Halogen bonded complexes between volatile anaesthetics (chloroform, halothane, enflurane, isoflurane) and formaldehyde: a theoretical study

The structures and intermolecular interactions in the halogen bonded complexes of anaesthetics (chloroform, halothane, enflurane and isoflurane) with formaldehyde were studied by ab initio MP2 and CCSD(T) methods. The CCSD(T)/CBS calculated binding energies of these complexes are between -2.83 and -4.21 kcal mol(-1). The largest stabilization energy has been found for the C-Br···O bonded halothane···OCH(2) complex. In all complexes the C-X bond length (where X = Cl, Br) is slightly shortened, in comparison to a free compound, and an increase of the C-X stretching frequency is observed. The electrostatic interaction was excluded as being responsible for the C-X bond contraction. It is suggested that contraction of the C-X bond length can be explained in terms of the Pauli repulsion (the exchange overlap) between the electron pairs of oxygen and halogen atoms in the investigated complexes. This is supported by the DFT-SAPT results, which indicate that the repulsive exchange energy overcompensates the electrostatic one. Moreover, the dispersion and electrostatic contributions cover about 95% of the total attraction forces, in these complexes.     

Nature of the Hydrogen Bond Enhanced Halogen Bond

The factors responsible for the enhancement of the halogen bond by an adjacent hydrogen bond have been quantitatively explored by means of state-of-the-art computational methods. It is found that the strength of a halogen bond is enhanced by ca. 3 kcal/mol when the halogen donor simultaneously operates as a halogen bond donor and a hydrogen bond acceptor. This enhancement is the result of both stronger electrostatic and orbital interactions between the XB donor and the XB acceptor, which indicates a significant degree of covalency in these halogen bonds. In addition, the halogen bond strength can be easily tuned by modifying the electron density of the aryl group of the XB donor as well as the acidity of the hydrogen atoms responsible for the hydrogen bond.     

A new unconventional halogen bond C?X···H?M between HCCX (X = Cl and Br) and HMH (M = Be and Mg): An ab initio study

In this article, a new type of halogen‐bonded complex YCCX···HMY (X = Cl, Br; M = Be, Mg; Y = H, F, CH₃) has been predicted and characterized at the MP2/aug‐cc‐pVTZ level. We named it as halogen‐hydride halogen bonding. In each YCCX···HMY complex, a halogen bond is formed between the positively charged X atom and the negatively charged H atom. This new kind of halogen bond has similar characteristics to the conventional halogen bond, such as the elongation of the C? X bond and the red shift of the C? X stretch frequency upon complexation. The interaction strength of this type of halogen bond is in a range of 3.34–10.52 kJ/mol, which is smaller than that of dihydrogen bond and conventional halogen bond. The nature of the electrostatic interaction in this type of halogen bond has also been unveiled by means of the natural bond orbital, atoms in molecules, and energy decomposition analyses. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

The origin of the two-electron/four-centers C--C bond in pi-TCNE(2)2- dimers: electrostatic or dispersion?

The structure and stability of the pi-TCNE(2)2- dimers in K2TCNE2 aggregates is revisited trying to find if the origin of their two-electron/four-centers C--C bond are the electrostatic K+-TCNE- interactions or the dispersion interactions between the anions. The study is done at the HF, B3LYP, CASSCF (2,2), and MCQDPT/CASSCF (2,2) levels using the 6-31+G(d) basis set. Our results show that the only minima of this aggregate that preserves the pi-TCNE(2)2- structure has the two K+ atoms placed in equatorial positions in between the two TCNE- planes. When the K+ atoms are placed along the D2h axis of the anions the structure is not a minimum. The main energetic component responsible for the stability of these aggregates comes from the cation-anion interactions. However, a proper accounting of the dispersion component (as done in the MCQDPT/CASSCF (2,2) calculations) is needed to make the closed-shell singlet more stable than the open-shell singlet. Thus, the bond results from the combination of the electrostatic and dispersion components, being the first the dominant one. The optimum geometry of the closed-shell singlet is very similar to the experimental one found in crystals.     

Cooperativity between the Halogen Bond and the Hydrogen Bond in H3N⋅⋅⋅XY⋅⋅⋅HF Complexes (X,Y=F,Cl, Br)

Ab initio calculations are used to provide information on H₃N???XY???HF triads (X, Y=F, Cl, Br) each having a halogen bond and a hydrogen bond. The investigated triads include H₃N???Br₂‐HF, H₃N???Cl₂???HF, H₃N???BrCI???HF, H₃N???BrF???HF, and H₃N???ClF???HF. To understand the properties of the systems better, the corresponding dyads are also investigated. Molecular geometries, binding energies, and infrared spectra of monomers, dyads, and triads are studied at the MP2 level of theory with the 6‐311++G(d,p) basis set. Because the primary aim of this study is to examine cooperative effects, particular attention is given to parameters such as cooperative energies, many‐body interaction energies, and cooperativity factors. The cooperative energy ranges from ?1.45 to ?4.64 kcal mol^?1, the three‐body interaction energy from ?2.17 to ?6.71 kcal mol^?1, and the cooperativity factor from 1.27 to 4.35. These results indicate significant cooperativity between the halogen and hydrogen bonds in these complexes. This cooperativity is much greater than that between hydrogen bonds. The effect of a halogen bond on a hydrogen bond is more pronounced than that of a hydrogen bond on a halogen bond.     

Ab initio study of the complexes of halogen-containing molecules RX (X=Cl, Br, and I) and NH3: towards understanding the nature of halogen bonding and the electron-accepting propensities of covalently bonded halogen atoms

Ab initio calculations have been performed on a series of complexes formed between halogen-containing molecules and ammonia to gain a deeper insight into the nature of halogen bonding. It appears that the dihalogen molecules form the strongest halogen-bonded complexes with ammonia, followed by HOX; the charge-transfer-type contribution has been demonstrated to dominate the halogen bonding in these complexes. For the complexes involving carbon-bound halogen molecules, our calculations clearly indicate that electrostatic interactions are mainly responsible for their binding energies. Whereas the halogen-bond strength is significantly enhanced by progressive fluorine substitution, the substitution of a hydrogen atom by a methyl group in the CH(3)X...NH(3) complex weakened the halogen bonding. Moreover, remote substituent effects have also been noted in the complexes of halobenzenes with different para substituents. The influence of the hybridization state of the carbon atom bonded to the halogen atom has also been examined and the results reveal that halogen-bond strengths decrease in the order HC triple bond CX > H(2)C=CHX approximately O=CHX approximately C(6)H(5)X > CH(3)X. In addition, several excellent linear correlations have been established between the interaction energies and both the amount of charge transfer and the electrostatic potentials corresponding to an electron density of 0.002 au along the R-X axis; these correlations provide good models with which to evaluate the electron-accepting abilities of the covalently bonded halogen atoms. Finally, some positively charged halogen-bonded systems have been investigated and the effect of the charge has been discussed.     

S···X halogen bonds and H···X hydrogen bonds in H2CS-XY (XY = FF, ClF, ClCl, BrF, BrCl, and BrBr) complexes: cooperativity and solvent effect

Using ab initio calculations, we have studied the structures, properties, and nature of halogen bonds in H(2)CS-XY (XY = FF, ClF, ClCl, BrF, BrCl, and BrBr) complexes. The results show that the ring-shaped complexes are formed by a halogen bond (S···X) and a secondary hydrogen bond (H···X). We also analyzed the H(2)CS-ClF-ClF and FCl-H(2)CS-ClF complexes to investigate the cooperative and diminutive halogen bonding. The cooperative effect of halogen bonding is found in the former, while the diminutive effect is present in the latter. We finally considered the solvent effect on the halogen bond in H(2)CS-BrCl complex and found that the solvent has a prominent enhancing effect on it. The complexes have also been analyzed with natural bond orbital, atoms in molecules, and symmetry adapted perturbation theory method.     

Theoretical study on intermolecular interactions in BrF/HnX adducts

Equilibrium geometries, interaction energies, and charge transfer for the intermolecular interactions between BrF and H_nX (HF, H₂O, and NH₃) were studied at the MP2/6-311++G(3d,3p) level. The halogen-bonded geometry and hydrogen-bonded geometry are observed in these interactions. The calculated interaction energies show that the halogen-bonded structures are more stable than the corresponding hydrogen-bonded structures. To study the nature of the intermolecular interactions, symmetry-adapted perturbation theory (SAPT) calculations were carried out and the results indicate that the halogen bonding interactions are dominantly inductive energy in nature, while electrostatic energy governs the hydrogen bonding interactions.     

