12 research outputs found
Novel Organoruthenium(II) Ī²āDiketonates as Catalysts for Ortho Arylation via CāH Activation
Five different fluorinated Ī²-diketone ligands in
the presence
of sodium methoxide easily react with the organoruthenium precursor
[(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuĀ(Ī¼-Cl)ĀCl]<sub>2</sub>, generating neutral complexes <b>1</b>ā<b>5</b> with typical āpiano-stoolā geometry. All synthesized
compounds were characterized by multinuclear NMR, X-ray diffraction,
and other standard physicochemical methods. These isolated organorutheniumĀ(II)
complexes are air-, moisture-, and UV-stable compounds and were tested
for catalytic activity. It was found that these compounds are ready
to use catalysts, which are efficient for direct arylation of 2-phenylpyridine.
With the use of 4-bromoacetophenone as arylating reagent, these complexes
show enhanced selectivity for monoarylated products. All reagents
are commercially available and relatively inexpensive, which makes
these catalysts generally available
Novel Organoruthenium(II) Ī²āDiketonates as Catalysts for Ortho Arylation via CāH Activation
Five different fluorinated Ī²-diketone ligands in
the presence
of sodium methoxide easily react with the organoruthenium precursor
[(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuĀ(Ī¼-Cl)ĀCl]<sub>2</sub>, generating neutral complexes <b>1</b>ā<b>5</b> with typical āpiano-stoolā geometry. All synthesized
compounds were characterized by multinuclear NMR, X-ray diffraction,
and other standard physicochemical methods. These isolated organorutheniumĀ(II)
complexes are air-, moisture-, and UV-stable compounds and were tested
for catalytic activity. It was found that these compounds are ready
to use catalysts, which are efficient for direct arylation of 2-phenylpyridine.
With the use of 4-bromoacetophenone as arylating reagent, these complexes
show enhanced selectivity for monoarylated products. All reagents
are commercially available and relatively inexpensive, which makes
these catalysts generally available
Novel Organoruthenium(II) Ī²āDiketonates as Catalysts for Ortho Arylation via CāH Activation
Five different fluorinated Ī²-diketone ligands in
the presence
of sodium methoxide easily react with the organoruthenium precursor
[(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuĀ(Ī¼-Cl)ĀCl]<sub>2</sub>, generating neutral complexes <b>1</b>ā<b>5</b> with typical āpiano-stoolā geometry. All synthesized
compounds were characterized by multinuclear NMR, X-ray diffraction,
and other standard physicochemical methods. These isolated organorutheniumĀ(II)
complexes are air-, moisture-, and UV-stable compounds and were tested
for catalytic activity. It was found that these compounds are ready
to use catalysts, which are efficient for direct arylation of 2-phenylpyridine.
With the use of 4-bromoacetophenone as arylating reagent, these complexes
show enhanced selectivity for monoarylated products. All reagents
are commercially available and relatively inexpensive, which makes
these catalysts generally available
Synthesis and Biological Evaluation of Organoruthenium Complexes with Azole Antifungal Agents. First Crystal Structure of a Tioconazole Metal Complex
Nine
organoruthenium complexes with azole antifungal agents (L)
clotrimazole (<b>ctz</b>), tioconazole (<b>tcz</b>), and
miconazole (<b>mcz</b>) with the general formulas [(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuCl<sub>2</sub>(L)], [(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuClĀ(L)<sub>2</sub>]ĀCl, and [(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuĀ(L)<sub>3</sub>]Ā(PF<sub>6</sub>)<sub>2</sub> were prepared and characterized by NMR, HRMS, IR, UVāvis,
and X-ray crystallography. Herein, we report the first crystal structure
