Ion Binding by Macrocyclic Depsipeptide Antibiotics: Mutual Replaceability of Amide and Ester Groups

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Macrocyclic depsipeptide antibiotic molecules have alternating sequence of amide and ester linkages constituting the backbone structure. In the current paper, cylindrical polar atomic coordinates of the conformations proposed by Shemyakin et al, of macro-cyclic depsipeptides antibiotics e.g.. Valinomycin and Enniatin B were generated by building, scale models. The coordinates were further refined by simulation of these models in a digital computer. The π-electronic charge densities on parts of the molecules containing double bonds, e.g., amide and ester groups, were calculated using the variable electro-negativity - Pariser, Parr, Pople (VE- PPP) method. The σ-electronic charge densities on the molecules, (including the conjugated parts of the molecules), were evaluated using the method of Del Re. Ion multipole interaction energy for Valinomycin – K+ - ion complex turns out to be - 107.83 K cals/mole and for Enniatin B – K+ -ion complex -85.01 K cals/mole. Mutual replaceability of amide and ester groups in these depsipeptides has been discussed on the basis of π and σ charge distributions. The calculations show that the amide and ester groups are mutually replaceable provided this replaceability does not grossly alter the secondary molecular structure of depsipeptides, although replacement of amide group by ester in case of valinomycin will lead to the loss of formation of intramolecular hydrogen bonds, when such replaceability by ester group involves even one amide residue.