Fluorine–Fluorine Interactions: NMR and AIM Analysis

The structure of a number of compounds that show experimental FsF coupling constants across the space has been studied using HF-DFT methods (B3LYP) and Atoms in Molecules (AIM) methodologies. For all the cases with strong coupling constants a bond critical point and the corresponding bond path between the fluorine atoms involved has been found in the electron density map. In an attempt to predict NMR properties, new compounds for which no experimental F-F coupling constants are available, but with the same characteristics in the electron density maps, have been calculated.     

An Exceptional Peroxide Birefringent Material Resulting from d–π Interactions

Birefringent materials, which can modulate the polarization of light, are almost exclusively limited to oxides. Peroxides have long been overlooked as birefringent materials, because they are usually not stable in air. Now, the first peroxide birefringent material Rb₂VO(O₂)₂F is reported, the single crystals of which keep transparency after being exposed in the air for two weeks. Interestingly, Rb₂VO(O₂)₂F does not feature an optimal anisotropic structure, but its birefringence (Δn=0.189 at 546 nm) exceeds those of the majority of oxides. According to the first-principles calculations, this exceptional birefringence should be attributed to the strong electronic interactions between localized π orbital of O₂²⁻ anions and V⁵⁺ 3d orbitals, which may be also favorable to the stability in the air for Rb₂VO(O₂)₂F. These findings distinguish peroxides as a brand-new class of birefringent materials that may possess birefringence superior to the traditional oxides.     

Weak Interactions Involving Fluorine in Suppramolecular Assemblies of Cu(Ⅱ)Complexes

Syntheses and X‐ray structural characterizations of two new Cu(II) complexes Cu(tfbz)₂(Htfbz)₂(phen) ( 1 ) (Htfbz=2,4,5‐trifluorobenzoic acid, phen=1,10‐phenanthroline) and [Cu(pfbz)₂(phen)]₂(Hpfbz)₂ ( 2 ) (Hpfbz=pentafluorobenzoic acid) are reported. The first complex crystallizes in the monoclinic space group C2/c with the crystal cell parameters a=1.9903(4) nm, b=1.3688(3) nm, c=1.3623(3) nm, β=97.90(3)°, V=3.6762(13) nm³ and Z=4. The second complex crystallizes in the triclinic space group P‐1 with the crystal cell parameters a=1.7965(4) Å, b=1.9236(2) Å, c=2.0916(2) Å, α=110.156(2) °, β=105.040(3) °, γ=98.123(3) °, V=6.3372(17) nm³ and Z=4. The crystallographic analyses revealed that F···H–C hydrogen bonds in both complexes lead to formation of infinite three‐dimensional supramolecular networks. A large number of F···F interactions in complex 2 ensure the stability of intricate crystal structure.     

Solid State Calix[4]arene Tubular Assemblies Based on Cation–π Interactions

Infinite tubular assemblies based on calix[4]arenes can be easily constructed using cation–π interactions of silver triflate with preorganised aromatic subunits (1,3-alternate or pinched cone conformations). X-ray crystallographic analysis shows that the overall self-assembly is held together by triflate anions playing the role of the bridges between the individual complexes.     

PI by NMR: Probing CH–π Interactions in Protein–Ligand Complexes by NMR Spectroscopy

While CH–π interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH–π interactions in drug–protein complexes. Herein, we present a fast and reliable methodology called PI (π interactions) by NMR, which can differentiate the strength of protein–ligand CH–π interactions in solution. By combining selective amino-acid side-chain labeling with ¹H-¹³C NMR, we are able to identify specific protein protons of side-chains engaged in CH–π interactions with aromatic ring systems of a ligand, based solely on ¹H chemical-shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH–π interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual π interactions rather than averaged measures of all interactions.     

Fluorine containing β-lactones

Summary Ring opening of -trifluoromethyl- -methyl- -propiolactone is unidirectional and leads to derivatives of -trifluoromethyl- -hydroxybutyric acid.     

Fluorine containing β-sultones

Summary The reaction between fluorine containing -sultones and mercaptans has been studied and a series of thioesters of substituted fluorosulfonylacetic acids has been obtained.     

Enhanced Macroanion Recognition of Superchaotropic Keggin Clusters Achieved by Synergy of Anion–π and Anion–Cation Interactions

Keggin clusters are the most widely used polyoxometalate building blocks for the construction advanced materials, but effective methods for precisely recognizing the isostructural analogues of Keggins are still limited. In this study we employed the zwitterionic molecule 4,4′-dipyridyl N,N′-dioxide as a recognition receptor to specifically bind to the three Keggin analogues PW₁₂O₄₀³⁻, PMo₁₂O₄₀³⁻, and SiW₁₂O₄₀⁴⁻, which separately co-assembled into three different types of spherical charged colloids of different sizes. The recognition phenomena were confirmed by electrochemical methods and their crystallization behavior. Compared with solely anion–cation interaction-driven systems, the synergism with the anion–π interactions between the superchaotropic Keggins and the electron-deficient pyridine rings is believed to enhance the recognition. This observation is intriguing as the long-range solution assembly of Keggins is mainly driven by short-range anion–π interactions. Our results show that the little-noticed hydration shell of Keggins is significantly influenced by the superchaotropic effect, leading to differentiated binding affinity to the receptors and more obvious recognition phenomena between tungsten/molybdenum Keggin analogues.     

