Pathway complexity, hierarchical organization, out of equilibrium, and metastable or kinetically trapped species are common terms widely used in recent, high‐quality publications in the field of supramolecular polymers. Often, the terminologies used to describe the different self‐assembly pathways, the species involved, as well as their relationship and relative stability are not trivial. Different terms and classifications are commonly found in the literature, however, in many cases, without clear definitions or guidelines on how to use them and how to determine them experimentally. The aim of this Minireview is to classify, differentiate, and correlate the existing concepts with the help of recent literature reports to provide the reader with a general insight into thermodynamic and kinetic aspects of complex supramolecular polymerization processes. A good comprehension of these terms and concepts should contribute to the development of new complex, functional materials.

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.

Herein, we report the rich morphological and conformational versatility of a biologically active peptide (PEP‐1), which follows diverse self‐assembly pathways to form up to six distinct nanostructures and up to four different secondary structures through subtle modulation in pH, concentration and temperature. PEP‐1 forms twisted β‐sheet secondary structures and nanofibers at pH 7.4, which transform into fractal‐like structures with strong β‐sheet conformations at pH 13.0 or short disorganized elliptical aggregates at pH 5.5. Upon dilution at pH 7.4, the nanofibers with twisted β‐sheet secondary structural elements convert into nanoparticles with random coil conformations. Interestingly, these two self‐assembled states at pH 7.4 and room temperature are kinetically controlled and undergo a further transformation into thermodynamically stable states upon thermal annealing: whereas the twisted β‐sheet structures and corresponding nanofibers transform into 2D sheets with well‐defined β‐sheet domains, the nanoparticles with random coil structures convert into short nanorods with α‐helix conformations. Notably, PEP‐1 also showed high biocompatibility, low hemolytic activity and marked antibacterial activity, rendering our system a promising candidate for multiple bio‐applications.

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.

In recent years, the development of sophisticated analytical tools, kinetic models and sample preparation methods has significantly advanced the field of supramolecular polymerization, where the competition of kinetic vs. thermodynamic processes has become commonplace for a wide range of building blocks. Typically, the kinetic pathways are identified in thermally controlled assembly experiments before they ultimately evolve to the thermodynamic minimum. However, there might be cases where the identification and thus the assessment of the influence of kinetic aggregates is not trivial, making the analysis of the self-assembly processes a hard task. Herein, we demonstrate that “hidden” kinetic pathways can have drastic consequences on supramolecular polymerization processes, to the point that they can even overrule thermodynamic implications. To this end, we analyzed in detail the supramolecular polymerization of a chiral Pd^II complex 1 that forms two competing aggregates (Agg I and Agg II) of which kinetic Agg II is formed through a “hidden” pathway, i.e. this pathway is not accessible by common thermal polymerization protocols. The hidden pathway exhibits two consecutive steps: first, Agg II is formed in a cooperative process, which subsequently evolves to clustered superstructures driven by rapid kinetics. At standard conditions, Agg II displays an extraordinary kinetic stability (>6 months), which could be correlated to its cooperative mechanism suppressing nucleation of thermodynamic Agg I. Furthermore, the fast kinetics of cluster formation sequester monomers from the equilibria in solution and prevents the system from relaxing into the thermodynamic minimum, thus highlighting the key implications of hidden pathways in governing supramolecular polymerization processes.