Chiral Heteroatom Cluster Unlocks High-Order Multiphoton Fluorescence in Single-Benzene Luminogens

Multiphoton fluorophores are typically based on extended π-conjugated architectures, resulting in structural complexity and limited tunability. Here, we report a chirality-guided strategy for constructing high-order multiphoton fluorophores from a minimalist single-aryl scaffold. Through solvent-assisted assembly, chirality and hydrogen-bonding interactions organize heteroatoms into ordered chiral heteroatom clusters (CHCs), enabling through-space conjugation and clusteroluminescence without direct aryl-aryl π-π stacking. Structural and chiroptical studies reveal that chirality is encoded into the emissive cluster states and governs clusteroluminescence. Donor-acceptor engineering further establishes CHC-mediated through-space charge transfer in which heteroatom clusters act as electronic bridges connecting spatially separated donor and acceptor units. The synergistic interplay between chirality-guided CHC organization and charge transfer enhances electronic delocalization and polarizability, leading to efficient two-, three-, and four-photon-excited fluorescence in an isolated aromatic framework. The enhanced nonlinear optical response enables deep imaging of three-dimensional tumor spheroids with penetration depths up to 160 μm. This work establishes chirality-guided heteroatom clustering as a general strategy for compact multiphoton fluorophores and nonlinear optical materials.