Crystal structure, antitumor activities and DNA-binding properties of the La(III) complex with Phthalazin-1(2H)-one prepared by a novel route

Article abstract of DOI:10.1016/j.jorganchem.2005.07.046

Phthalazin-1(2H)-one was prepared by a novel route. The La(III)-complex of phthalazin-1(2H)-one, [La(NO₃)₃ ? 4H₂O ? C₈H₇N₂O] ? H₂O, was synthesized and characterized on the basis

Full text of DOI:10.1016/j.jorganchem.2005.07.046

Journal of Organometallic Chemistry 690 (2005) 4557–4563
www.elsevier.com/locate/jorganchem
Crystal structure, antitumor activities and DNA-binding
properties of the La(III) complex with Phthalazin-1(2H)-one
prepared by a novel route
a
a,
b
b
c
*
Yan Wang , Zheng-Yin Yang , Qin Wang , Qi-Kuan Cai , Kai-Bei Yu
a
School of Chemistry and Chemical Engineering and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
b
School of Life Science, Lanzhou University, Lanzhou 730000, China
Analysis and Research Center, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
c
Received 23 May 2005; received in revised form 26 June 2005; accepted 4 July 2005
Available online 19 August 2005
Abstract
Phthalazin-1(2H)-one was prepared by a novel route. The La(III)-complex of phthalazin-1(2H)-one, [La(NO
3 3 2 8 7
) Æ 4H O Æ C H -
N O] Æ H O, was synthesized and characterized on the basis of elemental analysis, thermal analyses (TG/DTA) and X-ray crystal-
2
2
lography. In the complex, the coordination number of the La(III) ion is eleven. The interaction of the ligand and its complex with
calf thymus DNA was investigated by spectrophotometric methods and viscosity measurements, respectively. Experimental results
indicated that phthalazin-1(2H)-one and the complex can bind to DNA by intercalation modes, but the binding affinity of La(III)-
complex is higher than that of the ligand. Comparative antitumor activities of La(III)-complex was investigated by HL-60 and
ꢀ
8
ꢀ5
A-549. IC50 = 2.6 · 10 , 3.3 · 10 mg/mL are given.
2005 Elsevier B.V. All rights reserved.
ꢀ
Keywords: Novel route; Phthalazin-1(2H)-one; Intercalation; DNA binding; Antitumor
1
. Introduction
complexes of many rare earth metals have demonstrated
cytotoxicity in cell culture and antitumor activity in tu-
mor-bearing animals [10,11], with the discovery of rare
earth elements in medicine field the study for the synthe-
sis of rare earth complexes is appealing [12,13].
Over the years, due to lack of effective drugs, cancer is
a fatal disease, rating the top three causes of death [1,2].
Since DNA is an important cellular receptor, many
chemicals exert their antitumor effects through binding
to DNA thereby changing the replication of DNA and
inhibiting the growth of the tumor cell, which is the ba-
sis of designing new and more efficient antitumor drugs
and their effectiveness depends on the mode and affinity
of the binding [3–6]. A number of metal chelates have
been used as probes of DNA structure in solution [7],
as agents for mediation of strand scission of duplex
DNA and as chemotherapeutic agents [8,9]. However,
Phthalazin-1(2H)-one was synthesized many years
ago [14], its bioactivity has been researched extensively
[15–19]. However, its rare earth complexes seem not to
be reported. Recently, we have prepared phthalazin-
1(2H)-one by a novel route and got the crystal of
La(III)-complex. We separated the intermediate product
that was characterized on the basis of elemental analy-
1
ses, H NMR spectra, thermal analyses (TG/DTA)
and X-ray crystallography. The DNA binding proper-
ties of this complex have been investigated by spectro-
photometric methods and viscosity measurements. The
result shows the complex binds to DNA by intercalation
modes.
*
Corresponding author. Tel.: +86 931 891 3515; fax: +86 931 891
2582.
E-mail address: yangzy@lzu.edu.cn (Z.-Y. Yang).
