Dibridged bis(Zn2+-cyclen): A novel host molecule of malonate dianion in aqueous solution

Article abstract of DOI:10.1246/bcsj.20090226

A dinuclear zinc(II) complex, m,m-bis(Zn²⁺cyclen) was synthesized as a novel host molecule for a malonate dianion. The dizinc(II) complex has two zinc(II)cyclen moieties (cyclen = 1,4,7,10- tetraazacyclododecane) connected through two m-xylene bridges. The 1:1 association constant of log K (K = {[malonate-bound m,m-bis(Zn ²⁺-cyclen)]/[m,m-bis(Zn²⁺-cyclen)][malonate]}/M ^-1) was determined to be 3.6 by potentiometric pH titration at 25°C with I = 0.10M (NaNO₃) in aqueous solution. The H/D exchange reaction of methylene hydrogen atoms of malonate dianion was accelerated by m,m-bis(Zn²⁺-cyclen) in D₂O. The half-life was determined to be 80min for a 1:1 mixture (2mM) of malonate and m,m-bis(Zn ²⁺-cyclen) at 25°C and pD 7. From an aqueous solution of equimolar malonate and m,m-bis(Zn²⁺-cyclen) however, a cyclic 2:2 malonate/m,m-bis(Zn²⁺-cyclen) complex was isolated. The structure was confirmed by X-ray crystallography.

Full text of DOI:10.1246/bcsj.20090226

© 2010 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 83, No. 3, 267–272 (2010)
267
Dibridged Bis(Zn2+-cyclen): A Novel Host Molecule of
Malonate Dianion in Aqueous Solution
Haruto Fujioka,*1 Sayuri Kishida,1 Takashi Ishizu,1 Motoo Shiro,2 Eiji Kinoshita,3 and Tohru Koike3
1Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuen-cho, Fukuyama 729-0292
2Rigaku Corporation, 3-9-12 Matsubaracho, Akishima, Tokyo 196-8666
3Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553
Received August 28, 2009; E-mail: fujioka@fupharm.fukuyama-u.ac.jp
A dinuclear zinc(II) complex, m,m-bis(Zn2+-cyclen) was synthesized as a novel host molecule for a malonate
dianion. The dizinc(II) complex has two zinc(II)-cyclen moieties (cyclen = 1,4,7,10-tetraazacyclododecane) connected
through two m-xylene bridges. The 1:1 association constant of log K (K = {[malonate-bound m,m-bis(Zn2+-cyclen)]/
[m,m-bis(Zn2+-cyclen)][malonate]}/M¹1) was determined to be 3.6 by potentiometric pH titration at 25 °C with I =
0.10 M (NaNO3) in aqueous solution. The H/D exchange reaction of methylene hydrogen atoms of malonate dianion
was accelerated by m,m-bis(Zn2+-cyclen) in D2O. The half-life was determined to be 80 min for a 1:1 mixture (2 mM)
of malonate and m,m-bis(Zn2+-cyclen) at 25 °C and pD 7. From an aqueous solution of equimolar malonate and
m,m-bis(Zn2+-cyclen) however, a cyclic 2:2 malonate/m,m-bis(Zn2+-cyclen) complex was isolated. The structure was
confirmed by X-ray crystallography.
