Bioinspired catalytic conjugate additions of thiophenols to α,β-enones by a disubstituted benzoate-bridged nickel mimic for the active site of urease

Article abstract of DOI:10.1021/om100103u

A disubstituted benzoate polydentate ligand, 2,6-bis[bis(pyridinyl-2- methyl)aminoethoxyl]benzoate (HL), was prepared to synthesize nickel mimics for the active site of urease. Reaction of the deprotonated L^- with Ni(ClO⁴)²

Full text of DOI:10.1021/om100103u

2874 Organometallics 2010, 29, 2874–2881
DOI: 10.1021/om100103u
Bioinspired Catalytic Conjugate Additions of Thiophenols to
r,β-Enones by a Disubstituted Benzoate-Bridged Nickel Mimic
for the Active Site of Urease
Way-Zen Lee,*,† Huan-Sheng Tseng,† Tzu-Li Wang,† Hui-Lien Tsai,*,‡ and
Ting-Shen Kuo§
†Department of Chemistry, National Taiwan Normal University, Taipei 11650, Taiwan, ‡Department of
Chemistry, National Cheng Kung University, Tainan 70101, Taiwan, and Instrumentation Center,
§
Department of Chemistry, National Taiwan Normal University, Taipei 11650, Taiwan
Received February 10, 2010
A disubstituted benzoate polydentate ligand, 2,6-bis[bis(pyridinyl-2-methyl)aminoethoxyl]benzo-
ate (HL), was prepared to synthesize nickel mimics for the active site of urease. Reaction of the
deprotonated L- with Ni(ClO4)2 6H2O afforded a dinickel complex, [LNi2(CH3CN)(THF)](ClO4)3
(1), characterized by UV/vis spectroscopy and X-ray crystallography. Addition of urea to an
acetonitrile solution of 1 afforded a dinickel urea adduct, [LNi2(urea)2](ClO4)3 2CH3CN (2), which
3
3
1
was structurally and spectroscopically characterized. H NMR and ESI-MS spectra of 2 both
evidenced that urea molecules remained coordinated to the nickel centers of 2 in solution. With the
inspiration of urea coordination to the nickel centers of 1, the conjugate additions of thiophenols to
R,β-enones catalyzed by complex 1 were examined and found to proceed in good yields. In contrast,
the same catalytic reaction by Ni(ClO4)2 6H2O and HL was far less effective. Also, addition of
3
NaOAc or NaOAcPh2 to an acetonitrile solution of 1 gave tetranuclear nickel complexes, [LNi2-
(μ-OAc)]2(ClO4)4 3H2O (3) and [LNi2(μ-OAcPh2)]2(ClO4)4 5CH3CN 2THF (4), and their molec-
3
3
3
ular structures determined by X-ray diffraction can be described as dimers of dimers. Each dinickel
core of 3 and 4 closely mimics the active site of urease. The magnetic data of 1, 3, and 4 exhibited a
very weak antiferromagnetic coupling (J = -0.72 cm-1 for 1, -0.65 cm-1 for 3 and 4) between two
metal centers in the dinickel core.
Urease, which can catalyze the hydrolysis of urea, exists in
a variety of bacteria, fungi, and higher plants1 and permits
the organism to consume external or internal generated urea
as a nitrogen source.2 Hydrolysis of urea catalyzed by the
dinickel active site of urease produces CO2 and 2 equiv of
NH3.1 The degradation rate of urea by the enzyme is 1014
times faster than its spontaneous decomposition rate.3 Due
to this fast catalysis, soil bacterial urease can rapidly hydro-
lyze fertilizer urea to unproductive volatilized ammonia and
cause the damage of plants.2 Also, the existence of urease in
Helicobacter pylori, which causes gastric inflammation and
peptic ulcer disease, allows the bacteria to survive in the
gastric mucosa of patients at acidic pH.4 Two enzymatic
mechanisms of urease have been proposed,5,6 and the first
intermediate in both mechanisms is the urea-bound enzyme,
in which urea is proposed to coordinate to the nickel center in
the active site of urease. Many reported protein structures of
urease with high resolution7 reveal that two nickel ions exist
*To whom correspondence should be addressed. E-mail: wzlee@
ntnu.edu.tw.
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Chem. Soc. 1982, 104, 612–614.
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˚
in the active site of the enzyme with a separation of 3.5 A. The
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Res. 1997, 30, 330–337. (b) Benini, S.; Ciurli, S.; Rypniewski, W. R.; Wilson,
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r
pubs.acs.org/Organometallics
Published on Web 06/08/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 13, 2010 2875
Chart 1
Figure 1. Schematic representation of the active site of urease.
two nickel ions are bridged by a rather unusual carbamate
group, which is converted from the reaction of Lys217 with
carbon dioxide, and a hydroxide group.7a It has been con-
firmed that the binding of nickel ions into the active site of the
apoenzyme of urease requires the presence of carbon dioxide.8
Each nickel is coordinated by two histidine residues and a
water molecule, resulting in a distorted-square-pyramidal
geometry for Ni(1), and Ni(2) is terminally ligated to an
additional aspartate residue, forming a pseudooctahedral
ligand environment (Figure 1). Many model complexes for
the active site of urease have been reported,9-12 but only a few
nickel mimics were bridged by a disubstituted benzoate poly-
dentate ligand. Recently, we reported two dinickel mimics,
[L1Ni2(DMF)4](ClO4)3 and [L2Ni2(CH3CN)4](ClO4)3 (where
L1 = 2,6-bis[bis(pyridinyl-2-methyl)aminomethyl]benzoate
and L2 = 2,6-bis[bis(1-methylbenzimidazolyl-2-methyl)amino-
methyl]benzoate), in which urea can coordinate to the nickel
centers of the complexes.13 Due to the short length of the ligand
side arms of L1 and L2, the conformation of the dinickel core of
the dinickel complex 1 and found much higher yields compared
to those by Ni(ClO4)2 6H2O and HL. In addition, complex 1
3
can react with NaOAc and NaOAcPh2 to form two nickel
mimics, [LNi2(μ-OAc)]2(ClO4)4 (3) and [LNi2(μ-OAcPh2)]2-
(ClO4)4 (4), which possess dinickel cores having coordination
environments similar to that of the active site of urease. The
magnetic properties of complexes 1, 3, and 4 were studied.
Results and Discussion
Synthesis and Spectroscopic Characterization of the Di-
nickel Urea Adduct. In order to construct nickel mimics
possessing a coordination environment similar to that of
the active site of urease, a disubstituted benzoate ligand, HL,
which comprises side arms longer than those of the previous
ligands, L1 and L2,13 was prepared by modification of a
reported method.14 The prepared HL was deprotonated by
sodium methoxide in methanol to form a pale yellow solu-
tion, which was subsequently transferred into an acetonitrile
the two mimics becomes W-shaped, and the Ni Ni distances
3 3 3
solution of Ni(ClO4)2 6H2O to form a light blue solution.
3
of such complexes are much longer than that in the active site
of urease. In order to obtain nickel complexes which possess a
dinickel core with a Ni Ni distance similar to that of the
The light blue product was purified and recrystallized by the
slow diffusion method (THF/CH3CN). Nice needlelike crystals
of [LNi2(CH3CN)(THF)](ClO4)3 (1) were obtained in 73%
yield. Reaction of complex 1 with excess urea in acetonitrile
3 3 3
active site of urease, synthesis of a new ligand is indispensable. A
disubstituted benzoate with longer side arms, 2,6-bis[(2-bis-
(2-pyridylmethyl)aminoethoxy)]benzoic acid (HL; Chart 1),
was synthesized by modifying a reported method.14 Herein, we
demonstrate the synthesis of a dinickel complex, [LNi2(CH3-
CN)(THF)](ClO4)3 (1), bridged by the disubstituted benzoate
L and its ability to bind urea forming a urea adduct, [LNi2-
afforded a dinickel urea adduct, [LNi2(urea)2](ClO4)3 2CH3CN
3
(2), in which each nickel center of the complex was coordi-
nated by a urea molecule. Complex 2 was fully charac-
terized by IR, 1H NMR, and ESI-MS spectroscopy. The solid
FTIR spectrum (KBr pellet) of 2 exhibited the stretching
frequency for the carbonyl group of the bound urea at 1662
cm-1 shifted from that of free urea at 1690 cm-1. The1HNMR
spectra of complexes 1 and 2 showed relatively sharp reso-
nance signals for high-spin six-coordinated dinickel(II) species
(Figure 2).13,15 In comparison to the spectrum of 1, a pro-
nounced signal for the bound urea molecules in the spectrum
of 2 was observed at 4.69 ppm, an upfield shift from 4.81 ppm
(free urea in CD3CN). In addition, the ESI-MS spectrum of 2
indicated that urea molecules remained coordinated on the
nickel centers of 2 in solution (ESI-MS (m/z, amu): 440 for
[LNi2(urea)(ClO4)]2þ). Since the geometry of the nickel centers
in 2 remained the same as that in 1, the electronic absorption
spectra of 1 and 2 exhibited similar absorption bands of three
weak d-d transitions in the visible region. In spite of saturated
coordination on the nickel centers of 1, the nickel ions of 1
could bind urea to form the urea adduct of2. The coordination
of urea to the nickel centers of 2 is due to the electronic
deficiency of the dinickel core. With the inspiration of urea
coordination to the nickel centers of 2, the catalytic conjugate
additions of thiophenols to R,β-enones by complex 1 were
investigated.
(urea)2](ClO4)3 2CH3CN (2). As a result of urea coordination
3
to the nickel centers of 2, we were inspired to examine the
catalysis of conjugate addition of thiophenols to R,β-enones by
(8) Park, I.-S.; Hausinger, R. P. Science 1995, 267, 1156–1158.
(9) (a) Barrios, A. M.; Lippard, S. J. J. Am. Chem. Soc. 1999, 121,
11751–11757. (b) Barrios, A. M.; Lippard, S. J. J. Am. Chem. Soc. 2000,
122, 9172–9177.
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Chem. Eur. J. 1999, 5, 1617–1630. (b) Meyer, F.; Pritzkow, H. Chem.
Commun. 1998, 1555–1556.
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Richardson, J. F.; Li, Q.; Hendrickson, D. N. J. Am. Chem. Soc. 1989,
111, 4497–4498. (b) Koga, T.; Furutachi, H.; Nakamura, T.; Fukita, N.; Ohba,
M.; Takahashi, K.; Okawa, H. Inorg. Chem. 1998, 37, 989–996. (c) Carlsson,
H.; Haukka, M.; Bousseksou, A.; Latour, J.; Nordlander, E. Inorg. Chem.
