Theoretical study of chemosensor for fluoride anion and optical properties of the derivatives of diketopyrrolopyrrole

Spin trapping of hydroperoxyl radical (HOO^·) by the amide-linked conjugate of 5-carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO) to β-cyclodextrin (β-CD) was studied computationally using a two-layered ONIOM method. From a conformational perspective, the “internal” conformation of 5R-β-CD-AMPO is more favored than the “external” conformation in which the nitrone is located outside of the cavity of the β-CD. When the HOO^· addition product is formed, the most stable isomer has the nitroxyl (N₁–O₁) moiety pointing inside the cavity of the β-CD. Thus, this “internal” conformation might protect the N₁–O₁ moiety of the resulting spin adduct from access by reducing agents, thereby improving the lifetime of the radical adduct. The computed energetic barrier for HOO^· addition to the 5R-β-CD-AMPO is 8.7?kcal/mol, which is marginally smaller than spin trapping by the non-conjugated AMPO (that is, without the β-CD). To optimize the reactivity of the β-CD-AMPO conjugate, the effect of a spacer unit between the AMPO segment and the β-CD moiety with varying methylene units, (CH₂) _n (n?=?1, 2, 3), on the energetics of HOO^· addition was evaluated. The structure with only one methylene spacer (n?=?1) appears to be optimal as determined by the smaller activation barrier (6.2?kcal/mol) for HOO^· addition to the nitrone moiety. Compared with very time-consuming quantum mechanical methods, the ONIOM method appears to offer significant advantages for evaluation of the best β-CD-AMPO conjugate for trapping of such reactive oxygen species and providing for the rational design of novel nitrones as spin traps.