Examination of cobalt, nickel, copper and zinc(II) complex geometry and binding affinity in aqueous media using simple pyridylsulfonamide ligands

Article abstract of DOI:10.1039/b206279h

The sixteen neutral ML₂ complexes of Co, Ni, Cu and Zn(II) with the p-toluenesulfonamide and trifluoromethylsulfonamide derivatives of 2-aminomethylpyridine (L¹, L²) and its 6-Me homologue (L³, L⁴) have been characterised by low temperature X-ray crystallography (100-120 K). Complexes of Co and Zn invariantly adopted a distorted tetrahedral geometry and whilst Cu(II) complexes of L², L³ and L⁴ also took up a distorted tetrahedral geometry, that with L¹ was square planar. A database survey of the distortion from limiting tetrahedral/square planar geometry has been carried out, aided by a simple geometric analysis. The trifluoromethylsulfonamide ligands (L² and L³) were less basic, e.g. log K₁ 7.51(3) for L² vs. 12.23(6) for L¹ (80% MeOH/H₂O) and afforded a weaker ligand field, exemplified by the position of the visible d-d transition in Cu(II) complexes and the ease of reduction of the Cu(II) centre: E_1/2 values (MeCN vs. Ag/AgCl) are -430, -137, +55 and -240 mV for Cu(L¹)₂, Cu(L²)₂, Cu(L³)₂ and Cu(L⁴)₂. Ligand protonation and stepwise formation constants have been measured for L¹-L³ and derived species distribution diagrams reveal that for complexes with L² and L³, the predominant species present at pH 7.4 when zinc was in the nanomolar range was ZnL₂.

Full text of DOI:10.1039/b206279h

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Examination of cobalt, nickel, copper and zinc(II) complex geometry
and binding affinity in aqueous media using simple pyridylsulfonamide
ligandsy
Aileen Congreve, Ritu Kataky, Mark Knell, David Parker,* Horst Puschmann,
Kanthi Senanayake and Lisa Wylie
Department of Chemistry, University of Durham, South Road, Durham, UK DH1 3LE.
E-mail: david.parker@dur.ac.uk
Received (in Montpellier, France) 27th June 2002, Accepted 16th September 2002
First published as an Advance Article on the web 8th November 2002
The sixteen neutral ML2 complexes of Co, Ni, Cu and Zn(II) with the p-toluenesulfonamide and
trifluoromethylsulfonamide derivatives of 2-aminomethylpyridine (L1, L2) and its 6-Me homologue (L3, L4)
have been characterised by low temperature X-ray crystallography (100–120 K). Complexes of Co and Zn
invariantly adopted a distorted tetrahedral geometry and whilst Cu(II) complexes of L2, L3 and L4 also took up
a distorted tetrahedral geometry, that with L1 was square planar. A database survey of the distortion from
limiting tetrahedral/square planar geometry has been carried out, aided by a simple geometric analysis. The
trifluoromethylsulfonamide ligands (L2 and L3) were less basic, e.g. log K1 7.51(3) for L2 vs. 12.23(6) for
L1 (80% MeOH/H2O) and afforded a weaker ligand field, exemplified by the position of the visible d–d
1
transition in Cu(II) complexes and the ease of reduction of the Cu(II) centre: E values (MeCN vs. Ag/AgCl) are
2
ꢀ430, ꢀ137, +55 and ꢀ240 mV for Cu(L1)2 , Cu(L2)2 , Cu(L3)2 and Cu(L4)2 . Ligand protonation and stepwise
formation constants have been measured for L1–L3 and derived species distribution diagrams reveal that for
complexes with L2 and L3, the predominant species present at pH 7.4 when zinc was in the nanomolar range
was ZnL2 .
The binding of the Zn ion in aqueous media has attracted
attention recently in three different areas of chemistry. Firstly,
We set out to compare the co-ordination chemistry of the
series of simple pyridyl-sulfonamide ligands L1–L4. The intro-
duction of the a-methyl substituent was expected to sterically
inhibit formation of a square planar ML2 complex. The differ-
ing sulfonamide substituents (CF3 vs. tosyl) alter the electron
donating ability of the sulfonamide nitrogen. Furthermore,
the lower protonation constants of trifluoromethylsulfon-
amides (ca. 7.5) vs. arylsulfonamides (ca. 12) was expected to
inhibit protonation of the ML and ML2 complexes and
enhance complex stability at ambient pH. Our aim was to
identify a model ligand system from this series capable of
forming a well-defined neutral complex with zinc under ambi-
ent pH conditions, when the Zn concentration is of the order
of 100–0.1 nM. Such a system could then form the basis of
new luminescent or MR probes.
ˆ
stimulated by the need to probe the biological role of kineti-
cally labile zinc1 in synaptic neurotransmission2 and excito-
toxicity,3,4 a range of luminescent zinc probes has been
devised in which a chromophore or fluorophore is integrated
into the ligand structure.5–11 Such ligands need to bind the zinc
ion with high affinity in the physiological pH range and exam-
ples have been reported with micromolar,11 nanomolar4,5,8 or
sub-picomolar12 apparent dissociation constants. Secondly,
more lipophilic zinc binding ligands have been sought that
allow the selective extraction of the zinc ion from acidic aqu-
eous media into a non-polar organic phase. Examples have
included aza-carboxylates and phosphinates13,14 in which a tet-
rahedral binding geometry is imposed on the zinc by ligand
design. Finally, as a consequence of the pivotal role of zinc
in gene transcription and metalloenzyme function,1,15 a great
deal of work has been directed at devising zinc-binding ligands
that inhibit enzyme function and hence may allow develop-
ment of therapeutic agents. In just one example, inhibition
of carbonic anhydrase activity has been observed with a series
of sulfonamide ligands which bind to zinc via nitrogen.16 Thus,
various thiadiazole sulfonamides17,18 are active inhibitors, as is
the simple example trifluoromethylsulfonamide.19 Such work
has led to the parallel development of sulfonamide probes
for the fluorescence anisotropy detection of zinc with a carbo-
nic-anhydrase-based biosensor.20
y Electronic supplementary information (ESI) available: experimental
details for [M(L2)2], [M(L3)2] and [M(L4)2] (M ¼ Zn, Cu, Ni, Co);
species distribution plots. See http://www.rsc.org/suppdata/nj/b2/
b206279h/
98
New J. Chem., 2003, 27, 98–106
DOI: 10.1039/b206279h
This journal is # The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2003

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pH glass electrode, under an argon atmosphere. To solutions
of the ligand (typically 2 mM) in tetramethylammonium
nitrate solution (0.1 M, 80% aqueous methanol) was added a
fixed volume of 1.0 M HCl solution (Analar) to give the hydro-
chloride salt. The titrant was degassed sodium hydroxide solu-
tion (0.05 M, 80% MeOH/water) and the burette function
(volume increments, total volume delivered and the time inter-
val allowed for equilibration between each reading) was com-
puter controlled allowing smaller increments of titrant to be
added towards the end-point. Titration data for protonation
equilibria were collected between pH 3 and 11, typically
acquiring 80 data points, used in the subsequent analysis. In
measuring the metal complex formation constants, separate
titrations were carried out at 1:1 and 1:2 metal/ligand ratios,
and the pH range examined was from 3 to ca. 7.5, at which
point formation of the metal hydroxide was visually discerned.