Synthesis of i-Corona[6]arenes for Selective Anion Binding: Interdependent and Synergistic Anion–π and Hydrogen-Bond Interactions

i-Corona[3]arene[3]tetrazines were synthesized from the nucleophilic aromatic substitution reaction of resorcinol and its derivatives with 3,6-dichlorotetrazine in a one-pot fashion under mild conditions. All of the resulting macrocycles adopted 1,3,5-alternate conformation irrespective of the nature of the substituents on both upper- and lower-rims. i-Corona[3]arene[3]tetrazine was found to self-regulate its macrocyclic conformation and cavity to recognize anions with binding constants spanning from 26 M⁻¹ to 2.2×10³ M⁻¹ depending on the structure of the anions. The selective binding resulted from a significant interdependent and synergistic effect between multiple tetrazine π/anion and C_aryl–H/anion hydrogen bond interactions. Taking advantage of synergistic effect revealed, a cyanobenzene-embedded i-corona[3]arene[3]tetrazine was designedly synthesized and highly selective and very strong affinity toward nitrate with a binding constant of 2.2×10⁵ M⁻¹ was achieved.     

Anion–π Interactions in Light-Induced Reactions: Role in the Amidation of (Hetero)aromatic Systems with Activated N-Aryloxyamides

The importance of anion–π interactions as a driving force for chemical and biological processes is increasingly being recognized. In this communication, we describe for the first time its key participation in light-induced reactions. We show, in particular, how transient complexes formed through noncovalent anion–π interactions between electron-poor N-aryloxyamides and multiply-charged anions (such as carbonate or phosphate) can undergo facile light-promoted N−O cleavage, affording amidyl radicals that can subsequently be trapped by (hetero)aromatics.     

Synthesis of Electron-Deficient Corona[5]arenes and Their Selective Complexation with Dihydrogen Phosphate: Cooperative Effects of Anion–π Interactions

Reported here are the syntheses, conformational structures, electrochemical properties, and noncovalent anion binding of corona[5]arenes. A (3+2) fragment coupling reaction proceeded efficiently under mild reaction conditions to produce a number of novel heteroatom- and methylene-bridged corona[3]arene[2]tetrazine macrocycles. Selective oxidation of the sulfur atom between two phenylene rings afforded sulfoxide- and sulfone-linked corona[5]arenes in good yields. All corona[5]arenes synthesized adopted similar 1,2,4-alternate conformational structures, forming pentagonal cavities. The cavity sizes and the electronic properties such as redox potentials, were measured with CV and DPV, and were influenced by the different bridging units. As electron-deficient macrocycles, the acquired corona[3]arene[2]tetrazines served as highly selective hosts, forming complexes with the hydrogen-bonded dimer of dihydrogen phosphate through cooperative anion–π interactions.     

Does Fluorine Participate in Halogen Bonding?

When R is sufficiently electron withdrawing, the fluorine in the R?F molecules could interact with electron donors (e.g., ammonia) and form a noncovalent bond (F ??? N). Although these interactions are usually categorized as halogen bonding, our studies show that there are fundamental differences between these interactions and halogen bonds. Although the anisotropic distribution of electronic charge around a halogen is responsible for halogen bond formations, the electronic charge around the fluorine in these molecules is spherical. According to source function analysis, F is the sink of electron density at the F ??? N BCP, whereas other halogens are the source. In contrast to halogen bonds, the F ??? N interactions cannot be regarded as lump–hole interactions; there is no hole in the valence shell charge concentration (VSCC) of fluorine. Although the quadruple moment of Cl and Br is mainly responsible for the existence of σ‐holes, it is negligibly small in the fluorine. Here, the atomic dipole moment of F plays a stabilizing role in the formation of F ??? N bonds. Interacting quantum atoms (IQA) analysis indicates that the interaction between halogen and nitrogen in the halogen bonds is attractive, whereas it is repulsive in the F ??? N interactions. Virial‐based atomic energies show that the fluorine, in contrast to Cl and Br, stabilize upon complex formation. According to these differences, it seems that the F ??? N interactions should be referred to as “fluorine bond” instead of halogen bond.     

Pentafluorophenyl salicylamine receptors in anion–π interaction studies

A crystal structure analysis confirms the appropriateness of pentafluorophenyl salicylamine (1a) as a π-acceptor for anion–π interactions. Crystals of 1a·HCl show that the OH-group fixes the anion in a η²-type binding motif above the electron-deficient arene. Attempts to find some relevance for this weak intermolecular force in solution failed. Stronger CH–, NH– and OH–anion interactions are dominant over the weak anion–π interactions. Due to the hydrogen bonding, the non-fluorinated receptor exhibits the highest binding constants within this series.     

Are Heavy Pnictogen-π Interactions Really “π Interactions”?

The noncovalent interactions of heavy pnictogens with π-arenes play a fundamental role in fields like crystal engineering or catalysis. The strength of such bonds is based on an interplay between dispersion and donor/acceptor interactions, and is generally attributed to the presence of π-arenes. Computational studies of the interaction between the heavy pnictogens As, Sb and Bi and cyclohexane, in comparison with previous studies on the interaction between heavy pnictogens and benzene, show that this concept probably has to be revised. A thorough analysis of all the different energetic components that play a role in these systems, carried out with state-of-the-art computational methods, sheds light on how they influence one another and the effect that their interplay has on the overall system. Furthermore, the analysis of such interactions leads us to the unexpected finding that the presence of the pnictogen compounds strongly affects the conformational equilibrium of cyclohexane, reversing the relative stability of the chair and boat-twist conformers, and thus suggesting a possible application of tuneable dispersion energy donors to stabilise the desired conformation.