Tuning the Steric and Electronic Properties of Hemilabile NHC ligands for Gold(I/III) Catalyzed Oxyarylation of Ethylene: A Computational Study.

Mechanistic studies on 1,2-oxyarylation of ethylene promoted by gold catalysts bearing hemilabile N-Heterocyclic Carbene (NHC^X) ligands were conducted by DFT calculations, exploring the whole catalytic cycle. After highest energy transition state (TS) barriers were located for NHC^N gold catalyst, and experimental results with different iodoarenes and alcohols rationalized, the study was extended to modified NHC^X catalysts, to observe how electronic and steric effects could affect the rate determining step TS. Electronic effects were investigated on NHC^X (X=H, N, O, P, and S), whereas steric effects emerged when comparing catalysts with different N-R groups (R=Dipp, Mes, tBu and Me).

1,2,3-Triazole-Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid-State Studies.

Two new chiral 1,2,3-triazole-containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid-phase synthesis of linear precursors followed by high dilution macrocyclization reaction.

Hydroamination of alkynes catalyzed by NHC-Gold(I) complexes: the non-monotonic effect of substituted arylamines on the catalyst activity.

Imines are valuable key compounds for synthesizing several nitrogen-containing molecules used in biological and industrial fields. They have been obtained, as highly regioselective Markovnikov products, by reacting several alkynes with arylamines in the presence of three new N-Heterocyclic carbene gold(I) complexes (, and ) together with the known and gold complexes as well as silver complexes . Gold(I) complexes were investigated by means of NMR, mass spectroscopy, elemental analysis, and X-ray crystallographic studies.

NHC-Ag(I) and NHC-Au(I) Complexes with -Boc-Protected α-Amino Acidate Counterions Powerfully Affect the Growth of MDA-MB-231 Cells.

-Heterocyclic carbene (NHC) metal complexes are attracting scientists' interest as an alluring class of metallodrugs. Indeed, the versatile functionalization of NHC ligands makes them optimal scaffolds to be developed in medicinal chemistry. Besides, amino acids are great biological ligands for metals, such as silver and gold, even though their use is still under-investigated.

Macrocyclic Triazolopeptoids: A Promising Class of Extended Cyclic Peptoids.

Head-to-tail cyclization of linear oligoamides containing 4-benzylaminomethyl-1-1,2,3-triazol-1-yl acetic acid monomers afforded a novel class of "extended macrocyclic peptoids". The identification of the conformation in solution for a cyclodimer and the X-ray crystal structure of a cyclic tetraamide are reported.

N-Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin.

In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue.

Structural dynamism of chiral sodium peraza-macrocycle complexes derived from cyclic peptoids.

A variety of cyclen and hexacyclen derivatives decorated with (S)-1-phenylethyl side chains or (S)-pyrrolidine units have been prepared via a reductive approach from the corresponding cyclic peptoids containing N-(S)-(1-phenylethyl)glycine and l-proline residues. Spectroscopic and DFT studies on their Na complexes show that point chirality and ring size play a crucial role in controlling the structural dynamism of 1,2-diaminoethylene units and pendant arms. The detection of highly symmetric C- and C-symmetric metalated species demonstrates that a full understanding of the relationship between the structure and conformational properties of peraza-macrocyclic metal complexes is possible.

Peptoid-based siderophore mimics as dinuclear Fe chelators.

A practical synthesis of preorganized tripodal enterobactin/corynebactin-type ligands (consisting of a C-symmetric macrocyclic peptoid core, three catecholamide coordinating units, and C, C, and C spacers) is reported. The formation of complexes with Fe was investigated by spectrophotometric (UV-Vis) and spectrometric (ESI, negative ionization mode) methods and corroborated by theoretical (DFT) calculations. Preliminary studies revealed the intricate interplay between the conformational chirality of cyclic trimeric peptoids and metal coordination geometry of mononuclear species similar to that of natural catechol-based siderophores.

Reverse Turn and Loop Secondary Structures in Stereodefined Cyclic Peptoid Scaffolds.

