Synthesis, characterization, and biological activities of macrocyclic polyamine complexes

Article abstract of DOI:10.1080/00958972.2014.905685

Two new dinuclear macrocyclic polyamine complexes have been synthesized and characterized by infrared spectra, elemental analysis, ES-MS spectrum, and X-ray single crystal diffraction. The interactions of the complexes with CT-DNA have been measured by sp

Full text of DOI:10.1080/00958972.2014.905685

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Synthesis, characterization, and
biological activities of macrocyclic
polyamine complexes
Q.R. Chenga, D. Youa, H. Hua, H. Zhoua & Z.Q. Pana
a Key Laboratory for Green Chemical Process of Ministry of
Education, Wuhan Institute of Technology, Wuhan, PR China
Accepted author version posted online: 24 Mar 2014.Published
online: 14 Apr 2014.
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To cite this article: Q.R. Cheng, D. You, H. Hu, H. Zhou & Z.Q. Pan (2014) Synthesis,
characterization, and biological activities of macrocyclic polyamine complexes, Journal of
Coordination Chemistry, 67:5, 910-920, DOI: 10.1080/00958972.2014.905685
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Journal of Coordination Chemistry, 2014
Vol. 67, No. 5, 910–920, http://dx.doi.org/10.1080/00958972.2014.905685
Synthesis, characterization, and biological activities of
macrocyclic polyamine complexes
Q.R. CHENG, D. YOU, H. HU, H. ZHOU and Z.Q. PAN*
Key Laboratory for Green Chemical Process of Ministry of Education, Wuhan Institute of
Technology, Wuhan, PR China
(Received 8 October 2013; accepted 26 February 2014)
Two new dinuclear macrocyclic polyamine complexes have been synthesized and characterized by
infrared spectra, elemental analysis, ES-MS spectrum, and X-ray single crystal diffraction. The
interactions of the complexes with CT-DNA have been measured by spectroscopy, viscosity,
electrochemical measurements, and the agarose gel electrophoresis.
Two new dinuclear macrocyclic complexes, [Ni2L1(OAc)]·ClO4 (1) and [Co2L2(OAc)]·1.5
(ClO4)·0.5Na·2(CH3OH) (2) (where H2L1 and H2L2 are the condensation products of N,N-bis(3-
aminopropyl)-4-methoxybenzylamine with 2,6-diformyl-4-brominephenol and 2,6-diformyl-4-meth-
ylphenol in the presence of metal ions, respectively) have been synthesized and characterized by
infrared spectra, elemental analysis, electrospray mass spectra, and X-ray single crystal diffraction.
The interactions of the complexes with CT-DNA have been measured by UV-absorption titrations
and fluorescence quenching experiments.
Keywords: Polyamine; Macrocyclic dinuclear complex; Binding mode; DNA cleavage
1. Introduction
Polyamines have value in the study of biological activities and new materials [1]. Hettich
and Schneider synthesized a series of polyamine cobalt complexes by modifying cyclen and
*Corresponding author. Email: zhiqpan@163.com
© 2014 Taylor & Francis