Recently, molecular recognition of various molecules such
H
N
Zn2+
OH2
NH
as carbohydrates, nucleic acids, and drugs has attracted
considerable attention.1-3 Among artificial host molecules,
metal complexes with open coordination sites have found wide
use in molecular recognition.4,5 Coordination to metal ions
occurs typically with large enthalpies compared to those of
hydrogen bond formation or electrostatic interactions.6-9 Thus,
even a single coordinated bond may provide sufficient binding
energy to result in stable host-guest complexation in aqueous
solution. For example, Kimura’s group reported that a mono-
nuclear zinc(II) complex, zinc(II)-cyclen (cyclen = 1,4,7,10-
tetraazacyclododecane) 1 (Chart 1) is a new host for imide
anions such as thymine (pKa 9.9) and barbital (pKa 8.0) in
aqueous solution.4,10-17 The zinc(II) ion in the cyclen com-
plex is acidic enough to replace the imide proton at the
H
H
N
N
Zn2+
N
N
Zn2+
N
N
HN
H2O
OH2
N
H
N
N
H
H
H
H
Zn2+−cyclen
m-bis(Zn2+−cyclen)
1
2
H
H
N
N
N
N
N
N
N
N
H
H
¹
fifth coordination site. The resulting zinc(II)-N interaction is
enforced by the two complementary hydrogen bonds between
the imide oxygen atoms and cyclen NH groups. The anion
recognition involving metal coordination provides a new class
of host-guest interaction at physiological pH. Furthermore,
zinc(II)-cyclen can capture various anions derived from weak
acids such as thiol, carboxylic acids, and phosphoric acids.18-22
In 1996, we reported that attachment of another zinc(II)-
cyclen through a m-xylene bridge made a stronger ditopic host,
m,m-bis(cyclen)
3, L
H
N
H
N
N
Zn2+
N
N
H2O
m-bis(Zn2+-cyclen) 2 for a barbital dianion with two imide
Zn2+
N
OH2
¹
N
N
N
donors. The 1:1 affinity is 25 times greater than that of
H
H
the mononuclear zinc(II)-cyclen complex.15 The m-bis(Zn2+
-
cyclen) complex also showed stronger affinity, but not much,
to a bidentate guest, 4-nitrophenyl phosphate dianion. Recent-
ly, in the course of the synthesis of the m-bis(Zn2+-cyclen)
ligand, we incidentally isolated another compound 3. The new
product is a cyclophane ligand containing two cyclen moieties
m,m-bis(Zn2+−cyclen)
4, Zn2L
Chart 1.
Published on the web February 26, 2010; doi:10.1246/bcsj.20090226

268
Bull. Chem. Soc. Jpn. Vol. 83, No. 3 (2010)
Dibridged Bis(Zn2+-cyclen)
(4H, m, NCH2), 2.64-2.79 (4H, m, NCH2), 2.79-2.93 (8H, m,
NCH2), 2.99-3.39 (16H, m, NCH2), 4.25 (4H, d, J = 14.5 Hz),
4.35 (4H, d, J = 14.5 Hz), 7.54 (4H, d, J = 7.8 Hz, ArH), 7.61
(2H, t, J = 7.8 Hz, ArH), 7.72 (2H, s, ArH). 13C NMR (D2O): ¤
52.1, 54.2, 56.3, 61.0, 66.5, 139.6, 140.8, 141.8, 145.4.
connected through two m-xylene bridges. The novel ligand 3
was termed m,m-bis(cyclen), which is more rigid than the
monobridged ligand 2. Here, we report the synthesis and
characterization of 3 and its dizinc(II) complex, m,m-bis(Zn2+
cyclen) 4. Moreover, recognition behavior of m,m-bis(Zn2+
cyclen) toward malonate dianion is determined.
-
-
Syntheses of the Malonate-Bound m,m-Bis(Zn2+-cyclen)
Complex, 9.
An aqueous solution (200 mL) containing
Zn(NO3)3¢6H2O (0.32 g, 1.08 mmol) and malonic acid (0.11 g,
1.08 mmol) was added to an ethanol solution (10 mL) of m,m-
bis(cyclen) (0.30 g, 0.55 mmol). The solution pH was adjusted to
pH 7 with 1.0 M NaOH. The reaction mixture was heated to 70 °C
for 20 min and then cooled to room temperature. After the solvent
was evaporated, the residue was crystallized from water to obtain
colorless crystals, one of which was subject to X-ray crystallog-
raphy. The crystals were dried under 5 mmHg at 25 °C for 5 h to
Experimental
General Procedures. All reagents and solvents used were
of analytical quality and used without further purification. All
aqueous solutions were prepared using deionized and distilled
water. An aqueous solution of 0.100 M NaOH for potentiometric
pH titration was made by dilution of 10 M NaOH (Merck No.
6495) with decarbonated water and standardized with an aqueous
solution of 0.100 M HCl. The 10 M NaOH solution is kept in a
refrigerator below 5 °C for 3 days, where Na2CO3 in the solution is
less than 0.1 M, and then taken out before raising the solution
temperature. IR spectra with KBr pellets were recorded on a
¹
obtain white fine powder of 9¢4NO3 ¢4H2O (0.20 g) in 39% yield.
