Triazine Chalcogenones from Thiocyanate or Selenocyanate Addition to Tetrazine Ligands in Ruthenium Arene Complexes.

The chemistry of 1,2,4,5-tetrazines has attracted considerable interest both from a synthetic and applicative standpoint. Recently, regioselective reactions with alkynes and alkenes have been reported to be favored once the tetrazine ring is coordinated to Re(I), Ru(II), and Ir(III) centers. Aiming to further explore the effects of metal coordination, herein, we unveil the unexplored reactivity of tetrazines with chalcogenocyanate anions. Thus, ruthenium(II) tetrazine complexes, [RuCl{κ2N-3-(2-pyridyl)-6-R-1,2,4,5-tetrazine}(η6-arene)]+ (arene = p-cymene, R = H, [1a]+, R = Me, [1b]+, R = 2-pyridyl, [1c]+; arene = C6Me6, R = H, [1d]+, R = Me, [1e]+; PF6- salts), reacted quantitatively and in mild conditions with M(ECN) salts (M = Na, K, Bu4N; E = O, S, Se). The addition of thiocyanate or selenocyanate to the tetrazine ligand is regioselective and afforded, via N2 release, 1,2,4-triazine-5-chalcogenone heterocycles, the one with selenium being unprecedented. The novel ruthenium complexes [RuCl{κ2N-(2-pyridyl)}{triazine chalcogenone}(η6-arene)] 2a-e (sulfur), 3b, 3d, and 3e (selenium) were characterized by analytical (CHNS analyses, conductivity), spectroscopic (IR, multinuclear and two-dimensional (2D) NMR), and spectrometric (electrospray ionization mass spectrometry (ESI-MS)) techniques. According to density functional theory (DFT) calculations, the nucleophilic attack of SCN- on the tetrazine ring is kinetically driven. Compound 2b is selectively and reversibly mono-protonated on the triazine ring by HCl or other strong acids, affording a single tautomer. When reactions of chalcogenocyanates were performed on the 2,2'-bipyridine (bpy) complex [RuCl(bpy)(η6-p-cymene)]+, the chloride substitution products [Ru(ECN)(bpy)(η6-p-cymene)]+ (E = O, [4]+; E = S, [5]+; E = Se, [6]+) were obtained in 82-90% yields (PF6- salts). Combined spectroscopic data (IR, 1H/13C/77Se NMR) was revealed to be a useful tool to study the linkage isomerism of the chalcogenocyanate ligand in [4-6]+.

Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies.

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2-4) were obtained (45-92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(µ-CO){µ-η1:η3-C(Ph)═C(Ph)C(═O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η5-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1-3 by HBF4 afforded the corresponding µ-alkenyl derivatives 5-7, in 40-86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry (1, 2, 5, 7) and single-crystal X-ray diffraction (5, 7) analyses were performed on representative compounds. Complexes 5-7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5-7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru2Cp2(CO)x scaffold (x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.

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.

Dichloro(2,2'-bipyridine)copper/MAO: An Active and Stereospecific Catalyst for 1,3-Diene Polymerization.

Dichloro(2,2'-bipyridine)copper was synthesized by reacting copper dichloride with bypyridine, and its behavior, in combination with methylaluminoxane (MAO), in the polymerization of butadiene, isoprene, 2,3-dimethyl-1,3 butadiene, and 3-methyl-1,3-pentadiene was examined. The purpose of this study is to find catalytic systems that are more sustainable than those currently used for the polymerization of butadiene and isoprene (e.g., Co and Ni), but that are comparable in terms of catalytic activity and selectivity. Predominantly, syndiotactic 1,2 polybutadiene, crystalline syndiotactic 3,4 polyisoprene, crystalline syndiotactic 1,2 poly(3-methyl-1,3-pentadiene), and crystalline cis-1,4 poly(2,3-dimethyl-1,3-butadiene) were obtained in a manner similar to that observed with the analogous iron complex. As far as we know, the investigated catalytic system represents the first example of a copper-based catalyst in the field of stereospecific polymerization. Given the great availability of copper, its extremely low toxicity (and therefore high sustainability), and the similarity of its behavior to that of iron, the result obtained seems to us of considerable interest and worthy of further investigation.

Diiron Aminocarbyne Complexes with NCE- Ligands (E = O, S, Se).