Macrocyclic polyamine complexes
911
trpn ligands [2]. Simulation enzyme research on Schiff base macrocyclic complexes has
made progress, and Martell found that this kind of complex can simulate activity of tyrosine
[3]. Deoxyribonucleic acid (DNA) is the carrier of biological genetic information and plays
an important role in the process of life. Research has shown that there are two potential tar-
gets in medicine, DNA and tyrosine kinase, in cancer treatment drug design [4]. Therefore,
an important way for chemotherapy drugs research is to design new DNA-insertion agents.
The development of artificial metallonucleases as cellular regulators of DNA is of interest
in therapeutic and biochemical technology [5–7]. The search for artificial metallonucleases
that can cleave DNA hydrolytically is a particular challenge because of the long intrinsic
half-life for hydrolysis of DNA at pH 7 and 25 °C [8, 9]. Kandaswamy and co-workers
have synthesized a series of binuclear copper(II) complexes of macrocyclic polyamine
ligands with two phenol groups, and they found that this kind of complex binds to DNA in
an intercalative mode [10]. In contrast, nickel(II) complexes of macrocyclic polyamines
with two phenol groups have received much less attention. In fact, nickel(II) complexes
with macrocyclic ligands were also found to have potential DNA cleavage reactivity [11].
In numerous nuclease simulations, complexes formed by macrocyclic polyamines in coordi-
nation have good nucleic acid activity [12]. Researchers mainly determine the combination
model of complexes and DNA by methods such as ultraviolet, fluorescence, circular dichro-
ism, viscosity, and electrochemical experiments [13].
Macrocyclic polyamine complexes are widely used in many chemical fields and occupy
important positions in nucleic acid cutting and drug design of DNA targets because of their
flexible structures. This makes study of these complexes important. In order to establish cor-
relations between the binding structure and the reactivity toward DNA cleavage, we designed
two new dinuclear macrocyclic complexes and studied the DNA cleavage activity of the
complexes by spectroscopic analysis. The structures of the complexes are shown in scheme 1.
2. Experimental
2.1. Materials
All chemicals were purchased from commercial sources and used as received. Solvents
were dried according to standard procedures and distilled prior to use.
2,6-Diformyl-4-bromophenol was synthesized according to a procedure reported previ-
ously [14]. 4-Methoxybenzylamine and nickel(II) perchlorate hexahydrate were purchased
from Alfa Aesar. Tris(hydroxylmethyl)-amino-methane (Tris), bromophenol blue, ethidium
bromide (EB), agarose gel, and plasmid pBR322 DNA were purchased from Toyobo Co.
2.2. Synthesis of the complexes
2.2.1. N,N-bis(2-cyanoethyl)-4-methoxybenzylamine (cmba). Cmba was synthesized by
an improved literature method [15]. To a solution of 4-methoxybenzylamine (13.7 g, 0.1 M)
in distilled water (100 mL), acrylonitrile (16.0 g, 0.3 M) was added dropwise at 5 °C, then
the resulting mixture was refluxed for 90 h. After returning to room temperature, the mix-
ture was extracted with dichloromethane, and the organic layer was washed with brine and
dried with anhydrous sodium sulfate. After filtration, the solvent was removed to give the

912
Q.R. Cheng et al.
product as a yellow oil. Yield: 23.5 g (97%). The oil was used for the following reaction
without purification.
2.2.2. N,N-bis(3-aminopropyl)-4-methoxybenzylamine (amba). A mixture of cmba
(23.5 g, 0.097 M) in methanol (200 mL) and active Raney-Ni (10.0 g) was vigorously stir-
red, and a solution of NaBH4 (11 g, 0.291 M) in 8 M/L NaOH (70 mL) was added at such a
rate as to maintain the temperature at 60 °C. After the addition was complete, the reaction
mixture was stirred at room temperature overnight. The Raney-Ni catalyst was then
removed by filtration, and the solvent was removed under reduced pressure. The crude
amba was extracted with dichloromethane and dried with anhydrous sodium sulfate. After
filtration, the solvent was distilled off to obtain the crude product as a colorless oil. Yield:
21.5 g (88%). Amba·3HCl was prepared by acidifying amba with an HCl–EtOH solution,
and white precipitate was obtained. The precipitate was washed with EtOH several times
and dried in vacuo. The pure product was obtained as its trihydrochloride by recrystalliza-
tion from a minimum of water and ethanol [16]. Yield: 26.5 g (86%). Anal. Calcd for
C14H28ON3Cl3: C, 46.6; H, 7.8; N, 11.7. Found: C, 45.8; H, 7.3; N, 12.1. IR (KBr, cm−1):
1
3051, 2913 (C–H), 3359 (N–H), 1247, 1032 (C–O). H NMR (D2O, d/ppm): 7.13 (d, 2H,
2ArH), 6.83 (d, 2H, 2ArH), 3.67 (s, 3H, –O–CH3), 3.38 (s, 2H, Ar–CH2), 2.45 (t, 4H,
2CH2–NH2), 2.28 (t, 4H, 2N–CH2), 1.51 (m, 4H, 2–CH2–).
2.2.3. [Ni2L1(OAc)]·ClO4 (1). Amba·3HCl (0.18 g, 0.5 mM) was dissolved in H2O
(10 mL) and neutralized with NaOH (0.06 g, 1.5 mM), and the solution was added to a
mixture of 2,6-diformyl-4-bromophenol (0.082 g, 0.5 mM) and Ni(OAc)2·4H2O (0.124 g,
0.5 mM) in ethanol (10 mL). The mixture was stirred overnight, and then NaClO4·H2O
(0.07 g, 0.5 mM) in ethanol (10 mL) was added. After stirring for another 6 h, a yellow pre-
cipitate was collected. Green single crystals suitable for X-ray structure analysis were
obtained by evaporation of an acetonitrile solution of the complex. Yield: 0.13 g (50%).
Anal. Calcd for C46H53O10N6Ni2Br2Cl: C, 47.5; H, 4.6; N, 7.2. Found: C, 46.8; H, 5.0; N,
7.7. IR (KBr, cm−1): 3051, 2913 (C–H), 1642(C=N), 1081, 624 (ClO4−1), 1247, 1032
(C–O).
2.2.4. [Co2L2(OAc)]·1.5(ClO4)·0.5Na·2(CH3OH) (2). Amba·3HCl (0.18 g, 0.5 mM) was
dissolved in H2O (10 mL) and neutralized with NaOH (0.06 g, 1.5 mM). The organic phase
was extracted with chloroform (4 × 15 mL), and the combined organic phase was dried over
anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain
grease. The grease was dissolved in absolute methanol (10 mL) and added to a mixture of
2,6-diformyl-4-bromophenol (0.082 g, 0.5 mM) and Pb(OAc)2·4H2O (0.198 g, 0.5 mM) in
methanol (10 mL). The mixture was stirred overnight, and then Co(OAc)2·4H2O in metha-
nol (10 mL) was added. After stirring for 8 h, a brown precipitate was obtained. One more
equivalent of Co(OAc)2·4H2O (0.113 g, 0.5 mM) in methanol (10 mL) was added, and stir-
ring was continued for another 8 h when precipitation was complete. After filtration via vac-
uum and drying, a brown precipitate was collected. Brown single crystals suitable for X-ray
structure analysis were obtained by evaporation of an acetonitrile solution of the complex.
Yield: 0.15 g (52%). Anal. Calcd for C50H67O14N6Co2Cl1.5Na0.5: C, 51.8; H, 5.8; N, 7.2.

