Halogen Bonding and/or Covalent Bond: Analogy of 3c-4e N···I···X (X = Cl, Br, I, and N) Interactions in Neutral, Cationic, and Anionic Complexes.

X-ray structural measurements and computational analysis demonstrated the similarity of the geometries and electronic structures of the X-I···N (X = Cl, Br, I, and N) bonding in strong halogen-bonded (HaB) complexes and in the anionic or cationic halonium ions. In particular, I···N bond lengths in the solid-state associations formed by strong HaB donors (e.g., I2, IBr, ICl, and N-iodosuccinimide) and acceptors (e.g., quinuclidine or pyridines) were in the same range of 2.3 ± 0.1 Å as those in the halonium ions [e.g., the bis(quinuclidine)iodonium cation or the 1,1'-iodanylbis(pyrrolidine-2,5-dione) anion]. In all cases, bond lengths were much closer to those of the N-I covalent bond than to the van der Waals separations of these atoms. The strong N···I bonding in the HaB complexes led to a substantial charge transfer, lengthening and weakening of the I···X bonds, and polarization of the HaB donors. As a result, the central iodine atoms in the strong HaB complexes bear partial positive charges akin to those in the halonium ions. The energies and Mayer bond orders for both N···I and I···X bonds in such associations are also comparable to those in the halonium ions. The similarity of the bonding in such complexes and in halonium ions was further supported by the analysis of electron densities and energies at bond critical (3, -1) points in the framework of the quantum theory of atoms in molecules and by the density overlap region indicator. Overall, all these data point out the analogy of the symmetric N···I···N bonding in the halonium ions and the asymmetric X···I···N bonding in the strong HaB complexes, as well as the weakly covalent character of these 3c-4e interactions.

Anion-π Interactions: What's in the Name?

The studies of the anion-π interactions advanced during the last two decades from the discussion of the mere existence of this counter-intuitive bonding to its utilization for anion recognition and transport, catalysis, and other applications. Yet, there are substantial differences in the interpretation of nature and the driving forces of anion-π bonding. Most surprisingly, there are still different opinions about the meaning of this term (i. e., which associations can be considered anion-π complexes). After a brief overview of the studies in this area (including early examples of such complexes), we suggested that anion-π bonding occurs when there is evidence of a net attraction between a (close-shell) anion and the face of an electrophilic π-system. This definition encompasses fundamentally similar supramolecular complexes comprising diverse π-systems and anions and its general acceptance would facilitate a discussion of the nature and distinct driving forces of this fascinating interaction.

Exploring the Nature of Anion-π Interactions: Complexes of π-Acceptors with Fluoro- or Oxoanions Compared to the Associations with Halides.

The variations in the nature and properties of the anion-π complexes with different types of anions are identified via experimental (UV-vis and X-ray crystallographic) measurements and computational analysis of the associations of tetracyanopyrazine, tetrafluoro-, or dichlorodicyano-p-benzoquinone. Co-crystals of these π-acceptors with the salts of fluoro- and oxoanions (PF6-, BF4-, CF3SO3-, or ClO4-) comprised anion-π bonded alternating chains or 1:2 complexes showing interatomic contacts of up to 15% shorter than the van der Waals separations. DFT computations confirmed that binding energies between the neutral π-acceptors and polyatomic noncoordinating oxo- and fluoroanions are comparable to those in the previously reported anion-π complexes with more nucleophilic halides. Yet, while the latter show distinct charge-transfer bands in the UV-vis range, the absorption spectra of the solutions containing oxo- and fluoroanions and the π-acceptors were close to those of the individual reactants. The natural bond orbital (NBO) analysis revealed a very small charge transfer of Δq = 0.01-0.02 e in the complexes with oxo- or fluoroanions as compared to the Δq = 0.05-0.22 e found for analogous complexes with halides. These distinctions were related to the smaller frontier orbital energy gap and better overlap in the complexes with halides (since the highest occupied orbitals of these monoatomic anions are closer in energy to the lowest unoccupied orbitals of the π-acceptors) as compared to that in the multicenter-bonded associations with polyatomic oxo- and fluoroanions. In accordance with these data, the energy decomposition analysis showed that while the complexes of neutral π-acceptors with the fluoro- and oxoanions are formed predominantly via electrostatic interaction, the associations with halides comprised significant orbital (charge-transfer) interactions and they explain their spectral and structural features.

