Thermodynamic stabilities of complexes of synthetic macrocyclic valinomycin mimics with alkali, barium, and guanidinium cations

Association constants of the 1:1 complexes of a series of pyrido crown ethers 1 (n=0–6) and a number of large ring (27–33 ring atoms) benzo and dibenzo crown ethers 2,3 with alkali, barium and guanidinium chlorides have been determined potentiometrically in MeOH. For most of the ions besides a global maximum for 18-membered rings, a local maximum for the complexation with 30-membered rings is observed. The appearance of local maxima is attributed to the tennisball-seam like conformations that large macrocycles can adopt. The larger crown ethers show a remarkbly high K+ /Na+ selectivity similar to the antibiotic valinomycin, a structurally related 36-membered macrocycle. Therefore, these large ring crown ethers can be regarded as synthetically easy to modify valinomycin mimics. The effects of the solvation of the hosts, guests and complexes on the overall (co-)complexation is discussed. Comparison of data from extraction experiments with association constants clearly shows that differences in the distribution of the complexes between the aqueous and organic phases may be a dominating factor for the selective extraction of cations

pKa Determination of water-soluble calix[4]arenes

Neutral, water-soluble 5,11,17,23-tetrakis[bis-(2-hydroxyethyl)aminosulphonyl]calix[4]arene-25,26,27,28-tetraol and 5,11,17,23-tetranitrocalix[4]arene-25,26,27,28-tetraol have been synthesized and the pKa values of the OH groups determined in an aqueous system

Water-soluble molecular capsules: self-assembly and binding properties

The self-assembly and characterization of water-soluble calix[4]arene-based molecular capsules (12) is reported. The assemblies are the result of ionic interactions between negatively charged calix[4]arenes 1 a and 1 b, functionalized at the upper rim with amino acid moieties, and a positively charged tetraamidiniumcalix[4]arene 2. The formation of the molecular capsules is studied by 1H NMR spectroscopy, ESI mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC). A molecular docking protocol was used to identify potential guest molecules for the self-assembled capsule 1 a2. Experimental guest encapsulation studies indicate that capsule 1 a2 is an effective host for both charged (N-methylquinuclidinium cation) and neutral molecules (6-amino-2-methylquinoline) in water

Random mutagenesis and screening of complex glycoproteins: expression of human gonadotropins in Dictyostelium discoideum

The soil amoeba Dictyostelium discoideum is a host cell that provides simple genetics in combination with complex protein synthesis. We show that the complex human heterodimeric gonadotropins can be produced and secreted by this organism. Furthermore, both follicle stimulation hormone and choriogonadotropin produced by D. dictyostelium bind to their human receptors and elicit a biological response comparable to the wild-type hormones. We also show that structure-function analysis using random mutagenesis and screening of recombinant glycoprotein hormones is feasible. Thus, expression of gonadotropins in D. dictyostelium opens the way to the engineering of potential new therapeutic analogues.

Intraannular functionalization of macrocyclic polyethers via organolithium chemistry; x-ray structure of 2-sulfinyl-1,3-xylyl-15-crown-4

The conversion of 2-lithio-1,3-xylyl crown ethers (2), obtained by reaction of the 2-bromo-1,3-xylyl crown ethers (1) with n_-butyllithium at −70 °C, with an electrophile is a generally applicable method for the synthesis of 1,3-xylyl crown ethers with intraannular acidic groups