Design, synthesis, and biological evaluation of novel halogenated chlorido[N,N'-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes as anticancer agents.

Iron(III) complexes based on N,N´-bis(salicylidene)ethylenediamine (salene) scaffolds have demonstrated promising anticancer features like induction of ferroptosis, an iron dependent cell death. Since poor cellular uptake limits their therapeutical potential, this study aimed to enhance the lipophilic character of chlorido[N,N'-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes by introducing lipophilicity improving ligands such as fluorine (X1), chlorine (X2) and bromine (X3) in 5-position in the salicylidene moieties. After detailed characterization the binding to nucleophiles, logP values and cellular uptake were determined.

Early Stages of FUS Droplet Formation via Liquid-Liquid Phase Separation.

The phase behavior of complex biomolecular solutions may explain different cellular processes, including the organization of cells by membraneless organelles. The early stages of phase separation are crucial to understanding the underlying mechanism and identifying biomolecules that trigger or drive the transition. Here, we analyze the early events of liquid-liquid phase separation (LLPS) of FUS by multiangle time-resolved static and dynamic light scattering.

Impact of Additive Hydrophilicity on Mixed Dye-Nonionic Surfactant Micelles: Micelle Morphology and Dye Localization.

The nonionic surfactant pentaethylene glycol-monododecylether CE forms micelles in aqueous solutions with a lower critical solution temperature. This characteristic solution behavior of CE is independent of the pH. Such micelles are used to solubilize a large variety of active guest molecules like for instance dyestuffs.

Molecular Crowding: The History and Development of a Scientific Paradigm.

It is now generally accepted that macromolecules do not act in isolation but "live" in a crowded environment, that is, an environment populated by numerous different molecules. The field of molecular crowding has its origins in the far 80s but became accepted only by the end of the 90s. In the present issue, we discuss various aspects that are influenced by crowding and need to consider its effects.

On the Mechanism of Self-Assembly of Fibrinogen in Thrombin-free Aqueous Solution.

Fibrinogen dissolved in 0.12 M aqueous NaCl solution at a pH of 6.6 exhibits self-assembly in response to a lowering of the NaCl concentration to values equal to or lower than 60 mM.

SANS contrast matching for the unambiguous localization of anionic dye in cationic surfactant micelles.

Contrast variation in small-angle neutron scattering (SANS) was successfully applied to localize the anionic azo dye Blue in co-assemblies with the cationic surfactant dodecyltrimethylammoniumbromide (DTAB). For this purpose, the scattering contrast between DTAB and the aqueous solvent was eliminated by SANS contrast matching, leaving only the scattering signal from Blue to be detected. Results obtained by contrast matching were confirmed by NOESY NMR-spectroscopy, showing that Blue interacts with the positively charged DTAB head groups and with up to the 4 neighbouring methylene group of the DTAB C-alkyl chain.

Ethylene glycol energetically disfavours oligomerization of pseudoisocyanine dyestuffs at crowded concentrations.

The intriguing role of the intracellular crowded environment in regulating protein aggregation remains elusive. The convolution of several factors such as the protein sequence-dependence, crowder's shape and size and diverse intermolecular interactions makes it complex to identify systematic trends. One of the ways to simplify the problem is to study a synthetic model for self-assembling proteins.

A Comparative Study on Cyanine Dyestuffs as Sensor Candidates for Macromolecular Crowding In Vitro and In Vivo.

Pseudo isocyanine chloride (PIC) has been identified in a preceding work as a sensor suited to probe macromolecular crowding both in test tubes with solutions of synthetic crowding agents and in HeLa cells as a representative of living systems. The sensing is based on a delicate response of the self-assembly pattern of PIC towards a variation in macromolecular crowding. Based on a suitable selection of criteria established in the present study, four additional cyanine dyestuffs (TDBC, S071, S2275, and PCYN) were scrutinized for their ability to act as such a sensor, and the results were compared with the corresponding performance of PIC.