Data were analysed using HYPERQUAD23 and corrections to
pKw were applied to allow for solvent composition.24 Each of
the metal salt hydrolysis constants used in the data analysis
was taken from the IUPAC Stability Constants database Ver-
sion 5.12, published by IUPAC and Academic Software, 2000.
Values of protonation and metal complex formation constants,
determined by iterative fitting in Hyperquad, refer to the mean
of three independent titrations and gave satisfactory statistical
parameters (s ca. 2.5 to 3.5 and w2 of the order of 8 to 12).
Single crystal X-ray diffraction experiments were carried out
using SMART CCD area detectors and graphite-monochro-
mated Mo-Ka radiation. The structures were solved by direct
methods and refined against F2 of all data, using SHELXTL
programs.25 A summary of cell and refinement data is given
in Table 1.
Experimental
Solvents were dried from an appropriate drying agent where
required using standard procedures. Water was purified by
the ‘‘PuriteSTILL plus’’ system. Thin layer chromatography
was carried out using fluorescent (254 nm) silica plates (Merck
Art 5554). Preparative column chromatography was carried
out using silica (Merck silica gel 60, 230–400 mesh). Mass spec-
tra (ES MS) were recorded using a VG II Platform spectro-
meter (Fisons Instruments) with methanol as the carrier
solvent. FAB spectra were recorded by the EPSRC Mass Spec-
trometry Service at the University of Wales at Swansea. NMR
spectra were recorded on a Varian Unity 300 spectrometer at
299.91 MHz (1H) and 75.41 MHz (13C) or a Varian Mercury
200 spectrometer at 199.99 MHz (1H), 50.29 MHz (13C) or
188.18 MHz (19F) or a Bruker AC250 spectrometer at 62.90
MHz (13C). Chemical shifts are quoted with reference to the
residue residual protonated solvent and are given in ppm with
coupling constants in Hz. Infra-red spectra were recorded on a
Perkin-Elmer FT-IR 1720X spectrometer with GRAMS Ana-
lyst operating software. Ultraviolet absorbance spectra of the
complexes (1 mM) were recorded in acetonitrile on a Unicam
UV2 spectrometer operating with Vision software. Melting
points were determined on a Reichert-Koefler block melting
point apparatus and are uncorrected. Cyclic voltammetry of
the complexes (0.001 M) was carried out in a background elec-
trolyte of tetrabutylammonium perchlorate, TBAP (0.01 M),
in acetonitrile controlled with an EG&G PARC Model 273
potentiostat. Computer control and data storage were
achieved using EG&G PARC Model 270 Research Electro-
chemistry software. The auxiliary electrode was made of plati-
num foil, (area 1 cm2), connected to a copper wire mounted
in a glass body. The working electrode was made of glassy
carbon, purchased from BAS. The reference electrode was a
non-aqueous silver/silver chloride electrode, self-assembly
kit, purchased from BAS. The electrodes were mounted in a
circular Teflon cap and placed in a cylindrical cell (diameter
20 mm, length 65 mm), which was filled with 10 ml of the
desired solution and purged with argon. The cell assembly
was placed inside a Faraday cage to eliminate stray field
interference.
CCDC reference numbers 186296–186312. See http://
www.rsc.org/suppdata/nj/b2/b206279h/ for crystallographic
data in CIF or other electronic format.
Ligand synthesis
6-Methylpyridine-2-aldoxime was prepared as described in the
literature.26
2-(p-Toluenesulfonylaminomethyl)pyridine. L1. To a stirred
solution of p-toluenesulfonyl chloride (3.43 g, 0.018 mmol) in
pyridine (10 ml) cooled to ꢀ10 ꢁC was slowly added (2-amino-
methyl)pyridine (2.00 g, 0.018 mmol) in pyridine (5 ml). The
resulting reaction mixture was stirred at ꢀ10 ꢁC for 3 hours
and was held at 5 ꢁC overnight. The reaction mixture was
Potentiometric analyses were carried out using an apparatus
described previously.21,22 The stepwise protonation and metal
formation constants were evaluated by analysis of data
acquired using a computer-controlled alkalimetric titration at
298 K(water-jacketed titration cell), using a calibrated Corning
Table 1 Unit cell and crystallographic data for Zn, Cu, Ni and Co complexes of L1–L4
Space
group
3
Volume/A System
a/ꢁ
b/ꢁ
g/ꢁ
Z
m/mmꢀ1 T/K Rint (%) Rw (%) R (%)
˚
Complex a/A
˚
b/A
˚
c/A
˚
L1
26.831(4) 5.958(1) 16.576(2) 90
99.967(3) 90
123.815(3) 90
2610.1(6)
5543.8(9)
Monoclinic
Monoclinic
C2/c
C2/c
¯
P1
8
8
2
2
8
2
4
4
8
2
8
2
8
8
2
2
8
0.249
1.081
1.529
1.419
1.057
1.11
110
100
100
105
120
100
100
105
3.05
8.30
2.06
2.56
2.48
4.14
5.60
5.26
9.20
10.94
6.64
8.35
6.65
8.99
36.05
8.17
18.56
20.24
15.38
9.33
11.8
9.00
9.47
9.25
11.7
3.84
4.83
2.72
2.99
2.69
3.31
14.10
3.45
7.32
6.99
5.89
3.36
4.35
3.73
3.69
3.59
3.82
Zn(L1)2 30.505(2) 8.010(1) 27.309(1) 90
Zn(L2)2
Zn(L3)2
8.296(1) 9.721(1) 13.035(1) 93.193(4) 95.817(4) 107.145(4) 995.27(17) Triclinic
7.973(1) 9.432(1) 14.746(1) 81.984(1) 81.130(1) 81.744(10) 1076.38(5) Triclinic
¯
P1
Zn(L4)2 28.129(1) 12.033(1) 16.726(1) 90
91.701(1) 90
99.176(4) 90
5658.54(17) Monoclinic
1219.56(15) Monoclinic
I2/a
P21/c
Pc
Cu(L1)2
Cu(L2)2
7.293(1) 17.089(1) 9.912(7) 90
9.04(5) 10.29(5) 20.70(5) 90
b
91.71(5)
90
1923(10)
2138.19(10) Monoclinic
5680.9(3) Monoclinic
1213.25(8) Monoclinic
Monoclinic
1.442
1.301
0.96
Cu(L3)2 10.450(1) 14.023(1) 15.197(1) 90
Cu(L4)2 26.673(1) 14.539(1) 14.980(1) 90
106.221(1) 90
102.051(1) 90
99.139(1) 90
P21/c
C2/c
P21/c
110 15.03
Ni(L1)2
Ni(L2)2
Ni(L3)2
Ni(L4)2
7.335(1) 17.058(1) 9.822(1) 90
10.458(1) 16.052(2) 29.546(4) 90
7.936(1) 9.450(1) 14.716(1) 80.519(0) 80.609(1) 81.548(1) 1065.77(6) Triclinic
1.015
1.038
1.191
0.881
0.838
1.158
1.076
0.790
120
100
100
120
100
110
100
110
5.46
4.21
2.42
4.23
5.23
3.19
2.90
5.26
90
90
4960.1(11) Orthorhombic Pbca
¯
P1
32.016(1) 11.932(4) 16.782(8) 90
118.86(2) 90
121.349(5) 90
5615(4)
5345.2(17) Monoclinic
Triclinic
Monoclinic
C2/c
C2/c
¯
P1
¯
P1
C2/c
Co(L1)2 29.967(6) 7.977(1) 26.183(5) 90
Co(L2)2
Co(L3)2
8.270(1) 9.801(1) 13.050(1) 93.015(1) 95.599(1) 108.418(1) 994.84(6)
8.000(1) 9.372(1) 14.736(1) 82.625(1) 81.527(1) 81.726(1) 1074.89(6) Triclinic
119.72(1) 90
Co(L4)2 32.449(1) 12.065(1) 16.738(1) 90
5694.0(3)
Monoclinic
a
Remaining solvent electron density was refined to 0.13 molecules of water. b These crystals were badly twinned, despite appearing perfectly well formed. Satisfactory
anisotropic refinement was not possible.
