Stefan Immel

Guest-induced conformational change in a flexible host: mono-altro-β-cyclodextrin †

Mono-altro--cyclodextrin 1 ,a -cyclodextrin with one of the seven glucose units being configurationally changed to an altrose, is shown to be a flexible host undergoing a distinct conformational change within its altropyranose geometry upon intracavity inclusion of adamantanecarboxylate, thus representing an induced-fit model of binding rather than one following the rigid lock-and-key type pattern.

Cyclodextrins, cyclomannins, and cyclogalactins with five and six (1→4)-linked sugar units: A comparative assessment of their conformations and hydrophobicity potential profiles1

Abstract A molecular modeling study of the (1→4)-linked cyclooligosaccharides containing five and six α- D -glucose, α- D -mannose, and β- D -galactose units, respectively, provide a clear conception of their overall conformations, their contact surfaces, and their cavity proportions. A MOLCAD-based generation of their molecular lipophilicity potential (MLPs) gives a lucid picture of their hydrophobic and hydrophilic surface areas, and hence, a first estimation of their inclusion properties.

Insights into Sonogashira Cross-Coupling by High-Throughput Kinetics and Descriptor Modeling

A method is presented for the high-throughput monitoring of reaction kinetics in homogeneous catalysis, running up to 25 coupling reactions in a single reaction vessel. This method is demonstrated and validated on the Sonogashira reaction, analyzing the kinetics for almost 500 coupling reactions. First, one-pot reactions of phenylacetylene with a set of 20 different meta- and para-substituted aryl bromides were analyzed in the presence of 17 different Pd-phosphine complexes. In addition, the temperature-dependent Sonogashira reactions were examined for 21 different ArX (X=Cl, Br, I) substrates, and the corresponding activation enthalpies and entropies were determined by means of Eyring plots: ArI (DeltaH(not equal)=48-62 kJ mol(-1); DeltaS(not equal)=-71--39 J mol(-1) K; NO(2)-->OMe), ArBr (DeltaH(not equal)=54-82 kJ mol(-1), DeltaS(not equal)=-55-11 J mol(-1) K), and ArCl (DeltaH(not equal)=95-144 kJ mol(-1), DeltaS(not equal)=-6-100 J mol(-1) K). DFT calculations established a linear correlation of DeltaH( not equal) and the Kohn-Sham HOMO energies of ArX (X=Cl, Br, I) and confirmed their involvement in the rate-limiting step. However, despite different C--X bond energies, aryl iodides and electron-deficient aryl bromides showed similar activation parameters.

The Gilch Synthesis of Poly(p-phenylene vinylenes): Mechanistic Knowledge in the Service of Advanced Materials

A consistent picture is presented of the mechanistic details and intermediates of the Gilch polymerization leading to poly(p-phenylene vinylenes) (PPVs). In-situ generated p-quinodimethanes are shown to be the real monomers, and spontaneous formation of the initiating radicals is effected by dimerization of some of these monomers to dimer diradicals, the latter also being the reason why significant amounts of [2.2]paracyclophanes are formed as side-products. Chain propagation predominantly proceeds by radical chain growth, occasionally interrupted by polyrecombination events between the growing α,ω-macro-diradicals. Based on this knowledge, oxygen is identified as a very efficient molar-mass regulating agent, and the temporary gelation of the reaction mixtures is interpreted to be the consequence of a very high entanglement of the polymers immediately after their formation. Last but not least, it is rationalized why the usually considered constitutional defects in Gilch PPVs might not be the only and most relevant ones with respect to the efficiency and durability of the organic light emitting devices produced thereof, and why cis-configurated halide-bearing vinylene moieties should be perceived as being among the most critical candidates. These considerations result in the recommendation of straightforward measures that should lead to clearly improved PPVs.

Solution Geometries and Lipophilicity Patterns ofα-Cycloaltrin

The first thoroughly flexible cyclooligosaccharide, α-cycloaltrin, adopts various geometries between disk-shaped (1 a) and torus-type (1 b) conformations in water. This altrose analogue of α-cyclodextrin constitutes an ideal model with which to probe the induced-fit mode of guest–host interactions.

THE LIPOPHILICITY PATTERNS OF CYCLODEXTRINS AND OF NON-GLUCOSE CYCLOOLIGOSACCHARIDES

Computer-aided generation of the 3D-geometries and the contact surfaces for the cyclodextrins and cyclooligosaccharides composed of mannose, altrose, galactose, and fructose provide a lucid picture of their molecular architecture, most notably their cavity dimensions. The MOLCAD programs computation of the molecular lipophilicity patterns (MLPs), projected in color-coded form onto the respective contact surfaces, for the first time allow a detailed localization of hydrophobic and hydrophilic domains, which to a substantial degree determine the capabilities of these cyclooligosaccharides for inclusion complex formation.

Enterococcus faecalis utilizes maltose by connecting two incompatible metabolic routes via a novel maltose 6′-phosphate phosphatase (MapP)

Similar to Bacillus subtilis, Enterococcus faecalis transports and phosphorylates maltose via a phosphoenolpyruvate (PEP):maltose phosphotransferase system (PTS). The maltose‐specific PTS permease is encoded by the malT gene. However, E. faecalis lacks a malA gene encoding a 6‐phospho‐α‐glucosidase, which in B. subtilis hydrolyses maltose 6′‐P into glucose and glucose 6‐P. Instead, an operon encoding a maltose phosphorylase (MalP), a phosphoglucomutase and a mutarotase starts upstream from malT. MalP was suggested to split maltose 6‐P into glucose 1‐P and glucose 6‐P. However, purified MalP phosphorolyses maltose but not maltose 6′‐P. We discovered that the gene downstream from malT encodes a novel enzyme (MapP) that dephosphorylates maltose 6′‐P formed by the PTS. The resulting intracellular maltose is cleaved by MalP into glucose and glucose 1‐P. Slow uptake of maltose probably via a maltodextrin ABC transporter allows poor growth for the mapP but not the malP mutant. Synthesis of MapP in a B. subtilis mutant accumulating maltose 6′‐P restored growth on maltose. MapP catalyses the dephosphorylation of intracellular maltose 6′‐P, and the resulting maltose is converted by the B. subtilis maltose phosphorylase into glucose and glucose 1‐P. MapP therefore connects PTS‐mediated maltose uptake to maltose phosphorylase‐catalysed metabolism. Dephosphorylation assays with a wide variety of phospho‐substrates revealed that MapP preferably dephosphorylates disaccharides containing an O‐α‐glycosyl linkage.

Topography of the 1:1 α-cyclodextrin–nitromethane inclusion complex

Abstract Dissolution of α-cyclodextrin (α-CD) in 9:1 water–nitromethane smoothly generates the title compound, which crystallizes as the pentahydrate in the orthorhombic space group P212121 with a=9.452(4), b=14.299(3), c=37.380(10) A, and Z=4. Its crystal structure analysis revealed the α-CD macrocycle in an unstrained conformation stabilized through a ring of O-2⋯O-3′ hydrogen bonds between five of the six adjacent glucose residues. The nitromethane is located in the α-CD cavity in an orientation parallel to the plane of the macrocycle, and assumes two sites of equal population with the nitro group in excessive thermal motion; the guest is held by van der Waals contacts and C-H⋯O-type hydrogen bonds to the pyranose H-3 and H-5 protons. The packing of the macrocycles in the crystal lattice is of cage herringbone-type with an extensive intra- and intermolecular hydrogen bonding network. The ready formation of a nitromethane inclusion complex in aqueous nitromethane, and the subtleties of its molecular structure amply demonstrate the ease with which water is expelled from the α-CD cavity by a more hydrophobic co-solvent.

Atropdiastereoisomers of ellagitannin model compounds: configuration, conformation, and relative stability of d-glucose diphenoyl derivatives

Abstract Conformational analysis reveals a remarkable rigidity of 2,3-, 4,6-, 3,6-, and 2,4- O -( S )- and ( R )-diphenoyl (DP) bridged methyl β- d -glucosides, which were used as model compounds to evaluate the atropisomeric features of the natural ellagitannins, which possess at least one hexahydroxydiphenoyl (HHDP) moiety. The 2,3- and 4,6- O -( S )-DP bridged glucosides with 4 C 1 pyranose geometries are thermodynamically more stable than their ( R )-DP counterparts, whilst in the 3,6- and 2,4- O -linked series with 1 C 4 glucopyranose geometries the ( R )-DP configuration is preferred. The chiral scaffold of glucose exerts a strong atropdiastereoselective effect onto the diphenoyl units, which is mediated through 10- to 12-membered rings via ester linkages. The calculated results not only explain the observed ( S )-diastereoselectivity of di-esterification reactions of suitably protected racemic hexaoxydiphenic acids with 4,6-unsubstituted d -glucopyranose derivatives, but also correlate the observed configuration of axially chiral HHDP-moieties of natural ellagitannins with conformational parameters.

The 2,3-anhydro-α-cyclomannin−1-propanol hexahydrate: topography, lipophilicity pattern and solid-state architecture

Abstract As evidenced by its X-ray structural analysis, 2,3-anhydro-α-cyclomannin 6 , a cyclooligosaccharide consisting of six α-(1→4)-linked 2,3-anhydro -d- mannopyranose units, readily incorporates 1-propanol into its cavity such that hydrophobic and hydrophilic surface regions of guest and host match at their interfaces. Together with water, the macrocycle and its guest assemble into a unique solid-state architecture, featuring layers of head-to-head dimers of the macrocycle with its guest, separated by equally distinct layers of water molecules, which are engaged in an intense hydrogen bonding network with the 6-CH 2 OH and the propanol-OH groups. The overall guest–host topography is thus reverse to that of the respective ethanol inclusion complex. 1