Herein, the interaction of the hydrophobically associating polymer HP-1 with the anionic surfactant sodium dodecylbenzene sulfonate (SDS) was investigated using solution viscosity by Brookfield viscometer, rheology including steady shear rheology and dynamic frequency sweep rheology, ambient scanning electron microscopy, and fluorescence measurements and then simulated and analyzed using dissipative particle dynamics simulations (DPD). The results showed that as SDS concentration increased, the solution viscosity of the HP-1/SDS system first declined, then increased, reached a peak, and then decreased again before gradually leveling off. The rheology and microscopic morphology of the system exhibited similar patterns of change. The system’s solution shear rheology and viscoelasticity decreased with increasing SDS concentration, then increased and ultimately decreased, and the system’s reticulation structure changed from loose to tight and then again to loose, according to the law of composite viscosity. Moreover, the ratio of the emission peak intensities of the monomer fluorescence spectra of pyrene molecules in solution at 372 and 383 nm (I3/I1) first decreased, then increased, and finally stabilized. This implies that the above phenomenon is associated with the change in the number of HP-1’s hydrophobic interaction. Thus, SDS affects both the binding efficiency and number of binding groups of HP-1, resulting in a change in the properties of the solution. Finally, DPD simulations were performed to study the interaction between SDS and HP-1, confirming the experimental data-derived supposition. Upon the addition of SDS, it began to interact with HP-1 hydrophobic groups until all of the hydrophobic groups were coated with SDS, resulting in coiling of the HP-1 polymer chains. Meanwhile, SDS molecules adsorbed onto the polymer chain and aggregated with each other to form micelles, altering the properties of the solution.
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