Macrocyclic polyamine complexes
913
Found: C, 51.7; H, 5.9; N, 7.3. IR (KBr, cm−1): 3051, 2913 (C–H), 1642(C=N), 1081, 624
(ClO4−1), 1247, 1032 (C–O).
2.3. Physical measurements
1
IR spectra were measured using KBr disks on a Vector 22 FTIR spectrophotometer. H
NMR spectra were recorded on a Varian Mercury VX-300 spectrometer at 30 °C in D2O
with TMS as the internal reference. Elemental analyses were obtained on a Perkin-Elmer
240 analyzer. Electrospray mass spectra (ES-MS) were determined on a Finnigan LCQ ES-
MS mass spectrograph using methanol as the mobile phase with an approximate concentra-
tion of 1.0 mM dm−3. Absorption spectra of 190–700 nm were recorded on a Shimadzu
UV-2450 spectrophotometer. Fluorescence spectra were recorded on a Jasco FP-6500 spec-
trophotometer.
2.4. Structure determination
Diffraction intensity data were collected on a SMART CCD area-detector diffractometer at
291 K using graphite monochromated Mo Kα radiation (λ = 0.71073 Å). Data reduction and
cell refinement were performed with SMART and SAINT [17]. The structure was solved by
direct methods (Bruker SHELXTL) and refined on F2 by full-matrix least squares (Bruker
SHELXTL) using all unique data [18]. All non-hydrogen atoms were refined anisotropically
and hydrogens were refined on calculated positions using a riding mode. The crystal data
are listed in table 1. Selected bond lengths and angles are provided in table 2.
Table 1. Crystal data and details of the structure for 1 and 2.
Empirical formula
Formula weight
Crystal system
Space group
a, b, c [Å]
C46H53ClN6Br2Ni2O10
1162.63
Monoclinic
C50H67Cl1.5N6Co2O14Na0.5
1158.63
Monoclinic
P21/n
P21/c
16.505(2), 17.220(3), 18.368(3)
90, 97.088, 90
5180.6(13)
18.003(1), 20.113(1), 15.585(1)
90.00, 110.925, 90.00
5271.3(8)
α, β, γ [°]
Volume
Z
4
4
DCalcd
1.491
1.460
μ (Mo Kα) [/nm]
F (0 0 0)
2.380
2376
0.20 × 0.10 × 0.10
298(2)
0.780
2424
0.16 × 0.12 × 0.10
173(2)
Crystal size (mm3)
Temp. (K)
Mo Kα radiation (Å)
θ Range (°)
Index ranges
0.71073
1.96–25.5
−19 ≤ h ≤ 17, −20 ≤ k ≤ 18,
−22 ≤ l ≤ 22
9613, 607
0.71073
2.03–25.10
−21 ≤ h ≤ 21, −24 ≤ k ≤ 24,
−18 ≤ l ≤ 16
9363, 704
Nref, Npar
Tot., uniq. data R(int)
Observed data [I > 2.0σ(I)]
R, wR2, S
31,057, 9613, 0.0584
5754
0.0692, 0.1998, 1.103
−0.669, 0.945
31,174, 9363, 0.0720
6778
0.0737, 0.1932, 1.106
−0.924, 0.880
Min. and Max. Resd. Dens. [e Å−3
]

