Kay Severin

Multicomponent Assembly of Boronic Acid Based Macrocycles and Cages

Reference LCS-ARTICLE-2008-014doi:10.1002/anie.200705272View record in Web of Science Record created on 2008-02-15, modified on 2017-05-12

Boronic acids as building blocks for molecular nanostructures and polymeric materials

Boronic acids are versatile building blocks for the construction of complex molecular architectures. Using reversible condensation reactions, it is possible to obtain macrocycles, cages, dendritic structures, and rotaxanes, as well as 1-, 2-, and 3-dimensional polymers in one-pot reactions from simple starting materials. This perspective highlights important recent developments in this area.

A Coordination Cage with an Adaptable Cavity Size

A hexanuclear coordination cage can increase the size of its cavity from nearly zero to more than 500 Å(3), which allows the encapsulation of two coronene molecules.

Connection of Metallamacrocycles via Dynamic Covalent Chemistry: A Versatile Method for the Synthesis of Molecular Cages

A modular approach for the synthesis of cage structures is described. Reactions of [(arene)RuCl(2)](2) [arene = p-cymene, 1,3,5-C(6)H(3)Me(3), 1,3,5-C(6)H(3)(i-Pr)(3)] with formyl-substituted 3-hydroxy-2-pyridone ligands provide trinuclear metallamacrocycles with pendant aldehyde groups. Subsequent condensation reactions with di- and triamines give molecular cages with 3, 6, or 12 Ru centers in a diastereoselective and chemoselective (self-sorting) fashion. Some of the cages can also be prepared in one-pot reactions by mixing [(arene)RuCl(2)](2) with the pyridone ligand and the amine in the presence of base. The cages were comprehensively analyzed by X-ray crystallography. The diameter of the largest dodecanuclear complex is ∼3 nm; the cavity sizes range from 290 to 740 Å(3). An amine exchange process with ethylenediamine allows the clean conversion of a dodecanuclear cage into a hexanuclear cage without disruption of the metallamacrocyclic structures.

Synthesis of Molecular Nanostructures by Multicomponent Condensation Reactions in a Ball Mill

The condensation of multiple building blocks in a ball mill allows molecular cages with a size up to 3.1 nm to be built.

Transferring the concept of multinuclearity to ruthenium complexes for improvement of anticancer activity.

Multinuclear platinum anticancer complexes are a proven option to overcome resistance of established anticancer compounds. Transferring this concept to ruthenium complexes led to the synthesis of dinuclear Ru(II)-arene compounds containing a bis(pyridinone)alkane ligand linker. A pronounced influence of the spacer length on the in vitro anticancer activity was found, which is correlated to the lipophilicity of the complexes. IC(50) values in the same dimension as for established platinum drugs were found in human tumor cell lines. No cross-resistance to oxoplatin, a cisplatin prodrug, was observed for the most active complex in three resistant cell lines; in fact, a 10-fold reversal of sensitivity in two of the oxoplatin-resistant lines was found. (Bio)analytical characterization of the representative examples showed that the ruthenium complexes hydrolyze rapidly, forming predominantly diaqua species that exhibit affinity toward transferrin and DNA, indicating that both proteins and nucleobases are potential targets.

Self-assembled organometallic receptors for small ions

Trinuclear metallamacrocycles can be obtained by reactions of (arene)Ru, Cp*Rh and Cp*Ir complexes with pyridonate ligands. Using 3-oxy-pyridonate as the bridging ligand, organometallic analogues of 12-crown-3 are formed, which display an extremely high affinity and selectivity for lithium and sodium ions. In the presence of guest molecules, the redox-potential of the metallamacrocyclic hosts is shifted by more than 300 mV towards positive potential suggesting potential applications as chemosensors. The affinity of the metallacrown complexes is sufficient to allow the stabilization of molecular LiFHF and LiF. The fact that complexes of LiF can be isolated was used to construct a specific receptor for fluoride ions

Selective Recognition of Fluoride Anion Using a Li+–Metallacrown Complex

Reference LCS-ARTICLE-2002-004View record in Web of Science Record created on 2006-02-09, modified on 2017-05-12

A synthetic peptide ligase

The preparation of synthetic molecules showing the remarkable efficiencies characteristic of natural biopolymer catalysts remains a formidable challenge for chemical biology. Although significant advances have been made in the understanding of protein structure and function, the de novo construction of such systems remains elusive. Re-engineered natural enzymes and catalytic antibodies, possessing tailored binding pockets with appropriately positioned functional groups, have been successful in catalysing a number of chemical transformations, sometimes with impressive efficiencies. But efforts to produce wholly synthetic catalytic peptides have typically resulted in compounds with questionable structural stability, let alone reactivity. Here we describe a 33-residue synthetic peptide, based on the coiled-coil structural motif, which efficiently catalyses the condensation of two shorter peptide fragments with high sequence- and diastereoselectivity. Depending on the substrates used, we observe rate enhancements of tenfold to 4,100-fold over the background, with catalytic efficiencies in excess of 104. These results augur well for the rational design of functional peptides.

Autocatalytic networks: the transition from molecular self-replication to molecular ecosystems

The transition from inanimate to animate chemistry is thought to involve self-organised networks of molecular species whose collective emergent property gives rise to the overall characteristics of living systems. In the past, simple autocatalytic networks have been constructed that display basic forms of cooperative behaviour. These include reciprocal catalysis, autocratic, and hypercyclic networks. The design and emergent properties of these novel molecular networks are reviewed here.