Background: There has been different interpretation of kosmotropes and chaotropes without concern for the physicochemical characteristics of the macromolecule and for the link between Hofmeister phenomena with solution structure. The objectives of this research are: 1) To investigate  different ways of determining activity coefficient and activity of ionic osmolyte 2), to present a common theoretical basis for the interaction between reaction mixture components and Hofmeister phenomena and 3) determine the preferential interaction parameters and the Kirkwood-Buff integrals. Methods: A major theoretical research and partly experimental. Results and Discussion: Some equations in literature gave different values of activity coefficient and activity of solution components. The preferential interaction by binding is positive with ethanol only and at its higher concentration in the presence of ideal solution of different concentration of calcium chloride. There was positive m-value with ethanol. It was negative m-value in the presence of preferentially binding species, calcium ion and ethanol as against the excluded chloride ion. There was negative and positive change of solvation preference and interaction parameter due respectively to ethanol only and a mixture of it and the salt. Conclusion: Selected equations in literature may not give the same values of activity coefficient and activity of solution components. The presence of stabilising osmolyte, salt, and ethanol may not always yield positive m-values. The sign of the change of solvation preference with either binary or ternary mixture of osmolytes and, the cognate interaction parameter, may be a better indicator of the stability of a macromolecule. The kosmotropes and chaotropes may be cationic or anionic and their deficit or otherwise around the macromolecule and consequence, depend largely on net charge on the macromolecule at a given pH.