Iris Thondorf

Hydrogen-bonded dimers of tetraurea calix[4]arenes: unambiguous proof by single crystal X-ray analysis

Self-assembly of calix[4]arenes substituted by four urea residues at the wider rim leads to hydrogen-bonded dimers; the first single crystal X-ray analysis of such a dimer is reported.

The renal type H+/peptide symporter PEPT2: structure-affinity relationships

Summary.The H+/peptide cotransporter PEPT2 is expressed in a variety of organs including kidney, lung, brain, mammary gland, and eye. PEPT2 substrates are di- and tripeptides as well as peptidomimetics, such as β-lactam antibiotics. Due to the presence of PEPT2 at the bronchial epithelium, the aerosolic administration of peptide-like drugs might play a major role in future treatment of various pulmonary and systemic diseases. Moreover, PEPT2 has a significant influence on the in vivo disposition and half-life time of peptide-like drugs within the body, particularly in kidney and brain. PEPT2 is known to have similar but not identical structural requirements for substrate recognition and transport compared to PEPT1, its intestinal counterpart. In this review we compiled available affinity constants of 352 compounds, measured at different mammalian tissues and expression systems and compare the data whenever possible with those of PEPT1.

Selective derivatisation of resorcarenes: 1. The regioselective formation of tetra-benzoxazine derivatives

Abstract Four 5,6-benzo-1,3-oxazine rings are formed by the condensation of resorcarenes with various aliphatic or aromatic primary amines and formaldehyde. From four possible regioisomers only the C4 symmetrical compound is isolated in yields of up to 90%. Semiempirical calculations confirm its relative stability, which is due to the possible formation of four intramolecular OH…O hydrogen bonds. The regioselectivity of the reaction is further established for two examples by single crystal X-ray analysis. A solvent molecule is included in the extended cavity.

Regio- and diastereoselective condensation of resorcarenes with primary amines and formaldehyde

Abstract Mannich reactions of resorcarenes 1 with chiral amines yield single diastereomeric tetrakis-(benzodihydro-1,3-oxazine) derivatives 2 in high yields (80–90%). Epimerisation of these products occurs in the presence of acid.

1,2-Dithiins and precursors, XVII: Synthesis and properties of thieno anellated 1,2-dithiins, structural influence on colour ☆

Abstract Various thieno[3,2-c] anellated (5a, 26) and dithieno[3,2-c:2,3-e] anellated 1,2-dithiins (32 a-c, 45) were obtained starting from appropriate thiophene precursors. The absorption maxima covered the range from 430 to 467 nm indicating olefinic rather than aromatic character of the anellating thiophene units. Access to the isomeric thieno[2,3-c] anellated series failed due to competing reactions in the final stage, e.g. by the formation of the 12-membered cyclic bis-disulfide 53.

One-step synthesis of resorcarene dimers composed of two tetra-benzoxazine units

Abstract The condensation of resorcarene 1 with ethylenediamine and an excess of formaldehyde gives, under high dilution conditions, in up to 15% yield the octa-benzoxazine dimer 2 in which two molecules of 1 are connected by four bridges. The structure of 2 has been confirmed by 1 H NMR spectra and MALDI-TOF mass spectra and by hydrolysis of the oxazine rings yielding the secondary amine 3 .

Calix[4]arenes with alkylidene bridges, synthesis and conformational properties

Abstract Calix[4]arenes with one or two alkylidene bridges were synthesized by “2+2” fragment condensation. As predicted by molecular mechanics calculations aliphatic residues at the bridging carbon atom(s) prefer the equatorial position.

Dimeric capsules of tetraurea calix[4]arenes. MD simulations and X-ray structure, a comparison

The single crystal X-ray structure of a homodimer of a tetra(tolylurea) calix[4]arene including a tetraethylammonium cation as guest shows an expansion of the capsule and a distortion of its shape, in comparison to the structure of a similar dimer with an encapsulated benzene molecule. Thus, only 8 of 16 possible hydrogen bonds are present in the hydrogen bonded belt holding together the two hemispheres. The encapsulated cation is disordered over two equivalent positions with two methyl groups pointing to the equator, while two methyl groups pointing to the poles form CH–π interactions with the inner surfaces of the calixarene cavities. MD simulations are in agreement with the distorted X-ray structure for a short simulation time of 1–2 ns with a given orientation of the included cation and approach for longer simulation times (9 ns) the fourfold symmetry found by 1H NMR spectroscopy in solution.

Conformational properties of methylene bridged resorcarenes

Abstract Conformations and conformational interconversions of resorcarene 1c have been studied by molecular mechanics calculations. As with calix[4]arenes the general stability of the four basic conformations is cone > partial cone > 1,2-alternate > 1,3-alternate. The lowest energy is calculated for a pinched cone conformer with C2v symmetry stabilised by intramolecular hydrogen bonds of the two “parallel” resorcinol units as donors. The topomerisation of the cone conformation proceeds via the partial cone and 1,2-alternate intermediates with a calculated barrier of 9.9 kcal mol−1 which is in excellent agreement with the experimental value.

Structural Analysis of Guanylyl Cyclase-Activating Protein-2 (GCAP-2) Homodimer by Stable Isotope-Labeling, Chemical Cross-Linking, and Mass Spectrometry

AbstractThe topology of the GCAP-2 homodimer was investigated by chemical cross-linking and high resolution mass spectrometry. Complementary conducted size-exclusion chromatography and analytical ultracentrifugation studies indicated that GCAP-2 forms a homodimer both in the absence and in the presence of Ca2+. In-depth MS and MS/MS analysis of the cross-linked products was aided by 15  N-labeled GCAP-2. The use of isotope-labeled protein delivered reliable structural information on the GCAP-2 homodimer, enabling an unambiguous discrimination between cross-links within one monomer (intramolecular) or between two subunits (intermolecular). The limited number of cross-links obtained in the Ca2+-bound state allowed us to deduce a defined homodimeric GCAP-2 structure by a docking and molecular dynamics approach. In the Ca2+-free state, GCAP-2 is more flexible as indicated by the higher number of cross-links. We consider stable isotope-labeling to be indispensable for deriving reliable structural information from chemical cross-linking data of multi-subunit protein assemblies. Figureᇵ