of a tioconazole metal complex as well as the structure of the tioconazole
ligand itself and the bis-clotrimazole complex as a hexafluorophosphate
salt. The complexes possess a pseudooctahedral geometry typical for
organorutheniumĀ(II) compounds where half of the coordination sites
are occupied by the Ļ-bonded arene ligand <i>p</i>-cymene while the remaining sites are occupied by either the chlorido
ligands and/or the azole ligands. The stability of the compounds in
dmso solution was studied by NMR spectroscopy. The biological activity
of all nine complexes and the ruthenium precursor against the fungus <i>Culvularia lunata</i> was evaluated. The complexes showed antifungal
activity at low millimolar concentrations, where the activity decreased
with the increasing number of ligands. However at 0.5 mM concentrations
all tris-azole complexes statistically significantly reduced the radial
growth rate, and also at 0.01 mM concentrations the monoazole complexes
showed statistically significant effects. <b>Mcz</b> and its
complexes were also tested against the human parasite <i>Schistosoma
mansoni</i> and revealed schistocidal activity at 10ā100
Ī¼g/mL in vitro
New Water-Soluble Ruthenium(II) Terpyridine Complexes for Anticancer Activity: Synthesis, Characterization, Activation Kinetics, and Interaction with Guanine Derivatives
With
the aim of assessing whether rutheniumĀ(II) compounds with meridional
geometry might be utilized as potential antitumor agents, a series
of new, water-soluble, monofunctional rutheniumĀ(II) complexes of the
general formula <i>mer</i>-[RuĀ(L<sub>3</sub>)Ā(N-N)ĀX]Ā[Y]<sub><i>n</i></sub> (where L<sub>3</sub> = 2,2ā²:6ā²,2ā³-terpyridine
(tpy) or 4ā²-chloro-2,2ā²:6ā²,2ā³-terpyridine
(Cl-tpy), N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach),
or 2,2ā²-bipyridine (bpy); X = Cl or dmso-<i>S</i>; Y = Cl, PF<sub>6</sub>, or CF<sub>3</sub>SO<sub>3</sub>; <i>n</i> = 1 or 2, depending on the nature of X) were synthesized.
All complexes were fully characterized by elemental analysis and spectroscopic
techniques (IR, UV/visible, and 1D and 2D NMR), and for three of them,
i.e., [RuĀ(Cl-tpy)Ā(bpy)ĀCl]Ā[Cl] (<b>3</b><sub><b>Cl</b></sub>), [RuĀ(Cl-tpy)Ā(en)Ā(dmso-<i>S</i>)]Ā[Y]<sub>2</sub> [Y =
PF<sub>6</sub> (<b>6</b><sub><b>PF<sub>6</sub></b></sub>), CF<sub>3</sub>SO<sub>3</sub> (<b>6</b><sub><b>OTf</b></sub>)] and [RuĀ(Cl-tpy)Ā(bpy)Ā(dmso-<i>S</i>)]Ā[CF<sub>3</sub>SO<sub>3</sub>]<sub>2</sub> (<b>8</b><sub><b>OTf</b></sub>), the X-ray structure was also determined. The new terpyridine complexes,
with the exception of <b>8</b>, are well soluble in water (>25
mg/mL). <sup>1</sup>H and <sup>31</sup>P NMR spectroscopy studies
performed on the three selected complexes [RuĀ(Cl-tpy)Ā(N-N)ĀCl]<sup>+</sup> [N-N = en (<b>1</b>), dach (<b>2</b>), and bpy
(<b>3</b>)] demonstrated that, after hydrolysis of the Cl ligand,
they are capable of interacting with guanine derivatives [i.e., 9-methylguanine
(9MeG) or guanosine-5ā²-monophosphate (5ā²-GMP)] through
N7, forming monofunctional adducts with rates and extents that depend
strongly on the nature of N-N: <b>1</b> ā <b>2</b> ā« <b>3</b>. In addition, compound <b>1</b> shows
high selectivity toward 5ā²-GMP compared to adenosine-5ā²-monophosphate
(5ā²-AMP), in a competition experiment. Quantitative kinetic
investigations on <b>1</b> and <b>2</b> were performed
by means of UV/visible spectroscopy. Overall, the complexes with bidentate
aliphatic diamines proved to be superior to those with bpy in terms
of solubility and reactivity (i.e., release of Cl<sup>ā</sup> and capability to bind guanine derivatives). Contrary to the chlorido
compounds, the corresponding dmso derivatives proved to be inert (viz.,
they do not release the monodentate ligand) in aqueous media
