DOI: 10.1038/NCHEM.1496 Halogen-Bonding-Triggered Supramolecular Gel Formation Lorenzo Meazza, Jonathan A. Foster, Katharina Fucke, Pierangelo Metrangolo*, Giuseppe Resnati* and Jonathan W. Steed* Contents: 1. Synthesis and co-gels preparation... 2 2. Characterization of 1 3 co-gel...6 3. Characterization of 2 3 co-gel.10 4. Characterization of 4 5 co-gel. 12 5. Characterization of 4 1 co-gel.15 6. DSC data for 1 and 1 3 16 1 NATURE CHEMISTRY www.nature.com/naturechemistry 1
1. Synthesis and co-gel preparation General All NMR spectra were performed on a Varian Mercury-400 (400 MHz for 1H), Varian Inova-500 machine (500 MHz for 1H, 126 Hz for 13 C{ 1 H}) and were referenced to residual solvent. Low resolution mass spectroscopy was undertaken using a Thermo-Finnigan LTQ FT machine running in positive electron spray (ES) mode. HRMS were recorded on a LCT Premier XE ESI mass spectrometer (Waters Ltd., UK). Powder diffraction was performed on glass slides using a Bruker D8 X-Ray Diffractometers using CuKα radiation at a wavelength of 1.5406 Å. Differential scanning calorimetry was undertaken on a Perkin Elmer Pyris 1 DSC or TA instruments Q1000 DSC using 1 mg of sample weighed into the centre of an aluminium pan and heated from 0-220 C at 10 C per minute. Suitable single crystals were mounted using perflouropolyether on a thin glass fibre or preformed tip. Crystallographic measurements were carried out using a Bruker SMART 6K (6000 CCD), Oxford Diffraction Gemini. The instruments are equipped with a graphite monochromatic Mo-Kα radiation (λ = 0.71073). The data collection temperature was maintained using by an open flow N 2 Oxford Cryostream device. Integration was carried out using SAINT. Data sets were corrected for Lorentz and polarization effects and for the effects of absorption. Structures were solved using direct methods (SHELXS-97) 1 and developed using alternating cycles of least-squares refinement and difference Fourier synthesis using OLEX2. 2 All non-hydrogen atoms were treated as anisotropic. Hydrogen atoms were fixed in idealised positions and allowed to ride on the parent atom to which they are attached. Hydrogen atom thermal parameters were tied to those of the parent atom. Where possible N-H and O-H hydrogen atoms were located experimentally and their position and displacement parameters refined or their position parameters constrained to ideal distances from the parent atoms. Molecular graphics were produced using the program X-Seed. 3 Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre, and is provided in CIF format in the supplementary files: Cif_1-3 (CCDC reference 905040) and Cif_2-3 (CCDC 905041). CIFCHECK reveals alerts for low data completion to the very high θ values measured. The data are complete to the usual 25 o, however. Samples prepared for SEM were applied directly to silicon wafer chips (Agar Scientific) using a cocktail stick for gels or pipettes for liquids and the solvent allowed to evaporate. Samples were stored under vacuum at 1x10-5 mbar then sputter coated with 5nm platinum in a Cressington 328 coating unit, at 40mA (density 21.09 and tooling set at 1) with rotation and a 30 0 angle of tilt. Samples were imaged using a Hitachi S-5200 field emission scanning electron microscope at 1.5kV. Rheology experiments were performed using a TA Instruments Advanced Rheometer 2000. A 40 mm steel plate geometry was used with a gap of 500 µm and 4 ml of sample in each case. Samples were prepared by weighing 0.04 g of gelator into an 7 ml glass vial along with 4 ml of toluene (1 % w/v). The vials were sealed and heated until the gelator had fully dissolved (care must be taken due to pressure build up). The samples were rapidly cooled in a water bath and briefly sonicated at the first sign of precipitation to ensure homogeneous gel formation. The gel was transfered onto the centre of the plate of the rheometer using a spatula and the plate squashed the gel resulting in the loss of some solvent. Frequency sweep measurements were performed over a range of 1 to 100 Hz with a constant osc. stress of 10 Pa. Oscillatory stress measurements were performed over a range of 0.01-100 % strain at a constant frequency of 1 Hz. Oscillatory stress sweep measurements were preformed over a range of 0.01-300 Pa with a constant frequency value of 1 Hz. 2 NATURE CHEMISTRY www.nature.com/naturechemistry 2
Synthesis of gelator 4 A solution of 2,3,5,6-tetrafluoro-4-iodoaniline (0.7 g, 2.4 mmol) and triethylamine (0.045 ml) in 2 ml of toluene was added dropwise, over several hours, to a refluxing solution of 1,4-butane diisocyanate (0.152 ml, 1.2 mmol) in 5 ml of toluene. The mixture was then stirred under reflux for 4 days and the resulting precipitate isolated by filtration before being purified by trituration in methanol. Yield 0.34 g, 0.48 mmol, 40%. M.p. (217-219) C. 19 F NMR (DMSO-d 6 ), δ= 124.25 (dd, 2F, J = 23.0 and 6.8 Hz), 145.33 (dd, 2F, J = 24.4 Hz and 6.9). 1 H NMR (DMSO-d 6 ), δ= 1.43 (m, 2 CH 2 ), 3.08 (m, 2 CH 2 ), 6.55 (s, 2 NH), 8.35 (s, 2 NH). 13 C{ 1 H} NMR (DMSO-d 6 ), δ= 26.96, 119.22, 140.33, 142.66, 145.06, 147.51, 153.97. MS: m/z (%): 722 (M +, 100), 619 (35). The sample for analysis was further purified by recrystallization from DMF. Elemental analysis, calc. for 4 0.6DMF: C, 31.07, H, 2.14, N, 8.42 %; found, C, 31.45, H, 2.26, N, 8.11%. Presence of tightly bound DMF confirmed by 1 H NMR spectroscopy. HR-MS ES : m/z 720.8865 [M-H] -, calc. for C 18 H 11 N 4 O 2 F 8 I 2, 720.8844. HRMS and 13 C{ 1 H} NMR data shown below. 3 NATURE CHEMISTRY www.nature.com/naturechemistry 3
Preparation of 1 3 co-gel 0.01 g of 1 (0.03 mmol) and 0.012 g of 3 (0.03 mmol) are mixed in a small vial and 1 ml of the chosen solvent is added. The suspension is then sonicated and heated until the solid is dissolved. The hot vial is immerged in an ultrasonic bath for about one minute until a light white color appears and the transparency of the solution decreases. At this stage the bath is removed and the sample is left at room temperature for about one hour and a white gel is obtained (in some cases a CO 2 /Acetone bath has been used instead of the water bath). Preparation of 2 3 co-gel 0.01 g of 2 (0.023 mmol) and 0.092 g of 3 (0.023 mmol) are mixed in a small vial and 0.9 ml of a MeOH/water 5/4 mixture are added to the solid. The suspension is then sonicated and heated until the solid is dissolved. The hot vial is immerged in an acetone/dry ice bath for about one minute until a light white color appears and the transparency of the solution decreases. At this stage the bath is removed and the sample is left at room temperature for about one hour and a white gel is obtained. 4 NATURE CHEMISTRY www.nature.com/naturechemistry 4
