Anticooperative self-assembly of perylene diimide dyes in water unveiled by advanced molecular dynamics simulations

The self-assembly mechanism and the dynamics in water of π-stacked columnar aggregates of <i>N</i>,<i>N</i>-bis(2-(trimethylammonium)ethylene)perylene-3,4,9,10-tetracarboxylic acid bis-imide (PDI) have been investigated using classical molecular dynamics (MD) simulations based on an accurate quantum mechanically derived force field. Nano-scale aggregates composed of up to twelve monomers were studied through a combination of <i>bottom-up</i> and <i>top-down</i> approaches, complemented by enhanced sampling MD techniques. Our simulations provide unprecedented atomistic information on the anti-cooperative aggregation mechanism, consistent with experimental findings for PDIs with bulky imide substituents. Umbrella sampling simulations coupled with in-depth thermodynamic analysis reveal, indeed, that entropic contributions dominate the aggregation process, resulting in a non-linear growth mechanism that saturates with increasing aggregate size. Replica exchange MD runs confirm that experimental properties of these systems can be effectively described considering species up to tetramers or hexamers. Although larger aggregates may form, they represent only a minor fraction of the observed species. The stability and dynamics of PDI aggregates in water were further analyzed by means of specific geometric supramolecular descriptors designed to capture relative monomer motions. This analysis indicates that dimers, rather than monomers, act as the primary building blocks, with even-numbered aggregates behaving like strongly-bound interacting dimers. Monitoring water structure around PDI aggregates unveils a rather complex scenario, where the hydration of charged side chains is persistent across all aggregate sizes, while steric shielding within π-π stacks progressively reduces core solvation, though carbonyl oxygens maintain hydrogen-bond interactions with water. Analysis of hydrogen-bond statistics confirms a gradual decrease in solvation per monomer with aggregation, reaching a plateau at larger stack sizes. Complementary dynamical investigations demonstrated that water expulsion does not follow a simple concerted process, but instead proceeds through partially solvated intermediates reflecting the energetic cost of disrupting interfacial hydrogen bonding. Together, these findings highlight the critical entropic role of solvent reorganization in driving aggregation and may provide mechanistic insights relevant for optimizing photocatalytic activity through rational monomer design.