Iron, an essential element for nearly all forms of life, is generally denied to invading pathogenic organisms. Although abundant, iron is difficult to obtain from the environment due to its sparing solubility in aqueous solutions under aerobic conditions. In a host organism the problem posed by solubility is compounded. Denial of iron to invading organisms has long been recognized as the primary innate defense against bacterial infection. If iron is withheld from pathogenic bacteria then the bacteria do not cause disease. To overcome these obstacles many pathogenic bacteria secrete specialized metabolites called siderophores to aid in the acquisition of iron and other metals. Yersiniabactin (Ybt), a siderophore of Yersinia pestis, is known to chelate Fe(III), KD = 4x1036, but has not been proven to effectively transport zinc. To characterize siderophore-metal interaction binding energies of Fe(III) and Zn(II) with Ybt were calculated. The performance of dispersion corrected B3LYP, PBE0, and M06 functionals was investigated. Ground-state energies and frequencies of Ybt, Ybt-Fe(III) and [Ybt-Zn(II)]- complexes were calculated employing the Pople’s 6-311G** basis set. For the Ybt-Fe(III), different spin multiplicities for the metal cation were considered. Geometry optimizations returned structures in agreement with crystallographic reported by Miller, showing an octahedral structure with a 1:1 Ybt/metal cation ratio. The high-spin Ybt-Fe(III) complex was found to be more stable than the low-spin complex by 5.18, 11.32, and 24.96 kcal/mol for the B3LYP, PBE0, and M06 functionals, respectively. Relative to the high-spin complex, the mid-spin complex is unstable by 11.60, 15.06, and 22.63 kcal/mol, for the B3LYP, PBE0, and M06 functionals, respectively. ZPE corrected Gibbs binding energies of the complexes are shown in Table 1. The negatively-charged Ybt-Zn(II) complexes are unstable relative to the Ybt molecule, evincing the preference of the siderophore for binding Iron.

DFT study of yersiniabactin-metal complexes

2019 Spring National Meeting

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