Crystal structures and DNA-binding properties of PrIII complexes derived from 8-hydroxyquinoline-2-carboxaldehyde and three aroylhydrazines

Article abstract of DOI:10.1080/00958972.2014.972387

Pr^III and three synthesized ligands, 8-hydroxyquinoline-2-carboxaldehyde-(benzoyl)hydrazone, 8-hydroxyquinoline-2-carboxaldehyde-(2′-hydroxybenzoyl)hydrazone, and 8-hydroxyquinoline-2-carboxaldehyde-(isonicotinyl)hydrazone, respectively, can fo

Full text of DOI:10.1080/00958972.2014.972387

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Crystal structures and DNA-binding
properties of PrIII complexes
derived from 8-hydroxyquinoline-2-
carboxaldehyde and three
aroylhydrazines
Yong-Chun Liua, Ying-Ying Lia, Hui-Li Qia, Ke-Jun Zhanga, Rui-Xia
Leia & Jian-Ning Liua
a College of Chemistry and Chemical Engineering, Longdong
University & FLUOBON Surfactant Engineering Technology Center,
Click for updates
Longdong University, Qingyang, PR China
Accepted author version posted online: 03 Oct 2014.Published
online: 30 Oct 2014.
To cite this article: Yong-Chun Liu, Ying-Ying Li, Hui-Li Qi, Ke-Jun Zhang, Rui-Xia Lei & Jian-
Ning Liu (2014) Crystal structures and DNA-binding properties of PrIII complexes derived from 8-
hydroxyquinoline-2-carboxaldehyde and three aroylhydrazines, Journal of Coordination Chemistry,
67:22, 3689-3703, DOI: 10.1080/00958972.2014.972387
To link to this article: http://dx.doi.org/10.1080/00958972.2014.972387
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Journal of Coordination Chemistry, 2014
Vol. 67, No. 22, 3689–3703, http://dx.doi.org/10.1080/00958972.2014.972387
Crystal structures and DNA-binding properties of PrIII
complexes derived from 8-hydroxyquinoline-2-
carboxaldehyde and three aroylhydrazines
YONG-CHUN LIU*, YING-YING LI, HUI-LI QI, KE-JUN ZHANG, RUI-XIA LEI and
JIAN-NING LIU
College of Chemistry and Chemical Engineering, Longdong University & FLUOBON Surfactant
Engineering Technology Center, Longdong University, Qingyang, PR China
(Received 1 April 2014; accepted 10 September 2014)
PrIII and three synthesized ligands, 8-hydroxyquinoline-2-carboxaldehyde-(benzoyl)hydrazone, 8-
hydroxyquinoline-2-carboxaldehyde-(2′-hydroxybenzoyl)hydrazone, and 8-hydroxyquinoline-2-car-
boxaldehyde-(isonicotinyl)hydrazone, respectively, can form binuclear PrIII complexes with 1 : 1
metal-to-ligand stoichiometry and nine-coordination at PrIII indicated by X-ray crystal structural
analyses. Ligands are dibasic tetradentate, binding to PrIII through the phenolate oxygen, nitrogen of
quinolinato unit, the C=N of methylene, and –O–C=N– enolized and deprotonated from O=C–NH–
of the aroylhydrazone side chain. One DMF binds orthogonally to the ligand plane from one side to
the metal ion, while another DMF and a bidentate nitrate simultaneously bind from the other. Dimer-
ization of the monomeric unit occurs through the phenolate oxygen leading to a central planar four-
membered (PrO)2 ring. The crystal structures are similar to each other and to other nine-coordinate
lanthanide complexes with geometry of distorted edge-sharing mono-capped square-antiprism of
[LnL(NO3)(DMF)2]2 (Ln = LaIII, NdIII, SmIII, EuIII, TbIII, DyIII, HoIII, and ErIII) except for YbIII
with eight-coordinate YbIII center with distorted edge-sharing dodecahedron of [YbL(NO3)(DMF)]2,
*Corresponding author. Email: ychliu001@163.com
© 2014 Taylor & Francis

