Pt(II) Complexes with Tetradentate C

A series of four regioisomeric Pt(II) complexes (PtLa-n and PtLb-n) bearing tetradentate luminophores as dianionic ligands were synthesized. Hence, both classes of cyclometallating chelators were decorated with three n-hexyl (n = 6) or n-dodecyl (n = 12) chains. The new compounds were unambiguously characterized by means of multiple NMR spectroscopies and mass spectrometry. Steady-state and time-resolved photoluminescence spectroscopy as well quantum chemical calculations show that the effect of the regioisomerism on the emission colour and on the deactivation rate constants can be correlated with the participation of the Pt atom on the excited state. The thermal properties of the complexes were studied by DSC, POM and temperature-dependent steady-state photoluminescence spectroscopy. Three of the four complexes (PtLa-12, PtLb-6 and PtLb-12) present an intriguing thermochromism resulting from the responsive metal-metal interactions involving adjacent monomeric units. Each material has different transition temperatures and memory capabilities, which can be tuned at the intermolecular level. Hence, dipole-dipole interactions between the luminophores and disruption of the crystalline packing by the alkyl groups are responsible for the final properties of the resulting materials.

Direct Digital Photonic Patterning of Hydrogen-Bonded Cholesteric Liquid-Crystalline Films.

A modular tool box for photoresponsive cholesteric liquid crystals based on hydrogen-bonded assemblies is reported. By employing 3-azopyridines as photoswitch in cholesteric liquid-crystalline thin films, a fast and reversible blue shift is observed upon irradiation, allowing tuning of the structural color over the whole visible electromagnetic spectrum. Investigations of the materials via X-ray diffraction studies indicate that the blue shift is attributed to the photoinduced destruction of smectic clusters in the cholesteric phase, resulting in a contraction of the helical structure. Unprecedently, the use of a stereolithography 3D printer (SLA) allowed direct transfer of digital information into a multicolor photonic pattern, an important step toward photonic imaging and data storage.

Tuning the Fluorescence in Dynamic Covalent Bonded Liquid Crystals.

A series of emissive liquid crystalline materials based on salicylidene derivatives is reported and investigated with respect to their thermoresponsive and mechanochromic properties. Single-crystal analysis and temperature-dependent powder X-ray diffraction measurements allowed us to correlate the intermolecular organization of the mesogens with thermoresponsive changes in the fluorescence behavior. As a proof-of-principle study, we employed the dynamics of the imine bond in transamination reactions for postsynthetic tuning of the fluorescence behavior as a further step toward the development of adaptive materials.

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups.

The 14-3-3 protein family, one of the first discovered phosphoserine/phosphothreonine binding proteins, has attracted interest not only because of its important role in the cell regulatory processes but also due to its enormous number of interactions with other proteins. Here, we use a computational approach to predict the binding sites of the designed hybrid compound featuring aggregation-induced emission luminophores as a potential supramolecular ligand for 14-3-3ζ in the presence and absence of C-Raf peptides. Our results suggest that the area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational prediction of two C 2 related, dominating binding sites on 14-3-3ζ that may bind to two of the supramolecular ligand molecules.

Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity.

Invited for the cover of this issue are Christoph Hirschhäuser and his colleagues from the University of Duisburg-Essen. The image depicts a biotin-labelled transfection vector selectively channelling DNA into a cancer cell. The QR code on the label will lead you to a video abstract (https://youtu.be/OgXfBPZTKGA). Read the full text of the article at 10.1002/chem.202104618.

Evolution of Artificial Arginine Analogues-Fluorescent Guanidiniocarbonyl-Indoles as Efficient Oxo-Anion Binders.

