Unexpectedly Enhanced Solubility of Aromatic Amino Acids and Peptides in an Aqueous Solution of Divalent Transition-Metal Cations

We experimentally observed considerable solubility of tryptophan (Trp) in a ${\mathrm{CuCl}}_2$ aqueous solution, which could reach 2–5 times the solubility of Trp in pure water. Theoretical studies show that the strong cation-$\pi$ interaction between ${\mathrm{Cu}}^{2+}$ and the aromatic ring in Trp modifies the electronic distribution of the aromatic ring to enhance significantly the water affinity of Trp. Similar solubility enhancement has also been observed for other divalent transition-metal cations (e.g., ${\mathrm{Zn}}^{2+}$ and ${\mathrm{Ni}}^{2+}$), another aromatic amino acid (phenylalanine), and three aromatic peptides (Trp-Phe, Phe-Phe, and Trp-Ala-Phe).

Figure 1

(a) Optimized geometric structures and interaction energies (${\mathbf{E}}_{\text{ads}}$) between water molecule and Trp with and without ${\mathrm{Cu}}^{2+}$ adsorption. (b) Schematic drawings of experimental observations. In path I, tryptophan is added into $0.5\mathrm{mol}/\mathrm{L}$ (M) ${\mathrm{CuCl}}_2$ solution. Only a small amount of blue precipitate is observed in 4 h, but a large amount of blue precipitate forms after $\sim 9\mathrm{h}$. In contrast, the ${\mathrm{CuCl}}_2$ solid or solution is added into Trp aqueous solution in path II. After only $\sim 10\min$ min, some blue precipitates are observed; after $\sim 30\min$, a large amount can be observed. (c) Solubility ($\mathit{S}$) of Trp, phenylalanine (Phe), leucine (Leu), and three aromatic peptides (Trp-Phe, Phe-Phe, and Trp-Ala-Phe) in $0.5M$ ${\mathrm{CuCl}}_2$ aqueous solution (green pillar) and pure water (royal blue pillar) at room temperature. (d) ${\mathit{S}}_{\mathbf{\text{Trp}}}$ with $p\mathrm{H}$ (black line) and the $p\mathrm{H}$ (blue line, right blue axis) with a solution concentration of ${\mathrm{CuCl}}_2$ at room temperature. The shaded part is the $p\mathrm{H}$ of the ${\mathrm{CuCl}}_2$ solution used in our experiment. * data from Ref. [42], # data from Ref. [43], & data from Ref. [44].

Figure 2

(a) The half width at half maximum (HWHM) of the Lorentz function and the corresponding fitting curves (red lines) of Fick’s law for $\text{Trp}+{\mathrm{D}}_2\mathrm{O}$ (black squares) and $\text{Trp}+{\mathrm{D}}_2\mathrm{O}+{\mathrm{CuCl}}_2$ (blue squares) as a function of $Q^2$ (momentum transfer), respectively. (b) Fluorescence spectra of the Trp ($40\mu \mathrm{M}$, black solid line), methionine (Met, $200\mu \mathrm{M}$, orange dashed line) and ${\mathrm{CuCl}}_2$ ($80\mu \mathrm{M}$, green dashed line) in water solution and the mixed solution of Trp with ${\mathrm{CuCl}}_2$ (royal blue solid line), Trp with Met (pink dash line) and Trp with ${\mathrm{CuCl}}_2$ with Met (red solid line).

Figure 3

Adsorption energies ($\mathbf{\Delta }{\mathit{E}}_i$, red rectangles) of different divalent transition-metal cations (i.e., ${\mathrm{Zn}}^{2+}$, ${\mathrm{Ni}}^{2+}$, and ${\mathrm{Cu}}^{2+}$) with Trp, and water solubilities of Trp (${\mathit{S}}_{\mathbf{\text{Trp}}}$, royal blue rectangles) in $0.5M$ ${\mathrm{ZnCl}}_2$, ${\mathrm{NiCl}}_2$, and ${\mathrm{CuCl}}_2$ aqueous solutions, respectively.