Anal. Found: C, 44.8; H, 6.1; N, 14.9%. Calcd for C35H58N10-
O12Zn2: C, 44.6; H, 6.2; N, 14.9%. IR (KBr pellet): 3430 (br),
2938, 2879, 1598 (CO), 1476, 1442, 1384, 1249, 1107, 999, 970,
740, 719 cm¹1. 1H NMR (D2O): ¤ 1.97-2.12 (4H, m, NCH2), 2.18-
2.32 (4H, m, NCH2), 2.64-2.93 (24H, m, NCH2), 3.52 (2H, br s,
COCH2CO), 3.90 (4H, d, J = 14.8 Hz), 3.99 (4H, d, J = 14.8 Hz),
7.16 (4H, d, J = 7.4 Hz, ArH), 7.27 (2H, t, J = 7.4 Hz, ArH), 7.44
(2H, s, ArH). 13C NMR (D2O): ¤ 42.1, 44.2, 45.5 (CH2 of
malonate), 46.1, 50.7, 55.9, 128.8, 129.7, 132.0, 135.5, 174.5 (CO
of malonate).
1
Horiba FT-710 infrared spectrometer at 23 °C. H (500 MHz) and
13C (125 MHz) NMR spectra using 99.9 atom % D2O at 35 °C
were recorded on a JEOL JMN-LA500 spectrometer. Sodium 4,4-
dimethyl-4-silapentanesulfonate (in D2O) was used as an internal
reference for H and 13C NMR measurements. The NMR signal
1
1
assignments were achieved using H NOE differential 1D and 2D
(COSY, HMQC, and HMBC) experiments. Elemental analysis
(CHN) was performed on a Yanaco CHN CORDER MT-6. A
MALDI-TOF MS spectrum (positive reflector mode) was obtained
on a Voyager RP-3 BioSpectrometry Workstation (PerSeptive
Biosystems) equipped with a nitrogen laser (337 nm). A matrix
solution of 2,4,6-trihydroxyacetophenone in CH3CN was used.
Synthesis of m,m-Bis(Zn2+-cyclen) Complex, 4. A CHCl3
solution (50 mL) of 1,3-bis(bromomethyl)benzene (1.9 g, 7.2
mmol) was mixed with a CHCl3 solution (500 mL) of cyclen
(2.5 g, 14.5 mmol). After Na2CO3 (1.8 g, 17 mmol) was added into
the solution, the reaction mixture was stirred at room temperature
for 24 h. After the reaction mixture was washed with distilled water
(50 mL © 2), the organic solvent was evaporated. The oily residue
was purified by silica gel column chromatography (Fuji Silysia
silica gel 4B, eluent: CHCl3/MeOH/28% NH3aq = 25:5:1) fol-
lowed by crystallization from toluene to obtain 1,4,7,10,18,-
21,24,27-octaazapentacyclo[24.8.2.218,27.112,16.129,33]-tetraconta-
12,14,16(40),29,31,33,(39)-hexaene (m,m-bis(cyclen), 3) in 10%
yield based on cyclen (0.78 g): TLC (Wako silica gel 70F254 plate,
eluent: CHCl3/MeOH/28% NH3aq = 5:4:1) Rf = 0.63. IR (KBr
pellet): 3420 (br), 2792, 1620 (br), 1482, 1462, 1371, 1343, 1162,
Potentiometric pH Titrations. The electrode system consists
of a Horiba pH/Ion meter F-53, a Horiba combination pH
electrode 9611, and Hiranuma auto buret UCB-900. The pH
calibration method is as follows: An aqueous solution (50.0 mL)
containing 4.00 mM HCl and 96 mM NaNO3 (I = 0.10 M) was
prepared under nitrogen atmosphere (>99.999% purity) at 25.0 «