New J. Chem., 2003, 27, 98–106
99

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poured onto crushed ice resulting in the precipitation of a yel-
low solid, which was removed by filtration and washed with
water. The precipitate was dissolved in dichloromethane, dried
(NaSO4) and the solvent evaporated yielding pale yellow
crystals (2.12 g, 45%), mp 76–77 ꢁC; 1H NMR (200 MHz,
CD3OD): dH 2.40 (s, 3H, CH3), 4.15 (s, 2H, CH2), 7.22–7.45
(4H, m, H3, H5, H30, H50), 7.69 (3H, m, H4, H40, H60), 8.37
(1H, d, J 4.4, H6); 13C NMR (50.29 MHz, CDCl3): dc 21.15
(Me), 47.47 (CH2), 122.00 (C3 or C5), 122.32 (C3 or C5),
126.75 (C30 + C50), 129.29 (C20 + C60), 136.72 (C4), 142.92
(C40), 148.59 (C2), 155.34 (C10); m/z ES+: 546.7 (100%,
2M + Na), 284.5 (85%, M + Na); nmax (KBr)/cmꢀ1 3250 (n
NH), 1599 (n py), 1574 (n py), 1441 (n py), 1385 (d NH),
1329 (na SO2), 1165 (ns SO2), 1111 (d CH), 1089 (d CH),
1007, 901 (n N–S), 763 (d py), 662 (g NH), 543 (d SO2); Found:
C, 57.12; H, 5.58; N, 10.25. C13H14N2O2S.0.5H2O requires C,
57.54; H, 5.57; N, 10.32%.
yield a yellow oil which was crystallised from ethanol and
water (1%) to form a white solid (0.53 g, 53%); mp 83–84 ꢁC;
1H NMR (200 MHz, CDCl3): dH 2.38 (3H, s, CH3), 2.46
(3H, s, CH3), 4.18 (2H, d, J 5.2, CH2), 5.92 (1H, s, NH),
6.97 (2H, t, J 8.4, H3, H5), 7.22 (2H, d, J 7.8, H30, H50),
7.47 (1H, t, J 7.8, H4), 7.72 (2H, d, J 6.6, H20, H50); 13C
NMR (50.3 MHz, CDCl3): dc 21.37 (Me), 24.02 (Me), 47.35
(CH2), 118.74 (C40), 121.94 (C10), 127.08 (C30 + C50), 129.45
(C20 + C60), 136.63 (q, C6), 136.96 (C2), 143.17 (C3), 154.09
(C4), 157.68 (C2); m/z ES+: 574.7 (25%, 2M + Na+), 298.7
(100%, M + Na+); nmax (KBr)/cmꢀ1 1599 (n py), 1458 (n py),
1325 (na SO2), 1160 (ns SO2), 1090 (d CH), 816, 662 (g NH),
551 (d SO2). Found: C, 60.57; H, 5.77; N, 10.39. C13H14N2O2S
requires C, 60.85; H, 5.84; N, 10.14%.
2-(Trifluoromethanesulfonylaminomethyl)-6-methylpyridine
L3. Under anhydrous conditions in an argon atmosphere, a
cooled solution of 2-aminomethyl-6-methylpyridine (0.45 g,
3.69 mmol) in anhydrous pyridine (2.4 ml) was added slowly
to a stirred solution of trifluoromethanesulfonyl chloride
(0.62 g, 3.69 mmol) in anhydrous pyridine (6.6 ml), which
had been cooled to ꢀ40 ꢁC. The resulting yellow solution
was stirred at ꢃꢀ40 ꢁC for two hours then kept at ꢀ18 ꢁC
overnight before being added slowly to crushed ice. The ice
was stirred and allowed to melt resulting in the formation of
a green precipitate, which was filtered off under suction. This
precipitate was dissolved in dichloromethane (10 ml), washed
with water (2 ꢂ 10 ml), the combined organic phase was dried
(MgSO4), filtered and the solution evaporated under reduced
pressure to yield a yellow oil. The aqueous phase was extracted
with dichloromethane (3 ꢂ 50 ml), the combined organic
extracts were dried (MgSO4), filtered and evaporated under
reduced pressure to yield a yellow oil which was purified by
flash column chromatography (SiO2 , 1:1 ethyl acetate:hexane).
Clear crystals formed on the evaporation of the reduced elut-
2-(Trifluoromethylsulfonylaminomethyl)pyridine L2. Under
anhydrous conditions in an argon atmosphere, a solution of
(2-aminomethyl)pyridine (0.64 g, 5.93 mmol) in anhydrous
pyridine (5 ml) at ꢀ40 ꢁC was added dropwise, over 10 min-
utes, to a stirred solution of trifluoromethanesulfonyl chloride
(1.0 g, 5.93 mmol) in pyridine (10 ml) at ꢀ40 ꢁC. The resulting
bright yellow reaction mixture was stirred at ꢀ40 ꢁC for 2
hours and kept at 5 ꢁC overnight. The mixture was poured
slowly onto crushed ice and stirred. The precipitate that
formed was separated by filtration and washed with water.
