Carsten Schmuck

Self-Complementary Quadruple Hydrogen-Bonding Motifs as a Functional Principle: From Dimeric Supramolecules to Supramolecular Polymers

The self-association of individual molecules can lead to the formation of highly complex and fascinating supramolecular aggregates. However, for binding motifs which rely only on hydrogen bonds, a combination of several such weak interactions is necessary to observe self-association in solution. Systems based on four hydrogen bonds in a linear array can be obtained which efficiently aggregate at least in chloroform. Besides the physical-organic characterization of these aggregates and the factors influencing their stability, such quadruple hydrogen-bonding motifs can also be used in the field of materials science to synthesize, for the first time, supramolecular polymers through the self-association of self-complementary monomers. As the formation of noncovalent interactions is reversible and their strength depends significantly on the chemical environment (for example, solvent, temperature), the macroscopic properties of such polymers can be controlled by variation of these parameters; hence a first step towards intelligent materials with tailor-made properties is made.

SERS Labels for Red Laser Excitation: Silica‐Encapsulated SAMs on Tunable Gold/Silver Nanoshells

In a glass house: Silica-encapsulated self-assembled monolayers (SAMs) on tunable gold/silver nanoshells were used as labels for surface-enhanced Raman scattering (SERS). This concept combines the spectroscopic advantages arising from maximum surface coverage and uniform molecular orientation of the Raman reporter molecules within the complete monolayer together with the high chemical and mechanical stability of the glass shell.

Switchable supramolecular polymers from the self-assembly of a small monomer with two orthogonal binding interactions.

The low molecular weight heteroditopic monomer 1 forms supramolecular polymers in polar solution as shown, for example, by infrared laser-based dynamic light scattering (DLS), small-angle neutron scattering (SANS), electron microscopy (TEM, cryo-TEM), and viscosity measurements. Self-assembly of 1 is based on two orthogonal binding interactions, the formation of a Fe(II)-terpyridine 1:2 metal-ligand complex and the dimerization of a self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterion. Both binding interactions have a sufficient stability in polar (DMSO) and even aqueous solutions to ensure formation of linear polymers of considerable length (up to 100 nm). The supramolecular polymerization follows a ring-chain mechanism causing a significant increase in the viscosity of the solutions at millimolar concentrations and above. The linear polymers then further aggregate in solution into larger globular aggregates with a densely packed core and a loose shell. Both binding interactions can be furthermore switched on and off either by adding a competing ligand to remove the metal ion and subsequent readdition of Fe(II) or by reversible protonation and deprotonation of the zwitterion upon addition of acid or base. The self-assembly of 1 can therefore be switched back and forth between four different states, the monomer, a metal-complexed dimer or an ion paired dimer, and finally the polymer.

Carboxylate Binding by 2-(Guanidiniocarbonyl)pyrrole Receptors in Aqueous Solvents: Improving the Binding Properties of Guanidinium Cations through Additional Hydrogen Bonds

A series of guanidiniocarbonyl pyrrole receptors has been synthesized which bind carboxylates by ion pairing in combination with multiple hydrogen bonds. Their binding properties with various carboxylates have been investigated using NMR titration studies in 40% water/DMSO (v/v). The best receptor has association constants which are in the order of K approximately/= 10(3) mol(-1) and hence some 30 times larger than with the simple acetyl guanidinium cation. Through a systematic variation of the receptor structure, semiquantitative estimates for the energetic contributions of the individual binding interactions could be derived. These data show that the various hydrogen bonds are not equally important for the binding but differ significantly in their energetic contribution to the overall complexation process. Furthermore, the receptor can be made chiral and shows selectivity upon binding of enantiomeric amino acid carboxylates. Molecular modeling was used to obtain structural information for the various receptor carboxylate complexes and served as a basis to explain the observed differences in binding constants.

