Theoretical Study Of Halogen Bonding-A World Parallel To Hydrogen Bonding

Halogen bonding is the noncovalent intermolecular interaction between halogen atoms(Lewis acids)and neutral or anionic Lewis bases.Most of the energetic and structural features found in hydrogen-bonded complexes are reproduced in halogen-bonded complexes as well.By virtue of its strength,selectivity,and directivity,halogen bonding has led to a number of applications in fields as diverse as molecular recognition,enantiomers's separation,crystal engineering,and supramolecular architectures.Particularly,the utilization of this specific interaction in the context of drug design is nowadays coming to light.The thesis is of quantum chemical study on conventional and unconventional halogen bonds,such as bifurcated halogen bonds,negatively charge-assisted halogen bonds,C-X/Ï€interactions,and halogen trimers as well as the "amphiphilicity" of covalently-bonded halogen atoms.Covalently-bonded halogen atoms exhibit unique amphoteric character: electrophilic character along the axes of the C-X bonds and nucleophilic character along vectors perpendicular to these bonds.To provide a quantitative insight into the "amphiphilicity" of halogens,a series of complexes formed between bromine-containing molecules RBr and HF have been examined at the MP2(full)/aug-cc-pVDZ level of theory.Ab initio calculations reported have shown that the stronger the electron-withdrawing the substitution on the bromine is,the weaker is the hydrogen bond to which it gives rise,which is contrary to the trend detected in the RBr…NH₃ complexes.These give a strong indication that the stronger the electrophilic ability of the RBr species,the weaker their nucleophilicity.The topological parameters obtained in terms of Bader's atoms in molecules(AIM)theory have also been applied for the analysis of these Br…H interactions.The values of electron density and Laplacian of the electron density indicate the existence of hydrogen bonding and the closed-shell kind of interactions in these complexes.It has also been found that the topological parameters at HBCPs correlate well with the interaction energy.A detailed analysis of small model systems that contain halogen bonding elements commonly discovered in real systems should be of pivotal importance for our understanding of crystal packing and molecular recognition processes in biological systems.On the basis of these,an ab initio investigation of a series of dimeric complexes formed between bromobenzene and several electron donors has been carried out.Such small model systems are selected to mimic halogen bonding interactions found within crystal structures as well as within biological molecules.In all cases,the intermolecular distances are shown to be equal to or below sums of van der Waals radii of the atoms involved.Halogen bonding energies,calculated at the MP2/aug-cc-pVDZ level,span over a wide range,from -1.52 to -15.53 kcal/mol.The interactions become comparable to,or even prevail over,classical hydrogen bonding. For charge-assisted halogen bonds,calculations have shown that the strength decreases in the following order:OH-＞F-＞HCO₂-＞CI-＞Br-,while for neutral systems their relative strengths attenuate in the order:H₂CS＞H₂CO＞NH₃＞H₂S＞H₂O.These results agree with those of the quantum theory of atoms in molecules (QTAIM),since bond critical points(BCPs)are probed for these halogen bonds.The QTAIM analysis also suggests that strong halogen bonds are more covalent in nature, while weak ones are mostly electrostatic interactions.The electron densities at the BCPs are recommended as a good measure of the halogen bond strength.Finally, natural bond orbital(NBO)analysis has been applied to gain more insights into the origin of halogen bonding interactions.Bader's atoms in molecules(AIM)theory has been successfully applied to study properties of a variety of conventional and unconventional hydrogen bonds.In view of halogen bonds having analogies with H bonds,it is reasonable to ask whether they represent similar AIM properties or not.To answer this question,a systematic AIM study on a large number of complexes formed between halogen-containing molecules and several electron donors has been employed.Integrated atomic properties such as charge,energy,polarization moment,volume of the halogen bond donor atoms,and the corresponding changes(A)upon complexation have been calculated.It is shown that halogen bonds present different AIM properties as compared to well-studied hydrogen bonds.Calculations also indicate that the electron densities at the halogen bond critical points correlate with the interaction energies,which indicates that the electron density can serve as a convenient measure of the strength of the different types of halogen bonding.Similar to hydrogen bonds,halogen bonds can be classified in a range from weak bonds,which are regarded as electrostatic interactions,to strong bonds,which have some degree of covalent character.Bifurcated halogen bonds have attracted a great deal of interest in recent years because these weak three-center interactions play a crucial structural role in crystal