The new ligand 4-(isopropylbenzaldehyde)imidazo4,5-
f
1,10phenanthroline (ippip) and its complexes Ru(phen)
2
(ippip)
2+
(
1)
,Co(phen)
2
(ippip)
3+
(
2
),Ru(bpy)
2
(ippip)
2+
(
3
),Co(bpy)
2
(ippip)
...3+
(
4
)(bpy=2,2-bipyridine) and (phen=1,10-phenanthroline) were synthesized and characterized by ES
+
-MS,
1
H and
13
C NMR. The DNA binding properties of the four complexes were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that complexes bind to calf thymus DNA (CT-DNA) through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than 2, 3, 4 complexes under comparable experimental conditions. Furthermore, photocleavage studies reveal that singlet oxygen (
1
O
2
) plays a significant role in the photocleavage.
Ruthenium(II) complexes, Ru(en)
2
dppz
2+
(1), Ru(en)
2
qdppz
2+
(2), Ru(en)
2
acdppz
2+
(3), and Ru(en)
2
actatp
2+
(4), have been synthesized and characterized by IR,
1
H,
13
C-NMR and LC-MS. The ...interactions of these complexes with calf thymus (CT) DNA have been investigated by absorption, emission, viscosity, thermal denaturation, and circular dichroism. These techniques reveal that the complexes bind strongly to DNA. The apparent binding constants for the complexes decrease from 1 to 4 and are in the order of 8.5 ± 0.2 × 10
5
M
−1
(1), 7.3 ± 0.8 × 10
5
M
−1
(2), 4.3 ± 0.3 × 10
5
M
−1
(3), and 7.5 ± 0.5 × 10
4
M
−1
(4). The plot of log K versus log Na
+
yield slopes of −1.47, −1.44, −1.36, and −1.24 for 1, 2, 3, and 4, respectively. These complexes promote the photocleavage of pBR322 DNA. Cytotoxicities of these complexes suggest their possible anticancer activity.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The ligand 2-(2-fluronyl)1H-imidazo4,5-f1,10-Phenanthroline (fyip) was synthesized and four mixed ligand complexes Ru(phen)
2
fyip
2+
1
, Co(phen)
2
fyip
3+
2
, Ru(bpy)
2
fyip
2+
3
and Co(bpy)
2
fyip
...3+
4
are prepared. These complexes are characterized by IR,
1
H,
13
C NMR and mass. The interaction of these complexes with calf thymus DNA have been studied. DNA binding was monitored by absorption, fluorescence spectroscopy, viscosity and thermal denaturation studies. All complexes bind to DNA through an intercalative mode with comparable strength and their intrinsic binding constants follows the order
1
>
2
>
3
>
4
. These four complexes promote the photocleavage of plasmid pBR322 DNA upon irradiation at 302 nm. Antibacterial activity of these complexes have also been studied.
In the present paper, we synthesized and characterized four N-donor polypyridyl copper(II) complexes (C1-C4); Cu(mono-CN-PIP)22+ (C1), Cu(tri-OMe-PIP)22+ (C2), Cu(di-CF3-PIP)22+ (C3) and Cu(DPPZ)22+ ...(C4). The (Calf-Thymus) CT-DNA binding studies depicted that the complexes could interact with DNA via intercalative mode. All the complexes, particularly C3 and C4 attenuated the proliferation as well as migration of various cancer cells, indicating their anti-cancer and anti-metastatic activity. Additionally, chick embryo angiogenesis (CEA) assay exhibited the inhibition of vascular sprouting in presence of C3 and C4, suggesting their potential in inhibiting the blood vessel growth. Mechanistic studies revealed that the complexes induced the excessive production of cellular reactive oxygen species (ROS) leading to apoptosis through up regulation of p53 and downregulation of Bcl-xL, which might be the plausible mechanisms underlying their anti-cancer properties. To understand the feasibility of practical application of anti-cancer copper complexes C3 and C4, in vivo sub-chronic toxicity study (4 weeks) was performed in C57BL6 mice and the results exhibited almost non-toxic effects induced by these complexes in terms of haematology and serum biochemical analyses, suggesting their biocompatible nature. The current study provides the basis for future advancement of other novel biocompatible metal complexes that could be employed for the therapy of different cancers.
Schematic overview of plausible mechanism underlying the anti-cancer properties of copper (II) polypyridyl complexes. Display omitted
•Synthesis and characterizations of four N-donor polypyridyl copper(II) complexes (C1-C4).•Strong binding of the complexes with CT-DNA through intercalative mode.•Excellent anti-cancer activity of C1-C4 in three different types of cancer cells (B16F10, MDA-MB-231, SKOV3).•The complexes also possess the ability to attenuate the migration of cancer cells as evidenced by scratching assay.•Mechanistic investigation revealing the activation of apoptosis of cancer cells.•Western blot analysis exhibiting upregulation of apoptotic p53 protein and downregulation of anti-apoptotic Bcl-xL protein.•Feasibility for the practical biomedical applications with biocompatible nature observed through sub-chronic toxicity.
