Bis(N-Heterocyclic Carbene) Manganese(I) Complexes in Catalytic N-Formylation/N-Methylation of Amines Using Carbon Dioxide and Phenylsilane.

A series of six Mn(I) complexes with general formula [MnBr(bisNHC)(CO)3 ], having a bidentate bis(N-heterocyclic carbene) ligand (bisNHC), has been developed by varying the bridging group between the NHC donors, the nitrogen wingtip substituents and the heterocyclic ring. The synthesis of the complexes has been accomplished by in situ transmetalation of the bisNHC from the corresponding silver(I) complexes. Removal of the bromide anion affords the corresponding solvento complexes [Mn(bisNHC)(CO)3 (CH3 CN)](BF4 ). The influence of the bisNHC structure on its electron donor ability has been evaluated by FTIR and 13 C NMR spectroscopy, both in the neutral and cationic complexes. Finally, the isolated Mn(I)-bisNHC complexes have been employed as homogeneous catalysts in the reductive N-formylation and N-methylation of amines with CO2 as C1 source and phenylsilane as reducing agent, showing a high selectivity for the N-methylated product. Preliminary mechanistic investigations suggest that, in the adopted reaction conditions, the formylated product can be formed via different reaction pathways, either metal-catalyzed or not, while the methylation reaction requires the use of the Mn(I) catalyst.

Antioxidant Chimeric Molecules: Are Chemical Motifs Additive? The Case of a Selenium-Based Ligand.

We set up an in silico experiment and designed a chimeric compound integrating molecular features from different efficient ROS (Reactive Oxygen Species) scavengers, with the purpose of investigating potential relationships between molecular structure and antioxidant activity. Furthermore, a selenium centre was inserted due to its known capacity to reduce hydroperoxides, acting as a molecular mimic of glutathione peroxidase; finally, since this organoselenide is a precursor of a N-heterocyclic carbene ligand, its Au(I) carbene complex was designed and examined. A validated protocol based on DFT (Density Functional Theory) was employed to investigate the radical scavenging activity of available sites on the organoselenide precursor ((SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)), as well as on the organometallic complex ((SMD)-M06-2X/SDD (Au), 6-311+G(d,p)//ZORA-BLYP-D3(BJ)/TZ2P), considering HAT (Hydrogen Atom Transfer) and RAF (Radical Adduct Formation) regarding five different radicals. The results of this case study suggest that the antioxidant potential of chemical motifs should not be considered as an additive property when designing a chimeric compound, but rather that the relevance of a molecular topology is derived from a chemical motif combined with an opportune chemical space of the molecule. Thus, the direct contributions of single functional groups which are generally thought of as antioxidants per se do not guarantee the efficient radical scavenging potential of a molecular species.

Dinuclear gold(I) Complexes with Bidentate NHC Ligands as Precursors for Alkynyl Complexes via Mechanochemistry.

The use of alkynyl gold(I) complexes covers different research fields, such as bioinorganic chemistry, catalysis, and material science, considering the luminescent properties of the complexes. Regarding this last application, we report here the synthesis of three novel dinuclear gold(I) complexes of the general formula [(diNHC)(Au-C≡CPh)2]: two Au-C≡CPh units are connected by a bridging di(N-heterocyclic carbene) ligand, which should favor the establishment of semi-supported aurophilic interactions. The complexes can be easily synthesized through mechanochemistry upon reacting the pristine dibromido complexes [(diNHC)(AuBr)2] with phenylacetylene and KOH. Interestingly, we were also able to isolate the monosubstituted complex [(diNHC)(Au-C≡CPh)(AuBr)]. The gold(I) species were fully characterized by multinuclear NMR spectroscopy and mass spectrometry. The emission properties were also evaluated, and the salient data are comparable to those of analogous compounds reported in the literature.

Electrochemical Investigation of Iron-Catalyzed Atom Transfer Radical Polymerization.

