-3 M) with Cu(II) nitrate in DMSO (inset: plot of the titration curve) and (b) Job plot for the same complexation
system ([L3] ) 2.0 × 10-3 M) showing 2:1 (M/L) stoichiometry.
for transport of any of the other six metal ions present in
the respective source phases was observed under the condi-
tions employed, and thus, sole selectivity for Cu(II) was
achieved in each case.
As discussed previously3c transport efficiency is influenced
by both the strength of the ionophore metal binding and the
lipophilicity of the resulting complex in the organic phase.
The benzylated derivative L5 is associated with considerably
lower transport efficiency toward copper than found for the
parent macrocycle L4 (Figure 1a). In this case, the transport
behavior follows the respective log K data for Cu(II)
complexation3c even though the overall lipophilicity of the
system is expected to be higher for L5. While no stability
data are available for complexation of L1, the presence of a
phenyl substituent will almost certainly further reduce the
stability of the corresponding copper complex because of
the lower basicity of the substituted anilino amine12 and
perhaps also because of steric influences. In keeping with
this, the transport of Cu(II) by L1 was observed to be
significantly lower than occurs for L5.
Figure 3. Crystal structure of L1 ·HNO3 ·HPF6 ·CH3OH·H2O. Hydrogen
atoms (except NH protons), non-coordinating anions and solvents are
omitted.
L5 and its di-linked analogue (L6) under identical conditions.
On this basis, transport efficiency toward Cu(II) is reduced
somewhat for the trilinked species (Figure 1b) relative to
the other two ring systems. As discussed more fully later,
this may reflect the tendency of L3 to form a 2:1 (M/L) rather
than a 3:1 complex with Cu(II); the latter is based on the
results from spectrophotometric studies aimed at probing the
solution stoichiometry of this system (but it needs to be noted
that they were obtained under somewhat different conditions
It is instructive to compare the results for the tri-linked
systems L3 on a “per macrocyclic hole” basis with those
obtained previously3c for the benzylated mono-ring derivative
Inorganic Chemistry, Vol. 48, No. 7, 2009 2775

Seo et al.
DMSO-d6 (v/v 1:1) a clear 3:1 (Ag+/L3) complex was
indicated (Supporting Information, Figure S9).
X-ray Studies of Metal-Free Systems. A mixed anion
crystal of L1 · HNO3 · HPF6 suitable for X-ray analysis was
obtained by slow evaporation of a dichloromethane solution
of L1 containing several drops of both HNO3 and HPF6. The
structure of the product (Figure 3) shows that the macrocycle
adopts a conformation in which both oxygen donors
are directed into the macrocyclic cavity, with the bis-
methylene groups between the nitrogen and oxygen donors
adopting gauche arrangements. The N-phenyl pendant is
orientated nearly perpendicular to the ring cavity and shows
offset face-to-face π stacking with one of the ring benzo
groups.
The X-ray structure of the di-Boc protected intermediate
1 was also obtained and shows the presence of two
independent molecules in the unit cell (Supporting Informa-
tion, Figure S5). Both molecules correspond to the con-
nectivity predicted from the physical measurements and, not
unexpectedly, show that the macrocyclic ring conformation
in each structure differs considerably from that found for
protonated L1, with the three tertiary nitrogen donors
orientated exo to the cavity in each case.
In addition, an X-ray structure analysis was undertaken
using poor quality red crystals of L2 · 2HNO3 (Supporting
Information, Figure S6). The resulting determination was not
of high quality but was adequate to confirm the expected
atom connectivity and show that this compound also crystal-
lizes in two crystallographically independent forms, each with
similar configurations, in an antiparallel arrangement. Evi-
dence for intermolecular π-π stacking between adjacent
structures via their benzo-aza groups is present.
Dye-Attached Macrocycle L2 - Solution and Solid
State Studies. A number of chromoionophoric systems based
on metal-ion induced charge-transfer phenomena have now
been reported, including systems employing macrocyclic
rings as the metal-binding site.14 We now report a further
study of this type employing the azo-macrocyclic derivative
L2. It is noted that the dye-attached system L2 has a similar
macrocyclic metal coordination domain to that in L1, and
hence parallel metal binding behavior is expected for both
these ligands. The UV-vis spectrum of L2 in acetonitrile is
characterized by an intense band (ε ) 23000 M-1 cm-1)
centered at 495 nm, giving rise to a red solution. The
interaction of this ligand with Co(II), Ni(II), Cu(II), Zn(II),
Cd(II), Hg(II), Pb(II), and Ag(I) was investigated by
monitoring changes in the UV-vis spectra of L2 in aceto-
Figure 4. Changes in the UV-vis spectrum of L2 on addition of the metal
nitrates in acetonitrile (ligand concentration, 5.0 × 10-5 M; added metal
ion, 3.0 equiv).
to those employed for the membrane transport runs).
