Anthony Deally

Bio: Anthony Deally is an academic researcher from University College Dublin. The author has contributed to research in topics: Cyclopentadienyl complex & Titanocene dichloride. The author has an hindex of 13, co-authored 25 publications receiving 687 citations.

Novel benzyl-substituted N-heterocyclic carbene–silver acetate complexes: synthesis, cytotoxicity and antibacterial studies

Abstract: From the reaction of 1-methylimidazole (1a), 4,5-dichloro-1H-imidazole (1bII) and 1-methylbenzimidazole (1c) with p-cyanobenzyl bromide (2a), non-symmetrically substituted N-heterocyclic carbene (NHC) [(3a–c)] precursors, 5,6-dimethyl-1H-benzimidazole (1d) and 4,5-diphenyl-1H-imidazole (1e) with p-cyanobenzyl bromide (2a) and benzyl bromide (2b), symmetrically substituted N-heterocyclic carbene (NHC) [(3d–f)] precursors were synthesised. These NHC-precursors were then reacted with silver(I) acetate to yield the NHC–silver complexes (1-methyl-3-(4-cyanobenzyl)imidazole-2-ylidene)silver(I)acetate (4a), (4,5-dichloro-1-(4-cyanobenzyl)-3-methyl)imidazole-2-ylidene)silver(I)acetate (4b), (1-methyl-3-(4-cyanobenzyl)benzimidazole-2-ylidene)silver(I)acetate (4c), (1,3-bis(4-cyanobenzyl)5,6-dimethylbenzimidazole-2-ylidene) silver(I) acetate (4d), (1,3-dibenzyl-5,6-dimethylbenzimidazole-2-ylidene) silver(I) acetate (4e) and (1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene) silver(I) acetate (4f) respectively. Three NHC-precursors 3c–e and four NHC–silver complexes 4b and 4d–f were characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial activity of the NHC-precursors and NHC–silver complexes was investigated against Gram-positive bacteria Staphylococcus aureus, and Gram-negative bacteria Escherichia coli using the qualitative Kirby–Bauer disk-diffusion method. NHC–silver complexes have shown very high antibacterial activity compared to the NHC-precursors. All six NHC–silver complexes were tested for their cytotoxicity through MTT based in vitro tests on the human renal-cancer cell line Caki-1 in order to determine their IC50 values. NHC–silver complexes 4a–f were found to have IC50 values of 6.2 (±1.0), 7.7 (±1.6), 1.2 (±0.6), 10.8 (±1.9), 24.2 (±1.8) and 13.6 (±1.0) μM, respectively. These values represent improved cytotoxicity against Caki-1, most notably for 4c, which is a three times more cytotoxic than cisplatin (IC50 value = 3.3 μM) itself.

Synthesis, Cytotoxicity and Antibacterial Studies of p-Methoxybenzyl-Substituted and Benzyl-Substituted N-Heterocyclic Carbene-Silver Complexes

Abstract: p-Methoxybenzyl-substituted and benzyl-substituted N-heterocyclic carbene (NHC) [(3a-c) and (6a-c)] precursors were synthesised from the reaction of 1H-imidazole (1a), 4,5-dichloro-1H-imidazole (1b), and 1H-benzimidazole (1c) with p-methoxybenzyl bromide (2) and benzyl bromide (5). These NHC precursors were then treated with silver(I) acetate to yield the NHC-silver complexes [1,3-bis(4-methoxybenzyl)-imidazol-2-ylidene]silver(I) acetate (4a), [4,5-dichloro-1,3-bis(4-methoxybenzyl)imidazol-2-ylidene]silver(I) acetate (4b), [1,3-bis(4-methoxybenzyl)benzimidazol-2-ylidene]-silver(I) acetate (4c), (1,3-dibenzylimidazol-2-ylidene)silver(I) acetate (7a), (1,3-dibenzyl-4,5-dichloroimidazol-2-ylidene)-silver(I) acetate (7b), and (1,3-dibenzylbenzimidazol-2-ylidene)silver(I) acetate (7c), respectively. The NHC precursor 3c, four NHC-silver complexes 4c and 7a-c were characterised by single-crystal X-ray diffraction method. The preliminary antibacterial activity of all the compounds was studied against Gram-negative bacteria Escherichia coli, and Gram-positive bacteria Staphylococcus aureus using the Kirby-Bauer disk-diffusion method. Almost all the NHC-silver complexes have shown high antibacterial activity compared to the NHC precursors. In addition, the NHC-silver complexes had their cytotoxicity investigated through MTT-based preliminary in vitro testing on the Caki-1 cell lines in order to determine their IC 50 values. NHC-silver complexes 4a-c and 7a-c were found to have IC 50 values of 7.3 (+/-6), 12.7 (+/-3), 25.2 (+/-5), 2.5 (+/-3), 10.8 (+/-4) and 12.5 (+/-4) μM respectively on the Caki-1 cell line.