3690
Y.-C. Liu et al.
derived from 8-hydroxyquinoline-2-carboxaldehyde and aroylhydrazines. The ligands and PrIII com-
plexes can bind to calf thymus DNA through intercalation with binding constants at 105 M−1 and
probably be used as potential antitumor drugs.
Keywords: Rare earth metal; Praseodymium complex; X-ray crystallography; Calf thymus DNA;
Intercalation
1. Introduction
A number of metal chelates, as agents for mediation of strand scission of duplex DNA and
as chemotherapeutic agents, have been used as probes of DNA structure in solution [1–3].
Apart from magnetic and photophysical properties, the bioactivities of lanthanide complexes
such as antimicrobial, antitumor, antivirus, anticoagulant action, enhancing NK and Macro-
phage cell activities, prevention from arteriosclerosis, etc have been explored [4–7]. Schiff
bases are able to inhibit the growth of several animal tumors, and some metal chelates have
shown good antitumor activities against animal tumors [8, 9]. Well-designed organic ligands
can have special properties fine tuned by metal ions. The chemistry of quinoline and its
derivatives has also attracted special interest due to their therapeutic properties. Quinoline
sulphonamides have been used in the treatment of cancer, tuberculosis, diabetes, malaria,
and convulsions [10, 11]. Previously, a series of lanthanide complexes were prepared from
lanthanide metal ions with 8-hydroxyquinoline-2-carboxaldehyde-aroylhydrazones and
8-hydroxyquinoline-7-carboxaldehyde-aroylhydrazones
[12–21].
These
lanthanide
complexes have similar structures and present strong affinities of binding to DNA through
intercalation. In this study, three PrIII complexes prepared from 8-hydroxyquinoline-2-
carboxaldehyde with aroylhydrazines and their crystal structures and DNA-binding
properties will be addressed.
2. Experimental
2.1. Materials
Calf thymus DNA (CT-DNA) and ethidium bromide (EB) were obtained from Sigma-
Aldrich Biotech. Co., Ltd. The stock solution (1.0 mM) of the investigated compound was
prepared by dissolving the powdered material into appropriate amounts of DMF solution.
Deionized double distilled water and analytical grade reagents were used throughout. CT-
DNA stock solution was prepared by dissolving the solid material in 5 mM Tris–HCl buffer
(pH 7.20) containing 50 mM NaCl. The CT-DNA concentration in terms of base pair L−1
was determined spectrophotometrically by employing an extinction coefficient of
ε = 13,200 M−1 cm−1 (base pair)−1 at 260 nm, and the concentration in terms of nucleotide
L−1 was also determined spectrophotometrically by employing an extinction coefficient of
6600 M−1 cm−1 (nucleotide)−1 at 260 nm [22]. The stock solution was stored at −20 °C
until it was used. EB was dissolved in 5 mM Tris–HCl buffer (pH 7.20) containing 50 mM
NaCl and its concentration was determined assuming a molar extinction coefficient of
5600 M−1 cm−1 at 480 nm [23].

Praseodymium complexes
3691
2.2. Methods
The melting points of the compounds were determined on an XT4-100X microscopic melt-
ing point apparatus (Beijing). The IR spectra were recorded on a Nicolet Nexus 670 FT-IR
1
spectrometer using KBr disks from 4000 to 400 cm−1. H NMR spectra were recorded on a
Bruker Advance DRX 200-MHz spectrometer with tetramethylsilane as an internal stan-
dard.
Viscosity titration experiments were carried out on an Ubbelohde viscometer in a thermo-
stated water bath maintained at 25.00 0.01 °C. Data were presented as (η/ηo)1/3 versus the
ratio of the compound to DNA, where η is the viscosity of DNA in the presence of the
compound corrected from the solvent effect and ηo is the viscosity of DNA alone [23, 24].
Ultraviolet–visible (UV–vis) spectra were obtained using a Specord 50 (Analytik Jena)
UV–vis spectrophotometer with a 1 cm quartz cell. The binding constant (Kb) was
determined by the following equation [25, 26]:
½DNAꢀ ½DNAꢀ
1
¼
þ
(1)
ef ꢁ ea ef ꢁ eb Kbðef ꢁ ebÞ
where [DNA] is the molar concentration of DNA in base pairs, εa (M−1 cm−1) corresponds
to the extinction coefficient observed, εf (M−1 cm−1) corresponds to the extinction coeffi-
cient of the free compound, εb (M−1 cm−1) is the extinction coefficient of the compound
when fully bound to DNA, and Kb is the intrinsic binding constant. The ratio of slope to
intercept in the plot of [DNA]/(εf − εa) versus [DNA] gives the values of Kb.
Fluorescence spectra were recorded using a RF-7000 spectrofluorophotometer (Hitachi)
with a 1 cm quartz cell. The excitation and emission band widths were 10 nm. DNA-EB
quenching assay was performed according to the literature procedure [12–21]. DNA
(4.0 μM, nucleotides) solution was added incrementally to 0.32 μM EB solution, and then
small aliquots of concentrated solutions (1.0 mM) were added till the drop in fluorescence
intensity (λex = 525 nm, λem = 587 nm) reached a constant value. Measurements were made
after 5 min at 298 K. Stern–Volmer equation was used to determine the fluorescence
quenching mechanism [27]:
Fo=F ¼ 1 þ KSV½Qꢀ
(2)
where Fo and F are the fluorescence intensities in the absence and in the presence of a
compound at [Q] concentration, respectively; KSV is the Stern–Volmer dynamic quenching
constant.
2.3. Preparation of ligands (1a, 1b, and 1c)
The synthetic routes for 1a–c are presented in figure 1 [12–19]. Ligand 1a, 8-hydroxyquin-
oline-2-carboxaldehyde-(benzoyl)hydrazone, was prepared by refluxing and stirring a
10 mL ethanol solution of 8-hydroxyquinoline-2-carboxaldehyde (0.519 g, 3 mM) and a
10 mL 90% ethanol aqueous solution of benzoylhydrazine (0.408 g, 3 mM) for 8 h. After
cooling to room temperature, the precipitate was filtered, recrystallized from 80% methanol
aqueous solution, and dried in vacuum for 48 h to give a powder. Yield: 0.656 g, 74.7%.
Pale. M.p. 221 °C (d). IR (KBr) (υmax/cm−1): 3359 (NH), 3318 (OH), 1682 (C=O), 1602
(C=N, azomethine), 1546 (C=N, pyridine), 1267 (C−OH). UV–vis (λmax nm,
ε × 104 M−1 cm−1, DMF): 295, 3.55; 323, 2.11. NMR (1H DMSO-d6 (dimethyl sulfoxide

