Thomas Rehm

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.

Spermine‐Functionalized Perylene Bisimide Dyes—Highly Fluorescent Bola‐Amphiphiles in Water

A series of four spermine-functionalized perylene bisimide dyes without linkers (1) and with linkers (2-4) between the chromophore and the polyamine was synthesized. Protonation of the spermine moieties resulted in the formation of highly water-soluble dyes with up to six positively charged ammonium ions. The aggregation behavior of these strongly fluorescent bola-amphiphiles was studied in pure water as solvent by UV/Vis and fluorescence spectroscopy, and an astonishingly high fluorescence quantum yield of up to Phi(fl)=0.90 was observed for PBI 1. Atomic force microscopy and transmission electron microscopy were applied for the visualization of the aggregates on surfaces. Molecular modeling studies were performed by force-field calculations to explore the aggregate morphologies, which also provided valuable information on the influence of the additional alkylcarbonyl linkers. Our detailed spectroscopic and microscopic investigations revealed that the excellent optical properties of perylene bisimide chromophores can be used even in pure deionized water if their aggregation is efficiently suppressed.

A new type of soft vesicle-forming molecule: an amino acid derived guanidiniocarbonyl pyrrole carboxylate zwitterion.

The self-assembly of the l-alanine derived zwitterion 3 leads to the formation of soft vesicles in solution even though this surprisingly small molecule does not possess the classical amphiphilic features of other vesicle-forming monomers.

Interaction of spermine-alanine functionalized perylene bisimide dye aggregates with ds-DNA/RNA secondary structure

We report for the first time on the interaction of self-assembled perylene bisimide (PBI) dye aggregates with polynucleotides, revealing very high (nM) binding constants and exceptional thermal stabilization of double-stranded (ds)-DNA/RNA. Induced CD profiles of PBI dimer aggregates formed within DNA/RNA grooves show high sensitivity on the steric properties of the binding site, suggesting the applicability of such self-adjusting excitonically coupled PBI dimers for the sensing of the DNA/RNA secondary structure.

pH-switchable vesicles from a serine-derived guanidiniocarbonyl pyrrole carboxylate zwitterion in DMSO.

This work describes a new type of vesicles that can be reversibly opened and closed by changing the protonation state of a self-assembling zwitterion. Vesicles are interesting nanomaterials with potential applications such as delivery systems for drug targeting. For this purpose, however, external control of vesicle formation is required. To date, vesicle formation has often been based on the self-assembly of amphiphilic macromolecules such as lipid derivatives or block copolymers. 2] Recently, vesicle formation from other types of building blocks, such as shape-persistent macrocyles, cyclodextrins, or small peptides has also been reported. Most of these molecules are still classical amphiphiles and their self-assembly is mainly driven by hydrophobic or aromatic interactions. We have recently introduced a new type of vesicle forming-molecule, namely a self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterion derived from alanine. We have shown by NOESY NMR studies in combination with TEM and AFM experiments that, in DMSO, the zwitterion forms ion-paired dimers that then further aggregate into hollow vesicles of approximately 40–50 nm diameter. We have also used this special type of hydrogen-bond-assisted ion-pair formation between the guanidiniocarbonyl pyrrole cation and a carboxylate unit for the construction of other types of nanostructures such as dimers, loops, and supramolecular polymers. As the guanidiniocarbonyl pyrrole moiety has an approximate pKa value of 6–7, ion-pair formation with a carboxylate (pKa ca. 3–5) only occurs within a narrow pH range. This restriction offers the possibility to deliberately turn the ion-pair formation on or off by changing the pH from neutral to slightly acidic or basic. We therefore wanted to explore whether we can also trigger vesicle formation by using pH as an external signal. To test this hypothesis, we have synthesized a serine-derived guanidiniocarbonyl pyrrole carboxylate zwitterion 3 and studied its vesicle formation on surface with AFM as well as in solution by using dynamic light scattering (DLS) and a pulsed field gradient(PFG)-based NMR method. The latter method allows us to selectively detect the solvent molecules encapsulated in the vesicles and also to quantify the permeability of the vesicle membranes. We show herein that vesicle formation of 3 can indeed be switched on and off in a controlled manner by reversible changes of its protonation state. Furthermore, we found that the vesicles are rather impermeable and the measured exchange rate of solvent molecules across the membrane is very small. The synthesis of the serine-derived guanidiniocarbonyl pyrrole carboxylate zwitterion 3 is shown in Scheme 1. l-serine methyl ester hydrochloride 2 was coupled with the