New Uses for Old Drugs: Attempts to Convert Quinolone Antibacterials into Potential Anticancer Agents Containing Ruthenium
Continuing the study of the physicochemical
and biological properties of ruthenium-quinolone adducts, four novel
complexes with the general formula [Ru([9]ĀaneS<sub>3</sub>)Ā(dmso-ĪŗS)Ā(quinolonato-Īŗ<sup><i>2</i></sup>O,O)]Ā(PF<sub>6</sub>), containing the quinolones
levofloxacin (<b>1</b>), nalidixic acid (<b>2</b>), oxolinic
acid (<b>3</b>), and cinoxacin (<b>4</b>), were prepared
and characterized in solid state as well as in solution. Contrary
to their organoruthenium analogues, these complexes are generally
relatively stable in aqueous solution as substitution of the dimethylsulfoxide
(dmso) ligand is slow and not quantitative, and a minor release of
the quinolonato ligand is observed only in the case of <b>4</b>. The complexes bind to serum proteins displaying relatively high
binding constants. DNA binding was studied using UVāvis spectroscopy,
cyclic voltammetry, and performing viscosity measurements of CT DNA
solutions in the presence of complexes <b>1</b>ā<b>4</b>. These experiments show that the ruthenium complexes interact
with DNA via intercalation. Possible electrostatic interactions occur
in the case of compound <b>4</b>, which also shows the most
pronounced rate of hydrolysis. Compounds <b>2</b> and <b>4</b> also exhibit a weak inhibition of cathepsins B and S, which
are involved in the progression of a number of diseases, including
cancer. Furthermore, complex <b>2</b> displayed moderate cytotoxicity
when tested on the HeLa cell line
New Uses for Old Drugs: Attempts to Convert Quinolone Antibacterials into Potential Anticancer Agents Containing Ruthenium
Continuing the study of the physicochemical
and biological properties of ruthenium-quinolone adducts, four novel
complexes with the general formula [Ru([9]ĀaneS<sub>3</sub>)Ā(dmso-ĪŗS)Ā(quinolonato-Īŗ<sup><i>2</i></sup>O,O)]Ā(PF<sub>6</sub>), containing the quinolones
levofloxacin (<b>1</b>), nalidixic acid (<b>2</b>), oxolinic
acid (<b>3</b>), and cinoxacin (<b>4</b>), were prepared
and characterized in solid state as well as in solution. Contrary
to their organoruthenium analogues, these complexes are generally
relatively stable in aqueous solution as substitution of the dimethylsulfoxide
(dmso) ligand is slow and not quantitative, and a minor release of
the quinolonato ligand is observed only in the case of <b>4</b>. The complexes bind to serum proteins displaying relatively high
binding constants. DNA binding was studied using UVāvis spectroscopy,
cyclic voltammetry, and performing viscosity measurements of CT DNA
solutions in the presence of complexes <b>1</b>ā<b>4</b>. These experiments show that the ruthenium complexes interact
with DNA via intercalation. Possible electrostatic interactions occur
in the case of compound <b>4</b>, which also shows the most
pronounced rate of hydrolysis. Compounds <b>2</b> and <b>4</b> also exhibit a weak inhibition of cathepsins B and S, which
are involved in the progression of a number of diseases, including
cancer. Furthermore, complex <b>2</b> displayed moderate cytotoxicity
when tested on the HeLa cell line
New Uses for Old Drugs: Attempts to Convert Quinolone Antibacterials into Potential Anticancer Agents Containing Ruthenium
Continuing the study of the physicochemical
and biological properties of ruthenium-quinolone adducts, four novel
complexes with the general formula [Ru([9]ĀaneS<sub>3</sub>)Ā(dmso-ĪŗS)Ā(quinolonato-Īŗ<sup><i>2</i></sup>O,O)]Ā(PF<sub>6</sub>), containing the quinolones
levofloxacin (<b>1</b>), nalidixic acid (<b>2</b>), oxolinic
acid (<b>3</b>), and cinoxacin (<b>4</b>), were prepared
and characterized in solid state as well as in solution. Contrary