0
022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.07.046

4558
Y. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 4557–4563
2
. Results and discussion
Ligand, phthalazin-1(2H)-one, always was synthe-
Table 1
8 16 5
Crystal data and structure refinement for the LaC H N O15 complex
Compound
[La(NO
3
)
3
Æ 4H
2
O Æ C
8
H
7
N
2
2
O] Æ H O
Empirical formula
Formula weight
Temperature (K)
C
8
H
16LaN O
5 15
sized by the classical reaction of 2-carboxybenzalden-
hyde and hydrazine hydrate, however, the compound
can be formed by a novel route in the paper, which La
569.17
296(2)
0.71073
Triclinic
˚
Wavelength (A)
(
NO ) Æ 2H O reacts with one of three different raw
Crystal system
Space group
Unit cell dimensions
3
3
2
ꢀ
materials, such as 2-carboxybenzalde-hydeisonicotini-
chydrazone, 2-carboxybenzaldehyde-(4 -methoxy)-ben-
P1
0
˚
a (A)
7.182(1)
11.224(1)
12.819(2)
101.24(1)
103.22(1)
108.56(1)
912.6(2)
2
2.042
2.430
552
0.52 · 0.34 · 0.18
1.71–26.00
zoylhydrazone and 2-carboxybenzaldehydebenzoylhy
drazone in ethanol 95% solution, respectively. The re-
sults show that the performances of the three reactions
are the same, which all product white solid firstly, then
the white solid disappear and phthalazin-1(2H)-one
was formed. But if we use some transition metal salts,
˚
b (A)
˚
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
Volume (A )
Z
˚
3
such as Zn(OAc) Æ 2H O and Cu(OAc) Æ 2H O, phthal-
3
2
2
2
2
Density, calculated (Mg/m )
Absorption coefficient (mm
F(000)
Crystal size (mm)
h range for data collection (ꢁ)
ꢀ
1
azin-1(2H)-one cannot be produced. On the basis of
above evidence and analyses, we think: 1. La(III) ion
has an very important effect on the reactions. 2. The
middling product (white solid) is not stable and it may
be resolved under the La(III) ion catalyze. The mecha-
nism of the reactions is still investigated (Scheme 1).
)
Index ranges
0 6 h 6 8,
ꢀ
13 6 k 6 12,
ꢀ15 6 l 6 15
Reflections collected
Independent reflections
Reflections with I > 2r(I)
Absorption correction
Maximum and
minimum transmission
Refinement method
Data/restraints/parameters
3972
3540 (Rint = 0.0131)
3317
Empirical
2
2
.1. The structure of La(III) complex
.1.1. Elemental analysis
The crystal was analyzed for C, H, N with the follow-
0.9828 and 0.5231
2
Full-matrix least-squares on F
3540/11/307
1.089
ing results (found (%)/calculated (%)); [La(NO ) Æ
4
2
3
3
H O Æ C H N O] Æ H O, C = 17.15/17.12, H = 2.39/
2
2
8
7
2
2
Goodness-of-fit on F
.87, N = 12.71/12.48.
Final R indices [I > 2r(I)]
R indices (all data)
Extinction coefficient
Largest difference
1
R = 0.0212, wR = 0.0455
2
R
1
= 0.0193, wR
2
= 0.0450
0.0126(5)
0.684 and ꢀ0.697 (e A˚
2
.1.2. Thermal stability of the complex
The La(III) complex has an endothermic peak at
46 ꢁC and the corresponding TG curves show that
ꢀ3
)
peak and hole
1
the weight loss is equal to four water molecules. This
fact suggests that the complexes contain four coordi-
nated water molecules, this being also confirmed by X-
ray diffraction. Three exothermic peaks appear around
2.1.3. Structure of the complex
The molecular geometry of La(III)-complex was
shown by an X-ray diffraction study to have the struc-
ture depicted in Fig. 1 (with the geometrical data shown
2
83–520 ꢁC (Table 1).
O
C
COOH
COOH
CHO
O
C
benzene
R1 R2
+
H N
reflux 2h
2
N
R1 R2
N
H
C
N
H
H
+
La(NO ) 6H O
3
3
2
La(NO3)3 4H2O H2O
+
HOOC
R1 R2
ethanol 95%
reflux 4h
C
O
N
NH
R = N; R = C, R = H; R = C, R = OCH
1
1
2
1
2
3
Scheme 1.

