A novel rhodium(iii) complex Rh
(H
L
)Cl
(1) (H
L
= 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine) containing a pincer type, tridentate nitrogen-donor chelate system was synthesized. Single crystal ...X-ray structure analysis revealed that 1 crystallizes in the orthorhombic space group Pbcn with a = 20.7982(6), b = 10.8952(4), c = 10.9832(4) Å, V = 2488.80(15) Å
, and eight molecules in the unit cell. The rhodium center in the complex Rh
(H
L
)Cl
(1) is coordinated in a slightly distorted octahedral geometry by the tridentate N,N,N-donor and three chloro ligands, adopting a mer arrangement with an essentially planar ligand skeleton. Due to the tridentate coordination of the N,N,N-donor, the central nitrogen atom N1 is located closer to the Rh
center. The reactivity of the synthesized complex toward small biomolecules (l-methionine (l-Met), guanosine-5'-monophosphate (5'-GMP), l-histidine (l-His) and glutathione (GSH)) and to a series of duplex DNAs and RNA was investigated. The order of reactivity of the studied small biomolecules is: 5'-GMP > GSH > l-Met > l-His. Duplex RNA reacts faster with the Rh
(H
L
)Cl
complex than duplex DNA, while shorter duplex DNA (15mer GG) reacts faster compared with 22mer GG duplex DNA. In addition, a higher reactivity is achieved with a DNA duplex with a centrally located GG-sequence than with a 22GTG duplex DNA, in which the GG-sequence is separated by a T base. Furthermore, the interaction of this metal complex 1 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was examined by absorption (UV-Vis) and emission spectral studies (EthBr displacement studies). Overall, the studied complex exhibited good DNA and BSA interaction ability.
Two neutral enantiopure arene-ruthenium(II) complexes, (arene)Ru
II
(κ
2
(1S,3R)-Ar)Cl
2
(1, 2), arene = p-cymene, Ar = o-tolyl or mesityl, derived from the reaction of arene-ruthenium(II) dimers ...and 1,3-diamino camphor based derivatives, were synthesized. The N1-mesityl-2,2,3-trimethylcyclopentane-1,3-diamine ligand and complex 2 are characterized via X-ray crystallography. Single crystal X-ray structure analysis revealed that 2 crystallizes in monoclinic space group P21 with Z = 4, a = 7.7724(14), b = 14.262(3), c = 14.433(3) Å. Reactivity measurements using UV-Vis of the Ru
II
-arene complexes with guanosine-5′-monophosphate (5′-GMP), 9-methylguanine (9MeG), and L-methionine (L-Met) showed a high affinity towards these nucleophiles. Also, DFT calculations with 2 showed that the reaction with a guanine derivative is thermodynamically favored. Furthermore, the Ru
II
-arene complexes were found to interact with CT-DNA and HT-DNA, and protein BSA. The cytotoxicities of 1 and 2 have been evaluated against human breast cancer cell line (MDA-MB), human cancer colon cell line (HCT-116), human lung carcinoma epithelial cell line (A549), mouse melanoma cell line (B16F10), and mesenchymal stem cells (MSCs) and compared to cisplatin as standard analog. The complexes display relevant activities against all cancer cell lines.
The antimicrobial and antioxidant activities, as well as the DNA-binding of four square-planar Pd(II) complexes, Pd(terpy)Cl+ (C1), Pd(en)Cl2 (C2), Pd(DMEAImiPr)Cl2 (C3) and Pd(dach)Cl2 (C4) (terpy = ...2,2?:6?,2??- -terpyridine, en = ethylenediamine, dach = trans-1,2-diaminocyclohexane and DMEAImiPr = N2-((1,3-dihydro-1,3-diisopropyl-4,5-dimethyl)-2H-imidazol-2- ylidene)-N1,N1-dimethyl-1,2-ethanediamine are reported. The antimicrobial activities of the Pd(II) complexes with the appropriate ligands were tested using the microdilution method against 18 strains of microorganisms, whereby the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC) were determined. The antibiofilm activity of Pd(terpy)Cl+ and the corresponding ligand were determined on a formed biofilm. The intensity of antimicrobial activity varied depending on the type of microorganism and the tested compound. The C1 complex with the corresponding ligand demonstrated significantly greater overall antimicrobial activity than C2, C3 and C4. The antibacterial activity of the C1 complex was better than its antifungal activity that was overall greater than that of the positive control, fluconazole. The greatest sensitivity for C1 and L1 was with Penicillium italicum (MIC < 0.49 ?g mL-1) among the fungi, and with Proteus mirabilis ATCC 12453 (MIC = 0.98 ?g mL-1) among the tested bacteria. The tested compounds show low and moderate antibiofilm activity. The complexes showed weak antioxidant properties when tested using the DPPH (1,1-diphenyl-2- -picrylhydrazyl) method. The interaction of the metal complexes C1?C4 with calf thymus DNA (CT-DNA) was further examined by absorption (UV?Vis) and emission spectral studies (EthBr displacement studies). Overall, the investigated complexes exhibited good DNA interaction ability.
