Anti-cooperative Self-Assembly with Maintained Emission Regulated by Conformational and Steric Effects.

Herein, we present a strategy to enable a maintained emissive behavior in the self-assembled state by enforcing an anti-cooperative self-assembly involving weak intermolecular dye interactions. To achieve this goal, we designed a conformationally flexible monomer unit 1 with a central 1,3-substituted (diphenyl)urea hydrogen bonding synthon that is tethered to two BODIPY dyes featuring sterically bulky trialkoxybenzene substituents at the meso-position. The competition between attractive forces (H-bonding and aromatic interactions) and destabilizing effects (steric and competing conformational effects) limits the assembly, halting the supramolecular growth at the stage of small oligomers. Given the presence of weak dye-dye interactions, the emission properties of molecularly dissolved 1 are negligibly affected upon aggregation. Our findings contribute to broadening the scope of emissive supramolecular assemblies and controlled supramolecular polymerization.

Pathway and Length Control of Supramolecular Polymers in Aqueous Media via a Hydrogen Bonding Lock.

Programming the organization of π-conjugated systems into nanostructures of defined dimensions is a requirement for the preparation of functional materials. Herein, we have achieved high-precision control over the self-assembly pathways and fiber length of an amphiphilic BODIPY dye in aqueous media by exploiting a programmable hydrogen bonding lock. The presence of a (2-hydroxyethyl)amide group in the target BODIPY enables different types of intra- vs. intermolecular hydrogen bonding, leading to a competition between kinetically controlled discoidal H-type aggregates and thermodynamically controlled 1D J-type fibers in water. The high stability of the kinetic state, which is dominated by the hydrophobic effect, is reflected in the slow transformation to the thermodynamic product (several weeks at room temperature). However, this lag time can be suppressed by the addition of seeds from the thermodynamic species, enabling us to obtain supramolecular polymers of tuneable length in water for multiple cycles.

Hydrophobic domain flexibility enables morphology control of amphiphilic systems in aqueous media.

Herein, we introduce the concept of hydrophobic domain flexibility to control the morphology of aqueous assemblies. To this end, we examined two amphiphilic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes that differ in the flexibility of the hydrophobic residue (tetradecyl vs. cholesterol). This minor structural difference significantly affects the self-assembly behaviour (spherical vs. two-dimensional sheets) by overruling the packing parameters.

Synergistic repulsive interactions trigger pathway complexity.

Herein, we demonstrate the key impact of synergistic repulsive interactions on pathway complexity in aqueous media. To this end, we have examined the aqueous self-assembly of four new amphiphilic BODIPY dyes where the extent of repulsive interactions has been systematically varied.

Impact of Positional Isomerism on Pathway Complexity in Aqueous Media.

Pathway complexity has become an important topic in recent years due to its relevance in the optimization of molecular assembly processes, which typically require precise sample preparation protocols. Alternatively, competing aggregation pathways can be controlled by molecular design, which primarily rely on geometrical changes of the building blocks. However, understanding how to control pathway complexity by molecular design remains elusive and new approaches are needed. Herein, we exploit positional isomerism as a new molecular design strategy for pathway control in aqueous self-assembly. We compare the self-assembly of two carboxyl-functionalized amphiphilic BODIPY dyes that solely differ in the relative position of functional groups. Placement of the carboxyl group at the 2-position enables efficient pairwise H-bonding interactions into a single thermodynamic species, whereas meso-substitution induces pathway complexity due to competing hydrophobic and hydrogen bonding interactions. Our results show the importance of positional engineering for pathway control in aqueous self-assembly.

Hierarchical Self-Assembly of BODIPY Dyes as a Tool to Improve the Antitumor Activity of Capsaicin in Prostate Cancer.

Capsaicin (CAP) has been long known for its analgesic properties and more recently for its antitumor activity in various cell types. However, its pungency and the high doses needed to achieve a significant activity have precluded its application in cancer therapy. Herein, we propose a straightforward novel strategy to improve the antitumor effect of CAP based on the enhancement of its aggregation propensity in aqueous media by covalent attachment of a BODIPY (BDP) dye. The target CAP-BDP 1 self-assembles in aqueous solutions into weakly fluorescent globular assemblies that become highly emissive upon cell uptake-induced disassembly. Remarkably, due to the improved delivery to the tumour tissue upon aggregation, we have succeeded in reducing the doses of CAP-based drugs in vivo in prostate cancer by two orders of magnitude while maintaining a substantial antitumor activity.

Self-Assembly of 9,10-Bis(phenylethynyl) Anthracene (BPEA) Derivatives: Influence of π-π and Hydrogen-Bonding Interactions on Aggregate Morphology and Self-Assembly Mechanism.

9,10-Bis(phenylethynyl)anthracenes (BPEAs) are an important class of dyes in various applications including chemiluminescence emitters, materials for photon upconversion, and for optoelectronic devices. Some of these applications require control over the packing modes of the molecules within the active layer, which can be effected by bottom-up self-assembly. Studies aimed at controlling the molecular organization of BPEAs have primarily focused on bulk or liquid-crystal materials, whereas in-depth investigations of BPEA-based assemblies in solution remain elusive. In this article, the self-assembly of two new BPEA derivatives with hydrophobic side chains is reported, one of them featuring amide functional groups and the other one lacking them. Comparison of the self-assembly behavior of both systems in solution using spectroscopic (UV/Vis, fluorescence, and NMR), microscopic (AFM), and theoretical (PM6) studies reveals the crucial role of the amide groups in controlling the self-assembly. For both systems, the formation of H-type face-to-face π-stacks is proposed, whereas the interplay of π-stacking and H-bonding is responsible for driving the formation of 1D stacks and increasing the binding constant by two to three orders of magnitude. Our findings show that H-bonding is a prerequisite to create ordered BPEA assemblies in solution.