Controlling the network of intramolecular interactions encoded by α-chiral side chains and the equilibria between cis- and trans-amide junctions in cyclic peptoid architectures constitutes a significant challenge for the construction of stable reverse turn and loop structures. In this contribution, we reveal, with the support of NMR spectroscopy, single-crystal X-ray crystallography and density functional theory calculations, the relevant noncovalent interactions stabilizing tri-, tetra-, hexa-, and octameric cyclic peptoids (as free hosts and host-guest complexes) with strategically positioned -()-(1-phenylethyl)/-benzyl side chains, and how these interactions influence the backbone topological order. With the help of theoretical models and spectroscopic/diffractometric studies, we disclose new γ-/β-turn and loop structures present in α-peptoid-based macrocycles and classify them according ϕ, ψ, and ω torsion angles.

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands.

An overview on the catalytic properties of ruthenium complexes for olefin metathesis bearing monodentate unsymmetrical N-heterocyclic diaminocarbene ligands is provided. The non-symmetric nature of these NHC architectures strongly influences activity and selectivity of the resulting catalysts. The main achievements that have been accomplished in significant areas of olefin metathesis up to the current state of research are discussed.

Cation-Induced Molecular Switching Based on Reversible Modulation of Peptoid Conformational States.

Peptoids are oligomers of N-substituted glycines with predictable folding and strong potentials as guest-binding receptor molecules. In this contribution, we investigate the structural features of a series of designed symmetric cyclic octamer peptoids (with methoxyethyl/propargyl side chains) as free hosts and reveal their morphologic changes in the presence of sodium and alkylammonium guests as tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts, reporting the first case of reversible adaptive switching between defined conformational states induced by cationic guests (Na and benzylammonium ion) in the peptoid field. The reported results are based on H NMR data, theoretical models, and single-crystal X-ray diffraction analysis.

Cyclic Octamer Peptoids: Simplified Isosters of Bioactive Fungal Cyclodepsipeptides.

Cyclic peptoids have recently emerged as an important class of bioactive scaffolds with unique conformational properties and excellent metabolic stabilities. In this paper, we describe the design and synthesis of novel cyclic octamer peptoids as simplified isosters of mycotoxin depsipeptides bassianolide, verticilide A1, PF1022A and PF1022B. We also examine their complexing abilities in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB) salt and explore their general insecticidal activity.

Stable ruthenium olefin metathesis catalysts bearing symmetrical NHC ligands with primary and secondary N-alkyl groups.

Four novel stable Hoveyda-Grubbs-type catalysts containing N,N'-dineopentyl- and N,N'-dicyclohexyl-substituted N-heterocyclic carbene (NHC) ligands with syn and anti phenyl groups on the ring backbone were synthesized and fully characterized. The catalytic potential of these complexes was investigated in metathesis reactions of both standard and renewable substrates. Compared to the Hoveyda-Grubbs second generation catalyst (HGII), all of the new catalysts showed high performances in most of the examined metathesis transformations.

Cyclic Peptoids as Topological Templates: Synthesis via Central to Conformational Chirality Induction.

Chiral induction was utilized for the synthesis of diastereopure cyclic peptoids containing an N-benzyl alanine residue. Molecular modeling, NMR spectroscopy, single-crystal X-ray diffraction studies, and HPLC with chiral stationary phase demonstrated easy formation of free and sodium/benzylammonium complexed cyclic oligomers through strategic incorporation of a single stereogenic center in the oligomeric backbone. The synthesis of cyclic peptoids with defined conformational chirality and appropriate side chain topology is now possible.

Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties.

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins.

NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis.

The catalytic properties of olefin metathesis ruthenium complexes bearing N-heterocyclic carbene ligands with stereogenic centers on the backbone are described. Differences in catalytic behavior depending on the backbone configurations of symmetrical and unsymmetrical NHCs are discussed. In addition, an overview on asymmetric olefin metathesis promoted by chiral catalysts bearing C₂-symmetric and C₁-symmetric NHCs is provided.

Ruthenium olefin metathesis catalysts featuring unsymmetrical N-heterocyclic carbenes.

