Classical vs. nonclassical hydrophobic interactions underlying various interaction processes: Application of isothermal titration calorimetry
Bijan Kumar Paul
Abstract
Despite being enormously studied and almost unequivocally recognized as the most important solvent in chemistry, water continues to foster the nucleus multi-faceted dynamic research activities till date, especially when it is concerned about understanding the mechanism and impact of hydration of nonpolar or polar substances and/or residues of macromolecular entities in course of complex interactions involving biological and/or biomimicking assemblies. An adequate understanding of the reorganizations of solvation (hydration) structure accompanying such interactions becomes difficult to obtain particularly with a view to a direct experimental technique to probe the interactions and thus necessitates the choice of suitable experimental technique/methodology to be able to delve into the thermodynamics associated with the same. The present article is focused on discussions surrounding the predominant role of modulation of the dynamics of water of hydration underlying various interactions such as (i) interaction of small drug molecules/ligands with biological receptors (e.g., proteins, nucleic acids) (ii) interaction of small drug molecules/ligands with biomimicking assemblies (e.g., liposome membranes, noisome membranes), (iii) interaction of small drug molecules/ligands with potent drug delivery systems (e.g., cyclodextrins, micellar assemblies), and (iv) refolding of denatured proteins. To this effect, isothermal titration calorimetry (ITC) has been employed as a potential tool for investigation of the thermodynamics of the associated interaction phenomena through specifically designed experiments. The present article also discusses about the governing roles of “classical” and “nonclassical” hydrophobic effects underlying the interactions in specific cases.