N-heterocyclic Carbene Derivatives Research Articles

Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines.

Cu(I)–N-heterocyclic carbene complexes bearing a naphthyl substituent: synthesis, characterization, and antimicrobial activities

A series of 1-(alkyl)-3-(1-naphthyl)imidazolinium bromides (2a–d) as N-heterocyclic carbene (NHC) precursors were synthesized from 3-(1-naphthyl)-1H-imidazolinium chloride (1). By reacting these NHC precursors with fresh CuCl, Cu(I)–NHC complexes (3a–d) were synthesized. The structures of the compounds were elucidated using 1H, 13C-NMR, FT-IR, ESI-MS, X-ray diffraction, scanning electron microscopy with energy-dispersive X-ray spectroscopy analysis, and elemental analysis techniques. The thermal properties of selected complexes were determined. Salts (1, 2a–d) and Cu(I)–NHC complexes (3a–d) were investigated against test microorganisms to determine their antimicrobial potency. The imidazolinium salts 2b and 2d displayed remarkable antibacterial efficacy, particularly against gram-positive bacteria; however, the corresponding Cu(I)–NHC derivatives (3a–d) did not exhibit a similar level of potency probably due to limited solubility. Overall, it can be concluded that incorporation of N-substituent species with O-heteroatoms, instead of benzyl, allyl, or hexyl groups on NHC, can enhance the activity against microbial derivatives.

Mesomeric Betaines Based on Adamantylated 1,2,4-Triazolo[4,3-a]pyrimidin-5-ones: Synthesis, Structure and Conversion into Anionic N-Heterocyclic Carbenes.

The C-N coupling of 1,2,4-triazolo[1,5-a]pyrimidin-7-ones with 1-adamantanol/1-bromoadamantane leads to 1,2,4-triazolo[4,3-a]pyrimidinium-5-olates, which are represented as mesomeric betaines (MBs). The formation of MBs involves not only N-alkylation of heterocyclic framework but also the rearrangement leading to a change in the type of fusion between pyrimidine and 1,2,4-triazole fragments. The structures of the obtained products were confirmed by the X-ray analysis and measurements of 13 C-13 C (JCC ) coupling constants in the 1D 13 C NMR spectra of selectively 13 C-labeled samples. Treatment of the betaines with lithium bis(trimethylsilyl)amide (LiHMDS) gave anionic carbenes, which were detected by 13 C NMR spectroscopy and were trapped by reactions with phenyl isothiocyanate and sulfur. Density functional theory (DFT) and the quantum theory of atoms in molecules (QTAIM) analyses allowed for an insight into the electronic structure of the obtained betaines and N-heterocyclic carbene derivatives.

N-Heterocyclic carbene derivatives to modify gold superatom characteristics. Tailorable electronic and optical properties of [Au11(PPh3)7LCl2]+ as a cluster from relativistic DFT.

Atomically precise gold superatoms are useful building blocks whose properties can be tuned by the proper choice of ligands in the protecting ligand layer. Herein, different N-heterocyclic carbene (NHC) derivatives of the prototypical [Au11(PPh3)8Cl2]+ cluster were evaluated by the replacement of a single ligand, which led to isoelectronic [Au11(PPh3)7(NHC)Cl2]+ species, enabling further understanding of the possible changes in the resulting cluster properties. Our results reveal the great variation in the HOMO-LUMO gap and optical features when going from strong to weak σ-donor NHC ligands. The Au11 core retains similar features throughout the series, and the lowest unoccupied orbital (LUMO) is further stabilized, indicating greater π*-NHC character for the weaker σ-donor ligands, which favors directional core-ligand optical charge transfer to a single ligand. The ligand-tailored behavior of the [Au11(PPh3)7LCl2]+ cluster underlies its tunable characteristics, indicating its potential use in novel devices as building blocks of nanostructured materials, which favors further versatility and applications of superatomic clusters.