Nevertheless, from both electrostatic and statistical consid-
erations it is expected that the affinity of L3 for Cu(II) will
be reduced in a stepwise fashion as successive copper ions
bind. The situation is further complicated by the observation
that, at least in the solid state, there is X-ray evidence that
the ether oxygen donors in single-ring macrocycles of the
present type tend not to coordinate to Cu(II).13
Complexation of Tri-Linked Macrocycle L3 to
Cu(II). In view of the Cu(II) selectivity observed in the
membrane transport experiments, the solution complexation
of this ion was investigated further. The interaction of L3
with Cu(II) nitrate in DMSO was examined by means of a
UV-vis titration. Incremental addition of L3 to Cu(II) nitrate
in this solvent results in a marked increase in absorbance
(maximum ) 688.3 nm) up to 2.0 equiv, indicating clear
formation of a 2:1 (M/L) species (see inset in Figure 2a).
On further addition of ligand the absorption shows little
increase at this wavelength (although the λmax then shifts
toward longer wavelengths, most likely indicating the gradual
conversion of the 2:1 species to a new species that had not
completely formed at a ligand/metal ratio of 6.5:1). A Job
plot for the interaction of L3 with Cu(II) nitrate (Figure 2b)
yields an absorption maximum that also approximates the
formation of a 2:1 (M/L) species under the conditions
employed. In contrast to the above behavior, when a 1H NMR
titration of L3 with silver(I) nitrate was carried out in CDCl3/
(14) (a) Misumi, S.; Kaneda, T. J. Inclusion Phenom. Mol. Recognit. Chem.
1989, 7, 83. (b) Lo¨hr, H.-G.; Vo¨gtle, G. Acc. Chem. Res. 1985, 18,
65. (c) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S. Chem. ReV. 1991,
91, 1721. (d) Badaoui, F. Z.; Bourson, J. Anal. Chim. Acta 1995, 302,
341. (e) Kim, J. S.; Shon, O. J.; Lee, J. K.; Lee, S. H.; Kim, J. Y.;
Park, K.-M.; Lee, S. S. J. Org. Chem. 2002, 67, 1372. (f) Descalzo,
A. B.; Mart´ınez-Ma´n˜ez, R.; Radeglia, R.; Rurack, K.; Soto, J. J. Am.
Chem. Soc. 2003, 125, 3418. (g) Boiocchi, M.; Fabbrizzi, L.; Licchelli,
M.; Sacchi, D.; Va´zquez, M.; Zampa, C. Chem. Commun. 2003, 1812.
(h) Wager-Wysiecka, E.; Luboch, E.; Kowalczyk, M.; Biernat, J. F.
Tetrahedron 2003, 59, 4415. (i) Lee, S. J.; Jung, J. H.; Seo, J.; Yoon,
I.; Park, K.-M.; Lindoy, L. F.; Lee, S. S. Org. Lett. 2006, 8, 1641. (j)
Lee, H. G.; Lee, J.-E.; Choi, K. S. Inorg. Chem. Commun. 2006, 9,
582.
(13) (a) Adam, K. R.; Lindoy, L. F.; Lip, H. C.; Rea, J. H.; Skelton, B. W.;
White, A. H. J. Chem. Soc., Dalton Trans. 1981, 74. (b) Price, J. R.;
Fainerman-Melnikova, M.; Fenton, R. R.; Gloe, K.; Lindoy, L. F.;
Rambusch, T.; Skelton, W.; Turner, P.; White, A. H.; Wichmann, K.
Dalton Trans. 2004, 3715. (c) Gasperov, V.; Galbraith, S. G.; Lindoy,
L. F.; Rumbel, B. R.; Skelton, B. W.; Tasker, P. A.; White, A. H.
Dalton Trans. 2005, 139.
2776 Inorganic Chemistry, Vol. 48, No. 7, 2009

Complexation of Cu(II) with N3O2-Donor Macrocyclic Rings
Figure 5. UV-vis titrations of L2 (5.0 × 10-5 M) with Cu(II) nitrate (0-2.5 equiv) in DMSO: (a) spectral changes and (b) titration curves.
Table 4. Selected Bond Lengths (Å), Bond Angles (deg), and Torsion
Angles (deg) for 7
Cu1-N1
2.031(5)
1.921(4)
94.5(2)
173.03(19)
92.2(2)
Cu1-N3
2.027(5)
1.918(4)
95.56(19)
169.41(19)
-57.0(7)
Cu1-O9
Cu1-O9A
N3-Cu1-N1
O9a-Cu1-N1
O9a-Cu1-N3
N2-C11-C12-N3
O9-Cu1-N1
O9-Cu1-N3
N1-C9-C10-N2
-53.5(9)
a Symmetry operation: -x + 1, -y + 2, -z.