architecture.These soft and weak three-center interactions can be regarded as a "discriminator synthon" even in the presence of strong hydrogen bonds.To shed some light on the structural and energetic properties of bifurcated halogen bonds,ab initio calculations at the MP2(full)/aug-cc-pVDZ level of theory have been performed to investigated the complexes of CH₃NO₂ with RX.It has been shown that the three-center interactions in the chlorine-containing complexes are very weak,whereas the interactions in the bromine-containing complexesare relatively stronger. Bifurcated halogen bonds,where single intermolecular contacts are much longer than those of the two-center halogen bonds,exhibit weaker bond strength as compared to the two-center ones.The values of electron densities and their Laplacians indicate the existence of halogen bonds and the closed-shell kind of interactions in these complexes.Linear relationships have also been established between the distances d(X…O)and the corresponding ln(Pb).Noncovalent C-X/Ï€interactions are of vital importance in crystal engineering and possibly in biological systems.To understand the nature and strength of the C-X/Ï€interactions,ab initio calculations have been carried out to investigate the interactions between theÏ€face of benzene and several halocarbon molecules.The theoretical calculations described reveal the predominant noncovalent C-X/Ï€interactions in all the halocarbon-benzene complexes.The C-X/Ï€interactions are comparable in strength to the well-documented C-H/Ï€interactions.The significant gain of the attraction by electron correlation illustrates that the stabilities of the systems considered are primarily ascribed to the dispersion interaction.Charge transfer force plays a minor role in the C-X/Ï€interactions by virtue of the very small or even negligible amount of CT upon complex formation.The halogen-bonding nature of the C-X/Ï€interactions has been confirmed in terms of the bond critical point analysis within the atoms in molecules(AIM)theory.The halogen/Ï€complexes of aromatic donors with homo- or heteronuclear diatomic halogen molecules are particularly key pre-reactive complexes in the electrophilic halogenations of aromatic systems and occupy a crucial position in the history of electron donor-accept complexes.To provide some insights into the origin and magnitude of halogen/Ï€interactions,ab initio calculations have been performed to investigate the complexes formed between FCl and substituted benzenes.It is shown that substituents on benzene have a pronounced effect on the strength of halogen/Ï€interactions.While the presence of electron-donating groups(NH₂,CH₃, and OH)on benzene appreciably enhances the interaction energy,an opposite effect is observed for electron-accepting groups(NO₂,CN,Br,Cl,and F).The large gain of the attraction by electron correlation illustrates that the stabilities of the systems considered arise primarily from the dispersion interaction.Beside the dispersion interaction,the charge-transfer interaction also plays an important role in halogen/Ï€interactions,as a charge density analysis suggested.The existence of a halogen/Ï€interaction in the complexes considered has been confirmed by using the approach of atoms in molecules(AIM).Topological parameters at the bond critical points manifest the halogen-bonding nature of halogen/Ï€interactions.Negatively charge-assisted halogen bonds are of vital importance in crystal engineering due to their wide application in the design of novel materials possessing singular crystal structures and conducting properties.To gain a deeper insight into the nature and strength of theses interactions,a series of dimeric complexes formed between bromocarbon molecules and two anions(Br- and CN-)have been investigated by using MP2 method.The quantum theory of atoms in molecules (QTAIM)and the second-order perturbation natural bond orbital(NBO)approaches were applied to analyze the electron density distributions of these complexes and to explore the nature of charge-assisted halogen bonding interactions.As anticipated, these interactions are significantly stronger relative to the corresponding neutral ones. The results derived from ab initio calculations described reveal a major contribution from the electrostatic interaction on the stability of the systems considered.Beside the electrostatic interaction,the charge-transfer force and the second-order orbital interaction also play an important role in the formation of the complexes,as a NBO analysis suggested.The QTAIM analysis further supports the existence of halogen bonding interactions in the complexes,and the topological properties of the halogen bond critical points(BCPs),such as the electron density(ρb),its Laplacian(â–½²Ïb),the kinetic electron energy density(Gb),and the potential electron energy density(V b), have been shown to correlate well with the interaction energy,however the electron energy density(Hb)remains almost unchanged. Fluorine is frequently considered to not participate in halogen bonding interactions due to its extreme electronegativity and limited polarizability.However, the interfluorine