title: Epitope mapping of imidazolium cations in ionic liquid-protein interactions unveils the balance between hydrophobicity and electrostatics towards protein destabilisation.
abstract: We investigated imidazolium-based ionic liquid (IL) interactions with human serum albumin (HSA) to discern the level of cation interactions towards protein stability. STD-NMR spectroscopy was used to observe the imidazolium IL protons involved in direct binding and to identify the interactions responsible for changes in Tm as accessed by differential scanning calorimetry (DSC). Cations influence protein stability less than anions but still significantly. It was found that longer alkyl side chains of imidazolium-based ILs (more hydrophobic) are associated with a higher destabilisation effect on HSA than short-alkyl groups (less hydrophobic). The reason for such destabilisation lies on the increased surface contact area of the cation with the protein, particularly on the hydrophobic contacts promoted by the terminus of the alkyl chain. The relevance of the hydrophobic contacts is clearly demonstrated by the introduction of a polar moiety in the alkyl chain: a methoxy or alcohol group. Such structural modification reduces the degree of hydrophobic contacts with HSA explaining the lesser extent of protein destabilisation when compared to longer alkyl side chain groups: above [C2mim](+). Competition STD-NMR experiments using [C2mim](+), [C4mim](+) and [C2OHmim](+) also validate the importance of the hydrophobic interactions. The combined effect of cation and anion interactions was explored using (35)Cl NMR. Such experiments show that the nature of the cation has no influence on the anion-protein contacts, still the nature of the anion modulates the cation-protein interaction. Herein we propose that more destabilising anions are likely to be a result of a partial contribution from the cation as a direct consequence of the different levels of interaction (cation-anion pair and cation-protein).
authors.affiliation: REQUIMTE, UCIBIO, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516 Monte de Caparica, Portugal. am.figueiredo@fct.unl.pt ejc@fct.unl.pt.
authors.forename: Micael
authors.initials: M
authors.lastname: Silva
authors.forename: Angelo Miguel
authors.initials: AM
authors.lastname: Figueiredo
authors.forename: Eurico J
authors.initials: EJ
authors.lastname: Cabrita
mesh_terms: D002412:Cations / Q000737:chemistry; D018604:Epitope Mapping; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry*; D055550:Protein Stability; D012709:Serum Albumin / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D002412:Cations; D007093:Imidazoles; D052578:Ionic Liquids; D012709:Serum Albumin