Halogenated <i>N</i>-phenylpiperazine and 2-(piperazin-1-yl)pyrimidine as novel cucurbit[7]uril guests: experimental and computational insights into supramolecular binding.

ABSTRACT: This study presents a new class of halogenated N-phenylpiperazine and 2-(piperazin-1-yl)pyrimidine derivatives as guests for cucurbit[7]uril (CB[7]), expanding the space of CB[7]-binding ligands. Combining isothermal titration calorimetry (ITC), X-ray crystallography, and computation (attach-pull-release, APR; symmetry-adapted perturbation theory, SAPT), we quantify how halogen identity and position modulate host-guest binding. We find that halogenation provides two position-specific levers for tuning affinity. At the ortho position, both F and Cl enhance dispersion (Cl more strongly), while ortho-F additionally confers pre-organization (intramolecular C-H⋯F) that reduces the entropic penalty. Across the series, the lowest free energies of binding (ΔG) are obser

SUBMITTER: Rincon DA 

PROVIDER: S-EPMC12632625 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature