Stephan Sinn

Complexes de platine (II) comme ossatures dans les assemblages supramoléculaires: Cette thèse se concentre sur la synthèse et l’analyse photophysique de complexes de Pt(II) luminescents and leur assemblage après agrégation. Multiples motifs supramoléculaires ont été utilisé pour acquérir un contrôle sur l’assemblage de ces complexes plan-carrés.Des ossatures de type couronne-éther furent attachés à des complexes métalliques phosphorescents pour donner un bouton supramoléculaire qui peut être actionné par des cations potassium. De plus, l’altération de l’arrangement de l’empilage des Pt(II) après coordination d’un ligand fut exploité pour la réalisation d’un senseur chimique qui peut être utilisé pour la détection différentielle d’aza-hétérocylces. Par ailleurs, l’installation d’un motif pont hydrogène à un complexe de Pt(II) luminescent fut établie, donnant un composé ayant un organisation 2D sur graphène. Finalement, des complexes de Pt(II) amphiphiles qui s’auto-assemblent en solution aqueuse dans des agrégats hautement luminescents furent synthétisés. La série de complexes soluble dans l’eau, chargés négativement ou neutres furent caractérisés par rapport à leurs paramètres photophysiques et leurs interactions avec des protéines capsides virales.

Time-resolved supramolecular assays probe analyte-characteristic complexation and decomplexation rates. Consequently, even unselectively binding synthetic receptors can be used for analyte identification and quantification.

Competitive binding of an indicator dye and an optically silent guest was exploited to develop a powerful method for the accurate determination of the kinetic and thermodynamic parameters of host–guest complex formation.

The design and preparation of synthetic binders (SBs) applicable for small biomolecule sensing in aqueous media remains very challenging. SBs designed by the lock‐and‐key principle can be selective for their target analyte but usually show an insufficient binding strength in water. In contrast, SBs based on symmetric macrocycles with a hydrophobic cavity can display high binding affinities but generally suffer from indiscriminate binding of many analytes. Herein, a completely new and modular receptor design strategy based on microporous hybrid materials is presented yielding zeolite‐based artificial receptors (ZARs) which reversibly bind the neurotransmitters serotonin and dopamine with unprecedented affinity and selectivity even in saline biofluids. ZARs are thought to uniquely exploit both the non‐classical hydrophobic effect and direct non‐covalent recognition motifs, which is supported by in‐depth photophysical, and calorimetric experiments combined with full atomistic modeling. ZARs are thermally and chemically robust and can be readily prepared at gram scales. Their applicability for the label‐free monitoring of important enzymatic reactions, for (two‐photon) fluorescence imaging, and for high‐throughput diagnostics in biofluids is demonstrated. This study showcases that artificial receptor based on microporous hybrid materials can overcome standing limitations of synthetic chemosensors, paving the way towards personalized diagnostics and metabolomics.

Both thermodynamic and kinetic insights are needed for a proper analysis of association and dissociation processes of host–guest interactions. However, kinetic descriptions of supramolecular systems are scarce in the literature because suitable experimental protocols are lacking. We introduce here three time-resolved methods that allow for convenient determination of kinetic rate constants of spectroscopically silent or even insoluble guests with the macrocyclic cucurbit[n]uril family and human serum albumin (HSA) protein as representative hosts.

A simple change has important consequences: the guest-displacement assay (GDA) is introduced which allows for binding affinity determinations of supramolecular complexes with spectroscopically silent hosts and guests.

The self-assembly behaviour of platinum(II) neutral complexes has been explored in derivatives exposing oligothiophene substituents in order to organize the semiconducting units in ordered supramolecular structures. The morphology and the photophysical properties of the assemblies were studied by scanning electron microscopy, powder X-ray diffraction and photoluminescence techniques, and correlated to their charge transport properties measured in space-charge-limited current (SCLC) devices. The nature of the intermolecular Pt⋯Pt and/or π–π stacking interactions in the different supramolecular structures and in particular the inter-chromophoric distance were found to affect the hole mobility values estimated for the various semiconducting thiophene-based assemblies. The thiophene-containing architectures exhibit enhanced mobility values compared to the free ligand based ones. These results demonstrate that the supramolecular organization strategy can be applied to generate semiconducting materials via exquisite control over the arrangement of simple conjugated segments.

In this study, we report the first supramolecular indicator-displacement assay (IDA) based on cucurbit[n]uril (CBn) hosts that is operational in blood serum. Rational design principles for host–guest chemosensing in competitively binding media were derived through detailed mathematical simulations. It was shown that currently known CBn-based chemosensing ensembles are not suited for use in highly competitive matrices such as blood serum. Conversely, the simulations indicated that a combination of cucurbit[8]uril (CB8) and an ultra-high affinity dye would be a promising IDA reporter pair for the detection of Alzheimer's drug memantine in blood serum. Therefore, a novel class of [2.2]paracyclophane-derived indicator dyes for the host CB8 was developed that possesses one of the highest host–guest affinities (K_a > 10¹² M⁻¹ in water) known in supramolecular host–guest chemistry, and which provides a large Stokes shift (up to 200 nm). The novel IDA was then tested for the detection of memantine in blood serum in a physiologically relevant sub- to low micromolar concentration range.

The templated self‐assembly of two different chromophores attached to the same binding motif gives oligomers of statistical mixtures without any control on the resulting chromophore sequence. The first self‐assembled bichromophore system is reported, in which the resulting chromophore sequence is simply governed by the DNA template. A new ethynylpyrene‐diaminopurine 2′‐deoxynucleoside was combined with the ethynyl nile red‐modified 2′‐deoxyuridine to achieve this completely programmable sequence selective self‐assembly. The helical ordering of the two different chromophores by DNA templates with different mixtures of A‐T sequences yields precise control over the optical properties of the formed assemblies, which was proven by methods of optical spectroscopy.

Virus-like particles (VLPs) have been created from luminescent Pt(II)-complex amphiphiles, able to form supramolecular structures in water solutions, that can be encapsulated or act as templates of cowpea chlorotic mottle viruses (CCMV) capsid proteins. By virtue of a bottom-up molecular design, icosahedral and non-icosahedral (rod-like) VLPs have been constructed through diverse pathways and a relationship between the molecular structure of the complexes and the shape and size of the VLPs has been ob-served. A deep insight into the mechanism for the templated formation of the differently shaped VLPs was achieved, by electron microscopy measurements (TEM and STEM) and bulk analysis (FPLC, DLS, photophysical investigations). Interestingly, the ob-tained VLPs can be visualized by their intense emission at room temperature, generated by the self-assembly of the Pt(II)-complexes. The encapsulation of the luminescent species is further verified by their higher emission quantum yields inside the VLPs, which is due to the confinement effect of the protein cage. These hybrid materials demonstrate the potential of tailor-made supramolecular systems able to control the assembly of biological building blocks.