Orthogonal halogen and hydrogen bonds involving a peptide bond model

N-Methylacetamide, a well-known peptide bond model, and dihalotetrafluorobenzenes form co-crystals and show geometrically orthogonal hydrogen and halogen bonds sharing the same carbonyl oxygen atom.


S.1 Supramolecular synthesis
Starting materials 1 and 2a-f were purchased from commercial suppliers (Sigma-Aldrich, Apollo Scientific, and ABCR) and used without further purification. 1 was first mixed with each of the compounds 2a-f in a molar 1:1 ratio. Solid mixtures were then dissolved in chloroform and all samples were sonified for 10 min. In a second type of procedure the solid mixtures were heated up until complete melting, stirred for one hour, and cooled down to room temperature (RT).
S.2 Crystallization procedure and crystal structure determination 1, 3a, and 3b were in situ cryo-crystallized on the diffractometer in sealed 0.3 mm Lindemann capillaries according to the reported procedure. 1 3c-f were dissolved in and crystallized from chloroform by slow evaporation method at room temperature (from hours to days). Suitable crystals were chosen for the single crystal X-ray study. To check the reproducibility and to avoid any solvent interference, suitable single crystals were also obtained from their melts by slow cooling to RT, which resulted in the same crystal phases.
The crystals were measured using Mo-Kα radiation on a Bruker KAPPA APEX II diffractometer with a Bruker KRIOFLEX low temperature device. Crystal structures were solved by direct method and refined against F 2 using SHELXL97. 2 Packing diagrams were generated using the CSD software Mercury 3.3. 3 Intermolecular interactions were analyzed with PLATON. 4 The non-hydrogen atoms were refined anisotropically and hydrogen atoms were refined using difference Fourier map or positioned geometrically. The NMA molecule in all of the determined co-crystal structures is disordered, which appears mainly from a static randomness of molecular orientation. 5 For the measurement of distances and angles of intermolecular interactions in 3a-f, the major component atoms of the disordered NMA molecules were considered. Crystal structures were deposited in the CSD database. CCDC 899779 -899785 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

S.3 CSD survey
For the CSD search (ConQuest Version 1.15, 2013), following parameters were defined: Two component systems (number of chemical units = 2); oxygen atom of the R 2 C=O group shares both halogen and hydrogen bonds; intermolecular interactions are within the sum of VdW radii + 0.2 Å; angle X···O···Y (X = any halogen, Y = any atom of Y-H group). Outcome: 535 entries with a X···O···Y angle distribution in the range 26.27-176.75°

S.4 Differential Scanning Calorimetry (DSC) data
DSC analyses were performed using a Mettler Toledo DSC 823e instrument. 1.5-2.5 mg of each sample were measured in a closed aluminum pan with heating/cooling rates of 10 °C/min or 5 °C/min. In the case of 12-DBrTFB, two reversible phases were observed. 19 F-NMR spectrum of 2a (Fig. S2) confirmed the purity of the starting material. This thermal behavior of the sample may correspond to solid-solid phase transition between two polymorphic modifications and is not induced by impurities.   (2) 100 (2) 100 (2) 100 (2) 100 (2) 100 (2) 100(2) Adduct 3a crystallizes in monoclinic P2 1 /c space group and Z = 4 (Table S2) Adduct 3b was obtained in a monoclinic P2 1 /n space group with four molecules in the unit cell (Table S2). The intermolecular interactions and crystal packing are similar to those of 3a (Fig. S5b). As shown in  (Fig. S3). 3d crystallizes in a triclinic P-1 space group (Table S2)

S.8 Intermolecular interactions in 1 and 3a-f
Table S3 Intermolecular interactions in 1 and 3a-f. Interactions involved in the formation of the orthogonal XB/HB synthon are highlited in bold.

S.9 R 2 C=O in-and out-of-plane interactions
The plane was set through four atoms of an NMA molecule: C1, C2, N1 and O1. The angle between the R 2 C=O plane and an involved HB or XB was measured to determine the out-of-plane deviation.

Table S4
In-and out-of R 2 C=O plane angles for hydrogen and halogen bonds in 1 and 3a-f.