0.1 °C and then the first pH value (pH1) was read. After 0.100 M
NaOH (4.00 mL) was added to the acidic solution, the second pH
value (pH2) was read. The theoretical pH values corresponding
to pH1 and pH2 are calculated to be pH1¤ = 2.481 and pH2¤ =
2
ꢁ
þ
11.447, respectively, using log KW (KW ¼ aH ꢀ aOH =M ) =
¹14.00, log K¤W (K¤W = [H+][OH ]/M2) = ¹13.79, and fH
¹
þ
+
þ
þ
)
(=aH /H ) = 0.825). The correct pH values (pH = ¹log aH
can be obtained using the following equations: a = (pH2¤ ¹
pH1¤)/(pH2 ¹ pH1); b = pH2¤ ¹ a © pH2; pH = a © (pH-meter
reading) + b. The potentiometric pH titrations of 1.00 mM Zn2L
were carried out in the absence and presence of 1.00, 2.00, and
5.00 mM malonate at 25.0 « 0.1 °C with I = 0.10 M (NaNO3),
where two independent titrations were performed. The two
deprotonation constants (K1 and K2) and the malonate association
constant (K) were determined by means of the pH-titration pro-
gram BEST.23 The pH fit values (·) defined in the program are
smaller than 0.02 for K1 and K2, and 0.05 for K. Relative species
1
1116, 1086, 1033, 983, 755, 707 cm¹1. H NMR (D2O): ¤ 2.17-
2.43 (8H, m, NCH2), 2.43-2.56 (8H, m, NCH2), 2.56-2.71 (8H, m,
NCH2), 2.71-2.89 (8H, m, NCH2), 3.21 (8H, br s, ArCH2), 6.97
(4H, d, J = 7.3 Hz, ArH), 7.12 (2H, t, J = 7.3 Hz, ArH), 7.74 (2H,
s, ArH). 13C NMR (D2O): ¤ 44.5, 46.3, 50.3, 52.0, 58.5, 127.5,
129.2, 129.7, 140.0. MALDI-TOF MS: m/z 549.4 for M + H+.
An aqueous solution (10 mL) containing Zn(NO3)3¢6H2O
(0.32 g, 1.08 mmol) was added to an ethanol solution (10 mL) of
m,m-bis(cyclen) (0.30 g, 0.55 mmol). The reaction mixture was
allowed to stand for 20 min at 70 °C. After filtration of the
solution, the filtrate was cooled to room temperature to obtain
þ
concentrations (%) at various pH values (pH = ¹log{aH /M} =
¹log{[H+]/M} + 0.084) were calculated using the program
SPE.23
X-ray Crystallography. X-ray data of the 2:2 complex 9 were
collected on a Rigaku RAXIS RAPID imaging plate area detector
with graphite monochromated Cu K¡ radiation (- = 1.54187 ¡)
at ¹180 « 1 °C. The structure was solved by the direct method
(SHELX97 developed by G. M. Sheldrick) and expanded using
Fourier techniques (DIRDIF99).24 The non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were refined using the
riding model. All calculations were performed using the Crystal-
Structure25 crystallographic software package except for refine-
ment using SHELX97. The sequential numbers for each element
¹
m,m-bis(Zn2+-cyclen)¢4NO3 ¢1.5H2O as colorless fine crystals
(0.30 g) in 57% yield. Anal. Found: C, 40.3; H, 5.9; N, 17.4%.
