Regulating the aggregation of Aβ peptides via diverse approaches such as chemical transformations has been a long-lasting interest and challenge to alleviate the progression of AD. There has been controversy of the specific role of Aβ in AD, but recent reports continue to emphasize the necessity of our study. The demand of finding an appropriate reagent for PDT oxidatively modifying pathological factors in AD requires both effective 1 O2 production and nontoxic byproducts. Our structure-based computational modeling of small AQ-based molecules highlights the importance of the adequate level of the singlet-triplet energy gap associated with the reorganization energy throughout the ESIHT process. These conditions were met by incorporating additional hydroxyl groups to form two quasi-ring moieties that facilitate 1 O2 production. Spectroscopic and biochemical studies demonstrate the enhanced photoreactivity of the AQ-based reagents with two quasi-rings mediated by hydrogen bonding against metal-free Aβ and metal-Aβ, compared to the molecules that possess one or no intramolecular quasi-ring.