914
Q.R. Cheng et al.
Table 2. Selected bond distances (Å) and angles (°) for 1 and 2.
1
2
Bonds
Length (Å) Bonds
Length (Å) Bonds
Length (Å) Bonds
Length (Å)
N4–Ni1
N6–Ni1
N5–Ni1
Ni1–O1
Ni1–O6
Ni1–O2
2.066(5)
2.098(5)
2.214(5)
2.050(4)
2.054(5)
2.089(4)
N1–Ni2
N3–Ni2
N2–Ni2
Ni2–O5
Ni2–O2
Ni2–O1
2.074(5)
2.085(5)
2.193(5)
2.039(5)
2.054(4)
2.076(4)
Co1–O5
Co1–O2
Co1–O4
Co1–N6
Co1–N2
Co1–N1
2.062(3)
2.064(3)
2.102(4)
2.098(4)
2.101(4)
2.232(5)
Co2–O6
Co2–O4
Co2–O2
Co2–N3
Co2–N5
Co2–N4
2.077(3)
2.081(3)
2.111(3)
2.100(3)
2.123(4)
2.242(4)
Bond angles Values (°)
Bond angles Values (°)
Bond angles Values (°)
Bond angles Values (°)
O1–Ni1–O6 85.90(17)
O1–Ni1–O2 77.79(17)
O6–Ni1–O2 92.55(17)
O1–Ni1–N4 159.4(2)
O6–Ni1–N4 87.3(2)
O1–Ni1–N6 84.52(18)
N6–Ni1–N5 81.8(2)
O5–Ni2–O2 85.66(17)
O5–Ni2–O1 90.92(17)
O2–Ni2–O1 78.01(16)
O5–Ni2–N1 86.1(2)
O2–Ni2–N1 159.4(2)
N1–Ni2–N2 91.2(2)
N3–Ni2–N2 83.3(2)
O5–Co1–O4 91.41(14)
O2–Co1–O4 77.78(13)
O5–Co1–N6 87.32(16)
O2–Co1–N6 159.55(16) O6–Co2–N3 89.05(15)
O5–Co1–N2 163.95(17) O4–Co2–N3 158.95(15)
O2–Co1–N2 85.39(15)
O5–Co1–N1 86.93(16)
N6–Co1–N1 89.47(17)
N2–Co1–N1 81.77(17)
O6–Co2–O4 86.75(13)
O6–Co2–O2 92.98(14)
O4–Co2–O2 77.23(13)
O6–Ni1–N6 164.87(19) O5–Ni2–N3 166.8(2)
O2–Ni1–N6 96.83(19) O2–Ni2–N3 85.83(18)
O1–Ni1–N5 109.70(18) O1–Ni2–N3 97.18(19)
O6–Ni1–N5 90.43(19) O5–Ni2–N2 89.6(2)
O2–Ni1–N5 172.14(17) O2–Ni2–N2 107.54(18) O4–Co1–N1 171.85(14) O6–Co2–N4 86.43(15)
O6–Co2–N5 161.78(15)
O4–Co2–N5 84.83(15)
O2–Co1–N1 110.11(15) O2–Co2–N5 100.86(15)
N4–Ni1–O2 83.1(2)
N4–Ni1–N6 105.6(2)
N4–Ni1–N5 89.8(2)
O1–Ni2–N2 174.45(18) N6–Co1–O4 82.48(16)
O4–Co2–N4 111.49(15)
N1–Ni2–O1 83.30(19)
N1–Ni2–N3 105.2(2)
N2–Co1–O4 101.32(16) O2–Co2–N4 171.19(14)
N6–Co1–N2 103.86(17) N3–Co2–O2 82.40(14)
2.5. DNA-binding experiments
CT-DNA (20 mg) was dissolved in Tris–HCl buffer (100 mL, 50 mM Tris–HCl, 50 mM
NaCl, pH 7.2) and kept at 4 °C for less than four days. The absorption ratio A260/A280 was
within the range of 1.8–2.0. The DNA concentration was determined via absorption spec-
troscopy using the molar absorption coefficient of 6600 M−1 cm−1 (260 nm) for CT-DNA
[19].
The complex was dissolved in DMF at 5.09 × 10−5 M. UV absorption titrations were per-
formed by keeping the concentration of the complex fixed while varying the DNA concen-
tration. Complex-DNA solutions were allowed to incubate for 30 min at room temperature
before measurements were made. Absorption spectra were recorded using cuvettes of 1 cm
path length at room temperature. The intrinsic binding constant Kb was calculated according
to equation (1) [20]:
½DNAꢀ=Eap ¼ ½DNAꢀ=E þ 1=ðKbEÞ
Eap ¼ ea ꢁ ef ; E ¼ eb ꢁ ef
(1)
in which εa, εf, and εb are the molar extinction coefficients of solutions containing both
complex and DNA, free complex, and the complex bound to DNA, respectively.
Fluorescence quenching experiments were performed by adding a solution of the complex
(1.5 μL) to EB-bound CT-DNA solution (1.5 μL) at different concentrations (12.5–200 μM).
All experiments were carried out using cuvettes of 1-cm path length at room temperature.
Samples were excited at 520 nm and emission was recorded at 450–750 nm.

