Cyclic Photoisomerization of Azobenzene in Atomistic Simulations: Modeling the Effect of Light on Columnar Aggregates of Azo Stars

This computational study investigates the influence of light on supramolecular aggregates of three-arm azobenzene stars. Every star contains three azobenzene (azo) moieties, each able to undergo reversible photoisomerization. In solution, the azo stars build column-shaped supramolecular aggregates. Previous experimental works report severe morphological changes of these aggregates under UV–Vis light. However, the underlying molecular mechanisms are still debated. Here we aim to elucidate how light affects the structure and stability of the columnar stacks on the molecular scale. The system is investigated using fully atomistic molecular dynamics (MD) simulations. To implement the effects of light, we first developed a stochastic model of the cyclic photoisomerization of azobenzene. This model reproduces the collective photoisomerization kinetics of the azo stars in good agreement with theory and previous experiments. We then apply light of various intensities and wavelengths on an equilibrated columnar stack of azo stars in water. The simulations indicate that the aggregate does not break into separate fragments upon light irradiation. Instead, the stack develops defects in the form of molecular shifts and reorientations and, as a result, it eventually loses its columnar shape. The mechanism and driving forces behind this order–disorder structural transition are clarified based on the simulations. In the end, we provide a new interpretation of the experimentally observed morphological changes.

Columnar Aggregates of Azobenzene Stars: Exploring Intermolecular Interactions, Structure, and Stability in Atomistic Simulations

We present a simulation study of supramolecular aggregates formed by three-arm azobenzene (Azo) stars with a benzene-1,3,5-tricarboxamide (BTA) core in water. Previous experimental works by other research groups demonstrate that such Azo stars assemble into needle-like structures with light-responsive properties. Disregarding the response to light, we intend to characterize the equilibrium state of this system on the molecular scale. In particular, we aim to develop a thorough understanding of the binding mechanism between the molecules and analyze the structural properties of columnar stacks of Azo stars. Our study employs fully atomistic molecular dynamics (MD) simulations to model pre-assembled aggregates with various sizes and arrangements in water. In our detailed approach, we decompose the binding energies of the aggregates into the contributions due to the different types of non-covalent interactions and the contributions of the functional groups in the Azo stars. Initially, we investigate the origin and strength of the non-covalent interactions within a stacked dimer. Based on these findings, three arrangements of longer columnar stacks are prepared and equilibrated. We confirm that the binding energies of the stacks are mainly composed of π–π interactions between the conjugated parts of the molecules and hydrogen bonds formed between the stacked BTA cores. Our study quantifies the strength of these interactions and shows that the π–π interactions, especially between the Azo moieties, dominate the binding energies. We clarify that hydrogen bonds, which are predominant in BTA stacks, have only secondary energetic contributions in stacks of Azo stars but remain necessary stabilizers. Both types of interactions, π–π stacking and H-bonds, are required to maintain the columnar arrangement of the aggregates.

PEG-Modified tert-Octylcalix[8]arenes as Drug Delivery Nanocarriers of Silibinin

The hepatoprotective properties of silibinin, as well its therapeutic potential as an anticancer and chemo-preventive agent, have failed to progress towards clinical development and commercialization due to this material’s unfavorable pharmacokinetics and physicochemical properties, low aqueous solubility, and chemical instability. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-octylcalix[8]arene, to prepare various platforms for the delivery of silibinin, such as inclusion complexes and supramolecular aggregates thereof. The inclusion complex is characterized by various instrumental methods. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility increment of silibinin is attributed to the additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. PEG-modified tert-octylcalix[8]arenes, used as drug delivery carriers for silibinin, were additionally investigated for cytotoxicity against human tumor cell lines.

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability

This review focuses on key topics in the field of drug delivery related to the design of nanocarriers answering the biomedicine criteria, including biocompatibility, biodegradability, low toxicity, and the ability to overcome biological barriers. For these reasons, much attention is paid to the amphiphile-based carriers composed of natural building blocks, lipids, and their structural analogues and synthetic surfactants that are capable of self-assembly with the formation of a variety of supramolecular aggregates. The latter are dynamic structures that can be used as nanocontainers for hydrophobic drugs to increase their solubility and bioavailability. In this section, biodegradable cationic surfactants bearing cleavable fragments are discussed, with ester- and carbamate-containing analogs, as well as amino acid derivatives received special attention. Drug delivery through the biological barriers is a challenging task, which is highlighted by the example of transdermal method of drug administration. In this paper, nonionic surfactants are primarily discussed, including their application for the fabrication of nanocarriers, their surfactant-skin interactions, the mechanisms of modulating their permeability, and the factors controlling drug encapsulation, release, and targeted delivery. Different types of nanocarriers are covered, including niosomes, transfersomes, invasomes and chitosomes, with their morphological specificity, beneficial characteristics and limitations discussed.

Supramolecular Aggregates: Hardness Plus Softness

The properties of supramolecular aggregates cross several disciplines, embracing the sciences of nature and joining theory, experiment, and application. There are few articles centering on the problems of interdisciplinarity, and this paper gives an alternative approach, starting with scientific divulgation, bringing concepts from their origin, to facilitate the access of young scientists to the scientific content. Didactic examples are taken from the experience of the author in changing directions of research due to several circumstances of life (including maternity), starting from the view of a rigorous student of physics and evolving to several subjects in chemistry. The scientific part starts with concepts related to nuclear interactions, using the technique of neutron scattering in reactors, and evolves to research in molecular physics. Finally, it arrives at the academic context, with research in condensed matter physics, with X-ray and other techniques, starting with detergents forming nematic lyotropic liquid crystals and the phase transition sequence of isotropic to nematics to hexagonal. The scientific subjects evolved to biological and bio-inspired liquid crystals, including DNA and also specific lipids and phospholipids in biomimetic membranes. Special attention is given to the question of distribution of matter in these complex systems and the non-trivial connections between biochemistry, structures, auto-aggregation, and biology.

Porphyrin-Based Supramolecular Flags in the Thermal Gradients’ Wind: What Breaks the Symmetry, How and Why

The Spontaneous Symmetry Breaking (SSB) phenomenon is a natural event in which a system changes its symmetric state, apparently reasonless, in an asymmetrical one. Nevertheless, this occurrence could be hiding unknown inductive forces. An intriguing investigation pathway uses supramolecular aggregates of suitable achiral porphyrins, useful to mimic the natural light-harvesting systems (as chlorophyll). Using as SSB probe supramolecular aggregates of 5,10,15,20-tetrakis[p(ω-methoxypolyethyleneoxy)phenyl]porphyrin (StarP), a non-ionic achiral PEGylated porphyrin, we explore here its interaction with weak asymmetric thermal gradients fields. The cross-correlation of the experimental data (circular dichroism, confocal microscopy, atomic force microscopy, and cryo-transmission electron microscopy) revealed that the used building blocks aggregate spontaneously, organizing in flag-like structures whose thermally-induced circular dichroism depends on their features. Finally, thermal gradient-induced enantioselectivity of the supramolecular flag-like aggregates has been shown and linked to their size-dependence mesoscopic deformation, which could be visualized as waving flags in the wind.