3692
Y.-C. Liu et al.
4
5
3
6
O
20
17
7
O
N
19
N
N
H
R3
N
11
18
16
95% ethanol
OH
R1
OH
+
R2
O
1a (H2L1): R1=C, R2=H, R3=H
H2N
N
H
1b (H2L2): R1=C, R2=H, R3=OH
1c (H2L3): R1-R2=N, R3=H
R1
R3
R2
Figure 1. Synthetic routes for 1a–c.
with both methyl groups deuterated), 200 MHz, ppm, s: singlet, d: doublet, t: triplet, m:
3
multiplet): 8.637 (1H, s, 11-CH=N), 8.343 (1H, d, 4-CH, JHH = 8.8 Hz), 8.119 (1H, d, 3-
3
3
CH, JHH = 8.8 Hz), 7.936 (2H, d, 16,20-CH, JHH = 6.4 Hz,), 7.630–7.507 (3H, m,
3
17,18,19-CH), 7.467–7.387 (2H, m, 5,6-CH), 7.131 (1H, d, 7-CH, JHH = 5.0 Hz).
8-Hydroxyquinoline-2-carboxaldehyde-(2′-hydroxybenzoyl)hydrazone (1b) was obtained
from equimolar amounts of 8-hydroxyquinoline-2-carboxaldehyde and 2-hydrox-
ybenzoylhydrazine in the same way as 1a. Yield: 0.746 g, 81.0%. Yellow. M.p. 245–
247 °C (d). IR (KBr) (υmax/cm−1): 3464 (NH), 3250 (OH), 1643 (C=O), 1607 (C=N, azo-
methine), 1532 (C=N, pyridine), 1288 (C–OH). UV–vis (λmax nm, ε × 104 M−1 cm−1,
DMF): 294, 3.16; 329, 2.36. NMR (1H DMSO-d6, 200 MHz, ppm: 8.621 (1H, s, 11-
3
3
CH=N), 8.356 (1H, d, 4-CH, JHH = 8.6 Hz), 8.113 (1H, d, 3-CH, JHH = 8.6 Hz), 7.871
3
(1H, d, 20-CH, JHH = 7.8 Hz,), 7.469–7.395 (3H, m, 5,6,18-CH), 7.133 (1H, d, 7-CH,
J = 7.0 Hz,), 7.018–6.943 (2H, m, 17,19-CH).
8-Hydroxyquinoline-2-carboxaldehyde-(isonicotinyl)hydrazone (1c) was also obtained
from equimolar amounts of 8-hydroxyquinoline-2-carboxaldehyde and isonicotinylhydr-
azine in the same way as 1a. Yield: 0.622 g, 71.0%. Yellow. M.p. 162−164 °C (d). IR
(KBr) (υmax/cm−1): 3576 (NH), 3193 (OH), 1663 (C=O), 1613 (C=N, azomethine), 1557
(C=N, pyridine), 1271 (C–OH). UV–vis (λmax nm, ε × 104 M−1 cm−1, DMF): 290; 2.86;
3
325, 1.78. NMR (1H DMSO-d6, 200 MHz, ppm: 8.813 (2H, d, 17,19-CH, JHH = 5.2 Hz,),
3
8.657 (1H, s, 11-CH=N), 8.372 (1H, d, 4-CH, JHH = 8.8 Hz), 8.129 (1H, d, 3-CH,
3
3JHH = 8.8 Hz), 7.861 (2H, d, 16,20-CH, JHH = 5.2 Hz), 7.528–7.409 (2H, m, 5,6-CH),
7.148 (1H, d, 7-CH, 3JHH = 6.4 Hz).
2.4. Preparation of the PrIII complexes (2a, 2b, and 2c)
Complex 2a was prepared by refluxing and stirring equimolar amounts of Pr(NO3)3·6H2O
and a 40 mL methanol solution of 1a (0.0582 g, 0.2 mM) on a water bath. After refluxing
for 30 min, triethylamine (0.020 g, 0.2 mM) was added into the reaction mixture dropwise
to deprotonate the phenolic hydroxyl substituent of 8-hydroxyquinolinate. Then, the mixture
was refluxed and stirred continuously for 8 h. After cooling to room temperature, the pre-
cipitate was centrifuged, washed adequately with hot methanol, and dried in vacuum over
48 h to give a powder. Yield: 0.090 g, 70.5%. IR (KBr) (υmax/cm−1): 3439 (OH, H2O),
1591 (C=N, azomethine), 1544 (C=N, pyridine), 1493 (υ1), 1331 (υ4), 1102 (C−OM), 1058
(υ2), 933 (ρτ), 838 (υ3), 737 (υ5), 690 (ρw), 561 (MO), 487 (MN), υ1 − υ4 = 162. UV–vis
(λmax nm, ε × 104 M−1 cm−1, DMF): 321, 4.83; 368, 2.76.
Complex 2b was prepared from equimolar amounts of Pr(NO3)3·6H2O with 1b
(0.0614 g, 0.2 mM) as for 2a. Yield: 0.093 g, 67.3%. IR (KBr) (υmax/cm−1): 3441 (OH,