In this article, we present fluorescent guanidiniocarbonyl-indoles as versatile oxo-anion binders. Herein, the guanidiniocarbonyl-indole (GCI) and methoxy-guanidiniocarbonyl-indole (MGCI) were investigated as ethylamides and compared with the well-known guanidiniocarbonyl-pyrrole (GCP) concerning their photophysical properties as well as their binding behavior towards oxo-anions. Hence, a variety of anionic species, such as carboxylates, phosphonates and sulfonates, have been studied regarding their binding properties with GCP, GCI and MGCI using UV-Vis titrations, in combination with the determination of the complex stoichiometry using the Job method. The emission properties were studied in relation to the pH value using fluorescence spectroscopy as well as the determination of the photoluminescence quantum yields (PLQY). Density functional theory (DFT) calculations were undertaken to obtain a better understanding of the ground-lying electronic properties of the investigated oxo-anion binders. Additionally, X-ray diffraction of GCP and GCI was conducted. We found that GCI and MGCI efficiently bind carboxylates, phosphonates and sulfonates in buffered aqueous solution and in a similar range as GCP (Kass ≈ 1000-18,000 M-1, in bis-tris buffer, pH = 6); thus, they could be regarded as promising emissive oxo-anion binders. They also exhibit a visible fluorescence with a sufficient PLQY. Additionally, the excitation and emission wavelength of MGCI was successfully shifted closer to the visible region of the electromagnetic spectrum by introducing a methoxy-group into the core structure, which makes them interesting for biological applications.

Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity.

A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small-molecule approach paved the way for precise structure-activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA-binding motif tetralysine-guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR-based optimization. The new vector mediated biotin receptor (BR)-selective transfection of cell lines with different BR expression levels. Computer-based analyses of microscopy images revealed a preference of one order of magnitude for the BR-positive cell lines over the BR-negative controls.

Manipulation of Liquid Crystalline Properties by Dynamic Covalent Chemistry─En Route to Adaptive Materials.

Dynamic covalent bonds bear great potential for the development of adaptive and self-healing materials. Herein, we introduce a versatile concept not only for the design of low-molecular-weight liquid crystals but also for their in situ postsynthetic modification by using the dynamic covalent nature of imine bonds. The methodology allows systematic investigations of structure-property relationships as well as the manipulation of the materials' behavior (liquid crystallinity) and the introduction of additional properties (here, fluorescence) by a solvent-free method. For the first time, the transamination reaction is followed by variable-temperature 19F solid-state NMR in the mesophase, providing insights into the reaction dynamics in a liquid crystalline material. Finally, the application potential for the design of liquid crystalline materials with adaptive properties is demonstrated by a sequential combination of these reactions.

Selective Disruption of Survivin's Protein-Protein Interactions: A Supramolecular Approach Based on Guanidiniocarbonylpyrrole.

Targeting specific protein binding sites to interfere with protein-protein interactions (PPIs) is crucial for the rational modulation of biologically relevant processes. Survivin, which is highly overexpressed in most cancer cells and considered to be a key player of carcinogenesis, features two functionally relevant binding sites. Here, we demonstrate selective disruption of the Survivin/Histone H3 or the Survivin/Crm1 interaction using a supramolecular approach. By rational design we identified two structurally related ligands (LNES and LHIS ), capable of selectively inhibiting these PPIs, leading to a reduction in cancer cell proliferation.

Prospects of ultraviolet resonance Raman spectroscopy in supramolecular chemistry on proteins.

