Anion capture and sensing with cationic boranes: on the synergy of Coulombic effects and onium ion-centred Lewis acidity.

Stimulated by the growing importance and recognized toxicity of anions such as fluoride, cyanide and azides, we have, in the past few years, developed a family of Lewis acidic triarylboranes that can be used for the complexation of these anions in organic and protic solvents, including water. A central aspect of our approach lies in the decoration of the boranes with peripheral ammonium, phosphonium, sulfonium stibonium or telluronium groups. The presence of these cationic groups provides a Coulombic drive for the capture of the anion, leading to boranes that can be used in aqueous solutions where anion hydration and/or protonation are usually competitive. The anion affinity of these boranes can be markedly enhanced by narrowing the separation between the anion binding site (i.e. the boron atom) and the onium ion. In such systems, the latent Lewis acidity of the onium ion also plays a role as manifested by the formation of B-X→E (E = P, S, Sb, or Te; X = F, CN or N3) chelate motifs that provide additional stability to the resulting complexes. These effects, which are maximum in stibonium and telluronium boranes, show that the Lewis acidity of heavy onium ions can be exploited for anion coordination and capture. The significance of these advances is illustrated by the development of applications in anion sensing, fluorination chemistry and (18)F radiolabeling for positron emission tomography.

Lewis acid-assisted isotopic 18F-19F exchange in BODIPY dyes: facile generation of positron emission tomography/fluorescence dual modality agents for tumor imaging.

Positron emission tomography (PET) is a powerful technique for imaging biological pathways in vivo, particularly those that are key targets in disease processes. In contrast, fluorescence imaging has demonstrated to be a superior method for image-guided surgery, such as tumor removal. Although the integration of PET and optical imaging could provide an attractive strategy for patient management, there is a significant shortage of established platforms/methods for PET/optical probe construction. In this study, various reaction conditions were explored to develop a simple and fast method allowing for the introduction of [(18)F]-fluoride into BODIPY dyes. Through a systematic optimization of the reaction conditions, we found that BODIPY dyes, including commercial amine-reactive BODIPY succinimidyl esters, may be converted into their radioactive analogues in the matter of minutes via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid such as SnCl4. An integrin-targeting RGD peptide was also conjugated with [(18)F]BODIPY® R6G , derived from the commercially available BODIPY® R6G fluorescent tag, to provide a [(18)F]-RGD conjugate in 82% yield. In vivo evaluation of this imaging probe showed a discernible tumor uptake in the U87MG xenograft model. The dual modality imaging properties of the probe was confirmed by ex vivo fluorescence and microPET imaging experiments. In summary, in the matter of minutes, BODIPY dyes were converted into their "hot" radioactive analogues via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid. This approach, which can be applied to commercial BODIPY dyes, provides easy access to positron emission tomography/fluorescence dual modality imaging agents.

Orientation and stereodynamic paths of planar monodentate ligands in square planar nickel N2S complexes.

The well-established presence of histidine donors in binding sites of Ni-containing biomolecules prompts the study of orientational preference and stereodynamic nature of flat monodentate ligands (L = imidazoles, pyridine and an N-heterocyclic carbene) bound to planar N(2)SNi moieties. Square planar [N(2)SNiL](n+) complexes are accessed through bridge-splitting reactions of dimeric, thiolate-S bridged [N(2)SNi](2) complexes. The solid state molecular structures of three mononuclear products, and three monothiolate bridged dinickel complexes, reveal that the plane of the added monodentate ligand orients largely orthogonal to the N(2)SNiL square plane. Variable temperature (1)H NMR characterization of dynamic processes and ground state isomer ratios of imidazole complexes in their stopped exchange limiting spectra, readily correlate with density functional theory (DFT)-guided interpretation of Ni-L rotational activation barriers. Full DFT characterization finds Ni-L bond lengthening as well as a tetrahedral twist distortion in the transition state, reaching a maximum in the NHC complex, and relating mainly to the steric hindrance derived both from the ligand and the binding pocket. In the case of the imidazole ligands a minor electronic contribution derives from intramolecular electrostatic interactions (imidazole C-2 C-H(delta+)- - S(delta-) interaction). Computational studies find this donor-acceptor interaction is magnified in O-analogues, predicting coplanar arrangements in the ground state of N(2)ON(imid)Ni complexes.