Praseodymium complexes
3693
Figure 2. The structures of [PrL1a(NO3)(DMF)2]2 (A), [PrL1b(NO3)(DMF)2]2·DMF (B), and [PrL1c(NO3)
(DMF)2]2 (C).
H2O), 3188 (OH, phenolic), 1604 (C=N, azomethine), 1587 (C=N, pyridine), 1489 (υ1),
1333 (υ4), 1275 (C−OH), 1101 (C−OM), 1034 (υ2), 945 (ρτ), 837 (υ3), 732 (υ5), 671 (ρw),
563 (MO), 486 (MN), υ1 − υ4 = 166. UV–vis (λmax nm, ε × 104 M−1 cm−1, DMF): 324,
3.66; 385, 3.29.

3694
Y.-C. Liu et al.
Figure 2. (Continued)
Complex 2c was prepared from equimolar amounts of Pr(NO3)3·6H2O with 1c
(0.0584 g, 0.2 mM) by the same way as 2a. Yield: 0.096 g, 75.1%. IR (KBr) (υmax/cm−1):
3443 (OH, H2O), 1591 (C=N, azomethine), 1571 (C=N, pyridine), 1544 (C=N, pyridine),
1497 (υ1), 1333 (υ4), 1099 (C−OM), 1061 (υ2), 902 (ρτ), 842 (υ3), 734 (υ5), 612 (ρw), 561
(MO), 487 (MN), υ1 − υ4 = 164. UV–vis (λmax nm, ε × 104 M−1 cm−1, DMF): 330, 4.16;
374, 3.29.
2.5. Determination of crystal structures
The orange transparent, X-ray quality crystals of 2a, 2b, and 2c were obtained by vapor dif-
fusion of diethyl ether into DMF solution of the metal complexes at room temperature for
two weeks. The radiation used was graphite-monochromated Mo Kα radiation (0.71073 Å)
and the data were collected on a Bruker APEX area-detector diffractometer by the ω–2θ
scan technique at 298(2) or 296(2) K. The structures were solved by direct methods. All
non-hydrogen atoms were refined anisotropically by full-matrix least-squares on F2. Pri-
mary non-hydrogen atoms were found from direct methods and secondary non-hydrogen
atoms were found from difference maps. The hydrogens were added geometrically and their
positions and thermal vibration factors were constrained. All calculations were performed
using SHELXS-97 and SHELXL-97 [28]. Crystal data and structure refinements for the X-
ray structural analyses are presented in table 1.

Praseodymium complexes
3695
Table 1. Crystal data and structure refinement for the metal complexes.
[PrL1b(NO3)
(DMF)2]2·DMF
Complex
[PrL1a(NO3)(DMF)2]2
[PrL1c(NO3)(DMF)2]2
Chemical formula
Formula weight
T (K)
C46H50N12O14Pr2
1276.80
298(2)
C49H57N13O17Pr2
1381.90
298(2)
C44H48N14O14Pr2
1278.78
296(2)
Wavelength (Å)
Radiation
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α (°)
0.71073
Mo Kα
Monoclinic
P21/c
11.1675(11)
18.6030(17)
12.4937(12)
90.000
0.71073
Mo Kα
Monoclinic
P21/c
25.222(2)
17.7545(9)
13.0656(7)
90.000
0.71073
Mo Kα
Triclinic
P21/c
11.068(9)
18.550(15)
12.364(10)
90.000
β (°)
93.6490(10)
90.00
2590.3(4)
2
1.637
1.934
94.5170(10)
90.00
5832.5(6)
4
1.574
1.729
94.091(14)
90.00
2532(3)
γ (°)
V (Å3)
Z
2
Dc (g cm–3
)
1.677
1.980
1280
0.25 × 0.24 × 0.20
1.84–28.81
−14 ≤ h ≤ 10,
−24 ≤ k ≤ 24,
−15 ≤ l ≤ 16
15,709
μ (mm−1
F (0 0 0)
Crystal size (mm)
min/max (°)
)
1280
2784
0.15 × 0.09 × 0.06
2.61–25.02
−11 ≤ h ≤ 13,
−20 ≤ k ≤ 22,
−13 ≤ l ≤ 14
10,340
0.40 × 0.38 × 0.10
2.69–25.02
−30 ≤ h ≤ 21,
−19 ≤ k ≤ 21,
−15 ≤ l ≤ 15
29,047
θ
Index ranges
Reflections collected
Independent reflections 4549 (Rint = 0.1198)
10,269 (Rint = 0.0689)
Semi-empirical from
equivalents
0.8461 and 0.5447
6387 (Rint = 0.0691)
Semi-empirical from
equivalents
0.6928 and 0.6374
Absorption correction
Semi-empirical from
equivalents
Max. and min.
transmission
0.8928 and 0.7602
Refinement method
Full-matrix least-squares on Full-matrix least-squares on Full-matrix least-squares on
F2
F2
F2
Data/restraints/
parameters
4549/0/338
10,269/0/770
6387/0/339
Goodness-of-fit on F2
Final R indices [I > 2σ
(I)]
1.101
1.038
1.015
R1 = 0.0815, wR2 = 0.1393 R1 = 0.0502, wR2 = 0.0895 R1 = 0.0540, wR2 = 0.1398
R indices (all data)
R1 = 0.1714, wR2 = 0.1702 R1 = 0.1049, wR2 = 0.1161 R1 = 0.0883, wR2 = 0.1768
ρmin/max (e Å−3
)
1.730/−1.728
1.228/−0.725
1.214/−2.026
3. Results and discussion
3.1. The crystal structure of complexes
Comparing IR bands between ligands and powder PrIII complexes, phenolate oxygen, nitro-
gen of quinolinato unit, C=N azomethine group, O=C–NH– group of the aroylhydrazones
side chain, and coordinated waters participate in the PrIII complexes; bidentate nitrates par-
ticipate in PrIII complexes. All these PrIII complexes are orange and stable in air, soluble in
DMF and DMSO, slightly soluble in methanol, ethanol, acetonitrile, ethyl acetate, acetone,
THF, and CHCl3. The melting points of all the powder complexes exceed 300 °C. The
molar conductivities ΛM in DMF solution are 28.4, 46.1, and 42.2 cm2 Ω−1 M−1 for 2a, 2b,
and 2c, respectively, indicating that they are non-electrolytes [29].

3696
Y.-C. Liu et al.
Table 2. Comparison of the structural parameters of 1a, 1b, and 1c binding to PrIII centers.
[PrL1a(NO3)(DMF)2]2
[PrL1b(NO3)(DMF)2]2·DMF
[PrL1c(NO3)(DMF)2]2
M–O1
M–N1
M–N2
M–O2
2.490(9)
2.556(11)
2.588(11)
2.375(9)
2.437(8)
63.0(3)
61.2(4)
60.9(4)
4.0698(16)
2.488(5), 2.467(4)
2.579(6), 2.584(6)
2.627(6), 2.620(6)
2.435(5), 2.425(4)
2.453(5), 2.468(4)
63.79(18), 64.19(17)
60.7(2), 60.77(19)
60.69(19), 60.65(18)
4.0960(9), 4.0843(8)
2.441(4)
2.544(5)
2.577(5)
2.365(5)
2.436(4)
63.80(15)
61.09(18)
60.21(18)
4.051(2)
M’–O1
O1–M–N1
N1–M–N2
N2–M–O2
Distance between M⋯M′
3.1.1. The crystal structure of 2a. Figure 2(A) shows the structure of [PrL1a(NO3)
(DMF)2]2 for 2a. 1a is a dibasic tetradentate ligand, binding to PrIII through phenolate
–
oxygen, nitrogen of quinolinato unit, the C=N group, and O–C=N– enolized and deproto-
nated from O=C–NH– of the benzoylhydrazone side chain. One DMF binds orthogonally
to the ligand plane from one side to the metal ion, while another DMF and a bidentate
nitrate bind from the other side. Dimerization of this monomeric unit occurs through the
phenolate oxygens leading to a central planar four-membered (PrO)2 ring with a Pr⋯Pr sep-
aration of 4.0698(16) Å as shown in table 2. At the dimerization site, a 2 Å offset of the
two parallel “PrL1a-planes” takes place. The center of symmetry according to the crystallo-
graphic coordinates is located in the middle of the four-membered (PrO)2 ring formed by
the two Pr ions and the phenolic oxygens. This nine-coordinate structure of a binuclear
complex with a 1 : 1 metal-to-ligand stoichiometry is similar to that of [YL(NO3)
Figure 3. Effects of increasing amounts of the investigated compounds on the relative viscosity of CT-DNA in
5 mM Tris–HCl buffer solution (pH 7.20) containing 50 mM NaCl at 25.00 0.01 °C. The concentration of CT-
DNA was 50 μM (bps).