Ultraviolet resonance Raman scattering (UVRR) has been frequently used for studying peptide and protein structure and dynamics, while applications in supramolecular chemistry are quite rare. Since UVRR offers the additional advantages of chromophore selectivity and high sensitivity compared with conventional non-resonant Raman scattering, it is ideally suited for label-free probing of relatively small artificial/supramolecular ligands exhibiting electronic resonances in the UV. In this perspective article, we first summarize results of UVRR spectroscopy in supramolecular chemistry in the context of peptide/protein recognition. We focus on selected artificial ligands which were rationally designed as selective carboxylate binders (guanidiniocarbonyl pyrrole, GCP, and guanidiniocarbonyl indole, GCI) and selective lysine binder (molecular tweezer, CLR01), respectively, via a combination of non-covalent interactions involving electrostatics, hydrogen bonding, and hydrophobic effects/van der Waals forces. Current limitations of applying UVRR as a universally applicable method for label-free and site-specific probing of molecular recognition between supramolecular ligands and proteins are highlighted. We then propose solutions to overcome these limitations for transforming UVRR spectroscopy into a generic tool in supramolecular chemistry on proteins, with an emphasis on mono- and multivalent GCP- and GCI-based ligands. Finally, we outline specific cases of supramolecular ligands such as molecular tweezers where alternative approaches such as laser-based mid-IR spectroscopy are required since UVRR can intrinsically not provide the required molecular information.

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding.

The first example of halogen-bonded fluorescent liquid crystals based on the interaction of iodofluorobenzene derivatives with nitro-cyanostilbenes is reported. The systematic variation of the fluorination degree and pattern indicates the relevance of the halogen bond strength for the induction of liquid crystalline properties. The modular self-assembly approach enables the efficient tuning of the fluorescence behaviour and mesomorphic properties of the assemblies.

Ultraviolet resonance Raman spectroscopy with a continuously tunable picosecond laser: Application to the supramolecular ligand guanidiniocarbonyl pyrrole (GCP).

We present a UVRR spectroscopy setup which is equipped with a picosecond pulsed laser excitation source continuously tunable in the 210-2600 nm wavelength range. This laser source is based on a three-stage optical parametric amplifier (OPA) pumped by a bandwidth-compressed second harmonic output of an amplified Yb:KGW laser. It provides <15 cm-1 linewidth pulses below 270 nm, which is sufficient for resolving Raman lines of samples in condensed phase studies. For demonstrating the capability of this tunable setup for UVRR spectroscopy we present its application to the artificial ligand guanidiniocarbonyl pyrrole (GCP), a carboxylate binder used in peptide and protein recognition. A UVRR excitation study in the range 244-310 nm was performed for identifying the optimum laser excitation wavelength for UVRR spectroscopy of this ligand (λmax = 298 nm) at submillimolar concentrations (400 µM) in aqueous solution. The optimum UVRR spectrum is observed for laser excitation with λexc = 266 nm. Only in the relatively narrow range of λexc = 266-275 nm UVRR spectra with a sufficiently high signal-to-noise ratio and without severe interference from autofluorescence (AF) were detectable. At longer excitation wavelengths the UVRR signal is masked by AF. At shorter excitation wavelengths the UVRR spectrum is sufficiently separated from the AF, but the resonance enhancement is not sufficient. The presented tunable UVRR setup provides the flexibility to also identify optimum conditions for other supramolecular ligands for peptide/protein recognition.

Guanidiniocarbonyl-Pyrroles (GCP) - 20 Years of the Schmuck Binding Motif.

In this Minireview, an overview about the past 20 years of the guanidiniocarbonyl-pyrrole (GCP) binding motif, which was designed, investigated and applied by Prof. Dr. Carsten Schmuck, is presented. Here we highlight the first steps from design and discovery, initial binding studies, applications in material science to advanced biomedical use in protein modulation and delivery of genetic material.

Photo-switchable Fluorescence in Hydrogen-Bonded Liquid Crystals.

A series of hydrogen-bonded liquid crystals showing switchable fluorescence is reported. The fluorescence behavior results from the unique combination of hydrogen bonding, liquid crystallinity, and photobasicity. Thus, the molecular mobility in the mesophase is essential for the reversible photo-initiated proton transfer switching on the fluorescence of the assemblies. The application potential of the materials for photo-patterning was demonstrated.

Alkyl-Alkyl Interactions in the Periphery of Supramolecular Entities: From the Evaluation of Weak Forces to Applications.