Diiron µ-aminocarbyne complexes [Fe2Cp2(NCMe)(CO)(µ-CO){µ-CN(Me)(R)}]CF3SO3 (R = Xyl, [1aNCMe]CF3SO3; R = Me, [1bNCMe]CF3SO3; R = Cy, [1cNCMe]CF3SO3; R = CH2Ph, [1dNCMe]CF3SO3), freshly prepared from tricarbonyl precursors [1a-d]CF3SO3, reacted with NaOCN (in acetone) and NBu4SCN (in dichloromethane) to give [Fe2Cp2(kN-NCO)(CO)(µ-CO){µ-CN(Me)(R)}] (R = Xyl, 2a; Me, 2b; Cy, 2c) and [Fe2Cp2(kN-NCS)(CO)(µ-CO){µ-CN(Me)(CH2Ph)}], 3 in 67-81% yields via substitution of the acetonitrile ligand. The reaction of [1aNCMe-1cNCMe]CF3SO3 with KSeCN in THF at reflux temperature led to the cyanide complexes [Fe2Cp2(CN)(CO)(µ-CO){µ-CNMe(R)}], 6a-c (45-67%). When the reaction of [1aNCMe]CF3SO3 with KSeCN was performed in acetone at room temperature, subsequent careful chromatography allowed the separation of moderate amounts of [Fe2Cp2(kSe-SeCN)(CO)(µ-CO){µ-CN(Me)(Xyl)}], 4a, and [Fe2Cp2(kN-NCSe)(CO)(µ-CO){µ-CN(Me)(Xyl)}], 5a. All products were fully characterized by elemental analysis, IR, and multinuclear NMR spectroscopy; moreover, the molecular structure of trans-6b was ascertained by single crystal X-ray diffraction. DFT calculations were carried out to shed light on the coordination mode and stability of the {NCSe-} fragment.

Easily Available, Amphiphilic Diiron Cyclopentadienyl Complexes Exhibit in Vitro Anticancer Activity in 2D and 3D Human Cancer Cells through Redox Modulation Triggered by CO Release.

A straightforward two-step procedure via single CO removal allows the conversion of commercial [Fe2 Cp2 (CO)4 ] into a range of amphiphilic and robust ionic complexes based on a hybrid aminocarbyne/iminium ligand, [Fe2 Cp2 (CO)3 {CN(R)(R')}]X (R, R'=alkyl or aryl; X=CF3 SO3 or BF4 ), on up to multigram scales. Their physicochemical properties can be modulated by an appropriate choice of N-substituents and counteranion. Tested against a panel of human cancer cell lines, the complexes were shown to possess promising antiproliferative activity and to circumvent multidrug resistance. Interestingly, most derivatives also retained a significant cytotoxic activity against human cancer 3D cell cultures. Among them, the complex with R=4-C6 H4 OMe and R'=Me emerged as the best performer of the series, being on average about six times more active against cancer cells than a noncancerous cell line, and displayed IC50 values comparable to those of cisplatin in 3D cell cultures. Mechanistic studies revealed the ability of the complexes to release carbon monoxide and to act as oxidative stress inducers in cancer cells.

Hetero-Bis-Conjugation of Bioactive Molecules to Half-Sandwich Ruthenium(II) and Iridium(III) Complexes Provides Synergic Effects in Cancer Cell Cytotoxicity.

Four bipyridine-type ligands variably derivatized with two bioactive groups (taken from ethacrynic acid, flurbiprofen, biotin, and benzylpenicillin) were prepared via sequential esterification steps from commercial 2,2'-bipyridine-4,4'-dicarboxylic acid and subsequently coordinated to ruthenium(II) p-cymene and iridium(III) pentamethylcyclopentadienyl scaffolds. The resulting complexes were isolated as nitrate salts in high yields and fully characterized by analytical and spectroscopic methods. NMR and MS studies in aqueous solution and in cell culture medium highlighted a substantial stability of ligand coordination and a slow release of the bioactive fragments in the latter case. The complexes were assessed for their antiproliferative activity on four cancer cell lines, showing cytotoxicity to the low micromolar level (equipotent with cisplatin). Additional biological experiments revealed a multimodal mechanism of action of the investigated compounds, involving DNA metalation and enzyme inhibition. Synergic effects provided by specific combinations of metal and bioactive fragments were identified, pointing toward an optimal ethacrynic acid/flurbiprofen combination for both Ru(II) and Ir(III) complexes.

Diethylammonium iodide as catalyst for the metal-free synthesis of 5-aryl-2-oxazolidinones from aziridines and carbon dioxide.

