Solvation of a Small Metal-Binding Peptide in Room-Temperature Ionic Liquids

Abstract

Structural properties of a small hexapeptide molecule modeled after metal-binding siderochrome immersed in a room-temperature ionic liquid (RTIL) are studied via molecular dynamics simulations. We consider two different RTILs, each of which is made up of the same cationic species, 1-butyl-3-methylimidazolium (BMI + ), but different anions, hexafluorophosphate (PF6 − ) and chloride (Cl − ). We investigate how anionic properties such as hydrophobicity/hydrophilicity or hydrogen bonding capability affect the stabilization of the peptide in RTILs. To examine the effect of peptide-RTIL electrostatic interactions on solvation, we also consider a hypothetical solvent BMI − . This is ascribed to the good hydrogen-bond accepting power of chloride anions, which enables them to bind strongly to hydroxyl groups of the peptide and to stabilize its structure. Transport properties of the peptide are examined briefly. Translations of the peptide significantly slow down in highly viscous RTILs.

Do Ionic Liquids Exhibit the Required Characteristics to Dissolve, Extract, Stabilize, and Purify Proteins? Past-Present-Future Assessment

“…272 The relevance of H-bonding for protein stability in NILs was also demonstrated from simulation studies on the solvation of small cyclic hexapeptide in ILs, namely, [C 4 mim]Cl and [C 4 mim][PF 6 ]. 273 The H-bonding between the hydroxyl groups of the peptide and the IL anion was shown to stabilize the peptide in [C 4 mim]Cl compared to that in [C 4 mim]-[PF 6 ]. 273 Bermejo et al 274 also reported higher solubility of Candida antarctica lipase (12%) in [HOPmim][NO 3 ] containing a cation with an H-bonding site.…”

“…273 The H-bonding between the hydroxyl groups of the peptide and the IL anion was shown to stabilize the peptide in [C 4 mim]Cl compared to that in [C 4 mim]-[PF 6 ]. 273 Bermejo et al 274 also reported higher solubility of Candida antarctica lipase (12%) in [HOPmim][NO 3 ] containing a cation with an H-bonding site. Zhao et al 29 investigated the dissolution and stabilization of Candida antarctica lipase B in 18, nonfunctionalized and etherfunctionalized ammonium and imidazolium cation containing ILs, with [OAc], [HCOO], [dca], and [C 2 OSO 3 ] anions.…”

“…Molecular dynamics (MD) simulations offer an alternative to better understand the interactions taking place . Shim et al carried out MD studies on the solvation of cyclic hexa-peptides in the ILs [C 4 mim]Cl and [C 4 mim]­[PF 6 ], revealing peptide structure distortion by electrostatic interactions occurring between the peptides and both ILs. The distortion was lower in the [C 4 mim]Cl due to the stabilization of the peptide by intermolecular H-bonding .…”

“…Shim et al carried out MD studies on the solvation of cyclic hexa-peptides in the ILs [C 4 mim]Cl and [C 4 mim]­[PF 6 ], revealing peptide structure distortion by electrostatic interactions occurring between the peptides and both ILs. The distortion was lower in the [C 4 mim]Cl due to the stabilization of the peptide by intermolecular H-bonding . Burney et al simulated Candida rugosa lipase (CRL) in [C 4 mim]­[PF 6 ] and [C 4 mim]­[NO 3 ], concluding that ILs dampen protein dynamics, trapping the system near its initial structure due to electrostatic interactions.…”

Exploring the structure and stability of amino acids and glycine peptides in biocompatible ionic liquids

“…Consequently, the magnitude of the interaction of IL with AA is expected to vary as compared with the solubility of the AA in ILs aqueous solution. 106 5.1.The contribution of the peptide backbone unit (or glycyl residue) and various functional groups from water to ILs…”