Halogen bonding: an electrostatically-driven highly directional noncovalent interaction.

A halogen bond is a highly directional, electrostatically-driven noncovalent interaction between a region of positive electrostatic potential on the outer side of the halogen X in a molecule R-X and a negative site B, such as a lone pair of a Lewis base or the pi-electrons of an unsaturated system. The positive region on X corresponds to the electronically-depleted outer lobe of the half-filled p-type orbital of X that is involved in forming the covalent bond to R. This depletion is labeled a sigma-hole. The resulting positive electrostatic potential is along the extension of the R-X bond, which accounts for the directionality of halogen bonding. Positive sigma-holes can also be found on covalently-bonded Group IV-VI atoms, which can similarly interact electrostatically with negative sites. Since positive sigma-holes often exist in conjunction with negative potentials on other portions of the atom's surface, such atoms can interact electrostatically with both nucleophiles and electrophiles, as has been observed in surveys of crystallographic structures. Experimental as well as computational studies indicate that halogen and other sigma-hole interactions can be competitive with hydrogen bonding, which itself can be viewed as a subset of sigma-hole bonding.

[1]  Giuseppe Resnati,et al.  Halogen Bonding in Fluoroalkylhalides: A Quantum Chemical Study of Increasing Fluorine Substitution , 2000 .

[2]  Peter Politzer,et al.  σ‐Hole bonding and hydrogen bonding: Competitive interactions , 2007 .

[3]  Pavel Hobza,et al.  Investigations into the Nature of Halogen Bonding Including Symmetry Adapted Perturbation Theory Analyses. , 2008, Journal of chemical theory and computation.

[4]  Pavel Hobza,et al.  Blue shifts vs red shifts in σ-hole bonding , 2008, Journal of molecular modeling.

[5]  H. Torii.  The role of atomic quadrupoles in intermolecular electrostatic interactions of polar and nonpolar molecules , 2003 .

[6]  J. Murray,et al.  σ-hole bonding: molecules containing group VI atoms , 2007 .

[7]  J. Murray,et al.  Statistical analysis of the molecular surface electrostatic potential: an approach to describing noncovalent interactions in condensed phases , 1998 .

[8]  Chick C. Wilson,et al.  Imaging proton migration from X-rays and neutrons , 2004 .

[9]  W. Qian,et al.  Vibrational Spectroscopy of Hydrogen Bonding: Origin of the Different Behavior of the C−H···O Hydrogen Bond , 2002 .

[10]  T. Paolo,et al.  On the biological importance of the hydrogen bond breaking potency of fluorocarbons , 1974 .

[11]  H. Schaefer,et al.  Stable Hexacoordinated Neutral Complexes between Silyl Halides and Two Water or Two Ammonia Molecules: SiX4Y2(X = H, F, Cl; Y = H2O, NH3) , 2001 .

[12]  J. Murray,et al.  Simultaneous σ-hole and hydrogen bonding by sulfur- and selenium-containing heterocycles , 2008 .

[13]  P Shing Ho,et al.  Directing macromolecular conformation through halogen bonds , 2007, Proceedings of the National Academy of Sciences.

[14]  J. Murray,et al.  Why are dimethyl sulfoxide and dimethyl sulfone such good solvents? , 2008, Journal of molecular modeling.

[15]  R. Feynman.  Forces in Molecules , 1939 .

[16]  A. Gavezzotti.  Non-conventional bonding between organic molecules. The ‘halogen bond’ in crystalline systems , 2008 .

[17]  P Voth Regier Andrea and Ho Shing,et al.  The role of halogen bonding in inhibitor recognition and binding by protein kinases. , 2007 .

[18]  S. Ikuta.  Anisotropy of electron-density distribution around atoms in molecules: N, P, O and S atoms , 1990 .

[19]  R. Parthasarathy,et al.  Directional preferences of nonbonded atomic contacts with divalent sulfur in terms of its orbital orientations. 2. Sulfur.cntdot..cntdot..cntdot.sulfur interactions and nonspherical shape of sulfur in crystals , 1981 .

[20]  K. Molloy,,et al.  The structural chemistry of organotin derivatives of 5-mercapto-3-phenyl-1,3,4-thiadiazoline-2-thione: supramolecular structures involving intermolecular Sn⋯S, N–H⋯S or S⋯S interactions , 2002 .

[21]  Kenneth B. Wiberg,et al.  Comparison of atomic charges derived via different procedures , 1993, J. Comput. Chem..

[22]  E. Stevens.  Experimental electron density distribution of molecular chlorine , 1979 .

[23]  Ibon Alkorta,et al.  Competition of hydrogen bonds and halogen bonds in complexes of hypohalous acids with nitrogenated bases. , 2008, The journal of physical chemistry. A.

[24]  W. Levason,et al.  Arsenic(III) halide complexes with phosphine and arsine co-ligands: synthesis, spectroscopic and structural properties , 2002 .

[25]  Marcin Palusiak,et al.  On the nature of halogen bond – The Kohn–Sham molecular orbital approach , 2010 .

[26]  M. Iwaoka,et al.  Quantitative evaluation of weak nonbonded Se...F interactions and their remarkable nature as orbital interactions. , 2002, Journal of the American Chemical Society.

[27]  Anthony C. Legon,et al.  Prereactive Complexes of Dihalogens XY with Lewis Bases B in the Gas Phase: A Systematic Case for the Halogen Analogue B⋅⋅⋅XY of the Hydrogen Bond B⋅⋅⋅HX , 1999 .

[28]  Peter Politzer,et al.  Expansion of the σ-hole concept , 2009, Journal of molecular modeling.

[29]  Mark A Vincent,et al.  Density Functional and Semiempirical Molecular Orbital Methods Including Dispersion Corrections for the Accurate Description of Noncovalent Interactions Involving Sulfur-Containing Molecules. , 2007, Journal of chemical theory and computation.

[30]  B. Shainyan,et al.  PO Si intramolecular coordination in the derivatives of 1,4-phosphasilacyclohexane 1-oxides , 2009 .

[31]  Corradi,et al.  Halogen Bonding versus Hydrogen Bonding in Driving Self-Assembly Processes Perfluorocarbon-hydrocarbon self-assembly, part IX. This work was supported by MURST (Cofinanziamento '99) and EU (COST-D12-0012). We thank Dr. A. Lunghi and Dr. P. Cardillo (Stazione Sperimentale Combustibili, S. Donato Mila , 2000, Angewandte Chemie.

[32]  D. B. Miller,et al.  Observations on the Addition Compound of Silicon Tetrafluoride and Ammonia , 1955 .

[33]  Horst Köppel,et al.  Theoretical investigations on chalcogen-chalcogen interactions: what makes these nonbonded interactions bonding? , 2006, Journal of the American Chemical Society.

[34]  Peter Politzer,et al.  Quantitative analysis of molecular surfaces: areas, volumes, electrostatic potentials and average local ionization energies , 2010, Journal of molecular modeling.

[35]  A. Stone,et al.  The Nature of -Cl.cntdot..cntdot..cntdot.Cl- Intermolecular Interactions , 1994 .

[36]  P. F. Zhou,et al.  Topological definition of crystal structure: determination of the bonded interactions in solid molecular chlorine , 1995 .

[37]  P. Politzer,et al.  Characteristic features of the electrostatic potentials of singly negative monoatomic ions , 1989 .

[38]  R. Stewart.  On the mapping of electrostatic properties from bragg diffraction data , 1979 .

[39]  Peter Murray-Rust,et al.  Computer retrieval and analysis of molecular geometry. 4. Intermolecular interactions , 1979 .

[40]  Pierangelo Metrangolo,et al.  Halogen bonding based recognition processes: a world parallel to hydrogen bonding. , 2005, Accounts of chemical research.

[41]  Peter Politzer,et al.  A predicted new type of directional noncovalent interaction , 2007 .

[42]  K. Hermansson,et al.  X-ray and neutron diffraction studies and molecular dynamics simulations of liquid DMSO , 2004 .

[43]  A. Hector,et al.  Preparation and structure of the unique silicon(iv) cation [SiF3(Me3tacn)]+. , 2009, Chemical communications.

[44]  K. Hermansson.  Blue-shifting hydrogen bonds. , 2002 .

[45]  Frank H. Allen,et al.  The Nature and Geometry of Intermolecular Interactions between Halogens and Oxygen or Nitrogen , 1996 .

[46]  A. Cozzolino,et al.  The nature of the supramolecular association of 1,2,5-chalcogenadiazoles. , 2005, Journal of the American Chemical Society.

[47]  W. Cao,et al.  Theoretical Investigations of the Nature of Interaction of ClF with HF, H2O, and NH3. , 2007, Journal of chemical theory and computation.

[48]  Cheng Chang,et al.  Properties of atoms in molecules: atomic volumes , 1987 .

[49]  W. E. Billups,et al.  Cocrystallization with acetylene: molecular complexes with acetone and dimethyl sulfoxide. , 2003, Angewandte Chemie.

[50]  Peter Politzer,et al.  Directional tendencies of halogen and hydrogen bonds , 2010 .

[51]  J. Murray,et al.  Chlorotrinitromethane and its exceptionally short carbon–chlorine bond , 2009, Nature Chemistry.

[52]  T. Clark,et al.  Neighboring group stabilization by σ-holes , 2010, Journal of molecular modeling.

[53]  Peter Politzer,et al.  Surface electrostatic potentials of halogenated methanes as indicators of directional intermolecular interactions , 1992 .

[54]  S. J. Grabowski,et al.  Cooperativity halogen bonding effect – Ab initio calculations on H2CO⋯(ClF)n complexes , 2006 .

[55]  Pierangelo Metrangolo,et al.  Engineering functional materials by halogen bonding , 2007 .

[56]  Henry A. Bent,et al.  Structural chemistry of donor-acceptor interactions , 1968 .

[57]  T. Paolo,et al.  On the Hydrogen Bond Breaking Ability of Fluorocarbons Containing Higher Halogens , 1974 .

[58]  Chu-Xia Yan,et al.  Fluorine-containing donor-acceptor complex: infinite chain formed by oxygen...iodine interaction. , 2001, Journal of the American Chemical Society.

