Synthesis of ruthenium catalysts with chiral arene ligand derived from natural camphor

Ruthenium complex with chiral arene ligand [(camphor-arene)RuCl2]2 was synthesized by the reaction of RuCl3∙nH2O with the chiral diene, which was obtained from natural camphor in 3 steps. This complex catalyzed asymmetric hydrogenation of acetophenone (64-85% ee), but decomposed in the catalytic reactions involving C-H activation of 2-phenyl-pyridine or benzoic acid derivatives.

Fine Tuning of Cholinesterase and Glutathione-S-Transferase Activities by Organoruthenium(II) Complexes

Cholinesterases (ChEs) show increased activities in patients with Alzheimer’s disease, and remain one of the main therapeutic targets for treatment of this neurodegenerative disorder. A library of organoruthenium(II) complexes was prepared to investigate the influence of their structural elements on inhibition of ChEs, and on another pharmacologically important group of enzymes, glutathione S-transferases (GSTs). Two groups of organoruthenium(II) compounds were considered: (i) organoruthenium(II) complexes with p-cymene as an arene ligand, and (ii) organoruthenium(II) carbonyl complexes as CO-releasing molecules. Eight organoruthenium complexes were screened for inhibitory activities against ChEs and GSTs of human and animal origins. Some compounds inhibited all of these enzymes at low micromolar concentrations, while others selectively inhibited either ChEs or GSTs. This study demonstrates the importance of the different structural elements of organoruthenium complexes for their inhibitory activities against ChEs and GSTs, and also proposes some interesting compounds for further preclinical testing as ChE or GST inhibitory drugs.

Weak arene/nickel interaction lights on monoarylation of alcohols

Despite a growing body of work in nickel catalysis, the potential of organo-photocatalyst serving both as an arene ligand and a sensitizer remains underexplored. Here, we describe such an organo-photocatalyst to promote arylation of alcohols. Mechanistic studies suggest that the formation of sandwich complex via weak arene/nickel interaction and the resulting dexter energy transfer be responsible for this activity. This interaction provides a mechanistically alternative strategy for challenging carbon-oxygen bond assembly, where the elementary steps in transition metal catalysis previously facilitated by intermolecular photoevents replaced by more efficient intramolecular ones. With only 0.05 mol% photocatalyst loading and 8 mol% nickel bromide, a series of alcohols, diols and triols were (mono)arylated with (hetero)aryl bromides and chlorides. Importantly, many bioactive molecules and active pharmaceutical ingredients containing multiple hydroxyl groups could be efficiently monoarylated, too. This work provides a new approach to access bioactive aryl ethers, but also lights on a highly desirable direction to manipulate the catalytic reactivity of earth abundant nickel.

Assembly of polyoxometalate-thiacalix[4]arene-based inorganic–organic hybrids as efficient catalytic oxidation desulfurization catalysts

Three POM-thiacalix[4]arene-based organic–inorganic hybrids have been achieved by applying a tetrazole-functionalized thiacalix[4]arene ligand. Hybrids (1) and (3) exhibited efficient catalytic abilities for oxidation desulfurization reactions.

Terpyridine-Functionalized Calixarenes: Synthesis, Characterization and Anion Sensing Applications

Lanthanide complexes have been developed and are reported herein. These complexes were derived from a terpyridine-functionalized calix[4]arene ligand, chelated with Tb3+ and Eu3+. Synthesis of these complexes was achieved in two steps from a calix[4]arene derivative: (1) amide coupling of a calix[4]arene bearing carboxylic acid functionalities and (2) metallation with a lanthanide triflate salt. The ligand and its complexes were characterized by NMR (1H and 13C), fluorescence and UV-vis spectroscopy as well as MS. The photophysical properties of these complexes were studied; high molar absorptivity values, modest quantum yields and luminescence lifetimes on the ms timescale were obtained. Anion binding results in a change in the photophysical properties of the complexes. The anion sensing ability of the Tb(III) complex was evaluated via visual detection, UV-vis and fluorescence studies. The sensor was found to be responsive towards a variety of anions, and large binding constants were obtained for the coordination of anions to the sensor.

A New Scaffold for Molecular Design: The Preparative Scale-Syntheses of Ru- Centered Arene Compounds

Carbon centered molecules have been very well recognized in the past for both academic and industrial purposes. Utilizing inert element instead of carbon atom could bring more molecular complexity as well as potential binding in medicinal chemistry. We report, herein, a number of strategies for the syntheses of Ru-centered molecules starting from commercially available [RuCl2(η6-p-cymene)] dimer substituted phenyl-heterocycles via Concerted Metalation Deprotonation (CMD) processes. Halogen atom ligand exchange and arene ligand exchange from the skeleton have been achieved. Under such procedures, a collectively good number of (26) Ru-arene complexes have been prepared efficiently. The Ru-complexes prepared have covered broad spectrum of functional groups on the 4 possible positions. Moreover, the Suzuki coupling reaction on the Ru-centered complex was realized with good yield (90%). The access of a library of these compounds would allow molecular chemists to consider the utilization of these molecules rather than purely organometallic reagents for inorganic chemistry or catalysis.

Synthesis, Crystal Structure, and Biological Activity of a Multidentate Calix[4]arene Ligand Doubly Functionalized by 2-Hydroxybenzeledene-Thiosemicarbazone

The design and synthesis of a novel tert-butyl-calix[4]arene functionalized at 1, 3 positions of the lower rim with two terminal 2-hydroxybenzeledene-thiosemicarbazone moieties is reported. The new ligand with multi-dentate chelating properties was fully characterized by several techniques: ESI-Mass spectroscopy, FT-IR, 1H-NMR, and single crystal X-ray diffraction. The solid state structure confirms that the calix[4]arene macrocycle has the expected open cone conformation, with two opposite phenyl rings inclined outwards with large angles. The conformation of the two alkoxythiosemicarbazone arms produces a molecule with a C2 point group symmetry. An interesting chiral helicity is observed, with the two thiosemicarbazone groups oriented in opposite directions like a two-blade propeller. A water molecule is encapsulated in the center of the two-blade propeller through multiple H-bond coordinations. The antibacterial, antifungal, anticancer, and cytotoxic activities of the calix[4]arene-thiosemicarbazone ligand and its metal derivatives (Co2+, Ni2+, Cu2+, and Zn2+) were investigated. A considerable antibacterial activity (in particular against E. coli, MIC, and MBC = 31.25 μg/mL) was observed for the ligand and its metal derivatives. Significant antifungal activities against yeast (C. albicans) were also observed for the ligand (MIC = 31.25 μg/mL and MBC = 125 μg/mL) and for its Co2+ derivative (MIC = 62.5 μg/mL). All compounds show cytotoxicity against the tested cancerous cells. For the Saos-2 cell line, the promising anticancer activity of ligand L (IC50 < 25 μg/mL) is higher than its metal derivatives. The microscopic analysis of DAPI-stained cells shows that the treated cells change in morphology, with deformation and fragmentation of the nuclei. The hemo-compatibility study demonstrated that this class of compounds are suitable candidates for further in vivo investigations.

The Application of Reversible Intramolecular Sulfonamide Ligation to Modulate Reactivity in Organometallic Ruthenium(II) Diamine Complexes

Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5ʹ-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner.