Cation-π Interactions between Quaternary Ammonium Ions and Amino Acid Aromatic Groups in Aqueous Solution

Esam A. Orabi, Guillaume Lamoureux

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cation-π interactions play important roles in the stabilization of protein structures and protein-ligand complexes. They contribute to the binding of quaternary ammonium ligands (mainly RNH3 + and RN(CH3)3 +) to various protein receptors and are likely involved in the blockage of potassium channels by tetramethylammonium (TMA+) and tetraethylammonium (TEA+). Polarizable molecular models are calibrated for NH4 +, TMA+, and TEA+ interacting with benzene, toluene, 4-methylphenol, and 3-methylindole (representing aromatic amino acid side chains) based on the ab initio MP2(full)/6-311++G(d,p) properties of the complexes. Whereas the gas-phase affinity of the ions with a given aromatic follows the trend NH4 + > TMA+ > TEA+, molecular dynamics simulations using the polarizable models show a reverse trend in water, likely due to a contribution from the hydrophobic effect. This reversed trend follows the solubility of aromatic hydrocarbons in quaternary ammonium salt solutions, which suggests a role for cation-π interactions in the salting-in of aromatic compounds in solution. Simulations in water show that the complexes possess binding free energies ranging from -1.3 to -3.3 kcal/mol (compared to gas-phase binding energies between -8.5 and -25.0 kcal/mol). Interestingly, whereas the most stable complexes involve TEA+ (the largest ion), the most stable solvent-separated complexes involve TMA+ (the intermediate-size ion).

Original languageEnglish (US)
Pages (from-to)2251-2260
Number of pages10
JournalJournal of Physical Chemistry B
Volume122
Issue number8
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

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Aromatic Amino Acids
Ammonium Compounds
amino acids
Cations
Amino acids
Positive ions
Ions
aqueous solutions
proteins
Proteins
trends
cations
acids
Gases
Skatole
Ligands
vapor phases
Aromatic Hydrocarbons
ions
ligands

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

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title = "Cation-π Interactions between Quaternary Ammonium Ions and Amino Acid Aromatic Groups in Aqueous Solution",
abstract = "Cation-π interactions play important roles in the stabilization of protein structures and protein-ligand complexes. They contribute to the binding of quaternary ammonium ligands (mainly RNH3 + and RN(CH3)3 +) to various protein receptors and are likely involved in the blockage of potassium channels by tetramethylammonium (TMA+) and tetraethylammonium (TEA+). Polarizable molecular models are calibrated for NH4 +, TMA+, and TEA+ interacting with benzene, toluene, 4-methylphenol, and 3-methylindole (representing aromatic amino acid side chains) based on the ab initio MP2(full)/6-311++G(d,p) properties of the complexes. Whereas the gas-phase affinity of the ions with a given aromatic follows the trend NH4 + > TMA+ > TEA+, molecular dynamics simulations using the polarizable models show a reverse trend in water, likely due to a contribution from the hydrophobic effect. This reversed trend follows the solubility of aromatic hydrocarbons in quaternary ammonium salt solutions, which suggests a role for cation-π interactions in the salting-in of aromatic compounds in solution. Simulations in water show that the complexes possess binding free energies ranging from -1.3 to -3.3 kcal/mol (compared to gas-phase binding energies between -8.5 and -25.0 kcal/mol). Interestingly, whereas the most stable complexes involve TEA+ (the largest ion), the most stable solvent-separated complexes involve TMA+ (the intermediate-size ion).",
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Cation-π Interactions between Quaternary Ammonium Ions and Amino Acid Aromatic Groups in Aqueous Solution. / Orabi, Esam A.; Lamoureux, Guillaume.

In: Journal of Physical Chemistry B, Vol. 122, No. 8, 01.03.2018, p. 2251-2260.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cation-π Interactions between Quaternary Ammonium Ions and Amino Acid Aromatic Groups in Aqueous Solution

AU - Orabi, Esam A.

AU - Lamoureux, Guillaume

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N2 - Cation-π interactions play important roles in the stabilization of protein structures and protein-ligand complexes. They contribute to the binding of quaternary ammonium ligands (mainly RNH3 + and RN(CH3)3 +) to various protein receptors and are likely involved in the blockage of potassium channels by tetramethylammonium (TMA+) and tetraethylammonium (TEA+). Polarizable molecular models are calibrated for NH4 +, TMA+, and TEA+ interacting with benzene, toluene, 4-methylphenol, and 3-methylindole (representing aromatic amino acid side chains) based on the ab initio MP2(full)/6-311++G(d,p) properties of the complexes. Whereas the gas-phase affinity of the ions with a given aromatic follows the trend NH4 + > TMA+ > TEA+, molecular dynamics simulations using the polarizable models show a reverse trend in water, likely due to a contribution from the hydrophobic effect. This reversed trend follows the solubility of aromatic hydrocarbons in quaternary ammonium salt solutions, which suggests a role for cation-π interactions in the salting-in of aromatic compounds in solution. Simulations in water show that the complexes possess binding free energies ranging from -1.3 to -3.3 kcal/mol (compared to gas-phase binding energies between -8.5 and -25.0 kcal/mol). Interestingly, whereas the most stable complexes involve TEA+ (the largest ion), the most stable solvent-separated complexes involve TMA+ (the intermediate-size ion).

AB - Cation-π interactions play important roles in the stabilization of protein structures and protein-ligand complexes. They contribute to the binding of quaternary ammonium ligands (mainly RNH3 + and RN(CH3)3 +) to various protein receptors and are likely involved in the blockage of potassium channels by tetramethylammonium (TMA+) and tetraethylammonium (TEA+). Polarizable molecular models are calibrated for NH4 +, TMA+, and TEA+ interacting with benzene, toluene, 4-methylphenol, and 3-methylindole (representing aromatic amino acid side chains) based on the ab initio MP2(full)/6-311++G(d,p) properties of the complexes. Whereas the gas-phase affinity of the ions with a given aromatic follows the trend NH4 + > TMA+ > TEA+, molecular dynamics simulations using the polarizable models show a reverse trend in water, likely due to a contribution from the hydrophobic effect. This reversed trend follows the solubility of aromatic hydrocarbons in quaternary ammonium salt solutions, which suggests a role for cation-π interactions in the salting-in of aromatic compounds in solution. Simulations in water show that the complexes possess binding free energies ranging from -1.3 to -3.3 kcal/mol (compared to gas-phase binding energies between -8.5 and -25.0 kcal/mol). Interestingly, whereas the most stable complexes involve TEA+ (the largest ion), the most stable solvent-separated complexes involve TMA+ (the intermediate-size ion).

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