contacts(F…F)are ubiquitous in crystal structures,and the F…Y(Y is an electronegative atom)interactions have been nowadays observed in some molecular crystals.These interactions can be referred to as F bonding by analogy to classical H bonding.With a view to provide some insights into the strength and nature of fluorine bonding,ab initio calculations at the MP2 computational level have been performed on several complexes formed between fluorine-containing molecules and ammonia.The interactions in complexes are comparable in strength to conventional halogen bonds.The results derived from the calculations reveal a major contribution from the electrostatic interaction to the stability of the systems considered.As a NBO analysis suggested,the charge-transfer force plays a minor role in the formation of the complexes.Bond critical point analysis within the QTAIM theory demonstrates the halogen-bonding nature of fluorine bonding interactions.Triangular halogen…halogen…halogen interactions have attracted substantial interest in recent years since these interactions are of vital importance in crystal engineering.This trimeric alignment of halogen…halogen interactions can be regarded as a cohesive force in crystal structures.To explore the geometric changes, the binding energies,including the two- and three-body terms,and some selected vibrational frequency shifts upon complexation,several triangular halogen trimers (RX)₃ have been investigated using the density functional theory(DFT)in Perdew, Burke,and Emzerhof method.The results show that all trimer structures possess a cyclic array of halogen atoms in the typeâ…¡approach by virtue of the nonspherical atomic charge distribution around the halogens.The Br…...Br interactions in trimers are very weak,whereas the I…I interactions in trimers are relatively stronger.While all bromine trimers and most of iodine trimers are predicted to be noncooperative,three of iodine trimers show weak cooperativity.The analysis of vibration modes reveals that all halogen trimers exhibit no especially remarkable frequency shifts.It is also shown that the electrostatic contribution plays a major role in the halogen…halogen interactions in halogen trimers.In contrast to bromine trimers,the relative contribution of charge transfer component to the halogen…halogen interactions becomes more important for iodine trimers.Benchmark databases for various nonbonded interactions,such as hydrogen bonding,charge-transfer interactions,dipolar interactions,and weak interactions,are now available.Nonetheless,there is,to our knowledge,no benchmark study of halogen bonding.To establish a benchmark database for this specific intermolecular force,an ab initio benchmark investigation on a series of dimeric complexes formed between some halocarbon molecules and formaldehyde as well as water has been carried out.Full geometry optimizations are performed at the MP2 level of theory with the Dunning's correlation-consistent basis set,aug-cc-pVDZ.Binding energies are extrapolated to the complete basis set(CBS)limit by means of the three-point extrapolation method in combination with the aug-cc-pVXZ(X=D,T,Q)basis sets series.The CCSD(T)correction term,determined as a difference between CCSD(T) and MP2 binding energies,is estimated with the aug-cc-pVDZ basis set.In general, the inclusion of higher-order electron correlation effects leads to a repulsive correction with respect to those predicted at the MP2 level.On the basis of the benchmark database obtained,we have tested several DFT methods.Among these methods,PW91,PBE,B97-1,and MPWLYP give the best performance.These functionals are therefore recommended as efficient alternatives to ab initio theory for a reasonably good description of large systems(e.g.,biologically relevant molecules) associated with halogen bonding interactions.The ONOM method,which divides the system into several onion-like layers, treating the active center with the highest level ab initio QM method,while outer layers can be treated with less expensive methods,such as low level ab initio QM, semiempirical QM,or MM methods,has made larger molecular systems within reach of accurate calculations.To testify the accuracy of ONIOM method in the description of halogen-bonded large biologically relevant systems,a DNA junction(ID 1P54)in the structure of d(CCAGTACbr⁵UGG)has been selected for research purpose. Geometry optimizations are performed by means of the AM1,PM3,B3LYP,PBE, ONIOM(B3LYP:AMI)and ONIOM(PBE:AM1)approaches.It is shown that while the semiempirical AM1 method yield poor performance,DFT and ONIOM methods reproduce the X-ray structure fairly well.However,the RMSD values are still somewhat high.After including nine water molecules around the domain of halogen bonding,the RMSD values decrease significantly,which indicates that water molecules play an important role in the structures of biological macromolecules.The study described may provide some useful information of the nature and magnitude of halogen bonding interactions,which would be very useful in the design and synthesis of new materials and effective drugs involving halogenated compounds.