Search results for "N-heterocyclic carbene"

Highly Enantioselective Kinetic Resolution of Michael Adducts through N-Heterocyclic Carbene Catalysis: An Efficient Asymmetric Route to Cyclohexenes

2018

Ahighly efficient strategy for the kinetic resolu-tion of Michael adductswas realized using achiral N-het-erocyclic carbene catalyst.The kinetic resolution providesanew convenientroute to single diastereomers of cyclo-hexenes and Michael adducts in good yields with highenantiomeric excesses (up to 99 % ee with aselectivityfactor of up to 458). This “two flies with one swat” con-cept allows the synthesis of these two synthetically valua-ble compound classes at the same time by asingle trans-formation. peerReviewed

124I Radiolabeling of a AuIII‐NHC Complex for In Vivo Biodistribution Studies†

2020

Abstract AuIII complexes with N‐heterocyclic carbene (NHC) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Reported herein is the synthesis of new AuIII‐NHC complexes by direct oxidation with radioactive [124I]I2 as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET). While in vitro analyses provide direct evidence for the importance of AuIII‐to‐AuI reduction to achieve full anticancer activity, in vivo studies reveal that a fraction of the AuIII‐NHC prodrug is not immediately reduced after administration but able to reach the major…

STABILITY OF ELECTROGENERATED N-HETEROCYCLIC CARBENES FROM IONIC LIQUIDS. THE BOUNDARY CONDITIONS

Understanding the Mechanism of the Intramolecular Stetter Reaction. A DFT Study

2012

The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addi…

On the Mechanism of Gold/NHC Compounds Binding to DNA G-Quadruplexes: Combined Metadynamics and Biophysical Methods

2018

The binding modes and free-energy landscape of two AuI /N-heterocyclic carbene complexes interacting with G-quadruplexes, namely a human telomeric (hTelo) and a promoter sequence (C-KIT1), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the absolute gold complex/DNA binding free energy. This advanced in silico approach is valuable to achieve rational drug design of selective G4 binders.

N-Heterocyclic Carbenes with Inorganic Backbones: Electronic Structures and Ligand Properties

2008

The electronic structures of known N-heterocyclic carbenes (NHCs) with boron, nitrogen, and phosphorus backbones are examined using quantum chemical methods and compared to the experimental results and to the computational data obtained for a classical carbon analogue, imidazol-2-ylidene. The σ-donor and π-acceptor abilities of the studied NHCs in selected transition-metal complexes are evaluated using a variety of approaches such as energy and charge decomposition analysis, as well as calculated acidity constants and carbonyl stretching frequencies. The study shows that the introduction of selected heteroatoms into the NHC backbone generally leads to stronger metal−carbene bonds and theref…

Electronic Structures of Main-Group Carbene Analogues

2007

The electronic structures of 15 group 13−16 carbene analogues are analyzed using various quantum chemical methods and compared to the data obtained for the parent N-heterocyclic carbene (NHC), imidazol-2-ylidene. The results of this study present a uniform analysis of the similarities and differences in the electronic structures of p-block main-group carbene analogues. Though all systems are formally isovalent, the theoretical analyses unambiguously indicate that their electronic structures run the gamut from CC localized (group 13) to CN localized (group 16) via intermediate, more delocalized, systems. In particular, neither the stibenium ion nor any of the chalcogenium dications is a dire…

A σ-Donor with a Planar Six-π-Electron B2N2C2 Framework: Anionic N-Heterocyclic Carbene or Heterocyclic Terphenyl Anion?

2006

NB! The anionic ligand 2 was synthesized through deprotonation of a planar, formally zwitterionic diazadiborine precursor, isolated as a lithium salt, and structurally characterized. According to experimental evidence and theoretical calculations, 2 can be considered as an intermediate between two classical classes of ligands: N-heterocyclic carbenes 1 and terphenyls 3. peerReviewed

An Organometallic Gold(I) Bis‐N‐Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells

2020

Abstract The organometallic AuI bis‐N‐heterocyclic carbene complex [Au(9‐methylcaffeine‐8‐ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G‐quadruplex (G4) structures. This study sheds light on the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry‐based methods, including shotgun proteomics in A2780 ovarian cancer cells. In contrast to other metal‐based anticancer agents, this organogold compound is less prone to form coordinative bonds with biological nucleophiles and is expected to exert its drug effects mainly by non‐covalent interactions. Global protein expression changes of treated cancer cell…

Reactivity of antitumor coinage metal-based N-heterocyclic carbene complexes with cysteine and selenocysteine protein sites

2021

Abstract The reaction of the antitumor M(I)-bis-N-heterocyclic carbene (M(I)-NHC) complexes, M = Cu, Ag, and Au, with their potential protein binding sites, i.e. cysteine and selenocysteine, was investigated by means of density functional theory approaches. Capped cysteine and selenocysteine were employed to better model the corresponding residues environment within peptide structures. By assuming the neutral or deprotonated form of the side chains of these amino acids and by considering the possible assistance of an external proton donor such as an adjacent acidic residue or the acidic component of the surrounding buffer environment, we devised five possible routes leading to the binding o…