Macrocyclic polyamine complexes
915
3. Results and discussion
3.1. Synthesis and characterization
In the IR spectrum of 1, the sharp C=N stretching vibration bands corresponding to imine
groups of the macrocyclic framework are observed at 1642 cm−1, indicating that a macrocy-
clic complex has been synthesized. In addition, strong bands at 1081 and 624 cm−1 can be
ascribed to ClOꢁ4 .
The ES-MS spectrum of 1 in methanol solution (Supplementary data S1, see online sup-
plemental material at http://dx.doi.org/10.1080/00958972.2014.905685) is dominated by a
peak at m/z 1063.42, corresponding to [Ni2(OAc)L1]+ (C46H53O6N6Ni2Br2, Calcd 1063.12).
Theoretical and experimental isotope distribution of the main peaks of 1 is shown in the
inset, revealing good agreement between observed and calculated data. The other peaks in
the ES-MS of the nickel(II) complex are not discussed, due to their low abundance (<5%).
The ES-MS spectrum shows that [Ni2(OAc)L1]+ is stable in methanol solution.
In addition, 2 was synthesized using Pb(OAc)2 as template and metal ion exchange. The
similarity of the relative vibration bands of IR in 2 is in agreement with the comparability
of its crystal structure.
The ES-MS spectrum of 2 in methanol solution (Supplementary data S2) is dominated
by a peak at m/z 933.67, corresponding to [Co2(OAc)L2]+ (C48H59O6N6Co2, Calcd 933.87).
Theoretical and experimental isotope distribution of the main peaks of 2 is shown in the
inset, revealing good agreement between observed and calculated data. The other peaks in
the ES-MS of the Co(II) complex are not discussed, due to their low abundance (<5%). The
ES-MS spectrum shows that [Co2(OAc)L2]+ is stable in methanol.
3.2. Crystal structures
3.2.1. [Ni2L1(OAc)]ClO4 (1). A perspective view of [Ni2L1(OAc)]ClO4 is given in figure 1.
The nickel complex is composed of a [Ni2(OAc)L1]+ cation and a perchlorate. The two Ni
ions reside in the N3O2 sites of the macrocycle [L1]2−. Deviation of Ni(1) and Ni(2) from the
mean plane, formed by O1, O2, N5, and N6 and by O1, O2, N2, and N3, are 0.1711(8) and
Figure 1. Crystal structure of 1; hydrogens have been omitted for clarity (ellipsoids are drawn at 30% probability).