Comparative study of the co-assembly behaviour of 3-chloro-4-hydroxy-phenylazo dyes with DTAB.

The co-assembly of three one-fold negatively charged 3-chloro-4-hydroxy-phenylazo dyes (Yellow, Blue and Red) with the cationic surfactant dodecyltrimethylammoniumbromide (DTAB) was studied to probe dye-DTAB binding stoichiometry and assembly morphology. For each dye, phase separation was observed above a given dye : DTAB ratio with the ratio depending on the dye. While Yellow and DTAB showed liquid/liquid phase separation above Yellow : DTAB = 1 : 1.

Comparative study of the self-assembly behaviour of 3-chloro-4-hydroxy-phenylazo dyes.

The complexity of intermolecular interactions and the difficulty to predict assembly behaviour solely based on chemical constitution was demonstrated by studying the self-assembly of three one-fold negatively charged 3-chloro-4-hydroxy-phenylazo dyes (Yellow, Blue and Red). Dye self-assembly was investigated using UV/vis- and NMR-spectroscopy, light- and small-angle neutron scattering. Significant differences between the three dyes were observed.

Spatial Distribution of Intracellular Ion Concentrations in Aggregate-Forming HeLa Cells Analyzed by μ-XRF Imaging.

Protein aggregation is a hallmark of several severe neurodegenerative disorders such as Huntington's, Parkinson's, or Alzheimer's disease. Metal ions play a profound role in protein aggregation and altered metal-ion homeostasis is associated with disease progression. Here we utilize μ-X-ray fluorescence imaging in combination with rapid freezing to resolve the elemental distribution of phosphorus, sulfur, potassium, and zinc in huntingtin exon-1-mYFP expressing HeLa cells.

Targeted Synthesis of the Type-A Particle Substructure from Enzymatically Produced Eumelanin.

Eumelanin exhibits a defined supramolecular buildup that is deprived of at least three distinct particle species. To enable the full potential of its promising material properties, access to all particle types is crucial. In this work, the first protocol for the synthesis of the intermediate type-A particles in pure and stable dispersion form is described.

Mechanism and equilibrium thermodynamics of H- and J-aggregate formation from pseudo isocyanine chloride in water.

Pseudo isocyanine chloride (PIC) has a strong tendency to self-assemble with a concentration dependent temperature threshold separating a regime with small H-oligomers in equilibrium with monomeric PIC from a regime where large J-aggregates form. In complementing the known set of absorption spectra by the spectrum of a trimer, which represents all H-aggregates with ≥ 3, a full description of the sample composition of PIC in the regime of oligomers became possible by means of UV-vis spectroscopy and gave access to the equilibrium thermodynamics of oligomerisation. Successful interpretation of the concentration dependent temperature threshold as a ceiling temperature of J-aggregation made also accessible equilibrium thermodynamics of the formation of J-aggregates together with a full analysis of composition also in the regime of J-aggregates.

Self-Assembled Fibrinogen Hydro- and Aerogels with Fibrin-like 3D Structures.

The natural blood protein fibrinogen is a highly potent precursor for the production of various biomaterials due to its supreme biocompatibility and cell interaction. To gain actual materials from fibrinogen, the protein needs to undergo fibrillogenesis, which is mostly triggered via enzymatic processing to fibrin, electrospinning, or drying processes. All of those techniques, however, strongly limit the available structures or the applicability of the material.

Self-Assembly of Pseudo-Isocyanine Chloride as a Sensor for Macromolecular Crowding In Vitro and In Vivo.

Pseudo-isocyanine chloride (PIC) is a cationic dyestuff that exhibits self-assembly in aqueous solution, promoted either by increasing the PIC concentration or by decreasing the temperature. PIC-aggregates exhibit a characteristic and sharp absorption band as well as a fluorescence band at a wavelength of 573 nm making PIC an interesting candidate to analyze the self-assembly process in various environments. The present work developed PIC-based, synthetic model systems, suitable to investigate how macromolecular crowding influences self-assembly processes.