The catalytic potential of ammonium halide salts was explored in the coupling reaction of a model aziridine with carbon dioxide, highlighting the superior activity of [NH2Et2]I. Then, working at room temperature, atmospheric CO2 pressure and in the absence of solvent, the [NH2Et2]I-catalyzed synthesis of a series of 5-aryl-2-oxazolidinones was accomplished in good to high yields and excellent selectivity, from 2-aryl-aziridines with N-methyl or N-ethyl groups. NMR studies and DFT calculations outlined the pivotal role of both the diethylammonium cation and the iodide anion. The proposed method represents a convenient choice for obtaining a limited number of valuable molecules for which more complex and more expensive catalytic systems have been reported even in recent years.

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups.

Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η5-C5Me4R)Cl(µ-Cl)]2 (R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl mononuclear derivatives [Ir(η5-C5Me4R)(kN,kCPhPy)Cl] (2a-d), and the dimethylsulfoxide complex [Ir{η5-C5Me4(4-C6H4OH)}Cl2(κS-Me2S=O)] (3) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.

A Comprehensive Analysis of the Metal-Nitrile Bonding in an Organo-Diiron System.

Nitriles (N≡CR) are ubiquitous in coordination chemistry, yet literature studies on metal-nitrile bonding based on a multi-technique approach are rare. We selected an easily-available di-organoiron framework, containing both π-acceptor (CO, aminocarbyne) and donor (Cp = η5-C5H5) ligands, as a suitable system to provide a comprehensive description of the iron-nitrile bond. Thus, the new nitrile (2-12)CF3SO3 and the related imine/amine complexes (8-9)CF3SO3 were synthesized in 58-83% yields from the respective tris-carbonyl precursors (1a-d)CF3SO3, using the TMNO strategy (TMNO = trimethylamine-N-oxide). The products were fully characterized by elemental analysis, IR (solution and solid state) and multinuclear NMR spectroscopy. In addition, the structures of (2)CF3SO3, (3)CF3SO3, (5)CF3SO3 and (11)CF3SO3 were ascertained by single crystal X-ray diffraction. Salient spectroscopic data of the nitrile complexes are coherent with the scale of electron-donor power of the R substituents; otherwise, this scale does not match the degree of Fe → N π-back-donation and the Fe-N bond energies, which were elucidated in (2-7)CF3SO3 by DFT calculations.

Some Novel Cobalt Diphenylphosphine Complexes: Synthesis, Characterization, and Behavior in the Polymerization of 1,3-Butadiene.

Some novel cobalt diphenylphosphine complexes were synthesized by reacting cobalt(II) chloride with (2-methoxyethyl)diphenylphosphine, (2-methoxyphenyl)diphenylphosphine, and 2-(1,1-dimethylpropyl)-6-(diphenylphosphino)pyridine. Single crystals suitable for X-ray diffraction studies were obtained for the first two complexes, and their crystal structure was determined. The novel compounds were then used in association with methylaluminoxane (MAO) for the polymerization of 1,3-butadiene, and their behavior was compared with that exhibited in the polymerization of the same monomer by the systems CoCl2(PnPrPh2)2/MAO and CoCl2(PPh3)2/MAO. Some significant differences were observed depending on the MAO/Co ratio used, and a plausible interpretation for such a different behavior is proposed.

Bis-conjugation of Bioactive Molecules to Cisplatin-like Complexes through (2,2'-Bipyridine)-4,4'-Dicarboxylic Acid with Optimal Cytotoxicity Profile Provided by the Combination Ethacrynic Acid/Flurbiprofen.

A facile route to PtII complexes doubly functionalized with bioactive molecules through a bipyridine-type ligand is described. Initially, ligands LEE (containing two ethacrynic acid units), LEF (ethacrynic acid+flurbiprofen) and LEB (ethacrynic acid+biotin) were obtained in moderate to good yields from 2,2'-bipyridine-4,4'-dicarboxylic acid. Subsequent reaction of the ligands with [PtCl2 (DMSO)2 ] afforded complexes [PtCl2 (LEE )] (2), [PtCl2 (LEF )] (3) and [PtCl2 (LEB )] (4) in high yields. All compounds were fully characterized by analytical and spectroscopic methods. Complexes 2-4 are highly stable in water/DMSO solution at 37 °C after 72 h, whereas progressive release of the bioactive fragments was detected in a cell culture medium. The compounds were assessed for their in vitro antiproliferative activity towards tumorigenic A2780, A2780cisR and Y79 cells and non-tumourigenic HEK293 cells. In particular, the combination of ethacrynic acid and flurbiprofen in 3 overcomes cisplatin-based resistance and provides strong cancer cell selectivity. Enzyme inhibition assays on human GST P1 and human COX-2 and cross-experiments with complex 1, analogous to 2-4 but lacking bio-groups, revealed a clear synergy between the PtII frame and the bioactive organic components.

