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The estimation of thermodynamic parameters of N-Acetyl-L-cysteine (NAC) protonation were determined in NaCl (aq) , (CH 3 ) 4 NCl (aq) , (C 2 H 5 ) 4 NI (aq), employing various temperature and ionic strengths conditions, by potentiometric measurements. The interaction of NAC with some essential metal cations ( e.g. , Ca 2+ , Mg 2+ and Zn 2+ ) was investigated as well at 298.15 K in NaCl (aq) in the ionic strength range 0.1 ≤  I /mol dm -3  ≤ 1.0. The values of protonation constants at infinite dilution and at T  = 298.15 K are: log K 1 H  = 9.962 ± 0.005 (S-H) and log K values followed the trend (C 2 H  = 3.347 ± 0.008 (COO-H). In the presence of a background electrolyte, both log K 1 H and log K 2 H values followed the trend (C 2 H 5 ) 4 NI ≥ (CH 3 ) 4 NCl ≥ NaCl. The differences in the values of protonation constants among the three ionic media were interpreted in terms of variation of activity coefficients and formation of weak complexes. Accordingly, the determination of the stability of 4 species, namely: NaL - , NaHL 0 (aq) , (CH 3 ) 4 NL - , (CH 3 ) 4 NHL 0 (aq) was assessed. In addition, as regards the interactions of Mg 2+ , Ca 2+ and Zn 2+ with NAC, the main species where the ML 0 (aq) , ML(OH) - , and ML 2 2- , that were found to be important in the chemical speciation of NAC in real multicomponent solutions. The whole set of the data collected may be crucial for the development of NAC-based materials for natural fluids selective decontamination from heavy metals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier B.V. All rights reserved.)