Thermodynamics and Spectroscopy of Halogen- and Hydrogen-Bonded Complexes of Haloforms with Aromatic and Aliphatic Amines.

Similarities and differences of halogen and hydrogen bonding were explored via UV-Vis and 1H NMR measurements, X-ray crystallography and computational analysis of the associations of CHX3 (X=I, Br, Cl) with aromatic (tetramethyl-p-phenylenediamine) and aliphatic (4-diazabicyclo[2,2,2]octane) amines. When the polarization of haloforms was taken into account, the strengths of these complexes followed the same correlation with the electrostatic potentials on the surfaces of the interacting atoms. However, their spectral properties were quite distinct. While the halogen-bonded complexes showed new intense absorption bands in the UV-Vis spectra, the absorptions of their hydrogen-bonded analogues were close to the superposition of the absorption of reactants. Additionally, halogen bonding led to a shift in the NMR signal of haloform protons to lower ppm values compared with the individual haloforms, whereas hydrogen bonding of CHX3 with aliphatic amines resulted in a shift in the opposite direction. The effects of hydrogen bonding with aromatic amines on the NMR spectra of haloforms were ambivalent. Titration of all CHX3 with these nucleophiles produced consistent shifts in their protons' signals to lower ppm values, whereas calculations of these pairs produced multiple hydrogen-bonded minima with similar structures and energies, but opposite directions of the NMR signals' shifts. Experimental and computational data were used for the evaluation of formation constants of some halogen- and hydrogen-bonded complexes between haloforms and amines co-existing in solutions.

Solvent and Ionic Atmosphere Effects in Anion-π Interactions: Complexes of Halide Anions with p-Benzoquinones.

The interplay between the solvent polarity and ionic atmosphere in anion-π association was evaluated via an experimental and a computational study of the BQ·X- complexes between benzoquinones (BQ) and halide anions (X-). The UV-Vis spectral measurements showed that these complexes are characterized by the strong absorption bands in the 300-450 nm range and their effective formation constants, Keff, measured in dichloromethane in the absence (or at low concentrations) of the supporting electrolyte, Bu4NPF6, were higher than those in acetonitrile. The experimental data were consistent with the results of the computations, which showed that magnitudes of the interaction energy, ΔE, between BQ and X- decreased considerably with the increase in the polarity of the media. The addition of auxiliary electrolytes (e.g., Bu4NPF6) led to a decrease in the concentration of the BQ·X- complexes. These changes were related to the competing associations of the π-acceptors with halides and PF6- anions (since the interaction energies between BQ acceptors and common non-halide anions, e.g., PF6-, BF4-, and NO3-, were comparable to those in the BQ·X- complexes) and to the increased ionic strength of the solutions. The variations in strength of anion-π interactions with the solvent polarity and ionic atmosphere were related to the higher effective ionic radii of the complexes. Due to the larger effects of the auxiliary electrolytes in dichloromethane, the formation constants for the BQ·X- complexes measured at high ionic strength in this solvent were lower than those in more polar acetonitrile or propylene carbonate. Such a combination of the effects of the solvent and ionic atmosphere should be taken into account when comparing experimental data with the results of the calculations and in design of the systems for molecular recognition and catalysis.

From weak to strong interactions: structural and electron topology analysis of the continuum from the supramolecular chalcogen bonding to covalent bonds.