The biological activities of two binuclear copper(II) complexes containing S-alkenyl derivatives of thiosalicylic acid are reported alkenyl = propenyl (
L1
), isobutenyl (
L2
). The structure of the ...complex with the S-isobutenyl derivative (
C2
) was confirmed by single-crystal X-ray structure analysis, which revealed that the structure consists of centrosymmetric, dinuclear complex molecules Cu
2
(
S
-
i
-butenyl-thiosal)
4
(DMSO)
2
containing two Cu(II) centers bridged by four S-isobutyl-thiosalicylate ligands in a paddle-wheel type structure. The Cu(II) atom is situated in a distorted square-pyramidal environment formed by carboxylate oxygen atoms in the basal plane and a DMSO ligand in the axial position. The reactivities of the complexes toward guanosine-5′-monophosphate (5′-GMP) were investigated. Complex
C2
(Cu
2
(
S
-
i
-butenyl-thiosal)
4
(H
2
O)
2
) reacted more rapidly with 5′-GMP than complex
C1
. The interactions of complexes
C1
and
C2
with calf thymus DNA (CT-DNA) were examined by absorption (UV–Vis) and emission spectral studies (ethidium bromide displacement studies), revealing good DNA interaction abilities. The antimicrobial activities of the free ligands and their complexes were tested by microdilution method, and both minimal inhibitory and microbicidal concentrations were determined. All the tested substances demonstrated selective and moderate antibacterial activity on gram-positive bacteria, but low antibacterial activity on gram-negative bacteria. Also, the tested substances demonstrated low antifungal activity.
Interactions of copper(II) complexes which contain S-alkyl derivatives of thiosalicylic acid (alkyl = methyl, ethyl, propyl and butyl; aryl = benzyl), marked as 1-5, with guanosine-5′-monophosphate ...(5′-GMP) and calf thymus DNA (CT-DNA) were studied. Kinetics of substitution reactions of 1-5 with 5′-GMP and CT-DNA were investigated under pseudo-first-order conditions at 310 K and pH = 7.2 in 25 mM Hepes buffer using stopped-flow method. All complexes have high affinity toward studied bio-molecules. Additionally, interactions with CT-DNA were followed by absorption spectroscopy and fluorescence quenching measurements. The results indicate that complexes bind to DNA exhibiting high binding constants (K
b
= 10
4
M
−1
). During the examination of competitive reactions with ethidium bromide (EB), results showed that complexes can replace EB-bound DNA. In addition, a new crystal structure of the binuclear Cu(II) complex with S-substituted thiosalicylate derivative has been reported. In the present series of Cu(II) complexes the crystal structure is the first example of a complex comprising an S-aryl derivative of thiosalicylate ligand. Through comparative study of structural properties of six molecules from four crystal structures we examined the structural variations, potentially important for biological activity of these complexes.
Two copper(II) complexes with ligands derived from β-amino acids, 2-(1-aminocyclohexyl)acetic acid
L1
and 2-(1-amino-4-(
tert
-butyl)cyclohexyl)acetic acid
L2
, were synthesized and characterized by ...microanalysis, infrared, UV–Vis and EPR spectra. The spectroscopically predicted structure of the square-planar copper(II) complex with 2-(1-aminocyclohexyl)-acetic acid
C1
was confirmed by single-crystal X-ray analysis. The biological activities (antitumor activities and interaction with DNA) of the compounds were also investigated. The interactions of both complexes with calf thymus (CT) and herring testes (HT) DNA were examined by stopped-flow spectroscopy, by absorption (UV–Vis) and by emission spectral studies (ethidium bromide displacement studies). Both complexes were found to react a bit faster with HT-DNA than with CT-DNA. The obtained binding constants suggested a moderate intercalative binding mode between the complexes and DNA. In addition, fluorescence spectrometry of bovine serum albumin with the complexes showed a good fluorescence quenching of the complexes. The obtained copper(II) complexes have a relatively low cytotoxic effect on murine mammary carcinoma cell line, 4T1, a moderate effect on murine colon carcinoma cell line, CT26, and a relatively high cytotoxicity toward murine lung cancer cells, LLC1.
A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4',4″-tri-
-butyl-2,2':6',2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding ...properties of ZnCl
(terpy
) (
), {
-PtCl(NH
)
(
-pyrazine)ZnCl(terpy
)}(ClO
)
(
), {
-PtCl(NH
)
(
-pyrazine)ZnCl(terpy
)}(ClO
)
(
), {
-PtCl(NH
)
(
-4,4'-bipyridyl)ZnCl(terpy
)}(CIO
)
(
) and {
-PtCl(NH
)
(
-4,4'-bipyridyl)ZnCl(terpy
)}(CIO
)
(
) (where terpy
= 4,4',4″-tri-
-butyl-2,2':6',2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower
and
constant values compared to cisplatin analogs. The lowest
value belonged to complex
while
exhibited the highest. Molecular docking studies reveal that the binding of complex
to DNA is due to van der Waals forces, while that of
-
is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear
complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The
complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.
The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of ...previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5'-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.