Y. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 4557–4563
4559
in Table 2). The La(III) ion is linked to the three dibe-
nate chelating nitrates, to four water molecules and to
one O-donor atom of the phthalazin-1-(2H)-one. The
coordination number is eleven. The bond lengths C1–
˚
˚
O1 of 1.244 (3) A and N2–C8 of 1.290 (4) A clearly indi-
cate they are double bond, however, the bond length
˚
C1–N1 of 1.349 (4) A indicate it is single bond. The
bond length N1–H(N1) of 0.89 (4) A show that it is
˚
not –HOC@N–, but –CO–NH–. The bond length La–
˚
O1 of 2.475(2) A is the shortest in the average bond
˚
length La–O(2–14) of 2.664(2) A (Fig. 2). There is p,p-
stacking between phthalazin-1(2H)-one group in the
˚
crystal state, the distance is ca. 3.54 A and the angle is
ca. 0ꢁ (Fig. 3).
2
2
.2. Biological activity
.2.1. UV Spectra
The interaction of the compounds with the DNA was
investigated using absorption spectra. The absorption
spectra of two compounds in the absence and presence
of the DNA (at a constant concentration of the
Fig. 1. An ORTEP drawing of the complex showing the atomic
numbering scheme.
Table 2
˚
Selected bond lengths [A] and angles [ꢁ]
˚
Bond lengths [A]
La–O(1)
2.475(2)
2.554(2)
2.562(2)
2.574(2)
1.270(3)
1.226(3)
1.373(3)
1.290(4)
1.395(4)
La–O(11)
La–O(3)
La–O(2)
O(1)–C(1)
O(3)–N(3)
N(1)–C(1)
N(1)–H(1N)
C(1)–C(2)
C(2)–C(7)
2.617(2)
2.664(2)
2.717(2)
1.244(3)
1.250(3)
1.349(4)
0.89(4)
La–O(12)
La–O(14)
La–O(13)
O(2)–N(3)
O(4)–N(3)
N(1)–N(2)
N(2)–C(8)
C(2)–C(3)
1.445(4)
1.402(4)
Bond angles [ꢁ]
O(1)–La–O(12)
O(1)–La–O(11)
O(1)–La–O(8)
O(14)–La–O(8)
O(1)–La–O(5)
O(12)–La–O(3)
O(13)–La–O(3)
O(8)–La–O(3)
O(12)–La–O(2)
O(13)–La–O(2)
O(8)–La–O(2)
O(3)–La–O(5)
O(1)–La–O(9)
O(3)–La–O(9)
O(2)–La–O(6)
C(1)–O(1)–La
N(3)–O(2)–La
La–O(11)–H(11A)
C(1)–N(1)–N(2)
N(2)–N(1)–H(1N)
O(4)–N(3)–O(3)
O(3)–N(3)–O(2)
O(1)–C(1)–N(1)
141.58(8)
128.56(7)
137.55(7)
139.56(7)
66.87(7)
103.29(7)
110.10(7)
100.17(6)
130.42(7)
65.47(7)
70.64(7)
135.80(6)
129.52(7)
62.53(6)
153.35(7)
160.7(2)
96.04(15)
119(2)
O(1)–La–O(14)
O(1)–La–O(13)
O(12)–La–O(8)
O(13)–La–O(8)
O(1)–La–O(3)
O(14)–La–O(3)
O(11)–La–O(3)
O(1)–La–O(2)
O(14)–La–O(2)
O(11)–La–O(2)
O(3)–La–O(2)
O(2)–La–O(5)
O(1)–La–O(6)
O(2)–La–O(9)
O(3)–La–O(6)
N(2)–C(8)–C(7)
N(3)–O(3)–La
N(1)–C(1)–C(2)
C(1)–N(1)–H(1N)
C(8)–N(2)–N(1)
O(4)–N(3)–O(2)
C(3)–C(2)–C(7)
O(1)–C(1)–C(2)
73.77(8)
76.66(8)
80.24(7)
68.81(7)
69.05(7)
63.10(7)
161.91(6)
73.05(7)
109.39(7)
127.86(6)
47.19(6)
119.30(6)
80.32(7)
64.28(7)
122.92(6)
124.4(3)
99.18(15)
116.1(2)
120(2)
Fig. 2. Crystal packing of La(III) complex.
127.2(2)
113(2)
121.8(2)
117.6(2)
119.8(3)
116.0(2)
120.7(2)
120.7(3)
124.1(3)
Fig. 3. Crystal p,p-stacking of La(III) complex.

4560
Y. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 4557–4563
compounds) are given in Fig. 4. As the concentration of
DNA is increased, the Soret (at 212 and 210 nm) band
of the compounds exhibit hypochromism of ca. 44%
and 58%, and the bandochromism of 4 and 13 nm,
respectively. These spectral characteristics may suggest
that there are some interactions between the compounds
and DNA [20], but for the La(III)-complex, it inserts
into DNA more deeply.
To compare quantitatively the affinity of the complex
bound to DNA, the intrinsic binding constants K of it
was obtained by the luminescence titration method.
The concentration of the bound complex was calculated
0
max
0
by the equation [21]: C = C [(F ꢀ F )/(F
ꢀ F )].
b
t
C is the total complex concentration; F is the ob-
t
served fluorescence emission intensity at given DNA
0
concentration; F is the intensity in the absence of
max
DNA; and F
is the fluorescence of the totally bound
2
.2.2. Fluorescence spectra
The enhancements in the emission intensity of the
complex; C = C ꢀ C . According to the classical Scat-
b
t
chard equation, a plot of c/C vs. c, we obtained the
7
ꢀ1
La(III)-complex with increasing DNA concentration
are shown in Fig. 5. In the absence of DNA it emits
weak luminescence in Tris-buffer at ambient tempera-
ture, with a maximum appearing at 447 nm. Upon addi-
tion of DNA the emission intensity of the complex
grows steadily. Although the emission enhancement
could not be regarded as a criterion for binding mode,
they are related to the extent to which the complex gets
into a hydrophobic environment inside DNA and avoids
the complex effect of solvent water molecules. However,
there is no luminescence intensity changes in the fluores-
cence spectra of phthalazin-1(2H)-one, either in the ab-
sence or presence of DNA.
binding constants of 1.4 · 10 L mol from the fluores-
cence data (Fig. 6). c is binding ratio C /[DNA].
b
Further support for La(III)-complex to DNA by
intercalation mode is given through the emission
quenching experiment. Ethidium bromide (EB) was em-
ployed as a fluorescent probe [22,23]. Fig. 7 shows the
emission spectra of DNA-EB system upon the increas-
ing amounts of the complexes. The emission intensity
of the DNA-EB system (k = 578 nm) decreased appar-
ently as the concentration of the complexes increased
and an isobathic point appeared at 555 nm, which indi-
cated the formation of the new system of DNA. These
changes show that the complex replaced EB from the
DNA-EB system leading to the decreased emission of
the DNA-EB system. The results were caused by EB
changing from a hydrophobic environment to water
solution [1].
According to the classical Stern–Volmer equation
[
24]: F /F = K [Q] + 1, where F is the emission intensity
0 q 0
in the absence of quencher, F is the emission intensity in
the presence of quencher, K is the quenching constant
q
and [Q] is the quencher concentration. The shape of
Stern–Volmer plots can be used to characterize the
quenching was being predominantly dynamic or static.
Plots of F /F versus [Q] appear to be linear and K de-
pends on temperature [24]. The emission quenching of
addition of the complexes to the DNA-EB system at
0
q
Fig. 4. Absorption spectra of the compounds in the absence and
presence of increasing amounts of DNA concentration. The arrows
show the absorbance changes on increasing DNA concentration.
ꢀ1
ꢀ1
[
Compound] = 10 lmol L , [DNA] = 0–60 lmol L . (a) The spectra
of the ligand. (b) The spectra of the La(III)-complex.
2.4
1
1
1
1
1
80
60
40
20
00
2.2
2
1
1
1
.0
.8
.6
.4
1.2
1
0
0
0
.0
.8
.6
.4
8
6
4
2
0
0
0
0
0.514 0.516 0.518 0.520 0.522 0.524 0.526 0.528
4
00
420
440
460
480
500
Wavelength (nm)
Fig. 6. Schtchard plot of the fluorescence titration data of the
7
ꢀ1
Fig. 5. Electronic spectra of the complex addition of DNA.
complex, K = 1.4 · 10 L mol
.

Y. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 4557–4563
4561
1
1
1
1
1
1
1
1
.013
.012
.011
.010
.009
.008
.007
.006
50
40
30
20
10
0
Complex
Ligand
1.005
.004
1
0
.1
0.2
0.3
0.4
0.5
0.6
5
20
540
560
580
600
620
640
[
Complex]/[DNA]
Wavelength (nm)
ꢀ
1
Fig. 9. Effect of increasing amounts of the complexes on the relative
viscosity of DNA at 35 ꢁC.