Peptide Functionalized Polydiacetylene Liposomes Act as a Fluorescent Turn-On Sensor for Bacterial Lipopolysaccharide

Mixed polydiacetylene (PDA) liposomes functionalized on their surface with a fluorescent pentalysine peptide derivative and histidine in a ratio of 1:9 can identify bacterial lipopolysaccharide (LPS). Upon photopolymerization of the self-assembled liposomes the initial fluorescence of the peptide-diacetylene amphiphiles is quenched. Interaction with LPS in aqueous solution or on the surface of E. coli DH5α restores the fluorescence. This increase in fluorescence is selective for LPS relative to other negatively charged analytes including nucleotides and ctDNA. This simple turn-on fluorescent sensor allows detecting LPS even at low micromolar concentrations.

Ion-pair induced self-assembly in aqueous solvents

The intriguing advantages of supramolecular chemistry and particularly the application of self-assembly for the construction of defined nanostructures from small, preferably synthetically easily accessible molecules has become a promising area of modern chemistry in the last years. However, the main focus of early work was based on H-bond induced self-assembly which is limited to nonpolar organic solvents. In the past years the field started to shift more and more towards obtaining self-assembling architectures in polar solvents and even water. This tutorial review will discuss some representative examples for self-assembling systems in polar solvents in order to illustrate the different concepts and strategies that can be used. We will also briefly discuss the special properties of water as the ultimate protic solvent from the perspective of a supramolecular chemist to elucidate the challenges that this solvent still poses even today to obtain specific self-assembled nanostructures.

A molecular peptide beacon for the ratiometric sensing of nucleic acids.

A pyrene-functionalized cationic oligopeptide 1 efficiently binds to double-stranded DNA, as shown by different spectrophotochemical studies. Upon binding, the conformation of 1 changes from a folded to an extended form, which leads to a distinct change in the fluorescence properties. Thus, 1 functions as a molecular peptide beacon, and as it is easily taken up by cells, 1 can also be used for imaging of nucleic acids within cells.

Advances in switchable supramolecular nanoassemblies.

Supramolecular nanoassemblies are gaining increasing importance as promising new materials with considerable potential for novel and promising applications. Within supramolecular nanoassemblies the connectivity of the monomeric units is based on reversible noncovalent interactions, like van der Waals interactions, hydrogen bonding, or ionic interactions. As the strength of these interactions depends on the molecular surrounding, the formation of nanoassemblies in principle can be controlled externally by changing the environment and/or the molecular shape of the underlying monomer. This way it is not only possible to switch the self-assembly on or off, but also to change between different aggregation states. In this minireview we present some recent selected approaches to supramolecular stimuli-responsive nanoassemblies.

Molecular Recognition of Vesicles: Host–Guest Interactions Combined with Specific Dimerization of Zwitterions

The aggregation of beta-cyclodextrin vesicles can be induced by an adamantyl-substituted zwitterionic guanidiniocarbonylpyrrole carboxylate guest molecule (1). Upon addition of 1 to the cyclodextrin vesicles at neutral pH, the vesicles aggregate (but do not fuse), as shown by using UV/Vis and fluorescence spectroscopy, dynamic light scattering, zeta-potential measurements, cryogenic transmission electron microscopy, and atomic force microscopy. Aggregation of the vesicles is induced by a twofold supramolecular interaction. First, the adamantyl group of 1 forms an inclusion complex with beta-cyclodextrin. Second, at neutral pH the guanidiniocarbonylpyrrole carboxylate zwitterion dimerizes through the formation of hydrogen-bonded ion pairs. Because the dimerization of 1 depends on the zwitterionic protonation state of 1, the aggregation of the cyclodextrin vesicles is also pH dependent; the cyclodextrin vesicles do not interact at pH 5 or 9, at which 1 is either cationic or anionic and, therefore, not self-complementary. These observations are consistent with molecular recognition of the vesicles through a combination of two different supramolecular interactions, that is, host-guest inclusion and dimerization of zwitterions, at the bilayer membrane surface.