Tetrasubstituted Selenophenes from the Stepwise Assembly of Molecular Fragments on a Diiron Frame and Final Cleavage of a Bridging Alkylidene.

A series of 2,3-dicarboxylato-5-acetyl-4-aminoselenophenes, 5a-j, was obtained via the uncommon assembly of building blocks on a diiron platform, starting from commercial [Fe2Cp2(CO)4] through the stepwise formation of diiron complexes [2a-d]CF3SO3, 3a-d, and 4a-j. The selenophene-substituted bridging alkylidene ligand in 4a-j is removed from coordination upon treatment with water in air under mild conditions (ambient temperature in most cases), affording 5a-j in good to excellent yields. This process is highly selective and is accompanied by the disruption of the organometallic scaffold: cyclopentadiene (CpH) and lepidocrocite (γ-FeO(OH)) were identified by NMR and Raman analyses at the end of one representative reaction. The straightforward cleavage of the linkage between a bridging Fischer alkylidene and two (or more) metal centers, as observed here, is an unprecedented reaction in organometallic chemistry: in the present case, the carbene function is converted to a ketone which is incorporated into the organic product. DFT calculations and electrochemical experiments were carried out to give insight into the release of the selenophene-alkylidene ligand. Compounds 5a-j were fully characterized by elemental analysis, mass spectrometry, IR, and multinuclear NMR spectroscopy and by X-ray diffraction and cyclic voltammetry in one case.

Recent Advances in the Chemistry of Metal Carbamates.

Following a related review dating back to 2003, the present review discusses in detail the various synthetic, structural and reactivity aspects of metal species containing one or more carbamato ligands, representing a large family of compounds across all the periodic table. A preliminary overview is provided on the reactivity of carbon dioxide with amines, and emphasis is given to recent findings concerning applications in various fields.

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity.

A series of diiron/tetrairon compounds containing a S- or a Se-function (2a-d, 4a-d, 5a-b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)C2HC3(Me)}] (3) were prepared from the diiron µ-vinyliminium precursors [Fe2Cp2(CO)( µ-CO){ µ-η1: η3-C3(R')C2HC1N(Me)(R)}]CF3SO3 (R = R' = Me, 1a; R = 2,6-C6H3Me2 = Xyl, R' = Ph, 1b; R = Xyl, R' = CH2OH, 1c), via treatment with S8 or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a-d, 5a-b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.

Anticancer Potential of Diiron Vinyliminium Complexes.

Invited for the cover of this issue is the group of Fabio Marchetti at the Università di Pisa and Paul J. Dyson at Ecole Polytechnique Fédérale de Lausanne (EPFL). Read the full text of the article at 10.1002/chem.201902885.

Anticancer Potential of Diiron Vinyliminium Complexes.

Although ferrocene derivatives have attracted considerable attention as possible anticancer agents, the medicinal potential of diiron complexes has remained largely unexplored. Herein, we describe the straightforward multigram-scale synthesis and the antiproliferative activity of a series of diiron cyclopentadienyl complexes containing bridging vinyliminium ligands. IC50 values in the low-to-mid micromolar range were determined against cisplatin sensitive and resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines. Notable selectivity towards the cancerous cells lines compared to the non-tumoral human embryonic kidney (HEK-293) cell line was observed for selected compounds. The activity seems to be multimodal, involving reactive oxygen species (ROS) generation and, in some cases, a fragmentation process to afford monoiron derivatives. The large structural variability, amphiphilic character and good stability in aqueous media of the diiron vinyliminium complexes provide favorable properties compared to other widely studied classes of iron-based anticancer candidates.

Ubiquity of cis-Halide → Isocyanide Direct Interligand Interaction in Organometallic Complexes.

We recently reported a density functional theory (DFT) analysis of the Nb(V)-C bond in various NbCl5(L) complexes, discovering that the carbon ligand L receives electronic density from the metal (classical back-donation) and from the chlorides in the cis position (direct interligand interaction). Here we report the synthesis and the structural characterization of two new coordination compounds of niobium pentahalides, i.e., NbX5(CNXyl) (X = Cl, Br; Xyl = 2,6-C6H3Me2), and the corresponding DFT analyses of the Nb(V)-C bond using the Natural Orbitals for Chemical Valence-Charge Displacement (NOCV-CD) approach, confirming the presence of a cis-halide → isocyanide direct interligand interaction. To verify whether the latter is limited to Nb complexes or not, we performed a NOCV-CD analysis on a series of several organometallic complexes based on Ti(IV), Nb(V), Ta(V), Rh(III), Pd(II), and Au(III), all of which bear one halide ligand and m-xylyl-isocyanide in a mutual cis position, revealing that the cis-halide → isocyanide interaction is always present.

