Insights into the strength and nature of carbene···halogen bond interactions: a theoretical perspective

Halogen-bonding, a noncovalent interaction between a halogen atom X in one molecule and a negative site in another, plays critical roles in fields as diverse as molecular biology, drug design and material engineering. In this work, we have examined the strength and origin of halogen bonds between carbene CH₂ and XCCY molecules, where X?=?Cl, Br, I, and Y?=?H, F, COF, COOH, CF₃, NO₂, CN, NH₂, CH₃, OH. These calculations have been carried out using M06-2X, MP2 and CCSD(T) methods, through analyses of surface electrostatic potentials V _S(r) and intermolecular interaction energies. Not surprisingly, the strength of the halogen bonds in the CH₂···XCCY complexes depend on the polarizability of the halogen X and the electron-withdrawing power of the Y group. It is revealed that for a given carbene···X interaction, the electrostatic term is slightly larger (i.e., more negative) than the dispersion term. Comparing the data for the chlorine, bromine and iodine substituted CH₂···XCCY systems, it can be seen that both the polarization and dispersion components of the interaction energy increase with increasing halogen size. One can see that increasing the size and positive nature of a halogen’s σ-hole markedly enhances the electrostatic contribution of the halogen-bonding interaction.

A theoretical study on the halogen bonding interactions of C6F5I with a series of group 10 metal monohalides

The halogen bonding interactions between C₆F₅I and a series of transition metal monohalides trans-[M(X)(2-C₅NF₄)-(PR₃)₂] (M = Ni, Pd, Pt; X = F, Cl, Br; R = Me, Cy) have been studied with quantum chemical calculations. Optimized geometries of the halogen bonding complexes indicate that angles C₁-I···X are basically linear (178–180°) and angles I···X-M mainly range from 90 to 150°. The strength of these metal-influenced halogen bonds alters with different metal centers, metal-bound halogen atoms and the substitutes on phosphine ligands. Electrostatic potential and natural bond orbital analysis show that both of the electrostatic and orbital interactions make a contribution to the formation of halogen bonds, while the electrostatic term plays a dominant role. AIM analysis suggests that, for trans-[M(F)(2-C₅NF₄)-(PR₃)₂] (M = Ni, Pd, Pt) monomers, the formed halogen bonding complexes are stabilized by local concentration of the charge of intermediate character, while for the metal monomers containing chlorine and bromine, a typical closed-shell interaction exist. These results prove that the structures and geometries of these halogen bonding complexes can be tuned by changing the halogen atoms and metal centers, which may provide useful information for the design and synthesis of new functional materials.

The competition of C-X⋯O=P halogen bond and π-hole⋯O=P bond between halopentafluorobenzenes C6F5X (X=F, Cl, Br, I) and triethylphosphine oxide

Calculation predicted the interacting forms of halopentafluorobenzene C₆F₅X (X=F, Cl, Br, I) with triethylphosphine oxide which is biologically interested and easily detected by ³¹P NMR. The interaction energy and geometric parameters of resultant halogen or π-hole bonding complexes were estimated and compared. Moreover, the bonding constants were determined by ³¹P NMR. Both theory and experiments indicated the C₆F₆ and C₆F₅Cl interact with triethylphosphine oxide by π-hole bonding pattern, while C₆F₅I by halogen/σ-hole bonding form. For C₆F₅Br, two interactions are comparative and should coexist competitively. The calculated interaction energies of σ-hole bonding complexes, ?5.07 kcal mol^?1 for C₆F₅Br?O=P and ?8.25 kcal mol^?1 for C₆F₅I?O=P, and π-hole bonding complexes, ?7.29 kcal mol^?1 for C₆F₆?O=P and ?7.24 kcal mol^?1 for C₆F₅Cl?O=P, are consistent with the changing tendency of bonding constants measured by ³¹P NMR, 4.37, 19.7, 2.42 and 2.23 M^?1, respectively.

Interplay between halogen bonds and hydrogen bonds in OH/SH···HOX···HY (X = Cl, Br; Y = F, Cl, Br) complexes

The character of the cooperativity between the HOX···OH/SH halogen bond (XB) and the Y―H···(H)OX hydrogen bond (HB) in OH/SH···HOX···HY (X = Cl, Br; Y = F, Cl, Br) complexes has been investigated by means of second-order Møller?Plesset perturbation theory (MP2) calculations and “quantum theory of atoms in molecules” (QTAIM) studies. The geometries of the complexes have been determined from the most negative electrostatic potentials (V _S,min) and the most positive electrostatic potentials (V _S,max) on the electron density contours of the individual species. The greater the V _S,max values of HY, the larger the interaction energies of halogen-bonded HOX···OH/SH in the termolecular complexes, indicating that the ability of cooperative effect of hydrogen bond on halogen bond are determined by V _S,max of HY. The interaction energies, binding distances, infrared vibrational frequencies, and electron densities ρ at the BCPs of the hydrogen bonds and halogen bonds prove that there is positive cooperativity between these bonds. The potentiation of hydrogen bonds on halogen bonds is greater than that of halogen bonds on hydrogen bonds. QTAIM studies have shown that the halogen bonds and hydrogen bonds are closed-shell noncovalent interactions, and both have greater electrostatic character in the termolecular species compared with the bimolecular species.

