Synthesis and structures of zinc complexes with new binucleating ligands containing alkoxide bridges, and their activities in the hydrolysis of tris(p-nitrophenyl)phosphate

Article abstract of DOI:10.1016/j.ica.2008.12.012

Four new binucleating ligands featuring a hydroxytrimethylene linker between two coordination sites (1,3-bis{N-[3-(dimethylamino)propyl]-N-methylamino}propan-2-ol, HL¹; 1,3-bis{N-[2-(dimethylamino)ethyl]-N-methylamino}propan-2-ol, HL²

Full text of DOI:10.1016/j.ica.2008.12.012

Inorganica Chimica Acta 362 (2009) 2722–2727
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Synthesis and structures of zinc complexes with new binucleating ligands
containing alkoxide bridges, and their activities in the hydrolysis of
tris(p-nitrophenyl)phosphate
a
b
Katsura Mochizuki a, , Yukiko Ishima , Kiyoharu Hayano
*
a International Graduate School of Arts and Sciences, Yokohama City University, Yokohama 236-0027, Japan
b Hokkaido University of Education Sapporo, Sapporo 002-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 October 2008
Received in revised form 8 December 2008
Accepted 12 December 2008
Available online 25 December 2008
Four new binucleating ligands featuring a hydroxytrimethylene linker between two coordination sites
(1,3-bis{N-[3-(dimethylamino)propyl]-N-methylamino}propan-2-ol,
HL1;
1,3-bis{N-[2-(dimethyl-
amino)ethyl]-N-methylamino}propan-2-ol, HL2; 1,3-bis[bis(2-methoxyethyl)amino]propan-2-ol, HL3;
and 1-bis[(2-methoxyethyl)amino]-3-{N-[2-(dimethylamino)ethyl]-N-methylamino}propan-2-ol, HL4)
were synthesized, along with the corresponding zinc complexes. The structures of three dinuclear zinc
complexes ([Zn2L1(
l
-CH3COO)2]BPh4 (1), [Zn2L3(
l
-CH3COO)2]BPh4 (3), and [Zn2L4(
-CH3COO)]2( -OH)2}(BPh4)2 (2)) were
l-CH3COO)(CH3-
Keywords:
COO)(EtOH)]BPh4 (4)) and a tetranuclear zinc complex ({[Zn2L2(
l
l
Zinc complexes
Binucleating ligands
Synthesis
revealed by X-ray crystallography. Hydrolysis of tris(p-nitrophenyl)phosphate (TNP) by these zinc com-
plexes in an acetonitrile solution containing 5% Tris buffer (pH 8.0) at 30 °C was investigated spectropho-
tometrically and by 31P NMR. Although zinc complexes 1, 3, and 4 did not show hydrolysis activity, the
Hydrolysis
tetranuclear zinc complex 2, containing
l-hydroxo bridges, was capable of hydrolyzing TNP. This sug-
gests that the hydroxide moiety in the complex may have an important role in the hydrolysis reaction.
Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction
tially binucleating ligand (HL1, Scheme 1) [21]. In this work, in
order to investigate the coordination behavior of such ligands,
It is well known that the active sites of a number of enzymes
contain metal ions [1,2]. Dinuclear metal sites in enzymes have
been the subject of particular attention from coordination chem-
ists, especially with respect to the relationship between structure
and function. Accordingly, many binucleating ligands have been
synthesized and used in complexes modeling dinuclear metal sites
[1–3]; in particular, extensive studies have been carried out using
dinickel(II) complexes to model the active site of urease [4] and di-
zinc(II) complexes to model the trinuclear sites of P1 nuclease [5]
and alkaline phosphatase [5]. One strategy for the synthesis of
binucleating ligands involves the use of a 2-hydroxytrimethylene
linker which can bridge two metal ions proximately via an alkoxide
moiety [6–17]. In previous studies, we synthesized binucleating
bis(macrocyclic) ligands and studied their dinuclear metal com-
plexes [18–20]. In the course of our synthesis of a bis(macrocyclic)
ligand containing a 2-hydroxytrimethylene bridge, it was inciden-
tally found that methylation of the hexaamine ligand (HL) [20]
used as a starting material for the bis(macrocycle) resulted in deal-
kylation of the N,N-dimethylaminopropyl arms to afford a poten-
we synthesized four new binucleating ligands (HL1, HL2, HL3, and
HL4) containing a 2-hydroxytrimethylene linker between the two
coordination sites, as well as the corresponding zinc complexes.
The formation of dinuclear (HL1, HL3, and HL4) and tetranuclear
(HL2) zinc complexes was confirmed by X-ray crystallography. In
addition, the hydrolysis reaction of tris(p-nitrophenyl)phosphate
(TNP) by these zinc complexes was investigated.