Synthesis, cytotoxicity and antibacterial studies of symmetrically and non‐symmetrically benzyl‐ or p‐cyanobenzyl‐substituted N‐Heterocyclic carbene–silver complexes

Abstract: From the reaction of 1H-imidazole (1a), 4,5-dichloro-1H-imidazole (1b) and 1H-benzimidazole (1c) with p-cyanobenzyl bromide (2), symmetrically substituted N-heterocyclic carbene (NHC) [(3a–c)] precursors, 1-methylimidazole (5a), 4,5-dichloro-1-methylimidazole (5b) and 1-methylbenzimidazole (5c) with benzyl bromide (6), non-symmetrically substituted N-heterocyclic carbene (NHC) [(7a–c)] precursors were synthesized. These NHCprecursors were then reacted with silver(I) acetate to yield the NHC-silver complexes [1,3-bis(4-cyanobenzyl)imidazole-2-ylidene] silver(I) acetate (4a), [4,5-dichloro-1,3-bis(4-cyanobenzyl)imidazole-2-ylidene] silver(I) acetate (4b), [1,3-bis(4-cyanobenzyl)benzimidazole-2-ylidene] silver(I) acetate (4c), (1-methyl-3-benzylimidazole-2-ylidene) silver(I) acetate (8a), (4,5-dichloro-1-methyl-3-benzylimidazole-2-ylidene) silver(I) acetate (8b) and (1-methyl-3-benzylbenzimidazole-2-ylidene) silver(I) acetate (8c) respectively. The four NHC-precursors 3a–c, 7c and four NHC–silver complexes 4a–c and 8c were characterized by single crystal X-ray diffraction. The preliminary antibacterial activity of all the compounds was studied against Gram-negative bacteria Escherichia coli, and Gram-positive bacteria Staphylococcus aureus using the qualitative Kirby-Bauer disc-diffusion method. All NHC–silver complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 4 to 12 mm at the highest amount used, while the NHC-precursors showed significantly lower activity. In addition, all NHC–silver complexes underwent preliminary cytotoxicity tests on the human renal-cancer cell line Caki-1 and showed medium to high cytotoxicity with IC50 values ranging from 53 ( ± 8) to 3.2 ( ± 0.6) µM. Copyright © 2010 John Wiley & Sons, Ltd.

Synthesis, Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Nonsymmetrically 4-(Methoxycarbonyl)benzyl-Substituted N-Heterocyclic Carbene–Silver Acetate Complexes

Abstract: From the reaction of 1H-imidazole (1a), 4,5-dichloro-1H-imidazole (1b), 1H-benzimidazole (1c), 1-methyl-1H-imidazole (1d), and 1-methyl-1H-benzimidazole (1f) with methyl 4-(bromomethyl)benzoate (2), symmetrically and nonsymmetrically 4-(methoxycarbonyl)benzyl-substituted N-heterocyclic carbene (NHC) precursors, 3a–3f, were synthesized. These NHC precursors were then reacted with silver(I) acetate (AgOAc) to yield the NHC–silver acetate complexes (acetato-κO){1,3-bis[4-(methoxycarbonyl)benzyl]imidazol-2-ylidene}silver (4a), (acetato-κO){4,5-dichloro-1,3-bis[4-(methoxycarbonyl)benzyl]-2,3-dihydro-1H-imidazol-2-yl}silver (4b), (acetato-κO){1,3-bis[4-(methoxycarbonyl)benzyl]-2,3-dihydro-1H-benzimidazol-2-yl}silver (4c), (acetato-κO){1-[4-(methoxycarbonyl)benzyl]-3-methyl-2,3-dihydro-1H-imidazol-2-yl}silver (4d), (acetato-κO){4,5-dichloro-1-[4-(methoxycarbonyl)benzyl]-3-methyl-2,3-dihydro-1H-imidazol-2-yl}silver (4e), and (acetato-κO){1-[4-(methoxycarbonyl)benzyl]-3-methyl-2,3-dihydro-1H-benzimidazol-2-yl}silver (4f), respectively. The three NHC–AgOAc complexes 4a, 4c, and 4d were characterized by single-crystal X-ray diffraction. All compounds studied in this work were preliminarily screened for their antimicrobial activities in vitro against Gram-positive bacteria Staphylococcus aureus, and Gram-negative bacteria Escherichia coli using the qualitative disk-diffusion method. All NHC–AgOAc complexes exhibited weak-to-medium antibacterial activity with areas of clearance ranging from 4 to 7 mm at the highest amount used, while the NHC precursors showed significantly lower activity. In addition, NHC–AgOAc complexes 4a and 4b, and 4d–4f exhibited in preliminary cytotoxicity tests on the human renal-cancer cell line Caki-1 medium-to-high cytotoxicities with IC50 values ranging from 3.3±0.4 to 68.3±1 μM.

Synthesis, Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Non-Symmetrically p-Nitrobenzyl-Substituted N-Heterocyclic Carbene–Silver(I) Acetate Complexes

Abstract: From the reaction of 1H-imidazole (1a), 4,5-dichloro-1H-imidazole (1b), 1H-benzimidazole (1c), 1-methylimidazole (1d), 4,5-dichloro-1-methylimidazole (1e) and 1-methylbenzimidazole (1f) with p-nitrobenzyl bromide (2), symmetrically and non-symmetrically p-nitrobenzyl-substituted N-heterocyclic carbene (NHC) [(3a–f)] precursors were synthesised. These NHC-precursors were then reacted with silver(I) acetate to yield the NHC-silver acetate complexes [1,3-bis(4-nitrobenzyl)imidazol-2-ylidene]silver(I) acetate (4a), [4,5-dichloro-1,3-bis(4-nitrobenzyl)imidazol-2-ylidene]silver(I) acetate (4b), [1,3-bis(4-nitrobenzyl)benzimidazol-2-ylidene]silver(I) acetate (4c), [1-methyl-3-(4-nitrobenzyl)imidazole-2-ylidene] silver(I) acetate (4d), [4,5-dichloro-1-methyl-3-(4-nitrobenzyl)imidazole-2-ylidene] silver(I) acetate (4e) and [1-methyl-3-(4-nitrobenzyl)benzimidazole-2-ylidene] silver(I) acetate (4f), respectively. The two NHC–silver(I) acetate complexes 4a and 4e were characterised by single-crystal X-ray diffraction. All compounds studied in this work were preliminary screened for their antimicrobial activities in vitro against Gram-positive bacteria Staphylococcus aureus, and Gram-negative bacteria Escherichia coli using the qualitative Kirby–Bauer disk-diffusion method. All NHC–silver(I) acetate complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 3 to 7 mm at the highest amount used, whereas the NHC-precursors showed significantly lower activity. In addition, NHC–silver(I) acetate complexes 4a–f had their preliminary cytotoxicity tests on the human renal-cancer cell line Caki-1 and showed medium to high cytotoxicity with IC50 values ranging from 15 (+/–1) to 27 (+/–2) μM.

