Pilar Prados

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl(-)/HCO(3)(-) exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems.

Resorcinarenes with 2-benzimidazolone bridges: self-aggregation, self-assembled dimeric capsules, and guest encapsulation.

The synthesis and spectroscopic characterization of self-assembled dimeric resorcinarenes 1a–d containing four 2-benzimidazolone (cyclic urea) bridges are reported. The nanometer-size capsules are held together by a cyclic array of complementary hydrogen bonds. Unlike the related imide-bridged resorcinarenes reported by Rebek and coworkers [Heinz, T., Rudkevich, D. M. & Rebek, J., Jr. (1998) Nature (London) 394, 764–766], these strongly bound dimers aggregate in chloroform solutions yielding different self-organized structures, depending on the nature and length of the four carbon chains attached at the bottom of each resorcinarene platform, as revealed by transmission electron microscopy. Thus, phenethyl groups (dimer 1c⋅1c) produce long fibers, probably arising from tail to tail contacts and subsequent threading of the resulting linear self-assembled polymers, whereas long alkyl chains (dimers 1a⋅1a and 1b⋅1b) induce formation of large reverse vesicles of 0.8–2.2 μm diameter through side to side extensive stacking. Presumably, the rigidity of the dimer precludes folding of the aggregate into smaller vesicles. On the contrary, dimer 1d⋅1d, containing four nine-carbon chains and a cis-double bond, does not substantially aggregate and gives rise to reasonably resolved 1H NMR spectra. The compound was shown to be dimeric either by matrix-assisted laser desorption ionization–time-of-flight and vapor pressure osmometry. Encapsulation studies were followed by NMR. Propionic or pivalic acid was included in the capsules, probably as head to head hydrogen-bonded dimers in mesitylene-d12, a solvent too big to be a guest by its own. Longer dimeric carboxylic acids or larger substrates, like 2-adamantyl azide or cyclohexylcarbodiimide, do not encapsulate, but mixtures of a long and a short carboxylic acid (i.e., propionic-adamantyl or propionic-cyclohexyl) yield pairwise complexes.

A Synthetic Cation‐Transporting Calix[4]arene Derivative Active in Phospholipid Bilayers

One order of magnitude: The transport of Na+ and K+ ions through a phospholipid bilayer occurs with much higher conductance levels with 1 and 2 than with typical Na+ -transporting proteins or gramicidin. However, the cations do not appear to pass through the calix[4]arene ring, which has a rigid 1,3-alternate conformation. diazacrown=10-benyzl-1,10-diaza[18]crown-6 group.

Enantioselective Transport by a Steroidal Guanidinium Receptor

The cationic steroidal receptors 9 and 11 have been synthesized from cholic acid 3. Receptor 9 extracts N-acetyl-alpha-amino acids from aqueous media into chloroform with enantioselectivities (L:D) of 7-10:1. The lipophilic variant 11 has been employed for the enantioselective transport of N-acetylphenylalanine, a) through dichloromethane (DCM) and dichloroethane (DCE) bulk liquid membranes (U-tube apparatus), and b) through 2.5% (v/v) octanol/hexane via hollow fibre membrane contactors. Significant enantioselectivities and multiple turnovers were observed for both types of apparatus.

Recent Advances in Macrocyclic and Macrocyclic-Based Anion Receptors

The interest in anion coordination chemistry has grown enormously in the last few years. Macrocyclic and macrocyclic-based architectures are at the forefront of the development of new anion receptors. This mini review is intended to illustrate some of the goals achieved recently in this field highlighting examples that appeared in the literature over the period 2005–2006.

A Self‐Assembled Calix[4]arene Dimer Linked through Hydrogen‐Bonded 2‐Ureidopyrimidin‐4(1H)‐one Groups

Tightly linked! A linear array of complementary hydrogen bonds forms between two 2-ureidopyrimidin-4(1H)-one rings attached to the upper rims of facing 1,3-alternate calix[4]arenes (shown schematically). The strength of the binding (Kass >106  M-1 in chloroform) and the efficiency of the self-assembly open up interesting perspectives in the design of highly ordered multicomponent cages.

Toward an Artificial Acetylcholinesterase

The methanolysis of choline p-nitrophenylcarbonate in chloroform containing 1 % methanol is catalyzed with turnover by ditopic receptors 1 and 2, consisting of a calix[6]arene connected to a bicyclic guanidinium by means of a short spacer. The calix[6]arene subunit strongly binds to the trimethylammonium head group through cation–π interactions, whereas the guanidinium moiety is deputed to stabilize through hydrogen bonding reinforced by electrostatic attraction the anionic tetrahedral intermediate resulting from methoxide addition to the ester carbonyl. The observed cholinesterase activity had been anticipated on the basis of the ability of the ditopic receptors 1 and 2 to bind strongly to the choline phosphate DOPC, which is a transition state analogue for the BAc2-type cleavage of choline esters.

A stepwise synthesis of functionalized calix [4]arenes and a calix[6]arene with alternate electron-withdrawing substituents

Abstract Simple modifications of the TiCl4-induced cyclocondensation of phenol derivatives raise the yields of pure calix [4]arenes, even in the presence of electron-withdrawing substituents. The first example of a calix [6]arene with alternate substituents is given.

Enlarged cavitand-based coordination cages

Abstract Two new coordination cages 1a , b were prepared via metal-directed self-assembly of the tetrakis(benzonitrile) cavitands 2a , b with Pt(dppp)(CF 3 SO 3 ) 2 . Their large portals allow fast exchange on the NMR timescale of encapsulated counterions or guests with solvent molecules.

Synthesis of calix[6]arenes partially functionalized at the upper rim

Several new examples of calix[6]arenes selectively functionalized at the upper rim are reported. Starting from calix[6]arenes 1,3,5-tri-, 1,2,4,5-tetra- and 1,2,3,4,5-pentaalkylated at the lower rim, it is possible to isolate macrocycles 2,4,6-tri-, 3,6-di- and 6-mono functionalized at the upper rim (18?94% yield) with nitro, formyl, bromo, chloromethyl and 2-propenyl groups. Modifications of these moieties allow the synthesis of macrocycles bearing amino, amido, hydroxymethyl, carboxy, cyano and chloromethyl functions which can be used for further transformation and preparation of new molecular receptors, based on calix[6]arenes, which have different geometries. Examples of di- and triquinones on the hexameric macrocycle are also reported.