Use of iron-based catalysts in atom transfer radical polymerization (ATRP) is very interesting because of the abundance of the metal and its biocompatibility. Although the mechanism of action is not well understood yet, iron halide salts are usually used as catalysts, often in the presence of nitrogen or phosphorous ligands (L). In this study, electrochemically mediated ATRP (eATRP) of methyl methacrylate (MMA) catalyzed by FeCl3, both in the absence and presence of additional ligands, was investigated in dimethylformamide. The electrochemical behavior of FeCl3 and FeCl3/L was deeply investigated showing the speciation of Fe(III) and Fe(II) and the role played by added ligands. It is shown that amine ligands form stable iron complexes, whereas phosphines act as reducing agents. eATRP of MMA catalyzed by FeCl3 was investigated in different conditions. In particular, the effects of temperature, catalyst concentration, catalyst-to-initiator ratio, halide ion excess and added ligands were investigated. In general, polymerization was moderately fast but difficult to control. Surprisingly, the best results were obtained with FeCl3 without any other ligand. Electrogenerated Fe(II) effectively activates the dormant chains but deactivation of the propagating radicals by Fe(III) species is less efficient, resulting in dispersity > 1.5, unless a high concentration of FeCl3 is used.

Synthesis and Biological Studies on Dinuclear Gold(I) Complexes with Di-(N-Heterocyclic Carbene) Ligands Functionalized with Carbohydrates.

The design of novel metal complexes with N-heterocyclic carbene (NHC) ligands that display biological activity is an active research field in organometallic chemistry. One of the possible approaches consists of the use of NHC ligands functionalized with a carbohydrate moiety. Two novel Au(I)-Au(I) dinuclear complexes were synthesized; they present a neutral structure with one bridging diNHC ligand, having one or both heterocyclic rings decorated with a carbohydrate functionality. With the symmetric diNHC ligand, the dicationic dinuclear complex bearing two bridging diNHC ligands was also synthesized. The study was completed by analyzing the antiproliferative properties of these complexes, which were compared to the activity displayed by similar mononuclear Au(I) complexes and by the analogous bimetallic Au(I)-Au(I) complex not functionalized with carbohydrates.

Light-Driven Water Oxidation with the Ir-blue Catalyst and the Ru(bpy)32+/S2O82- Cycle: Photogeneration of Active Dimers, Electron-Transfer Kinetics, and Light Synchronization for Oxygen Evolution with High Quantum Efficiency.

Light-driven water oxidation is achieved with the Ru(bpy)32+/S2O82- cycle employing the highly active Ir-blue water oxidation catalyst, namely, an IrIV,IV2(pyalc)2 µ-oxo-dimer [pyalc = 2-(2'-pyridyl)-2-propanoate]. Ir-blue is readily formed by stepwise oxidation of the monomeric Ir(III) precursor 1 by the photogenerated Ru(bpy)33+, with a quantum yield ϕ of up to 0.10. Transient absorption spectroscopy and kinetic evidence point to a stepwise mechanism, where the primary event occurs via a fast photoinduced electron transfer from 1 to Ru(bpy)33+, leading to the Ir(IV) monomer I1 (k1 ∼ 108 M-1 s-1). The competent Ir-blue catalyst is then obtained from I1 upon photooxidative loss of the Cp* ligand and dimerization. The Ir-blue catalyst is active in the Ru(bpy)32+/S2O82- light-driven water oxidation cycle, where it undergoes two fast photoinduced electron transfers to Ru(bpy)33+ [with kIr-blue = (3.00 ± 0.02) × 108 M-1 s-1 for the primary event, outperforming iridium oxide nanoparticles by ca. 2 orders of magnitude], leading to a IrV,V2 steady-state intermediate involved in O-O bond formation. The quantum yield for oxygen evolution depends on the photon flux, showing a saturation regime and reaching an impressive value of ϕ(O2) = 0.32 ± 0.01 (corresponding to a quantum efficiency of 64 ± 2%) at low irradiation intensity. This result highlights the key requirement of orchestrating the rate of the photochemical events with dark catalytic turnover.

Possible Synthetic Approaches for Heterobimetallic Complexes by Using nNHC/tzNHC Heteroditopic Carbene Ligands.

