Marie-Noëlle Rager

A sol–gel matrix to preserve the viability of encapsulated bacteria

E. coli bacteria were encapsulated within silica gels and aged at room temperature in the absence of nutrients. Their viability was studied as a function of time using different viability tests. The plate count technique gives the number of culturable bacteria that remain able to form colonies in the presence of a culture medium. Their metabolic activity toward glycolysis was followed by 14C titration and 13C NMR spectroscopy. Several sol–gel matrices were tested in order to improve the viability of the trapped bacteria. The best results were obtained when encapsulation is performed in the presence of glycerol showing that almost 50% of the bacteria were still able to form metabolites after one month of ageing. Moreover, this study demonstrates that a wide range of viability tests can be adapted for use with cells encapsulated in mineral matrices.

Calixarene‐Based Copper(I) Complexes as Models for Monocopper Sites in Enzymes

A cavity that acts as a molecular funnel is formed from calix[6]arene 1 and [CuI (NCCH3 )4 ]PF6 [Eq. (a)]. An exchange of the well-protected acetonitrile ligand for other nitriles RCN is only possible with small R groups. The protection of the copper ions precludes oxidative dimerization; thus, the complexes mimic the mononuclear site of copper enzymes.

Biomimetic Copper(I)–CO Complexes: A Structural and Dynamic Study of a Calix[6]arene-Based Supramolecular System

Four novel calix[6]arene-based cuprous complexes are described. They present a biomimetic tris(imidazole) coordination core associated with a hydrophobic cavity that wraps the apical binding site. Each differs from the other by the methyl or ethyl substituents present on the phenoxyl groups (OR1) and on the imidazole arms (NR2) of the calix[6]arene structure. In solution, stable CO complexes were obtained. We have investigated their geometrical and dynamic properties with respect to the steric demand. IR and NMR studies revealed that, in solution, these complexes adopted two distinct conformations. The preferred conformation was dictated only by the size of the OR1 group. When R1 was an ethyl group, the complex preferentially adopted a flattened C3-symmetrical structure. The corresponding helical enantiomers were in conformational equilibrium, which, however, was slow on the 1H NMR time scale at -80 degrees C. When R1 was a methyl group, the low-temperature NMR spectra revealed the partial inclusion of one tBu group. The complex wobbled between three dissymmetric but equivalent conformations. Hence, small differences in the steric demand of the calixarenes skeleton changed the geometry and dynamics of the system. Indeed, this supramolecular control was promoted by the strong conformational coupling between the metal center and the host structure. Interestingly, this was not only the result of a covalent preorganization, but also stemmed from weak interactions within the hydrophobic pocket. The vibrational spectra of the bound CO were revealed to be a sensitive gauge of this supramolecular behavior, similar to copper proteins in which allosteric effects are common.

Selective estrogen-receptor modulators (SERMs) in the cyclopentadienylrhenium tricarbonyl series: Synthesis and biological behaviour

A series of organometallic antiestrogens based on the OH‐tamoxifen (OH‐Tam) skeleton and bearing the (η5‐C5H4)ReI(CO)3 unit has been prepared by using McMurry coupling for the purpose of studying their biological behaviour. The cyclopentadienylrhenium tricarbonyl moiety is indeed stable in biological media, compact, lipophilic and easy to handle. Furthermore, this study allowed us to select the best candidates for subsequent use as radiopharmaceuticals either for imaging or therapy by using appropriate radionucleides, namely 99mTc and 188Re. In these molecules the β‐phenyl group of OH‐Tam has been replaced by the (η5‐C5H4)Re(CO)3 moiety, and the length of the dimethylamino side chain O(CH2)nN(CH3)2 was varied (n=2, 3, 4, 5 and 8). The compounds 7 a–7 e were obtained as mixtures of their Z and E isomers, which could be separated by semipreparative HPLC. Unlike their ferrocene homologues, the compounds do not isomerise in solution. Structural identification was carried out with NMR spectroscopy by using the HMBC and NOE techniques and was confirmed by the X‐ray structural determination of (E)‐7 a (n=2). These molecules were more lipophilic than OH‐Tam (log Po/w=4.5–6.3) and they were all reasonably well recognized by the two forms of the estrogen receptor (ERα and ERβ). For example, (Z)‐7 b (n=3) has high relative binding affinity (RBA) values of 31 % for ERα and 16.8 % for ERβ. The antiproliferative effects of two pairs of isomers, (Z)‐ and (E)‐7 b (n=3) and (Z)‐ and (E)‐7 d (n=5), were studied at a molarity of 1 μM on two breast‐cancer cell lines, MCF7 (ERα positive) and MDA‐MB231 (ERα negative). These molecules had an antiproliferative effect on MCF7 cells slightly higher than that of OH‐Tam and no effect on MDA‐MB231 cells. Thus, the antiproliferative effect observed on the MCF7 cells seemed essentially to be linked to an antiestrogenic effect. Molecular modelling studies have allowed us to rationalise these effects and select the best compounds for future development of a radioactive series.