Fig. 7. The emission spectra of DNA-EB system (10 lmol L DNA
and 0.33 lmol L
ꢀ1
EB), kex = 500 nm, kem = 520–650 nm, in the
absence (---) and presence (—) of increasing amount of La(III)
complex.
to accommodate the binding ligand, leading to the
increase of DNA viscosity. In contrast, a partial, non-
classical intercalation of ligand could bend (or kink)
the DNA helix, reduce its effective length and, concom-
itantly, its viscosity [25,26]. The effects of the com-
pounds on the viscosity of rod-like DNA at 35 ꢁC are
shown in Fig. 9. With an increasing amount of the com-
pounds, the relative viscosity of DNA increased steadily,
which suggests that two complexes can bind to DNA by
classical intercalation. But the binding affinity of La(III)
complex is higher than that of the ligand.
2
5 ꢁC is shown in Fig. 8. The quenching plots illustrate
that the quenching of EB bound to DNA by complex is
in good agreement with the linear Stern–Volmer equa-
tion, which also proves that the two complexes bind to
DNA. In the plots of F /F versus [complex]/[DNA],
0
K is given by the ratio of the slope to intercept. The
q
3
ꢀ1
K value is 6.2 · 10 L mol
q
.
2
.2.3. Viscosity measurements
To further clarify the interactions between the com-
2.3. Antitumor activity
pounds and DNA, viscosity measurements were carried
out. Hydrodynamic measurements that are sensitive to
length change (i.e. viscosity and sedimentation) are re-
garded as the least ambiguous and the most critical tests
of binding in solution in absence of crystallographic
structural data. A classical intercalation model results
in lengthening the DNA helix as base pairs are separated
Because La(III)-complex can bind to DNA by inter-
calation modes, which indicates the La(III)-complex
maybe have better antitumor activity, we investigate
that the inhibiting effects of La(III)-complex against
two kinds of tumor cells (A-549 and HL-60) were stud-
ied and the result are listed in Tables 3 and 4. From
these two tables, it can be seen that the antitumor activ-
ities are in accord with the experiment results at the con-
centration for the complex, which increases with the
increase of the concentration. It submits a reference
for the further research.
1
1
.5
.4
1
1
.3
.2
3
. Experimental
3.1. Measurements
Elemental analyses were carried out on an Elemental
Vario EL analyzer. The thermal behavior was moni-
tored on a PCT-2 differential thermal analyzer (Beijing
Guangxue Instrument Factory, China). UV spectra were
obtained using a Shimadzu Unicam UV-240 spectro-
photometer in the 190–325 nm (Hitachi, Japan). The
melting points of the compounds were determined on
1
1
.1
.0
0
10
20
30
[
40
50
60
70
80
M] (10E-6 M)
Fig. 8. Stern–Volmer equation.

4562
Y. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 4557–4563
Table 3
Inhibition effect against human leukemia HL-60
Compound
Average inhibition effect (%)
Equation
IC50, mg/mL
a
a
a
a
C
1
C
2
C
3
C
4
ꢀ8
Complex (24 h)
77
65
54
33
y = 7.7x + 108.4
2.6 · 10
IC50 values were calculated from regression lines where: x was log of the tested compound concentration and y was percent inhibition of the tested
compounds. When the percent inhibition of the tested compounds was 50%, the tested compound concentration was IC50
.
a
ꢀ6
ꢀ7
ꢀ8
ꢀ10
C
i (i = 1–4) = 5 · 10 , 5 · 10 , 5 · 10 , 5 · 10
mg/mL.
Table 4
Inhibition effect against lung adenocarinoma A-549
Compound
Average inhibition effect (%)
Equation
IC50, mg/mL
a
a
a
a
C
1
C
2
C
3
C
4
ꢀ5
Complex (48 h)
88
78
54
40
y = 12.2x + 104.7
3.3 · 10
a
ꢀ1
ꢀ3
ꢀ4
ꢀ5
C
i (i = 1–4) = 1 · 10 , 1 · 10 , 1 · 10 , 1 · 10 mg/mL.