Cooperativity between fluorine-centered halogen bonds: investigation of substituent effects

This article analyzes the substitution effects on cooperativity between fluorin-centered halogen bonds in NCF?·?·?·?NCF?·?·?·?NCX and CNF?·?·?·?CNF?·?·?·?CNX complexes, where X?=?H, F, Cl, CN, OH, and NH₂. These effects are investigated theoretically in terms of geometric and energetic features of the complexes, which are computed by ab initio methods. The topological analysis, based on the quantum theory of atoms in molecules (QTAIM), is used to characterize the interactions and analyze their enhancement with varying electron density at bond critical points. It is found that the complexes with electron-donating groups exhibit a strong cooperativity, while a much weaker cooperativity occurs in the NCF?·?·?·?NCF?·?·?·?NCCN and CNF?·?·?·?CNF?·?·?·?CNCN trimers. An excellent correlation is found between the cooperative energy in the ternary complexes and the calculated three-body interaction energies. The energy decomposition analysis (EDA) indicates that the electrostatic and dispersion effects play a main role in the cooperativity of fluorine-centered halogen bonding.

Theoretical studies of the interaction between enflurane and water

Increase of the atmospheric concentration of halogenated organic compounds is partially responsible for a change of the global climate. In this work we have investigated the interaction between halogenated ether and water, which is one of the most important constituent of the atmosphere. The structures of the complexes formed by the two most stable conformers of enflurane (a volatile anaesthetic) with one and two water molecules were calculated by means of the counterpoise CP-corrected gradient optimization at the MP2/6–311++G(d,p) level. In these complexes the CH…O_w hydrogen bonds are formed, with the H…O_w distances varying between 2.23 and 2.32 Å. A small contraction of the CH bonds and the blue shifts of the ν(CH) stretching vibrations are predicted. There is also a weak interaction between one of the F atoms and the H atom of water, with the H_w…F distances between 2.41 and 2.87 Å. The CCSD(T)/CBS calculated stabilization energies in these complexes are between ?5.89 and ?4.66 kcal?mol^?1, while the enthalpies of formation are between ?4.35 and ?3.22 kcal?mol^?1. The Cl halogen bonding between enflurane and water has been found in two complexes. The intermolecular (Cl···O) distance is smaller than the sum of the corresponding van der Waals radii. The CCSD(T)/CBS stabilization energies for these complexes are about ?2 kcal?mol^?1.

Chalcogen- and halogen-bonds involving SX<Subscript>2</Subscript> (X = F,Cl, and Br) with formaldehyde

The capacity of SX₂ (X = F, Cl, and Br) to engage in different kinds of noncovalent bonds was investigated by ab initio calculations. SCl₂ (SBr₂) has two σ-holes upon extension of Cl (Br)?S bonds, and two σ-holes upon extension of S?Cl (Br) bonds. SF₂ contains only two σ-holes upon extension of the F?S bond. Consequently, SCl₂ and SBr₂ form chalcogen and halogen bonds with the electron donor H₂CO while SF₂ forms only a chalcogen bond, i.e., no F···O halogen bond was found in the SF₂:H₂CO complex. The S···O chalcogen bond between SF₂ and H₂CO is the strongest, while the strongest halogen bond is Br···O between SBr₂ and H₂CO. The nature of these two types of noncovalent interaction was probed by a variety of methods, including molecular electrostatic potentials, QTAIM, energy decomposition, and electron density shift maps. Termolecular complexes X₂S···H₂CO···SX′₂ (X = F, Cl, Br, and X′ = Cl, Br) were constructed to study the interplay between chalcogen bonds and halogen bonds. All these complexes contained S···O and Cl (Br)···O bonds, with longer intermolecular distances, smaller values of electron density, and more positive three-body interaction energies, indicating negative cooperativity between the chalcogen bond and the halogen bond. In addition, for all complexes studied, interactions involving chalcogen bonds were more favorable than those involving halogen bonds.

