Aggregation of the Dipeptide Leu–Gly in Alcohol–Water Binary Solvents Elucidated from the Solvation Structure for Each Moiety

Abstract

The aggregation of a dipeptide, L-leucine-glycine (Leu−Gly), at 100 mmol dm −3 has been observed in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)−water and 2-propanol (2-PrOH)−water solvents at various alcohol mole fractions, x A , using the dynamic light scattering technique and molecular dynamics (MD) simulations. Leu−Gly was dissolved into the HFIP solvents at the concentration over the entire x A range, while the dipeptide was not dissolved in the 2-PrOH solvents above x A = 0.6. Interestingly, the MD snapshots showed different shapes of Leu−Gly aggregates in the HFIP and 2-PrOH solvents. A linear-shaped aggregate forms in the former; in contrast, a spherical-shaped aggregate is generated in the latter. The solvation structure of each moiety of Leu−Gly in the HFIP and 2-PrOH solvents was observed using experimental and theoretical techniques, 1 H and 13 C NMR, IR, and 19 F− 1 H HOESY measurements and MD simulations. These results gave us the reasons for the different shapes of Leu−Gly aggregates in both solvents. In the HFIP solvents, most of the moieties of the dipeptide are easily solvated by HFIP. This induces the elongated structure of Leu−Gly, leading to the electrostatic interaction between the N-(NH 3 + group) and C-(COO − group) terminals of dipeptide molecules. On the other hand, in the 2-PrOH solvents, water molecules that initially solvate the moieties of Leu−Gly, such as the N-and C-terminals and the peptide linkage, are not easily eliminated even as the x A is close to 0.6. The water molecules can bridge such moieties of Leu−Gly to form spherical-shaped aggregates. The diffusion coefficients of Leu−Gly in both alcohol−water binary solvents were experimentally determined by NMR DOSY to estimate the geometries of the aggregates in the solvents. The sizes of Leu−Gly aggregates obtained by DOSY for both solvent systems were consistent with those estimated from the MD snapshots.

YAFAF-Based Hydrogel: Characterization, Mechanism, and Factors Influencing Micro-organization

“…as a result of the replacement of water. , When the YAFAF stock solutions were diluted with deionized water, i.e., with a low fraction of HFIPA, the hydrophobic interaction forced the peptide side chains to aggregate inward into rigid rods. When the fraction of HFIPA increased, the formation of C–F···H–C between hydrophobic side chains of peptide molecules and solvent elongated the molecules . The formation of C–F···H–C weakened the π–π interaction between phenyl groups.…”

“…On the basis of the previous investigation on the solvated structures of amino acid and peptide, − we hypothesized that arrangements of peptide, which depended upon the ratio of HFIPA in solvents, affected the formation of hydrogels. To investigate the effect of the specific fraction of HFIPA in composite solvents on the organization of assemblies, the samples were prepared with YAFAF with different x A and observed via AFM.…”

“…When the fraction of HFIPA increased, the formation of C−F•••H−C between hydrophobic side chains of peptide molecules and solvent elongated the molecules. 35 The formation of C−F•••H−C weakened the π−π interaction between phenyl groups. Therefore, the conformation of the supramolecule became looser, and cross-links between fibers became less.…”

“…Among these factors, the solvent ratio is regarded as the most effective and easiest to control. , In the literature, investigations using computational chemistry to study solvent–solute interactions have been reported. Takahiro and co-workers described the changes of conformation of molecules and interactions between polar and nonpolar groups and solvents in different fractions of alcohols in composite solvents using molecular dynamics simulations, nuclear magnetic resonance, and dynamic light scattering techniques. − …”

Antioxidative, cytotoxic, and antibacterial properties of self-assembled glycine-histidine-based dipeptides with or without silver nanoparticles in bio-inspired film

“…Most dipeptide moieties easily solved in all solvents. They generally assumed a film-like morphology, probably owing to hydrogen bonding between the N-H (NH 2 group) and O-H (COOH group) terminals of dipeptide molecules ( 24 ). However, their structures differ: dipeptides solved in HFIP self-assembled in a spherical structure ( Figure 1a ), and those dissolved in chloroform assumed square structure ( Figure 1e ).…”