Organometallic Anticancer Compounds

Abstract: The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed.1,2 Despite their tremendous success, these platinum compounds suffer from two main disadvantages: they are inefficient against platinum-resistant tumors, and they have severe side effects such as nephrotoxicity. The latter drawback is the consequence of the fact that the ultimate target of these drugs is ubiquitous: It is generally accepted that Pt anticancer drugs target DNA, which is present in all cells.3,4 Furthermore, as a consequence of its particular chemical structure, cisplatin in particular offers little possibility for rational improvements to increase its tumor specificity and thereby reduce undesired side effects. In this context, organometallic compounds, which are defined as metal complexes containing at least one direct, covalent metal−carbon bond, have recently been found to be promising anticancer drug candidates. Organometallics have a great structural variety (ranging from linear to octahedral and even beyond), have far more diverse stereochemistry than organic compounds (for an octahedral complex with six different ligands, 30 stereoisomers exist!), and by rational ligand design, provide control over key kinetic properties (such as hydrolysis rate of ligands). Furthermore, they are kinetically stable, usually uncharged, and relatively lipophilic and their metal atom is in a low oxidation state. Because of these fundamental differences compared to “classical coordination metal complexes”, organometallics offer ample opportunities in the design of novel classes of medicinal compounds, potentially with new metal-specific modes of action. Interestingly, all the typical classes of organometallics such as metallocenes, half-sandwich, carbene-, CO-, or π-ligands, which have been widely used for catalysis or biosensing purposes, have now also found application in medicinal chemistry (see Figure ​Figure11 for an overview of these typical classes of organometallics). Figure 1 Summary of the typical classes of organometallic compounds used in medicinal chemistry. In this Perspective, we report on the recent advances in the discovery of organometallics with proven antiproliferative activity. We are emphasizing those compounds where efforts have been made to identify their molecular target and mode of action by biochemical or cell biology studies. This Perspective covers more classes of compounds and in more detail than a recent tutorial review by Hartinger and Dyson.(5) Furthermore, whereas recent reviews and book contributions attest to the rapid development of bioorganometallic chemistry in general,6,7 this Perspective focuses on their potential application as anticancer chemotherapeutics. Another very recent review article categorizes inorganic anticancer drug candidates by their modes of action.(8) It should be mentioned that a full description of all currently investigated types of compounds is hardly possible anymore in a concise review. For example, a particularly promising class of organometallic anticancer compounds, namely, radiolabeled organometallics, has been omitted for space limitations. Recent developments of such compounds have been reviewed in detail by Alberto.(9)

Beyond catalysis: N-heterocyclic carbene complexes as components for medicinal, luminescent, and functional materials applications.

Abstract: This tutorial review compiles the advances that have been achieved in using transition metal complexes containing N-heterocyclic carbene ligands as components for materials. Applications of metal carbene complexes in fields different from catalysis are remarkably scarce. During the last few years, promising results have been accomplished in particular by utilizing such complexes as antimicrobial and cytotoxic agents, as photoactive sites in luminescent materials, for self-assembly into liquid crystalline materials and metallosupramolecular structures, and as synthons for molecular switches and conducting polymeric materials. These initial achievements clearly underline the great potential of N-heterocyclic carbene complexes in various fields of materials science.

Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs

Abstract: The discovery of cisplatin's antitumor activity in 1969 prompted the search for novel metal-containing complexes as potential anticancer drugs. Among these novel complexes, metal N-heterocyclic carbene (NHC) complexes have recently gained considerable attention because they perfectly fit prerequisites for efficient drug design and fast optimization. Moreover, most of them have shown higher cytotoxicity than cisplatin. This review describes the advances that have been achieved in using transition metal (Ag, Au, Pt, Pd, Cu, Ni, and Ru) complexes containing NHC ligands as antitumor agents. Their modes of action at the cellular lever are further discussed. All these initial achievements clearly demonstrate the great potential of metal–NHC complexes as antitumor agents.