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Graphical Abstract Molecular electrostatic potential and contour map of the Laplacian of the electron density in Cl₂S···H₂CO···SCl₂ complex

     

Theoretical description of halogen bonding – an insight based on the natural orbitals for chemical valence combined with the extended-transition-state method (ETS-NOCV)

In the present study we have characterized the halogen bonding in selected molecules H₃N–ICF₃ (1-NH ₃ ), (PH₃)₂C–ICF₃ (1-CPH ₃ ), C₃H₇Br–(IN₂H₂C₃)₂C₆H₄ (2-Br), H₂–(IN₂H₂C₃)₂C₆H₄ (2-H ₂ ) and Cl–(IC₆F₅)₂C₇H₁₀N₂O₅ (3-Cl), containing from one halogen bond (1-NH ₃ , 1-CPH ₃ ) up to four connections in 3-Cl (the two Cl–HN and two Cl–I), based on recently proposed ETS-NOCV analysis. It was found based on the NOCV-deformation density components that the halogen bonding C–X ^… B (X-halogen atom, B-Lewis base), contains a large degree of covalent contribution (the charge transfer to X ^… B inter-atomic region) supported further by the electron donation from base atom B to the empty σ*(C–X) orbital. Such charge transfers can be of similar importance compared to the electrostatic stabilization. Further, the covalent part of halogen bonding is due to the presence of σ-hole at outer part of halogen atom (X). ETS-NOCV approach allowed to visualize formation of the σ-hole at iodine atom of CF₃I molecule. It has also been demonstrated that strongly electrophilic halogen bond donor, [C₆H₄(C₃H₂N₂I)₂][OTf]₂, can activate chemically inert isopropyl bromide (2-Br) moiety via formation of Br–I bonding and bind the hydrogen molecule (2-H ₂ ). Finally, ETS-NOCV analysis performed for 3-Cl leads to the conclusion that, in terms of the orbital-interaction component, the strength of halogen (Cl–I) bond is roughly three times more important than the hydrogen bonding (Cl–HN).

Theoretical study on cooperative effects between X⋯N and X⋯Carbene halogen bonds (X = F,Cl,Br and I)

Quantum chemical calculations are performed to study the interplay between halogen?nitrogen and halogen?carbene interactions in NCX?NCX?CH₂ complexes, where X?=?F, Cl, Br and I. Molecular geometries and interaction energies of dyads and triads are investigated at the MP2/aug-cc-pVTZ level of theory. It is found that the X?N and X?C_carbene interaction energies in the triads are larger than those in the dyads, indicating that both the halogen bonding interactions are enhanced. The estimated values of cooperative energy E _coop are all negative with much larger E _coop in absolute value for the systems including iodine. The nature of halogen bond interactions of the complexes is analyzed using parameters derived from the quantum theory atoms in molecules methodology and energy decomposition analysis.

Non-covalent interactions – QTAIM and NBO analysis

MP2(full)/6-311++G(3df,3pd) calculations were carried out on complexes linked through various non-covalent Lewis acid – Lewis base interactions. These are: hydrogen bond, dihydrogen bond, hydride bond and halogen bond. The quantum theory of ´atoms in molecules´ (QTAIM) as well as the natural bond orbitals (NBO) method were applied to analyze properties of these interactions. It was found that for the A-H…B hydrogen bond as well as for the A-X…B halogen bond (X designates halogen) the complex formation leads to the increase of s-character in the A-atom hybrid orbital aimed toward the H or X atom. In opposite, for the A…H-B hydride bond, where the H-atom possesses negative charge, the decrease of s-character in the B-atom orbital is observed. All these changes connected with the redistribution of the electron charge being the effect of the complex formation are in line with Bent´s rule. The numerous correlations between energetic, geometrical, NBO and QTAIM parameters were also found.

Competition between halogen, dihalogen and hydrogen bonds in bromo- and iodomethanol dimers

O-H…X and O-H…O H-bonds as well as C-X…X dihalogen and C-X…O halogen bonds have been investigated in halomethanol dimers (bromomethanol dimer, iodomethanol dimer, difluorobromomethanol…bromomethanol complex and difluoroiodomethanol…iodomethanol complex). Structures of all complexes were optimized at the counterpoise-corrected MP2/cc-pVTZ level and single-point energies were calculated at the CCSD(T)/aug-cc-pVTZ level. Energy decomposition for the bromomethanol dimer complex was performed using the DFT-SAPT method based on the aug-cc-pVTZ basis set. OH…O and OH…X H-bonds are systematically the strongest in all complexes investigated, with the former being the strongest bond. Halogen and dihalogen bonds, being of comparable strength, are weaker than both H-bonds but are still significant. The strongest bonds were found in the difluoroiodomethanol…iodomethanol complex, where the O-H…O H-bond exceeds 7 kcal mol^-1, and the halogen and dihalogen bonds exceed 2.5 and 2.3 kcal mol^-1, respectively. Electrostatic energy is dominant for H-bonded structures, in halogen bonded structures electrostatic and dispersion energies are comparable, and, finally, for dihalogen structures the dispersion energy is clearly dominant.

A theoretical investigation of the characteristics of hydrogen/halogen bonding interactions in dibromo-nitroaniline

In this work, computations of density functional theory (DFT) were carried out to investigate the nature of interactions in solid 2,6-dibromo-4-nitroaniline (DBNA). This system was selected to mimic the hydrogen/halogen bonding found within crystal structures as well as within biological molecules. DFT (M06-2X/6-311++G**) calculations indicated that the binding energies for different of interactions lie in the range between ?1.66 and ?9.77 kcal mol^?1. The quantum theory of atoms in molecules (QTAIM) was applied to provide more insight into the nature of these interactions. Symmetry-adapted perturbation theory (SAPT) analysis indicated that stability of the Br···Br halogen bonds is predicted to be attributable mainly to dispersion, while electrostatic forces, which have been widely believed to be responsible for these types of interactions, play a smaller role. Our results indicate that, for those nuclei participating in hydrogen/halogen bonding interactions, nuclear quadrupole resonance parameters exhibit considerable changes on going from the isolated molecule model to crystalline DBNA.

Theoretical study of the triangular bonding complex formed by carbon tetrabromide, a halide, and a solvent molecule in the gas phase

MP2(full)/aug-cc-pVDZ(-PP) computations predict that new triangular bonding complexes (where X^? is a halide and H–C refers to a protic solvent molecule) consist of one halogen bond and two hydrogen bonds in the gas phase. Carbon tetrabromide acts as the donor in the halogen bond, while it acts as an acceptor in the hydrogen bond. The halide (which commonly acts as an acceptor) can interact with both carbon tetrabromide and solvent molecule (CH₃CN, CH₂Cl₂, CHCl₃) to form a halogen bond and a hydrogen bond, respectively. The strength of the halogen bond obeys the order CBr₄???Cl^? > CBr₄???Br^? > CBr₄???I^?. For the hydrogen bonds formed between various halides and the same solvent molecule, the strength of the hydrogen bond obeys the order C-H???Cl^? > C-H???Br^? > C-H???I^?. For the hydrogen bonds formed between the same halide and various solvent molecules, the interaction strength is proportional to the acidity of the hydrogen in the solvent molecule. The diminutive effect is present between the hydrogen bonds and the halogen bond in chlorine and bromine triangular bonding complexes. Complexes containing iodide ion show weak cooperative effects.

Halogen bond tunability II: the varying roles of electrostatic and dispersion contributions to attraction in halogen bonds

In a previous study we investigated the effects of aromatic fluorine substitution on the strengths of the halogen bonds in halobenzene…acetone complexes (halo?=?chloro, bromo, and iodo). In this work, we have examined the origins of these halogen bonds (excluding the iodo systems), more specifically, the relative contributions of electrostatic and dispersion forces in these interactions and how these contributions change when halogen σ-holes are modified. These studies have been carried out using density functional symmetry adapted perturbation theory (DFT-SAPT) and through analyses of intermolecular correlation energies and molecular electrostatic potentials. It is found that electrostatic and dispersion contributions to attraction in halogen bonds vary from complex to complex, but are generally quite similar in magnitude. Not surprisingly, increasing the size and positive nature of a halogen’s σ-hole dramatically enhances the strength of the electrostatic component of the halogen bonding interaction. Not so obviously, halogens with larger, more positive σ-holes tend to exhibit weaker dispersion interactions, which is attributable to the lower local polarizabilities of the larger σ-holes.

Modulating weak intramolecular interactions through the formation of beryllium bonds: complexes between squaric acid and BeH2

The electronic structure of the two most stable isomers of squaric acid and their complexes with BeH₂ were investigated at the B3LYP/6-311?+?G(3df,2p)// B3LYP/6-31?+?G(d,p) level of theory. Squaric acid forms rather strong beryllium bonds with BeH₂, with binding energies of the order of 60 kJ?mol^?1. The preferential sites for BeH₂ attachment are the carbonyl oxygen atoms, but the global minima of the potential energy surfaces of both EZ and ZZ isomers are extra-stabilized through the formation of a BeH···HO dihydrogen bond. More importantly, analysis of the electron density of these complexes shows the existence of significant cooperative effects between the beryllium bond and the dihydrogen bond, with both becoming significantly reinforced. The charge transfer involved in the formation of the beryllium bond induces a significant electron density redistribution within the squaric acid subunit, affecting not only the carbonyl group interacting with the BeH₂ moiety but significantly increasing the electron delocalization within the four membered ring. Accordingly the intrinsic properties of squaric acid become perturbed, as reflected in its ability to self-associate.

