High-valent metal oxides such as LiCoO₂ (LCO) and related materials are of increasing environmental concern due to the large-scale use in lithium-ion batteries and potential for metal ion release into aqueous systems. A key aspect of the environmental chemistry of these materials is the potential role redox chemistry plays in their transformations as well as their influence on the surrounding environment (i.e., biomolecules, organisms etc.). In recent work, we showed that LCO interacts with the biomolecule nicotinamide adenine dinucleotide (NADH), an essential molecule for electron transport, oxidizing NADH as well as increasing Co release from LCO. This redox behavior was observed for the high-valent Co-containing materials but not low-valent Co-containing controls. In the present work, we aim to elucidate the mechanism of biological impact by examining the role of the ribose and the nicotinamide components of NADH in the transformation of LCO nanomaterials. To build an understanding of the interaction mechanism, we used fluorescence spectroscopy to measure the changes in redox state and inductively coupled plasma-mass spectrometry to measure the changes in dissolved Co. Our results reveal new insights into the role of phosphate and nicotinamide groups in controlling the overall reactivity. We further established the generality of the results with LCO by examining other high-valent transition metal oxides. This work is important to understanding the impact of industrially relevant transition metal oxides on naturally occurring biological redox processes in the environment.