2004, 43, 8252–8262. (d) Uozumi, S.; Furutachi, H.; Ohba, M.; Okawa, H.;
Fenton, D. E.; Shindo, K.; Murata, S.; Kitko, D. J. Inorg. Chem. 1998, 37,
6281–6287.
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A.; Suzuki, S. J. Am. Chem. Soc. 1997, 119, 5752–5753. (b) Volkmer, D.;
Hommerich, B.; Griesar, K.; Haase, W.; Krebs, B. Inorg. Chem. 1996, 35,
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2008, 2538–2541.
(14) Gutkina, E. A.; Trukhan, V. M.; Pierpont, C. G.; Mkoyan, S.;
Strelets, W.; Norlander, E. Dalton Trans. 2006, 492–501.
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Latour, J.-M.; Le Pape, L. J. Am. Chem. Soc. 2001, 123, 8053–8066.

2876 Organometallics, Vol. 29, No. 13, 2010
Lee et al.
Figure 2. 1H NMR spectra of (a) [LNi2(CH3CN)(THF)](ClO4)3 (1) and (b) [LNi2(urea)2](ClO4)3 (2).
Table 1. Thia-Michael Addition of Thiophenols to r,β-Enones
Catalytic Studies. Conjugate addition of thiols to R,β-
unsaturated carbonyl compounds (thia-Michael addition)
is one of the most important synthetic strategies for C-S
bond formation.16 Several metal complexes have been re-
ported to facilitate the thia-Michael addition.17 Only a few
nickel complexes have shown the capability of catalyzing
such conjugate additions.18 Recently, we have reported a
low-coordinated nickel bis(benzimidazoyl) complex, which
possessed effective catalysis toward the conjugate additions
of thiophenols to R,β-enones.18a To extend this study, we
further examined the catalytic ability of complex 1 for the
previous reactions. 2-Cyclohexenone (5) was first selected as
a test Michael acceptor, and 4-methoxythiophenol (10) was
employed as a test Michael donor in the presence of catalyst 1.
An almost quantitative yield of 3-(4-methoxyphenylsulfanyl)-
cyclohexenone was produced in 2 h by using 1 mol% of 1
in acetonitrile (0.25 M) at room temperature (Table 1, entry 1).
Under the same reaction conditions, Ni(ClO4)2 6H2O and
3
(16) (a) Fluharty, A. L. In The Chemistry of the Thiol Group; Patai, S.,
Ed.; Wiley: New York, 1974; Part 2, p 589. (b) Clark, J. H. Chem. Rev. 1980,
80, 429–452. (c) Fujita, E.; Nagao, Y. J. Bioorg. Chem. 1977, 6, 287–309. (d)
Trost, B. M.; Keeley, D. E. J. Org. Chem. 1975, 40, 2013–2013. (e) Shono,
T.; Matsumura, Y.; Kashimura, S.; Hatanaka, K. J. Am. Chem. Soc. 1979,
101, 4752–4753. (f) Nishimura, K.; Ono, M.; Nagaoka, Y.; Tomioka, K. J.
Am. Chem. Soc. 1997, 119, 12974–12975.
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(b) Saito, M.; Nakajima, M.; Hashimoto, S. Chem. Commun. 2000, 1851–
1852. (c) Emori, E.; Arai, T.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc.
1998, 120, 4043–4044. (d) Delp, S. A.; Munro-Leighton, C.; Goj, L. A.;
Ramirez, M. A.; Gunnoe, T. B.; Petersen, J. L.; Boyle, P. D. Inorg. Chem.
2007, 46, 2365–2367. (e) Bandini, M.; Cozzi, P. G.; Giacomini, M.;
Melchiorre, P.; Selva, S.; Umani-Ronchi, A. J. Org. Chem. 2002, 67,
3700–3704. (f) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68,
2109–2114. (g) Ranu, B. C.; Mandal, T. Synlett 2004, 1239–1242. (h)
Kawatsura, M.; Komatsu, Y.; Yamamoto, M.; Hayase, S.; Itoh, T. Tetra-
hedron 2008, 64, 3488–3493. (i) Matsumoto, K.; Watanabe, A.; Uchida, T.;
Ogi, K.; Katsuki, T. Tetrahedron Lett. 2006, 47, 1291–1293. (j) Garg, S. K.;
Kumar, R.; Chakraborti, A. K. Tetrahedron Lett. 2005, 46, 1721–1724.
(18) (a) Lee, W.-Z.; Wang, T.-L.; Tseng, H.-S.; Liu, C.-Y.; Chen,
C.-T.; Kuo, T.-S. Organometallics 2009, 28, 652–655. (b) Evans, D. A.;
Seidel, D. J. Am. Chem. Soc. 2005, 127, 9958–9959. (c) Kanemasa, S.;
Oderaotoshi, Y.; Wada, E. J. Am. Chem. Soc. 1999, 121, 8675–8676.
a Yield of the reaction catalyzed by Ni(ClO4)2 6H2O: 64%; by HL: 33%.