New ruthenium Grubbs' and Hoveyda-Grubbs' second generation catalysts bearing N-alkyl/N-isopropylphenyl N-heterocyclic carbene (NHC) ligands with syn or anti backbone configuration were obtained and compared in model olefin metathesis reactions. Different catalytic efficiencies were observed depending on the size of the N-alkyl group (methyl or cyclohexyl) and on the backbone configuration. The presence of an N-cyclohexyl substituent determined the most significant reactivity differences between catalysts with syn or anti phenyl groups on the backbone.

Study of the activity of Grubbs catalyst-functionalized multiwalled carbon nanotubes in the ring opening metathesis polymerization.

The synthesis of polynorbornene by ring opening metathesis polymerization (ROMP), in the presence of 1st and 2nd generation Grubbs catalyst-functionalized multiwalled carbon nanotubes (MWCNT), has been studied. MWCNTs were obtained by catalytic chemical vapour deposition (CCVD) of ethylene. A full characterization of the 1st and 2nd generation Grubbs catalyst-functionalized nanotubes was performed by FTIR and TG-DTG-MS.

The pivotal role of symmetry in the ruthenium-catalyzed ring-closing metathesis of olefins.

The synthesis of Ru-based precatalysts with N-heterocyclic carbene (NHC) ligands bearing syn- and anti-methyl groups on the NHC backbone and aryl N-substituents with differing steric bulk was carried out. The catalytic behavior of the monophospine Ru precatalysts (7a, 7b, 8a, and 8b) was compared to the corresponding family of phosphine-free catalysts (9a, 9b, 10a and 10b) in the ring-closing metathesis (RCM) of olefins. These catalysts showed high efficiency in RCM reactions and the syn-isomers 7a and 9a, in particular, proved to be among the most active catalysts in the formation of tetrasubstituted olefins through RCM.

Gold- and platinum-catalyzed cycloisomerization of enynyl esters versus allenenyl esters: an experimental and theoretical study.

Ester-way to heaven: Unexpected formation of bicyclo[3.1.0]hexene 4 was the main focus of combined experimental and theoretical studies on the Au-catalyzed cycloisomerization of branched dienyne 1 (see scheme), which provided better understanding of the mechanistic details governing the cyclization of enynes bearing a propargylic ester group.

Identification and characterization of a new family of catalytically highly active imidazolin-2-ylidenes.

A new class of easily accessible and stable imidazolin-2-ylidenes has been synthesized where the side chains are comprised of substituted naphthyl units. Introduction of the naphthyl groups generates C 2 -symmetric ( rac) and C s- symmetric ( meso) atropisomers, and interconversion between the isomers is studied in detail both experimentally and computationally. Complete characterization of the carbenes includes rare examples of crystallographically characterized saturated NHC structures.

Steric and electronic properties of N-heterocyclic carbenes (NHC): a detailed study on their interaction with Ni(CO)4.

N-heterocyclic carbene ligands IMes (1), SIMes (2), IPr (3), SIPr (4), and ICy (5) react with Ni(CO)(4) to give the saturated tricarbonyl complexes Ni(CO)(3)(IMes) (8), Ni(CO)(3)(SIMes) (9), Ni(CO)(3)(IPr) (10), Ni(CO)(3)(SIPr) (11), and Ni(CO)(3)(ICy) (12), respectively. The electronic properties of these complexes have been compared to their phosphine analogues of general formula Ni(CO)(3)(PR(3)) by recording their nu(CO) stretching frequencies. While all of these NHCs are better donors than tertiary phosphines, the differences in donor properties between ligands 1-5 are surprisingly small.

Origin of enantioselectivity in the asymmetric Ru-catalyzed metathesis of olefins.

The mechanism of enantioselectivity in the asymmetric Ru-catalyzed metathesis of olefins is investigated with a theoretical approach. The models are based on the chiral N-heterocyclic (NHC)-based catalysts developed by Grubbs. Our analysis indicates that the origin of enantioselectivity in the ring-closing metathesis of achiral trienes is correlated to the chiral folding of the N-bonded aromatic groups, which is imposed by the Ph groups in positions 4 and 5 of the imidazole ring of the NHC ligand.