Josette Canceill

Channel-type molecular structures. Part 4. Transmembrane transport of alkali-metal ions by ‘bouquet’ molecules

This report describes transport experiments with ‘bouquet’ molecules designed to act as artificial ion channels. The ‘bouquets’ are based on a central macrocycle which is either an 18-crown-6 (BM) or a cyclodextrin derivative (BCD) to which are attached polyethylene oxide [poly(oxyethylene)] chains (BMo and BCDo) or polyalkyl chains (BMc and BCDc) tipped with carboxylate endgroups. The ‘bouquets’ were studied in liposomes prepared from egg phosphatidylcholine (egg PC), dipalmitoyl phosphatidylcholine (DPPC) and a mixture of egg PC, stearylamine and cholesterol. Opposing gradients in Li+ and Na+ concentration were created and the transport of alkali-metal ions down their concentration gradients was followed directly by 7Li and 23Na NMR spectroscopy. ‘Bouquets’ were found to cause a one-for-one exchange of Na+ for Li+(antiport). In order to estimate transport rates, the extent of Na+ entry into liposomes was followed as a function of time. All ‘bouquets’ transported ions at similar rates in fluid membranes. Comparison of transport rates in fluid-(egg PC) and gel-state membranes (DPPC) was used to distinguish carrier and channel mechanisms. Control experiments demonstrated that a known carrier (monensin A) gave significantly lower transport rates in gel-state membranes. Two ‘bouquets’, BMc and BCDc, were found to transport Na+ at similar rates in fluid- and gel-state membranes; this suggests that ion passage occurs preferentially by the channel mechanism and not by the carrier mechanism. Variation of transport rate with ‘bouquet’ concentration was probed for BMo and BMc and the rates were found to increase with BMc concentration but not with BMo concentration. Since the transport rate is expected to be proportional to transporter concentration in both the carrier and channel mechanisms, this indicates that BMo uses neither a carrier nor a channel mechanism. The mechanism by which ‘bouquet’ molecules operate and the criteria which may be used to decide whether functioning channels have been created are discussed.

Recherches sur les substances mesogenes—VIII : Preparation et proprietes mesomorphes de series isometriques

Resume La synthese et les proprietes mesomorphes de diverses series de composes mesogenes isometriques sont decrites. Il se confirme que des molecules mesogenes isometriques peuvent, selon la place du noyau rigide polaire, etre nematogenes et/ou smectogenes.

Analysis of the conformational behaviour of perfunctionalized β-cyclodextrins. Part 1. Evidence for insertion of one of the rim substituents into the cyclodextrin cavity in organic solvents

Several functionalized β-cyclodextrins have been shown to exhibit conformational isomerism. The analysis of the conformational behaviour of several derivatives strongly suggests that a slow exchange occurs between C7 and C1 conformers, the C1 probably involving insertion of one of the primary rim substituents in the cyclodextrin cavity. The significance of the structural features of cyclodextrin substituents for the occurrence of conformational isomerism is examined. The relevance of the use of cyclodextrins for the design of molecular devices is discussed.

An approach to channel-type molecular structures. Part 3. Incorporation studies of the bouquet-shaped BM and BCD in phosphatidylcholine vesicles

Incorporation of bouquet-shaped molecules based either on a macrocyclic (BM) or on a β-cyclodextrin (BCD) core in phosphatidylcholine vesicular bilayers has been investigated. As can be shown by numerous techniques, these molecules are incorporated in moderate to high yields within vesicle membranes. Possible incorporation modes are then discussed.

Two-step synthesis of D3 and C3h cryptophanes

Dihalides X–(Z)–X, [Z =(CH2)n; n= 1–7 or CH2CHCHCH2] react with the phenol group of vanillyl alcohol to give the dialkylated derivatives HOCH2–Ar–O–(Z)–O–Ar–CH2OH (2), which in turn, in the presence of formic acid, afford the corresponding D3 cryptophanes (3), with, in some cases, minor amounts of the C3h isomers (4).

A new bis-cyclotribenzyl cavitand capable of selective inclusion of neutral molecules in solution. Crystal structure of its CH2Cl2 cavitate

The Structure of a new bis-cyclotribenzyl cavitand, (2), forming an internal 1 : 1 Complex (‘cavitate’) with dichloromethane, has been determined by single X-ray crystallography.

Dynamic behavior of a perfunctionalized β-cyclodextrin as probed by NMR and molecular modeling

Abstract Conformational analysis of a perfunctionalized β-cyclodextrin by NMR and molecular modeling has revealed that this compound exists as an equilibrium mixture of C1 and C7 conformers in slow exchange. From carbon chemical shifts, interglycosidic vicinal heteronuclear coupling constants and NOESY volumes, it has been demonstrated that the macrocyclic conformation is responsable for the asymmetry in the C1 form. Several dynamic processes such as rapid conformational averaging, localized chemical exchange and the C 1 C 7 equilibrium have been shown to occur on widely separated timescales. In parallel, a molecular modeling study has revealed that the accessible conformational space of β-CDs is not significantly reduced with respect to that of the related disaccharide, β-maltose. All of the dynamic phenomena appear to be related to the macrocylic puckering and two distinct modes of variation in puckering have emerged from MD trajectories: transitions are either auto-compensated without perceptible change in macrocycle puckering or irreversible leading to considerable variation in macrocycle puckering. Optimization of the NMR-defined theoretical structures leads to auto-complexation of an exocyclic substituent.

Water-soluble cryptophane binding lipophilic guests in aqueous solution

The first water-soluble cryptophane (4) has been synthesized in three steps from cryptophane-A (1); (4) has been found to complex chloroform and dichloromethane strongly in D2O, with binding constants in the range 103–104 dm3/mol.

Selective recognition of neutral molecules: 1H n.m.r. Study of the complexation of CH2Cl2 and CH2Br2 by cryptophane-D in solution and crystal structure of its CH2Cl2cavitate

The complexation of CH2Cl2 and CH2Br2 by cryptophane-D (2), a new bis-cyclotribenzyl cavitand, has been studied by 1H n.m.r. spectroscopy and the structure of the internal 1 : 1 (2)·CH2Cl2 complex (cavitate) has been determined by single crystal X-ray crystallography.

New D3 and C3h cryptophanes with ethylenic bridges: syntheses, structural assignments, and absolute configurations and circular dichroism of the D3 isomers

Abstract Two (D3/C3h) cryptophane pairs, (I/J) and (K/L), in which the two cyclotriveratrylene caps are linked by three trans (I/J) or cis (K/L) OCH2CHCHCH2O bridges have been synthesised, and their structures established by mass spectrometry, NMR, optical activity and circular dichroism data. The D3 cryptophanes I and K have been obtained in racemic and resolved forms, and their absolute configurations have been determined by chemical correlation with the known P-(-)-cyclotriguaiacylene. The circular dichroism spectra of I and K could be satisfactorily analyzed in the light of the exciton model, extended to the coupling of six equivalent chomophores in a D3 array.