Calcd for C32H53N12O13.5Zn2: C, 40.3; H, 5.6; N, 17.6%. IR (KBr
pellet): 3440 (br), 3250, 2934, 2880, 1639, 1477, 1380, 1295,
1078, 1001, 971, 825, 742, 628 cm¹1. 1H NMR (D2O): ¤ 2.25-2.36

H. Fujioka et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 3 (2010)
269
Table 1. Crystallographic Data for 9
H
N
H
Crystal color, Habit
Formula
Colorless, needle
C70H138N20O35Zn4
2081.49
N
N
N
N
N
Br
Br
+
H
N
N
N
H
H
H
H
in CHCl3
Formula weight
Crystal dimensions/mm3
Crystal system
Space group
a/¡
b/¡
c/¡
V/¡3
m-bis(cyclen)
HN
NH
0.20 © 0.06 © 0.03
Orthorhombic
Pca21 (#21)
66.1658(11)
16.1102(2)
17.4020(3)
18549.6(5)
8
1.491
8784
19.701
30848
5
N
H
cyclen
3
+ 2 equiv Zn2+
in H2O
H
H
N
N
N
N
+malonate
H
H
H
O-
-O
O
Zn2+
Zn2+
4
H
N
N
N
N
K1
H
H
K
O
O
-H+
Z
D
H
m,m-bis(Zn2+−cyclen)−malonate
8, Zn2L−malonate
H
H
H
N
N
N
N
N
O-
¹3
calcd/Mg m
H
Zn2+
N
Zn2+
O
H
O
H
F(000)
N
N
H
H
¹1
in H2O in Crystal
®/cm
m,m-bis(Zn2+−cyclen)-OH-
6, Zn2L-OH-
No. of observations
No. of variables
2324
H
H
N
N
N
N
N
Zn2+
-H+
Zn2+
R1 = - ««Fo« ¹ «Fc««/- «Fo«, (I > 2·(I))
wR2 = [- (w(Fo ¹ Fc ) )/- w(Fo ) ]
(All reflections)
0.0951
K2
N
N
2
2 2
2 2 0.5
N
H
H
O-
H
O-
0.2906
O
O
O
H
H
H
H
N
HO-
N
N
H
N
O-
O-
O
H
N
Zn2+
N
Zn2+
N
-OH
H
N
N
N
N
N
H
Zn2+
H
Zn2+
were adopted for the X-ray crystal structure: Zn(1-8), C(1-140),
N(1-40), and O(1-70). Crystallographic data and refinement
parameters are listed in Table 1. The crystal data have been
deposited at the Cambridge Crystallographic Data Center; the
deposition number is CCDC 744746. Copies of this information
may be obtained free of charge via www.ccdc.cam.ac.uk/data_
request/cif, by emailing: data_request@ccdc.cam.ac.uk, or contact-
ing CCDC, 12, Union Road, Cambridge, CB2 1EZ, U.K. [Fax:
+44 1223 336033].
N
N
N
N
H
H
m,m-bis(Zn2+−cyclen)-(OH-)2
7, Zn2L-(OH-)2
9, (Zn2L−malonate)2
Figure 1. Synthesis
(Zn2+-cyclen) 4.
and
equilibria
of
m,m-bis-
Equilibria in Aqueous Solution. The potentiometric pH
titrations were performed with an aqueous solution of 1.00 mM
4 (Zn2L) at 25 °C with I = 0.10 M (NaNO3). A typical pH
titration curve for Zn2L is shown in Figure 2a. The titration
data were analyzed for two deprotonation equilibria (1) and (2).
The deprotonation constants (pK1 and pK2) of 6.39 « 0.03
and 8.15 « 0.03 are assigned according to Figure 1. The first
deprotonation occurs at lower pH and the second one at higher
pH compared with the zinc(II)-bound water of zinc(II)-cyclen
1 (pKa = 7.9).18 The nonequivalent pKa values of zinc(II)-
Results and Discussion
Syntheses of m,m-Bis(cyclen) and Its Zinc(II) Complexes.
A
macrocyclic tetraamine, 1,4,7,10-tetraazacyclododecane
(cyclen) was allowed to react with equimolar amounts of
1,3-bis(bromomethyl)benzene in CHCl3 at room temperature.
Two main products, 1,4,7,10,18,21,24,27-octaazapentacyclo-
[24.8.2.218,27.112,16.129,33]-tetraconta-12,14,16(40),29,31,33,(39)-
hexaene (3) (m,m-bis(cyclen), L) and 1,3-bis[(1,4,7,10-tetra-
azacyclododecan-1-yl)methyl]benzene (5) (m-bis(cyclen)) were
obtained in 10% and 15% yields, respectively (Figure 1). The
dizinc(II) complex, m,m-bis(Zn2+-cyclen) 4 (Zn2L) was crys-
tallized as nitrate salts from an aqueous EtOH solution
containing equimolar amounts of 3 and Zn(NO3)2¢6H2O.
