Aggregate Engineering: Distinct Photophysical Properties and Organelle Targeting in Mesoionic Luminogens

Aggregate science, which studies how molecular aggregates exhibit properties distinct from those of individual molecules, is fundamental to understanding molecular interactions in various fields, including chemistry, physics, and the life sciences. However, precisely controlling aggregate structures and their properties without altering intrinsic molecular properties remains a significant challenge. Here, we report a versatile platform built on a unique mesoionic luminogens TPO (thiazolo[3,2-a]pyridin-4-ium-3-olate), to systematically investigate and modulate structure-property relationships in aggregates. By introducing alkyl chains of varying lengths, three TPO derivatives (TPO-X, X = 2, 8, or 12) enable fine-tuning of aggregate morphologies and photophysical behaviors. Mechanistic studies reveal that intermolecular interactions between the TPO core govern excited-state energy pathways, leading to distinct emission properties and reactive oxygen species (ROS) generation abilities. Moreover, TPO-X showed distinct organelle targeting abilities: TPO-2 for mitochondria, TPO-8 for endoplasmic reticulum, and TPO-12 for cell membrane, respectively, and further achieved excellent tumor cell killing effect via different cell death pathways. This platform demonstrates strong adaptability for the study of aggregate science, enabling the design and regulation of novel aggregate materials in various research fields.Aggregate science, which studies how molecular aggregates exhibit properties distinct from those of individual molecules, is fundamental to understanding molecular interactions in various fields, including chemistry, physics, and the life sciences. However, precisely controlling aggregate structures and their properties without altering intrinsic molecular properties remains a significant challenge. Here, we report a versatile platform built on a unique mesoionic luminogens TPO (thiazolo[3,2-a]pyridin-4-ium-3-olate), to systematically investigate and modulate structure-property relationships in aggregates. By introducing alkyl chains of varying lengths, three TPO derivatives (TPO-X, X = 2, 8, or 12) enable fine-tuning of aggregate morphologies and photophysical behaviors. Mechanistic studies reveal that intermolecular interactions between the TPO core govern excited-state energy pathways, leading to distinct emission properties and reactive oxygen species (ROS) generation abilities. Moreover, TPO-X showed distinct organelle targeting abilities: TPO-2 for mitochondria, TPO-8 for endoplasmic reticulum, and TPO-12 for cell membrane, respectively, and further achieved excellent tumor cell killing effect via different cell death pathways. This platform demonstrates strong adaptability for the study of aggregate science, enabling the design and regulation of novel aggregate materials in various research fields.