The synthesis of heterobimetallic complexes remains a synthetic challenge in the field of organometallic chemistry. A possible approach in this regard might be the use of a bidentate heteroditopic bis(carbene) ligand that combines an imidazol-2-ylidene (nNHC) with a 1,2,3-triazol-5-ylidene (tzNHC) connected by an organic spacer. The optimized strategy to heterobimetallic complexes with this type of ligand involves a 3-step procedure: (i) Coordination of the nNHC, functionalized with a 1,2,3-triazole ring, to a metal center; (ii) formation of the triazolium ring by alkylation of the triazole N-3; (iii) deprotonation of the tzNHC precursor and coordination of the second metal center. Following this procedure, a novel Au(I)-Ag(I) dinuclear complex was isolated and its properties were compared to the analogous homobimetallic Ag(I)-Ag(I) and Au(I)-Au(I) complexes. The study was completed by the determination of the molecular structures of some synthetic intermediates.

Insights into the Halogen Oxidative Addition Reaction to Dinuclear Gold(I) Di(NHC) Complexes.

Gold(I) dicarbene complexes [Au2 (MeIm-Y-ImMe)2 ](PF6 )2 (Y=CH2 (1), (CH2 )2 (2), (CH2 )4 (4), MeIm=1-methylimidazol-2-ylidene) react with iodine to give the mixed-valence complex [Au(MeIm-CH2 -ImMe)2 AuI2 ](PF6 )2 (1 a(I) ) and the gold(III) complexes [Au2 I4 (MeIm-Y-ImMe)2 ](PF6 )2 (2 c(I) and 4 c(I) ). Reaction of complexes 1 and 2 with an excess of ICl allows the isolation of the tetrachloro gold(III) complexes [Au2 Cl4 (MeIm-CH2 -ImMe)2 ](PF6 )2 (1 c(Cl) ) and [Au2 Cl4 (MeIm-(CH2 )2 -ImMe)2 ](Cl)2 (2 c(Cl) -Cl) (as main product); remarkably in the case of complex 2, the X-ray molecular structure of the crystals also shows the presence of I-Au-Cl mixed-sphere coordination. The same type of coordination has been observed in the main product of the reaction of complexes 3 or 4 with ICl. The study of the reactivity towards the oxidative addition of halogens to a large series of dinuclear bis(dicarbene) gold(I) complexes has been extended and reviewed. The complexes react with Cl2 , Br2 and I2 to give the successive formation of the mixed-valence gold(I)/gold(III) n a(X) and gold(III) n c(X) (excluding compound 1 c(I) ) complexes. However, complex 3 affords with Cl2 and Br2 the gold(II) complex 3 b(X) [Au2 X2 (MeIm-(CH2 )3 -ImMe)2 ](PF6 )2 (X=Cl, Br), which is the predominant species over compound 3 c(X) even in the presence of free halogen. The observed different relative stabilities of the oxidised complexes of compounds 1 and 3 have also been confirmed by DFT calculations.

Advances in Transition-Metal-Catalysed Alkyne Hydroarylations.

We present herein a personal account of our achievements in the development of novel catalytic systems based on late-transition-metal complexes for the hydroarylation of alkynes. In particular, our targets were intermolecular hydroarylation reactions with arene or heteroarene substrates devoid of directing groups. We have shown that complexes of palladium, platinum or gold with N-heterocyclic carbene (NHC) ligands can be particularly useful catalysts for this reaction; the NHC ligand imparts greater stability to the complex and renders the catalytic system more productive. Furthermore, we have identified promoters and reaction media that allow to significantly improve the catalytic activity under mild conditions, to control the reaction chemoselectivity and to steer it towards more complex products; thus making this reaction considerably more attractive for the synthetic chemist.

Insights on the Anion Effect in N-heterocyclic Carbene Based Dinuclear Gold(I) Catalysts.

Dinuclear bisNHC (bis(N-heterocyclic carbene)) gold(I) complexes 3 a and 4 a of general formula [Au2 Br2 (bisNHC)] were tested as catalysts in the cycloisomerization of N-(prop-2-yn-1-yl)benzamide and in the hydromethoxylation of 3-hexyne in the presence of silver(I) activators bearing different counteranions. The catalytic performance of mononuclear NHC complexes (1 a, 2 a) in the same reactions was also studied. The results highlighted the fundamental role of both NHC ligand and counterion in the catalytic cycles and activation process: dinuclear catalysts exhibit higher initial activity even under milder conditions but suffer in terms of stability with respect to mono NHCs. Furthermore, a new dinuclear bisNHC gold(I) complex 4 b of general formula [Au2 (OTs)2 (bisNHC)] (OTs=p-toluenesulfonate) was successfully synthesized and characterized by means of NMR and ESI-MS analyses.