to their organoruthenium analogues, these complexes are generally
relatively stable in aqueous solution as substitution of the dimethylsulfoxide
(dmso) ligand is slow and not quantitative, and a minor release of
the quinolonato ligand is observed only in the case of <b>4</b>. The complexes bind to serum proteins displaying relatively high
binding constants. DNA binding was studied using UVāvis spectroscopy,
cyclic voltammetry, and performing viscosity measurements of CT DNA
solutions in the presence of complexes <b>1</b>ā<b>4</b>. These experiments show that the ruthenium complexes interact
with DNA via intercalation. Possible electrostatic interactions occur
in the case of compound <b>4</b>, which also shows the most
pronounced rate of hydrolysis. Compounds <b>2</b> and <b>4</b> also exhibit a weak inhibition of cathepsins B and S, which
are involved in the progression of a number of diseases, including
cancer. Furthermore, complex <b>2</b> displayed moderate cytotoxicity
when tested on the HeLa cell line
Structure-Related Mode-of-Action Differences of Anticancer Organoruthenium Complexes with Ī²āDiketonates
A series
of organorutheniumĀ(II) chlorido complexes with fluorinated O,O-ligands
[(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuĀ(F<sub>3</sub>C-acac-Ar)ĀCl]
(<b>1a</b>ā<b>6a</b>) and their respective 1,3,5-triaza-7-phosphaadamantane
(pta) derivatives [(Ī·<sup>6</sup>-<i>p</i>-cymene)ĀRuĀ(F<sub>3</sub>C-acac-Ar)Āpta]ĀPF<sub>6</sub> (<b>1b</b>ā<b>6b</b>) were synthesized and fully characterized in both solution
and solid state. All complexes were inactive against nonmalignant
keratinocytes but displayed variable activity against cancer cell
models (ovarian, osteosarcoma). Compounds with a ligand containing
the 4-chlorophenyl substituent (<b>6a</b> and <b>6b</b>) exhibited the strongest anticancer effects. Despite a marginally
lower cellular Ru accumulation compared to the chlorido complexes,
pta analogues showed higher activity especially in the osteosarcoma
model. Reduction of glutathione levels by buthionine sulfoximine (BSO)
significantly enhanced the activity of all compounds with the most
pronounced effects being observed for the pta series resulting in
IC<sub>50</sub> values down to the nanomolar range. While all chlorido
complexes potently induce reactive oxygen species, DNA damage, and
apoptosis, the respective pta compounds widely lacked ROS production
but blocked cell cycle progression in G0/G1 phase
Physicochemical Studies and Anticancer Potency of Ruthenium Ī·<sup>6</sup>-<i>p</i>-Cymene Complexes Containing Antibacterial Quinolones
With the aim of exploring the anticancer properties of organometallic compounds with bioactive ligands, Ru(arene) compounds of the antibacterial quinolones nalidixic acid (<b>2</b>) and cinoxacin (<b>3</b>) were synthesized, and their physicochemical properties were compared to those of chlorido(Ī·<sup>6</sup>-<i>p</i>-cymene)(ofloxacinato-Īŗ<sup>2</sup><i>O</i>,<i>O</i>)ruthenium(II) (<b>1</b>). All compounds undergo a rapid ligand exchange reaction from chlorido to aqua species. <b>2</b> and <b>3</b> are significantly more stable than <b>1</b> and undergo minor conversion to an unreactive [(cym)Ru(Ī¼-OH)<sub>3</sub>Ru(cym)]<sup>+</sup> species (cym = Ī·<sup>6</sup>-<i>p</i>-cymene). In the presence of human serum albumin <b>1</b>ā<b>3</b> form adducts with this transport protein within 20 min of incubation. With guanosine 5ā²-monophosphate (5ā²-GMP; as a simple model for reactions with DNA) very rapid reactions yielding adducts via its N7 atom were observed, illustrating that DNA is a possible target for this compound class. A moderate capacity of inhibiting tumor cell proliferation in vitro was observed for <b>1</b> in CH1 ovarian cancer cells, whereas <b>2</b> and <b>3</b> turned out to be inactive