Controlled Dissociation of Iron and Cyclopentadienyl from a Diiron Complex with a Bridging C3 Ligand Triggered by One-Electron Reduction.

The one-electron reduction of a diiron cationic complex revealed unique features: cleavage of the diiron structure occurred despite a multidentate bridging C3 ligand and was accompanied by the clean dissociation of one η5-cyclopentadienyl ring and one iron as isolated units. Thus, the iron(II)-iron(II) µ-vinyliminium complex [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C3(Et)C2HC1N(Me)(Xyl)}][SO3CF3] ([1a]SO3CF3) reacted with cobaltocene in tetrahydrofuran (THF), affording the iron(II) vinylaminoalkylidene [FeCp(CO){C1N(Me)(Xyl)C2HC3(Et)C(═O)}] (2a) in 77% yield relative to the C3 ligand. Analogously, [FeCp(CO){C1N(Me)(Xyl)C2HC3(CH2OH)C(═O)}] (2b) was obtained in 64% yield from the appropriate diiron precursor and CoCp2. The formation of 2a is initiated by the one-electron reduction of [1a]+, followed by a reversible intramolecular rearrangement terminating with the irreversible release of CpH (NMR and gas chromatography-mass spectrometry) and Fe [electron paramagnetic resonance (EPR) and magnetometry]. The key intermediate iron(I) ferraferrocene (3) was detected by EPR and IR spectroelectrochemistry, while the related species 3-H-3 was isolated after the addition of a hydrogen source and then identified by X-ray diffraction. A plausible mechanism for the route from [1a]+ to 3 was ascertained by density functional theory calculations. The dication [1a]2+, displaying both carbonyl ligands in terminal positions, and the anion [3]- were electrochemically generated. The functionalized diiron compounds 4 (52% yield) and 5 (62%) were afforded through the activation of O2 and S8 by a radical intermediate along the reductive pathway of [1a]+. The reaction of [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(SiMe3)CHCN(Me)(Xyl)}][SO3CF3] ([1c]SO3CF3) with CoCp2 in THF afforded [Fe2Cp2(C≡CSiMe3)(CO)(µ-CO){µ-CNMe(Xyl)}] (6) in 65% yield.

α-Diimines as Versatile, Derivatizable Ligands in Ruthenium(II) p-Cymene Anticancer Complexes.

α-Diimines are among the most robust and versatile ligands available in synthetic coordination chemistry, possessing finely tunable steric and electronic properties. A series of novel cationic ruthenium(II) p-cymene complexes bearing simple α-diimine ligands, [(η6- p-cymene)RuCl{κ2 N-(HCNR)2}]NO3 (R = Cy, [1]NO3; R = 4-C6H10OH, [2]NO3; R = 4-C6H4OH, [3]NO3), were prepared in near-quantitative yields as their nitrate salts. [2]NO3 displays high water solubility. The potential of the α-diimine ligand in [3]NO3 as a carrier of bioactive molecules was investigated via esterification reactions with the hydroxyl groups. Thus, the double-functionalized derivatives [(η6- p-cymene)RuCl{κ2 N-(HCN(4-C6H4OCO-R))2}]NO3 (R = aspirinate, [5]NO3; valproate, [6]NO3) and also [4]Cl (R = Me) were obtained in good-to-high yields. UV-vis and multinuclear NMR spectroscopy and cyclic voltammetric studies in aqueous solution revealed only minor ruthenium chloride hydrolytic cleavage, biologically accessible reduction potentials, and pH-dependent behavior of [3]NO3. Density functional theory analysis was performed in order to compare the Ru-Cl bond strength in [1]+ with the analogous ethylenediamine complex, showing that the higher stability observed in the former is related to the electron-withdrawing properties of the α-diimine ligand. In vitro cytotoxicity studies were performed against tumorigenic (A2780 and A2780cisR) and nontumorigenic (HEK-293) cell lines, with the complexes bearing simple α-diimine ligands ranging from inactive to IC50 values in the low micromolar range. The complexes functionalized with bioactive components, i.e., [5]NO3 and [6]NO3, exhibited a marked increase in the cytotoxicity with respect to the precursor [3]NO3.