Synthesis and characterization of a new asymmetric dinucleating ligand and its dinuclear nickel(II) complex with (μ-n2)2 phosphate ester bridge

Article abstract of DOI:10.1007/s11243-009-9313-x

A new asymmetric phenol-based "end-off" dinucleating ligand HL was prepared using a modified methodology through a four-step synthesis. The ligand comprises two different coordination moieties, namely, a rigid 1,4-dimethyl-1,4,7-triazacyclononane unit and

Full text of DOI:10.1007/s11243-009-9313-x

Transition Met Chem (2010) 35:191–195
DOI 10.1007/s11243-009-9313-x
Synthesis and characterization of a new asymmetric dinucleating
ligand and its dinuclear nickel(II) complex with (l–g2)2 phosphate
ester bridge
•
•
•
Yan-wei Ren Ai-zhi Wu Hai-yang Liu
Huang-feng Jiang
Received: 17 September 2009 / Accepted: 13 November 2009 / Published online: 3 December 2009
Ó Springer Science+Business Media B.V. 2009
Abstract A new asymmetric phenol-based ‘‘end-off’’
dinucleating ligand HL was prepared using a modified
methodology through a four-step synthesis. The ligand
comprises two different coordination moieties, namely, a
rigid 1,4-dimethyl-1,4,7-triazacyclononane unit and a more
flexible N-(2-pyridyl)methyl-N-2-(2-pyridylethyl)amine unit.
Its dinuclear Ni(II) complex containing two phosphate esters
in a l-g2 binding mode was synthesized and characterized
by X-ray crystallography, in which each nickel atom is
six-coordinate and adopts a slightly distorted octahedral
coordination geometry.
than that of the native Zn(II) enzyme, while the Cu(II)-
substituted enzyme has similar activity to the native one
[5]. Although different coordination environments are
found for the two metal centers in many dinuclear metal-
loenzymes, a large number of the enzyme mimics reported
so far are based on symmetric dinucleating ligands [6–13].
These ligands generally result in the formation of dinuclear
complexes with identical coordination geometries for the
two metal centers. Less attention has been paid to the
preparation of asymmetric dinuclear complexes, especially
dinickel(II) complexes [14–16]. Synthesis and comparison
of asymmetric and symmetric dinuclear enzyme models
should provide deeper insight into the structure and
mechanism of those enzymes and help to design more
effective metalloenzyme models.
Introduction
Bimetallic cores exist at the active sites of many metallo-
enzymes and play an essential role in biological systems
[1, 2]. Urease is one such bimetallic hydrolase which
hydrolyzes urea to ammonia and carbamate at its di-Ni(II)
active site [3]. A previous study of the crystal structure of
an urease from K. Aerogenes reveals that the two Ni(II)
In our view, straightforward and flexible synthetic
methodology for the preparation of asymmetric dinucleating
ligands is highly desirable since these ligands force the two
metal atoms in the resulting complex into well-defined and
tunable but different chemical and/or coordination envi-
ronments. This will ultimately result in the formation of
more realistic enzyme mimics. In this article, we describe a
modified methodology for the synthesis of a new asym-
metric phenol-based ‘end-off’ dinucleating ligand, namely,
4-bromo-2-(1,4-dimethyl-1,4,7-triazacyclononane-7-ylme-
thyl)-6-{[N-(2-pyridyl)methyl-N-2-(2-pyridylethyl)amine]-
methyl}-phenol (HL) and its dinuclear nickel(II) complex
with a (l–g2)2 phosphate ester bridge.
˚
atoms are *3.5 A apart and bridged by a bidentate
carbamate side chain, having different coordination num-
ber and geometry for each nickel atom [3]. This structural
asymmetry at the active site is consistent with the different
roles played by two metal ions [4]. Interestingly, Ni(II)-
substituted phosphotriesterase has higher specific activity
Y. Ren (&) Á H. Liu Á H. Jiang
School of Chemistry and Chemical Engineering, South China
University of Technology, 510640 Guangzhou, China
e-mail: renyw@scut.edu.cn
Experimental
1,4-Dimethyl-1,4,7-triazacyclononane was prepared as
described in the literature [17] The other reagents were of
analytical grade from commercial sources and were used
A. Wu
School of Chinese Medicine, Guangzhou University of Chinese
Medicine, 510006 Guangzhou, China
123

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Transition Met Chem (2010) 35:191–195
without any further purification. Elemental analysis was
performed with a Vario EL-III instrument. The IR spectra
were recorded on an Equinox 55 spectrophotometer in the
4,000–400 cm-1 region using powdered samples on a KBr
plate. Electronic absorption spectra were determined on a
CARY 300 Bio UV–Vis spectrophotometer. Mass spec-
tra were measured on a Thermo Finnigan LCQ mass
spectrometer.
(CDCl3): d = 10.22, 1H; 7.72, 1H; 7.41, 1H; 3.83, 2H;
2.83–2.94, 12H; 2.40, 6H. MS (FAB, m/z): M ? 1 = 371.
Synthesis of 4-bromo-2-hydroxymethyl-6-(1,4-
dimethyl-1,4,7-triazacyclononane-7-ylmethyl)-phenol
(III)
Sodium borohydride (1.48 g, 39 mmol) was added in bat-
ches to a stirred solution of II (4.8 g, 13 mmol) in meth-
anol (30 mL) within 1 h. The resulting solution was stirred
overnight at room temperature and then refluxed for 1 h.
After cooling to room temperature, the solution was treated
with hydrochloric acid (12 M, 8 mL) and vigorously stir-
red for 30 min. The solution was adjusted to pH 8–9 with
sodium hydroxide solution (5 M). Precipitated sodium
borate was filtered off, and the solvent was distilled under
reduced pressure. The residue was suspended in water
(40 mL) and extracted with dichloromethane. The organic
phase was dried over anhydrous Na2SO4. Evaporation of
the solvent gave the product III as a light orange solid
(4.5 g, 93% yield). 1H-NMR (CDCl3): d = 7.06, 1H; 7.02,
1H; 4.84, 2H; 3.96, 2H; 2.64-2.94, 12H; 2.42, 6H. MS
(FAB, m/z): M ? 1 = 373.
Warning: Perchlorate salts are dangerous to handle, and
only small quantities should be used. We did not encounter
any difficulties during this work.
Synthesis of N-(2-pyridyl)methyl-N-2-(2-pyridylethyl)
amine (I)
A solution of 2-(2-aminoethyl) pyridine (1.22 g, 10.0 mmol)
in methanol (5 mL) was added to a stirred solution of
2-pyridinecarboxaldehyde (1.07 g, 10.0 mmol) in metha-
nol (15 mL). The mixture was stirred at room temperature
for 2 h. Sodium borohydride (0.756 g, 20.0 mmol) was
then added in batches within 1 h. The reaction mixture was
stirred overnight and then refluxed for 1 h. After cooling to
room temperature, the solution was treated with hydro-
chloric acid (3 mL, 12 M) and vigorously stirred for
30 min. The mixture was adjusted to pH 8–9 with 5 M
sodium hydroxide solution. Precipitated sodium borate was
filtered off, and the solvent was distilled under reduced
pressure. The residue was suspended in water (20 mL) and
extracted with dichloromethane. The organic phase was
dried over anhydrous sodium sulfate. Evaporation of the
solvent gave the product as a light yellow oil with 85%
yield. 1H-NMR (CDCl3): d = 8.52, 2H; 7.60, 2H; 7.28, 1H;
7.16, 1H; 7.08, 2H; 3.95, 2H; 3.00–3.05, 4H; 2.25, 1H. MS
(FAB, m/z): M ? 1 = 214.
Synthesis of 4-bromo-2-chloromethyl-6-(1,4-dimethyl-
1,4,7-triazacyclononane-7-ylmethyl)-phenol (IV)
Freshly distilled thionyl chloride (15 mL) was added
dropwise to III (2.24 g, 6 mmol) at 0 °C. The solution was
stirred at room temperature for 3 h. Thionyl chloride was
then distilled out under reduced pressure at 30–40 °C, and
the product IV was washed several times with hexane and
dichloromethane (yield ca. 100%).