3
HL were examined as control catalysts to evaluate the
catalytic ability of complex 1. The yields of the same reaction
catalyzed by Ni(ClO4)2 6H2O and by HL are 64% and 33%,
3
respectively. Apparently, complex 1 behaves as a more
effective catalyst for the conjugate additions of thiophenols to
R,β-enones. With this preliminary success, thia-Michael addi-
tions to other Michael acceptors such as 3-pentenone (6) and
5-methyl-3-hexenone (7) by 4-methoxythiophenol and

Article
Organometallics, Vol. 29, No. 13, 2010 2877
Table 2. Thia-Michael Addition of Thiophenols to Cycloenones
entry
Michael acceptor
Michael donor
n = 1
yield (%)
1
2
3
5
5
5
4-CH3OC6H4SH
3-CH3OC6H4SH
2-CH3OC6H4SH
96 (5a)
78 (5d)
58 (5e)
n = 0
4
5
6
8
8
8
4-CH3OC6H4SH
3-CH3OC6H4SH
2-CH3OC6H4SH
74 (8a)
77 (8d)
51 (8e)
Figure 4. Thermal ellipsoid representation of [LNi2(urea)2](ClO4)3
(2), at the 50% probability level. Hydrogen atoms, solvent mole-
cules, and the counteranions of 2 are omitted for clarity. Selected
n = 2
˚
˚
7
8
9
9
9
9
4-CH3OC6H4SH
3-CH3OC6H4SH
2-CH3OC6H4SH
89 (9a)
86 (9d)
81 (9e)
bond lengths for 2: Ni1-N1=2.059 A, Ni1-N2=2.043 A, Ni1-
˚
˚
˚
N3 = 2.081 A, Ni1-O1 = 2.197 A, Ni1-O2 = 1.985 A, Ni1-
˚
˚
˚
O3=2.031 A, Ni2-N6=2.057 A, Ni2-N7=2.047 A, Ni2-N8=
2.076 A, Ni2-O4=2.184 A, Ni2-O5=1.978 A, Ni2-O6=2.034 A.
˚
˚
˚
˚
Obviously, the decrease in reaction yield is caused by the steric
hindrance of the methoxy group of (methoxythio)phenol on
meta and ortho positions. In the case of the system for 4-, 3-, and
2-(methoxythio)phenols and 2-cyclopentenone (8), the indivi-
dual yields of the conjugate additions were lower than those for
the system of 2-cyclohexenone, specifically for 4-(methoxythio)-
phenol (Table 2, entries 4-6). Also, the reaction yields did not
follow their trend of bulkiness. The yield for entry 5 is higher
than that for entry 4. This result may be rationalized by the
stronger nucleophilicity of 3-(methoxythio)phenol compared to
that of 4-(methoxythio)phenol. For the system of 2-cyclohepte-
none, the yields of the Michael products for entries 7-9 in
Table 2 are similar. This phenomenon could be attributed to the
flexibility of the large ring size of cycloheptene. The overall result
suggests that complex 1 serves as an effective catalyst for the
conjugate additions of thiophenols to R,β-enones.
X-ray Structures of Nickel Complexes. The X-ray structure
of complex 1 reveals a dinickel complex, in which two nickel
ions are bridged by the central benzoate group of L (Figure 3).
Each nickel ion is coordinated by three nitrogen donors, i.e. one
amine and two pyridines, from a side arm of L and a solvent
molecule, CH3CN or THF. In addition, the oxygen atoms of
the ether groups in L coordinate to the nickel centers, causing
Figure 3. Thermal ellipsoid representation of [LNi2(CH3CN)-
(THF)](ClO4)3 (1) at the 50% probability level. Hydrogen atoms,
solvent molecules, and the counteranions of 1are omitted for clarity.
˚
Selected bond lengths for 1: Ni1-N1 = 2.062 A, Ni1-N2 =
˚
˚
˚
2.053 A, Ni1-N3 = 2.027 A, Ni1-N4 = 2.104 A, Ni1-O1 =
˚
˚
˚
2.173 A, Ni1-O2 = 1.970 A, Ni1A-O8A = 2.095 A.
its three derivatives, 4-(methylthio)phenol, thiophenol, and
4-(nitrothio)phenol, were further explored. When the nucleo-
philicity of thiophenols is decreased by installing an electron-
withdrawing substituent at the para position of thiophenols, the
yields for the conjugate additions are decreased (Table 1, entries
1-4). In addition, if the β-position of the alkene moiety in the
enones is more sterically hindered, the yields of the conjugate
additions are also decreased (Table 1, entries 1, 5, and 9). As
represented in the thia-Michael additions to substrate 7, the
reaction rates drop by 3-10 times. The data given in Table 1
clearly reveal that the yield for the thia-Michael addition of
4-methoxythiophenol to cyclohexenone (Table1, entry 1) is
much superior to those for other thia-Michael addition com-
binations. Therefore, the conjugate additions of 4-, 3-, or
2-(methoxythio)phenols to cycloenones with different ring sizes
were further investigated. When the methoxy substituent of the
Michael donor (methoxythio)phenol was changed from the
para to the ortho position, the yields of the conjugate additions
dropped dramatically from 96% to 58% (Table 2, entries 1-3).
complex 1 to form a W-shaped dinickel core with a Ni Ni
3 3 3
˚
separation of 5.8 A. Both nickel ions possess a distorted-
octahedral geometry, and the three nitrogen donors occupy
the meridional plane of the nickel coordination sphere. Com-
plex 2 was also structurally characterized by X-ray crystallo-
graphy. The molecular structure of 2 is similar to that of 1
(Figure 4). The dinickel core of 2 is W-shaped with a Ni Ni
3 3 3
˚
separation of 5.88 A.
Addition of acetate or diphenylacetate to an acetonitrile
solution of 1 afforded the tetranuclear nickel complexes
[LNi2(μ-OAc)]2(ClO4)4 (3) and [LNi2(μ-OAcPh2)]2(ClO4)4
(4), respectively. The molecular structures of 3 and 4
(Figure 5), determined by X-ray crystallography, display
an arrangement of a dimer of dimers.11c,13 Each dimer con-
sists of two nickel ions which are symmetrically bridged by
an acetate in 3 or a diphenylacetate in 4 and asymmetrically

2878 Organometallics, Vol. 29, No. 13, 2010
Lee et al.
Scheme 1
Figure 5. Thermal ellipsoid representations of (a) [LNi2(μ-OAc)]2-
(ClO4)4 (3), and (b) [LNi2(μ-OAcPh2)]2(ClO4)4 (4) at the 50%
probability level. Hydrogen atoms, solvent molecules, and the
counteranions of 3 and 4 are omitted for clarity. Selected bond
˚
˚
lengths for 3: Ni1-N1=2.055 A, Ni1-N2=2.138 A, Ni1-N3=
˚
˚
˚
2.044 A, Ni1-O2=2.162 A, Ni1-O3=2.173 A, Ni1-O5=2.000
A, Ni2-N4=2.039 A, Ni2-N5=2.062 A, Ni2-N6=2.062 A,
Ni2-O3 = 2.010 A, Ni2-O4 = 2.176 A, Ni2-O6 = 2.048 A.
Selected bond lengths for 4: Ni1-N4=2.036 A, Ni1-N5=2.142
A, Ni1-N6=2.037 A, Ni1-O1=2.145 A, Ni1-O2=2.187 A,
Ni1-O5=1.998 A, Ni2-N1=2.040 A, Ni2-N2=2.064 A, Ni2-
N3=2.041 A, Ni2-O2=2.003 A, Ni2-O3=2.154 A, Ni2-O6=
2.059 A, Ni3-N7=2.137 A, Ni3-N8=2.031 A,Ni3-N9=2.051 A,
Ni3-O7 = 2.172 A, Ni3-O8 = 2.151 A, Ni3-O11 = 1.998 A,
Ni4-N10=2.052 A, Ni4-N11=2.062 A, Ni4-N12=2.044 A,
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
˚
and 1/χM per nickel versus temperature for complexes 1, 3,
and 4 are given in Figures 7 and 8, respectively. The values of
χMT for complexes 1, 3, and 4 were 2.60, 2.38, and 2.26 cm3
mol-1 K at 300.0 K, respectively, and gradually decreased
upon cooling to 2.40, 2.06, and 2.16 cm3 mol-1 K at 30.0 K.
After the temperature was lowered to 30.0 K, the values
rapidly decreased to 0.96, 0.92, and 1.02 cm3 mol-1 K at 1.8
K. The observed χMT change over temperature is a typical
behavior of the antiferromagnetically coupled magnetic pair.
The magnetic exchange coupling between the nickel centers
for complexes 1, 3, and 4 was analyzed on the basis of the
Curie-Weiss expression and a dimer magnetic model. The
effective magnetic moment (μeff) was obtained from the slope
˚
˚
˚
Ni4-O7=2.008 A, Ni4-O10=2.192 A, Ni4-O12=2.049 A.
bridged by the central benzoate group of L. As acetate or
diphenylacetate replaced the bound solvent molecule on the
nickel center of 1, one ether oxygen atom of the side arm of L
and the central benzoate were dissociated from the nickel
center of the dinuclear 1, forming an open dimer. Subse-
quently, a dimer of dimers was constructed by the coordina-
tion of the acetate or diphenylacetate to the benzoate bound
nickel center of an adjacent open dimer and the bidentate
bonding of the central benzoate from the adjacent open dimer
to the nickel center of the first open dimer (Scheme 1). In
addition tothe similarity of the first coordinationsphereof the
dinickel core of 3 or 4 to that of the active site of urease, we
notice that the distance between two nickel ions in the dinickel
of those plots in the high-temperature region, in which the
2
data obey the Curie-Weiss law, χM = C/(T - Θ) = Nμeff
/
3k(T - Θ), where C, Θ, N, and k are the Curie, Weiss,
Avogadro, and Boltzmann constants, respectively. All three
data sets follow a linear Curie-Weiss law behavior, and the
effective magnetic moments (μeff) per Ni ion and Weiss
constants for complexes 1, 3, and 4 can be determined. The
effective magnetic moments per Ni of complexes 1, 3, and 4
are 3.24, 3.06, and 3.01 μB, respectively, which are typical
˚
cores of 3 and 4 is about 3.7 A, similar to that in the enzyme
(Figure 6).
Magnetic Properties. The magnetic properties of polycrys-
talline samples of 1, 3, and 4 have been studied at 1 kG over
temperatures ranging from 1.8 to 300.0 K. The product χMT
per nickel dimer, where χM is the molar magnetic susceptibility,

Article
Organometallics, Vol. 29, No. 13, 2010 2879
Figure 6. Ball and stick representations of a dimer moiety in 3 (left) and the active site of urease (right).
Figure 7. Plots of the product of molar magnetic susceptibilities
with temperature, χMT, versus temperature for polycrystalline
samples of complexes 1 (0), 3 (O), and 4 (4). The solid lines are
the best fits for eq 1.