The 2:2 cyclen/m-xylene composition of m,m-bis(cyclen)
was determined by 1D and 2D NMR, elemental analysis (C,
H, N), MALDI-TOF MS, and potentiometric pH titration. The
¹
bound waters indicate that the zinc(II)-bound OH and H2O
molecule in 6 stay in a distance for electrostatic interaction
¹
such as Zn-OH £H2O£H2O-Zn (Figure 1). Further deproto-
nation or precipitation of Zn(OH)2 was not observed below
pH 11. NMR spectra of 4 (pD 5), 6 (pD 7), and 7 (pD 11)
disclosed a symmetric structure for the two zinc(II)-cyclen
moieties in D2O solution, so that the proton exchange reaction
between the Zn2+-OH2 and Zn2+-OH in 6 is sufficiently fast
in aqueous solution.
¹
1
obtained evidence is as follows: i) The H NMR signals of 3
are assigned to a symmetric 1,3-substituted benzene derivative.
ii) The 13C NMR of 3 showed nine signals, which is consistent
with a structure containing a 1,4-substituted cyclen moiety.
iii) The nuclear overhauser effects, NOEs of the benzyl protons
of 3 were observed with two kinds of Bz-NCH2 protons (e.g.,
C1, C2, C3, and C8), but not with HNCH2 protons (e.g., C4,
C5, C6, and C7): the carbon atom numbers are shown in the X-
ray crystallography section. iv) The MS signal of 3 (M + H+)
was observed at m/z 549.4. v) The dizinc(II) complex 4 has
two pKa values assigned to two zinc(II)-bound water molecules
(see below).
Zn2L ð4Þ ¼ Zn2L-OHꢁ ð6Þ þ Hþ;
K1 ¼ ð½Zn2L-OHꢁꢂaH =½Zn2LꢂÞ=M
ð1Þ
ð2Þ
þ
Zn2L-OHꢁ ð7Þ ¼ Zn2L-ðOHꢁÞ2 ð7Þ þ Hþ;
K2 ¼ ð½Zn2L-ðOHꢁÞ2ꢂaH =½Zn2L-OH ꢂÞ=M
ꢁ
þ
The association constant of the 1:1 malonate-bound di-
zinc(II) complex (1.0 mM) was determined by the potentio-
metric pH titrations in the presence of 1.0, 2.0, and 5.0 mM
malonate dianion at 25 °C with I = 0.10 M (NaNO3). A typical
titration curve with 2.0 mM disodium malonate salt is presented

270
Bull. Chem. Soc. Jpn. Vol. 83, No. 3 (2010)
Dibridged Bis(Zn2+-cyclen)
11
10
100
80
Zn2L-malonate
Zn2L-(OH-)2
Zn2L-OH-
10 11
9
60
pH
8
b
40
20
a
7
Zn2L
6
5
4
0
5
6
7
8
pH
9
0
1
2
equiv(OH-)
Figure 3. Distribution diagram for 2 mM 4 (Zn2L) in the
þ
presence of 2 mM malonate as a function of pH (¹log aH
)
Figure 2. Typical pH titration curves for 1 mM 4 (Zn2L) at
25 °C with I = 0.10 M (NaNO3) in aqueous solution: (a) in
the absence of malonate and (b) in the presence of 2 mM
at 25 °C with I = 0.10 M (NaNO3). The data for malonate
monoanion (pKa = 5.28) and malonate dianion are omitted
for clarity.
¹
malonate. equiv(OH ) is the number of equivalents of base
added.
