Study on the interaction between 2,6-dihydroxybenzoic acid nicotine salt and human serum albumin by multi-spectroscopy and molecular dynamics simulation

As a new form of nicotine introduction for novel tobacco products, the interaction of nicotine salt with biological macromolecules may differ from that of free nicotine and thus affect its transport and distribution in vivo. Hence, the mechanism underlying the interaction between 2,6-dihydroxybenzoic acid nicotine salt (DBN) and human serum albumin (HSA) was investigated by multi-spectroscopy, molecular docking, and dynamic simulation. Experiments on steady-state fluorescence and fluorescence lifetime revealed that the quenching mechanism of DBN and HSA was dynamic quenching, and binding constant was in the order of 10<^>4 L mol(-1). Thermodynamic parameters exhibited that the binding was a spontaneous process with hydrophobic forces as the main driving force. Fluorescence competition experiments revealed that DBN bound to site I of HSA IIA subdomain. According to the results of synchronous fluorescence, 3D fluorescence, FT-IR spectroscopy, circular dichroism (CD) spectroscopy, and molecular dynamics (MD) simulation, DBN did not affect the basic skeleton structure of HSA but changed the microenvironment around the amino acid residues. Computer simulations positively corroborated the experimental results. Moreover, DBN decreased the surface hydrophobicity and weakened the esterase-like activity of HSA, leading to the impaired function of the latter. This work provides important information for studying the interaction between DBN as a nicotine substitute and biological macromolecules and contributes to the further development and application of DBN. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the interaction mechanism between DBN and HSA using multi-spectroscopy, molecular docking, and dynamic simulation. The results showed that the binding of DBN and HSA was a spontaneous process driven by hydrophobic forces. DBN changed the microenvironment around HSA and decreased its surface hydrophobicity, leading to impaired esterase-like activity.