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      An overlooked yet ubiquitous fluoride congenitor: binding bifluoride in triazolophanes using computer-aided design.

      Journal of the American Chemical Society
      American Chemical Society (ACS)

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          Abstract

          Despite its ubiquity during the binding and sensing of fluoride, the role of bifluoride (HF2(-)) and its binding properties are almost always overlooked. Here, we give one of the first examinations of bifluoride recognition in which we use computer-aided design to modify the cavity shape of triazolophanes to better match with HF2(-). Computational investigation indicates that HF2(-) and Cl(-) should have similar binding affinities to the parent triazolophane in the gas phase. Evaluation of the binding geometries revealed a preference for binding of the linear HF2(-) along the north-south axis with a smaller Boltzmann weighted population aligned east-west and all states being accessed rapidly through in-plane precessional rotations of the anion. While the (1)H NMR spectroscopy studies are consistent with the calculated structural aspects, binding affinities in solution were determined to be significantly smaller for the bifluoride than the chloride. Computed geometries suggested that a 20° tilting of the bifluoride (stemming from the cavity size) could account for the 25-fold difference between the two binding affinities, HF2(-) < Cl(-). Structural variations to the triazolophane's geometry and electronic modifications to the network of hydrogen bond donors were subsequently screened in a stepwise manner using density functional theory calculations to yield a final design that eliminates the tilting. Correspondingly, the bifluoride's binding affinity (K ∼ 10(6) M(-1)) increased and was also found to remain equal to chloride in the gas and solution phases. The new oblate cavity appeared to hold the HF2(-) in a single east-west arrangement. Our findings demonstrate the promising ability of computer-aided design to fine-tune the structural and electronic match in anion receptors as a means to control the arrangement and binding strength of a desired guest.

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          Journal
          24559019
          10.1021/ja500125r

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