Halogen as halogen-bonding donor and hydrogen-bonding acceptor simultaneously in ring-shaped H3N·X(Y)·HF (X = Cl, Br and Y = F, Cl, Br) complexes

A series of ring-shaped molecular complexes formed by H(3)N, HF and XY (X = Cl, Br and Y = F, Cl, Br) have been investigated at the MP2/aug-cc-pVTZ level of theory. Their optimized geometry, stretching mode, and interaction energy have been obtained. We found that each complex possesses two red-shifted hydrogen bonds and one red-shifted halogen bond, and the two hydrogen bonds exhibit strong cooperative effects on the halogen bond. The cooperativity among the NH(3)···FH, FH···XY and H(3)N···XY interactions leads to the formations of these complexes. The AIM analysis has been performed at the CCSD(T)/aug-cc-pVQZ level of theory to examine the topological characteristics at the bond critical point and at the ring critical point, confirming the coexistence of the two hydrogen bonds and one halogen bond for each complex. The NBO analysis carried out at the B3LYP/aug-cc-pVTZ level of theory demonstrates the effects of hyperconjugation, hybridization, and polarization coming into play during the hydrogen and halogen bonding formations processes, based on which a clockwise loop of charge transfer was discovered. The molecular electrostatic potential has been employed to explore the formation mechanisms of these molecular complexes.     

A polarizable ellipsoidal force field for halogen bonds

The anisotropic effects and short‐range quantum effects are essential characters in the formation of halogen bonds. Since there are an array of applications of halogen bonds and much difficulty in modeling them in classical force fields, the current research reports solely the polarizable ellipsoidal force field (PEff) for halogen bonds. The anisotropic charge distribution was represented with the combination of a negative charged sphere and a positively charged ellipsoid. The polarization energy was incorporated by the induced dipole model. The resulting force field is “physically motivated,” which includes separate, explicit terms to account for the electrostatic, repulsion/dispersion, and polarization interaction. Furthermore, it is largely compatible with existing, standard simulation packages. The fitted parameters are transferable and compatible with the general AMBER force field. This PEff model could correctly reproduces the potential energy surface of halogen bonds at MP2 level. Finally, the prediction of the halogen bond properties of human Cathepsin L (hcatL) has been found to be in excellent qualitative agreement with the cocrystal structures. © 2013 Wiley Periodicals, Inc.     

Disproportionation of pyrazine in NH+...N hydrogen-bonded complexes: new materials of exceptional dielectric response

Centrosymmetric pyrazinium NH+...N bonded complexes allow their dielectric properties to be analyzed separately from the bulk ferroelectric polarization observed in the noncentrosymmetric DABCO monosalts. The method of dielectric permittivity measurements has been employed for monitoring polarization fluctuations generated by proton transfers in the NH+...N bonded linear polycations. The revealed dielectric response of [C4H5N2]+BF4- and [C4H5N2]+ClO4- cannot be reconciled with the centrosymmetric symmetry of their structures, but suggests formation of polar defects or nanoregions. Unique transformations of the pyrazine [C4H5N2]+BF4- complex between linear NH+...N hydrogen-bonded polycationic aggregates antiparallel in phase gamma, perpendicular chains in phase beta, and with NH+...N bonds broken in phase alpha have been observed. The [C4H5N2]+ClO4- and [C4H5N2]+BF4- complexes as grown at 290 K are isostructural in orthorhombic phase , space group Pbcm, with linear polycationic chains arranged antiparallel. On heating, the tetrafluoroborate and perchlorate salts each undergoes two first-order phase transitions at similar temperatures about 340-360 K, while on cooling only one phase transition has been observed. An extremely unique sequence of two phase transitions subsequently lowering the symmetry of the [C4H5N2]+BF4- crystal when temperature is increased has been evidenced: the orthorhombic phase heated above 343 K transforms into the monoclinic C2/c-symmetric phase beta, in which the NH+...N bonded linear chains assume perpendicular arrangement; and at about 353-357 K the anions and cations adopt a typical ionic-crystal packing without homonuclear NH+...N hydrogen bonds in a still lower-symmetry monoclinic P21/n-symmetric structure. The exceptional perpendicular arrangement of the linear NH+...N bonded chains in phase beta constitutes a unique system where polarization of small regions can assume various orientations within a plane, depending on the H+ sites. No phase transitions or anomalous dielectric response were observed in the NH+...O bonded [C4H5N2]+NO3- complex. The unprecedented structure-property relations of the pyrazinium complexes fully confirm the role of the NH+...N bond transformations for the dielectric response of analogous DABCO ferroelectrics.     

