Designing organometallic compounds for catalysis and therapy

Bioorganometallic chemistry is a rapidly developing area of research. In recent years organometallic compounds have provided a rich platform for the design of effective catalysts, e.g. for olefin metathesis and transfer hydrogenation. Electronic and steric effects are used to control both the thermodynamics and kinetics of ligand substitution and redox reactions of metal ions, especially Ru(II). Can similar features be incorporated into the design of targeted organometallic drugs? Such complexes offer potential for novel mechanisms of drug action through incorporation of outer-sphere recognition of targets and controlled activation features based on ligand substitution as well as metal- and ligand-based redox processes. We focus here on η(6)-arene, η(5)-cyclopentadienyl sandwich and half-sandwich complexes of Fe(II), Ru(II), Os(II) and Ir(III) with promising activity towards cancer, malaria, and other conditions.     

High-resolution investigation of the excited electronic states of CaSH and SrSH by laser excitation spectroscopy – ARTICLE WITHDRAWN

WITHDRAWN TO APPEAR IN SPECIAL ISSUE IN 2007     

Racemization of secondary alcohols catalyzed by ruthenium: application to chemoenzymatic dynamic resolution

In this paper, we have shown that the [RuCl₂(p-cymene)]₂ complex associated with simple hemisalen ligands is able to racemize (S)-1-phenylethanol. The influence on the racemization process of the ligand’s structure as well as the nature of a co-catalyst have been evaluated and optimized. This [RuCl₂(p-cymene)]₂/Ligand/TEMPO racemization system was then associated with the Candida Antarctica B lipase in order to carry out dynamic kinetic resolution experiments on rac-phenylethanol. This led us to identify the best conditions for effective DKR, which was then applied to various secondary benzylic and aliphatic alcohols. It was thus possible to obtain (R)-1-cyclohexylethyl acetate from rac-1-cyclohexylethanol in quantitative conversion and with high enantioselectivity (98%).     

Preparation of porous manganese oxide nanomaterials by one-pot synthetic sol–gel method

For the first time, the simple epoxide addition, sol–gel method has been employed to successfully prepare porous, high surface area manganese (II) aerogel nanomaterials. These uniform materials can then undergo calcination at relatively low temperature to selectively yield the mixed-valent Mn₃O₄ complex illustrating both an ease of preparation and synthesis versatility.     

Wigner optics in the metaxial regime

A consistent methodology is developed, using the Wigner matrix associated with the Helmholtz equation, to treat metaxial optical systems. The propagation equation of this matrix is derived and its relationship with the corresponding paraxial propagation equation is clarified.     

The thermodynamics and kinetics of the proton-transfer reactions between bromophenol blue and some aromatic amines in aprotic solution

The equilibria and the stopped-flow kinetics of the reaction between the acid bromophenol blue (BPB) and several aromatic amines in toluene to form ion pairs have been investigated. Contrary to expectations, the rate of the proton-transfer increases with increasing activation enthalpy. This is explained in terms of the entropy of the transition state. The role of the electronic structure of the amine and of the solvent are discussed. Solvent effects were further investigated by comparing the activation parameters for the reaction between BPB and pyridine in chlorobenzene, toluene, and benzene. The solvent clearly plays a vital role in determining the rate of proton-transfer via the entropy of activation. The mechanism of the reaction (that proton-transfer is almost complete in the transition state, and is followed by amine migration and ring opening) is confirmed. © 1993 John Wiley & Sons, Inc.     

First synthesis and structural determination of a monomeric, unsolvated lithium amide, LiNH(2)

Alkali metal amides typically aggregate in solution and the solid phase, and even in the gas phase. In addition, even in the few known monomeric structures, the coordination number of the alkali metal is raised by binding of Lewis-basic solvent molecules, with concomitant changes in structure. In contrast, the simplest lithium amide LiNH(2) has never been made in a monomeric form, even though its structure has been theoretically predicted several times. Here, the first experimental structural data for a monomeric, unsolvated lithium amide are determined using a combination of gas-phase synthesis and millimeter/submillimeter-wave spectroscopy. All data point to a planar structure for LiNH(2). The r(o) structure of LiNH(2) has a Li-N distance of 1.736(3) A, an N-H distance of 1.022(3) A, and a H-N-H angle of 106.9(1) degrees. These results are compared with theoretical predictions for LiNH(2), and experimental data for oligomeric, solid-phase samples, which could not resolve the question of whether LiNH(2) is planar or not. In addition, comparisons are made with revised gas-phase and solid-phase data and calculated structures of NaNH(2).     

Finding multiactivity substructures by mining databases of drug-like compounds

We have developed a method, given a database of molecules and associated activities, to identify molecular substructures that are associated with many different biological activities. These may be therapeutic areas (e.g. antihypertensive) and/or mechanism-based activities (e.g. renin inhibitor). This information helps us avoid chemical classes that are likely to have unanticipated side effects and also can suggest combinatorial libraries that might have activity on a variety of receptor targets. The method was applied to the USPDI and MDDR databases. There are clearly substructures in each database that occur in many compounds and span a variety of therapeutic categories. Some of these are expected, but some are not.