Figure 8. Plots of inverse magnetic susceptibilities (1/χM) versus
temperature for polycrystalline samples of complexes 1 (9), 3
(b), and 4 (2). The solid lines are best linear fits for the
Curie-Weiss law.
data χMT per nickel dimer versus temperature for complexes
1, 3, and 4 are illustrated in Figure 7. The magnetic para-
meters obtained are as follows: for complex 1, g = 2.24, J =
-0.72 cm-1 and TIP = 4.9 ꢀ 10-4 emu mol-1; for complex 3,
3
values of six-coordinated Ni(II) and establish A2 ground
states. The values of μeff are larger than the spin-only value of
2.83 μB, and these are commonly observed for the Ni(II)
centers due to incomplete quenching and arise from the spin-
orbital coupling. The Weiss constants are -2.95, -3.95, and
-1.75 K for complexes 1, 3, and 4, respectively. The negative Θ
values indicate antiferromagnetic exchange interactions bet-
ween nickel centers.
The magnetic interactions between the nickel centers can be
treated as a nickel dimer model. Assuming an isotropic model,
the exchange expression for two equivalent S=1ionsbasedon
g = 2.06, J = -0.65 cm-1, and TIP = 8.4 ꢀ 10-4 emu mol-1
;
for complex 4,g= 2.13, J=-0.65 cm-1, andTIP=2.4ꢀ 10-5
emu mol-1. Such a weak antiferromagnetic interaction was also
observed in the active site of urease.19 Although the Ni Ni
3 3 3
separation is shorter for complexes 3 and 4 than for complex 1,
the carboxylate bridge ligands are not good pathways for
magnetic coupling, and antiferromagnetic interaction constants
of the three complexes are near -0.7 cm-1
.
the spin Hamiltonian, H = -2JS1 S2, is given by
3
Concluding Remarks
Ng2β2 2 expð2J=kTÞ þ 10 expð6J=kTÞ
χM
¼
þ TIP
The dinickel complex 1 coordinated by solvent molecules,
CH3CN and THF, was synthesized by reacting the disubsti-
kT 1 þ 3 expð2J=kTÞ þ 5 expð6J=kTÞ
ð1Þ
tuted benzoate L- with Ni(ClO4)2 6H2O. The labile coordi-
3
nation of CH3CN and THF in 1 allows the coordination of
urea or anionic OAc- or OAcPh2- to the nickel centers of 1
The symbols N, β, g and k have their usual meanings.
Jrepresents the exchange coupling interaction, and TIP is the
temperature-independent paramagnetism of nickel dimer
centers. Least-squares fitting of eq 1 to the experimental
(19) Clark, P. A.; Wilcox, D. E. Inorg. Chem. 1989, 28, 1326–1333.

2880 Organometallics, Vol. 29, No. 13, 2010
Table 3. Selected X-ray Crystallographic Data for Complexes 1-4
Lee et al.
1
2
3
4
empirical formula
fw
T (K)
C
41H46Cl2N7Ni2O13
C41H49Cl3N12Ni2O18
1221.69
200(2)
C74H84Cl4N12Ni4O31
2014.17
200(2)
C116H123Cl4N17Ni4O30
2611.95
200(2)
1033.17
200(2)
cryst syst
space group
monoclinic
C2/c
30.6691(5)
9.5065(2)
18.3372(4)
90
114.5660(10)
90
4862.38(17)
4
1.411
monoclinic
C2/c
26.8326(12)
26.1759(12)
17.3070(8)
90
119.0910(10)
90
10622.4(8)
8
1.528
monoclinic
C2/c
21.0070(3)
34.1810(6)
16.9250(4)
90
112.1910(10)
90
11252.7(4)
4
1.189
monoclinic
P21/c
23.8448(2)
20.2926(2)
24.8296(2)
90
96.57
90
11935.50(18)
4
1.454
˚
a (A)
˚
b (A)
˚
c (A)
R (deg)
β (deg)
γ (deg)
3
˚
V (A )
Z
Dcalcd (g/cm3)
μ (mm-1
)
0.951
0.48 ꢀ 0.30 ꢀ 0.15
0.941
0.24 ꢀ 0.15 ꢀ 0.06
0.822
0.45 ꢀ 0.40 ꢀ 0.40
0.795
0.25 ꢀ 0.20 ꢀ 0.10
cryst size (mm)
goodness of fit F2
R1
1.111
0.0664
0.2044
1.103
0.0619
0.1666
1.059
0.0722
0.2194
1.018
0.0645
0.1614
wR2
to form the urea adduct of 2 or tetranuclear 3 or 4. For the
urea adduct of 2, both 1H NMR and ESI-MS spectra have
evidenced that the bound urea molecules did not dissociate
from the nickel centers of the complex in solution. The
coordination of urea in 2 suggests that nucleophiles, such
as R,β-enones or thiols, could also bind to the nickel centers
of 1. The conjugate additions of thiophenols to R,β-enones
catalyzed by complex 1 was observed, and the yield of the
thia-Michael additions is mainly governed by the steric
hindrance of R,β-enones and the nucleophilicity of thiophe-
nols. Notably, the dinickel cores of 3 and 4 structurally
mimic the active site of urease.
product of 1 was isolated and dissolved in acetonitrile for
recrystallizationbythe slowdiffusion of THFintothe acetonitrile
solution at ambient temperature. Blue crystals were obtained in 1
week in 73% yield (0.8864 g). Anal. Calcd for [LNi2(CH3CN)-
(THF)](ClO4)3 (Ni2C41H46N7Cl3O17): C, 43.48; H, 4.09; N, 8.66.
