Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)2{μ-η1:η3-CH═C(C(OH)(R))C(═O)}] (2a-c; Cp = η5-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)2{μ-η1:η3-C(Ph)═C(Ph)C(═O)}] (1) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)3{μ-η1:η2-CH═C═R}]BF4 (3a-c) in 85-93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV-vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a. The cytotoxicity in vitro of 2b and 3a-c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17α-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b, 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion

Ring-Opening Reactions of the <i>N</i>‑4-Nosyl Hough–Richardson Aziridine with Nitrogen Nucleophiles

Dinosylated α-d-glucopyranoside was directly transformed into α-d-altropyranosides via in situ formed <i>N</i>-4-nosyl Hough–Richardson aziridine with nitrogen nucleophiles under mild conditions in fair to excellent yields. The scope of the aziridine ring-opening reaction was substantially broadened contrary to the conventional methods introducing solely the azide anion at high temperatures. If necessary, the <i>N</i>-4-nosyl Hough–Richardson aziridine can be isolated by filtration in a very good yield and high purity

Structural, Magnetic, and Redox Diversity of First-Row Transition Metal Complexes of a Pyridine-Based Macrocycle: Well-Marked Trends Supported by Theoretical DFT Calculations

A series of first-row transition metal complexes with 15-membered pyridine-based macrocycle (3,12,18-triaza-6,9-dioxabicyclo[12.3.1]­octadeca-1(18),14,16-triene = <b>L</b>) was prepared ([M^II(<b>L</b>)­Cl₂], where M = Mn, Co, Ni, Zn (<b>1</b>, <b>3</b>, <b>4</b>, <b>6</b>); [Fe^III(<b>L</b>)­Cl₂]Cl (<b>2</b>), [Cu^II(<b>L</b>)­Cl]Cl (<b>5</b>)) and thoroughly characterized. Depending on the complexated metal atom, the coordination number varies from 7 (Mn, Fe, Co), through 5 + 2 for Ni and 4 + 1 for Cu, to 5 for Zn accompanied by changes in the coordination geometry from the pentagonal bipyramid (<b>1</b>–<b>4</b>) to the square pyramid (<b>5</b> and <b>6</b>). Along the series, the metal–oxygen distances were prolonged in such manner that their bonding character was investigated, apart from X-ray structural analysis, also by ab initio calculations (Mayer’s bond order, electron localization function), which confirmed that, in <b>4</b> and <b>5</b>, two and one oxygen donor atoms are semicoordinated, respectively, and one and two oxygen atoms are uncoordinated in <b>5</b>, and <b>6</b>, respectively. On the basis of the temperature variable magnetic susceptibility measurements, <b>1</b> and <b>2</b> behave as expected for 3d⁵ high-spin configuration with negligible zero-field splitting (ZFS). On the other hand, a large axial ZFS (<i>D</i>(Co) ≈ 40 cm^–1, <i>D</i>(Ni) ≈ −6.0 cm^–1) was found for <b>3</b> and <b>4</b>, and rhombic ZFS (<i>E</i>/<i>D</i> ≈ 0.15) for <b>4</b>. Antiferromagnetic exchange coupling was observed for <b>4</b> and <b>5</b> (<i>J</i>(Ni) = −0.48 cm^–1, and <i>J</i>(Cu) = −2.43 cm^–1, respectively). The obtained results correlate well with ab initio calculations of ZFS parameters as well as <i>J</i>-values, which indicate that the antiferromagnetic exchange is mediated by hydrogen bonds. The complexes were also investigated by cyclic voltammetry in water or acetonitrile. A quasi-reversible couple Mn­(II)/Mn­(III) at 1.13/0.97 V, an almost reversible couple Fe­(II)/Fe­(III) at 0.51/0.25 V, and a one-step/multistep reduction/oxidation of Cu­(II) complex <b>5</b> at −0.33 V/0.06–0.61 V were detected

Experimental and Theoretical Investigations of Magnetic Exchange Pathways in Structurally Diverse Iron(III) Schiff-Base Complexes