916
Q.R. Cheng et al.
0.1710(8) Å, respectively. The dihedral angle between the planes is 27.9°. The angle between
the two benzene rings in each complex is 59.58°. The basal bond distances around Ni(1) are
2.050–2.214 Å. The apical bond distances are Ni(1)–N(6) = 2.098(5) Å and Ni(1)–O(6) =
2.054(5) Å, with the bond angle O(6)–Ni(1)–N(6) = 164.87(19)°. The bond distances around
Ni(2) are 2.054–2.193 Å. The apical bond distances are Ni(2)–N(3) = 2.085(5) Å, Ni(2)–O(5)
= 2.039(5) Å, with the bond angle O(5)–Ni(2)–N(3) = 166.8(2)°. The nickel–nickel separation
bridged by the two phenolic oxygens is 3.148 Å with Ni–O–Ni angles of 99.43° and 98.93°.
3.2.2. [Co2L2(OAc)]·1.5(ClO4)·0.5Na·2(CH3OH)
(2). A
perspective
view
of
[Co2L2(OAc)]·1.5(ClO4)·0.5Na·2(CH3OH) (2) is given in figure 2. The Co(II) complex is
composed of a [Co2(OAc)L2]+, a perchlorate, and two methanols. There is a position occu-
pied by a perchlorate or Na+, the probability of 50% each one. The two Co ions reside in
the N3O2 sites of the macrocycle [L2]2−. Deviation of Co(1) and Co(2) from the mean plane,
formed by O2, O4, N1, and N6, and O2, O4, N3, and N4, are 0.1891(7) Å and 0.1946 Å,
respectively. The dihedral angle between the planes is 30.39°. The angle between the two
benzene rings in each complex is 64.38°. The basal bond distances around Co(1) are 2.062–
2.232 Å. The apical bond distances are Co(1)–N(2) = 2.101(4) Å, Co(1)–O(5) = 2.062(3) Å,
with the bond angle O(5)–Co(1)–N(2) = 163.95(17)°. The bond distances around Co(2) are
2.077–2.242 Å. The apical bond distances are Co(2)–N(5) = 2.123 Å, Co(2)–O(6) = 2.077 Å,
with the bond angle N(5)–Co(2)–O(6) = 161.78°. The cobalt–cobalt separation bridged by
the two phenolic oxygens is 3.175 Å with Co–O–Co angles of 98.73° and 99.00°.
3.3. Spectroscopic analysis of DNA-binding activity
Electronic absorption spectroscopy is one of the most useful methods for DNA-binding
studies of metal complexes. Intercalative binding of a complex to DNA generally results in
hypochromism along with a redshift of the band [21].
Figure 2. Crystal structure of 2; hydrogens have been omitted for clarity (ellipsoids are drawn at 30% probability).

Macrocyclic polyamine complexes
917
The absorption spectra of the nickel(II) complex in the absence and presence of CT-DNA
at different concentrations (0–150 μM) are given in figure 3.
The spectrum of the Ni(II) complex shows a very strong absorption at 393 nm, which is
attributed to a metal-to-ligand charge transfer (MLCT) [22, 23]. The band shows a batho-
chromic shift of 19 nm and hypochromism of 15.8% after adding DNA. The value of Kb
was obtained from the ratio of slope to the intercept from the plot of [DNA]/(εa − εf) versus
[DNA] as 2.04 × 104 M−1.
Absorption spectra of the Co(II) complex in the absence and presence of CT-DNA at dif-
ferent concentrations (0–150 μM) are given in figure 4.
The spectrum of the Co(II) complex shows a very strong absorption at 391 nm, which is
attributed to a MLCT. Different from 1, hyperchromic effect occurred in 2 absorption spec-
tra. Hyperchromic effect means that the secondary structure of DNA was destroyed by the
complexes. The band shows the max bathochromic shift of 34 nm and hyperchromism of
36.6% after adding DNA. The insert mode between complexes and DNA results in a hypo-
chromic effect. Therefore, the binding mode between 2 and DNA is not the insert mode.
The Kb value is 1.22 × 105 M−1. We deduce that the Co(II) complex binds to DNA with a
moderate groove mode.
Compared to other complexes, Kb of 1 is lower than those of the nickel(II) complexes
Ni(HAdr)2 (4.3 × 104), [Ni(L)(SCN)2] (1.07 × 105), and [Ni2L1(ClO4)]+ (2.8 × 105) [24–26]
and slightly higher than that of the nickle(II) complex [Ni(QTS)2]+ (3.27 × 103) [27]. Kb of
2 is higher than those of the cobalt(II) complexes [Co(bmbb)2](pic)2 (7.95 × 104) and [Co
(DCA)(bipy)(H2O)] (4.02 × 104) [28, 29].
Mixed solutions of DNA and EB show very strongly enhanced fluorescence emission
[30] due to intercalation of EB to DNA. The binding of the complex to DNA can be deter-
mined according to the classical Stern–Volmer equation (2):
I0=I ¼ 1 þ K½Qꢀ
(2)
Figure 3. UV–visible spectra of 1 in the presence of increasing amounts of CT-DNA in 50 mM Tris–HCl buffer
solution (pH 7.2). [M1] = 50 μM; 2–6: [M1] + [DNA]. [DNA] = 16, 33, 45, 70, 145 μM.