2. Experimental
2.1. Synthesis of binucleating ligands
1,3-Bis{N-[3-(dimethylamino)propyl]-N-methylamino}propan-2-
ol (HL1): To an ethanol solution (10 ml) of N,N,N0-trimethyl-1,3-
propanediamine (2.0 g, 17.21 mmol) were added triethylamine
(3.0 g, 29.65 mmol) and epichlorohydrin (0.8 g, 8.65 mmol), and
the mixture was refluxed for 15 h. The solution was then evapo-
rated to half its original volume and basified to ca. pH 12 by the
addition of a 6 mol dmꢀ3 NaOH solution. The product was ex-
tracted three times with dichloromethane (10 ml). The yellow ex-
tract was dried over sodium sulfate and evaporated to dryness to
yield viscous oil. The free ligand was purified by conversion of
the crude ligand to its hydrochloride salt and re-extraction of the
* Corresponding author. Tel.: +81 45 787 2186; fax: +81 45 787 2413.
E-mail address: katsura@yokohama-cu.ac.jp (K. Mochizuki).
0020-1693/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2008.12.012

K. Mochizuki et al. / Inorganica Chimica Acta 362 (2009) 2722–2727
2723
0.29 g, 56%. HRMS (FAB) calc. for [C19H41N4O564Zn2]+: m/z
533.1660, found: m/z 533.1662. IR (KBr):
m
1601 cmꢀ1 (CH3COOꢀ),
1470 cmꢀ1, 1429 cmꢀ1, 704 cmꢀ1. Crystals suitable for X-ray anal-
ysis were obtained by recrystallization from acetonitrile/ethanol.
{[Zn2L2(
l-CH3COO)]2(l-OH)2}(BPh4)2 (2): To an ethanol solution
(5 ml) of HL2 (0.130 g, 0.50 mmol) was added Zn(CH3COO)2ꢁ2H2O
(0.24 g, 1.09 mmol), and the solution was heated at 60 °C for 2
hours. The addition of NaBPh4 (0.40 g, 1.17 mmol) resulted in the
formation of a white precipitate, which was filtered and dried in
vacuum. Yield: 0.16 g, 41%. Anal. Calc. for C78H110N8O8B2Zn4: C,
59.64; H, 7.06; N, 7.13. Found: C 59.48, H 7.27, N 7.05%. MS
(ESI): m/z 1251.4 [M-BPh4]+, 465.1 [Zn2L2(CH3COO)(OH)]+. IR
(KBr):
m
3656 cmꢀ1 sharp (OHꢀ), 1593 cmꢀ1 (CH3COOꢀ),
1466 cmꢀ1, 1421 cmꢀ1, 706 cmꢀ1. Crystals suitable for X-ray anal-
ysis were obtained by recrystallization from nitromethane/
diethylether.
[Zn2L3(
l-CH3COO)2]BPh4 (3): To an ethanol solution (5 ml) of
HL3 (0.10 g, 0.31 mmol) was added Zn(CH3COO)2ꢁ2H2O (0.14 g,
0.64 mmol). The solution was heated at 60 °C for 2 h. The addition
of the NaBPh4 (0.11 g, 0.32 mmol) resulted in the formation of a
white precipitate, which was filtered and dried in vacuum. Yield:
0.18 g, 64%. Crystals suitable for X-ray analysis were obtained by
recrystallization from nitromethane/diethylether. Anal. Calc. for
C43H59N2O9B1Zn2: C, 58.06; H, 6.69; N, 3.15. Found: C, 58.28; H,
6.70; N, 3.28%.
Scheme 1. Syntheses and structure formulae.
ligand from a basic aqueous solution. Yield: 83%. HRMS (APCI) calc.
for [C15H36N4O1+H]+: m/z 289.2967, found: m/z 289.2967. 13C NMR
(CDCl3): d 25.6 (t), 43.0 (q), 45.6 (q), 55.9 (t), 57.9 (t), 62.3 (t), 66.0
(d) ppm.
[Zn2L4(
l-CH3COO)(CH3COO)(EtOH)]BPh4 (4): To an ethanol solu-
tion (5 ml) of HL4 (0.10 g, 0.34 mmol) was added
Zn(CH3COO)2ꢁ2H2O (0.20 g, 0.91 mmol), and the solution was
heated at 60 °C for 2 h. The addition of NaBPh4 (0.23 g, 0.67 mmol)
resulted in the formation of a white precipitate, which was filtered
and dried in vacuum. Yield: 0.26 g. Anal. Calc. for C44H64N3O8B1Zn2:
C, 58.42; H, 7.13; N, 4.63. Found: C, 58.35; H, 7.12; N, 4.73%. Crys-
tals were obtained by recrystallization from nitromethane/
diethylether.
1,3-Bis{N-[2-(dimethylamino)ethyl]-N-methylamino}propan-2-ol
(HL2): HL2 was prepared by a similar procedure to HL1, but using
N,N,N0-trimethylethylenediamine instead of N,N,N0-trimethyl-1,3-
propanediamine. Yield: 41%. HRMS (EI) calc. for [C13H33N4O1]+:
m/z 261.2654, found: m/z 261.2646. 13C NMR (CDCl3): d 43.4 (q),
45.3 (q), 55.7 (t), 57.1 (t), 62.0 (t), 66.1 (d) ppm.
1,3-Bis[bis(2-methoxyethyl)amino]propan-2-ol (HL3): HL3 was
prepared by a similar method to HL1 and using bis(2-methoxy-
ethyl)amine. Yield: 59%. HRMS (APCI) calc. for [C15H34N2O5+H]+:
m/z 323.2546, found: m/z 323.2561. 13C NMR (CDCl3): d 54.5 (q),
58.2 (t), 59.2 (t), 66.5 (d), 71.0 (t) ppm.
2.3. Physical measurements
13C NMR spectra were recorded using a Bruker DRX 300 spec-
trometer and a JEOL EPC-400 spectrometer. Mass spectra were
measured using a JEOL DX-303 spectrophotometer and high reso-
lution mass spectra were measured at the Center for Instrumental
Analysis of Hokkaido University.
1-Bis[(2-methoxyethyl)amino]-3-{N-[2-(dimethylamino)ethyl]-N-
methylamino}propan-2-ol (HL4): To an ethanol solution (10 ml) of
epichlorohydrin (1.4 g, 15.13 mmol) was added dropwise an etha-
nol solution (5 ml) of bis(methoxyethyl)amine (2.0 g, 15.02 mmol).
After the mixture had been heated at 80 °C for 3 h, the solution was
cooled to 60 °C and NaOH (0.60 g, 15.0 mmol) in a minimum
amount of water was added. N,N,N’-Trimethylethylenediamine
(1.50 g, 14.7 mmol) was added to the mixture, which was then fur-
ther heated at 80 °C for 3 h. The solution was cooled to room tem-
perature, evaporated to its half volume, and basified to ca. pH 12 by
the addition of a 6 mol dmꢀ3 NaOH solution. The product was ex-
tracted with dichloromethane (10 ml) three times. The resulting
yellow extract was dried over sodium sulfate and evaporated to
dryness to yield a yellow viscous oil (3.2 g). The crude free ligand
was purified by column chromatography on silica gel (Merck silica
gel 60, CHCl3:MeOH = 1:1). Yield: 1.43 g, 33%. HRMS (EI) calc. for
[C14H34N3O3]+: m/z 292.2600, found: m/z 292.2602. 13C NMR
(CDCl3): d 43.2 (q), 45.0 (q), 54.7 (t), 55.0 (t), 56.8 (t), 58.5 (q),
59.4 (t), 61.7 (t), 66.3 (d), 70.9 (t) ppm.
2.4. Crystallographic studies
X-ray crystallography of single crystals was carried out on a
MAC Science MXC3k four-circle (x-2h scan: 1 and 3, x-scan: 2
and 4) diffractometer with graphite-monochromatized Mo K
a
radiation (k = 0.71073 Å). The structures were solved by the direct
method (SIR92 and SIR97 [22]), and refined on F2 by the full-matrix
least-squares method SHELXL-97 [23]). The u-scan was applied for
absorption correction [24]. All non-hydrogen atoms were refined
using anisotropic thermal parameters (riding model refinement).
Hydrogen atoms were placed by SHELXL [23]. All calculations were
carried out using a SiliconGraphics O2 work station (MAXUS program
system provided by MAC Science). Structural diagrams were drawn
using ORTEP-3 for Windows [25]. Crystallographic data for the
complexes are listed in Table 1. Because [Zn2L4(
COO)(EtOH)]BPh4 (4) was unstable in air due to loss of solvent mol-
ecules, crystal covered with epoxy resin was used for
l-CH3COO)(CH3-
2.2. Synthesis of zinc complexes
a
measurement. During analysis of 4, disorder was found in the coor-
dinated ethanol, which was treated using the SHELXL commands
PART 1 (65.4%) and PART 2 (34.6%), with restraints on the HO–
CH2 and CH2–CH3 distances between the two parts (data/re-
straints/parameters: 10724/2/545). No restraints were applied
for the other complexes.
[Zn2L1(
l-CH3COO)2]BPh4 (1): To an ethanol solution (5 ml) of
HL1 (0.20 g, 0.70 mmol) was added Zn(CH3COO)2ꢁ2H2O (0.33 g,
1.50 mmol), and the solution was heated at 60 °C for 2 h. The addi-
tion of NaBPh4 (0.24 g, 0.70 mmol) resulted in the formation of a
white precipitate, which was filtered and dried in vacuum. Yield:

2724
K. Mochizuki et al. / Inorganica Chimica Acta 362 (2009) 2722–2727
Table 1
Crystallographic data of complexes.
Complex
1
2
3
4
Empirical formula
Formula weight
T (K)
BC43H61N4O5Zn2
855.56
298(2)
B2C78H110N8O8Zn4
1570.94
298(2)
B1C43H59N2O9Zn2
889.53
298(2)
B1C44H64N3O8Zn2
904.59
298(2)
k (Å)
0.71070
0.71070
0.71070
0.71070
Crystal system
Space group
Unit cell dimensions
a (Å)
b (Å)
c (Å)
triclinic
P1
monoclinic
P21/c
triclinic
P1
monoclinic
P21/c
ꢀ
ꢀ
9.5640(14)
15.309(2)
16.507(2)
74.502(8)
77.309(10)
83.877(10)
2269.1(5)
2
12.255(4)
13.835(4)
29.425(8)
10.947(3)
14.260(6)
14.690(3)
103.26(2)
93.34(2)
91.14(3)
2226.9(11)
2
14.247(4)
18.104(3)
18.335(3)
a
(°)
b (°)
120.02(4)
99.15(2)
c
(°)
V (Å3)
4320(2)
4
1.208
1.150
4669(2)
4
1.287
1.079
Z
Dcalc (Mg mꢀ3
)
1.252
1.102
1.326
1.131
l
(mmꢀ1
)
F(000)
904
1656
936
1912
Crystal size (mm)
0.50 ꢂ 0.40 ꢂ 0.20
0.50 ꢂ 0.50 ꢂ 0.30
0.50 ꢂ 0.20 ꢂ 0.20
0.80 ꢂ 0.30 ꢂ 0.10
Reflections collected
Independent reflections [Rint
Goodness-of-fit (GOF)
11046
9884
10649
11059
]
10238 [0.0093]
1.153
9884 [0.0012]
1.131
10236 [0.0447]
1.055
10724 [0.0467]
1.019
Final R indices [I > 2
r(I)]
R1 = 0.0465, wR2 = 0.1529
1.923 and ꢀ0.705
R1 = 0.0883, wR2 = 0.2709
2.003 and ꢀ0.608
R1 = 0.0674, wR2 = 0.1957
1.142 and ꢀ0.423
R1 = 0.0603, wR2 = 0.1110
0.529 and ꢀ0.450
Largest difference in peak and hole (e Åꢀ3
)
2.5. Hydrolysis of tris(p-nitrophenyl)phosphate (TNP)
The hydrolysis reactions of tris(p-nitrophenyl)phosphate (TNP)
by the zinc complexes synthesized in this study were evaluated
spectrophotometrically. The zinc complex and TNP were dissolved
in an acetonitrile solution containing 5% Tris buffer
(2 ꢂ 10ꢀ3 mol dmꢀ3, pH 8.0) aqueous solution. The spectral change
of the mixture from 350 to 500 nm was monitored at 30 °C.
The hydrolysis of TNP in CD3CN was confirmed by measure-
ment of 31P NMR spectra using a 10 mm tube with 85% phosphoric
acid as an external standard in the inner capillary tube. 31P NMR
spectra were measured at 26 °C using a JEOL FX-90Q spectrometer.
3. Results and discussion
As dealkylation of the N,N-dimethylaminopropyl arms of HL to
give HL1 occurred during a separate investigation [21], in this
study we attempted to synthesize HL1, which was expected to
act as a binucleating ligand, by another pathway (Scheme 1). HL1
was synthesized by the reaction of epichlorohydrin with N,N’,N’-
trimethylpropanediamine, as were the analogous ligands HL2
(N,N-dimethylaminoethyl arms), HL3 (methoxyethyl arms), and
HL4 (unsymmetrical arms).
As expected, all ligands synthesized in this study acted as binu-
cleating ligands to form zinc complexes with a ligand-to-metal ra-
tio of 1:2. The hydroxy group in each ligand was deprotonated and
coordinated to two zinc ions. Although three of the ligands—HL1,
HL3, and HL4—formed dinuclear zinc complexes under similar syn-
thetic conditions, only HL2, which contains N,N-dimethylamino-
ethyl arms, formed a tetranuclear zinc complex, in which two
dinuclear units were linked by two hydroxide ions.
Fig. 1. ORTEP drawing of cation portion of 1. Selected bond lengths (Å) and angles
(°): Zn(1)–O(20) 2.001(2), Zn(1)–O(42) 2.019(2), Zn(1)–O(32) 2.041(2), Zn(1)–N(1)
2.158(3), Zn(1)–N(5) 2.180(3), Zn(2)–O(20) 2.004(2), Zn(2)–O(43) 2.016(3), Zn(2)–
O(33) 2.016(3), Zn(2)–N(13) 2.150(3), Zn(2)–N(9) 2.164(3), Zn(1)–Zn(2) 3.2590(6),
Zn(1)–O(20)–Zn(2) 108.92(10), O(20)–Zn(1)–O(42) 100.65(9), O(20)–Zn(1)–O(32)
91.63(9), O(42)–Zn(1)–O(32) 105.02(11), O(20)–Zn(1)–N(1) 162.94(10), O(42)–
Zn(1)–N(1) 96.12(10), O(32)–Zn(1)–N(1) 86.98(10), O(20)–Zn(1)–N(5) 80.00(10),
O(42)–Zn(1)–N(5) 107.82(11), O(32)–Zn(1)–N(5) 147.06(11), N(1)–Zn(1)–N(5)
91.98(11), O(20)–Zn(2)–O(43) 99.26(10), O(20)–Zn(2)–O(33) 91.11(10), O(43)–
Zn(2)–O(33) 110.16(13), O(20)–Zn(2)–N(13) 167.03(12), O(43)–Zn(2)–N(13)
93.43(13), O(33)–Zn(2)–N(13) 86.97(12), O(20)–Zn(2)–N(9) 80.45(11), O(43)–
Zn(2)–N(9) 105.14(12), O(33)–Zn(2)–N(9) 144.60(13), N(13)–Zn(2)–N(9) 93.73(13).
C(11), C(12), and N(13) adopted chair conformations. The two
methyl groups, C(16) and C(17), were placed in syn-geometry with
respect to the plane containing N(5), O(20), and N(9), as were the
two N,N-dimethylaminopropyl arms.
In complex 1 (Fig. 1), which contains N,N-dimethylaminopropyl
arms, the two zinc ions were linked by two acetates and one alkox-
ide. Zn(1) and Zn(2) adopted five-coordinate geometries consisting
of distorted square-pyramids with O(42) and O(43), respectively,
Complex 1 showed a temperature-dependent 13C NMR spec-
trum in CD3CN (Supplementary Fig. S1). At 27 °C, two broad methyl
signals were observed around 47 ppm, which were assigned as
N,N-dimethylamino groups, while at a low temperature (ꢀ40 °C)
these signals sharpened and appeared clearly at 44.0 and
48.9 ppm. As the temperature was increased, the two methyl sig-
nals gradually collapsed, almost disappearing by 60 °C. This
at the top. The
= (
ꢀ b)/60 ꢂ 100 (
gle of X–Zn–X, respectively: ideal square-pyramid:
gonal bipyramid: = 100) [26]. The six-membered rings consisting
of Zn(1), N(1), C(2), C(3), C(4), and N(5), and Zn(2), N(9), C(10),
s
values were 26.5 (Zn(1)) and 37.4 (Zn(2)), where
and b are the largest and second largest an-
= 0, ideal tri-
s
a
a
s
s

K. Mochizuki et al. / Inorganica Chimica Acta 362 (2009) 2722–2727
2725
temperature-dependent signal change was reversible and was not
observed for the other zinc complexes investigated in this study.
Shortening the arms by replacing trimethylene with ethylene
resulted in a dramatic change in coordination geometry. HL2, con-
taining N,N-dimethylaminoethyl arms, formed the tetranuclear
zinc complex 2 (Fig. 2), in which two dinuclear units were linked
by two hydroxide ions; in the IR spectrum of 2, a sharp peak was
observed at 3656 cmꢀ1, ascribable to
m(OH). An inversion center
was present in the middle of the tetranuclear complex. In the dinu-
clear unit, Zn(1) and Zn(2) adopted five-coordinate distorted trigo-
nal bipyramidal geometries [s = 74.7 (Zn(1)), s = 62.2 (Zn(2))]
which were different from those of complex 1; N(4) and O(32),
and N(8) and O(33), respectively, were at the top. The five-mem-
bered rings consisting of Zn(1), N(1), C(2), C(3), and N(4), and
Zn(2), N(8), C(9), C(10), and N(11) adopted gauche conformations.