Zinc and cobalt complexes based on tripodal ligands: synthesis, structure and reactivity toward lactide.

The coordination chemistry of a series of pro-ligands ([L¹]-[L⁶]) with cobalt and zinc derivatives has been studied. All complexes have been characterized by multinuclear NMR, elemental analysis, and by single-crystal X-ray diffraction studies. Polymerization of rac-lactide takes place at 130 °C in the presence of cobalt and zinc complexes to yield polymers under solvent free conditions with controlled molecular masses and narrow polydispersities.

Botryolins A and B, two tetramethylsqualene triethers from the green microalga Botryococcus braunii

Two new triterpenoid polyethers with a tetramethylsqualene carbon skeleton, botryolins A and B, have been isolated from the green microalga Botryococcus braunii. Their structures were determined by means of spectral analyses including 2D NMR.

Multimodal Study of Secondary Interactions in Cp*Ir Complexes of Imidazolylphosphines Bearing an NH Group

Hydrogen bonding phenomena are explored using a combination of X-ray diffraction, NMR and IR spectroscopy, and DFT calculations. Three imidazolylphosphines R(2)PImH (ImH = imidazol-2-yl, R = t-butyl, i-propyl, phenyl, 1a-1c) and control phosphine (i-Pr)(2)PhP (1d) lacking an imidazole were used to make a series of complexes of the form Cp*Ir(L(1))(L(2))(phosphine). In addition, in order to suppress intermolecular interactions with either imidazole nitrogen, 1e, a di(isopropyl)imidazolyl analogue of 1b was made along with its doubly (15)N-labeled isotopomer to explore bonding interactions at each imidazole nitrogen. A modest enhancement of transfer hydrogenation rate was seen when an imidazolylphosphine ligand 1b was used. Dichloro complexes (L(1) = L(2) = Cl, 2a-2c,2e) showed intramolecular hydrogen bonding as revealed by four X-ray structures and various NMR and IR data. Significantly, hydride chloride complexes [L(1) = H, L(2) = Cl, 3a-3c and 3e-((15)N)(2)] showed stronger hydrogen bonding to chloride than hydride, though the solid-state structure of 3b evinced intramolecular Ir-H...H-N bonding reinforced by intermolecular N...H-N bonding between unhindered imidazoles. These results are compared to literature examples, which show variations in preferred hydrogen bonding to hydride, halide, CO, and NO ligands. Surprising differences were seen between the dichloro complex 2b with isopropyl groups on phosphorus, which appeared to exist as a mixture of two conformers, and related complex 2a with tert-butyl groups on phosphorus, which exists in chlorinated solvents as a mixture of conformer 2a-endo and chelate 5a-Cl, the product of ionization of one chloride ligand. This difference became apparent only through a series of experiments, especially (15)N chemical shift data from 2D (1)H-(15)N correlation. The results highlight the difficulty of characterizing hemilabile, bifunctional complexes and the importance of innocent ligand substituents in determining structure and dynamics.

Braunicetals: acetals from condensation of macrocyclic aldehydes and terpene diols in Botryococcus braunii.

Two series of braunicetals were isolated from the green microalga Botryococcus braunii. Based on spectroscopic and chemical evidence, their structures were determined to be acetals formed by the condensation of C32 and C34 macrocyclic aldehydes with C33 and C34 methylated squalene diols (series I), or a C40 lycopaene diol (series II).

A di-O-dihydrogeranylgeranyl glycerol from Thermococcus S 557, a novel ether lipid, and likely intermediate in the biosynthesis of diethers in Archæa

Abstract The lipids of a deep-sea hydrothermal vent archaeon, Thermococcus S 557, were isolated, purified and structurally determined. Based on acid methanolysis and spectroscopic studies, the polar lipids were shown to comprise diphytanyl glycerol and dibiphytanyl diglycerol, typical membrane lipids of Archaea. From the neutral lipids, 2,3-di- O -dihydro-14,15-geranylgeranyl glycerol was isolated. This novel ether lipid is, very likely, a close intermediate in the biosynthesis of diphytanyl glycerol diether in Archaea.

Six novel tetraterpenoid ethers, lycopanerols B-G, and some other constituents from the green microalga Botryococcus braunii

Six novel tetraterpenoid ethers, lycopanerols B-G, were isolated from lipidic extracts of the green microalga Botryococcus braunii (L race), along with a series of phytyl esters and alpha- and beta-tocopherols. The structures of the compounds were determined by means of spectral analyses including 2D NMR techniques. A biogenetic relationship is proposed between lycopanerols and lycopadiene, the acyclic diunsaturated tetraterpenoid hydrocarbon synthesized by the alga.