Found: C, 43.12; H, 4.06; N, 8.92. UV-vis (CH3CN, λmax, nm
(ε, cm-1 M-1)): 361 (88), 564 (40), 860 (42). IR (KBr, cm-1): 2061
(νCN), 1605 (νpy), 1560 (νpy), 1446, 1397, 1291, 1146 (νClO ), 1117
-
4
(νClO
-
), 1086(νClO
-
), 766, 727, 635(νClO
-
), 627(νClO ). ESI-MS
-
4
4
4
4
(m/z, amu): 919 [LNi2(ClO4)2]þ, 410 [LNi2(ClO4)]2þ, 254
[LNi2(CH3CN)]3þ, 240 [LNi2]3þ
[LNi2(urea)2](ClO4)3 2CH3CN (2). Urea (0.0242 g, 0.4 mmol)
.
3
was dissolved in methanol (10 mL) and transferred into a blue
acetonitrile solution (10 mL) of complex 1 (0.2264 g, 0.2 mmol).
The reaction mixture was stirred for 2 h; then the solvent of the
resulting mixture was removed under vacuum to give a blue
residue. The resulting residue was dissolved in acetonitrile for
recrystallization by the slow diffusion of diethyl ether into the
acetonitrile solution of 2 at ambient temperature. Light blue
crystals were obtained in 1 week in 67% yield (0.1558 g). Anal.
Experimental Section
Methods and Materials. All manipulations were performed
under nitrogen using standard Schlenk techniques. Methanol
was dried over magnesium iodide prior to use. Acetonitrile was
distilled once from P2O5 and freshly distilled from CaH2 before
use. Dichloromethane was distilled from CaH2 before use.
Diethyl ether and THF were dried by distillation from sodium
benzophenone prior to use. All reagents were obtained from
commercial sources and used as received without further pur-
ification. UV-vis spectra were recorded on Hitachi U-3501
spectrophotometers. IR spectra were recorded using KBr pellets
on a Perkin-Elmer Paragon 500 spectrometer. NMR spectra
were recorded on Bruker Avance-400 MHz FT NMR spectro-
meters. ESI-MS spectra were recorded on a Thermo Finnigan
LCQ Advantage spectrometer. Elemental analyses for C, H, and
N were performed on a Perkin-Elmer 2400 analyzer at the NSC
Regional Instrumental Center at National Taiwan University,
Taipei, Taiwan.
2,6-Bis[(2-bis(2-pyridylmethyl)aminoethoxy)]benzoic Acid (HL).
HL was prepared by adopting a reported method.14 1H NMR
(400 MHz, CDCl3, ppm): 8.33-8.32 (m, 4H, Ar), 7.69-7.64 (m,
8H, Ar), 7.08-7.07 (m, 4H, Ar), 6.93 (t, 1H, Ar, J = 8.4 Hz), 6.21
(d, 2H, Ar, J = 8.4 Hz), 4.06 (t, 4H, CH2, J = 4.4 Hz), 3.98 (s, 8H,
CH2), 3.03 (t, 4H, CH2, J = 4.4 Hz). 13C NMR (100 MHz, CDCl3,
ppm): 167.9, 159.4, 155.7, 148.3, 137.3, 130.3, 123.8, 122.3, 116.3,
104.7, 66.6, 60.7, 53.4. ESI-MS (m/z, amu): 605 [M þ H]þ.
[LNi2(CH3CN)(THF)](ClO4)3 (1).NaOMe (0.0577 g, 1.07 mmol)
was added to a methanol solution (80 mL) of HL (0.6471 g,
1.07 mmol) and reacted for 2 h. The reaction mixture was then
Calcd for [LNi2(urea)2](ClO4)3 CH3CN (Ni2C39H46N11Cl3O18):
3
C, 39.68; H, 3.93; N, 13.05. Found: C, 39.29; H, 4.12; N, 13.14. mp:
212-214 °C. UV-vis (CH3CN, λmax, nm (ε, cm-1 M-1)): 362sh
(78), 573 (42), 894 (42). IR (KBr, cm-1): 3204 (νNH), 1662 (νCO),
1651 (νCOO-), 1632 (νCOO-), 1606 (νpy), 1557 (νpy), 1446, 1399,
1240, 1144 (νClO -), 1116 (νClO -), 1088 (νClO -), 766, 636 (νClO -),
4
4
4
4
627 (νClO -). ESI-MS (m/z, amu): 919 [LNi2(ClO4)2]þ, 440
4
[LNi2(urea)(ClO4)]2þ, 410 [LNi2(ClO4)]2þ, 240 [LNi2]3þ
.
[LNi2(μ-OAc)]2(ClO4)4 3H2O(3). NaOAc (0.0164 g, 0.2 mmol)
3
was dissolved in 10 mL of methanol and transferred into an
acetonitrile solution (30 mL) of complex 1 (0.2264 g, 0.2 mmol)
to form a light blue solution. The reaction mixture was stirred for
2 h. The solvent of the resulting mixture was then removed under
vacuum to give a blue residue. The residue was washed by THF
(40 mL ꢀ 3) to remove NaClO4. The blue product of 3 was isolated
and dissolved in acetonitrile for recrystallization by the slow
diffusion of THF into the acetonitrile solution at ambient tem-
perature. Light blue crystals were obtained for 1 week in 78% yield
(0.1588 g). Anal. Calcd for [LNi2(μ-OAc)]2(ClO4)4 3H2O (Ni4-
3
C74H84N12Cl4O31): C, 44.13; H, 4.21; N, 8.35. Found: C, 44.46; H,
4.70; N, 8.62. Mp: 282-284 °C. UV-vis (CH3CN, λmax, nm (ε,
cm-1 M-1)): 358 sh (70), 587 (64), 1003 (58). IR (KBr, cm-1): 3401
(νOH), 1607 (νpy), 1574 (νpy), 1483, 1446, 1382, 1242, 1146 (νClO -),
4
1114 (νClO -), 1089 (νClO -), 1026, 767, 636 (νClO -), 626 (νClO -).
