Halogen Bond Energy Research Articles

Fluxional halogen bonds in linear complexes of tetrafluorodiiodobenzene with dinitrobenzene.

The fluxional nature of halogen bonds (XBs) in small molecular clusters, supramolecules, and molecular crystals has received considerable attention in recent years. In this work, based on extensive density-functional theory calculations and detailed electrostatic potential (ESP), natural bonding orbital (NBO), non-covalent interactions-reduced density gradient (NCI-RDG), and quantum theory of atoms in molecules (QTAIM) analyses, we unveil the existence of fluxional halogen bonds (FXBs) in a series of linear (IC6F4I)m(OONC6H4NOO)n (m + n = 2-5) complexes of tetrafluorodiiodobenzene with dinitrobenzene which appear to be similar to the previously reported fluxional hydrogen bonds (FHBs) in small water clusters (H2O)n (n = 2-6). The obtained fluxional mechanisms involve one FXB in the systems which fluctuates reversibly between two linear CI···O XBs in the ground states (GS and GS') via a bifurcated CI O2N van der Waals interaction in the transition state (TS). The cohesive energies (Ecoh) of these complexes with up to four XBs exhibit an almost perfect linear relationship with the numbers of XBs in the systems, with the average calculated halogen bond energy of Ecoh/XB = 3.48 kcal·mol-1 in the ground states which appears to be about 55% of the average calculated hydrogen bond energy (Ecoh/HB = 6.28 kcal·mol-1) in small water clusters.

Anticooperativity of Multiple Halogen Bonds and Its Effect on Stoichiometry of Cocrystals of Perfluorinated Iodobenzenes.

To investigate influences on the topicity of perfluorinated halobenzenes as halogen bond (XB) donors in the solid state, we have conducted a database survey and prepared 18 novel cocrystals of potentially ditopic (13ditfb, 14ditfb) and tritopic (135titfb) XB donors with 15 monotopic pyridines. 135titfb shows high tendency to be mono- or ditopic, but with strong bases it can act as a tritopic XB donor. DFT calculations have shown that binding of a single acceptor molecule on one of the iodine atoms of the XB donor reduces the ESPmax on the remaining iodine atoms and dramatically decreases their potential for forming further halogen bonds, which explains both the high occurrence of crystal structures where the donors do not achieve their maximal topicity and the observed differences in halogen bond lengths. Despite the fact that this effect increases with the basicity of the acceptor, when the increase of halogen bond energy due to the basicity of the acceptor compensates its decrease due to the reduction of the acidity of the donor, it enables strong bases to form cocrystals in which a potentially polytopic XB donor achieves its maximal topicity.

The nature of halogen bond in model OC∙∙∙XY systems from the energy decomposition analysis perspective

This work represents the theoretical study results of the halogen bond's nature, based upon six model complexes of OC∙∙∙XY type, in which X and Y are halogen atoms. Local Molecular Orbital Energy Decomposition Analysis (LMOEDA), Quantum Theory Atom in Molecules (QTAIM), including geometrical parameters, the values and energy of intermolecular interaction and Molecular Electrostatic Potential (MESP) have been referred to in this investigation. A critical assessment of the LMOEDA studies is also presented. This shows a strong dependency of the results on calculation methods. Some DFT methods have as expected given very consistent results; however, Grimme’s dispersion corrections and some long-range separated functions in DFT do not work with the used decomposition energy procedure. Electron density and Laplacian values confirm linear dependencies in connection to halogen bond energy than in the case of ΔEint = f(RC∙∙∙X). MESP calculations also confirm the usefulness of σ-hole theory.

The Amine Group as Halogen Bond Acceptor in Cocrystals of Aromatic Diamines and Perfluorinated Iodobenzenes

In order to study the proclivity of primary amine groups to act as halogen bond acceptors, three aromatic diamines (p-phenylenediamine (pphda), benzidine (bnzd) and o-tolidine (otol)) were cocrystallised with three perfluorinated iodobenzenes (1,4-tetrafluorodiiodobenzene (14tfib), 1,3-tetrafluorodiiodobenzene (13tfib) and 1,3,5-trifluorotriiodobenzene (135tfib)) as halogen bond donors. Five cocrystals were obtained: (pphda)(14tfib), (bnzd)(13tfib)2, (bnzd)(135tfib)4, (otol)(14tfib) and (otol)(135tfib)2. In spite of the variability of both stoichiometries and structures of the cocrystals, in all the prepared cocrystals the amine groups form exclusively I···N halogen bonds, while the amine hydrogen atoms participate mostly in N–H⋯F contacts. The preference of the amine nitrogen atom toward the halogen bond, as opposed to the hydrogen bond (with amine as a donor), is rationalised by means of computed hydrogen and halogen bond energies, indicating that the halogen bond energy between a simple primary amine (methylamine) and a perfluorinated iodobenzene (pentafluoroiodobenze ne) is ca. 15 kJ mol−1 higher than the energy of the (H)NH∙∙∙NH2 hydrogen bond between two amine molecules.

