Claire A. Tessier

The medicinal applications of imidazolium carbene-metal complexes.

Ofele and Wanzlick reported the synthesis of the first N-heterocyclic carbene (NHC) metal complexes in 1968.1,2 The isolation of the first free carbene by Arduengo in 1991 set the scene for an ever-growing interest and advancement in the field of N-heterocyclic carbene chemistry.3 Shortly thereafter, the use of these ligands in organometallic chemistry, particularly in catalysis dramatically increased.4,5 N-heterocyclic carbenes are neutral 2-electron donors, with an ability to bond to both hard and soft metals making them more versatile ligands than phosphines.6 As an added advantage, not only are NHCs easier to synthesize and functionalize than phosphines but they also form a stronger bond to metals and therefore form more stable metal complexes than metal phosphine complexes.7,8 The N-heterocyclic carbene ligands interact with metal centers primarily through strong σ-donation and to a lesser degree through π-backdonation (Figure 1).9,10 Figure 1 Orbital diagram of NHC bonding to metal center. Ghosh and coworkers11,12,13,14,15,16 as well as others17,18,19 took special interest in the exceptional stability of several metal-NHC complexes and conducted in depth analyses in order to gain better insights into the structure and bonding. In particular, the metal-ligand donor-acceptor interactions were inspected using the charge decomposition analysis (CDA). CDA is a tool used to quantitatively estimate the degree of NHC → metal σ-donation, designated by d, and NHC ← metal π-back donation, designated by b.20,21 Thus a higher d/b ratio emphasizes the ability of NHC to function as an effective σ-donor, whereas a lower d/b ratio highlights the greater NHC ← metal π-back donation. Interestingly, in the studies conducted by Ghosh, greater NHC ← metal π-back donation was observed in Pd-NHC complexes exhibiting lower d/b ratios ranging between 2.59 – 3.9913,14 and Au-NHC complexes with d/b ratios ranging between 5.23 – 5.8815,16 as compared to the Ag-NHC complexes with d/b ratios ranging between 7.8 – 12.6811,12,16. This observation could attest to why silver-NHC complexes are particularly better transmetallating agents. The newly emerging interest in the medicinal applications of stable metal NHCs led us to examine the few accounts available in the literature dealing with this area of research. This review will discuss in detail the medicinal applications of various transition metal-NHC complexes including silver, gold, rhodium, ruthenium, and palladium. The antimicrobial, antitumor, and resistance properties, along with proposed mechanisms of action to suppress the bacterial growth or proliferation of tumor cells will be discussed.

Synthesis, Stability, and Antimicrobial Studies of Electronically Tuned Silver Acetate N-Heterocyclic Carbenes

A series of methylated imidazolium salts with varying substituents on the 4 and 5 positions of the imidazole ring were synthesized. These salts were reacted with silver acetate to afford their corresponding silver N-heterocyclic carbene (NHC) complexes. These complexes were then evaluated for their stability in water as well as for their antimicrobial efficacy against a variety of bacterial strains associated with cystic fibrosis and chronic lung infections.

Synthesis and structural characterization of a [Ag4]4+ cluster stabilized by a mixed-donor N-heterocyclic carbene linked cyclophane and the first reported synthesis of a N-heterocyclic carbene complex in water

Abstract The synthesis of the tetranuclear Ag44+ cluster stabilized by a N-heterocyclic carbene macrocycle (3)[PF6]4. Decomposition of the tetranuclear cluster (3)[PF6]4 in light forms the dimeric species (2)[PF6]2. In situ synthesis of the dimeric silver N-hetrocyclic carbene complex (2)[Br]2 in water.

Predicting the crystal structure of organic molecular materials

This paper describes a novel method for predicting the crystal structure of organic molecular materials which employs a series of successive approximations to focus on structures of high probability, without resorting to a brute force search and energy minimization of all possible structures. The problem of multiple local minima is overcome by assuming that the crystal structure is closely packed, thereby eliminating 217 of the 230 possible space groups. Configurations within the 13 remaining space groups are searched by rotating the reference molecule about Cartesian axes in rotational increments of 15°. Initial energy minimization is performed using (6–12) Lennard–Jones pair potentials to produce a set of closely packed structures. The structures are then refined with the introduction of a Coulombic potential calculated using molecular multipole moments. This method has successfully located local minima which correspond to the observed crystal structures of several saturated and unsaturated hydro-C atoms with no a priori information provided. For large polycyclic aromatic hydrocarbons, additional refinements of the energy calculations are required to distinguish the experimental structure from a small number of closely packed structures. Our methodology for a priori crystal structure prediction represents the most efficient algorithm presented to date, in a field where the first successes have only been described within the past year and have been few and far between. Since our algorithm is capable of locating a large number of reasonable structures with similar energy in a short period of time, and is more likely to locate a minimum corresponding to the experimental structure, our program provides a superior framework to determine the level of theory required to calculate the intermolecular potential. For all but highly asymmetric hydrocarbons, however, distinguishing the observed structure from a large number of highly probable structures requires more rigorously calculated intermolecular interactions than pair potentials, plus an ad hoc electrostatic potential, and is thus beyond the scope of this paper. All calculations were performed on the Ohio Supercomputer Centers Cray Y-MP.

