Theoretical and X-ray Crystallographic Evidence of a Fluorine-Imine Gauche Effect: An Addendum to Dunathan's Stereoelectronic Hypothesis

The preference of β‐fluoroimines to adopt a gauche conformation has been studied by single‐crystal X‐ray diffraction analysis and DFT methods. Empirical and theoretical evidence for a preferential gauche arrangement around the NCCF torsion angle (?) is presented ((E)‐2‐fluoro‐N‐(4‐nitrobenzylidene)ethanamine: ?_NCCF=70.0°). In the context of this study, the analysis of a pyridoxal‐derived β‐fluoroaldimine was performed, a species that is implicated in the inhibition of pyridoxal phosphate (PLP)‐dependent enzymes by β‐fluoroamine derivatives. The gauche preference of the internal aldimine (=NCH₂CH₂F) that can be rationalized by stereoelectronic arguments does not hold for the corresponding external system (N?CHCH₂F) (E_min when ?_NCCF=120°). Moreover, the C? F bond is lengthened by more than 0.02 Å at ?_NCCF=±90°, when it is exactly antiperiplanar to the conjugated imine. This activation of the C? F σ bond by an adjacent π system constitutes an addendum to Dunathan’s stereoelectronic hypothesis.     

Designing Fluorinated Cinchona Alkaloids for Enantioselective Catalysis: Controlling Internal Rotation by a Fluorine‐Ammonium Ion gauche Effect (φNCCF)

The C9 position of cinchona alkaloids functions as a molecular hinge, with internal rotations around the C8? C9 (τ₁) and C9? C4′ (τ₂) bonds giving rise to four low energy conformers ( 1 ; anti‐closed, anti‐open, syn‐closed, and syn‐open). By substituting the C9 carbinol centre by a configurationally defined fluorine substituent, a fluorine‐ammonium ion gauche effect (σ_C?H→σ_C?F*; F^δ????N⁺) encodes for two out of the four possible conformers ( 2 ). This constitutes a partial solution to the long‐standing problem of governing internal rotations in cinchonium‐based catalysts relying solely on a fluorine conformational effect.     

Building a Better Halide Receptor: Optimum Choice of Spacer,Binding Unit,and Halosubstitution

Quantum calculations are used to measure the binding of halides to a number of bipodal dicationic receptors, constructed as a pair of binding units separated by a spacer group. A number of variations are studied. A H atom on each binding unit (imidazolium or triazolium) is replaced by Br or I. Benzene, thiophene, carbazole, and dimethylnaphthalene are considered as spacer groups. Each receptor is paired with halides F^?, Cl^?, Br^?, and I^?. Substitution with I on the binding unit yields a large enhancement of binding, as much as 13 orders of magnitude; a much smaller increase occurs for substitution with Br. Imidazolium is a more effective binding agent than is triazolium. Benzene and dimethylnaphthalene represent the best spacers, followed by thiophene and carbazole. F^? binds much more strongly than do the other halides, which obey the order Cl^?>Br^?>I^?.     

On the Interaction between Deprotonated Cytosine [C(−H)]− and Ba2+: Infrared Multiphoton Spectroscopy and Dynamics

Gas-phase interactions between Ba²⁺ and deprotonated cytosine (C_(−H)) were studied in [C_(−H)Ba]⁺ and [C_(−H)BaC]⁺ complexes by IRMPD spectroscopy coupled to tandem mass-spectrometry in combination with DFT calculations. For the [C_(−H)BaC]⁺ complex only one [C_(−H)KAN1O−Ba-C_anti]⁺ isomer was found, although the presence of another structure cannot be excluded. This isomer features a central tetracoordinated Ba²⁺ that simultaneously interacts with keto-amino [C_(−H)]⁻ deprotonated on N1 and neutral keto-amino C. Both moieties are in different planes as a consequence of an additional NH…O=C hydrogen bond between C and [C_(−H)] ⁻ . A sequential IRMPD dynamics is observed in this complex. For the [C_(−H)Ba]⁺ complex produced by electrospray ionization two isomers ([C_(−H)KAN1OBa]⁺ and [C_(−H)KAN3OBa]⁺) were identified, in which Ba²⁺ interacts simultaneously with the C=O group and the N1 or N3 atom of the keto-amino [C_(−H)]⁻, respectively. A comparison with the related [C_(−H)Pb]⁺ complex (J. Y. Salpin et al., Chem. Phys. Chem. 2014 , 15, 2959–2971) is also presented.     

Modelling zwitterions in solution: 3-fluoro-γ-aminobutyric acid (3F-GABA)

The conformations and relative stabilities of folded and extended 3-fluoro-γ-aminobutyric acid (3F-GABA) conformers were studied using explicit solvation models. Geometry optimisations in the gas phase with one or two explicit water molecules favour folded and neutral structures containing intramolecular NH···O-C hydrogen bonds. With three or five explicit water molecules zwitterionic minima are obtained, with folded structures being preferred over extended conformers. The stability of folded versus extended zwitterionic conformers increases on going from a PCM continuum solvation model to the microsolvated complexes, though extended structures become less disfavoured with the inclusion of more water molecules. Full explicit solvation was studied with a hybrid quantum-mechanical/molecular-mechanical (QM/MM) scheme and molecular dynamics simulations, including more than 6000 TIP3P water molecules. According to free energies obtained from thermodynamic integration at the PM3/MM level and corrected for B3LYP/MM total energies, the fully extended conformer is more stable than folded ones by about -4.5 kJ mol(-1). B3LYP-computed (3)J(F,H) NMR spin-spin coupling constants, averaged over PM3/MM-MD trajectories, agree best with experiment for this fully extended form, in accordance with the original NMR analysis. The seeming discrepancy between static PCM calculations and experiment noted previously is now resolved. That the inexpensive semiempirical PM3 method performs so well for this archetypical zwitterion is encouraging for further QM/MM studies of biomolecular systems.     

Chemical Reactivity Controlled by Negative Hyperconjugation: A Theoretical Study

Negative hyperconjugation is a general phenomenon that can be observed in many areas of chemistry. The knowledge of its impact on structural parameters and conformational issues is well established, but little is known about its importance for chemical reactivity. Here we present a systematic study of different aspects of negative hyperconjugation on the reactivity of complex heterocyclic systems using density functional theory. Intermediates from the reaction of nitrogen‐based nucleophiles with bis(1,3,4‐thiadiazolo)‐1,3,5‐triazinium halides serve as benchmark systems to demonstrate the effects of negative hyperconjugation on bond lengths, on the relative stability of conformational isomers and transition structures and, most importantly, on the different reaction pathways of these species. The computational results provided here are in part supported by experiments reported elsewhere.     

Hydrogen Bonding between Metal‐Ion Complexes and Noncoordinated Water: Electrostatic Potentials and Interaction Energies

The hydrogen bonding of noncoordinated water molecules to each other and to water molecules that are coordinated to metal‐ion complexes has been investigated by means of a search of the Cambridge Structural Database (CSD) and through quantum chemical calculations. Tetrahedral and octahedral complexes that were both charged and neutral were studied. A general conclusion is that hydrogen bonds between noncoordinated water and coordinated water are much stronger than those between noncoordinated waters, whereas hydrogen bonds of water molecule in tetrahedral complexes are stronger than in octahedral complexes. We examined the possibility of correlating the computed interaction energies with the most positive electrostatic potentials on the interacting hydrogen atoms prior to interaction and obtained very good correlation. This study illustrates the fact that electrostatic potentials computed for ground‐state molecules, prior to interaction, can provide considerable insight into the interactions.