1,3‐Bis(tricyanoborane)imidazoline‐2‐ylidenate Anion—A Ditopic Dianionic N‐Heterocyclic Carbene Ligand

The 1,3‐bis(tricyanoborane)imidazolate anion 1 was obtained in high yield from lithium imidazolate and B(CN)3−pyridine adduct. Anion 1 is chemically very robust and thus allowed the isolation of the corresponding H5O2 + salt. Furthermore, monoanion 1 served as starting species for the novel dianionic N‐heterocyclic carbene (NHC), 1,3‐bis(tricyanoborane)imidazoline‐2‐ylidenate anion 3 that acts as ditopic ligand via the carbene center and the cyano groups at boron. First reactions of this new NHC 3 with methyl iodide, elemental selenium, and [Ni(CO)4] led to the methylated imidazolate ion 4, the dianionic selenium adduct 5, and the dianionic nickel tricarbonyl complex 6. These NHC derivatives provide a first insight into the electronic and steric properties of the dianionic NHC 3. Especially the combination of properties, such as double negative charge, different coordination sites, large buried volume and good σ‐donor and π‐acceptor ability, make NHC 3 a unique and promising ligand and building block.

Stable N-heterocyclic carbene derivatives of copper(i) and silver(i) containing radical anion redox active ligands

N-Heterocyclic carbene is a versatile ligand for the preparation of copper( i ) and silver( i ) derivatives bearing the radical anion forms of redox active o-benzoquinone and o-iminobenzoquinone. The paramagnetic three-coordinated copper( i ) and silver( i ) o-benzosemiquinone and o-iminobenzosemiquinone complexes were prepared and characterized by EPR spectroscopy and X-ray diffraction analysis.

New 2-hydroxyethyl substituted N-Heterocyclic carbene precursors: Synthesis, characterization, crystal structure and inhibitory properties against carbonic anhydrase and xanthine oxidase

Here, the synthesis, spectral and the structural studies of 2-hydroxyethyl substituted N-heterocyclic carbene (NHC) precursors and the enzyme inhibition activities of the NHC precursors were investigated against the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and hCA II), and xanthine oxidase (XO). The IC50 values of NHC precursors against these enzymes were determined by spectrophotometric method. The spectra of new NHC precursors have been obtained by using 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. The structure of a new NHC precursor was established by using single-crystal X-ray diffraction method. The results of inhibition experiment indicated that all 2-hydroxyethyl substituted NHC derivatives showed remarkable inhibition activity toward hCA I, hCA II and XO. The range of IC50 values for hCA I, hCA II and XO inhibition was determined as 0.1565–0.5127, 0.1524–0.5368 and 1.253–5.342 μM. Especially, trimethylbenzyl derivative of 2-hydroxyethyl substituted NHC precursor has demonstrated high inhibition effect on all studied enzymes due to steric bulk of this substituent.

Silylated Ge9 Clusters as New Ligands for Cyclic (Alkyl)amino and Mesoionic Carbene Copper Complexes.

The coordination of Ge9 Zintl clusters at (carbene)CuI moieties is explored, and the complexes [(CAAC)Cu]2[η3-Ge9{Si(TMS)3}2] (1), (CAAC)Cu[η3-Ge9{Si(TMS)3}3] (2), and (MIC)Cu[η3-Ge9{Si(TMS)3}3] (3) are compared with their known N-heterocyclic carbene (NHC) derivatives (A and B), where CAAC = cyclic (alkyl)amino carbene, MIC = mesoionic carbene, and TMS = trimethylsilane. In analogy to the NHC derivatives, the synthesis of 1-3 proceeds by single-step reactions of (CAAC)CuCl or (MIC)CuCl with the [Ge9R2]2- and [Ge9R3]- [R = Si(TMS)3] cluster ligands, respectively, and yields complexes of (carbene)CuI (carbene = CAAC, MIC) moieties exhibiting η3-coordination modes of the Ge9 deltahedron to the Cu atom. In 1, [Ge9R2]2- acts as a η3-bridging unit for two (CAAC)CuI moieties, and 2 and 3 feature single (carbene)CuI (CAAC and MIC) fragments η3-connected to [Ge9R3]- units. Analysis of the bond lengths in comparison with known examples shows a bond expansion within the coordinated Ge3 triangular faces for all (carbene)CuIGe9 complexes (carbene = NHC, MIC, CAAC). All compounds are characterized by single-crystal X-ray diffractometry, NMR spectroscopy [1H, 13C{1H}, and 29Si{1H}], electrospray ionization mass spectometry, elemental analysis (C, H, and N), and for the first time also by IR and Raman investigations (for 2 and 3). The new complexes add to the known NHC derivatives and extend the exploration of Ge9 clusters with carbene ligands at CuI atoms.

