Non‐Covalent Interactions of Organic Halogen Compounds with Aromatic Systems – Analyses of Crystal Structure Data

Abstract

The Cambridge Structural Database showed in mid 2002 about 20.000 structures containing halogen atoms and aryl rests with distances d between the aryl center and the halogen atom, which would allow both hydrogen bonds with the aromatic hydrogens and/or van der Waalsinteractions with the π‐cloud. The latter are characterized by short distances d and by small angles α between the vector along the aryl centroid–halogen line and the perpendicular vector originating in the aryl center (the plane normal). The cases with d < 3.0 Å for F; and d < 3.5 Å for Cl, Br or I (outliers neglected), and α ≈ 10 ± 5°, indicating predominating van der Waals forces, amount to several hundreds. The majority of fragments exhibit larger d and α values, in line with avoidance of electrostatic repulsion between the negative partial charges of the halogens and the π‐cloud center, and with an increasing electrostatic attraction with the aromatic hydrogen atoms. The corresponding hydrogen bonds are characterized by longer distances d and by angle values of α > 60° (about 40 % of the fragments), with only very few cases close to linear hydrogen bonds (then with α = 90°). Compounds containing metal–halogen bonds were omitted in view of possible strong orientational interferences. The structures were screened with four different halogen binding modes, all of them containing the halogen attached to a carbon atom, but with different hybrizations at the connecting carbon centers. The results show only small differences in the distance distributions, with a slight preference for smaller α values for sp2 frameworks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Sigma-Holes in Battery Materials Using Iso-Electrostatic Potential Surfaces

“…Notable differences for the larger halogens include larger σ-hole circumference at identical isopotential values [24]; the size of the exposed region for phenyl halogens follows the trend PhI > PhBr > PhCl at the ±0.3 V isopotentials. This approach confirms existing literature about increasing halogen capabilities of participating in these types of nonbonding interactions due to differences in size [49,50]. A second case is given by chlorobenzene C6H5Cl, shown in Figure 3.…”

More than a Simple Lipophilic Contact: A Detailed Thermodynamic Analysis of Nonbasic Residues in the S1 Pocket of Thrombin

“…This geometry resembles the preferred orientation, observed frequently for chlorine atoms pointing towards aromatic ring systems in a large dataset of small molecule crystal structures in the Cambridge Structural Database. 33 In terms of a recent evaluation of chlorine-π interactions in proteinligand complexes 14 , this orientation is characterized as the "edge on" geometry.…”

A 19F NMR study of C–I⋯π halogen bonding

“…As stated above, halogen bonds involving a p-system can also occur and the applications for these C-XÁ Á Áp interactions are mainly found in biochemical processes [7,10] and supramolecular chemistry [6,39], while only little information on the nature of this type of interaction is available in the literature [23,40]. In order to verify 19 F NMR spectroscopy can also be used as a tool to study the C-XÁ Á Áp halogen bonds, we have studied the formation of a C-IÁ Á Áp halogen bond formed between toluene-d 8 and the perfluoroiodopropanes 1-C 3 F 7 I and 2-C 3 F 7 I.…”