Project Details Categorizing Halogen Bonding and Other Noncovalent Interactions Involving Halogen Atoms

Project No.:
2009-032-1-100
Start Date:
01 January 2010
End Date:
01 August 2013
Division Name:
Physical and Biophysical Chemistry Division
Division No.:
100

Objective

To take a comprehensive look at intermolecular interactions involving halogens as electrophilic species and classify them. To give a modern definition of halogen bonding, which takes into account all current experimental and theoretical pieces of information on both gaseous and condensed halogen-bonded systems in chemical and biological systems.

Description

Halogen atoms in organic compounds typically can be found at the periphery of molecules. For this reason, they are ideally positioned to be involved in intermolecular interactions. In fact, thanks to the large number of halogenated drugs and inhibitors, interactions involving halogen atoms are frequently observed in protein-ligand complexes. Halogens also occur naturally in biological systems. The best-known examples of this are probably the iodinated thyroid hormones, such as thyroxine. The crystal structure of the transport protein transthyretin complexed with thyroxine showed multiple iodine to carbonyl oxygen contacts involved in hormone binding.
It is well-known that the electron density around the halogen nucleus is highly anisotropic so that halogens can serve both as electron-acceptors and -donors. While we acknowledge that the terminology used to name noncovalent interactions given by halogen atoms has to be as unifying as possible, it is our opinion it has always to be done in keeping with the electrophile/nucleophile role the halogen atom plays. The term halogen bonding has been introduced for describing any noncovalent interaction involving halogens as acceptors of electron density. The general scheme D···X-Y thus applies to halogen bonding (XB), wherein X is the halogen (Lewis acid, XB-donor), D is any electron-donor (Lewis base, XB-acceptor), and Y is carbon, halogen, nitrogen, etc. The definition itself sheds light on the nature of XB, which possesses numerous similarities with hydrogen bonding (HB), wherein hydrogen functions as the acceptor of electron density.
In our opinion, the use of the term halogen bonding has to be limited to those interactions wherein halogens function as acceptors of electron density. Its use also to address interactions in which halogen atoms functions as electron-donors is conceptually misleading and contrasts with the clear tendency, well-documented in the literature, to name such -X···H-Y interactions differently (i.e. hydrogen bonds).

This project will attempt to give a modern definition of halogen bonding that is as inclusive as possible. Also, intermolecular interactions will be categorized logically considering the physical forces involved.

Progress

> project announcement in Chem. Int. Mar-Apr 2010

The whole community of researchers dealing with the study and use of intermolecular interactions will be called to be involved in this Project. A dedicated web-site (https://www.halogenbonding.eu) will be set-up as a public discussion forum for consideration of public comments. The Project will be advertised in major meetings relevant to related fields (e.g. the 26th European Crystallography Meeting in Darmstadt, 29 August – 2 September 2010 and the XXII General Assembly and Congress of the International Union of Crystallography (IUCr) to be held in Madrid, Spain, in 22-29 August 2011). In the second year of the Project, an international symposium open to the public will be organized, for consideration of public comments, presentation, and dissemination of results.

The kick-off meeting of the Project will be organized in Milan next 7 May 2010, where the Politecnico di Milano will host the 2nd International Workshop on Halogen Bonding. > see flyer (pdf -30 KB)

Jan 2011 update – The program of the satellite meeting to be held during the XXII General Assembly and Congress of the International Union of Crystallography (IUCr) to be held in Madrid, Spain, in 22-29 August 2011 is available – follow link under ‘Program’ or see flyer (pdf -108 KB)

March 2011 update – “Pierangelo Metrangolo and Giuseppe Resnati celebrate the bicentenary of the discovery of iodine – a good time to also bring to its conclusion an international project that aims to define and categorize halogen bonding.” … Nature Chemistry Vol. 3, p. 260 (2011) doi:10.1038/nchem.998 published online 21 February 2011.

Jan 2012 – A report from the IUCr Satellite workshop (22-29 Aug 2011), by David L. Bryce is published in Chem Int 34(1), p. 27.

July 2012 – the provisional recommendations titled “Definition of the Halogen Bond” was made available for public review until 30 Nov 2012.

July 2013 – Project complete – the Definition of the halogen bond (IUPAC Recommendations 2013) has been published in Pure Appl. Chem., 2013, Vol. 85, No. 8, pp. 1711-1713; https://dx.doi.org/10.1351/PAC-REC-12-05-10

last updated 3 Sep 2013