The two N,N-dimethylaminoethyl arms showed syn-geometry with
respect to the plane containing N(4), O(20), and N(8). The intra-
dinuclear and inter-dinuclear distances between zinc ions were
3.521(1) Å for Zn(1)ꢁ ꢁ ꢁZn(2) and 3.391(1) Å for Zn(1)ꢁ ꢁ ꢁZn(20),
respectively; thus, the Znꢁ ꢁ ꢁZn distance when the zinc atoms were
Fig. 3. ORTEP drawing of cation portion of 3. Selected bond lengths (Å) and angles
(°): Zn(1)–O(22) 1.977(4), Zn(1)–O(42) 1.983(5), Zn(1)–O(32) 2.041(4), Zn(1)–O(2)
2.138(5), Zn(1)–N(9) 2.179(5), Zn(1)–O(6) 2.402(5), Zn(2)–O(22) 1.994(4), Zn(2)–
O(43) 1.999(5), Zn(2)–O(33) 2.048(5), Zn(2)–N(13) 2.175(5), Zn(2)–O(16) 2.210(5),
Zn(2)–O(20) 2.369(5), O(22)–Zn(1)–O(42) 100.3(2), O(22)–Zn(1)–O(32) 98.5(2),
O(42)–Zn(1)–O(32) 99.4(2), O(22)–Zn(1)–O(2) 159.8(2), O(42)–Zn(1)–O(2) 98.8(2),
O(32)–Zn(1)–O(2) 84.5(2), O(22)–Zn(1)–N(9) 80.8(2), O(42)–Zn(1)–N(9) 160.2(2),
O(32)–Zn(1)–N(9) 100.0(2), O(2)–Zn(1)–N(9) 79.0(2), O(22)–Zn(1)–O(6) 90.9(2),
O(42)–Zn(1)–O(6) 86.0(2), O(32)–Zn(1)–O(6) 168.0(2), O(2)–Zn(1)–O(6) 84.1(2),
N(9)–Zn(1)–O(6) 74.2(2), O(22)–Zn(2)–O(43) 102.0(2), O(22)–Zn(2)–O(33) 99.2(2),
O(43)–Zn(2)–O(33) 98.2(2), O(22)–Zn(2)–N(13) 79.9(2), O(43)–Zn(2)–N(13)
161.3(2), O(33)–Zn(2)–N(13) 99.8(2), O(22)–Zn(2)–O(16) 157.5(2), O(43)–Zn(2)–
O(16) 99.1(2), O(33)–Zn(2)–O(16) 85.4(2), N(13)–Zn(2)–O(16) 77.6(2), O(22)–
Zn(2)–O(20) 90.7(2), O(43)–Zn(2)–O(20) 85.4(2), O(33)–Zn(2)–O(20) 168.4(2),
N(13)–Zn(2)–O(20) 76.0(2), O(16)–Zn(2)–O(20) 83.2(2), Zn(1)–O(22)–Zn(2)
106.3(2).
linked by a
bridge.
l-hydroxo bridge was shorter than that of the l-alkoxo
HL3, which contains double methoxyethylene arms, also formed
a dinuclear zinc complex 3 (Fig. 3). In the complex, two zinc ions
were linked by one alkoxide and two acetates, adopting distorted
octahedral six-coordination geometries, in contrast to the com-
plexes described above which contain single-arm ligands. Four
five-membered chelate rings around Zn(1) and Zn(2) took gauche
forms. Two methoxyethyl chains containing O(6) and O(20),
respectively, adopted syn-geometry with respect to the plane con-
sisting of N(9), O(22), and N(13).
It can be seen that the presence of N,N-dimethylaminoethyl and
N,N-dimethylaminopropyl arms favored five-coordination geome-
try for zinc, while double methoxyethyl arms favored six-coordina-
tion. The non-symmetrical ligand HL4, bearing N,N-
dimethylaminoethyl and double methoxyethyl arms, formed the
dinuclear zinc complex 4 (Fig. 4), which featured two kinds of coor-
dination geometry—a distorted square-pyramidal five-coordinate
structure (s = 39.6, with N(20) at the top) for Zn(1) and the N,N-
dimethylaminoethyl arm, and a distorted octahedral six-coordi-
nate structure for Zn(2) and the bis(methoxyethylene) arm. The
most remarkable feature of this complex, which was not seen in
the symmetrical zinc complexes, is that the acetate oxygen atom
O(25), coordinated to Zn(1) as a monodentate ligand, is thought
to interact through hydrogen bonding (ca. 2.68 Å) with the ethanol
oxygen atom O(21) which is coordinated to Zn(2).
