Michel Luhmer

Calix[6]tris(thio)ureas: heteroditopic receptors for the cooperative binding of organic ion pairs.

The straightforward syntheses of C3v symmetrical calix[6]trisureas and -thiourea have been achieved. NMR studies have shown that these flexible compounds possess a major cone conformation. While these neutral hosts can strongly bind anions such as AcO(-) or HSO4(-) through induced fit processes, they can also behave as unique heteroditopic receptors for organic ion pairs with a remarkable positive cooperativity in the complexation process, the anion acting as an allosteric effector.

Unprecedented copper(I) bifluoride complexes: synthesis, characterization and reactivity.

To be or not to bifluoride: Two synthetic pathways to unprecedented N-heterocyclic carbene copper(I) bifluoride complexes have been developed. Catalytic tests demonstrated that copper(I) bifluorides are very efficient catalysts, which do not require any additional activating agent. The first Cu-catalyzed diastereoselective allylation of (R)-N-tert-butanesulfinyl aldimines was also established. The method enables efficient, simple and general synthesis of enantiomerically enriched homoallylic amines at room temperature in high yields.

An allosteric heteroditopic receptor for neutral guests and contact ion pairs with a remarkable selectivity for ammonium fluoride salts.

Two novel calix[6]cryptamides bearing a tren-based cap have been synthesized and their host-guest properties have been investigated by (1)H and (19)F NMR spectroscopy. One of them behaves as a remarkable heteroditopic receptor toward either polar neutral guests, anions or contact ion pairs. It has been shown that only F(-) can be encapsulated into the tris-amido cap of this host. Moreover, the fluoride anion acts as an allosteric activator by favoring the inclusion of ammonium ions into the calixarene cavity. The ammonium fluoride salts are bound as contact ion pairs and, remarkably, the calix[6]cryptamide host is reluctant to other ammonium salts. To our knowledge, such an highly cooperative and selective process toward contact ammonium fluoride salts is unique in the literature. Allosteric regulation of all the host-guest systems can also be achieved through protonation of the aza-cap. Indeed, guest release can be triggered by addition of various acids. In comparison to related calixarene-based receptors, all these unique properties are due to the smallness and the higher preorganization of the binding site provided by the convergent hydrogen bond donor groups of the tris-amido cap.

Induced‐Fit Encapsulation by a 1,3,5‐Alternate Calix[6]arene

A little bit of flexibility: Charged or neutral species can be accommodated in solution and in the solid state by the closed hydrophobic cavity of the first calix[6]arene to adopt a 1,3,5-alternate conformation (see picture, Boc=tertbutoxycarbonyl). The encapsulation involves an induced-fit process that is reminiscent of the rotation of a door and is characterized by large activation barriers for guest exchange.

Variable-field relaxometry of iron-containing human tissues: A preliminary study

Excess iron is found in brain nuclei from neurodegenerative patients (with Parkinsons, Alzheimers and Huntingtons diseases) and also in the liver and spleen of cirrhosis, hemochromatosis and thalassaemia patients. Ferritin, the iron-storing protein of mammals, is known to darken T(2)-weighted MR images. Understanding NMR tissue behavior may make it possible to detect those diseases, to follow their evolution and finally to establish a protocol for non-invasive measurement of an organs iron content using MRI methods. In this preliminary work, the MR relaxation properties of embalmed iron-containing tissues were studied as well as their potential correlation with the iron content of these tissues. Relaxometric measurements (T(1) and T(2)) of embalmed samples of brain nuclei (caudate nucleus, dentate nucleus, globus pallidus, putamen, red nucleus and substantia nigra), liver and spleen from six donors were made at different magnetic fields (0.00023-14 T). The influence of the inter-echo time on transverse relaxation was also studied. Moreover, iron content of tissues was determined by inductively coupled plasma atomic emission spectroscopy. In brain nuclei, 1/T(2) increases quadratically with the field and depends on the inter-echo time in CPMG sequences at high fields, both features compatible with an outer sphere relaxation theory. In liver and spleen, 1/T(2) increases linearly with the field and depends on the inter-echo time at all fields. In our study, a correlation between 1/T(2) and iron concentration is observed. Explaining the relaxation mechanism for these tissues is likely to require a combination of several models. The value of 1/T(2) at high field could be used to evaluate iron accumulation in vivo. In the future, confirmation of those features is expected to be achieved from measurements of fresh (not embalmed) human tissues.

Formation of a Dinuclear Mercury(II) Complex with a Regular Bis‐Strapped Porphyrin Following a Tunable Cooperative Process