Structure,properties, and nature of the BrF‐HX complexes: An Ab initio study

Structure and properties of complexes (energies and charge transfer) of complexes BrF‐HX (X = F, Cl, Br, I) have been investigated at the MP2/aug‐cc‐pVDZ (aug‐cc‐pVDZ‐pp basis sets for I) level. Two types of geometries (hydrogen‐bonded and halogen‐bonded) are observed. The calculated interaction energies show that the halogen bonded structures are more stable than the corresponding hydrogen‐bonded structures. To study the nature of the intermolecular interactions, symmetry‐adapted perturbation theory (SAPT) energy decomposition analysis reveals that the BrF‐HX complexes are dominantly electrostatic in nature. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Halogen Bonding: An Interim Discussion

Halogen bonding is a noncovalent interaction that is receiving rapidly increasing attention because of its significance in biological systems and its importance in the design of new materials in a variety of areas, for example, electronics, nonlinear optical activity, and pharmaceuticals. The interactions can be understood in terms of electrostatics/polarization and dispersion; they involve a region of positive electrostatic potential on a covalently bonded halogen and a negative site, such as the lone pair of a Lewis base. The positive potential, labeled a σ hole, is on the extension of the covalent bond to the halogen, which accounts for the characteristic near‐linearity of halogen bonding. In many instances, the lateral sides of the halogen have negative electrostatic potentials, allowing it to also interact favorably with positive sites. In this discussion, after looking at some of the experimental observations of halogen bonding, we address the origins of σ holes, the factors that govern the magnitudes of their electrostatic potentials, and the properties of the resulting complexes with negative sites. The relationship of halogen and hydrogen bonding is examined. We also point out that σ‐hole interactions are not limited to halogens, but can also involve covalently bonded atoms of Groups IV–VI. Examples of applications in biological/medicinal chemistry and in crystal engineering are mentioned, taking note that halogen bonding can be “tuned” to fit various requirements, that is, strength of interaction, steric factors, and so forth.     

Theoretical Studies on the Halogen Bond between Propargyl Radical and Dihalogen Molecules

MP2/aug‐cc‐pVDZ calculations are carried out on the geometries, vibrational frequencies, interaction energies and topological properties for the π‐type halogen‐bonded complexes between propargyl radical and dihalogen molecules ClF, BrF and BrCl. There are two kinds of geometries: complex ( a ) involves the interaction between the X (X=Cl, Br) atom and the midpoint of C(1) –C(2) bond, complex ( b ) involves the interaction between the X atom and C(3) atom. The lengths of the halogen bond, the frequencies of the halogen bond, the elongation extent of the X–Y (XY=ClF, BrF, BrCl) bond, topological parameters at the BCPs of the halogen bond and X–Y bond are all well consistent with the interaction energies. The interaction of complex ( a ) is stronger than that of complex ( b ); the interaction of propargyl···BrF is stronger than that of propargyl···ClF and propargyl···BrCl. For the complexes ( a ) and ( b ), the charge transfer is observed from propargyl radical to XY, the atomic energy, the dipolar polarization, and the volume of the halogen atom X decrease upon complex formation.     

Halogen Bonds in Adenine-5-Bromouracil Complexes

Ab initio and density functional calculations were employed to investigate the bonding patterns in theadenine-5-bromouracil (AT+) complexes. It is shown that the Br atom in 5-bromouracil (T+) is involved in bonding both with the hydrogen atom of the amino group of adenine (A) and with N7(A) (or N1(A)). With this motif, the Br atom interacts with a nucleophile (H) in a "head-on" fashion and an electrophile(N) in a "side-on" fashion, forming both hydrogen and halogen bonds. Electrostatic attraction between the Br atom in T+ and N7 (or N1) of adenine was found via the electrostatic potential analysis. The existence of the Br···N interactions in the pairs was further conˉrmed by means of Bader's atoms in molecules theory. A bond critical point is identiˉed for the halogen bonds and the topological parameters at the bond critical point indicate the typical closed-shell interactions in the pairs. Natural bond orbital analysis suggests that the charge transfer from the lone pair of the nitrogen atom of adenine is mainly directed to the C-Br antibonding orbital. Finally, halogen bonds in the T+AT+A tetrads were also explored.     

Charged versus Neutral Hydrogen‐Bonded Complexes: Is There a Difference in the Nature of the Hydrogen Bonds?

A theoretical study on some carboxylic acid dimers formed by positively or negatively charged molecules has been carried out by using DFT methods. The resulting dimers possess either a charge of +2 or ?2. In addition, the corresponding neutral complexes have also been considered. The electron density distribution described by the atoms in molecules and the natural bond orbital methods, as well as the electric field maps of the systems, have been analyzed and compared without finding significant differences between the neutral and ionic complexes. The interaction energy along the dissociation path of the charged dimers shows both a local minimum and a local maximum, defining a stability region between them. When this energetic profile is recalculated by removing the repulsion between the charged groups, it resembles to those of the neutral molecules. Hence, the characteristics of the charged dimers are similar to those of the neutral ones: the addition of a repulsion term for the charged groups permits to retrieve the energetic profiles dependence with the distance in the charged system. The interacting quantum atom (IQA) method has been used to calculate the interaction energy terms, including the classic Coulombic term between the whole molecules and the corresponding of the carboxylic acid groups. The IQA results show repulsive electrostatic interactions when the whole molecules are considered in the ionic complexes, but attractive ones between the carboxylic groups in both neutral and ionic complexes.     