Synthesis and characterization of Pt(II) and Au(I) complexes with N-oxy-heterocyclic carbene ligands (NOHCs).

Two N-alkyloxy-N'-phenylimidazolium proligands and the corresponding platinum(II) cyclometalated N-alkyloxyimidazol-2-ylidene complexes with ß-diketonate auxiliary ligands, [(CNOHC^C*)Pt(L∩L)] (L∩L = acetyacetonate (acac) or 1,3-bis(2,4,6-trimethylphenyl)-propane-1,3-dionato (mesacac)) were synthesized and fully characterized. In addition, a Au(I) monocarbene complex was synthesized, isolated and characterized. Solid-state structures of two cyclometalated platinum(II) NOHC complexes and the Au(I) NOHC complex were obtained providing structural proof.

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts.

Mono- and dinuclear gold complexes with N-heterocyclic carbene (NHC) ligands have been employed as catalysts in the intermolecular hydroarylation of alkynes with simple unfunctionalised arenes. Both mono- and dinuclear gold(III) complexes were able to catalyze the reaction; however, the best results were obtained with the mononuclear gold(I) complex IPrAuCl. This complex, activated with one equivalent of silver tetrafluoroborate, exhibited under acidic conditions at room temperature much higher catalytic activity and selectivity compared to more commonly employed palladium(II) catalysts. Moreover, the complex was active, albeit to a minor extent, even under neutral conditions, and exhibited lower activity but higher selectivity compared to the previously published complex AuCl(PPh(3)). Preliminary results on intramolecular hydroarylations using this catalytic system indicate, however, that alkyne hydration by traces of water may become a serious competing reaction.

Blue-emitting dinuclear N-heterocyclic dicarbene gold(I) complex featuring a nearly unit quantum yield.

Dinuclear N-heterocyclic dicarbene gold(I) complexes of general formula [Au(2)(RIm-Y-ImR)(2)](PF(6))(2) (R = Me, Cy; Y = (CH(2))(1-4), o-xylylene, m-xylylene) have been synthesized and screened for their luminescence properties. All the complexes are weakly emissive in solution whereas in the solid state some of them show significant luminescence intensities. In particular, crystals or powders of the complex with R = Me, Y = (CH(2))(3) exhibit an intense blue emission (λ(max) = 450 nm) with a high quantum yield (Φ(em) = 0.96). The X-ray crystal structure of this complex is characterized by a rather short intramolecular Au···Au distance (3.272 Ǻ). Time dependent density functional theory (TDDFT) calculations have been used to calculate the UV/vis properties of the ground state as well as of the first excited state of the complex, the latter featuring a significantly shorter Au···Au distance.

Dinuclear gold(I) complexes with N-phosphanyl, N-heterocyclic carbene ligands: synthetic strategies, luminescence properties and anticancer activity.

A small library of dinuclear gold(I) complexes with the title ligands has been prepared, encompassing neutral, mono- and dicationic complexes. The luminescence properties of the complexes in the solid state have been evaluated, and it turns out that neutral and monocationic complexes not presenting a rigid metallamacrocyclic structure can exhibit rather strong emissions that extend towards the red region of the visible spectrum. The in vitro anticancer activity of the complexes has been also preliminarly evaluated; cytotoxicity seems to correlate with complex lipophilicity, whereas selectivity towards cancer cells can be apparently enhanced upon a judicious choice of the ligands.

Effect of the Sulfonation on the Swollen State Morphology of Styrenic Cross-Linked Polymers.

