A Study of the Solvation Structure of l‐Leucine in Alcohol–Water Binary Solvents through Molecular Dynamics Simulations and FTIR and NMR Spectroscopy

Abstract

The solvation structures of l-leucine (Leu) in aliphatic-alcohol-water and fluorinated-alcohol-water solvents are elucidated for various alcohol contents by using molecular dynamics (MD) simulations and IR, and (1) H and (13) C NMR spectroscopy. The aliphatic alcohols included methanol, ethanol, and 2-propanol, whereas the fluorinated alcohols were 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol. The MD results show that the hydrophobic alkyl moiety of Leu is surrounded by the alkyl or fluoroalkyl groups of the alcohol molecules. In particular, TFE and HFIP significantly solvate the alkyl group of Leu. IR spectra reveal that the Leu C-H stretching vibration blueshifts in fluorinated alcohol solutions with increasing alcohol content, whereas the vibration redshifts in aliphatic alcohol solutions. When the C-H stretching vibration blueshifts in the fluorinated alcohol solutions, the hydrogen and carbon atoms of the Leu alkyl group are magnetically shielded. Consequently, TFE and HFIP molecules may solvate the Leu alkyl group through the blue-shifting hydrogen bonds.

Solvation Structures of Tetraethylammonium Bromide and Tetrafluoroborate in Aqueous Binary Solvents with Ethanol, Trifluoroethanol, and Acetonitrile

“…The specific interaction may act between the outside ethyl groups of TEA + and the TFE C–F bonds, such as the C–H···F–C weak hydrogen bonds. This weak hydrogen bond has been reported by many chemists. − …”

“…However, the hydrogen-bond acceptability of the TFE oxygen atom is much lower than that of EtOH due to the electron drawal by the three fluorine atoms. In contrast, the trifluoromethyl group of TFE may interact with the hydrophobic alkyl chain of TEA + through the C–H···F–C weak hydrogen bonds, as reported in the literature. − On the contrary, AN does not act as a hydrogen-bonding donor but acts as a hydrogen-bonding acceptor. The dipole moment (11.47 × 10 –30 C m) of AN is higher than those (5.67 × 10 –30 and 6.77 × 10 –30 C m, respectively) of EtOH and TFE .…”

“…In particular, the slightly positive H atoms of the TEA + ethyl groups may attract the F atoms of TFE with the higher electron density due to high electronegativity. The shielding of the positively charged TEA + H and C atoms is more remarkable than those of the neutral diol and amino acid. , For the formation of the C–H···F–C hydrogen bonds, the H and C atoms of the C–H bonds within the hydrogen-bond donor are often shielded with strengthening the hydrogen bonds. In fact, as shown in Figure , all of the H and C atoms of the TEA + ethyl groups are shielded with increasing x TFE .…”

Solvent Effects on the Self-Assembly of an Amphiphilic Polypeptide Incorporating α-Helical Hydrophobic Blocks

“…That is, MeOH can tend to interact with water molecules, and IPA favors a hydrophobic environment compared with MeOH. In addition, Takamuku et al reported that the alcohol with a long alkyl chain showed effective interaction with the Leu alkyl chain in the order of IPA > EtOH > MeOH . These differences of physical properties of alcohol molecules having various alkyl chains suggested that IPA and EtOH may penetrate a hydrophobic layer of the peptide assembly more and deeper than MeOH and may therefore loosen the packing of amphiphilic peptides, resulting in a lower curvature and a larger diameter of the nanotube assembly.…”

“…Next, we studied the effect of a binary solvent on the hydration shell around each component of peptide S30L12 using the monomers Leu, Aib, and Sar in order to further understand the behavior of alcohols with S30L12. The nature of the interaction of the Leu side chain with different alcohols was understood by the simulation and IR experimental studies by Takamuku et al 62 IR spectra of the C−H stretching vibrational band of the Leu side chain in H 2 O with varying ratios of aliphatic alcohols (MeOH, EtOH, and IPA) indicated that the water molecule around the Leu alkyl chain was gradually decreased by increasing the alcohol content, which was evidenced by the red-shift in the IR spectra. Consequently, the length of the contracted Leu alkyl C−H bond in aqueous condition was recovered by the addition of aliphatic alcohol, indicating the reduction of the hydration shell in the alcohol/ H 2 O mixture.…”