Chemical Reactivity Properties, p Ka Values, AGEs Inhibitor Abilities and Bioactivity Scores of the Mirabamides A⁻H Peptides of Marine Origin Studied by Means of Conceptual DFT

Abstract

The MN12SX density functional, in connection with the Def2TZVP basis set, was assessed, together with the SMD solvation model (Solvation Model based on the Density), for calculation of the molecular properties and structure of a group of peptides of marine origin named Mirabamides A⁻H. All the chemical reactivity descriptors for the systems were calculated via Conceptual Density Functional Theory (CDFT). The active sites suitable for nucleophilic, electrophilic, and radical attacks were chosen by linking them with the Fukui function indices, nucleophilic and electrophilic Parr functions, and condensed Dual Descriptor Δ f ( r ) , respectively. Additionally, the p K a values for the different peptides are predicted with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which constitutes a useful knowledge for the development of drugs for fighting Diabetes, Alzheimer and Parkinson diseases. Finally, the bioactivity scores for the Mirabamides A⁻H are predicted through different methodologies.

Keywords: Mirabamides A–H; bioactivity scores; chemical reactivity; computational chemistry; conceptual DFT.

Figure 1

Graphical sketches of the molecular structures (a) Mirabamide A; (b) Mirabamide B; (c) Mirabamide C; (d) Mirabamide D; (e) Mirabamide E; (f) Mirabamide F; (g) Mirabamide G and (h) Mirabamide H—The numbered arrows indicate the atomic reactive sites according to Tables 3–10.

Figure 2

Electrophilic Fukui functions $f^{-}\left(\mathbf{r}\right)$ for (a) Mirabamide A; (b) Mirabamide B; (c) Mirabamide C; (d) Mirabamide D; (e) Mirabamide E; (f) Mirabamide F; (g) Mirabamide G and (h) Mirabamide H—This graphic has been plotted following the ChemCraft style where the following colors have been assigned to the atoms: C: lilac, H: red, N: yellow, O: green and Cl: blue, and orange and purple are assigned to positive and negative surfaces, respectively.

Figure 3

Nucleophilic Fukui functions $f^{+}\left(\mathbf{r}\right)$ for (a) Mirabamide A; (b) Mirabamide B; (c) Mirabamide C; (d) Mirabamide D; (e) Mirabamide E; (f) Mirabamide F; (g) Mirabamide G and (h) Mirabamide H–This graphic has been plotted following the ChemCraft style where the following colors have been assigned to the atoms: C: lilac, H: red, N: yellow, O: green and Cl: blue, and orange and purple are assigned to positive and negative surfaces, respectively.