The relationship between covalent and supramolecular bonding, and the criteria of the assignments of different interactions were explored via the review of selenium and tellurium containing structures in the Cambridge Structural Database and their computational analysis using Quantum Theory of Atoms in Molecules (QTAIM). This combined study revealed continuums of the interatomic Se⋯Br and Te⋯I distances, dCh⋯X, in the series of associations from the sums of the van der Waals radii of these atoms (rCh + rX) to their covalent bond lengths. The electron densities, ρ(r), at Bond Critical Points (BCPs) along the chalcogen bond paths increased gradually from about 0.01 a.u. common for the non-covalent interactions to about 0.1 a.u. typical for the covalent bonds. The log ρ(r) values fell on the same linear trend line when plotted against normalized interatomic distances, RXY = dCh⋯X/(rCh + rX). The transition from the positive to negative values of the energy densities, H(r), at the BCPs (related to a changeover of essentially non-covalent into partially covalent interactions) were observed at RXY ≈ 0.80. Synchronous changes of bonding characteristics with RXY (similar to that found earlier in the halogen-bonded systems) designated normalized interatomic separation as a critical factor determining the nature of these bondings. The uninterrupted continuums of Te⋯I and Se⋯Br bond lengths and BCPs' characteristics signified an intrinsic link between limiting types of bonding involving chalcogen atoms and between covalent and supramolecular bonding in general.

Examining a Transition from Supramolecular Halogen Bonding to Covalent Bonds: Topological Analysis of Electron Densities and Energies in the Complexes of Bromosubstituted Electrophiles.

The transition from weak (noncovalent) interactions to fully developed covalent bonds is examined using the quantum theory of atoms in molecules in a series of halogen-bonded (XB) complexes of bromosubstituted electrophiles, RBr, with 1,4-diazabicyclo[2.2.2]octane (DABCO) and Cl- and Br- anions. The gradual decrease in the XB lengths in these associations, d Br···Y (where Y = Cl-, Br-, or N), was accompanied by the exponential increase in the binding energies and charge transfer, as well as electron densities and magnitudes of the kinetic and potential energy densities at the bond critical points (BCPs) on the Br···Y bond path. These indices, as well as characteristics of the adjacent bonds in the XB donor, followed remarkably close trend lines when plotted against the normalized XB length R BrY = d Br···Y/(r Br + r Y) (where r Br and r Y are the van der Waals radii) regardless of the methods [MP2/6-311+G(d,p) or M062X/6-311+G(d,p)], media (gas phase or dichloromethane), and nucleophiles (Cl-, Br-, or DABCO). In the systems with an R BrY higher than about 0.78, the energy densities H(r) at BCPs at the Br···Y bond path were small and positive, and XBs did not substantially affect the characteristics of the adjacent R-Br covalent bond in the XB donor. Accordingly, the XB can be identified as noncovalent in this range. In the complexes with R BrY values between about 0.67 and 0.78, energy densities H(r) at Br···Y BCPs were negative, and their magnitudes increased with the decrease in the Br···Y separation. In this range, formation of XBs was accompanied by the increase in the R-Br bond length in the XB donor and the decrease in the magnitude of the (negative) H(r) values at the BCPs of the R-Br bonds. XBs can be classified as partially covalent in this R BrY range. At an R BrY less than about 0.67, electron densities were larger, and energy densities were more negative at BCPs of the Br···Y bond than those at BCPs of the R-Br bond in the XB donor. This indicates that Br···Y bonds were stronger than R-Br bonds, and these (Br···Y) XBs can be regarded as essentially covalent. The synchronous change of a variety of (R-Br and Br···Y) bonding characteristics with R BrY suggests that the normalized XB bond length can be used as a basic parameter in the identification of the type of intermolecular interaction. A continuity of these characteristics suggests an inherent relationship between limiting (covalent and noncovalent) types of XBs and thus an onset of molecular-orbital interactions in the weaker bonds.

"Anti-electrostatic" Halogen Bonding between Ions of Like Charge.