Highlights in bioorganic chemistry : methods and applications

Foreword.Preface.List of Contributors.PART 1: BIOMOLECULES AND THEIR CONFORMATION.1.1 Equilibria of RNA Secondary Structures (R. Micura & C. Hobartner).1.2 Synthesis and Application of Proline and Pipecolic Acid Derviatives: Tools for Stabilization of Peptide Secondary Structures (W. Maison).1.3 Stabilization of Peptide Microstructures by Coordination of Metal Ions (M. Albrecht).1.4 Conformational Restriction of Sphingolipids (T. Kolter).1.5 s-Amino Acids in Nature (F. von Nussbaum & P. Spiteller).1.6 Biosynthesis of s-Amino Acids (P. Spiteller & F. von Nussbaum ).PART 2: NON-COVALENT INTERMOLECULAR INTERACTIONS.2.1 Carbohydrate Recognition by Artificial Receptors (A. Lutzen).2.2 Cyclopeptides as Macrocyclic Host Molecules for Charged Guests (S. Kubik).2.3 Bioorganic Receptors for Amino Acids and Peptides: Combining Rational Design with Combinatorial Chemistry (C. Schmuck, et al.).2.4 Artficial Receptors for the Stabilization of s-Sheet Structures (T. Scrader, et al.).2.5 Evaluation of the DNA-binding Properties of Cationic Dyes by Absorption and Emission Spectroscopy (H. Ihmels, et al.). 2.6 Interaction of Nitrogen Monoxide and Peroxynitrite with Hemoglobin and Myoglobin (S. Herold).2.7 Synthetic Approaches to Study Multivalent Carbohydrate-Lectin Interactions (V. Wittmann).PART 3: STUDIES IN DRUG DEVELOPMENTS.3.1 Building a Bridge Between Chemistry and Biology-Molecular Forceps that Inhibit the Farnesylation of RAS (H. Nestler).3.2 Inhibitors Against Human Mast Cell Tryptase: A Potential Approach to Attack Asthma? (T. Martin).3.3 Preparation of Novel Steroids by Microbiological and Combinatorial Chemistry (C. Huwe, et al.).3.4 Enantiomeric Nucleic Acids-Spiegelmers (S. Klussmann).3.5 Aspartic Proteases Involved in Alzheimers Disease (B. Schmidt & A. Siegler).3.6 Novel Polymer and Linker Reagents for the Preparation of Protease-inhibitor Libraries (J. Rademann).PART 4: STUDIES IN DIAGNOSTIC DEVELOPMENTS.4.1 Selectivity of DNA Replication (A. Marx, et al.).4.2 Homogeneous DNA Detection (O. Seitz).4.3 Exploring the Capabilities of Nucleic Acid Polymerases by Use of Directed Evolution (S. Brakmann & M. Schlicke).4.4 Labeling of Fusion Proteins with Small Molecules.in vito (S. Gendreizig, et al.).4.5 Oxidative Splitting of Pyrimidine Cyclobutane Dimers (U. Wille).4.6 Charge Transfer in DNA (H. Wagenknecht).PART 5: CATALYSIS.5.1 Protease-catalyzed Formation of C-N Bonds (F. Bordusa).5.2 Twin Ribozymes (S. Muller, et al.).5.3 RNA as a Catalysts: The Diels-Alderase Ribozyme (S. Keiper, et al.).5.4 Combinatorial Methods for the Discovery of Catalysts (H. Wennemers).PART 6: METHODOLOGY, BIOENGINEERING AND BIOINSPIRED ASSEMBLIES.6.1 Linkers for Solid-phase Synthesis (K. Knepper, et al.).6.2 Small Molecule Arrays (R. Breinbauer, et al.).6.3 Biotechnological Production of d-Pantothenic Acid and its Precursor d-Pantolactone (M. Kesseler).6.4 Microbially Produced Functionalized Cyclohexadiene-trans-diols as a New Class of Chiral Building Block in Organic Synthesis: On the Way to Green and Combinatorial Chemistry (V. Lorbach, et al.).6.5 Artifical Molecular Rotary Motors Based on Rotaxanes (T. Felder & C. Schalley).6.6 Chemical Approaches for the Preparation of Biologically-inspired Supramolecular Architectures and Advanced Polymeric Materials (H. Klok).Index.