[59]  Peter Politzer,et al.  σ-hole bonding between like atoms; a fallacy of atomic charges , 2008, Journal of molecular modeling.

[60]  P Shing Ho,et al.  Halogen bonds as orthogonal molecular interactions to hydrogen bonds. , 2009, Nature chemistry.

[61]  S. J. Grabowski,et al.  Halogen bonding in crystal structure of 1-methylpyrrol-2-yl trichloromethyl ketone , 2007 .

[62]  Kevin E. Riley,et al.  Insights into the strength and origin of halogen bonding: the halobenzene-formaldehyde dimer. , 2007, The journal of physical chemistry. A.

[63]  Peter Politzer,et al.  The complementary roles of molecular surface electrostatic potentials and average local ionization energies with respect to electrophilic processes , 2002 .

[64]  M. Lehmann,et al.  Nature of S ⋯· O interaction in short X –S ⋯· O contacts: charge density experimental studies and theoretical interpretation , 1984 .

[65]  Pavel Hobza,et al.  Br···O Complexes as Probes of Factors Affecting Halogen Bonding: Interactions of Bromobenzenes and Bromopyrimidines with Acetone. , 2009, Journal of chemical theory and computation.

[66]  Timothy Clark,et al.  Halogen bonding: the σ-hole , 2007 .

[67]  F. Temple Burling,et al.  Computational studies of nonbonded sulfur-oxygen and selenium-oxygen interactions in the thiazole and selenazole nucleosides , 1992 .

[68]  Weizhou Wang,et al.  Theoretical Study on the Blueshifting Halogen Bond , 2004 .

[69]  L. Johnson,et al.  Alternative binding modes of an inhibitor to two different kinases. , 2003, European journal of biochemistry.

[70]  R E Cachau,et al.  Ultrahigh resolution drug design I: Details of interactions in human aldose reductase–inhibitor complex at 0.66 Å , 2004, Proteins.

[71]  A. Masunov,et al.  Geometric features of halogen-halogen intermolecular contacts in organic crystals , 1992 .

[72]  J. Dunitz,et al.  Directional preferences of nonbonded atomic contacts with divalent sulfur. 1. Electrophiles and nucleophiles , 1977 .

[73]  R. S. Mulliken.  Molecular Compounds and their Spectra. II , 1952 .

[74]  A. Wojtczak,et al.  Structure of rat transthyretin (rTTR) complex with thyroxine at 2.5 A resolution: first non-biased insight into thyroxine binding reveals different hormone orientation in two binding sites. , 2001, Acta crystallographica. Section D, Biological crystallography.

[75]  S. F. Boys,et al.  The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors , 1970 .

[76]  Eric Westhof,et al.  Halogen bonds in biological molecules. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[77]  R. L. Flurry.  Molecular Orbital Theory of Electron Donor-Acceptor Complexes. I. A Simple Semiempirical Treatment , 1965 .

[78]  Gautam R. Desiraju,et al.  The nature of halogen ⋯ halogen interactions and the crystal structure of 1,3,5,7-tetraiodoadamantane , 1994 .

[79]  Anthony C Legon,et al.  The halogen bond: an interim perspective. , 2010, Physical chemistry chemical physics : PCCP.

[80]  W. Wong-Ng,et al.  Anisotropic atom–atom forces and the space group of solid chlorine , 1979, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[81]  Peter Murray-Rust,et al.  Intermolecular interactions of the carbon-fluorine bond: the crystallographic environment of fluorinated carboxylic acids and related structures , 1983 .

[82]  Monica C. Concha,et al.  Electrostatically driven complexes of SiF4 with amines , 2009 .

[83]  Peter Murray-Rust,et al.  Angular preferences of intermolecular forces around halogen centers: preferred directions of approach of electrophiles and nucleophiles around carbon-halogen bond , 1986 .

[84]  Stefan Grimme,et al.  Semiempirical GGA‐type density functional constructed with a long‐range dispersion correction , 2006, J. Comput. Chem..

[85]  P. Metrangolo,et al.  Design and Synthesis of New Tectons for Halogen Bonding-driven Crystal Engineering , 2003 .

[86]  Pavel Hobza,et al.  Blue-Shifting Hydrogen Bonds. , 2000, Chemical reviews.

[87]  P. Metrangolo,et al.  Halogen bonding and pi...pi stacking control reactivity in the solid state. , 2004, Journal of the American Chemical Society.

[88]  Yunxiang Lu,et al.  Triangular halogen trimers. A DFT study of the structure, cooperativity, and vibrational properties. , 2005, The journal of physical chemistry. A.

[89]  Peter Politzer,et al.  An overview of halogen bonding , 2007, Journal of molecular modeling.

[90]  Zhong-yuan Lu,et al.  Unusual halogen-bonded complex FBrδ+⋯Brδ+F and hydrogen-bonded complex FBrδ+⋯Hδ+F formed by interactions between two positively charged atoms of different polar molecules , 2007 .

[91]  Peter Politzer,et al.  Halogen bonding and the design of new materials: organic bromides, chlorides and perhaps even fluorides as donors , 2007, Journal of molecular modeling.