an XT4-100X microscopic melting point apparatus (Bei-
jing Electrooptical Instrument Factory, China). Fluores-
cence measurements were made on a Shimadzu RF-540
mens P4 diffractometer operating in x/2h scan mode
with graphite-monochromated Mo Ka radiation
˚
(0.71073 A),
h
range: 1.71 6 h 6 26.00, 0 6 h 6 8,
1
spectrofluorophotometer (Hitachi, Japan). H NMR
ꢀ13 6 k 6 12, ꢀ15 6 l 6 15, 3972 unique reflections
were collected at 296 (2) K, 3570 observed [I > 2(I)] of
which were used to solve the structure and least-squares
spectra were recorded on a Varian VR 300-MHz spec-
trometer with TMS (tetramethylsilane) as an internal
standard. Mass spectra was performed on a VG ZAB-
HS (FAB, fast atom bombardment ion source)
instrument.
refinement. The refinement converged at R = 0.0212
1
and wR = 0.0451 values for reflections. The absolute
2
configuration of the space group was assigned on the ba-
sis of Flack parameter. The final geometrical calcula-
tions were carried out with SHELXTL-97 and Patterson
programs used for structure solution and refinement
All the experiments involving the interaction of
La(III)-complex with DNA was carried out in doubly
ꢀ
1
distilled water buffer containing 5 mmol L Tris (tris
ꢀ
1
2
(
hydroxymethyl) aminomethane) and 50 mmol L
on F using all reflections.
NaCl and adjusted to pH 7.0 with hydrochloric acid.
A solution of DNA in Tris–HCl (Tris buffer) gave a ra-
tio of UV absorbance at 260 and 280 nm, A260/A280, of
about 1.8–1.9:1, indicating that the DNA was suffi-
ciently free of protein [27]. EB was prepared as
3.3. Preparation of La(III) complex
2-Carboxybenzaldenhyde was prepared according to
the literature [28]. A benzene solution (200 mL) of 2-
carboxybenzaldehyde (3.0 g, 20 mmol) and isonictinyl
hydrazine (2.8 g, 20 mmol) was refluxed for 4 h. After
cooling to room temperature, the white precipitated so-
lid was filtered, washed with benzene, and recrystallized
from benzene to give the 2-carboxybenzalde-hydeisonic-
otinichydrazone in a yield of 95%; m.p. 196–197 ꢁC.
ꢀ
1
1
.0 mg L by dissolving in doubly distilled water. The
DNA concentration was determined spectrophotometri-
cally by employing an extinction coefficient of
ꢀ
1
ꢀ1
6
600 M cm at 260 nm.
Viscosity experiments were carried on an Ubbelodhe
viscometer, immersed in a thermostated water-bath
maintained at 35 ꢁC. Titrations were performed for the
complex and it was introduced into DNA solution
+
FAB-MS: m/z = 270 [M+H] . A ethanol 95% solution
(50 mL) of 2-carboxybenzalde-hydeisonicotinichydraz-
one (0.269 g, 1 mmol) and La(NO ) Æ 6H O (0.433 g,
ꢀ
1
(
50 lmol L ) present in the viscometer. Data were pre-
3
3
2
1
/3
sented as (g/g0) versus binding ratio where g is the vis-
1 mmol) was refluxed for 10 min and there was a white
precipitate in the solution. After 0.5 h, the white precip-
itate was disappeared and the color of solution became
yellow. The reflux last 4 h and then the solution was
concentrated to 5 mL. The reaction solution was placed
and the single crystals were formed at the bottom of the
solution after 20 days. The crystals was filtered and a
white solid (Phthalazin-1(2H)-one) was obtained by col-
umn chromatographic (petroleum:ether-ethyl ace-
cosity of DNA in the presence of complex, and g is the
0
viscosity of DNA alone. Viscosity values were calculated
from the observed flow time of DNA-containing solu-
tion corrected from the flow time of buffer alone (t0),
g = t ꢀ t0.
3
.2. Crystal structure determination
A prismatic white transparent crystal of dimensions
.52 · 0.34 · 0.18 mm was centered on a four-circle Sie-
tate = 8:1) from the mother water. m.p. 182–183 ꢁC.
1
0
H NMR (DMSO-d ) d (ppm): 7.82–8.22 (4H, m,
6

Y. Wang et al. / Journal of Organometallic Chemistry 690 (2005) 4557–4563
4563
ArH); 8.35 (1H, s, –CH@N); 12.63 (1H, s, H–N). Then
[11] H. Elo, Inorg. Chim. Acta 136 (1987) 149.
[12] A. Quaroni, G. Semenza, B.E. Furie, J. Biol. Chem. 11 (1976)
250.
13] D.M. Kramsch, A.J. Aspen, L.J. Rozler, Science 213 (1981)
511.