Guanidiniocarbonylpyrrole-aryl derivatives: structure tuning for spectrophotometric recognition of specific DNA and RNA sequences and for antiproliferative activity.

We present a systematic study of different guanidiniocarbonylpyrrole-aryl derivatives designed to interact with DNA or RNA both through intercalation of an aromatic moiety into the base stack of the nucleotide and through groove binding of a guanidiniocarbonylpyrrole cation. We varied 1) the size of the aromatic ring (benzene, naphthalene, pyrene and acridine), 2) the length and flexibility of the linker connecting the two binding groups, and 3) the total number of positive charges present at different pH values. The compounds and their interactions with DNA and RNA were studied by UV/Vis, fluorescence and CD spectroscopy. Antiproliferative activities against human tumour cell lines were also determined. Our studies show that efficient interaction with, for example, DNA requires a significantly large aromatic ring (pyrene) connected through a flexible linker to the pyrrole moiety. However, a positive charge, as in 12, is also needed. Compound 12 allows for base-pair-selective recognition of ds-DNA at physiological pH values. The antiproliferative activities of these compounds correlate with their binding affinities towards DNA, suggesting that their biological effects are most probably due to DNA binding.

Sensing of Double‐Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes

A broad series of homochiral perylene bisimide (PBI) dyes were synthesized that are appended with amino acids and cationic side chains at the imide positions. Self-assembly behavior of these ionic PBIs has been studied in aqueous media by UV/Vis spectroscopy, revealing formation of excitonically coupled H-type aggregates. The interactions of these ionic PBIs with different ds-DNA and ds-RNA have been explored by thermal denaturation, fluorimetric titration and circular dichroism (CD) experiments. These PBIs strongly stabilized ds-DNA/RNA against thermal denaturation as revealed by high melting temperatures of the formed PBI/polynucleotide complexes. Fluorimetric titrations showed that these PBIs bind to ds-DNA/RNA with high binding constants depending on the number of the positive charges in the side chains. Thus, spermine-containing PBIs with six positive charges each showed higher binding constants (logKs =9.2-9.8) than their dioxa analogues (logKs =6.5-7.9) having two positive charges each. Induced circular dichroism (ICD) of PBI assemblies created within DNA/RNA grooves was observed. These ICD profiles are strongly dependent on the steric demand of the chiral substituents of the amino acid units and the secondary structure of the DNA or RNA. The observed ICD effects can be explained by non-covalent binding of excitonically coupled PBI dimer aggregates into the minor groove of DNA and major groove of RNA which is further supported by molecular modeling studies.

Self-assembly of a triple-zwitterion in polar solutions: hierarchical formation of nanostructures

The self-assembly of triple-zwitterion 1 in dimethyl sulfoxide is described. 1 forms dimers which polymerize upon increasing concentration into flexible twisted ribbons. These ribbons finally coil into soft nanospheres. The step-wise aggregation process is primarily based on the very strong tendency of the self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterion to form H-bond assisted ion paired dimers (K > 1010 M−1 in DMSO). Using a variety of analytical techniques such as diffusion ordered NMR spectroscopy (DOSY NMR), small angle neutron scattering (SANS), as well as atomic force microscopy (AFM) and molecular modelling for visualization, a consistent picture of the hierarchical self-assembly process of triple-zwitterion 1 in solution is obtained.