Potential of N-heterocyclic carbene derivatives from Au13(dppe)5Cl2gold superatoms. Evaluation of electronic, optical and chiroptical properties from relativistic DFT

N-heterocyclic carbene (NHC) introduction into well-defined atomically precise gold superatoms allows efficient control of structural, optical, chiroptical and emission features of the Au13Cl2core, related to the classical chiral [Au13Cl2(dppe)5]3+nanocluster.

Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular uptake and DNA-interaction

Fluorescent 4-ethylthio-1,8-naphthalimides containing rhodium(I) N-heterocyclic carbene (NHC) and ruthenium (II) NHC fragments were synthesised and evaluated for their antiproliferative effects, cellular uptake and DNA-binding activity. Both types of organometallics triggered ligand dependent efficient cytotoxic effects against tumor cells with the rhodium(I) NHC derivatives causing stronger effects than the ruthenium (II) NHC analogues. Antiproliferative effects could also be observed against several pathogenic Gram-positive bacterial strains, whereas the growth of Gram-negative bacteria was not substantially affected. Cellular uptake was confirmed by atomic absorption spectroscopy as well as by fluorescence microscopy indicating a general ligand dependent accumulation in the cells. An in-depth study on the interaction with DNA confirmed insertion of the naphthalimide moiety between the planar bases of B-DNA via an intercalation mechanism, as well as its stacking on top of the quartets of G-quadruplex structures. Furthermore, additional coordinative binding of the organometallic complexes to the model DNA base 9-ethylguanine could be detected. The studied compounds thus represent promising bioorganometallics featuring strong pharmacological effects in combination with excellent cellular imaging properties.

Synthesis and structural investigation of mono- and dimetallic N-heterocyclic carbene complexes of group VII transition metals

N-heterocyclic carbene complexes of group VII transition metals (Mn and Re) were synthesized and the electronic and structural aspects theoretically investigated. The synthesis yielded carbene complexes of type [Mx(CO)yL(NHC)] where M represents Mn or Re, x = 1, y = 4 and L = Cl, Br, I or M = Mn, x = 2, y = 9, L = CO. The synthesis of the mono- and dimetallic NHC complexes involved the substitution of labile carbonyl ligands for symmetrical and asymmetrical 1,3-disubstituted NHC ligands. Both aliphatic and aromatic N-substituent groups were incorporated into the heteroatomic, aromatic backbone of the imidazolylidene ligands. Coordination of the carbene ligand to the metal centre generated different results when comparing manganese NHC complexes to the rhenium NHC analogues. Analysis of the results indicated that only monometallic, halogenated NHC complex of Re could be synthesized and isolated, whereas the coordination of the imidazolium salts to Mn2(CO)10 produced axially substituted dimetallic carbene complexes. Spectroscopic (IR, NMR (1H and 13C) and structural (X-ray)) properties are reported and compared to those of other N-heterocyclic carbene derivatives. The structural features, coordination patterns and reactivity centres were examined to provide insight into the electronic and bonding environments of the metal-metal bond and the metal-NHC moiety.

A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs

Rhodium(I) complexes bearing N-heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry, but there are very few reports of biological properties of these organometallics. A series of Rh(I)-NHC derivatives with 1,5-cyclooctadiene and CO as secondary ligands were synthesized, characterized, and biologically investigated as prospective antitumor drug candidates. Pronounced antiproliferative effects were noted for all complexes, along with moderate inhibitory activity of thioredoxin reductase (TrxR) and efficient binding to biomolecules (DNA, albumin). Biodistribution studies showed that the presence of albumin lowered the cellular uptake and confirmed the transport of rhodium into the nuclei. Changes in the mitochondrial membrane potential (MMP) were observed as well as DNA fragmentation in wild-type and daunorubicin- or vincristine-resistant Nalm-6 leukemia cells. Overall, these studies indicated that Rh(I)-NHC fragments could be used as partial structures of new antitumor agents, in particular in those drugs designed to address resistant malignant tissues.

