Biophysical Insights into the Interaction of Phthalate Esters With Collagen

Phthalate esters are widely used as plasticizers in consumer and medical products, with growing evidence linking their exposure to endocrine- and collagen (COL)-related disorders. To elucidate their structural impact, we examined the interactions of dimethyl terephthalate, diethyl phthalate, dibutyl phthalate, and dioctyl phthalate with type I COL using spectroscopic, calorimetric, light-scattering, and computational methods. Ultraviolet and fluorescence analyses revealed conformational perturbations associated with tyrosine exposure, whereas circular dichroism and infrared spectroscopy indicated distinct secondary-structure alterations. Dynamic light scattering demonstrated reduced aggregate size, reflecting disrupted supramolecular assembly. In contrast, differential scanning calorimetry showed counterintuitive thermal stabilization of the complexes, consistent with hydrophobic effects and hydrogen-bonding interactions identified by docking simulations that contribute to overall stability. Although each phthalate analogue exerted a different degree of impact, the outcomes were complementary in showing that COL's integrity and organization are altered at multiple structural levels. Collectively, these findings highlight the molecular complexity of COL-phthalate interactions and underscore the need to assess the long-term effects of chronic, low-dose exposure.