Halogen bonding occurs between molecules featuring Lewis acidic halogen substituents and Lewis bases. It is often rationalized as a predominantly electrostatic interaction and thus interactions between ions of like charge (e. g., of anionic halogen bond donors with halides) seem counter-intuitive. Herein, we provide an overview on such complexes. First, theoretical studies are described and their findings are compared. Next, experimental evidences are presented in the form of crystal structure database analyses, recent examples of strong "anti-electrostatic" halogen bonding in crystals, and the observation of such interactions also in solution. We then compare these complexes to select examples of "counter-intuitive" adducts formed by other interactions, like hydrogen bonding. Finally, we comment on key differences between charge-transfer and electrostatic polarization.

"Anti-electrostatic" halogen bonding in solution.

Halogen-bonded (XB) complexes between halide anions and a cyclopropenylium-based anionic XB donor were characterized in solution for the first time. Spontaneous formation of such complexes confirms that halogen bonding is sufficiently strong to overcome electrostatic repulsion between two anions. The formation constants of such "anti-electrostatic" associations are comparable to those formed by halides with neutral halogenated electrophiles. However, while the latter usually show charge-transfer absorption bands, the UV-Vis spectra of the anion-anion complexes examined herein are determined by the electronic excitations within the XB donor. The identification of XB anion-anion complexes substantially extends the range of the feasible XB systems, and it provides vital information for the discussion of the nature of this interaction.

Effects of structural variations on π-dimer formation: long-distance multicenter bonding of cation-radicals of tetrathiafulvalene analogues.

The multicenter (pancake) bonding between cation-radicals of tetramethyltetraselenafulvalene, TMTSF+˙, tetramethyltetrathiafulvalene, TMTTF+˙, and bis(ethylenedithio)-tetrathiafulvalene, ET+,˙ was compared to that of tetrathiafulvalene, TTF+˙. To minimize counter-ion effects, the cation-radical salts with weakly coordinating anions (WCA), tetrakis(3,5-trifluoromethylphenyl)borate, dodecamethylcarborane and hexabromocarborane were prepared. Solid-state (X-ray and EPR) measurements revealed diamagnetic π-dimers in the TMTSF and ET salts and the separate monomers in the TTF salts with all WCAs, while TMTTF existed as a dimer in one and a monomer in two salts. The variable-temperature UV-Vis studies of these salts in solution showed that the thermodynamics of formation of the π-bonded dimers of TMTTF+˙ was close to that of TTF+˙, while TMTSF+˙ and ET+˙ showed a higher propensity for π-dimerization. These data indicated that the replacement of sulfur with heavier selenium or insertion of ethylenedithia-substituents into the TTF core increases the π-dimers' stability. Yet, computational analysis indicated that the weakly covalent component of π-bonding decreases in the order TTF > TMTTF > TMTSF > ET. The higher stability of the π-dimers of TMTSF+˙ and ET+˙ cation-radicals was related to a decrease of the electrostatic repulsion between cationic counter-parts and an increase of dispersion components in these associations.

Diversity and uniformity in anion-π complexes of thiocyanate with aromatic, olefinic and quinoidal π-acceptors.

Despite the progress in the study of anion-π interactions, there are still inconsistencies in the use of this term and the experimental data about factors affecting the strength of such bonding are limited. To shed light on these issues, we explored supramolecular associations between NCS- anions and a series of aromatic, olefinic or quinoidal π-acceptors. Combined experimental and computational studies revealed that all these complexes were formed by an attraction of the anion to the face of the π-system, and the arrangements of thiocyanate followed the areas of the most positive potentials on the surfaces of the π-acceptors. The stabilities of the complexes increased with the π-acceptor strength (reflected by their reduction potentials), and were essentially independent of the magnitudes of the maximum electrostatic potentials on their surfaces. The complexes showed intense absorption bands in the UV-Vis range, and the energies of these bands were correlated with the difference of the redox potentials of the anions and π-acceptors. Such features, as well as results of atoms-in-molecules and non-covalent index analyses suggested that besides electrostatics, molecular orbital interactions play a substantial role in the formation of these complexes. The unified trends in variations of the characteristics of the complexes between thiocyanate and a variety of π-acceptors point to their common nature. To embrace diversity and uniformity of the anion-π associates, we suggest (following the halogen bond's definition) that anion-π bonding occurs when there is evidence of a net attraction between the anions and the face of the electrophilic π-system.

Halogen Bonding Between Anions: Association of Anion Radicals of Tetraiodo-p-benzoquinone with Iodide Anions.

Halogen bonding between two negatively charged species, tetraiodo-p-benzoquinone anion radicals (I4 Q-. ) and iodide anions, was observed and characterized for the first time. X-ray structural and EPR/UV-Vis spectral studies revealed that the anion-anion bonding led to the formation of crystals comprising 2D layers of I4 Q-. anion radicals linked by iodides and separated by Et4 N+ counter-ions. Computational analysis suggested that the seemingly antielectrostatic halogen bonds in these systems were formed via a combination of several factors. First, an attenuation of the interionic repulsion by the solvent facilitated close approach of the anions leading to their mutual polarization. This resulted in the appearance of positively charged areas (σ-holes) on the surface of the iodine substituents in I4 Q-. responsible for the attractive interaction. Finally, the solid-state associations were also stabilized by multicenter (4:4) halogen bonding between I4 Q-. and iodide.

Intermolecular Interactions between Halogen-Substituted p-Benzoquinones and Halide Anions: Anion-π Complexes versus Halogen Bonding.

Intermolecular interactions between halo-substituted p-benzoquinones (BQ) and halide anions were examined in solution, solid-state and/or in silico. While X-ray crystallography revealed only halogen bonding (XB) between tetraiodo-p-benzoquinone (I4 Q) and halides, the results of a UV-Vis study in solutions were consistent with the formation of 1 : 1 anion-π complexes. DFT computations showed that the anion-π complexes of halides with most halo-substituted BQ molecules were more stable (by 2-7 kcal/mol) than their XB analogues, but the stabilities of different complexes of I4 Q were essentially the same. Thus, the structural features of the co-crystals with I4 Q were related to multicenter XB interactions between BQs and halides, thus leading to the formation of 3D networks. The observation of anion-π complexes in solutions was attributed to their higher molar absorptivity (by more than an order of magnitude) than that of their XB analogues. Overall, the stabilities of anion-π and XB complexes between BQs and halides were well correlated with the values of highest electrostatic potentials on the surfaces of BQ molecules when their polarizations were taken into account.

Molecular Bases for Anesthetic Agents: Halothane as a Halogen- and Hydrogen-Bond Donor.

Although instrumental for optimizing their pharmacological activity, a molecular understanding of the preferential interactions given by volatile anesthetics is quite poor. This paper confirms the ability of halothane to work as a hydrogen-bond (HB) donor and gives the first experimental proof that halothane also works as a halogen-bond (HaB) donor in the solid state and in solution. A halothane/hexamethylphosphortriamide co-crystal is described and its single-crystal X-ray structure shows short HaBs between bromine, or chlorine, and the phosphoryl oxygen. New UV/Vis absorption bands appear upon addition of diazabicyclooctane and tetra(n-butyl)ammonium iodide to halothane solutions, indicating that nitrogen atoms and anions may mediate the HaB-driven binding processes involving halothane as well. The ability of halothane to work as a bidentate/tridentate tecton by acting as a HaB and HB donor gives an atomic rationale for the eudismic ratio shown by this agent.

Complexes of Diiodine with Heteroaromatic N-Oxides: Effects of Halogen-Bond Acceptors in Halogen Bonding.