In an attempt to probe the origins of the above observed
spectrophotometric changes, the solution behavior of selected
complexes of L2 was investigated in further detail. In
particular, spectrophotometric titration of L2 with Cu(II)
nitrate (Figure 5a) was carried out in DMSO; in this case
the ligand absorption at 465 nm gradually decreased while
the complex absorption centered at 321 nm increased giving
rise to a corresponding isosbestic point at 390 nm. According
to the titration curves in Figure 5b, both for the ligand (465
nm) and complex (321 nm) absorptions, the spectral features
are consistent with a 1:1 binding ratio between Cu(II) and
ligand. The Job plots for L2 complexation with Cu(II) and
Ni(II) also indicated 1:1 stoichiometries (Supporting Infor-
mation, Figure S7).
While investigating the metal-ion complexation and metal-
induced color changes for L2 discussed above, a spectral
dependence on the anion employed was observed in indi-
vidual cases. To probe this effect further, changes in the
UV-vis spectra of L2 were recorded on the addition of Cu(II)
as its chloride, nitrate, perchlorate, acetate, and sulfate salts.
In each case a blue shift (and corresponding color change)
was observed (Figure 6). These anion-induced shifts to lower
Figure 6. Changes in the UV-vis spectrum of L2 on addition of the Cu(II)
salts in acetonitrile (ligand concentration, 5.0 × 10-5 M; added metal ion,
3.0 equiv).
Table 3. Selected Bond Lengths (Å), Bond Angles (deg), and Torsion
Angles (deg) for 6
Cu1-N1
2.007(5)
2.007(5)
86.4(2)
150.1(2)
177.3(2)
51.9(7)
Cu1-N2
2.081(5)
1.972(4)
86.3(2)
96.11(19)
92.0(2)
Cu1-N3
Cu1-O7
-
-
wavelength fall in the order NO3 , ClO4 > Cl-, OAc-
>
N1-Cu1-N2
N3-Cu1-N1
O7-Cu1-N2
N1-C9-C10-N2
N3-Cu1-N2
O7-Cu1-N1
O7-Cu1-N3
N2-C11-C12-N3
SO42-. While it is noted that this order shows correlation
with the Hofmeister series of relative anion lipophilicities,15
it is difficult to offer a convincing rationale for such a trend
in the absence of detailed information concerning the
respective solution structures involved. For example, the
above sequence does not follow the expected relative binding
strengths of these anions for Cu(II); thus the relatively weak
coordinating ClO4- has a larger effect than the more strongly
53.5(7)
nitrile on addition of each of these ions as their metal nitrate
salts. The spectrophotometric changes are shown in Figure
4; in each case there is a hypochromic shift14 in the
absorption maxima (λmax) upon metal complexation and a
concurrent reduction in molar absorptivity; the largest λmax
shift (to 321 nm; ∆λmax ) 174 nm) is induced by Cu(II)
resulting in a solution color change from red to pale-yellow.
(15) (a) Hofmeister, F. Arch. Exp. Pathol. Pharmakol. 1887, 24, 247. (b)
Morf, W. E.; Simon, W. HelV. Chim. Acta 1986, 68, 1120.
Inorganic Chemistry, Vol. 48, No. 7, 2009 2777

Seo et al.
Figure 7. Endo-coordinated structure of 6, [Cu(L2)NO3]NO3 ·CH2Cl2 (pale-yellow crystals). Hydrogen atoms, non-coordinating anions and solvents are
omitted.
Figure 8. Exo-coordinated dimeric structure of 7, [{Cu(L2)}2(µ-OH)2](ClO4)2 ·2CH2Cl2 ·2H2O (dark-red crystals). Hydrogen atoms, non-coordinating anions,
and solvents are omitted.
binding Cl- anion. Clearly, the situation appears more
complicated than simply reflecting anion coordination to the
Cu(II) center. Nevertheless, a related anion influence has been
noted previously for a N-chromogenic calix[4]azacrown
system.14e
bound to three exo-oriented secondary amine nitrogens from
one macrocyclic ring and the two bridging OH- groups; both
macrocyclic rings adopt a bent configuration. As found for the
Cu(II) complexes of other related O2N3-donor macrocycles of
the present type, the macrocyclic oxygen donors of each
macrocycle in the dimeric arrangement do not coordinate.13a,c,17
The tertiary (anilino) amine N2 occupies an axial position with
respect to the square-plane to yield an overall distorted square-
pyramidal coordination geometry. It is noteworthy that the
Cu1-N2, (2.519(5) Å) bond distance in 7 is much longer than
occurs for the corresponding bond in 6 [Cu1-N2, 2.081(5) Å].