This precipitate was dissolved in dichloromethane (50 ml),
washed with water (2 ꢂ 25 ml) and the organic phase was dried
(MgSO4), filtered and evaporated under reduced pressure to
give a solid which was recrystallised from ethyl acetate and
hexane to yield pale brown crystals (0.72 g, 50%), mp 80–
84 ꢁC; 1H NMR (300 MHz, CDCl3): dH 4.49 (2H, s, CH2),
7.24 (2H, m, H3 + H5), 7.69 (1H, t of d, J 1.8, 7.8, H4), 8.46
(1H, d, J 5.1, H6); 13C NMR (50.3 MHz, CDCl3): dC 48.05
(CH2), 123.10 (C2), 123.87 (C4), 138.20 (C5), 149.30 (C6),
154.47 (q, CF3); 19F NMR (188 MHz, CD3CN): dF ꢀ79.44
(s, CF3); m/z (ES+): 263 (100%, M + Na+), 241 (20%,
M + H+); nmax (KBr)/cmꢀ1 1601 (n py), 1434 (n py), 1379 (d
NH), 1367 (na SO2), 1176 (ns SO2), 1143 (d CH), 1087 (d
CH), 599 (g NH); Found: C, 35.30; H. 3.01; N. 11.52.
C7H7N2O2SF3 requires C. 35.00; H. 2.94; N. 11.66%.
1
ing solvent (0.25 g, 30%), mp 73–74 ꢁC. H NMR (200 MHz,
CDCl3): dH 2.47 (3H, s, CH3), 4.53 (2H, s, CH2), 7.08 (2H,
t, J 7, H3, H5), 7.61 (1H, t, J 7.8, H4); 13C NMR (50.3
MHz, CDCl3): dC 12.60 (CH3), 47.80 (CH2), 116.72 (q, C6),
119.49 (C5), 123.17 (C3), 137.64 (C4), 152.77 (C2), 158.34
(CF3); 19F NMR (188 MHz, CDCl3): dF ꢀ77.70 (s, CF3);
m/z (ES+): 255 (100%, MH+); nmax (KBr)/cmꢀ1 1606 (n py),
1369 (na SO2), 1191 (ns SO2), 1145 (d CH), 1069 (d CH), 611
(g NH); Found: C, 37.73; H. 3.55; N. 10.91. C8H9N2O2SF3
requires C. 37.80; H. 3.57; N. 11.02%.
2-Aminomethyl-6-methylpyridine. 10% Pd/C (0.114 g) was
added to 6-methylpyridine-2-aldoxime (1.102 g, 8.09 mmol)
dissolved in absolute ethanol (60 ml). The mixture was hydro-
genated in a Parr hydrogenation apparatus at room tempera-
ture under 40 psi H2for 4 hours. The mixture was filtered
through celite, which was washed thoroughly with ethanol
and dichloromethane, the solvent was evaporated under
reduced pressure to yield a clear colourless oil (0.915 g,
93%); 1H NMR (200 MHz, CDCl3): dH 2.47 (3H, s, CH3),
3.87 (2H, s, CH2), 6.93–7.08 (2H, m, H3, H5), 7.47 (1H, t, J
7.6, H4); 13C NMR (200 MHz, CDCl3): dC 24.56 (CH3),
47.85 (CH2), 118.35 (C5), 119.43 (q, C6), 121.61 (C3), 137.09
(C4), 158.12 (C2); m/z (ES+): 122.9 (100%, MH+).
Synthesis of metal complexes
The following are representative methods. Full details of
remaining complexes are given in the ESI.y
Zn(C13H13N2O2S)2 [Zn(L1)2]. 2-(p-Toluenesulfonylamino-
methyl)pyridine L1 (72 mg, 0.27 mmol) and zinc acetate (30
mg, 0.14 mmol) were dissolved in methanol (6 ml), and the
resulting solution was heated under reflux for 6 hours. The
solution was allowed to cool to room temperature. On stand-
ing overnight white crystals formed. These were collected by
filtration and washed with cold methanol; mp 220 ꢁC
(decomp.); 1H NMR (200 MHz, CD3OD): dH 8.4 (2H, d, J
5, H6), 8.0 (2H, t, J 5, H4), 7.8 (4H, d, J 8, tos), 7.5 (4H, m,
H5, H3), 7.2 (4H, d, J 8, tos), 4.4 (4H, s, CH2), 2.3 (6H, s,
Me); m/z (FAB): 587 (100%, ZnL2), 431 (39%, ZnL2 ꢀ tos),
325 (22%, ZnL), 263 (25%, LH); nmax (KBr)/cmꢀ1 1611 (n
py), 1568 (n py), 1442 (n py), 1277 (na SO2), 1151 (ns SO2),
1104 (d CH), 1087 (d CH), 970, 762 (d py), 670 (g NH), 560
(d SO2); Found: C, 52.53; H, 4.44; N, 9.40. Zn(C13H13N2-
O2S)2ꢄ0.5MeOH requires C, 52.69; H, 4.67; N, 9.27%.
2-(p-Toluenesulfonylaminomethyl)-6-methylpyridine L4. To a
stirred solution of p-toluenesulfonyl chloride (192 mg, 1.0
mmol) in pyridine (0.6 ml) cooled to ꢀ10 ꢁC was slowly added
a solution of 2-aminomethyl-6-methylpyridine (123 mg, 1.0
mmol) in pyridine (1 ml). The resulting yellow reaction mixture
was stirred at ꢀ10 ꢁC for 3 hours and was held at 5 ꢁC over-
night. The reaction mixture was poured onto crushed ice,
which was allowed to melt resulting in the formation of an
oil. A precipitate formed upon scratching. The solid was
removed by filtration, dissolved in dichloromethane (5 ml)
and washed with water (2 ꢂ 5 ml). The organic phase was dried
(MgSO4), filtered and evaporated under reduced pressure to
Cu(C13H13N2O2S)2 [Cu(L1)2]. 2-(p-Toluenesulfonylamino-
methyl)pyridine L1 (52 mg, 0.2 mmol) and copper acetate (40
mg, 0.2 mmol) were dissolved in methanol (10 ml) and heated
under reflux for 18 hours. The solution was allowed to cool to
100
New J. Chem., 2003, 27, 98–106

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room temperature. On standing overnight blue and brown
cubic crystals formed, these were collected by filtration and
washed with cold methanol; mp 180–182 ꢁC; m/z (FAB): 911
(11%, CuL3), 650 (16%, Cu2L2), 608 (32%, CuL2 + Na), 586
(100%, CuL2) 325 (71%, CuL), 263 (22%, L + H); nmax
(KBr)/cmꢀ1 1609 (n py), 1570 (n py), 1447 (n py), 1276 (na
SO2), 1139 (ns SO2), 1106 (d CH), 1085 (d CH), 844, 813, 673
(g NH), 557 (d SO2); lmax(MeCN) 638 nm (e 67 dm3 molꢀ1
cmꢀ1); Found: C, 53.17; H, 4.46; N, 9.49. Cu(C13H13N2O2S)2
requires C, 53.27; H, 4.47; N, 9.55%.
crystals formed after several days. These were collected by fil-
tration and washed with cold methanol; mp 240 ꢁC (decomp.);
m/z FAB: 604 (37%, CoL2 + Na), 582 (100%, CoL2), 426
(39%, CoL2 ꢀ tos), 320 (23%, CoL); nmax (KBr)/cmꢀ1 1609
(n py), 1439 (n py), 1278 (na SO2), 1145 (ns SO2), 1085 (d
CH), 947, 760 (d py), 669 (g NH), 559 (d SO2); lmax
(MeCN)/nm 513 and 579 (e/dm3 molꢀ1 cmꢀ1 302 and 291);
Found: C, 53.20; H, 4.35; N, 9.51. Co(C13H13N2O2S)2ꢄ
0.25MeOH requires C, 53.48; H, 4.61; N, 9.50%.