918
Q.R. Cheng et al.
Figure 4. UV–visible spectra of 2 in the presence of increasing amounts of CT-DNA in 50 mM Tris–HCl buffer
solution (pH 7.2). [M2] = 50 μM; 2–6: [M2] + [DNA]. [DNA] = 16, 21.5, 33, 45, 70 μM.
Scheme 1. Chemical structure of the complexes.
in which I0 and I are the fluorescence intensities of EB-DNA in the absence and presence
of complex, respectively, K is the linear Stern–Volmer quenching constant, and [Q] is the
concentration of the complex [31]. The fluorescence intensity at 605 nm (λex = 520 nm) of
EB in the bound form was plotted against the compound concentration.
Emission spectra of EB bound to DNA in the absence and presence of 1 are given in
Supplementary data S3. When the Ni(II) complex was added to the EB-DNA system, the
emission intensity was reduced. The constant is 2.3 × 103 M−1, which is smaller than those
of DNA-intercalative complexes, so we deduce that the Ni(II) complex binds to DNA with
a moderate intercalative mode.

Macrocyclic polyamine complexes
919
Similar to 1, when the Co(II) complex was added to the EB-DNA system, the emission
intensity was reduced. The emission spectra of EB bound to DNA in the absence and pres-
ence of 2 are given in Supplementary data S4. The constant is 2.12 × 103 M−1. From the
ultraviolet spectrum variation of 2, we deduce that 2 binds to DNA with a moderate groove
mode.
Compared to other complexes, Kq of 1 is lower than those of the nickel(II) complexes
Ni(HAdr)2 (3.4 × 104), [Ni(L)(SCN)2] (6.9 × 104), [Ni2L1(ClO4)]+ (1 × 107), and [Ni
(L)2]4·EtOH (3.2 × 105) [24–26, 32], and Kq of 2 is also lower than those of the cobalt(II)
complexes [Co(bmbb)2](pic)2 (3.76 × 104) and [Co(DCA)(bipy)(H2O)] (1.08 × 1015) [28,
29].
4. Conclusion
Two new macrocyclic complexes have been synthesized and structurally characterized. The
biological activities of the complexes toward calf thymus DNA were studied by UV absorp-
tion and fluorescence spectroscopy. The binding constants of 1 and 2 are 2.04 × 104 M−1
and 1.22 × 105 M−1, respectively. The linear Stern–Volmer quenching constants calculated
from fluorescence experiments for 1 and 2 are 2.3 × 103 M−1 and 2.12 × 103 M−1, respec-
tively. The results indicate that 1 binds to DNA by a moderate intercalation mode and 2
binds to DNA by a moderate groove mode.
Supplementary material
Crystallographic data for the structures reported in this article have been deposited at the Cam-
bridge Crystallographic Data Center, CCDC Nos. 963138 and CCDC 963139. Copies of the data
can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [Fax: +44 1223 336-033; E-mail: deposit@ccdc.cam.ac.uk].
Funding
We are thankful for the financial support from the National Nature Science Foundation of China
[grant numbers 21301131, 51374158]; the Nature Science Foundation of Hubei Province [grant
number 2013CFB313]; the open fund of Engineering Research Center of Nano-Geo Materials of
Ministry of Education China University of Geosciences, Wuhan [grant number CU-
GNGM201311]; and the scientific research fund of Wuhan Institute of Technology [grant num-
ber 10122013].
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