Theoretical and NMR experimental insights on urea, thiourea and diindolyurea as fluoride carriers

Abstract

Urea and thiourea derivatives are widely known as anion transporters. The pristine urea and thiourea compounds were theoretically and spectroscopically evaluated as fluoride ligands, since transportation of F− is involved in many biochemical processes and this anion is suitable to be analyzed through NMR. Conformational changes induced by anions can be useful to probe ligand-anion complexation, but urea and thiourea do not undergo conformational isomerization. Thus, diindolylurea (DIU) was computationally investigated to search for its conformational preferences upon complexation with fluoride. Overall, the NMR proton signal for urea and thiourea moved downfield and broadened upon addition of one equivalent of fluoride anion in DMSO solution, indicating complexation. The 19F signal for the thiourea-F- mixture also shifted relative to the anion source. However, a J(N)H,F coupling constant was not observed, probably because of entropy and bulk solvation effects. In addition, the conformational preference of DIU changed drastically after simulated complexation with fluoride, in agreement with previous studies with other anions. This confirms the potential of urea derivatives as fluoride carriers.