The Molecular Mechanism of Polymer Formation of Farnesylated Human Guanylate-binding Protein 1.

The human guanylate-binding protein 1 (hGBP1) belongs to the dynamin superfamily proteins and represents a key player in the innate immune response. Farnesylation at the C-terminus is required for hGBP1's activity against microbial pathogens, as well as for its antiproliferative and antitumor activity. The farnesylated hGBP1 (hGBP1) retains many characteristics of the extensively studied nonfarnesylated protein and gains additional abilities like binding to lipid membranes and formation of hGBP1 polymers.

Controlling Self-Assembly with Light and Temperature.

Complexes between the anionic polyelectrolyte sodium polyacrylate (PA) and an oppositely charged divalent azobenzene dye are prepared in aqueous solution. Depending on the ratio between dye and polyelectrolyte stable aggregates with a well-defined spherical shape are observed. Upon exposure of these complexes to UV light, the trans → cis transition of the azobenzene is excited resulting in a better solubility of the dye and a dissolution of the complexes.

On Protein Folding in Crowded Conditions.

The interior of a cell is a highly packed environment that can be occupied up to 40% by different macromolecules. Such crowded media influence different biochemical processes like protein folding, enzymatic activity, and gene regulation. In this work, we use simulations to study protein stability under the presence of crowding agents that interact with the protein by excluded volume interactions.

Ion-selective binding as a new trigger for micellization of block copolyelectrolytes with two anionic blocks.

This work presents well-defined and switchable micelles of block copolymers consisting of the two anionic polyelectrolytes sodium polyacrylate (NaPA) and sodium polystyrene sulfonate (NaPSS). Micellization occurs due to the specific binding of Ca2+ to acrylate groups, which results in neutralization of the corresponding block and thereby formation of the hydrophobic core of the micelles. In contrast, the PSS block remains charged and forms the stabilizing shell.

Self-Assembly of Fibrinogen in Aqueous, Thrombin-Free Solutions of Variable Ionic Strengths.

Fibrinogen not only forms fibrin networks if assisted by thrombin but also exhibits self-assembly in dilute aqueous solutions in the absence of thrombin. It could be shown that self-assembly can be triggered in a controlled way by diluting the ionic strength set to a value of 0.14 M NaCl in the starting solutions.

Polyacrylates in the presence of an extraordinary monovalent cation-Solution behavior and metal nanoparticle formation.

Sodium polyacrylate (NaPA) in dilute aqueous solution at an ionic strength of [NaNO] = 0.01M establishes a rich phase behavior in the presence of low amounts of silver cations, which were introduced at a few millimoles or less by replacing the corresponding amount of Na cations. Beyond an extremely low level of Ag cations, anionic PA chains aggregate.

Secondary Particle Formation during the Nonaqueous Synthesis of Metal Oxide Nanocrystals.

This study aims to elucidate the aggregation and agglomeration behavior of TiO and ZrO nanoparticles during the nonaqueous synthesis. We found that zirconia nanoparticles immediately form spherical-like aggregates after nucleation with a homogeneous size of 200 nm, which can be related to the metastable state of the nuclei and the reduction of surface free energy. These aggregates further agglomerate, following a diffusion-limited colloid agglomeration mechanism that is additionally supported by the high fractal dimension of the resulting agglomerates.

Effect of ionic strength on the structure and elongational kinetics of vimentin filaments.

Intermediate filaments are a major structural element in the cytoskeleton of animal cells that mechanically integrate other cytoskeletal components and absorb externally applied stress. Their role is likely to be linked to their complex molecular architecture which is the product of a multi-step assembly pathway. Intermediate filaments form tetrameric subunits which assemble in the presence of monovalent salts to form unit length filaments that subsequently elongate by end-to-end annealing.