Praseodymium complexes
3697
(DMF)2]2Cl2·2(DMF) or [LaL(NO3)(MeOH)2]2(NO3)2, where L-H is 2-[(8-hydroxyquinoli-
nyl)methylene]hydrazineecarboxamide and is tetradentate to yttrium(III) or lanthanum(III)
through the phenolate oxygen, nitrogen of quinolinato unit, the C=N and C=O of the semi-
carbazone side chain [5]. However, there are some marked differences between them.
Importantly, O=C–NH– group of the benzoylhydrazone side chain has enolized and depro-
tonated into –O–C=N– group after the formation of [PrL1a(NO3)(DMF)2]2, where the C–
O− band length is 1.279(14) Å and the N=C double band length is 1.353(17) Å (The nor-
mal band lengths of C=O, C–N, C–O and C=N are 1.19–1.23, 1.47–1.50, 1.30–1.39 and
1.34–1.38 Å, respectively [30]). Carbonyl groups of the semicarbazone side chains have not
enolized in [YL(NO3)(DMF)2]2Cl2·2(DMF) and [LaL(NO3)(MeOH)2]2(NO3)2. The deproto-
nation and enolization may arise from triethylamine added to the reaction mixtures to
deprotonate the phenolic hydroxyl substituent of 8-hydroxyquinolinate during formation of
the PrIII complex. As a result, [PrL1a(NO3)(DMF)2]2 is neutral and non-electrolyte as
proved by the values of molar conductivity in DMF solution, while both [YL(NO3)
(DMF)2]2Cl2·2(DMF) and [LaL(NO3)(MeOH)2]2(NO3)2 are electrolytes.
3.1.2. The crystal structure of 2b. The structure of [PrL1b(NO3)(DMF)2]2·DMF for 2b
with a 1 : 1 metal-to-ligand stoichiometry and nine-coordination is shown in figure
2(B), which indicates that there are two same molecules and a free DMF in the crystal
unit cell. Similarly to 1a, ligand 1b is dibasic tetradentate, binding to PrIII through the
phenolate oxygen, nitrogen of quinolinate and the C=N group (methylene), –O–C=N–
group enolized and deprotonated from O=C–NH– of the 2′-hydroxybenzoylhydrazone
side chain, in which the –O–C and N=C band lengths are 1.262(9) and 1.331(10) Å
for Pr(1) molecule, and 1.275(8) and 1.321(9) Å for Pr(2) molecule, respectively. Also,
one DMF binds orthogonally to the ligand plane from one side to the metal ion, while
another DMF and a bidentate nitrate bind from the other side. Dimerization of the
monomeric unit occurs through phenolate oxygens leading to a central four-membered
(PrO)2 ring with Pr(1)⋯Pr(1) separation of 4.0960(9) Å in one molecule and Pr(2)⋯Pr
(2) separation of 4.0843(8) Å in another. At the dimerization site, a 2 Å offset of the
two parallel “PrL1b-planes” takes place. The center of symmetry is located in the mid-
dle of the four-membered (PrO)2 ring formed by two Pr ions and the phenolic oxy-
gens. The 2′-hydroxyl substituent linked with benzoylhydrazone does not take part in
binding to PrIII, largely due to the long distance (5.990 Å) between the substituent and
PrIII, but it may be involved in an intramolecular hydrogen band with the adjacent
nitrogen, forming a stabilized six-membered ring. A DMF is not coordinated in Pr(2)
complex, indicating that this DMF has two roles when binding to PrIII.
3.1.3. The crystal structure of 2c. Figure 2(C) shows the structure of [PrL1c(NO3)
(DMF)2]2. This nine-coordinate structure with a 1 : 1 metal-to-ligand stoichiometry is simi-
lar to those of 2a and 2b. 1c also is a dibasic tetradentate ligand, binding to PrIII through
–
the phenolate oxygen, nitrogen of quinolinate, the C=N (methylene), and O–C=N– eno-
–
lized and deprotonated from O=C–NH– of the isonicotinylhydrazone side chain with O–C
and N=C band lengths of 1.254(8) and 1.306(10) Å. One DMF binds orthogonally to the
ligand plane from one side to the metal ion, while another DMF and a bidentate nitrate bind
from the other side. Dimerization of this monomeric unit also occurs through the phenolate
oxygens leading to a central four-membered (PrO)2 ring with a Pr⋯Pr separation of 4.051

3698
Y.-C. Liu et al.
(A)
(B)
Figure 4. Plots of [DNA]/(εf − εa) vs. [DNA] for ligands (A) and PrIII complexes (B).
Table 3. Kb, KSV ,and FC50 for ligands and PrIII complexes.
Compound
Kb × 105 M−1
KSV × 104 M−1
FC50 (μM) (Ccompound/CDNA, nucleotides)
1a
1b
1c
2a
2b
2c
0.9032 0.0444
0.9142 0.0495
0.2767 0.0559
1.262 0.139
1.085 0.139
0.9381 0.0591
2.086 0.014
2.352 0.018
1.405 0.013
9.245 0.551
5.684 0.420
3.166 0.366
48.18 (12.05 : 1)
38.95 (9.738 : 1)
66.30 (16.58 : 1)
16.46 (4.115 : 1)
24.90 (6.226 : 1)
31.36 (7.841 : 1)
(2) Å. At the dimerization site, a 2 Å offset of the two parallel “PrL1c-planes” takes place.
The center of symmetry is located in the middle of the four-membered (PrO)2 ring formed
by the two Pr atoms and the phenolic oxygens.
However, the three crystal structures are similar to each other and similar to other lantha-
nide complexes derived from 8-hydroxyquinoline-2-carboxaldehyde and aroylhydrazones as
reported [12–19]. All these complexes are non-electrolytes. Lanthanide ions and structurally
similar Schiff bases can form a series of structurally similar binuclear and 1 : 1 metalto-
ligand complexes by nine-coordination at LnIII with geometry of distorted edge-sharing
mono-capped square-antiprism of [LnL(NO3)(DMF)2]2 (Ln = La3+, Nd3+, Sm3+, Eu3+,