0
2
-carboxybenzaldehyde-(4 -methoxy)benzoylhydrazone
3
[
29] and 2-carboxybenzalde-hydebenzoylhydrazone [30]
[
were used to replace 2-carboxybenzalde-hydeisonicotin-
ichydrazone in the same reaction, phthalazin-1(2H)-one
was obtained, too.
1
[14] S. Gabriel, A. Neumann, Ber. 26 (1893) 521.
[15] A.H. Hofstra, L.C. Matassa, J.P. Uetrecht, J. Rheumatol. 18
(
1991) 1673.
[16] R. Bottinelli, V. Cappelli, S.E.J.N. Morner, C. Reggiani, J.
Muscle Res. Cell. Motil. 14 (1993) 110.
Acknowledgments
[
[
17] Z. Fijalek, E. Szyszko, Acta Pol. Pharm. 34 (1981) 439.
18] G. Beaton, W.J. Moree, J.K. Rueter, R.S. Dahl, D.L. McElligott,
P. Goldman, A.J. Demaggio, E. Christenson, D. Herendeen,
K.W. Fowler, D. Huang, J.A. Bertino, L.H. Bourdon, D.J.
Fairfax, Q. Jiang, H.A. Reisch, R.H. Song, P.E. Zhichkin, (Icos
Corporation, USA). PCI Int. Appl. (2003), 229 pp. CODEN:
PIXXD2 WO 2003015785 A1 20030227.
The project was supported by the National Natural
science Foundation in China (20475023) and Gansu
NSF (3ZS041-A25-016).
[
[
19] (Zambon S.p.A., Italy), Jpn. Kokai Tokkyo Koho (1989), 8 pp.
CODEN: JKXXAF JP 01151561 A2 19890614.
20] Q.X. Zhen, B.H. Ye, Q.L. Li, J.G. Liu, Y. Xiong, L.N. Ji, L.
Wang, J. Inorg. Chem. 76 (1999) 47.
References
[
1] J. Zhou, L.F. Wang, J.Y. Wang, N. Tang, J. Inorg. Biochem. 83
2001) 41.
(
[21] A. Wolf, G.J. Shimer Jr., T. Meehan, Biochemistry 26 (1987)
6392.
[
[
2] D.R. Williams, Chem. Rev. 72 (1972) 203.
3] Y.B. Zeng, N. Yang, W.S. Liu, N. Tang, J. Inorg. Biochem. 97
[22] S.J. Lippard, Acc. Chem. Res. 11 (1978) 211.
[23] J.B. Lepecq, C. Paoletti, J. Mol. Biol. 27 (1967) 81.
[24] M.R. Efink, C.A. Ghiron, Anal. Biochem. 114 (1981) 199.
[25] X.H. Zou, B.H. Ye, H. Li, J.G. Liu, Y. Xiong, L.N. Ji, J. Chem.
Soc., Dalton Trans. (1999) 1423.
[26] D.S. Sigman, A. Mazumder, D.M. Perrin, Chem. Rev. 93 (1993)
2295.
[27] C.V. Kumar, E.H. Asuncion, J. Am. Chem. Soc. 115 (1993)
8547.
(2003) 258.
[
[
[
4] A.E. Friedman, C.V. Kumar, N.J. Turro, J.K. Barton, Nucl.
Acids Res. 19 (1991) 2595.
5] A.M. Pyle, T. Morii, J.K. Barton, J. Am. Chem. Soc. 112 (1990)
9432.
6] J.K. Barton, J.M. Goldberg, C.V. Kumar, N.J. Turro, J. Am.
Chem. Soc. 108 (1986) 20818.
[
[
[
7] S. Mahdevan, M. Palaniandavar, Inorg. Chim. Acta 254 (1997) 291.
8] S.J. Lippard, Acc. Chem. Res. 11 (1978) 211.
9] S.M. Hecht, Acc. Chem. Res. 19 (1986) 383.
[28] J.H. Gardner, C.A.Jr. Naylor, Org. Synth. 2 (1951) 523.
[29] Y. Wang, Z.Y. Yang, B.D. Wang, Synth. React. Inorg. Met-Org.
Nano-Met. Chem. 35 (2005) 237.
[
10] A.T. Beverly, T.A. Michael, W.R. Kristina, Cancer Res. 50 (1990)
971.
6
[30] Z.Y. Yang, R.D. Yang, J. Rare Earths 20 (2002) 366.