4
4
4
4
added to an acetonitrile solution (15 mL) of Ni(ClO4)2 6H2O
ESI-MS (m/z, amu): 879 [L2Ni4(μ-OAc)2(ClO4)2]2þ, 553 [L2Ni4-
3
(0.7818 g, 1.07 mmol) to form a light blue solution. After the
mixture was stirred for 2 h, the solvent of the blue solution was
removed under vacuum to give a blue residue. The residue was
washed by THF (80 mL ꢀ 3) to remove NaClO4. The blue
(μ-OAc)2(ClO4)]3þ, 390 [L2Ni4(μ-OAc)2]4þ
[LNi2(μ-OAcPh2)]2(ClO4)4 5CH3CN 2THF (4). The pre-
paration of complex 4 was the same as for complex 3. Light
.
3
3
blue crystals of 4 were obtained in 1 week in 86% yield. Anal.

Article
Calcd for [LNi2(μ-OAcPh2)]2(ClO4)4 3CH3CN THF (Ni4C108
Organometallics, Vol. 29, No. 13, 2010 2881
-
109N15Cl4O29): C, 52.78; H, 4.47; N, 8.55. Found: C, 52.67; H,
solved by direct methods using SIR92 or SIR97 and refined using
SHELXL-97. Solvent molecules packing in the crystal lattices of
1-4 were severely disordered and were squeezed by the Platon
program. An empirical absorption correction by multiscans was
applied to all structures. All non-hydrogen atoms were refined with
anisotropic displacement factors. Hydrogen atoms were placed in
ideal positions and fixed with relative isotropic displacement
parameters. Selected crystallographic data for 1-4 are given in
Table 3, and their detailed crystallographic data are provided as
CIF files in the Supporting Information. CCDC reference num-
bers are 737500, 750896, 737501, and 737502.
Magnetic Measurements. Variable-temperature dc magnetic
susceptibility and ac magnetic susceptibility measurements were
collected on microcrystalline samples, restrained in eicosane to
prevent torquing, on a Quantum Design MPMS-XL SQUID
magnetometer equipped with a 7.0 T magnet and operating in
the range of 1.8-300.0 K. Diamagnetic corrections were esti-
mated from Pascal’s constants20 and subtracted from the ex-
perimental susceptibility data to obtain the molar paramagnetic
susceptibility of the compounds.
3
3
H
4.63; N, 8.68. Mp: 284-287 °C. UV-vis (CH3CN, λmax, nm
(ε, cm-1 M-1)): 363 sh (99), 588 (67), 993 (63). IR (KBr, cm-1):
2072 (νCN), 1608 (νpy), 1576 (νpy), 1483, 1449, 1393, 1275, 1243, 1146
(νClO -), 1117 (νClO -), 1088 (νClO -), 765, 707, 635 (νClO -), 626
4
4
4
4
(νClO -). ESI-MS (m/z, amu): 1032 [L2Ni4(μ-OAcPh)2(ClO4)2]2þ
,
4
655 [L2Ni4(μ-OAcPh)2(ClO4)]3þ, 466 [L2Ni4(μ-OAcPh)2]4þ
.
General Procedure for the Conjugate Additions Catalyzed by
Complex 1. To a blue acetonitrile solution (4 mL) of complex 1
(0.0164 g, 0.02 mmol) was added an R,β-enone (2.0 mmol) under
a nitrogen atmosphere with stirring for 5 min. As the thiol
(1.0 mmol) was added to the reaction mixture, the solution
became brick red. The resulting solution was stirred at room
temperature for 2 h, and the solvent was evaporated under
vacuum. The residue was then purified by column chromato-
graphy on silica gel (hexane/AcOEt, 9/1) to give the conjugate
adduct. Characterization of the conjugate addition products are
listed in Supporting Information.
X-ray Structure Determination. Crystals of a suitable size for
CCD X-ray diffractometry were selected under a microscope and
mounted on the tip of a glass fiber fashioned on a copper pin. X-ray
data for complexes 1 and 2 were collected on a Bruker-Nonius
Kappa CCD diffractometer, and data for complexes 3 and 4 were
collected on a Bruker Kappa Apex II diffractometer. Both instru-
ments employed graphite-monochromated Mo KR radiation (λ =
Acknowledgment. We acknowledge financial support
from the National Science Council of Taiwan (Grant No.
NSC 97-2113-M-003-004-MY2 to W.-Z.L.).
˚
Supporting Information Available: CIF files giving X-ray
crystallographic data for complexes 1-4 and text and figures
giving additional details of the syntheses and 1H and 13C NMR
data and spectra of the conjugate addition products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
0.7107 A) at 200 K and a θ-2θ scan mode. The space groups for
complexes 1-4 were determined on the basis of systematic ab-
sences and intensity statistics, and the structures of 1-4 were
(20) Boudreaux, E. A.; Mulay, L. N. Theory and Application of
Molecular Paramagnetism; Wiley: New York, 1976; p 491.