Classification of So-Called Non-Covalent Interactions Based on VSEPR Model

The variety of interactions have been analyzed in numerous studies. They are often compared with the hydrogen bond that is crucial in numerous chemical and biological processes. One can mention such interactions as the halogen bond, pnicogen bond, and others that may be classified as σ-hole bonds. However, not only σ-holes may act as Lewis acid centers. Numerous species are characterized by the occurrence of π-holes, which also may play a role of the electron acceptor. The situation is complicated since numerous interactions, such as the pnicogen bond or the chalcogen bond, for example, may be classified as a σ-hole bond or π-hole bond; it ultimately depends on the configuration at the Lewis acid centre. The disadvantage of classifications of interactions is also connected with their names, derived from the names of groups such as halogen and tetrel bonds or from single elements such as hydrogen and carbon bonds. The chaos is aggravated by the properties of elements. For example, a hydrogen atom can act as the Lewis acid or as the Lewis base site if it is positively or negatively charged, respectively. Hence names of the corresponding interactions occur in literature, namely hydrogen bonds and hydride bonds. There are other numerous disadvantages connected with classifications and names of interactions; these are discussed in this study. Several studies show that the majority of interactions are ruled by the same mechanisms related to the electron charge shifts, and that the occurrence of numerous interactions leads to specific changes in geometries of interacting species. These changes follow the rules of the valence-shell electron-pair repulsion model (VSEPR). That is why the simple classification of interactions based on VSEPR is proposed here. This classification is still open since numerous processes and interactions not discussed in this study may be included within it.     

Influence of changes in water properties on reactivity in strongly acidic microemulsions

Replacing the counterion in sodium bis(2-ethylhexyl)sulfosuccinate (NaOT, usually known as AOT or Aerosol OT) with H+ (HOT) allows strongly acidic microemulsions to be obtained through the effect of a change in the solvation mechanism of the surfactant, where the Na+...OH2 interaction is displaced by a stronger H+...OH2 interaction. This raises the proportion of water bound to the counterion, which is reflected in the FT-IR spectrum for water trapped in the microemulsion and the 1H NMR spectrum for the hydrogen atoms in the water molecules. In NaOT microemulsions, the resonance signal for hydrogen atoms in the water molecules increases from delta approximately 3.9 ppm at W = 2 (with W = [H2O]/[NaOT]) to delta approximately 4.8 ppm at W = 50. In HOT microemulsions, the disparate strength of Na+...OH2 and H+...OH2 interactions results in a decrease in the resonance signal for the hydrogen atoms in the water molecules from delta approximately 8.6 ppm at W = 2 to delta approximately 4.9 ppm at W = 50. These changes in the physical properties of water alter chemical reactivity in a way that is clearly apparent in solvolytic processes in NaOT and HOT microemulsions. Thus, the rate constants of reactions involving an associative mechanism increase with decreasing W in NaOT microemulsions, but decrease with decreasing W in HOT microemulsions. The disparate behavior is a result of a decreased nucleophilicity of interfacial water in HOT microemulsions relative to NaOT microemulsions. For a dissociative process the rate constants are greater in HOT microemulsions than in NaOT ones, and increase with increasing W in both types of microemulsions, which can be ascribed to an increased electrophilicity of interfacial water in HOT microemulsions.     

Disentanglement of orthogonal hydrogen and halogen bonds via natural orbital for chemical valence: A charge displacement analysis

As known, the electron density of covalently bound halogen atoms is anisotropically distributed, making them potentially able to establish many weak interactions, acting at the same time as halogen bond donors and hydrogen bond acceptors. Indeed, there are many examples in which the halogen and hydrogen bond coexist in the same structure and, if a correct bond analysis is required, their separation is mandatory. Here, the advantages and limitations of coupling the charge displacement analysis with natural orbital for chemical valence method (NOCV-CD) to separately analyze orthogonal weak interactions are shown, for both symmetric and asymmetric adducts. The methodology gives optimal results with intermolecular adducts but, in the presence of an organometallic complex, also intramolecular interactions can be correctly analyzed. Beyond the methodological aspects, it is shown that correctly separate and quantify the interactions can give interesting chemical insights about the systems.