Phosphine Oxides as Spectroscopic Halogen Bond Descriptors: IR and NMR Correlations with Interatomic Distances and Complexation Energy.

An extensive series of 128 halogen-bonded complexes formed by trimethylphosphine oxide and various F-, Cl-, Br-, I- and At-containing molecules, ranging in energy from 0 to 124 kJ/mol, is studied by DFT calculations in vacuum. The results reveal correlations between R–X⋅⋅⋅O=PMe3 halogen bond energy ΔE, X⋅⋅⋅O distance r, halogen’s σ-hole size, QTAIM parameters at halogen bond critical point and changes of spectroscopic parameters of phosphine oxide upon complexation, such as 31P NMR chemical shift, ΔδP, and P=O stretching frequency, Δν. Some of the correlations are halogen-specific, i.e., different for F, Cl, Br, I and At, such as ΔE(r), while others are general, i.e., fulfilled for the whole set of complexes at once, such as ΔE(ΔδP). The proposed correlations could be used to estimate the halogen bond properties in disordered media (liquids, solutions, polymers, glasses) from the corresponding NMR and IR spectra.

Spectroscopic Measurement of a Halogen Bond Energy.

Halogen bonding (XB) has emerged as an important bonding motif in supramolecules and biological systems. Although regarded as a strong noncovalent interaction, benchmark measurements of the halogen bond energy are scarce. Here, a combined anion photoelectron spectroscopy and density functional theory (DFT) study of XB in solvated Br- anions is reported. The XB strength between the positively-charged σ-hole on the Br atom of the bromotrichloromethane (CCl3 Br) molecule and the Br- anion was found to be 0.63 eV (14.5 kcal mol-1 ). In the neutral complexes, Br(CCl3 Br)1,2 , the attraction between the free Br atom and the negatively charged equatorial belt on the Br atom of CCl3 Br, which is a second type of halogen bonding, was estimated to have interaction strengths of 0.15 eV (3.5 kcal mol-1 ) and 0.12 eV (2.8 kcal mol-1 ).

Spectroscopic Measurement of a Halogen Bond Energy

AbstractHalogen bonding (XB) has emerged as an important bonding motif in supramolecules and biological systems. Although regarded as a strong noncovalent interaction, benchmark measurements of the halogen bond energy are scarce. Here, a combined anion photoelectron spectroscopy and density functional theory (DFT) study of XB in solvated Br− anions is reported. The XB strength between the positively‐charged σ‐hole on the Br atom of the bromotrichloromethane (CCl3Br) molecule and the Br− anion was found to be 0.63 eV (14.5 kcal mol−1). In the neutral complexes, Br(CCl3Br)1,2, the attraction between the free Br atom and the negatively charged equatorial belt on the Br atom of CCl3Br, which is a second type of halogen bonding, was estimated to have interaction strengths of 0.15 eV (3.5 kcal mol−1) and 0.12 eV (2.8 kcal mol−1).

Electrostatics and polarization determine the strength of the halogen bond: a red card for charge transfer

A series of 20 halogen bonded complexes of the types R–Br•••Br− (R is a substituted methyl group) and R´–C≡C–Br•••Br− are investigated at the M06-2X/6–311+G(d,p) level of theory. Computations using a point-charge (PC) model, in which Br− is represented by a point charge in the electronic Hamiltonian, show that the halogen bond energy within this set of complexes is completely described by the interaction energy (ΔEPC) of the point charge. This is demonstrated by an excellent linear correlation between the quantum chemical interaction energy and ΔEPC with a slope of 0.88, a zero intercept, and a correlation coefficient of R2 = 0.9995. Rigorous separation of ΔEPC into electrostatics and polarization shows the high importance of polarization for the strength of the halogen bond. Within the data set, the electrostatic interaction energy varies between 4 and −18 kcal mol–1, whereas the polarization energy varies between −4 and −10 kcal mol–1. The electrostatic interaction energy is correlated to the sum of the electron-withdrawing capacities of the substituents. The polarization energy generally decreases with increasing polarizability of the substituents, and polarization is mediated by the covalent bonds. The lower (more favorable) ΔEPC of CBr4---Br− compared to CF3Br•••Br− is found to be determined by polarization as the electrostatic contribution is more favorable for CF3Br•••Br−. The results of this study demonstrate that the halogen bond can be described accurately by electrostatics and polarization without any need to consider charge transfer.

Can halogen bond energy be reliably estimated from electron density properties at bond critical point? The case of the (A)nZ—Y•••X− (X, Y = F, Cl, Br) interactions

AbstractRelationships between the Y•••X bond critical point (BCP) properties or the Y•••X distance and the halogen bond interaction energy were analyzed in detail by theoretical methods for the series of structures [(A)nZ—Y•••X]− (X,Y = F, Cl, Br; totally 441 structures). No relationship was found for the whole set of structures or for the series [(A)nZ—F•••X]−, [(A)nZ—Cl•••X]−, and [(A)nZ—Br•••X]−. The interaction energies may be roughly estimated from the BCP properties for the series [(A)nZ—Y•••F]−, [(A)nZ—Y•••Cl]−, and [(A)nZ—Y•••Br]− as well as for [(A)nZ—Y•••X]− (when (A)nZ is variable, X and Y are constant) with the mean absolute deviation values 2.04‐4.38 kcal/mol. The corresponding recommended relationships are provided and they are significantly different from the popular dependencies deduced previously for other types of noncovalent interactions. Tremendous effect of the computational method and basis set on the relationships under analysis was discovered. Computational results clearly indicate that, for practical purposes, the Eint(BCP property) dependencies should be established not simply for each global type of interactions (hydrogen bond, halogen bond, chalcogen bond, etc.) but for each combination of the first and second order atoms taking into account also the computational method and basis set.

A Room-Temperature Hybrid Lead Iodide Perovskite Ferroelectric.

Organic-inorganic hybrid perovskite, [CH3NH3]PbI3, holds a great potential for next-generation solar devices. However, whether the ferroelectricity exists in [CH3NH3]PbI3 and results in the ultrahigh performance is not at present clear. Beyond that, no hybrid lead iodide perovskite ferroelectric has yet been found. Here, using precise molecular modifications, we successfully designed a room-temperature hybrid perovskite ferroelectric, [(CH3)3NCH2I]PbI3. Because of the high-symmetry and nearly spherical shape of [(CH3)4N]+ cation, [(CH3)4N]PbI3 crystallizes in a centrosymmetric space group P63/ m at room temperature and undergoes a structural phase transition at 184 K. Accompanied by the introduction of halogen atoms on the cation from F to I, the phase transition temperature gradually increases to 312 K and the space group transforms into a polar C2 at room temperature. The strongest halogen bond energy of [(CH3)3NCH2I]-I and the largest volume of [(CH3)3NCH2I]+ among these compounds might be possible reasons for the stabilization of ordered [(CH3)3NCH2I]+ cation array and further reservation of its ferroelectricity at relatively high temperature. This work provides an efficient molecular design strategy toward the targeted harvest of room-temperature organic-inorganic perovskite ferroelectrics, and should inspire further exploration of the interplay between structure and ferroelectricity. The discovery of lead iodide perovskite ferroelectric also offers a foothold to the possibility for the existence of ferroelectricity in [CH3NH3]PbI3.

Halogen, Chalcogen, and Pnicogen Bonding Involving Hypervalent Atoms.

The additional substituents arising from hypervalency present a number of complicating issues for the formation of noncovalent bonds. The XF5 molecule (X=Cl, Br, I) was allowed to form a halogen bond with NH3 as the base. Hypervalent chalcogen bonding is examined by way of YF4 and YF6 (Y=S, Se, Te), and ZF5 (Z=P, As, Sb) is used to model pnicogen bonding. Pnicogen bonds are particularly strong, with interaction energies approaching 50 kcal mol-1 , and also involve wholesale rearrangement from trigonal bipyramidal in the monomer to square pyramidal in the complex, subject to a large deformation energy. YF4 chalcogen bonding is also strong, and like pnicogen bonding, is enhanced by a heavier central atom. XF5 halogen bond energies are roughly 9 kcal mol-1 , and display a unique sensitivity to the identity of the X atom. The crowded octahedral structure of YF6 permits only very weak interactions. As the F atoms of SeF6 are replaced progressively by H, a chalcogen bond appears in combination with SeH⋅⋅⋅N and NH⋅⋅⋅F H-bonds. The strongest such chalcogen bond appears in SeF3 H3 ⋅⋅⋅NH3 , with a binding energy of 7 kcal mol-1 , wherein the base is located in the H3 face of the Lewis acid. Results are discussed in the context of the way in which the positions and intensities of σ-holes are influenced by the locations of substituents and lone electron pairs.