Synthesis and structural characterization of two bis(imidazol-2-ylidene) complexes of Pt(II)

The air stable syntheses of two new chelating N-heterocyclic carbene complexes of Pt(II), bis(1,1′- n -butylimidazolium)-3,3′-methylenePtI 2 ( 2 ) and bis[bis(1,1′- n -butylimidazolium)-3,3′-methylene]PtI 2 ( 3 ) are described.

Synthesis, characterization, and antimicrobial activity of silver carbene complexes derived from 4,5,6,7- tetrachlorobenzimidazole against antibiotic resistant bacteria †

Silver N-heterocyclic carbene complexes have been shown to have great potential as antimicrobial agents, affecting a wide spectrum of both Gram-positive and Gram-negative bacteria. A new series of three silver carbene complexes (SCCs) based on 4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested against a panel of clinical strains of bacteria. The imidazolium salts and their precursors were characterized by elemental analysis, mass spectrometry, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. The silver carbene complexes, SCC32, SCC33, and SCC34 were characterized by elemental analysis, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. These complexes proved highly efficacious with minimum inhibitory concentrations (MICs) ranging from 0.25 to 6 μg mL(-1). Overall, the complexes were effective against highly resistant bacteria strains, such as methicillin-resistant Staphylococcus aureus (MRSA), weaponizable bacteria, such as Yersinia pestis, and pathogens found within the lungs of cystic fibrosis patients, such as Pseudomonas aeruginosa, Alcaligenes xylosoxidans, and Burkholderia gladioli. SCC33 and SCC34 also showed clinically relevant activity against a silver-resistant strain of Escherichia coli based on MIC testing.

PREPARATION OF CARBOSILANE DENDRIMERS AND THEIR CHARACTERIZATION USING 1H/13C/29SI TRIPLE RESONANCE 3D NMR METHODS

In this paper we show the utility of 1H/13C/29Si triple resonance, 3D, and pulse field gradient (PFG) NMR techniques for characterizing organosilicon based polymers. The dendrimers studied are first generation Si(CH2CH2SiHMe2)4 and second generation Si[CH2CH2SiMe(CH2CH2SiHMe2)2 ]4 polycarbosilanes. The signals from one-bond and two-bond connectivities among 1H atoms coupled to both 13C and 29Si at natural abundance have been selectively detected. The spectral dispersion and the atomic connectivity information present in the 3D NMR spectra provide resonance assignments and a definitive structure proof.

Synthesis and structural characterization of two bis-imidazolium-linked cyclophanes: precursors toward ‘carbeneporphyrinoid’ ligands

Abstract The synthesis and spectroscopic characterization of the imidazolium-linked cyclophanes [ 1 ][PF6]2 and [ 2 ][PF6]2 are described. Cyclophane [ 1 ][PF6]2 contains two imidazolium rings bridged by a 2,6-bis(methyl)-pyridine unit and a 2,5-bis(methyl)-pyrrole unit. Cyclophane [ 2 ][PF6]2 contains two imidazolium rings bridged by two 2,5-bis(methyl)-pyrrole units. Cyclophanes [ 1 ][PF6]2 and [ 2 ][PF6]2 have been structurally characterized by X-ray crystallography.

Synthesis and characterization of the sterically hindered iridium(III)–silyl complex: (Et3P)3(H)2Ir[Si(H)Cl(C6H3-Mes2-2,6)] and the generation of the cationic iridium(III)-silylene complex: [(Et3P)3(H)2IrSi(H)(C6H3-Mes2-2,6)][B(C6F5)4]

The oxidative addition reaction of (Et 3 P) 3 IrCl with H 3 Si(C 6 H 3 -Mes 2 -2,6) (Mes = 2,4,6-trimethylphenyl) affords the sterically hindered iridium(III)-silyl complex (Et3P) 3 (H) 2 Ir[Si(H)Cl(C 6 H 3 -Mes 2 -2,6)] (1) via a H/Cl exchange reaction at silicon. Complex 1 is characterized by 1 H-, 1 3 C-, 3 1 P-, and 2 9 Si-NMR and IR spectroscopy. The solid state structure of 1 is determined by X-ray crystallography. Complex 1 undergoes a halide abstraction reaction with LiB(C 6 F 5 ) 4 (OEt 2 ) to afford the cationic iridium(III)-silylene complex [(Et 3 P) 3 (H) 2 Ir=Si(H)(C 6 H 3 -Mes 2 -2,6)][B(C 6 F 5 ) 4 ] (4). Complex 4 is characterized by 1 H-, 1 3 C-, 3 1 P-, and 2 9 Si-NMR spectroscopy.

Synthesis and structural characterization of a silver complex of a mixed-donor N-heterocyclic carbene linked cyclophane

The synthesis of a dicationic imidazolium-linked cyclophane and a dimeric silver-N-heterocyclic carbene complex, that is the first silver complex with a N-heterocyclic carbene ligand involved in a pi-bonding interaction, is reported.