This weaker coordination in the fifth (axial) position [Cu1-N2,
2.519(5)] in the latter case can in part be rationalized in terms
of the dominance of the strongly bound rhomboidal Cu-(OH)2-
Cu core on copper complexation resulting in weaker Cu1-N2
bond formation. In parallel with this, only a very minor color
change of the solid state complex is observed relative to that
of the uncomplexed ligand. These results demonstrate how
variation of the macrocyclic ring coordination mode, which
corresponds to endo coordination in 6 but exo in 7, markedly
influences the strength of binding of the tertiary nitrogen
containing the pendent azo function and which, in turn, is
reflected by the respective colors of the individual complexes.
Thus clearly the above results demonstrate that the color of the
pendent phenylaza chromophore is markedly dependent on the
strength of metal binding of the attached nitrogen donor.
Nevertheless, it is important to note that the similarity of the
solution spectra of the nitrate and perchlorate species (Figure
6) relative to the different colors of the solid state complexes
strongly suggests, at least in the case of the perchlorate species,
that the solid state and solution structures are different under
the conditions employed, perhaps reflecting the relatively
X-ray structures of the Cu(II) nitrate (6) and Cu(II)
perchlorate (7) complexes of L2 have been obtained. In the
case of complex 6, the X-ray analysis confirmed a 1:1 species
of type [Cu(L2)NO3]NO3 · CH2Cl2 (Figure 7 and Table 3) in
which the Cu(II) ion has a pseudo six-coordinate environ-
ment, with the copper being bound to the three nitrogen
donors of L2 and an oxygen from a bound monodentate
nitrato ligand; two ether oxygens from the macrocyclic ligand
also interact weakly with the copper: Cu1-O1 3.048,
Cu1-O2 2.912 Å. The second nitrate anion is not coordi-
nated (Cu1 · · · O10 4.333 Å, not shown). The presence of
the Cu1-N2 bond [2.081(5) Å] involving the tertiary
nitrogen with attached azo-substituent is undoubtedly im-
portant in inducing the observed color change from red in
the free ligand to pale-yellow for the present complex; in
this category of chromoionophore, it is the net electronic
charge transfer from the donor group (tertiary nitrogen) to
the acceptor group (the benzo-aza chromophore) that will
influence the color of the chromophore.14
Next, the reaction of L2 with Cu(II) perchlorate yielded dark-
red crystals of 7 whose X-ray analysis confirmed a dimeric
structure of type [{Cu(L2)}2(µ-OH)2](ClO4)2 ·2CH2Cl2 ·
2H2O (Figure 8 and Table 4). Since there is an imposed
inversion at the center of the two copper atoms, the asymmetric
unit contains one molecule of L2, one copper atom, one
hydroxide ion, and one perchlorate ion (not shown).16 The
structure contains a rhomboidal Cu-(OH)2-Cu core connecting
two bound macrocycles. Each Cu(II) is five-coordinate being
(16) Kuzelka, J.; Mukhopadhyay, S.; Springler, B.; Lippard, S. J. Inorg.
Chem. 2004, 43, 1751.
(17) Baldwin, D. S.; Duckworth, P. A.; Leong, A. J.; Lindoy, L. F.;
McPartlin, M.; Tasker, P. A. J. Chem. Soc., Dalton Trans. 1993, 1013.
2778 Inorganic Chemistry, Vol. 48, No. 7, 2009

Complexation of Cu(II) with N3O2-Donor Macrocyclic Rings
stronger affinity of nitrate over perchlorate for the copper(II)
center, especially with respect to the solid state.
transition and post transition metal ions present in the
aqueous phase. When compared on an “available macrocyclic
cavity” basis, the linking of macrocyclic rings resulted in
decreased metal ion extraction efficiency relative to related
single-ring ligand systems.
Conclusion
In this report, the complexation of Cu(II) with selected
N3O2-donor macrocyclic rings has been explored. One such
system, L2, incorporating a pendant benzo-diazonium center
has been demonstrated to undergo metal-dependent hypo-
chromic shifts in its electronic spectrum, with strongly bound
copper inducing the largest shift. X-ray studies have assisted
in defining the structure-function relationship underlying
the observed color change of red to yellow in this case. In
seven-metal competitive transport experiments across bulk
chloroform membranes, L1 and L3 were demonstrated to
yield sole selectivity for Cu(II) over the remaining six
Acknowledgment. S.S.L. thanks the financial support
from the Korea Research Foundation (2007-314-C00157).
L.F.L. thanks the Australian Research Council for support.
Supporting Information Available: X-ray crystallographic files
in CIF format and NMR and mass data. This material is available
free of charge via the Internet at http://pubs.acs.org.
IC801265Y
Inorganic Chemistry, Vol. 48, No. 7, 2009 2779