displayed in Figure 3, which shows an appropriate pH for the
anion complexation is around pH 6. In the H NMR analysis
1
in Figure 2b. From the comparison of the titration curves in the
presence and absence of malonate, we concluded that a
malonate-bound complex 8 (Zn2L-malonate) is formed in the
of 8, we found that the methylene hydrogen atoms (¤ 3.2 at
2 mM 8) of the zinc(II)-bound malonate dianion were readily
exchanged for deuterium in D2O. The half-life for the H/D
exchange was determined to be 80 min for 1:1 mixture
(2.0 mM) of malonate and m,m-bis(Zn2+-cyclen) at 25 °C and
pD 7.0. Under the experimental conditions, the pseudo-first-
order rate constant is 1.4 © 10¹4 s¹1. After the end of the
reaction, the solution pD was not changed and the other C-
bound proton and carbon signals remained the same as those
of freshly prepared sample, indicating that no side reaction
(e.g., decarboxylation) occurred. In the absence of 4, no H/D
exchange of the methylene group was observed after leaving
for 24 h. Since the reported pseudo-first-order rate constant for
¹
titration pH range from 5 to 8, but the OH -bound complexes 6
and 7 coexist at alkaline pH. Elaborate calculations using
the titration data are consistent with the equilibrium (3) and the
1:1 association constant, log K value of 3.6 « 0.1. Even at 5
equivalents of malonate (5 mM), 2:1 and 2:2 malonate/m,m-
bis(Zn2+-cyclen) complexes were not confirmed from the pH
titration data. We proposed a structure of 1:1 malonate-bound
complex containing a zinc(II)-bound water, 8 in Figure 1 from
the following facts: i) The distance between two anionic
oxygen atoms of malonate (O £O distance less than 5 ¡) is
too short to bridge the intramolecular two zinc(II) ions of m,m-
bis(Zn2+-cyclen) (the Zn£Zn distance more than 7 ¡), as
shown by its CPK molecular model and the X-ray crystal of 2:2
malonate/m,m-bis(Zn2+-cyclen) complex (see next section). ii)
The pH difference of the titration region at 0 < equiv(OH ) <
1 between the absence and presence of 2 mM malonate is much
larger than that at 1 < equiv(OH ) < 2 (Figure 2). This fact
indicates that the malonate coordination would be stabilized by
an intramolecular hydrogen bond with the zinc(II)-bound water
(Zn-malonate£H2O-Zn). In addition, the following deproto-
¹
¹
¹1
the H/D exchange of malonate dianion is 1.2 © 10¹6 s at
25 °C at pD 7,26 the acceleration factor of 2 mM m,m-bis(Zn2+
-
cyclen) is about 102. Furthermore, we determined similar H/D
exchange reactions using 2-methyl malonate and succinate
diaions. Under the same conditions used for malonate, the half-
life of 500 min for deuteration of the methine hydrogen of
2-methyl malonate was estimated to be a greater value than
that for malonate, which is possibly due to an electron donor
of the methyl group. On the other hand, the hydrogen atoms
of a 2-methyl group showed no H/D exchange even after
1 day. As for succinate dianon, no H/D exchange reaction of
the methylene groups was observed under the experimental
conditions.
¹
¹
¹
nation of the zinc(II)-bound water of 8 (i.e., OH binding)
would destabilize the 1:1 malonate complex by electrostatic
repulsion between the Zn-unbound carboxylate anion and
¹
Zn-OH ). iii) The 1H NMR signals of 8 (2 mM) in D2O
solution at 35 °C are almost the same as shown those for the
symmetric m,m-bis(Zn2+-cyclen), so that the ligand exchange
reaction between malonate dianion and water molecule in 8 is
sufficiently fast in aqueous solution.
Synthesis and X-ray Crystal Structure of 2:2 Malonate/
m,m-Bis(Zn2+-cyclen) Complex 9.