Controlling the spin state of diphenylcarbene via halogen bonding: A theoretical study

AbstractHalogen bonding has recently become an effective tool to control the spin state of reactive carbenes. In this work, a series of the complexes of diphenylcarbene (DPC) that has a triplet ground state with several halogen bond donors RX were theoretically studied, and in particular, the influence of the formation of halogen bonding on the spin state of DPC was extensively explored. The spin flip depends on the difference of halogen bond energies between triplet and singlet, that is, when the difference is large enough a spin flip may occur. Furthermore, the variations of the geometries on complexation may induce the potential energy surfaces of different spin states to intersect, thus leading to intersystem crossing. Based on the energy analysis of the minimum energy crossing points (MECPs), the systems with a smaller MECP‐triplet energy barrier go through intersystem crossing more easily. Halogen bonds in the complexes, where a spin flip takes place, exhibit a partially covalent character, while other complexes show conventional behaviors of halogen bonding. According to charge decomposition analysis, the charge transfer from HOMO (DPC) to LUMO (RX) is identified as a prominent stabilizing interaction in the whole complexes.

Halogen and Hydrogen Bonding between (N-Halogeno)-succinimides and Pyridine Derivatives in Solution, the Solid State and In Silico.

A study of strong halogen bonding within three series of halogen-bonded complexes, derived from seven para-substituted pyridine derivatives and three N-halosuccinimides (iodo, bromo and chloro), has been undertaken with the aid of single-crystal diffraction, solution complexation and computational methods. The halogen bond was compared with the hydrogen bond in an equivalent series based on succinimide. The halogen-bond energies are in the range -60 to -20 kJ mol-1 and change regularly with pyridine basicity and the Lewis acidity of the halogen. The halogen-bond energies correlate linearly with the product of charges on the contact atoms, which indicates a predominantly electrostatic interaction. The binding enthalpies in solution are around 19 kJ mol-1 less negative due to solvation effects. The optimised geometries of the complexes in the gas phase are comparable to those of the solid-state structures, and the effects of the supramolecular surroundings in the latter are discussed. The bond energies for the hydrogen-bonded series are intermediate between the halogen-bond energies of iodine and bromine, although there are specific differences in the geometries of the halogen- and hydrogen-bonded complexes.

Characteristics and nature of halogen bonds in linear clusters of NCX (X=Cl, and Br): an ab initio, NBO and QTAIM study

A theoretical study was performed to examine intermolecular halogen bond properties in one-dimensional NCX chains (X=Cl and Br). Geometries, binding energies, and charge-transfer of linear (NCCl)2–10 and (NCBr)2–10 chains were investigated by means of second-order Møller–Plesset perturbation theory (MP2) and DFT methods. All MP2, B3LYP and M06/aug-cc-pVTZ results indicate that the magnitudes of the interaction energies increase with increasing halogen size. Considering MP2/aug-cc-pVTZ results, it can be seen that the (NCBr)10 cluster is bound −12.72 kcal/mol more strongly than (NCCl)10. The n-dependent trend of charge-transfer is reasonably correlated with cooperative effects in halogen bond energies. According to the quantum theory of atoms in molecules, the capability of the (NCX)2–10 clusters for electron localization, at the C–X ··· N bond critical point (BCPs), depends on the cluster size and thereby leads to cooperative changes in the C–X ··· N strength, and charge-transfer. It is also revealed that for all intermolecular C–X ··· N interactions, total electronic energy densities are all greater than zero, suggesting that the interactions are significantly electrostatic in nature.

Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors

For proof-of-concept of halogen bonding in drug design, a series of halogenated compounds were designed based on a lead structure as new inhibitors of phosphodiesterase type 5. Bioassay results revealed a good correlation between the measured bioactivity and the calculated halogen bond energy. Our X-ray crystal structures verified the existence of the predicted halogen bonds, demonstrating that the halogen bond is an applicable tool in drug design and should be routinely considered in lead optimization.