Praseodymium complexes
3699
(A)
(B)
Figure 5. The Stern–Volmer plots for ligands (A) and PrIII complexes (B) in EB-DNA systems. λex = 525 nm,
em = 587 nm, 298 K. The concentration of DNA is 4.0 μM (nucleotides) and the concentration of EB is 0.32 μM.
λ
Tb3+, Dy3+, Ho3+, and Er3+) except for YbIII which has eight-coordination with geometry of
distorted edge-sharing dodecahedron for [YbL(NO3)(DMF)]2. This difference may be due
to the small size of YbIII.
3.2. DNA-binding properties
3.2.1. Viscosity titration measurements. Viscosity titration measurements were carried
out to clarify the interaction modes between the investigated compounds and CT-DNA.
Hydrodynamic measurements that are sensitive to length change of DNA (i.e. viscosity and
sedimentation) are regarded as the least ambiguous and the most critical criteria for binding
modes in solution in absence of crystallographic structural data, as viscosity is proportional
to L3 for rod-like DNA of length L [23, 31]. Intercalation involves the insertion of a planar
molecule between DNA base pairs, resulting in a decrease in the DNA helical twist and
lengthening of the DNA; therefore, intercalators cause the unwinding and lengthening of

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Y.-C. Liu et al.
DNA helix as base pairs become separated to accommodate the binding compound [32].
Agents bound to DNA through groove binding do not alter the relative viscosity of DNA,
and agents bound to DNA through electrostatic binding will bend or kink the DNA helix,
reducing its effective length and its viscosity, concomitantly [33, 34]. With the ratio of the
investigated compound to DNA (bps) increasing, the relative viscosity of DNA increases
steadily as shown in figure 3, indicating that intercalation takes place between the com-
pounds with DNA helix, though there are not significant differences between ligands and
complexes.
3.2.2. UV–vis spectroscopic study. The UV–vis absorption spectra of the investigated
compounds in the absence and in the presence of CT-DNA were obtained in DMF:
Tris−HCl buffer (5 mM, pH 7.20) containing 50 mM NaCl of 1 : 100 solutions, respec-
tively. The UV–vis spectra of ligands have two types of absorption bands of λmax at 295 nm
(ε = 3.55 × 104 M−1 cm−1)
and
323 nm
(ε = 2.11 × 104 M−1 cm−1),
294 nm
(ε = 3.16 × 104 M−1 cm−1) and 329 nm (ε = 2.36 × 104 M−1 cm−1), and 290 nm
(ε = 2.86 × 104 M−1 cm−1) and 325 nm (ε = 1.78 × 104 M−1 cm−1), respectively, for 1a, 1b,
and 1c, while the UV–vis spectra of PrIII complexes have two typical bands of λmax at
321 nm (ε = 4.83 × 104 M−1 cm−1) and 368 nm (ε = 2.76 × 104 M−1 cm−1), 324 nm
(ε = 3.66 × 104 M−1 cm−1) and 385 nm (ε = 3.29 × 104 M−1 cm−1), and 330 nm
(ε = 4.16 × 104 M−1 cm−1) and 374 nm (ε = 3.29 × 104 M−1 cm−1), respectively, for 2a, 2b,
and 2c, which can be assigned to π–π* transition of aromatic rings, π–π* of conjugated
aromatic rings, and the charge transfer from ligand-to-metal ions (L→Pr3+), respectively
[35, 36]. Upon successive addition of CT-DNA (bps), the UV–vis absorption bands of 1a,
1b, and 1c show a progressive hypochromism of 34.3% at 295 nm, 30.1% at 294 nm, and
8.4% at 290 nm by approximately saturated titration end points at CDNA : Cligand
=
1.4–2.2 : 1, respectively, with 1, 3, and 0 nm red shifts of absorption bands. Ligands 1a, 1b,
and 1c show progressive hypochromism of 11.1% at 323 nm, 18.1% at 329 nm, and 1.0%
at 325 nm, respectively, with 1, 3, and 0 nm blue shifts. Similarly, upon successive addi-
tions of CT-DNA (bps), the UV–vis absorption bands of 2a, 2b, and 2c show progressive
hypochromism of 47.1% at 321 nm, 43.5% at 324 nm, and 40.6% at 330 nm by approxi-
mately saturated titration end points at CDNA : Ccomplex = 1.5 : 1, respectively, with 0, 0, and
2 red shifts of absorption bands. Complexes 2a, 2b, and 2c show progressive hypochro-
mism of 50.9% at 368 nm, 45.3% at 385 nm, and 46.2% at 374 nm, respectively, with 2, 3,
and 0 nm blue shifts. The obvious hypochromisms further indicate the strong stacking inter-
action between the aromatic chromophore of the compound and base pairs of DNA rather
than non-covalent intercalative binding of compound to DNA helix [37, 38]. The magnitude
of hypochromism is parallel to the intercalative strength and the affinity of a compound
binding to DNA [31]. Figure 4(A) and (B) shows plots of [DNA]/(εf − εa) versus [DNA]
for ligands and complexes, respectively. The binding constants (Kb = 0.2767–
0.9142 × 105 M−1 for ligands, Kb = 0.9381–1.262 × 105 M−1 for PrIII complexes) of DNA
were determined (listed in table 3). Compared with EB (classical intercalative agent) bind-
ing to DNA (Kb = 0.3068 × 105 M−1) investigated at the same conditions [20], these PrIII
complexes present higher binding abilities to DNA than either ligands or EB. There is no
significant difference in binding to DNA between these PrIII complexes and those derived
from 3-carbaldehyde chromone with isonicotinyl hydrazine, 1-phenyl-3-methyl-4-formyl-2-
pyrazolin-5-one (PMFP) with isonicotinyl hydrazine, and PMFP with 4-aminophenazone, in
which Ln = La3+, Nd3+, Sm3+, Tb3+, Dy3+, and Yb3+ and Kb = 2.44–7.6 × 105 M−1