The malonate/m,m-
bis(Zn2+-cyclen) complex was crystallized as its nitrate salt
from an aqueous solution (pH 7) containing m,m-bis(cyclen),
two equivalent of zinc(II) nitrate, and two equivalents of
disodium malonate. After drying under a pressure of 5 mmHg
at 25 °C, the colorless crystals changed to white powder, which
indicated that some lattice water molecules in the crystal are
easily removed. The elemental analysis (C, H, N) and its NMR
Zn2L ð4Þ þ malonate ¼ Zn2L-malonate ð8Þ;
K ¼ ð½Zn2L-malonateꢂ=½Zn2Lꢂ½malonateꢂÞ=Mꢁ1
ð3Þ
A typical diagram for species distribution as a function of
pH at [total dizinc(II) complex] = [total malonate] = 2 mM is

H. Fujioka et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 3 (2010)
271
Table 2. Selected Bond Lengths/¡ and Angles/° around
Zinc(II) Ions of 9
Zn1-O1
Zn1-N2
Zn1-N4
Zn2-N5
Zn2-N7
Zn3-O3
Zn3-N10
Zn3-N12
Zn4-N13
Zn4-N15
1.944(6)
2.195(5)
2.135(6)
2.185(5)
2.118(5)
1.954(6)
2.195(5)
2.137(5)
2.188(4)
2.123(5)
Zn1-N1
Zn1-N3
Zn2-O5
Zn2-N6
Zn2-N8
Zn3-N9
Zn3-N11
Zn4-O7
Zn4-N14
Zn4-N16
2.199(5)
2.119(6)
1.947(6)
2.198(5)
2.135(5)
2.192(5)
2.118(5)
1.976(6)
2.197(4)
2.142(5)
O1-Zn1-N1
O1-Zn1-N3
N1-Zn1-N2
N1-Zn1-N4
N2-Zn1-N4
O5-Zn2-N5
O5-Zn2-N7
N5-Zn2-N6
N5-Zn2-N8
N6-Zn2-N8
O3-Zn3-N9
O3-Zn3-N11
N9-Zn3-N10
N9-Zn3-N12
N10-Zn3-N12 134.6(2)
O7-Zn4-N13
O7-Zn4-N15
N13-Zn4-N14 81.11(18)
N13-Zn4-N16 81.80(19)
N14-Zn4-N16 134.3(2)
103.1(2)
121.1(2)
80.8(2)
O1-Zn1-N2
O1-Zn1-N4
N1-Zn1-N3
N2-Zn1-N3
N3-Zn1-N4
O5-Zn2-N6
O5-Zn2-N8
N5-Zn2-N7
N6-Zn2-N7
N7-Zn2-N8
O3-Zn3-N10 101.7(2)
O3-Zn3-N12 123.2(2)
N9-Zn3-N11 136.2(2)
N10-Zn3-N11 82.4(2)
N11-Zn3-N12 81.6(2)
O7-Zn4-N14 105.8(2)
O7-Zn4-N16 119.3(2)
N13-Zn4-N15 136.0(2)
N14-Zn4-N15 82.15(18)
N15-Zn4-N16 81.5(2)
105.3(2)
119.3(2)
135.4(2)
82.3(2)
Figure 4. One of the crystallographically independent
molecules of 9. Atoms are drawn with 50% probability
ellipsoids. Four nitrate ions, hydrogen atoms, and 15 water
molecules are omitted for clarity.
81.5(2)
134.7(2)
106.7(2)
116.5(2)
81.16(19)
81.8(2)
134.6(2)
104.4(2)
118.6(2)
81.07(19)
81.8(2)
81.8(2)
104.2(2)
120.9(2)
136.3(2)
82.2(2)
data of the obtained powder suggested the formula (Zn2L-
malonate¢(NO3)2¢2H2O)n. The crystal of the malonate/m,m-
bis(Zn2+-cyclen) complex was subjected to X-ray structure
analysis at ¹180 °C. The crystal structure provided unequiv-
ocal evidence for the 2:2 malonate/m,m-bis(Zn2+-cyclen)
complex 9, which is shown in Figure 4. We failed to isolate
the originally intended 1:1 complex 8 with various other
81.8(2)
¹
¹
2¹
120.9(2)
102.7(2)
counter anions such as Cl , ClO4 , or SO4 . The complex 9
has a cyclic structure constructed with two malonate dianions
and two m,m-bis(Zn2+-cyclen) complexes. The malonate
dianion bridges the two Zn2L units through the Zn2+-O
¹
bonds. Each zinc(II) ion is surrounded in a distorted tetragonal
pyramidal environment by the four nitrogen atoms of each
cyclen and an anionic malonate oxygen. Selected bond lenghs
and angles around zinc(II) ions are listed in Table 2. The
We are grateful to Dr. Eiichi Kimura (Professor emeritus of
Hiroshima University) for many helpful discussions on the
macrocyclic polyamine complexes.
¹
average Zn2+-O bond length of 1.96 ¡ is shorter than of the
Zn2+-N bond length of 2.16 ¡. As we estimated, the intra-
molecular distances between two zinc(II) ions (ca. 9.3 ¡) are
much longer than those between two oxygen anions of
malonate moieties (ca. 4.1 ¡) in 9. The cyclic structure of 9
is similar to that of the previous m-bis(Zn2+-cyclen) complex
with barbital dianion.16
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