ETS-NOCV description of σ-hole bonding

The ETS-NOCV analysis was applied to describe the σ-hole in a systematic way in a series of halogen compounds, CF₃-X (X?=?I, Br, Cl, F), CH₃I, and C(CH3)_nH_3-n-I (n?=?1,2,3), as well as for the example germanium-based systems. GeXH₃, X?=?F, Cl, H. Further, the ETS-NOCV analysis was used to characterize bonding with ammonia for these systems. The results show that the dominating contribution to the deformation density, Δρ ₁ , exhibits the negative-value area with a minimum, corresponding to σ-hole. The “size” (spatial extension of negative value) and “depth” (minium value) of the σ-hole varies for different X in CF₃-X, and is influenced by the carbon substituents (fluorine atoms, hydrogen atoms, methyl groups). The size and depth of σ-hole decreases in the order: I, Br, Cl, F in CF₃-X. In CH₃-I and C(CH3)_nH_3-n-I, compared to CF₃-I, introduction of hydrogen atoms and their subsequent replacements by methyl groups lead to the systematic decrease in the σ-hole size and depth. The ETS-NOCV σ-hole picture is consistent with the existence the positive MEP area at the extension of σ-hole generating bond. Finally, the NOCV deformation density contours as well as by the ETS orbital-interaction energy indicate that the σ-hole-based bond with ammonia contains a degree of covalent contribution. In all analyzed systems, it was found that the electrostatic energy is approximately two times larger than the orbital-interaction term, confirming the indisputable role of the electrostatic stabilization in halogen bonding and σ-hole bonding.

Theoretical study of X- · 1 · YF (1 = triazine,X = Cl,Br and I,Y = H,Cl, Br,I, PH2 and AsH2): noncovalently electron-withdrawing effects on anion-arene interactions

The ternary complexes X^- · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH₂ and AsH₂) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes (1 · X^-), both weak σ-type and anion-π complexes can be formed for Cl^- and Br^-, but only anion-π complex can be formed for I^-. Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl^- and Br^-. Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl^- and Br^- in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl^- and Br^- can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I^- is different from that for Cl^- and Br^- in two aspects. First, the anion-π complex for I^- can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I^- is the global minimum when it can retain as a stable structure.     

Modulating the strength of tetrel bonding through beryllium bonding

Quantum chemical calculations were performed to investigate the stability of the ternary complexes BeH₂···XMH₃···NH₃ (X?=?F, Cl, and Br; M?=?C, Si, and Ge) and the corresponding binary complexes at the atomic level. Our results reveal that the stability of the XMH₃···BeH₂ complexes is mainly due to both a strong beryllium bond and a weak tetrel–hydride interaction, while the XMH₃···NH₃ complexes are stabilized by a tetrel bond. The beryllium bond with a halogen atom as the electron donor has many features in common with a beryllium bond with an O or N atom as the electron donor, although they do exhibit some different characteristics. The stability of the XMH₃···NH₃ complex is dominated by the electrostatic interaction, while the orbital interaction also makes an important contribution. Interestingly, as the identities of the X and M atoms are varied, the strength of the tetrel bond fluctuates in an irregular manner, which can explained by changes in electrostatic potentials and orbital interactions. In the ternary systems, both the beryllium bond and the tetrel bond are enhanced, which is mainly ascribed to increased electrostatic potentials on the corresponding atoms and charge transfer. In particular, when compared to the strengths of the tetrel and beryllium bonds in the binary systems, in the ternary systems the tetrel bond is enhanced to a greater degree than the beryllium bond.

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Graphical Abstract A tetrel bond can be strengthened greatly by a beryllium bond

     

Penta- and heteropentadienyl ligands coordinated to beryllium

In this work we have performed a systematic study of new organometallic complexes containing penta- and heteropentadienyl (CH₂CHCHCHX, X?=?CH₂, O, NH, S) ligands coordinated to beryllium. Calculated complexes were studied using the density functional theory (PBE) in combination with the 6-311++G(3d,2p) basis set. The coordination number on the beryllium atom varies according to the type of ligand. Pentadienyl ligand shows hapticities η¹ and η⁵, while heteropentadienyl ligands display η¹ and η² hapticities. A Wiberg bond indices study was performed in order to get information about their bond orders.