Synthesis of HL
Synthesis of 5-bromo-2-hydroxy-3-(1,4-dimethyl-1,4,7-
triazacyclononane-7-ylmethyl)-benzaldehyde (II)
The above product IV (6.0 mmol) was suspended in dried
acetonitrile (40 mL). The flask was cooled to -40 °C in a
liquid N2–acetone cold trap and Et3N (4.2 mL) was added
dropwise with stirring. A solution of I (1.28 g, 6.0 mmol)
and of Et3N (2.5 mL) in dried acetonitrile (20 mL) was
then added dropwise. The resulting solution was stirred for
24 h at room temperature and then for 48 h at 30–40 °C.
After cooling in an ice-water bath, the resulting white
precipitate was filtered off. Evaporation of the solvent
produced an orange oil that was suspended in aqueous
Na2CO3 (30 mL, 3%, pH *9.0) and extracted with
dichloromethane. The organic phase was dried over
Na2SO4. Evaporation of the solvent gave the product as an
orange oil that was purified by silica gel column chroma-
tography (eluting with 10:1 (v/v) MeOH–Et3N), gave pure
HL as an orange oil. Yield: 1.4 g (42%). 1H-NMR
A solution of paraformaldehyde (0.72 g, 24 mmol) in eth-
anol (5 mL) was added to a stirred solution of 1,4-dimethyl-
1,4,7-triazacyclononane (3.14 g, 20 mmol) in ethanol
(10 mL). The mixture was heated to 80 °C for 1 h and then
5-bromo-2-hydroxy-benzaldehyde (4.03 g, 20 mmol) in
ethanol (40 mL) was added. The resulting solution was
refluxed for 72 h under argon. Evaporation of the solvent
gave an oily residue that was suspended in aqueous Na2CO3
(30 mL, 5%) and extracted with dichloromethane. The
organic phase was dried over anhydrous Na2SO4. The sol-
vent was evaporated under reduced pressure to give a yellow
oil that was purified by column chromatography on silica gel
(CH2Cl/MeOH/Et3N, 50/10/1, followed by MeOH/Et3N,
10/1) to afford II (2.2 g, 30% yield) as a yellow oil. 1H-NMR
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Transition Met Chem (2010) 35:191–195
193
˚
(CD2Cl2): d = 8.43, 2H; 7.52, 2H; 7.22, 2H; 7.02–7.08,
4H; 3.78, 2H; 3.68, 4H; 2.78–2.96, 8H; 2.55–2.61, 8H;
2.29, 6H. IR (KBr, cm-1): 3,438 (w), 2,934 (w), 2,802 (w),
1,590 (w), 1,456 (m), 1,439 (m), 1,370 (w), 1,215 (w),
1,119 (w), 755 (w). MS (FAB, m/z): M ? 1 = 568.
Table 1 Selected bond distances (A) and angles (°) for complex
[Ni2L(l-BPP)2]BPh4
Ni(1)–O(1)
2.089(3)
2.114(4)
2.095(3)
2.153(3)
2.073(3)
2.083(3)
3.816
Ni(2)–O(1)
Ni(2)–N(4)
Ni(2)–N(5)
Ni(2)–N(6)
Ni(2)–O(3)
Ni(2)–O(7)
2.151(2)
2.102(4)
2.093(4)
2.149(3)
2.029(3)
2.044(3)
Ni(1)–N(1)
Ni(1)–N(2)
Ni(1)–N(3)
Synthesis of [Ni2L(l-BPP)2]BPh4
Ni(1)–O(2)
Ni(1)–O(6)
A solution of nickel perchlorate (0.073 g, 0.2 mmol) and
sodium biphenyl phosphate (NaBPP) (0.054 g, 0.2 mmol)
in water (2 mL) was added to a solution of HL (0.057 g,
0.1 mmol) in ethanol (2 mL). The reaction mixture was
then stirred for 1 h at 25 °C. A green precipitate was
afforded after adding a solution of NaBPh4 (0.068 g,
2 mmol) in ethanol (1 mL). The crude product was col-
lected by filtration and then washed with water and ethanol.
Green block-shaped crystals suitable for single crystal X-
ray study were obtained by recrystallization from 1:2 (v/v)
MeCN–EtOH solution (4 mL) with a yield of 52%. Ele-
mental analysis for C77H72BBrN6Ni2O9P2: found (calcd.
%): C, 62.19 (61.83); H, 5.23 (4.81); N, 5.45 (5.62). IR
(KBr, cm-1): 3,062 (w), 1,605 (m), 1,592 (m), 1,489 (s),
1,458 (m), 1,446 (m), 1,233 (s), 1,205 (s), 1,115 (s), 1,067
(s), 785 (m), 756 (m), 622 (m), 544 (m), 516 (m).
Ni(1)–Ni(2)
O(2)–P(2)–O(3)
O(4)–P(2)–O(5)
Ni(1)–O(1)–Ni(2)
121.2(2)
103.6(2)
128.2(1)
O(6)–P(1)–O(7)
O(8)–P(1)–O(9)
121.0(2)
103.4(2)
four-step synthesis from 5-bromosalicyladehyde and two
different synthetically easily accessible secondary amines
(1,4-dimethyl-1,4,7-triazacyclononane and N-(2-pyridyl)-
methyl-N-2-(2-pyridylethyl)amine). The first key step in
the preparation was accomplished by an aromatic Mannich
reaction, introducing a secondary amine group into position
3 of 5-bromosalicyladehyde. Next, NaBH4 was used to
reduce the aldehyde to a hydroxymethyl group, which was
then converted into a chloromethyl group using SOCl2.
This allowed the subsequent alkylation with a second
amine that was different from the first one. This four-step
synthesis affords the desired ligand in gram quantities with
an overall yield of ca. 35%. By this means, many similar
asymmetric ligands that are chemically distinct on both
sides of the phenolic ring moiety can be created. Previ-
ously, Gahan et al. [21] and Neves et al. [22] prepared
analogous asymmetric ligands by a statistical synthesis
from 2,6-bis(chloromethyl)-4-methylphenol.
Crystal structure analysis
A single green crystal of the complex with dimensions
0.20 mm 9 0.30 mm 9 0.15 mm was attached to a glass
fiber and mounted on a Rigaku R-AXIS SPIDER X-ray
diffractometer with graphite monochromatized Mo Ka
˚
radiation (k = 0.71073 A) at 293 K. The structure was
solved by direct methods and refined on F2 by full-matrix
least squares technique with SHELXTL-97 [18]. All non-
hydrogen atoms were refined anisotropically, and all
hydrogen atoms of the ligands were located and included at
their calculated positions. Crystal data: C77H72BBrN6
Ni2O9P2, M = 1501.53, orthorhombic, space group Pna21,
Characterization of [Ni2L(l-BPP)2]BPh4
The IR spectrum of the complex [Ni2L(l-BPP)2]BPh4
displays characteristic sharp bands at 1,233, 1,205 and
1,115 cm-1, assigned the symmetric and asymmetric
vibrations of BPP bridges [23], which is confirmed by the
X-ray crystal structure (see below). There are three bands in
the electronic absorption spectrum of the complex in ace-
tonitrile, with peak positions at 535, 710 and 859 nm, which
are attributed to the d–d transitions of 3A2g ? 3T1g(p),
3A2g ? 3T1g and 3A2g ? 3T2g of Ni(II) ion in octahedral
field [24], respectively.
˚
a = 23.937 (5), b = 24.913 (5), c = 11.788 (2) A,
-3
3
˚
a = b = c = 90°, V = 7,030 (2) A , Dc = 1.419 g cm
,
l = 1.213 mm-1, Z = 4, MoKa radiation, k = 0.71,073 A,
T = 293 K, Final R indices [I [ 2sigma(I)]: R1 = 0.0405,
wR2 = 0.0898, R indices (all data): R1 = 0.0635, wR2 =
0.1028, GOF = 1.046 for 12,363 unique reflections and 871
parameters. Selected bond distances and bond angles are
given in Table 1.
