Flotation is a widely used separation technique in mineral processing that relies on surface chemistry to recover valuable metals from low-grade ores. This study presents a theoretical evaluation of O-O type chelating collectors in the selective flotation of copper minerals, emphasizing their interactions at the colloidal and interfacial levels. Using advanced computational methods, key surface chemistry parameters—including adhesion mechanisms, electron density distributions, and binding energies—were analyzed to assess the efficiency and selectivity of these collectors. The findings demonstrate that O-O type chelating collectors establish strong and specific interactions with copper mineral surfaces, enhancing hydrophobicity and improving attachment to air bubbles. Among the studied collectors—Cupferon, Neocupferon, 2-nitroso-1-naphthol, 2,4-pentanedione, Octyl hydroxamate, and 2-Acetyl-acetanalid—Octyl hydroxamate exhibited the highest stability and affinity for Cu²⁺ ions, while 2-Acetyl-acetanalid showed the weakest performance. This study provides fundamental insights into the interfacial mechanisms governing flotation efficiency and offers guidance for optimizing reagent selection. By contributing to the design of more selective and sustainable collectors, these findings support advancements in mineral processing, environmental technologies, and interfacial science.