The synthesis, and the structural and magnetic properties, of the following new iron­(III) Schiff base complexes with the {O′,N,O″}-chelating ligand H₂L (2-hydroxyphenylsalicylaldimine) are reported: K­[FeL₂]·H₂O (<b>1</b>), (Pr₃NH)­[FeL₂]·2CH₃OH (<b>2</b>), [FeL­(bpyO₂) (CH₃OH)]­[FeL₂]·CH₃OH (<b>3</b>), [Fe₂L₃(CH₃OH)]·2CH₃OH·H₂O (<b>4</b>), and [{Fe₂L₂}­(μ–OH)₂{FeL­(bpyO₂)}₂]­[BPh₄]₂·2H₂O (<b>5</b>), where Pr₃NH⁺ represents the tripropylammonium cation and bpyO₂ stands for 2,2′-bipyridine-<i>N</i>-dioxide. A thorough density functional theory (DFT) study of magnetic interactions (the isotropic exchange) at the B3LYP/def-TZVP level of theory was employed, and calculations have revealed superexchange pathways through intramolecular/intermolecular noncovalent contacts (π–π stacking, C–H···O and O–H···O hydrogen bonds, diamagnetic metal cations) and/or covalent bonds ((μ-O_Ph, μ-OH) or bis­(μ-O_Ph) bridging modes), which helped us to postulate trustworthy spin Hamiltonians for magnetic analysis of experimental data. Within the reported family of compounds <b>1</b>–<b>5</b>, the mediators of the antiferromagnetic exchange can be sorted by their increasing strength as follows: π–π stacking (<i>J</i>^DFT = −0.022 cm^–1/<i>J</i>^mag = −0.025(4) cm^–1 in <b>2</b>) < C–H···O contacts and π–π stacking (<i>J</i>^DFT = −0.19 cm^–1/<i>J</i>^mag = −0.347(9)­cm^–1 in <b>1</b>) < O–H···O hydrogen bonds (<i>J</i>^DFT = −0.53 cm^–1/<i>J</i>^mag = −0.41(1) cm^–1 in <b>3</b>) < bis­(μ-O_Ph) bridge (<i>J</i>^DFT = −13.8 cm^–1/<i>J</i>^mag = −12.3(9) cm^–1 in <b>4</b>) < (μ-O_Ph, μ-OH) bridge (<i>J</i>^DFT = −18.0 cm^–1/<i>J</i>^mag = −17.1(2) cm^–1 in <b>5</b>), where <i>J</i>^DFT and <i>J</i>^mag are the isotropic exchange parameters derived from DFT calculations, and analysis of the experimental magnetic data, respectively. The good agreement between theoretically calculated and experimentally derived isotropic exchange parameters suggests that this procedure is applicable also for other chemical and structural systems to interpret magnetic data properly

Experimental and Theoretical Investigations of Magnetic Exchange Pathways in Structurally Diverse Iron(III) Schiff-Base Complexes

The synthesis, and the structural and magnetic properties, of the following new iron­(III) Schiff base complexes with the {O′,N,O″}-chelating ligand H₂L (2-hydroxyphenylsalicylaldimine) are reported: K­[FeL₂]·H₂O (<b>1</b>), (Pr₃NH)­[FeL₂]·2CH₃OH (<b>2</b>), [FeL­(bpyO₂) (CH₃OH)]­[FeL₂]·CH₃OH (<b>3</b>), [Fe₂L₃(CH₃OH)]·2CH₃OH·H₂O (<b>4</b>), and [{Fe₂L₂}­(μ–OH)₂{FeL­(bpyO₂)}₂]­[BPh₄]₂·2H₂O (<b>5</b>), where Pr₃NH⁺ represents the tripropylammonium cation and bpyO₂ stands for 2,2′-bipyridine-<i>N</i>-dioxide. A thorough density functional theory (DFT) study of magnetic interactions (the isotropic exchange) at the B3LYP/def-TZVP level of theory was employed, and calculations have revealed superexchange pathways through intramolecular/intermolecular noncovalent contacts (π–π stacking, C–H···O and O–H···O hydrogen bonds, diamagnetic metal cations) and/or covalent bonds ((μ-O_Ph, μ-OH) or bis­(μ-O_Ph) bridging modes), which helped us to postulate trustworthy spin Hamiltonians for magnetic analysis of experimental data. Within the reported family of compounds <b>1</b>–<b>5</b>, the mediators of the antiferromagnetic exchange can be sorted by their increasing strength as follows: π–π stacking (<i>J</i>^DFT = −0.022 cm^–1/<i>J</i>^mag = −0.025(4) cm^–1 in <b>2</b>) < C–H···O contacts and π–π stacking (<i>J</i>^DFT = −0.19 cm^–1/<i>J</i>^mag = −0.347(9)­cm^–1 in <b>1</b>) < O–H···O hydrogen bonds (<i>J</i>^DFT = −0.53 cm^–1/<i>J</i>^mag = −0.41(1) cm^–1 in <b>3</b>) < bis­(μ-O_Ph) bridge (<i>J</i>^DFT = −13.8 cm^–1/<i>J</i>^mag = −12.3(9) cm^–1 in <b>4</b>) < (μ-O_Ph, μ-OH) bridge (<i>J</i>^DFT = −18.0 cm^–1/<i>J</i>^mag = −17.1(2) cm^–1 in <b>5</b>), where <i>J</i>^DFT and <i>J</i>^mag are the isotropic exchange parameters derived from DFT calculations, and analysis of the experimental magnetic data, respectively. The good agreement between theoretically calculated and experimentally derived isotropic exchange parameters suggests that this procedure is applicable also for other chemical and structural systems to interpret magnetic data properly

Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent

We conducted a systematic study on the reactivity of [Ru2Cp2(CO)(4)] (Cp = eta(5)-C5H5) with isocyanides and the subsequent methylation reaction to produce [Ru2Cp2(CO)(2)(mu-CO){mu-CNMe(R)}]+ complexes as CF3SO3- salts, [2a-h]+ [R = Me, cyclohexyl (Cy), 2,6-C6H3Me2 (Xyl), 1H-indol-5-yl, 2-naphthyl, 4-C6H4OMe, (S)-CHMe(Ph), CH2Ph (Bn)]. The resulting products, including five novel ones, underwent structural characterization by IR and multinuclear NMR spectroscopy, with five of them further confirmed via single crystal X-ray diffraction. Compounds [2a-e,h]CF(3)SO(3 )exhibit appreciable water solubility, substantial amphiphilic character and outstanding stability in physiological-like solutions (negligible degradation after 72 hours in DMEM at 37(degrees)C). Representative complexes [2b](+) and [2c](+ )were additionally characterized through cyclic voltammetry in CH2Cl2 and in aqueous phosphate buffer solution. Compounds [2a-d]CF3SO3 were assessed for in vitro cytotoxicity against A2780, A2080R and MCF-7 human cancer cell lines, and [2a-c]CF3SO3 revealed significant-to-moderate cytotoxicity, outperforming cisplatin in several cases. The most favourable IC50 values were observed for [2d]CF3SO3, ranging from 3.7 to 13.0 mu M. Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for [2b-d]CF3SO3, with the highest selectivity indexes (SI) calculated as 10.1 (ratio of IC(50 )on MRC-5/IC50 on A2780) and 8.5 (ratio of IC50 on MRC-5/IC(50 )on A2780R) for [2d]CF3SO3. Subsequently, [2d]CF3SO3 was tested across a panel of HOS, A549, PANC1, CaCo2, PC3 and HeLa cancer cells, showing variable cytotoxicity with IC50 values in the range of 9.7 to 20.3 mu M. The cellular effects of [2d](+ )on A2780 cells were investigated using flow cytometry assays, focusing on the cell cycle modification, time-resolved cellular uptake, intracellular ROS production, mitochondrial membrane depolarization, induction of cell death through apoptosis, activation of caspases 3/7 and induction of autophagy. Overall, the results suggest a diphasic mechanism of action for [2d]+, inducing metabolic stress and arresting proliferation in the first/fast phase, followed by the induction of apoptosis and autophagy in the second/slower phase

Late First-Row Transition-Metal Complexes Containing a 2‑Pyridylmethyl Pendant-Armed 15-Membered Macrocyclic Ligand. Field-Induced Slow Magnetic Relaxation in a Seven-Coordinate Cobalt(II) Compound