˚
The X-ray crystal structure of [Ni2L(l-BPP)2]BPh4
(Fig. 1) shows that the two nickel atoms are bridged by an
endogenous cresolic oxygen atom from L and two exoge-
nous phosphate ester groups from the anionic BPP ligand in
syn–syn mode. Each nickel atom is six-coordinate and
adopts a slightly distorted octahedral coordination geome-
try. Around atom Ni(1), the N3O3 donor set is comprised of
a bridging cresolic-O, two bridging phosphodiester-O and
Results and discussion
The synthetic route to HL is illustrated in Scheme 1, which
is modified on the basis of the reaction procedures reported
previously [19, 20]. HL was obtained as an orange oil via
123

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Transition Met Chem (2010) 35:191–195
Br
Br
Br
(ii)
(iii)
N
N
N
N
OH
OH
O
OH
O
OH
N
N
(III)
(II)
(iv)
Br
Br
NH
N
(i)
(v)
+
+
N
N
NH2
N
N
N
N
N
OH
O
Cl
OH
N
N
N
N
N
(IV)
HL
(I)
Scheme 1 Reagents and conditions: (i) NaBH4 (2 equiv.) reflux, (ii) 1,4-dimethyl-1,4,7-triazacyclononane (1 equiv.), (CH2O)n (1 equiv.), EtOH,
24 h, reflux, (iii) NaBH4 (3 equiv.), 1 h, reflux, (iv) SOCl2, 3 h and (v) Et3N (5 equiv.), MeCN, 25 °C, 48 h
pendant are stronger than those of the bipyridyl pendant.
Furthermore, different coordination features can also be
revealed by the different distances of the P–O bonds boun-
ded to the two nickel atoms. The intra-ring O(2)–P(2)–O(3)
and O(6)–P(1)–O(7) angles are expanded by ca. 10° from the
ideal value of 109.5°, to 121.2(2)° and 121.0(2)°, respec-
tively, whereas the other angles around the two phosphorus
atoms only deviate slightly from tetrahedral. The distortion
around the phosphoryl center appears to derive from the
bridging bidentate coordination mode to the two nickel
atoms. Similar expansion has been already found in other
dimetallic complexes containing l–g2 phosphate esters
[27, 28]. The distance between the two nickel atoms is 3.816
˚
A, longer than that in a previously reported di-Ni(II) com-
plex with alkoxide and one BPP bridges [27], but slightly
shorter than that of a di-Ni(II) complex that possesses two
phosphate esters in a (l–g2)2 binding mode with no addi-
tional ligand between the two metals [28]. The appropriate
intermetallic separation can facilitate the cooperative action
for the phosphate bridging, reminiscent of substrate activa-
Fig. 1 Cationic structure of complex [Ni2L(l-BPP)2]BPh4. The four
benzyl rings on BPPs and all hydrogen atoms are omitted for clarity.
Thermal ellipsoids are at 30% probability
tion by the metal centers in dinuclear metallohydrolases [1].
In conclusion, we have developed a convenient and
versatile procedure to synthesize a new asymmetric phe-
nol-based ‘‘end-off’’ dinucleating ligand. In the dinickel(II)
complex, the ligand forces the two metal ions into prox-
imity with different chemical environments, as in related
natural dinuclear metalloenzymes.
three tertiary amine-N atoms, while in other pendant, the
Ni(2) atom is coordinated by a tertiary amine-N, two
bridging phosphodiester-O and two pyridyl-N atoms. The
average Ni(1)–N and Ni(2)–N distances are 2.121 and
˚
2.115 A, respectively, which are similar to those previously
reported in other Ni(II) complexes with macrocyclic tri-
Supplementary data
amine [25] and multipyridine ligands [26–28]. The bond
˚
length of Ni(1)–O(1) (2.089 A) is obviously shorter than that
˚
of Ni(2)–O(1) (2.151 A), presumably because the coordi-
CCDC reference number is 739403. See http://www.ccdc.
cam.au.uk or email: deposite@ccdc.cam.au.uk for crystal-
lographic file in CIF or other electronic format.
nation ability and geometrical rigidity of the macrocyclic
123

Transition Met Chem (2010) 35:191–195
195
Acknowledgment We are grateful to Dr.Yuan-fu Deng and Prof.
Zhi-yong Fu for the crystal structural solution and refinement.
15. Greatti A, Brito MA, Bortoluzzi AJ, Ceccato AS (2004) J Mol
Struct 688:185
16. Greatti A, Scarpellini M, Peralta RA, Casellato A, Bortoluzzi AJ,
Xavier FR, Jovito R, Brito MA, Szpoganicz B, Tomkowicz Z,
Rams M, Haase W, Neves A (2008) Inorg Chem 47:1107
17. Flassbeck C, Wieghardt K (1992) Z Anorg Allg Chem 60:608
18. Sheldrick GM (1997) SHELXTL-97, Crystal structure solution
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