Transmembrane anion transport mediated by halogen-bond donors

In biology and chemistry, the transport of anions across lipid bilayer membranes is usually achieved by sophisticated supramolecular architectures. Significant size reduction of transporters is hampered by the intrinsically hydrophilic nature of typical anion-binding functionalities, hydrogen-bond donors or cations. To maximize the atom efficiency of anion transport, the hydrophobic nature, directionality, and strength of halogen bonds seem promising. Unlike the ubiquitous, structurally similar hydrogen bonds, halogen bonds have not been explored for anion transport. Here we report that transport across lipid bilayers can be achieved with small perfluorinated molecules that are equipped with strong halogen-bond donors. Transport is observed with trifluoroiodomethane (boiling point=−22 °C); that is, it acts as a 'single-carbon' transporter. Contrary to the destructive action of small-molecule detergents, transport with halogen bonds is leakage-free, cooperative, non-ohmic and highly selective, with anion/cation permeability ratios <37

Ditopic ion transport systems: anion-pi interactions and halogen bonds at work

Single-atom exchange series are introduced to extract the individual contributions of halogen bonds and anion–π interactions to the transport of anions across lipid bilayer membranes. Known cation binding sites are used for counterion activation of the neutral calix[4]arene transporters. The experimental evidence for anion transport with halogen bonds is unprecedente

Unusual electronic effects of electron-withdrawing sulfonamide groups in optically and magnetically active self-assembled noncovalent heterodimetallic d-f podates

The segmental ligand 2-(6-(N,N-diethylcarbamoyl)pyridin-2-yl)-1,1'-dimethyl-2'-(5-(N,N-diethylsulfonamido)-pyridin-2-yl)-5,5'-methylenebis[1H-benzimidazole] (L3) is synthesized via a multistep strategy that allows the selective introduction of an electron-withdrawing sulfonamide group into the ligand backbone and its subsequent hydrolysis to the hydrophilic sulfonate group. Compared to that of the methylated analogue L1, the affinity of the bidentate binding unit of L3 for H+ and for trivalent lanthanide ions (LnIII) in [Ln(L3)3]3+ and [Ln2(L3)3]6+ is reduced because the electron-withdrawing sulfonamide substituent weakens sigma-bonding, but improved retro-pi-bonding between the bidentate binding units of L3 and soft 3d-block ions (M(II) = FeII, ZnII) overcomes this effect and leads to homometallic complexes [Mn(L(i))m]2n+ (i = 1, 3) displaying similar stabilities. Theoretical ab initio calculations associate this dual effect with a global decrease in energy of pi and sigma orbitals when the sulfonamide group replaces the methyl group, with an extra stabilization for the LUMO (pi). The reaction of L3 with a mixture of LnIII and M(II) (M = Fe, Ni, Zn) in acetonitrile gives the noncovalent podates [LnM(L3)3]5+ in which LnIII is nine-coordinated by the three wrapped tridentate segments, while the bidentate binding units provide a facial pseudooctahedral site around M(II). The X-ray structure of [EuZn(L3)3](ClO4)4(PF6)(CH3NO2)3(H2O) reveals that the bulky sulfonamide group at the 5-position of the pyridine ring only slightly increases the Zn-N bond distances as a result of sigma/pi compensation effects. The introduction of spectroscopically and magnetically active FeII and NiII into the pseudooctahedral site allows the detailed investigation of the electronic structure of the bidentate segment. Absorption spectra, combined with electrochemical data, experimentally demonstrate the dual effect associated with the attachment of the sulfonamide group (decrease of the sigma-donating ability of the pyridine lone pair and increase of the pi-accepting properties of the coordinated bidentate binding unit). The influences on the ligand field strength and on tunable room-temperature FeII spin-crossover processes occurring in [LnFe(L3)3]5+ are discussed, together with the origin of the entropic control of the critical temperature in these thermal switches

Synthesis, Structure, and Antimalarial Activity of Some Enantiomerically Pure, cis-fused cyclopenteno-1,2,4-trioxanes

Two pairs of enantiomerically pure cis-fused cyclopenteno-1,2,4-trioxanes (7, ent-7 and 8, ent-8) are prepared (Schemes 1-3). Their identities are established by dye-sensitized photo-oxygenation of ent-7 and 8, ent-8 to the allylichydroperxides, reduction to the corresponding alcohols, and conversion to the (1S)-camphanates (Scheme 4), the structures of which are determined by X-ray analysis. The dynamic properties of ent-7 are investigated by NMR spectroscopy and PM3 calculations. Evidence for an easily accessible twist-boat conformation is obtained. The in vitro and in vivo antimalarial activities of 7, ent-7,8, and ent-8 as well as those of the racemic mixtures are evaluated against Plasmodium falciparum, P. berghei, and P. yoelii. No correlation is observed between configuration and activity. Racemates and pure enantiomers have commensurate activities. The mode of action on the intraerythrocytic parasite is rationalized in terms of close docking by the twist-boat conformer of the trioxane on the surface of a molecule of heme, single-electron transfer to the O--O d* orbital, and scission to the acetal radical which then irreversibly isomerizes to a C-centered radical, the ultimate lethal agent (Scheme 5)

Octafluorocalix[4]pyrrole: a chloride/bicarbonate antiport agent

Meso-Octamethyloctafluorocalixpyrrole, a simple tetrapyrrolic macrocycle, has been shown to function as both a chloride/nitrate and a chloride/bicarbonate antiport agent for lipid bilayer transmembrane anion transport. This is the first example of a synthetic macrocyclic pyrrole-based receptor capable of transmembrane bicarbonate transport.<br/