Halogen bonding (XB) in complexes of diiodine with heteroaromatic N-oxides was examined via a combination of UV-vis spectral and X-ray structural measurements, as well as computational analysis. While all of these associates were formed by analogous I···O bonds, they showed considerable variations of formation constants (5-1500 M-1) and intermolecular I···O bond length (2.3-3.2 Å). In the solid state, both atoms of I2 molecules were involved in XB, and the I···O separations were determined by the electron-donor abilities of N-oxides and the strength of the bonding on the opposite side of the ditopic XB donor. The solution-phase formation constants of 1:1 complexes, K, as well as magnitudes of the calculated interaction energies, ΔE, increased with the shift of the values of the most negative potentials on the surfaces of N-oxides' oxygen atoms, Vmin, toward more negative values. Yet, the interatomic contacts consistently deviated from the locations of Vmin. Instead, the structures of complexes were well suited for highest occupied molecular orbital/lowest unoccupied molecular orbital interactions of reactants. The values of K, ΔE, and the intermolecular distances dI···O in the calculated complexes were highly correlated with the charge-transfer interaction energies derived from the natural bond orbital analysis. This indicated that, besides electrostatic, molecular orbital interactions play a substantial role in XB between diiodine and N-oxides. This conclusion was supported by the analysis of the complexes using the quantum theory of atoms in molecules, noncovalent interaction index, and density overlap region indicator, which showed that the covalent character of I···O bonding increases with the rise of interaction energies in the complexes.

Anion-π Complexes of Halides with p-Benzoquinones: Structures, Thermodynamics, and Criteria of Charge Transfer to Electron Transfer Transition.

Interchange of complex formation and electron-transfer reactions between halide anions and p-benzoquinones were established via UV-vis spectral and X-ray structural measurements and computational analysis. Solution-phase interaction of the p-benzoquinone acceptors with Cl-, Br-, or I- donors led to the formation of anion-π complexes showing strong absorption bands in the UV-vis range. Formation constants and calculated interaction energies of these complexes increased, and donor/acceptor separations decreased with increasing reduction potentials of p-benzoquinones. Mulliken correlation and NBO analysis indicated a charge-transfer nature of these anion-π associates. Most notably, the increase of the acceptor strength led to a transition between the formation of the persistent anion-π complexes and electron-transfer reactions. Thermodynamic analysis accounted for the experimental observations of anion radicals and trihalide anions in solutions of p-benzoquinones with iodide or (for the strongest acceptor) bromide donors. Kinetics of these processes indicated that anion-π complexes represent critical intermediates of the redox reactions. In contrast to Cl-, Br-, or I- anions, interaction of p-benzoquinones with F- anions led to the formation of σ-complexes, and the appearance of anion radicals in such systems was related to the follow-up reactions of these complexes.

Resolving the halogen vs. hydrogen bonding dichotomy in solutions: intermolecular complexes of trihalomethanes with halide and pseudohalide anions.

Halogen- and hydrogen-bonded complexes between trihalomethanes, CHX3, and (pseudo-)halide anions, A-, co-existing in acetonitrile solutions were identified and characterized via a combination of UV-vis and NMR spectral measurements with the results of X-ray structural and computational analyses. Halogen-bonded [CHX3, A-] complexes displayed strong absorption bands in the UV range (showing Mulliken correlations with the frontier orbital energies of the interacting species) and a decreased shift of the NMR signal of trihalomethanes' protons. Hydrogen bonding led to the opposite (increased) NMR signal shift and the UV-vis absorption bands of the hydrogen-bonded [CHX3, A-] complexes were similar in intensity to those of the separate CHX3 molecules. The simultaneous multivariable treatment of the results of UV-vis and NMR titrations of CHX3 with A- anions afforded formation constants of both halogen- and hydrogen-bonded complexes between these species, which existed side-by-side in the acetonitrile solutions. The relative values of the formation constants were consistent with the magnitudes of the positive potentials on the surfaces of the halogen or hydrogen atoms if the effects of the polarization of the trihalomethanes due to the presence of the anions were taken into account.

Continuum of covalent to intermolecular bonding in the halogen-bonded complexes of 1,4-diazabicyclo[2.2.2]octane with bromine-containing electrophiles.

A gradual change of BrN bond lengths and strengths from the values typical for intermolecular associates to that characteristic of a covalent bond was observed in a series of halogen-bonded complexes. This continuum reveals a fundamental relationship between the limiting types of bonding and implies the onset of covalency in the intermolecular interactions.