Ni(C13H13N2O2S)2 [Ni(L1)2]. 2-(p-Toluenesulfonylamino-
methyl)pyridine L1 (66 mg, 0.25 mmol) was dissolved in
methanol (2.5 ml), and neutralised with 0.1 M KOH solution
(2.5 ml, 0.25 mmol), the solvent was evaporated under reduced
pressure. The resulting brown oil was dissolved in methanol (7
ml) and nickel acetate (31 mg, 0.12 mmol) was added. The
resulting clear green solution was heated under reflux with stir-
ring for one hour. The solution was allowed to cool to room
temperature. An orange precipitate formed overnight, which
was collected by filtration and washed with cold methanol
and water; mp 220 ꢁC (decomp.); m/z (FAB): 603 (14%,
NiL2 + Na), 581 (63%, NiL2), 425 (9%, NiL2 ꢀ tos), 263
(100%, LH); nmax (KBr)/cmꢀ1 1611 (n py), 1478 (n py), 1281
(na SO2), 1139 (ns SO2), 1084 (d CH), 681 (g NH), 557 (d
SO2); Found: C, 53.57; H, 4.68; N, 9.58. Ni(C13H13N2O2S)2
requires C, 53.72; H, 4.51; N, 9.64%.
Results and discussion
Ligand and complex synthesis and X-ray structural
characterisation
The ligands L1–L4 were prepared by reaction of the appropri-
ate 2-(aminomethyl)pyridine with p-toluenesulfonyl chloride
or CF3SO2Cl in dry pyridine. The precursor 6-methyl-2-(ami-
nomethyl)pyridine was prepared by reaction of the 6-aldehyde
with hydroxylamine followed by reduction of the oxime26 by
catalytic hydrogenation over Pd/C. Formation of the ML2
complex was undertaken by mixing two molar equivalents of
ligand with one of the M(OAc)2 salt in boiling methanol. On
cooling, crystals of the neutral complex were deposited
slowly—often over a period of several days. Each complex
could be recrystallised from MeOH or EtOH. In the case of
[Ni(L1)2] and [Co(L1)2] it was found necessary to form the
potassium salt of the ligand, prior to complex formation.
The structure of each of the sixteen neutral complexes has
been determined by X-ray crystallography at 100–120 K
(Tables 1–3; Fig. 1). The coordination geometry at Co(II)
and Zn(II) was invariably a distorted tetrahedron, reflecting
the minimisation of steric congestion, and for Co(II) the
slightly favourable ligand field stabilisation effect. With Cu(II),
the less sterically demanding ligand L1 allowed formation of a
square planar complex, whereas in complexes with L2, L3 and
Co(C13H13N2O2S)2 [Co(L1)2]. 2-(p-Toluenesulfonylamino-
methyl)pyridine L1 (131 mg, 0.5 mmol) was dissolved in
methanol (5 ml), and neutralised with 0.1 M KOH solution
(5 ml, 0.5 mmol) and the solvent evaporated under reduced
pressure. The resulting brown oil was dissolved in methanol
(10 ml) and cobaltous acetate hexahydrate (62 mg, 0.25 mmol)
was added. The resulting dark purple solution was heated
under reflux with stirring for seven hours. The solution was
allowed to cool to room temperature. On standing purple
a
˚
Table 2 Bond lengths, in A, from the central metal ion to the coordinating nitrogens
˚
M–N11/A
˚
M–N12/A
˚
M–N21/A
˚
M–N22/A
Complex
Average M–N1
Average M–N2
Average M–N
[Zn(L1)2]
[Zn(L2)2]
[Zn(L3)2]
[Zn(L4)2]
[Cu(L1)2]
[Cu(L2)2]
[Cu(L3)2]
[Cu(L4)2]A
[Cu(L4)2]B
[Ni(L1)2]
[Ni(L2)2]
[Ni(L3)2]
[Ni(L4)2]
[Co(L1)2]
[Co(L2)2]
[Co(L3)2]
[Co(L4)2]
2.049(3)
2.023(2)
2.048(2)
2.050(7)
1.996(1)
1.949
1.942(3)
1.972(2)
1.965(2)
1.954(2)
1.998(1)
1.939
2.049(3)
2.043(2)
2.057(2)
2.089(2)
1.996(1)
1.998
1.956(3)
1.967(2)
1.966(2)
1.929(2)
1.998(2)
1.916
2.049
2.033
2.052
2.069
1.996
1.974
1.971
2.043
2.063
1.924
2.075
2.025
2.027
2.034
2.030
2.038
2.056
1.949
1.969
1.965
1.941
1.998
1.928
1.971
1.932
1.916
1.960
2.111
1.944
1.917
1.949
1.965
1.969
1.947
1.999
2.001
2.009
2.004
1.997
1.951
1.971
1.988
1.989
1.942
2.093
1.9845
1.972
1.9915
1.9975
2.0035
2.001
1.979(2)
2.067(5)
2.067(5)
1.924(5)
2.090(3)
2.021(2)
2.040(2)
2.031(2)
2.028(2)
2.040(2)
2.061(2)
1.973(2)
1.920(5)
1.914(5)
1.960(5)
2.123(3)
1.941(2)
1.905(2)
1.960(2)
1.962(2)
1.972(2)
1.934(2)
1.962(2)
2.019(5)
2.058(5)
1.924(5)
2.060(3)
2.028(2)
2.014(2)
2.037(2)
2.031(2)
2.035(2)
2.052(2)
1.969(2)
1.944(5)
1.918(5)
1.960(5)
2.099(3)
1.946(2)
1.929(2)
1.937(2)
1.968(2)
1.965(2)
1.960(2)
a
In CN ¼ 4, mean ionic radii for Zn, Cu, Ni and Co(II) ions are 0.60, 0.57, 0.55 and 0.58 A.27 [Cu(L4)2]: This complex has two independent mole-
˚
cules in the unit cell.
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Table 3 Bond angles, in degrees, between the central metal ion and the co-ordinating nitrogen atoms
Complex
N11–M–N12
N11–M–N21
N11–M–N22
N12–M–N21
N12–M–N22
N21–M–N22
[Zn(L1)2]
[Zn(L2)2]
[Zn(L3)2]
[Zn(L4)2]
[Cu(L1)2]
[Cu(L2)2]a
[Cu(L3)2]
[Cu(L4)2]A
[Cu(L4)2]B
[Ni(L1)2]
[Ni(L2)2]
[Ni(L3)2]
[Ni(L4)2]
[Co(L1)2]
[Co(L2)2]
[Co(L3)2]
[Co(L4)2]
82.96(11)
83.12(6)
82.81(6)
82.8(2)
122.40(10)
124.98(6)
113.20(6)
113.3(2)
121.54(11)
124.75(6)
125.79(7)
129.8(3)
96.77(6)
105.6
117.73(11)
114.93(7)
123.81(7)
117.47(8)
96.77(6)
105.6
134.92(11)
131.99(7)
131.73(7)
134.01(8)
180.00(7)
154.7
82.59(10)
82.44(6)
83.32(6)
82.01(7)
83.23(6)
81.0
83.23(6)
82.3
180.00(8)
147.3
84.07(8)
83.0(2)
82.2(2)
150.57(9)
140.66(19)
128.82(19)
180.00(17)
91.01(12)
108.20(7)
110.69(8)
122.08(9)
125.16(8)
115.13(8)
114.45(8)
112.72(8)
109.3(2)
115.0(2)
85.6(2)
103.40(8)
107.2(2)
110.6(2)
85.6(2)
131.34(9)
145.0(2)
145.4(2)
83.92(8)
84.2(2)
82.7(2)
94.4(2)
180.0(3)
94.4(2)
79.48(12)
82.13(7)
81.82(8)
81.85(9)
82.25(8)
82.88(8)
81.97(8)
94.27(13)
124.26(8)
116.45(8)
119.28(10)
122.17(8)
124.51(8)
119.17(8)
97.31(13)
124.25(7)
133.00(8)
119.19(10)
116.01(9)
127.66(9)
128.57(8)
173.27(13)
137.32(8)
134.63(8)
137.24(10)
135.44(8)
129.35(9)
134.20(8)
80.18(13)
82.23(7)
81.64(7)
82.59(9)
81.83(8)
82.12(8)
81.94(7)
a
Twinned crystal. Structure of poor quality. ESD’s are estimated at ꢅ5 in the last digit.
Fig. 1 View of the crystal structures (100 to 120 K) of the Co(II), Ni(II), Cu(II) and Zn(II) complexes of L1–L4, revealing distorted tetrahedral
geometry except for [Cu(L1)2], [NiL1] (square planar), and [Ni(L2)2(EtOH)2] (octahedral).
102
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L4, the distorted tetrahedral arrangement that characterised
zinc and cobalt complex formation is favoured. Finally, for
Ni(II) complexes, once again complexes with L3 and L4
adopted distorted tetrahedral arrangements, while [Ni(L1)2]
was square planar and [Ni(L2)2] took up an octahedral geome-
try, with two ethanol molecules cis-coordinated and the sulfo-
namide nitrogens trans-related.
L2 possesses an angular deviation of close to 25ꢁ. The remain-
ing two copper structures (sum of angles 665 to 670ꢁ), each of
the zinc and cobalt complexes and the three tetracoordinate
nickel complexes form a cluster around 18–20ꢁ. Once again,
for the complexes examined here, the degree of distortion is
primarily related to the 5-ring chelate bite angle of about 82ꢁ
imposed by the ligand structure.
Geometric parameters are summarised in Tables 2 and 3.
Within the series of zinc and cobalt complexes, average bond
lengths to the sulfonamide N were marginally longer with
the more electron poor trifluoromethyl-substituted pair of
complexes. At the same time, the M–Npy bond length was
slightly longer for the complexes with the 6-methyl substituent.
Bond lengths to pyridyl and sulfonamide nitrogens were
in line with literature values for 4- or 5-coordinate zinc
complexes.28–31 For example, in the 2,2-bipyridylzinc complex
of cyclohexane-1,2-diylbis(methanesulfonamide) the sulfon-
This method for analysing distortion from a regular poly-
hedron may be extended to related octahedral or trigonal
bipyramidal structures. For the unique case of tetrahedral dis-
tortion, an alternative (1-D) analysis involves an examination
of the dihedral angle between the two ML2 planes, with limits
at 90ꢁ and 0ꢁ for ideal tetrahedral and square planar geometry.
This method has one advantage in giving the absolute config-
uration for chiral systems. Such an analysis has been carried
out for the 16 structures defined herein. For each of the tetra-
hedrally distorted cobalt, nickel and zinc complexes, the devia-
tion from the tetrahedral (90ꢁ) limit was not more than 10ꢁ.
Distortion was more evident with the copper complexes; for
[Cu(L2)2] the dihedral angle was 45ꢁ whilst for [Cu(L3)2] and
[Cu(L4)2], the values were 29 and 33ꢁ respectively. The 2-D
plot shown in Fig. 2 intrinsically provides additional informa-
tion. Tetragonal distortion of a square planar complex gives an
angle sum of near to 720ꢁ and an angular distortion of > 40ꢁ;
no cases were found for first row elements with O and N
donors, only two examples with M–M (Cu/Cu and Co/Cu)
bonding fall on this limit.
˚
amide N–Zn bond length was 1.94 A with a bpy–N–Zn length
˚
28
of 2.05 A. With the copper(II) complexes, average bond
lengths were slightly longer for the square planar example.
The X-ray structure of [Cu(L1)2] has been reported indepen-
dently at 293 K very recently;32,33 structural details echo those
reported herein. Overall, there is a remarkable constancy in the
M–N bond lengths. This can be related to the fixed chelate bite
angle, associated with each ligand. Thus, the intra-ligand N–
M–N0 bond angles in the series average 83ꢁ and 82ꢁ for the
set of zinc and cobalt complexes respectively (Table 3). This
relatively constant bite angle is also found (83 ꢅ 3ꢁ) in the
square planar and octahedral Ni(II) complexes.
Absorption spectroscopy and cyclic voltammetry
There are two limiting geometries for four-coordinate com-
plexes: square planar and tetrahedral. In order to quantify the
deviation from these limits in the complexes examined here, a
search of the CSD was undertaken examining all first row
four-coordinate complexes with N and O donors only. In the
April 2001 version, 284 of these were for zinc complexes.
The geometry around the central ion is defined by six bond
angles and these were obtained from the database. For a
square planar complex, the sum of these angles is 720ꢁ; around
a tetrahedron the sum is 656ꢁ. However, the sum itself is not a
sufficient measure of geometry, because in the limiting case of
the perfect tetrahedron each of the six angles needs to be iden-
tical, whilst for a square planar arrangement two of the angles
have to be 180ꢁ and the remaining four are 90ꢁ. A measure of
distortion is obtained by calculating the average deviation of
all six angles; for a perfect tetrahedron this is zero and for a
perfect square plane it is 40ꢁ [(2 ꢂ 60 + 4 ꢂ 30)/6]. A plot of
the average angular deviation (y axis) versus the sum of the
six angles is given for all of the CN ¼ 4 first row transition
metal complexes with N and O donors only in the CSD
(Fig. 2). In this Figure, the copper complex of L1 appears
in the top right hand corner, whilst the copper complex of
Absorption spectra were recorded for each of the coloured com-
plexes in acetonitrile solution at a 1 mM concentration when
observing the d–d bands, and in more dilute solution when
charge-transfer bands were also observed. For the Co(II)
complexes, the absorption spectra were similar except for
[Co(L4)2], which was much more pale-coloured in the MeCN
solution (Fig. 3). Molar absorption coefficients, e, decreased in
the sequence [Co(L2)2] ꢆ [Co(L1)2] < [Co(L3)2] < [Co(L4)2].
