Heterolytic cleavage, which is a deprotonation reaction leaving an electron pair:

This deprotonation occurs at increased pH and generates perhydroxyl anions (Feinman et al. 1991).

A third pathway is derived by a combination of homolytic and heterolytic cleavage and generates active oxygen that is both an anion and a free radical:

Active oxygen is attracted to electron-rich areas of stain molecules and cleaves double bond to reduce color or remove the compound (Albers 1991).

Despite the well-known chemistry of hydrogen peroxide and its application to establish the chromophore theory, many issues remain unsolved. Studies using Fourier Transform Infra-Red (FTIR) and Raman spectroscopies failed to detect chromophores or their breakdown products in the enamel, and are inconsistent with the chromophore theory (Darchuk et al. 2008; Eimar et al. 2012; Fattibene et al. 2005). Thus, continued investigation is required to fully understand the mechanisms of hydrogen peroxide in eliminating stains.

Ideally, as hydrogen peroxide moves from the external tooth surface into the enamel and dentin, its oxidizing action should be limited to organic chromophores until it reaches a certain saturation point, or whitening threshold. Oxidizing action beyond the whitening threshold—characterized by the depletion of chromophores—has been cautioned against as it might compromise tooth structure. Indeed, review of the literature suggests hydrogen peroxide has significant interactions with the organic and inorganic components of enamel and dentin well before the saturation point. This may account for alterations in the physical properties of the tooth substrate after the whitening treatment (Attin et al. 2005).

Extensive studies using ion-selective electrode probes, FT-Raman spectroscopy, and a combination of scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer and microcomputerized tomography suggest that hydrogen peroxide interacts with the tooth structure, and changes the chemical composition of enamel and dentin (Kwon and Wertz 2016). While evidence exists that peroxide-based materials do not irreversibly influence the chemistry of enamel and dentin beyond clinical relevance (Arcari et al. 2005; Cavalli et al. 2011; Goo et al. 2004; Lee et al. 2006; Mc Cracken and Haywood 1996; Rodrigues et al. 2007), several studies have demonstrated significant changes in the calcium/phosphate ratio, indicative of alterations in the inorganic components of hydroxyapatite (Al-Saleni et al. 2007; Berger et al. 2010; Bizhang et al. 2006; de Freitas et al. 2004; Efeoglu et al. 2005; Efeoglu et al. 2007; Rotstein et al. 1996; Rotstein et al. 1992). Microcomputerized tomography studies of enamel treated with 10 % or 35 % carbamide peroxide demonstrated a demineralization depth of 50 μm and 250 μm, respectively (Efeoglu et al. 2005; Efeoglu et al. 2007). Furthermore, infrared spectroscopic analysis showed changes in the enamel that was both concentration and time dependent.

It is worth noting that changes in the organic component of enamel and dentin are likely due to the oxidizing ability of hydrogen peroxide, while changes in the mineral component are mainly attributed to its acidity (Jiang et al. 2007). Several studies provide evidence supporting that the organic matrix of enamel and dentin is oxidized by hydrogen peroxide. X-ray diffraction analysis of hydroxyapatite suggests hydrogen peroxide influences the organic tissue, and Nuclear Magnetic Resonance-based measurements indicate that proline and alanine may be more susceptible to an attack by the hydroxyl radical (Kawamoto and Tsujimoto 2004; Sato et al. 2013; Toledano et al. 2011). Other studies assessing morphological changes in the enamel and dentin used atomic force microscopy (AFM) and FTIR to show that the tooth enamel matrix protein or organic matrix of dentin had partially lysed, causing these effects (Abouassi et al. 2011; Chng et al. 2005; Hegedüs et al. 1999; Mahringer et al. 2009; Sato et al. 2013; Ubaldini et al. 2013). Moreover, other studies have implicated that proteolysis by dentin metalloproteinases and cathepsin B might also compromise the organic component of dentin (Sato et al. 2013; Toledano et al. 2011).

Collectively, these studies demonstrate that hydrogen peroxide indeed interacts with all components of dentin and enamel. Thus, it may not only target chromophore stains, but also whiten by modifying the organic substances within the tooth. Future studies must identify the clinical significance of interactions between hydrogen peroxide and each tooth layer.