Praseodymium complexes
3701
[39–41]. However, these PrIII complexes show slightly weaker binding to DNA than those
derived from lanthanide metal ions with 8-hydroxyquinoline-7-carbaldehyde-(isonicotinyl)
hydrazone (Kb = 9.5–16.7 × 105 M−1) and 8-hydroxyquinoline-7-carbaldehyde-(benzoyl)
hydrazone (Kb = 2.938–26.13 × 105 M−1) [20, 21]. Moreover, they show weaker binding to
CT-DNA than Sm(III) complex derived from Congo red (CR) binding to herring sperm
DNA, in which the Kb of Sm(III)(CR)3 complex is 6.25 × 106 M−1 at 18 °C and
1.11 × 107 M−1 at 26 °C [42].
3.2.3. DNA-EB quenching assay. The fluorescence emission intensity of DNA-EB system
decreased dramatically upon increasing amounts of either ligands or PrIII complexes. Stern–
Volmer plots are shown in figure 5 and the data of Stern–Volmer quenching constants are col-
lected in table 1. The values of KSV are 1.405−9.245 × 104 M−1 for ligand and PrIII com-
plexes and the loss of fluorescence intensity at the maximum wavelength indicates that most
of the EB molecules have been displaced from EB-DNA complex by the quencher at the
approximately saturated end point, which indicates further that the intercalative binding takes
place between the investigated compound and DNA. Stern–Volmer quenching constant can
also be interpreted as the association or binding constant of the complexation reaction [43].
Compared with the values of KSV of other lanthanide complexes derived from 8-hydroxy-
quinoline-2(7)-carboxaldehyde with aroylhydrazines, these PrIII complexes present middle
levels of binding to DNA [12–19]. DNA intercalators have been used extensively as antitu-
mor, antineoplastic, antimalarial, antibiotic, and antifungal agents [31]. There is a criterion
for screening antitumor drugs from others by DNA-EB fluorescent tracer method, i.e. a com-
pound may be used as a potential antitumor drug if it causes a 50% loss of DNA-EB
fluorescence intensity by fluorescent titration before the molar concentration ratio of the
compound to DNA (nucleotides) does not overrun 100 : 1 [44]. FC50 value is introduced to
denote the molar concentration of a compound that causes a 50% loss in the fluorescence
intensity of the EB-DNA system. According to the data of FC50 and the molar ratios of
compounds to DNA as shown in table 3, at FC50, all the molar concentration ratios of the
investigated compounds to DNA (4.115−16.58 : 1) are significantly under 100 : 1, indicating
that all these investigated compounds are probably used as potential antitumor drugs and the
antitumor activities of PrIII complexes may be better than that of ligands. However, their
pharmacodynamical, pharmacological and toxicological properties should be further
studied in vivo.
4. Conclusion
PrIII and three synthesized ligands form binuclear PrIII complexes with 1 : 1 metal-to-
ligand stoichiometry and nine-coordinate PrIII indicated by X-ray crystal structural analy-
ses. Ligands are dibasic tetradentates, binding to PrIII through the phenolate oxygen,
nitrogen of quinolinate, the C=N of methylene, and −O–C=N– enolized and deprotonated
from O=C–NH– of the aroylhydrazone side chain. Dimerization of the monomeric unit
occurs through the phenolate oxygens leading to a planar four-membered (PrO)2 ring.
These crystal structures are similar to each other and to other nine-coordinate lanthanide
complexes with geometry of distorted edge-sharing mono-capped square-antiprism of
[LnL(NO3)(DMF)2]2 (Ln = LaIII, NdIII, SmIII, EuIII, TbIII, DyIII, HoIII, ErIII) except for

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Y.-C. Liu et al.
eight-coordinate YbIII with distorted edge-sharing dodecahedron of [YbL(NO3)(DMF)]2,
derived from 8-hydroxyquinoline-2-carboxaldehyde and aroylhydrazines. The ligands and
PrIII complexes can bind to CT-DNA through intercalation with the binding constants of
105 M−1. Compared with other lanthanide complexes derived from 8-hydroxyquinoline-2
(7)-carboxaldehyde with aroylhydrazines, these PrIII complexes present middle levels or
slight weaker binding to DNA, even weaker binding to CT-DNA than Sm(III) complex
derived from CR binding to herring sperm DNA. However, they may be useful as
potential antitumor drugs. Future research efforts will focus on achieving their biological
and other properties.
Supplementary material
CIF files for the X-ray crystal structures have been deposited with the Cambridge Crystallo-
graphic Data Center (CCDC 993157, 993160 and 993159). Copies of this information may
be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge, CB2
1EZ, UK (Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.
cam.ac.uk). Supplementary materials associated with this article can be found in the online
version.
Acknowledgements
The study was supported by Gansu Key Subject of Applied Chemistry (GSACKS20130113)
and Longdong University Doctor Fund.
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