Jef A. J. M. Vekemans

Helical self-assembled polymers from cooperative stacking of hydrogen-bonded pairs.

The double helix of DNA epitomizes this molecules ability to self-assemble in aqueous solutions into a complex chiral structure using hydrogen bonding and hydrophobic interactions. Non-covalently interacting molecules in organic solvents are used to design systems that similarly form controlled architectures. Peripheral chiral centres in assemblies and chiral side chains attached to a polymer backbone have been shown to induce chirality at the supramolecular level, and highly ordered structures stable in water are also known. However, it remains difficult to rationally exploit non-covalent interactions for the formation of chiral assemblies that are stable in water, where solvent molecules can compete effectively for hydrogen bonds. Here we describe a general strategy for the design of functionalized monomer units and their association in either water or alkanes into non-covalently linked polymeric structures with controlled helicity and chain length. The monomers consist of bifunctionalized ureidotriazine units connected by a spacer and carrying solubilizing chains at the periphery. This design allows for dimerization through self-complementary quadruple hydrogen bonding between the units and solvophobically induced stacking of the dimers into columnar polymeric architectures, whose structure and helicity can be adjusted by tuning the nature of the solubilizing side chains.

Highly sustainable catalytic dehydrogenation of alcohols with evolution of hydrogen gas

The catalytic dehydrogenation of alcohols into aldehydes and ketones in the absence of H-acceptors was studied with several transition metal catalysts in order to develop a large-scale procedure. Applying Ru(OCOCF3)2(CO)(PPh3)2, the so called Robinson catalyst, several secondary alcohols could be dehydrogenated with high selectivity into the corresponding ketones in relatively short reaction times. Highly effective atom utilization could be realized avoiding solvents and giving hydrogen gas as the sole by-product. However, in contrast to Robinsons work the catalytic dehydrogenation of primary alcohols appeared to be problematic due to decarbonylation with concomitant catalyst deactivation and aldol condensation under the strong acid or basic conditions applied.

Controlled Supramolecular Oligomerization of C3‐Symmetrical Molecules in Water: The Impact of Hydrophobic Shielding

The supramolecular oligomerization of three water-soluble C(3)-symmetrical discotic molecules is reported. The compounds all possess benzene-1,3,5-tricarboxamide cores and peripheral Gd(III)-DTPA (diethylene triamine pentaacetic acid) moieties, but differ in their linker units and thus in their propensity to undergo secondary interactions in H(2)O. The self-assembly behavior of these molecules was studied in solution using circular dichroism, UV/Vis spectroscopy, nuclear magnetic resonance, and cryogenic transmission electron microscopy. The aggregation concentration of these molecules depends on the number of secondary interactions and on the solvophobic character of the polymerizing moieties. Hydrophobic shielding of the hydrogen-bonding motif in the core of the discotic is of paramount importance for yielding stable, helical aggregates that are designed to be restricted in size through anti-cooperative, electrostatic, repulsive interactions.

Unravelling the fine structure of stacked bipyridine diamine-derived C-3-discotics as determined by X-ray diffraction, quantum-chemical calculations, Fast-MAS NMR and CD spectroscopy

An in depth investigation of the fine structure adopted by the helical stacks of C3-discotics 1 incorporating three 3,3′-diamino-2,2′-bipyridine units is described. In the bulk the molecules display liquid crystalline behaviour in a temperature window of >300 K and an ordered rectangular columnar mesophase (Colro) with an inter-disc distance of 3.4 A is assigned. X-Ray diffraction on aligned samples has also revealed a helical superstructure in the liquid crystalline state, and a rotation angle of 13–16° between consecutive discs. The proposed superstructure in the bulk phase has been further substantiated by a combination of quantum-chemical calculations and solid-state NMR spectroscopy. Dilute solution NMR spectroscopy and elaborate CD spectroscopy on aggregated samples have revealed an isodesmic growth pattern of the C3-discotics. From the combined results it has become evident that the fine tuning interaction responsible for the highly ordered helical architectures is not weak intermolecular hydrogen bonding, but rather rigidification, due to propeller formation after preorganisation by π–π interactions. Although all the techniques used underpin the structural features proposed, none of them individually is able to point to a unique structure. However, together the techniques give very strong evidence for a confined ship-screw arrangement in which all amidic carbonyl oxygens point in one direction.

Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2).

Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, this is achieved with mineralocorticoid receptor antagonists, however, aldosterone synthase (CYP11B2) inhibitors may offer a promising alternative. In this study, we used three-dimensional modeling of CYP11B2 to model the binding modes of the natural substrate 18-hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead MOERAS115 (4-((5-phenyl-1H-imidazol-1-yl)methyl)benzonitrile) displaying an IC(50) for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC(50) for CYP11B2 6.0 nM, selectivity 19.8). Molecular docking of the inhibitors in the models enabled us to generate posthoc hypotheses on their binding modes, providing a valuable basis for future studies and further design of CYP11B2 inhibitors.

Dynamic and bio-orthogonal protein assembly along a supramolecular polymer

Dynamic protein assembly along supramolecular columnar polymers has been achieved through the site-specific covalent attachment of different SNAP-tag fusion proteins to self-assembled benzylguanine-decorated discotics. The self-assembly of monovalent discotics into supramolecular polymers creates a multivalent, bio-orthogonal and self-regulating framework for protein assembly. The intrinsic reversibility of supramolecular interactions results in reorganization and exchange of building blocks allowing for dynamic intermixing of protein-functionalized discotics between different self-assembled polymers, leading to self-optimization of protein arrangement and distance as evidenced by efficient energy transfer between fluorescent proteins.

The mechanism of the oxidation of benzyl alcohol by iron(III)nitrate: Conventional versus microwave heating

The mechanism of the oxidation of benzyl alcohol with iron(III)nitrate nonahydrate under conventional and under microwave heating conditions has been investigated and the reaction conditions have been optimized. A series of redox reactions leads to the formation of benzaldehyde and other products. Direct comparison between conventional and microwave heating revealed identical conversions profiles. Mastering the microwave induced heat, absence of a real microwave effect and byproduct formation are the major factors to advise a traditional batch-wise way of process development to a larger scale.

Oligoheterocycles by the Stille-coupling reaction

In this paper the applicability of the Stille-coupling reaction for the synthesis of a variety of oligoheterocyclic compounds is presented. Despite some experimental difficulties (destannylation, purification) we have been able to synthesize a wide variety of compounds based on combinations of pyrrole, thiophene and benzene units in reasonable yields.

Ladderlike oligomers : intramolecular hydrogen bonding, push-pull character, and electron affinity

Symmetrical 2,5-bis(2-aminophenyl)pyrazines have been synthesized by application of the Stille coupling strategy. These cotrimers feature three important properties, namely strong intramolecular hydrogen bonding, push-pull character, and high electron affinity. The presence of intramolecular hydrogen bonds has been confirmed by 1H NMR, IR spectroscopy, and single-crystal X-ray diffraction. The hydrogen bond strength can be increased by substituting the amino groups with stronger electron-withdrawing functionalities. Despite the anticipated enhanced pi-conjugation through planarization, a hypsochromic shift was observed in the UV/Vis spectra, explained by a decrease in push-pull character. The electron affinity of the cotrimers was deduced from the first reduction potentials measured by cyclic voltammetry and is related to the electron-withdrawing character of the amino substituents. The results obtained have been compared with those of the corresponding 4-aminophenyl analogues and show that intramolecular hydrogen bonds can be used to design polymers with enhanced pi conjugation as well as a high electron affinity.

The Influence of Lithium Perchlorate on Discotic Liquid Crystals and the Ion Conduction of their Mixtures

Abstract A C3-symmetric trimesic amide derivative with peripheral oligo(ethylene oxide) side chains (compound 1) shows discotic mesomorphism in a broad temperature range due to stacking of the extended core (Tg ∼ -50[ddot]C; Tcl ∼ 240[ddot]C). Mixtures of 1 and lithium perchlorate (LiClO4) also exhibit liquid crystalline (LC) properties as shown by polarization microscopy, DSC and X-ray diffraction studies. An increase of the Tg as well as a decrease of the clearing temperature are observed with increasing salt concentration. The ion conducting properties of the LiClO4-mixtures of 1 have been measured by complex impedance spectroscopy; promising levels of conductivity, up to 10−6 S/cm at room temperature, have been recorded.