It is generally appreciated that visible transitions in tetrahedral
cobalt(II) complexes are an order of magnitude more intense
than for equivalent octahedral systems. Absorption spectra tend
4
to be dominated by the 4A2 ! T1(P) transition for tetrahedral
4
systems, and 4T1g(F) ! T1g(P) transition for octahedral exam-
ples. Fine structure is imposed by a number of transitions to
doublet excited states, which gain intensity by spin–orbit
coupling. Thus for [Co(L2)2], the complex must be octahedral
in solution, binding to two additional solvent molecules (viz.
Fig. 1 for [Ni(L2)2(EtOH)2]). Indeed, the reflectance spectra
for each cobalt complex—obtained on crystalline samples—
were more or less identical in intensity, supporting this idea.
Fig. 2 Plot of the sum of the six bond angles (x axis) versus the aver-
age deviation of these angles for all 4-coordinate first row transition
metal complexes involving N and O donors (CSD 2001). The com-
plexes in this paper are represented by squares (see Table 3).
Fig. 3 Absorption spectra of neutral cobalt(II) complexes of L1–L4
(1 mM complex, (2 mM for L2), MeCN).
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Table 4 Selected absorption spectral data (MeCN, 295 K) for cobalt,
nickel and copper(II) complexes (lmax ; e/Mꢀ1 cmꢀ1 in parentheses)
Table 5 Selected ligand protonation and successive metal complex
formation constants (298 K, I ¼ 0.1 M NMe4NO3 , 80% MeOH–
20% H2O)
Co(II)
Ni(II)
Cu(II)
a
log K1
log K2 log KZnL log KZnL log KCuL log KCuL
2 2
L1 513 (300), 579 (290) insoluble
639 (70)
672 (230)
L1 12.23(6) 3.31(3) 7.66(6)
6.91(7)
5.12(7)b
11.40(5)
6.74(5)
6.26(4)
9.16(7)
6.42(8)
6.09(8)
L2 500 (45)
367 (50), 597 (3)
L2
L3
7.51(3) 2.69(3) 5.25(5)b
L3 533 (400), 564 (380) 544 (190), 733 (50) 410 (405), 764 (70)
c
c
L4 532 (580), 564 (540) 544 (70), 760 (30)
448 (2020), 784 (215)
7.61(3) 3.23(3)
a
Defining the successive protonation constants: K1 ¼ [LH]/[Lꢀ][H+]
and K2 ¼ [LH2+]/[LH][H+]. Values for Co complexes were: log
b
c
KCoL 5.11(6); log KCoL 5.19(5). Precipitation occurred under these
conditions.
The tetrahedrally distorted copper complexes, [Cu(L3)2] and
[Cu(L4)2], were lime-green and orange-brown in solution
(Table 4 and Fig. 4), reflecting the influence of the relatively
intense LMCT bands at 410 and 448 nm respectively. The por-
tion of the d–d transition was shifted to the red in the sequence
[Cu(L1)2] > [Cu(L2)2] > [Cu(L3)2] > [Cu(L4)2] associated with
the increase in LFSE for square-planar complexes, with the
more polarisable NTs ligand in L1 affording the greatest crys-
2
[Cu(L4)2], more complex behaviour was noted with an appar-
ent redox couple at ca. ꢀ240 mV.
Selected ligand protonation and metal complex formation
constants: speciation at ambient pH
II
I
tal field splitting. The Cu /Cu redox couple was examined by
cyclic voltammetry (MeCN, Bu4NClO4 , 295 K) for each of the
four copper complexes (Fig. 5). For the complexes lacking
Equilibrium constants associated with stepwise protonation
of the anionic ligands L1–L3 were measured by standard
1
the 6-Me substituent, the E values (vs. Ag/AgCl) were ꢀ430
2
[Cu(L1)2] and ꢀ137 mV ([Cu(L2)2]), reflecting the greater stabi-
lisation of the copper(II) state in the tosylamide complex
with square planar geometry and a large ligand field stabi-
lisation energy (Table 4). The tetrahedrally distorted complex
3
1
2
[Cu(L )2] is much more readily reduced, E ¼ +55 mV, consis-
tent with the destabilisation of the Cu(II) state. In each of
these cases, quasi-reversible behaviour was exhibited (ip ꢇ ia
i
ia / n1/2), whereas for the tetrahedrally distorted complex
Fig. 4 Absorption spectra of neutral copper(II) complexes of L1–L4,
2
2
the inset highlights the position of the E2g ! T2g transition.
Fig. 6 Species distribution plots for Zn2+/L2: upper, 10 mM ligand, 1
mM Zn2+; centre, 1 mM L2, 0.1 mM Zn2+; lower, 0.1 mM L2, 0.1 mM
Zn2+ (80% MeOH, 20% H2O; 298 K; 0.1 M Me4NNO3). Plots at a
fixed L/M ratio of 2 are given in the ESI.y
Fig. 5 Cyclic voltammograms (295 K, 0.1 M Bu4NClO4 , v ¼ 100
mV sꢀ1) of the copper(II) complexes of L1–L4.
104
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is not possible here, owing to the insolubility of the zinc
complex under the standard conditions used. The difference
in stability of the copper and zinc complexes is much greater
with L1, as the copper complex in that case is square planar
and the zinc is tetrahedral. The relative magnitude of the step-
wise formation constants (log KML vs. log KML ) for zinc, cop-
2
per and cobalt was very similar, although there was no
evidence for the positive cooperativity in formation of the
ML2 complex, that was apparently a feature of the behaviour
of the related quinolylsulfonamides (e.g. Zinquin5). It should
be noted that the analysis of the data reported in that case
(‘‘we conclude that that the 1:1 and 2:1 Zn/Zinquin complexes
differ by at least two orders of magnitude’’5) only gives a limit
to the difference in values as no direct titrations were reported
at 1:1 stoichiometry and there was no direct account taken of
metal ion hydrolysis in the data analysis.