The 2-pyridylmethyl <i>N</i>-pendant-armed heptadentate macrocyclic ligand {3,12-bis­(2-methylpyridine)-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]­octadeca-1,14,16-triene = <b>L</b>} and [M­(<b>L</b>)]­(ClO₄)₂ complexes, where M = Mn­(II) (<b>1</b>), Fe­(II) (<b>2</b>), Co­(II) (<b>3</b>), Ni­(II) (<b>4</b>), and Cu­(II) (<b>5</b>), were prepared and thoroughly characterized, including elucidation of X-ray structures of all the compounds studied. The complexes <b>1</b>–<b>5</b> crystallize in non-centrosymmetric Sohncke space groups as racemic compounds. The coordination numbers of 7, 6 + 1, and 5 were found in complexes <b>1</b>–<b>3</b>, <b>4</b>, and <b>5</b>, respectively, with a distorted pentagonal bipyramidal (<b>1</b>–<b>4</b>) or square pyramidal (<b>5</b>) geometry. On the basis of the magnetic susceptibility experiments, a large axial zero-field splitting (ZFS) was found for <b>2</b>, <b>3</b>, and <b>4</b> (<i>D</i>(Fe) = −7.4(2) cm^–1, <i>D</i>(Co) = 34(1) cm^–1, and <i>D</i>(Ni) = −12.8(1) cm^–1, respectively) together with a rhombic ZFS (<i>E</i>/<i>D</i> = 0.136(3)) for <b>4</b>. Despite the easy plane anisotropy (<i>D</i> > 0, <i>E</i>/<i>D</i> = 0) in <b>3</b>, the slow relaxation of the magnetization below 8 K was observed and analyzed either with Orbach relaxation mechanism (the relaxation time τ₀ = 9.90 × 10^–10 s and spin reversal barrier <i>U</i>_eff = 24.3 K (16.9 cm^–1)) or with Raman relaxation mechanism (<i>C</i> = 2.12 × 10^–5 and <i>n</i> = 2.84). Therefore, compound <b>3</b> enlarges the small family of field-induced single-molecule magnets with pentagonal-bipyramidal chromophore. The cyclic voltammetry in acetonitrile revealed reversible redox processes in <b>1</b>–<b>3</b> and <b>5</b>, except for the Ni­(II) complex <b>4</b>, where a quasi-reversible process was dominantly observed. Presence of the two 2-pyridylmethyl pendant arms in <b>L</b> with a stronger σ-donor/π-acceptor ability had a great impact on the properties of all the complexes (<b>1</b>–<b>5</b>), concretely: (i) strong pyridine–metal bonds provided slight axial compression of the coordination sphere, (ii) substantial changes in magnetic anisotropy, and (iii) stabilization of lower oxidation states

Slow Magnetic Relaxation in Octahedral Cobalt(II) Field-Induced Single-Ion Magnet with Positive Axial and Large Rhombic Anisotropy

Pseudooctahedral mononuclear cobat­(II) complex [Co­(abpt)₂(tcm)₂] (<b>1</b>), where abpt = 4-amino-3,5-bis­(2-pyridyl)-1,2,4-triazole and tcm = tricyanomethanide anion, shows field-induced slow relaxation of magnetization with <i>U</i> = 86.2 K and large axial and rhombic single-ion zero-field-splitting parameters, <i>D</i> = +48(2) cm^–1 and <i>E</i>/<i>D</i> = 0.27(2) (<i>D</i> = +53.7 cm^–1 and <i>E</i>/<i>D</i> = 0.29 from ab initio CASSCF/NEVPT2 calculations), thus presenting a new example of a field-induced single-ion magnet with transversal magnetic anisotropy

Tetranuclear Lanthanide Complexes Containing a Hydrazone-type Ligand. Dysprosium [2 × 2] Gridlike Single-Molecule Magnet and Toroic

A multidentate hydrazone-type ligand (<i>Z</i>,<i>Z</i>)-bis­(1-(pyridin-2-yl)-1-amino-methylidene)­oxalohydrazide (H₂L) was utilized in the synthesis of three new isomorphous tetranuclear complexes of the general formula [Ln₄(HL)₄(H₂L)₂­(NO₃)₄]­(NO₃)₄·4CH₃OH (Ln = Gd^III, <b>1</b>, Tb^III, <b>2</b>, Dy^III, <b>3</b>) with the gridlike [2 × 2] topology. The analysis of the static magnetic data revealed weak anti-ferromagnetic interaction among lanthanide­(III) atoms, whereas dynamic magnetic data led to the observation of the single-molecule magnet behavior in zero static magnetic field for the Dy₄ compound <b>3</b> with <i>U</i>_eff = 42.6 K and τ₀ = 1.50 × 10^–5 s. The theoretical CASSCF calculations supported also the presence of the net toroidal magnetic moment, which classifies compound <b>3</b> also as a single-molecule toroic