Supramolecular chemistry is based on weak intermolecular forces which nevertheless are of importance for chemical processes. In this report the relevance of alkyl-alkyl interactions in supramolecular assemblies is discussed. We show how hierarchically formed helicates can be used to evaluate weak interactions of alkyl groups based on solvent-supported London dispersion. In addition, the role of nano-segregation of alkyl groups in the periphery of supramolecular assemblies is described, as well as how this can be used to improve the properties of liquid-crystalline materials by controlling the alkyl-chain-mediated aggregation process.

Smart Glycopolymeric Nanoparticles for Multivalent Lectin Binding and Stimuli-Controlled Guest Release.

The synthesis and self-assembly of a polymer featuring a self-complementary supramolecular binding motif guanidiniocarbonyl pyrrole carboxylate zwitterion (GCP-zwitterion) bearing lactose moieties are reported. The GCP-zwitterion acts as a cross-linker to facilitate self-assembly of the polymeric chain into nanoparticles (NPs) at neutral pH in an aqueous medium. The formation of polymeric NPs can be controlled by addition of external stimuli (acid or base), which disfavors self-assembly of the GCP-zwitterion because of protonation or deprotonation of the GCP units in the polymer chain. The small-sized (<40 nm) NPs have a hydrophobic cavity and accessible lactose units on the outer shell for multivalent lectin binding. The multivalent interaction between NPs and the lectin peanut agglutinin was confirmed by agglutination experiments. In addition, the stimuli-responsive property of NPs was exploited for the uptake and release of a hydrophobic guest Nile red. Furthermore, the selectivity toward different cell lines (HEK 296T, HeLa, and Hep2G) was tested, and a cellular uptake of cargo-loaded NPs was found for Hep2G cells bearing the lactose-specific asialogylcoprotein receptor, whereas all other cells showed no NP interaction.

Functional Disruption of the Cancer-Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand.

The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein-protein interaction of Survivin and its functionally relevant binding partner Histone H3. Ligand L1 is based on the guanidiniocarbonyl pyrrole cation and serves as a highly specific anion binder in order to target the interaction between Survivin and Histone H3. NMR titration confirmed binding of L1 to Survivin's Histone H3 binding site. The inhibition of the Survivin-Histone H3 interaction and consequently a reduction of cancer cell proliferation were demonstrated by microscopic and cellular assays.

Photo-switching and -cyclisation of hydrogen bonded liquid crystals based on resveratrol.

A series of hydrogen-bonded liquid crystals based on resveratrol and resveratrone is reported and investigated with respect to their photo-switchability (at 405 nm) and photo-cyclisation (at 300 nm).

Polymorphism of hydrogen-bonded star mesogens - a combinatorial DFT-D and FT-IR spectroscopy study.

A comprehensive study combining detailed computational analyses with temperature-variable FT-IR experiments was performed in order to elucidate the structure of the hydrogen-bonded liquid crystals based on phloroglucinol and azopyridine in their mesophase. Conformational analysis revealed three relevant conformers: star, λ- and E-shape. The results demonstrate an entropy-driven unfolding mechanism of the assembly. The stability of the conformers is given by intermolecular π-π and dispersion interactions of the azopyridine side chains. Correlating the calculated vibrational frequency with experimental FT-IR spectra suggests a λ-folded conformation of the assemblies as the predominant species in the mesophase.

Alkylated Aromatic Thioethers with Aggregation-Induced Emission Properties-Assembly and Photophysics.

In this contribution, we present the synthesis and self-assembly of alkylated thioethers with interesting photophysical properties. To this end, the emission, absorption and excitation spectra in organic solvents and as aggregates in water were measured as well as the corresponding photoluminescence quantum yields and lifetimes. The aggregates in aqueous media were visualized and measured using transmission electron microscopy. Besides that, crystal structures of selected compounds allowed a detailed discussion of the structure-property relationship. Furthermore, the mesomorphic behavior was investigated using polarized optical microscopy (POM) as well as differential scanning calorimetry (DSC).