Tuning σ-Holes: Charge Redistribution in the Heavy (Group 14) Analogues of Simple and Mixed Halomethanes Can Impose Strong Propensities for Halogen Bonding

Halogen bonding between halide sites (in substituted organic molecules or inorganic halides) and Lewis bases is a rapidly progressing area of exploration. Investigations of this phenomenon have improved our understanding of weak intermolecular interactions and suggested new possibilities in supramolecular chemistry and crystal engineering. The capacity for halogen bonding is investigated at the MP2(full) level of theory for 100 compounds, including all 80 MH(4-n)X(n) systems (M = C, Si, Ge, Sn, and Pb; X = F, Cl, Br, and I). The charge redistribution in these molecules and the (in)stability of the sigma-hole at X as a function of M and n are catalogued and examined. For the mixed MH(3-m)F(m)I compounds, we identify a complicated dependence of the relative halogen bond strengths on M and m. For m = 0, for example, the H(3)C-I----NH(3) halogen bond is 6.6 times stronger than the H(3)Pb-I----NH(3) bond. When m = 3, however, the F(3)Pb-I----NH(3) bond is shorter and approximately 1.6 times stronger than the F(3)C-I----NH(3) bond. This substituent-induced reversal in the relative strengths of halogen bond energies is explained.

An unconventional halogen bond with carbene as an electron donor: An ab initio study

An unconventional halogen bond has been proved to exist in H2C–BrH complex. The halogen bond energy of H2C–BrH complex is calculated at four levels of theory [MP2, MP4, CCSD, and CCSD(T)]. The result shows that the carbene is a better electron donor. The substitution effect is prominent in this interaction. For example, the interaction energy in H2C–BrCN complex is increased by more than 300% relative to H2C–BrH complex. The analyses of NBO, AIM, and energy components were used to unveil the nature of the interaction. The results show that this novel halogen bond has similar characteristics to hydrogen bonds.

Synthesis and Properties of Oligonucleotides with Iodo-Substituted Aromatic Aglycons: Investigation of Possible Halogen Bonding Base Pairs

Ab initio calculations of halogen bond energies of artificial base pairs constructed between iodinated aromatic nucleobase mimics and nitrogen-containing acceptor molecules such as pyridine and imidazole suggest that modified base pairs are converted to optimized planar base pairs with weak Delta E values of -0.19 to -3.93 kcal/mol. To evaluate the contribution of halogen bonding toward duplex stabilization of such modified nucleobase mimics introduced into artificial base pairs, we synthesized three C-nucleoside analogues 1-3 with several iodinated aromatic rings and an imidazole nucleoside derivative 4 and incorporated them into oligodeoxynucleotides. Hybridization studies of modified oligodeoxynucleotides incorporating iodoaromatic bases showed their unique universal base-like ability; however, no indication of halogen bond formation was observed. A more sophisticated design is required for the development of new base pairs stabilized by halogen bonding.

Mechanism of the solid-phase reaction of magnesium with organic halides

Low-temperature solid-phase reactions of magnesium with monosubstituted benzene halides and primary alkane halides have been investigated. On the basis of EPR and chromatographic data on the reactions products it was found that the carbon—halogen bond energy substantially influences the mechanism of formation of Grignard reagents.

Mean Palladium and Platinum–Halogen Bond Energies in Complexes of the Divalent and Tetravalent Metals

THE approximate calculations of the mean energies of platinum and palladium-halogen bonds, described in this communication were originally required for comparison with other thermodynamic data for these metals, but are also interesting in their own right. First, they demonstrate that, in common with other metal ions, platinum and palladium are only class “b” or “soft acids” in solution and that in the gas phase they exhibit normal class “a” or “hard acid” character, in that they form stronger bonds with chlorine than with bromine. Second, there are many examples where the properties of the octahedral complexes of tetravalent platinum and palladium can be understood by considering the corresponding square-planar complexes of the divalent metal and adding two “inert” ligands, one above and one below the square plane, which barely alter the original metal-ligand bonds1. For example, consider the following points, (i) The covalent radii of the divalent and tetravalent metals are almost equal2,3, (ii) The Pt-Cl bond lengths in K2PtCl4 (ref. 4) and K2PtCl0 (ref. 5) are equal (2.33 A). (iii) The Pt-Cl and Pt-N bonds in the platinum (II) complex, illustration are very similar6, (iv) The infrared spectra of trans-[Pt(SMe2)2X4], where X is a halide ion, can be interpreted as a superposition of the spectra of square planar [PtX4]2− and linear Me2S-Pt-SMe2 units7, (v) The net charges on the metal atoms in K2MCl6 and K2MC14 determined from the chlorine nuclear quadrupole resonance frequencies, assuming in each case that the halide bonding orbitals have 15% s-character, 85% p-character and 0% d-character, are very similar: (Et4N)2PdCl4, Pd + 0.72 (ref. 8); K2PdCl6, Pd + 0.58 (ref. 9); K2PtCl4, Pt + 0.68 (ref. 10); K2PtCl6, Pt + 0.64 (ref. 11). Open image in new window