The chemical structure and morphology of a set of sulfonic gel-type poly(styrene-divinylbenzene) resins (2 mol% DVB) prepared with different synthetic approaches were investigated by solid state NMR, Inverse Size Exclusion Chromatography (ISEC), FT-IR and elemental analysis to compare their swollen state structure. FT-IR and solid state NMR clearly show that the sulfonation mainly occurs in the para- position with respect the main polymer chain. Sensible proportions of sulfone bridges were found in the materials obtained with oleum and chlorosulfonic acid. With oleum, the presence of the sulfone bridges is clearly associated to a reduced ability to swell in the water medium relative to the proton exchange capacity. This highlights the cross-linking action of the sulfone bridges according to ISEC results, showing a high proportion of a dense polymer fraction in the swollen material. An even higher degree of sulfone-bridging, lower swelling ability, and a high proportion of a dense polymer fraction in the swollen material are found in the resin obtained with chlorosulfonic acid. As a matter of fact, Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (CP-MAS 13C-NMR), elemental analysis, and ion exchange capacity, show that oleum and chlorosulfonic acid produced resins with remarkably smaller pores and lower swollen gel volume in polar solvents, with respect to concentrated sulfuric acid.

Novel iridium complexes with N-heterocyclic dicarbene ligands in light-driven water oxidation catalysis: photon management, ligand effect and catalyst evolution.

Iridium complexes [IrClCp*diNHC]PF6, with N-heterocyclic dicarbene (diNHC) and pentamethylcyclopentadienyl (Cp*) ligands, have been investigated in light driven water oxidation catalysis within the Ru(bpy)32+/S2O82- cycle (bpy = 2,2'-bipyridine). In particular, the effect of different diNHC ligands was evaluated by employing the complex 1a (diNHC = 1,1'-dimethyl-3,3'-ethylenediimidazol-2,2'-diylidene) and the novel and structurally characterised 2 (diNHC = 1,1'-dimethyl-3,3'-ethylene-5,5'-dibromodiimidazol-2,2'-diylidene) and 3 (diNHC = 1,1'-dimethyl-3,3'-ethylene-dibenzimidazol-2,2'-diylidene). The presented results include: (i) a photon management analysis of the 1a/Ru(bpy)32+/S2O82- system, revealing two regimes of O2 evolution rate, being dependent on the light intensity at low photon flux, where the system reaches an overall quantum yield up to 0.17 ± 0.01 (quantum efficiency 34 ± 2%), while being independent of light intensity at high photon flux thus indicating a change of limiting step; (ii) a trend of O2 evolution activity that follows the order 1a > 2 > 3 both under low and high photon flux conditions, with the reactivity that is favoured by the electron donating nature of the diNHC ligand, quantified on the basis of the carbene carbon chemical shift; (iii) an analogous trend also in the bimolecular rate constants of electron transfer kET from the iridium species to photogenerated Ru(bpy)33+, with kET values in the range 4.2-6.1 × 104 M-1 s-1, thus implying a significant reorganisation energy to the iridium sphere; (iv) the evolution of 1a, as the most active Ir species in the series, to mononuclear iridium species with lower molecular weight and originating from oxidative transformation of the organic ligand scaffold, as proven by converging UV-Vis, MALDI-MS and 1H-NMR evidences. These results can be used for the further design and engineering of novel catalysts.

Reactions of diazo compounds with alkenes catalysed by [RuCl(cod)(Cp)]: effect of the substituents in the formation of cyclopropanation or metathesis products.

The reaction of diazo compounds with alkenes catalysed by complex [RuCl(cod)(Cp)] (cod = 1,5-cyclooctadiene, Cp = cyclopentadienyl) has been studied. The catalytic cycle involves in the first step the decomposition of the diazo derivative to afford the reactive [RuCl(Cp){=C(R(1))R(2)}] intermediate and a mechanism is proposed for this step based on a kinetic study of the simple coupling reaction of ethyl diazoacetate. The evolution of the Ru-carbene intermediate in the presence of alkenes depends on the nature of the substituents at both the diazo N(2)=C(R(1))R(2) (R(1), R(2) = Ph, H; Ph, CO(2)Me; Ph, Ph; C(R(1))R(2) = fluorene) and the olefin substrates R(3)(H)C=C(H)R(4) (R(3), R(4) = CO(2)Et, CO(2)Et; Ph, Ph; Ph, Me; Ph, H; Me, Br; Me, CN; Ph, CN; H, CN; CN, CN). A remarkable reactivity of the complex was recorded, especially towards unstable aryldiazo compounds and electron-poor olefins. The results obtained indicate that either cyclopropanation or metathesis products can be formed: the first products are favoured by the presence of a cyano substituent at the double bond and the second ones by a phenyl.

