Binding Interaction between Nicotine and Human Serum Albumin by High Performance Affinity Chromatography

Abstract

Several reports have confirmed that nicotine can bind to serum albumin, but the exact strength, location and number of the binding sites used during this process remain unclear. In this work, frontal analysis investigation showed that the binding isotherm of nicotine to human serum albumin (HSA) best fitted the Langmuir model, suggesting a single kind of binding site for nicotine on HSA. Competitive studies with probe compounds revealed that nicotine is in direct competition with l-tryptophan, indicated that nicotine binds to Sudlow site II (i.e., the indole–benzodiazepine site of HSA). No interactions were seen between nicotine and S-warfarin, tamoxifen or digitoxin. The association constant of nicotine binding to HSA was (8.60 ± 2.26) × 104 M−1 at pH 7.2 and 37 °C. The value of ∆G for this reaction was −42.75 kJ mol−1 at 37 °C, with an associated change in enthalpy (∆H) of 6.7 kJ mol−1 and a change in entropy (∆S) of 116.4 J mol-1 K−1, demonstrating that the interaction was driven mainly by entropy, and that hydrophobic interaction was the main power behind the binding process. These results will help provide a more detailed description of how nicotine is transported in the blood and how it may interact with other drugs in the body.