The richness of metalloporphyrin chemistry is an important source of innovative features which justifies active investigation of their coordination properties towards post-transition elements. Mercury(II) complexation by porphyrins was first motivated by the observation of its catalytic effect on the complexation of other elements (Cu, Zn), and regained attention in view of the sensing of toxicological organomercury(II) compounds. Although first studies appeared in the 1970s, the coordination of mercury by porphyrins is still largely misunderstood. Solution studies, mostly performed with “naked” porphyrins, revealed various Hg–porphyrin stoichiometries, such as 1:1, 2:1, 2:2, and 3:2, on the basis of spectroscopic investigations. Equilibria between the different species are often solvent-, concentration-, and pHdependent, and there are no definite elements in the literature for a possible correlation between an XRD-based coordination mode and the corresponding species observed in solution. Such analysis is crucial for a better understanding of the complexation processes and could also provide elements for the rational design of mercury-based porphyrinoid objects. To the best of our knowledge, XRD structures of mercury–porphyrin complexes are very scarce. Five of the six reported examples involve an N-modified macrocycle, 7] a single report being related to a regular porphyrin. In this mononuclear complex, the mercury atom is four-coordinate to the four nitrogen atoms of the porphyrin, and is sitting 0.60 above the 24-atom mean plane with an average covalent mercury to nitrogen bond length of 2.20 . In this context, the design of new porphyrin ligands with purposely introduced coordinating groups deserves particular attention. We recently reported a centrosymmetrical homodinuclear complex of lead(II) with the L ditopic ligand 1 (Scheme 1). We reasoned that, in the case of mercury(II), such a bis-strapped chelate with hanging COOH groups could provide a means to obtain discrete species, rather than sandwich assemblies, and better control of the nuclearity. Herein, we describe the first solid-state structure of a dinuclear mercury(II) complex with a regular porphyrin, and report on the evidence for a tunable cooperative process for its formation. Mercury insertion was performed at room temperature in pyridine with a 3 equivalent excess of mercury acetate (Scheme 1). The reaction was monitored by UV/Vis spectroscopy and a final pattern showing three absorption bands at l = 448, 550, and 576 nm was obtained after 15 min. After solvent evaporation, the green solid was taken up in neutralized CH2Cl2, and excess mercury salt was removed by filtration on celite. The mercury complex was isolated upon precipitation with pentane (82 % yield). Elemental analysis indicated a 1:2 1/Hg stoichiometry, which is in agreement with the formation of dinuclear bis(mercury) complex 1·Hg2. [9]

Binding of Ru(II) polyazaaromatic complexes to DNA: A 23Na NMR spin-lattice relaxation study

The possibility of using sodium-23 spin-lattice relaxation rate measurements to probe the interaction modes of Ru11 polyazaaaromatic complexes with DNA is investigated. The following complexes are considered: Ru(phen)3(2+) (phen = 1.10-phenanthroline), Ru(phen)2HAT2+ (HAT = 1,4,5,8,9,12-hexaazatriphenylene), and Ru(diMeTAP)3(2+) (diMeTAP = 2,7-dimethyl-1,4,5,8-tetraazaphenanthrene). The addition of Ru(diMeTAP)3(2+) to a solution of NaDNA leads to a decrease in the sodium-23 spin-lattice relaxation rate (R1) similar to the effect observed upon addition of Mg2+. This indicates that Ru(diMeTAP)3(2+) interacts like Mg2+ with DNA and consequently that the electrostatic interaction dominates the association with DNA, Ru(phen)3(2+) and Ru(phen)2HAT2+ diminish R1 more efficiently than Mg2+, in a manner similar to ethidium bromide, which is known for its intercalation properties. Thus interactions other than electrostatic occur between these two complexes and DNA. These results are in agreement with data obtained from other techniques, according to which Ru(phen)3(2+) and Ru(phen)2HAT2+ are located partially inside the DNA double helix, in contrast to Ru(diMeTAP)3(2+) which remains in the ionic atmosphere around the phosphate backbone.

NMR study of the reversible trapping of SF6 by cucurbit[6]uril in aqueous solution.

The complexation of sulfur hexafluoride (SF(6)), a highly potent greenhouse gas, by cucurbit[6]uril (CB) was studied at various temperatures in Na(2)SO(4) aqueous solutions by (19)F and (1)H NMR. CB shows a remarkable affinity for SF(6), suggesting that it is a suitable molecular container for the design of materials tailored for SF(6) trapping. At 298 K, the equilibrium constant characterizing the inclusion of SF(6) by CB is 3.1 x 10(4) M(-1) and the residence time of SF(6) within the CB cavity is estimated to be of the order of a few seconds. The enthalpic and entropic contributions to the free energy of encapsulation were determined and are discussed. This work also reports on the interest of SF(6) in the framework of the spin-spy methodology. The advantages and drawbacks of solution-state (19)F NMR of SF(6) with respect to (129)Xe NMR are discussed. SF(6) comes forward as a versatile and informative spin-spy molecule for probing systems in solution because its detection limit by (19)F NMR reaches the micromolar range with standard equipment and because quantitative integral measurements, relaxation time measurements, and demanding experiments, such as translational diffusion coefficient measurements, are easily carried out in addition to chemical shift measurements. Solution-state (19)F NMR of SF(6) emerges as a promising alternative to (129)Xe NMR for probing cavities and for other applications relying on the encapsulation of an NMR active gaseous probe.

Translocation-coupled transmetalation at the origin of a dinuclear lead porphyrin complex: implication of a hanging-atop coordination mode

Translocation of a lead cation from the N-core of a porphyrin to a hanging carboxylate group is coupled to a transmetalation process with a second lead cation, leading to a dinuclear species. A novel hanging-atop coordination mode is responsible for the dynamic and stereocontrolled binding of lead to the porphyrin core.

Study of NMR relaxation of xenon-131 in quadrupolar solvents

Abstract An experimental and theoretical study of the quadrupolar relaxation of xenon-131 by quadrupolar solvents has been performed. The electric-field-gradient (EFG) fluctuations at the xenon nucleus are considered to be of purely electrostatic origin and are calculated by means of a new theoretical model called PISA (pair interactions structureless approximation), which is based on a simplified description of the structure of molecular liquids. The PISA results are compared to those of a Monte Carlo simulation. The influence of self- and cross-correlation functions on the total EFG correlation function is discussed. Calculated EFG fluctuations are then used, together with experimental relaxation rates, to determine effective correlation times. These correlation times are analyzed by considering different solvent motions.