The relationship between the Znꢁ ꢁ ꢁZn distance and the Zn–O(al-
koxo)–Zn angle of the l-acetato bridge may be discussed with ref-
erence to the various zinc complexes. The Znꢁ ꢁ ꢁZn distances in the
complexes with double -acetato bridges, (3: 3.179(2) Å, 1:
3.2590(6) Å), were shorter than those in the complexes with single
-acetato bridges (4: 3.4360(8) Å, 2: 3.521(1) Å). Moreover, the
l
l
Znꢁ ꢁ ꢁZn distance was reasonably proportional to the Zn–O(al-
koxo)–Zn angle (3: 106.3(2)°, 1: 108.92(10)°, 4: 121.85(13)°, and
2: 127.8(2)°). Thus, it was concluded that the Znꢁ ꢁ ꢁZn distance in
these dinuclear complexes is strongly influenced by the number
Fig. 2. ORTEP drawing of cation portion of 2. Selected bond lengths (Å) and angles
(°): Zn(1)–O(340) 1.943(5), Zn(1)–O(20) 1.967(5), Zn(1)–O(32) 2.065(5), Zn(1)–N(1)
2.110(6), Zn(1)–N(4) 2.258(6), Zn(1)–Zn(2) 3.5206(14), Zn(2)–O(20) 1.953(5),
Zn(2)–O(34) 1.964(5), Zn(2)–O(33) 2.083(6), Zn(2)–N(11) 2.150(7), Zn(2)–N(8)
2.223(7), O(340)–Zn(1)–O(20) 126.5(2), O(340)–Zn(1)–O(32) 92.4(2), O(20)–Zn(1)–
O(32) 95.8(2), O(340)–Zn(1)–N(1) 16.3(2), O(20)–Zn(1)–N(1) 116.2(2), O(32)–
Zn(1)–N(1) 91.4(2), O(340)–Zn(1)–N(4) 95.6(2), O(20)–Zn(1)–N(4) 82.0(2), O(32)–
Zn(1)–N(4) 171.3(2), N(1)–Zn(1)–N(4) 82.1(2), O(20)–Zn(2)–O(34) 129.1(2), O(20)–
Zn(2)–O(33) 95.7(2), O(34)–Zn(2)–O(33) 94.0(3), O(20)–Zn(2)–N(11) 116.9(3),
O(34)–Zn(2)–N(11) 113.5(3), O(33)–Zn(2)–N(11) 86.6(3), O(20)–Zn(2)–N(8)
83.1(2), O(34)–Zn(2)–N(8) 97.3(3), O(33)–Zn(2)–N(8) 166.4(3), N(11)–Zn(2)–N(8)
82.0(3), Zn(2)–O(20)–Zn(1) 127.8(2), Zn(10)–O(34)–Zn(2) 120.4(3).
of
l
-acetato bridges.
Tetranuclear zinc complexes with analogous structures have
been reported previously, including a -phenoxo and -hydroxo
bridged complex [27], a -alkoxo and -acetato bridged complex
[28], and a -phenoxo and -hydroxo bridged complex 5 [29]. In
l
l
l
l
l
l
5, two dinuclear zinc complexes with phenoxo linkages are further
bridged by two hydroxides, similarly to the tetranuclear complex
synthesized in this study. The Znꢁ ꢁ ꢁZn distance in the dinuclear
unit in 2 is 3.521(1) Å, which is longer than that of the phenoxo-

2726
K. Mochizuki et al. / Inorganica Chimica Acta 362 (2009) 2722–2727
Scheme 2. Hydrolysis of TNP.
sponded to one observed in the reaction between 2 and p-nitro-
phenolate under the same reaction conditions, it was assumed to
be due to the formation of a complex between 2 and p-nitrophe-
nolate formed during the hydrolysis of TNP. The initial rate of
the change in absorption accelerated as the concentration of the
zinc complex increased (Supplementary Fig. S2). In addition, the
change in absorption was slowed when the pH of the reaction solu-
tion was changed from 8.0 to 7.0 and when the water content in
the system was lowered from 5% to 1% (see Supplementary
Fig. S3). These results suggest that a hydroxo–zinc species (Zn–
OH), such as a dinuclear zinc complex with a hydroxide ion, which
may be produced by dissociation of the tetranuclear complex, may
act as the active species in this hydrolysis reaction. The 13C NMR
spectrum of 2 in CD3CN actually showed more complicated signals
than expected for a symmetrical tetranuclear complex, suggesting
that the tetranuclear complex may undergo partial dissociation in
solution (Supplementary Fig. S4). In addition, the ESI-mass spec-
trum of 2 in acetonitrile showed the peak at m/z 465.1 ascribable
Fig. 4. ORTEP drawing of cation potion of 4 (PART 1). Selected bond lengths (Å) and
angles (°): Zn(1)–O(14) 1.958(3), Zn(1)–O(23) 2.006(3), Zn(1)–N(20) 2.097(3),
Zn(1)–O(27) 2.118(3), Zn(1)–N(16) 2.239(3), Zn(1)–Zn(2) 3.4360(8), Zn(2)–O(29)
1.950(3), Zn(2)–O(14) 1.973(3), Zn(2)–N(7) 2.130(4), Zn(2)–O(31) 2.151(4), Zn(2)–
O(3) 2.238(3), Zn(2)–O(10) 2.272(4), O(14)–Zn(1)–O(23) 145.20(14), O(14)–Zn(1)–
N(20) 111.03(13), O(23)–Zn(1)–N(20) 103.15(15), O(14)–Zn(1)–O(27) 90.79(12),
O(23)–Zn(1)–O(27) 93.78(14), N(20)–Zn(1)–O(27) 93.12(14), O(14)–Zn(1)–N(16)
80.39(12), O(23)–Zn(1)–N(16) 97.25(14), N(20)–Zn(1)–N(16) 83.99(14), O(27)–
Zn(1)–N(16) 168.97(14), O(29)–Zn(2)–O(14) 106.27(13), O(29)–Zn(2)–N(7)
163.36(16), O(14)–Zn(2)–N(7) 82.59(13), O(29)–Zn(2)–O(31) 95.49(18), O(14)–
Zn(2)–O(31) 90.44(13), N(7)–Zn(2)–O(31) 98.55(17), O(29)–Zn(2)–O(3) 94.92(15),
O(14)–Zn(2)–O(3) 158.68(13), N(7)–Zn(2)–O(3) 77.47(15), O(31)–Zn(2)–O(3)
85.20(14), O(29)–Zn(2)–O(10) 87.36(16), O(14)–Zn(2)–O(10) 97.42(14), N(7)–
Zn(2)–O(10) 77.39(15), O(31)–Zn(2)–O(10) 170.55(14), O(3)–Zn(2)–O(10)
85.58(15), Zn(1)–O(14)–Zn(2) 121.85(13).
bridged complex 5 (3.23 Å), although the distances between the
dinuclear units are very similar in the two complexes (2: 3.39 Å,
5: 3.41 Å) and are close to that found in the dinuclear zinc active
site of P1-nuclease (3.3 Å) [29].
The hydrolysis of tris(p-nitrophenyl)phosphate (TNP) by zinc
complexes has been reported previously [30–36]. We investigated
the abilities of the dinuclear zinc complexes for TNP hydrolysis by
spectrophotometric means. Only 2, a tetranuclear zinc complex
with l-hydroxo bridges, showed activity in this regard. HPLC anal-
ysis showed that the hydrolysis product was bis(p-nitro-
phenyl)phosphate (BNP). As shown in Fig. 5, a new absorption
band around 380 nm due to the hydrolysis product increased as
the reaction proceeded (see Scheme 2). Because this band corre-
Fig. 5. Change in absorption spectrum during hydrolysis of TNP
Fig. 6. Change in 31P NMR spectrum during the reaction between TNP
(9.78 ꢂ 10ꢀ3 mol dmꢀ3) and 2 (4.92 ꢂ 10ꢀ3 mol dmꢀ3) in CD3CN at 27 °C (upper:
before reaction, middle: after 2 days, bottom: after 10 days).
(1.0 ꢂ 10ꢀ4 mol dmꢀ3
)
by complex
2
(5.27 ꢂ 10ꢀ3 mol dmꢀ3
) in an acetonitrile
solution containing 5% Tris buffer (pH 8.0) at 30 °C. Scan interval: 10 min.

K. Mochizuki et al. / Inorganica Chimica Acta 362 (2009) 2722–2727
2727
to [Zn2L2(CH3COO)(OH)]+, which was assumed to arise from the
dissociation of 2.
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The hydrolysis of TNP in CD3CN was confirmed by measure-
ment of 31P NMR spectra. Fig. 6 shows the time dependence of
the 31P NMR spectrum measured at 26 °C for a CD3CN solution con-
taining 2 (4.92 ꢂ 10ꢀ3 mol dmꢀ3) and TNP (9.78 ꢂ 10ꢀ3 mol dmꢀ3).
The phosphorous signal of TNP appeared at ꢀ21 ppm against the
reference signal of 85% phosphoric acid at 0.0 ppm. At first, only
the signal of TNP was observed. As the reaction proceeded, the sig-
nal intensity of TNP decreased but the intensity of the signal as-
cribed to the hydrolysis product, BNP, at ꢀ13.5 ppm increased.
After 10 days, the BNP signal was observed with strong intensity,
while the TNP signal had become very small. When a ca. tenfold
excess of TNP (10.07 mmol dmꢀ3
)
was reacted with
2
(1.02 mmol dmꢀ3), the integrated TNP:BNP intensity ratio was
4.16:1.0. These results suggest that the tetranuclear zinc complex
has the potential to hydrolyze two molecules of TNP in neat
CD3CN. The other zinc complexes, 1, 3, and 4, did not show such
hydrolysis activity. It was concluded that the hydroxide bridging
dinuclear zinc units is essential for the hydrolysis of the phospho-
ester bonds of TNP.
In conclusion, new binucleating ligands with various arm struc-
tures were synthesized, along with the corresponding zinc com-
plexes, and their structures were determined by X-ray
crystallography. Ligand HL2, which contains N,N-dimethylamino-
ethyl arms, was found to form a tetranuclear zinc complex in
which two dinuclear complex units were linked by two hydroxide
ions. The tetranuclear zinc complex showed activity for hydrolysis
of TNP in aqueous acetonitrile and neat CD3CN, which was con-
firmed by visible absorption spectroscopy and 31P NMR studies.
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Appendix A. Supplementary material
CCDC 703817, 703818, 703819 and 703820 contain supplemen-
tary crystallographic data for 1, 2, 3 and 4. These data can be ob-
tained free of charge from the Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.ica.2008.12.012.
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