Structural and Luminescent Properties of Homoleptic Silver(I), Gold(I), and Palladium(II) Complexes with nNHC-tzNHC Heteroditopic Carbene Ligands.

Novel silver(I), gold(I), and palladium(II) complexes were synthesized with bidentate heteroditopic carbene ligands that combine an imidazol-2-ylidene (nNHC) with a 1,2,3-triazol-5-ylidene (tzNHC) connected by a propylene bridge. The silver(I) and gold(I) complexes were dinuclear species, [M2(nNHC-tzNHC)2](PF6)2 (M = Ag or Au), with the two bidentate ligands bridging the metal centers, whereas in the palladium(II) complex [Pd(nNHC-tzNHC)2](PF6)2, the two ligands were chelated on the same metal center. Because of the presence of two different carbene units, isomers were observed for the gold(I) and palladium(II) complexes. The molecular structures of the head-to-tail isomer for gold(I) complexes, with a twisted or folded-syn conformation of the bridge between the carbene units, were determined by X-ray diffraction analysis. The study was completed with a systematic structural investigation through density functional theory (DFT) calculations. For palladium(II) species, the head-to-head form was structurally characterized. The dinuclear gold(I) complexes were emissive in the solid state in the blue region (PLQY up to 8%); time-dependent density functional theory (abbreviated as TD-DFT) calculations disclosed that the absorption bands have metal-to-ligand-charge-transfer character and evidenced that the emission occurs from the T1 level (phosphorescence).

Psychiatric Disorders and Oxidative Injury: Antioxidant Effects of Zolpidem Therapy disclosed In Silico.

Zolpidem (N,N-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide) is a well-known drug for the treatment of sleeping disorders. Recent literature reports on positive effects of zolpidem therapy on improving renal damage after cisplatin and on reducing akinesia without sleep induction. This has been ascribed to the antioxidant and neuroprotective capacity of this molecule, and tentatively explained according to a generic structural similarity between zolpidem and melatonin. In this work, we investigate in silico the antioxidant potential of zolpidem as scavenger of five ROSs, acting via hydrogen atom transfer (HAT) mechanism; computational methodologies based on density functional theory are employed. For completeness, the analysis is extended to six metabolites. Thermodynamic and kinetic results disclose that indeed zolpidem is an efficient radical scavenger, similarly to melatonin and Trolox, supporting the biomedical evidence that the antioxidant potential of zolpidem therapy may have a beneficial effect against oxidative injury, which is emerging as an important etiopathogenesis in numerous severe diseases, including psychiatric disorders.

A square planar gold(iii) bis-(1,1'-dimethyl-3,3'-methylene-diimidazol-2,2'-diylidene) trication as an efficient and selective receptor towards halogen anions: the cooperative effect of AuX and XHC interactions.

Treatment of the tricationic gold(iii) [Au(MeImCH2ImMe)2](PF6)3 complex 1-3PF6 (Im = imidazol-2-ylidene) with excess halides affords complexes 1-3X (X = Cl, Br, and I), resulting from counter anion PF6-/X- exchange. The 1H chemical shift of the CH3 groups and particularly that of the CH2 linker in DMSO-d6 are different in the three complexes, thus suggesting selective XHC interactions. Complex 13+ can therefore be used as a halide sensor in DMSO and water. The host-guest interaction between the tricationic gold(iii) complex and the halides Cl-, Br- and I- in solution and in the solid state has been investigated by means of NMR titration experiments, DFT calculations and X-ray structure analysis. The electrostatic interaction between the halides and the triple formal positive charge on the metal centre, together with the CHX hydrogen bonding between the NHC ligand and halides, contributes to the formation of stable supramolecular aggregates in solution and in the solid state. The complexing properties of 13+ are strongly influenced by the nature of the solvent. Formation of the 1 : 1 and 1 : 2 species (1X2+ and 1X2+) is observed in DMSO-d6, while that of only the 1 : 1 aggregates (1X2+) is observed in D2O (X = Cl, Br, and I). Moreover, the selectivity towards the various halides is reversed in the two solvents, being in the order Cl- > Br- > I- in DMSO-d6 and I- > Br- > Cl- in D2O. The formation constants of the species 1X2+ and 1X2+ in DMSO and 1X2+ in water have been determined by fitting the NMR titration curves.