The harder trifluoromethylsulfonamide N favours binding
to Cu(II) less than the more basic and softer tosylamide N in
L1. Hard donors—such as phosphinates—have previously
been shown to disfavour binding to Zn2+ less than to Cu2+
,
in related 4 or 5-coordinate aza-phosphinate complexes.21
Furthermore, systems favouring tetrahedral coordination
should also enhance the relative stability of Zn(II) compared
to Cu(II), as the LFSE contribution is significantly diminished
for Cu(II) when deviations from planarity or square pyramidal
geometry occur.13,14,22
Fig. 7 Species distribution plots for Zn2+/L1: upper, 10 mM ligand, 1
mM Zn2+; lower, 0.1 mM L1, 10 mM Zn2+
.
Using the data in Table 5, species distribution diagrams as
a function of pH and M/L concentration may be obtained,
in which the percentage of the insoluble metal hydroxide is
calculated by extrapolation. Considering the Zn2+/L1 and L2
systems (Figs. 6 and 7), the pH-dependent distribution of com-
plex species has been calculated at fixed ligand concentrations
of 10 mM, 1 mM and 0.1 mM, with varying [Zn2+] values.
Distributions at a fixed 2:1 ligand to metal ratio are given in
the ESI.y With the Zn2+/L2 system, a particular feature is that
the [Zn(L2)2] species predominates at ambient pH and even
with [L2]tot ¼ 0.1 mM and [Zn2+] ¼ 0.1 mM, more than 80%
of all Zn bound species is [Zn(L2)2]. On the other hand, with
the tosylamide ligand L1 (log K1 ¼ 12.2) even at 10 mM
pH-metric methods in 80% MeOH/H2O, in a background of
0.1 M NMe4NO3 . Data were corrected24 to allow for the var-
iation of the water dissociation constant at this solvent com-
position and were analysed using the programme
HYPERQUAD.23 The log K1 values (Table 5) measured for
L2 and L3 were 7.51 and 7.61 respectively, similar to the litera-
ture values for simple trifluoromethylsulfonamides.19 The
p-toluenesulfonyl analogue, L1, possesses a much more basic
sulfonamide N, log K1 ¼ 12.23, in line with data for related
arylsulfonamides.34 The pyridyl nitrogen is much less basic
in each case, and the introduction of the 6-methyl substituent
slightly enhances proton affinity (L2 vs. L3: log K2 ¼ 2.69 and
3.32). Thus, around ambient pH conditions, the ligands L2 and
L3 exist as almost 50% of the monoanionic species.
Metal complex formation constants have been measured for
Cu(II) and Zn(II) complexes of L1–L3, taking account of metal
ion hydrolysis.23 Separate titrations at 1:1 and 1:2 metal/
ligand ratios were undertaken in order to measure both the
ML and the ML2 formation constants. The ligand L2 formed
slightly more stable complexes with copper than zinc, in accord
with the Irving–Williams series,35 although a direct com-
parison of the tetrahedrally distorted Cu–L3/Zn–L3 systems
[L1]tot and 1 mM [Zn2+
]tot , the major species at pH 7.4 is
the metal hydroxide with significant [ZnL1] formed. At lower
ligand concentrations, only a small percentage fraction of the
[ZnL1] species is present. Given that L2 and L3 may be readily
derivatised at C-6 or alpha to the sulfonamide N, these ligands
offer some scope as the basis for Zn2+ probes in neutral
aqueous media.
For the Cu(II)/L1 system, exhibiting, as expected, the highest
stepwise formation constants for any of the systems examined
here, it is possible to vary the pH over the range 4 to 8 in order
to control the relative proportion of [CuL1] and [Cu(L2)2]
Fig. 8 Left: Species distribution plot for Cu2+/L1 (10 mM L1, 5 mM Cu2+, 298 K, 80% MeOH, 20% H2O, 0.1 M NMe4NO3); right: cyclic
voltammograms recorded under the same conditions at pH 4.9, 5.65 and 8.81 (v ¼ 100 mV sꢀ1).
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9
P. D. Zalewski, S. H. Millard, I. J. Forbes, O. Kapaniris, A.
Slavotinek, W. H. Betts, A. D. Ward, S. F. Lincoln and I.
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species (Fig. 8 left). Thus, for a ligand concentration of 10 mM
(or 1 mM), at pH 5 the predominant species is [CuL1], whereas
at pH > 7, [Cu(L2)2] is the major species. With this in mind,
cyclic voltammetry was used to examine the Cu(II)/Cu(I) redox
couple as a function of pH (Fig. 8 right). At pH 4.9 (10 mM L1;
5 mM Cu(CF3SO3)2 ; 298 K; 0.1 M NMe4NO3 , 80% MeOH/
H2O), the reversible wave observed at ca. ꢀ10 mV may be
ascribed to [CuL1], whereas at pH 8.8, the redox couple shifts
to ꢀ315 mV and is associated with the square planar complex
[Cu(L2)2]. At the intermediate pH value of 5.65, both species
are present in nearly equal amounts, and the observation of
separate redox waves for each species is consistent with the
rate of electron transfer being faster than any associative
ligand exchange process involving [CuL1] and [Cu(L2)2]. Given
that different redox active ML species may be observed simul-
taneously, for example using differential pulse voltammetry,
and that their relative concentration is pH dependent, such
work suggests that by immobilising ligands related to L1 at
an electrode surface, the selective detection and assay of a mix-
ture of metal ions may be expedited using sensitive stripping
voltammetric techniques.
10 W. D. Qian, C. A. Aspinwall, M. A. Battiste and R. T. Kennedy,
Anal. Chem., 2000, 72, 711.
11 O. Reany, T. Gunnlaugsson and D. Parker, J. Chem. Soc., Perkin
Trans. 2, 2000, 1819.
12 Y. Hitomi, C. E. Outten and T. V. O’Halloran, J. Am. Chem.
Soc., 2001, 123, 8614.
13 C. D. Edlin, D. Parker, J. J. B. Perry, C. Chartroux and K. Gloe,
New J. Chem., 1999, 23, 819.
14 G. B. Bates, D. Parker and P. A. Tasker, J. Chem. Soc., Perkin
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17 E. E. Chufan, S. Garcia-Granda, M. R. Diaz, J. Borras and J. C.
Pedregosa, J. Coord. Chem., 2001, 54, 303.
18 C. T. Supuran and A. Scozzafava, Eur. J. Med. Chem., 2000,
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19 K. Hakansson and A. Liljas, FEBS Lett., 1994, 350, 319.
20 D. Elbaum, S. K. Nair, M. W. Patcham, R. B. Thompson and
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21 G. B. Bates, E. Cole, R. Kataky and D. Parker, J. Chem. Soc.,
Dalton Trans., 1996, 2693.
In summary, ligands L2 and L3 are suitable basic ligand sys-
tems that form ML2 complexes at ambient pH when the free
zinc concentration is in the micro to nanomolar range. Suitable
derivatives are therefore being evaluated allowing their inte-
gration into practicable luminescent or MRI probes.
22 G. B. Bates and D. Parker, J. Chem. Soc., Perkin Trans. 2, 1996,
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We thank EPSRC (AC, HP, MK) and the University of
Durham for support.
25 SHELXTL version 6.12, Bruker AXS, Madison, Wisconsin, USA,
2001.
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