Covalency in CeIV and UIV Halide and N‐Heterocyclic Carbene Bonds

Oxidative halogenation with trityl chloride provides convenient access to Ce(IV) and U(IV) chloroamides [M(N{SiMe(3)}(2))(3)Cl] and their N-heterocyclic carbene derivatives, [M(L)(N{SiMe(3)}(2))(2)Cl] (L = OCMe(2)CH(2)(CNCH(2)CH(2)NDipp) Dipp = 2,6-iPr(2)C(6)H(3)). Computational analysis of the bonding in these and a fluoro analogue, [U(L)(N{SiMe(3)}(2))(2)F], provides new information on the covalency in this relative rare oxidation state for molecular cerium complexes. Computational studies reveal increased Mayer bond orders in the actinide carbene bond compared with the lanthanide carbene bond, and natural and atoms-in-molecules analyses suggest greater overall ionicity in the cerium complexes than in the uranium analogues.

Base-Promoted Tautomerization of Imidazole Ligands to N-Heterocyclic Carbenes and Subsequent Transmetalation Reaction

Imidazole complexes of manganese(I) are transformed into their corresponding N-heterocyclic carbene derivatives by means of acid−base treatments; the subsequent sequential transmetalation reaction of the carbene to gold(I) proceeds through isolable heterometallic intermediate species.

Novel Structures and Pauson−Khand Activities of N-Heterocyclic Carbene Dicobalt Complexes

N-Heterocyclic carbene derivatives of dicobalt octacarbonyl have been synthesized for the first time and tested in the Pauson−Khand reaction. Two complexes with both NHC and PPh3 ligands represent the only examples of structurally characterized dicobalt hexacarbonyl complexes with two different non-CO ligands.

Imidazolinium salts as catalysts for the ring-opening alkylation of meso epoxides by alkylaluminum complexes.

[reaction: see text] Imidazolinium salts and their N-heterocyclic carbene (NHC) derivatives catalyze the alkylation of a variety of meso epoxides in the presence of triethylaluminum (yield = 70-90%), under mild conditions. Imidazolinium salts are better catalysts than their NHC derivatives but can lead to dimerization side reactions under extended reaction time. Preformed NHC.AlEt(3) complexes and Wanzlick-type olefins, which are dimers of free NHCs, are also catalysts for this reaction.

N,N‘-Diferrocenyl-N-heterocyclic Carbenes and Their Derivatives

In continuation of our work on Wanzlick/Arduengo carbenes containing redox-active ferrocenyl substituents we report on the synthesis of N,N‘-diferrocenyl imidazol(in)ium salts as precursors of imidazol(in)-2-ylidenes. The necessary starting material for this chemistry is aminoferrocene, which was prepared by an improved and large-scale synthesis by the sequence solid lithioferrocene, iodoferrocene, N-ferrocenylphthalimide, aminoferrocene. The preparation of N,N‘-diferrocenyl heterocycles involves condensation of aminoferrocene with glyoxal to afford N,N‘-diferrocenyldiazabutadiene [Fc-DAB], reduction, condensation with formaldehyde, and oxidation with trityl salts to yield N,N‘-diferrocenylimidazol(in)ium salts. In situ deprotonation and trapping with electrophiles yielded the expected metal complexes and derivatives in some cases [Ag+ or S8], but attempted reaction with other transition metals [e.g., Pd(II)] failed to give the corresponding complexes, due to (i) steric hindrance by the two N-ferrocenyl substituents, (ii) reduced acidity of the imidazol(in)ium precursors, and (iii) inaccessibility of the free carbenes. Spectroscopic [IR, Raman, UV−vis, MS, NMR (1H, 13C, 109Ag)], structural [X-ray], and electrochemical [CV] properties are reported and compared to those of other N-heterocyclic carbene derivatives.