A series of four polypyridyl Ru(II) complexes such as Ru(L)
4
(PIP)
2+
and Ru(L)
4
PPIP
2+
where L is 4-amino pyridine and Pyridine (PIP = 2-phenylimidazo4,5-f 1, 10 phenanthroline), ...(PPIP = 2-(4′-phenoxy-phenyl) imidazo4,5-1, 10phenanthroline) have been synthesized and characterized by elemental analysis, physicochemical methods such as UV–vis, IR and NMR spectroscopic techniques. The DNA-binding behavior of these complexes was investigated by electronic absorption titrations, fluorescence spectroscopy, viscosity measurements and salt-dependent studies. The experimental results indicate that all these complexes can bind to DNA through an intercalation mode, the DNA-binding affinities of these complexes follow the order Ru(4-APy)
4
(PPIP)
2+
(
1
) > Ru(Py)
4
PPIP
2+
(
2
) > Ru(4-APy)
4
(PIP)
2+
(
3
) > Ru(Py)
4
PIP
2+
(
4
). Noticeably, these complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA. Further, all four complexes screened for their antimicrobial activity indicate that the complexes show appreciable activity against
Escherichia coli
and
Neurospora Crassa
. In addition, in the presence of Co
2+
, the emission of DNA-Ru(L
4
)PPIP/PIP
2+
can be quenched and recovered by the addition of EDTA, which exhibited the DNA “light switch” properties.
Three symmetric ligands 7-methyl dipyrido-3,2-a;2′,3′-cphenazine (dppz-CH
3
), 7-nitro dipyrido-3,2-a;2′,3′-cphenazine (dppz-NO
2
) and benzoidipyrido-3,2-a;2′,3′-cphenazine (dppn) and their ...ruthenium(II) complexes Ru(en)
2
(L)ClO
4
2
(en= ethylenediamine), L= dppz-CH
3
, dppz-NO
2
and dppn have been synthesized and characterized by IR,
1
H,
13
C NMR and Mass spectra. The interactions of these complexes with calf thymus DNA have been investigated by spectrophotometric, spectrofluorimetric, circular dichroism, viscosity and thermal denaturation studies. As the planar extension of the intercalative ligand increases, the interaction of the complex with DNA increases, indicating that the size and shape of the intercalalative ligand has a marked effect on the strength of interaction. The plot of log K versus log Na
+
yield a slope of -1.26, -1.53, -1.60 for the complexes 1, 2 and 3 respectively. These three complexes have been found to promote the cleavage of plasmid pBR 322 DNA upon irradiation.
A series of cobalt(III) mixed ligand complexes of type Co(en)
2
L
+3
, where L is bipyridine, 1,10-phenanthroline, imidazole, methylimidazole, ethyleimidazole, dimethylimidazole, urea, thiourea, ...acetamide, thioacetamide, semicarbazide, thiosemicarbazide, or pyrazole, have been isolated and characterized. The structural elucidation of these complexes has been explored by using absorption, infrared, and
1
H NMR nuclear magnetic resonance spectral methods. The infrared spectral data of all these complexes exhibit a band at 1450/cm and 1560-1590/cm, which correspond to C = C and C = N, a band at 575/cm for Co-N (en), and a band at 480/cm for Co-L (ligand). All these complexes were found to be potent antimicrobial agents. The antibacterial activity was studied in detail in terms of zone inhibition, minimum bactericidal, and time period of lethal action. Among all, complexes bipyridine, 1,10-phenanthroline, dimethylimidazole, and pyrazole, possess the highest antibacterial activity. Antifungal activity was done by disc-diffusion assay and 50% inhibitory concentrations that possess high antifungal activity.Key words: cobalt(III) complexes, ethylenediamine, antimicrobial, antifungal.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Four asymmetric cobalt(III) complexes, Co(bpy)
2
(aip)
3+
, Co(bpy)
2
(pyip)
3+
, Co(phen)
2
(aip)
3+
, and Co(phen)
2
(pyip)
3+
(bpy = 2,2,bipyridine, phen = 1,10-phenathroline), ...(pyip = 2-(1-pyrenyl)-1H-imidazo4,5-fphen, (aip = 2-(9-anthryl)-1H-imidazo4,5,-fphen, have been synthesized and characterized. Their interaction with calf thymus DNA (CT-DNA) was investigated by physico-chemical methods and photocleavage. The size and shape of the ligands have a marked effect on the DNA-binding affinity of the complexes. Irradiation of pBR322 DNA with these novel cobalt(III) complexes results in nicking of the plasmid DNA. Toxicity and induced cell death investigations revealed that the complexes of pyip had higher toxicity than those of aip.
The kinetics and equilibria for the axial ligation of pyridine and substituted pyridines to bromomethyl(aqua)cobaloxime have been measured spectrophotometrically in aqueous solutions of ionic ...strength l·0 M (KC1) at 25°C as a function of pH. The binding constants and rate of formation increase in the order 4-NH
2
Py > 4-EtPy > 4-MePy > Py > 2-NH
2
Py > 2-EtPy. The data have been interpreted based on the basicity of the ligand,
π
-back bonding from Co(III) → L and hard and soft interactions. The rate of substitution of H
2
O varies with the pKa of the incoming ligand, thus establishing the existence of nucleophilic participation of the ligand in the transition state. We have investigated the DNA binding of bromomethyl(aqua)cobaloxime with DNA. Bromomethyl(ligand)cobaloximes were isolated and characterized by elemental analysis, IR and NMR (
1
H,
13
C) spectra.
PDF