Preparation of 4 5 co-gel 0.01 g of 4 (0.014 mmol) and 0.006 g of 5 (0.042 mmol) are mixed in a small vial and 1 ml of a mixture DMSO/water 6/2 is added to the solid. The suspension is then sonicated and heated until the solid is dissolved. The hot vial is immerged in the sonicator water bath for about one minute until the transparency of the solution decreases. At this stage the bath is removed and the sample is left at room temperature for about one hour and a gel is obtained. Preparation of 4 1 co-gel 0.005 g of 4 (0.007 mmol) and 0.003 g of 1 (0.007 mmol) are mixed in a small vial and 1 ml of a mixture DMSO/water 6/2 is added to the solid. The suspension is then sonicated and heated until the solid is dissolved. The hot vial is immerged in the sonicator water bath for about one minute, the bath is then removed and the sample is left at room temperature for about one hour and a very transparent gel is obtained. 5 NATURE CHEMISTRY www.nature.com/naturechemistry 5
2. Characterization of 1 3 co-gel Figure S1: XRPD pattern of the 1 3 xerogel Figure S2: Comparison of the experimental XRPD pattern of the 1 3 xerogel (shown in blue) with the calculated pattern obtained from the single crystal of the complex 1 3 (shown in red) 6 NATURE CHEMISTRY www.nature.com/naturechemistry 6
Figure S3: Comparison of the XRPD pattern of the 1 3 xerogel obtained from MeOH/Water 8/2 (shown in blue) with the one obtained from MeOH (shown in red) 7 NATURE CHEMISTRY www.nature.com/naturechemistry 7
Figure S4: Comparison of the XRPD pattern of the 1 3 xerogel obtained from MeOH using 2 equivalents of compound 3 (shown in blue) with the one obtained from MeOH using 1 equivalent of compound 3 (shown in red) Figure S5: Comparison of the XRPD pattern of the 1 3 xerogel obtained from MeOH/Water 8/2 (shown in blue) with the one obtained from DMSO/Water 7/3 (shown in red) Figure S6: SEM images of compound 1 8 NATURE CHEMISTRY www.nature.com/naturechemistry 8
DOI: 10.1038/NCHEM.1496 Figure S7: SEM images of 1 3 xerogel Figure S8: Stress sweep rheology of 1 3 co-gel obtained using 1 equivalent of compound 3 (closed circles) compared with the same measurement for 1 3 co-gel obtained using 0,3 equivalents of compound 3 (open circles). Solvent: MeOH/Water 8/2 NATURE CHEMISTRY www.nature.com/naturechemistry 9 9
3. Characterization of 2 3 co-gel Figure S9: XRPD pattern of the 2 3 xerogel Figure S10: Comparison of the experimental XRPD pattern of the 2 3 xerogel (shown in blue) with the calculated pattern obtained from the single crystal of the complex 2 3 (shown in red) 10 NATURE CHEMISTRY www.nature.com/naturechemistry 10
Figure S11: SEM images of 2 3 xerogel Figure S12: Stress sweep rheology of 2 3 co-gel 11 NATURE CHEMISTRY www.nature.com/naturechemistry 11
4. Characterization of 4 5 co-gel Figure S13: 19 F-NMR of 4 5 co-gel (the co-gel was filtered and dissolved in DMSO-d 6 ) 12 NATURE CHEMISTRY www.nature.com/naturechemistry 12
Figure S14: 1 H-NMR of 4 5 co-gel (the co-gel was filtered and dissolved in DMSO-d 6 ) Figure S15: XRPD pattern of the 4 5 xerogel 13 NATURE CHEMISTRY www.nature.com/naturechemistry 13
DOI: 10.1038/NCHEM.1496 Figure S16: SEM images of 4 5 xerogel Figure S17: Stress sweep rheology of 4 5 co-gel obtained using 2 equivalents of compound 5 (closed circles) compared with the same measurement for 4 5 co-gel obtained using 3 equivalents of compound 5 (open circles) NATURE CHEMISTRY www.nature.com/naturechemistry 14 14
DOI: 10.1038/NCHEM.1496 5. Characterization of 4 1 co-gel Figure S18: SEM images of 4 1 xerogel NATURE CHEMISTRY www.nature.com/naturechemistry 15 15
Figure S19: DSC data for 1 and cocrystal 1 3. 1 SHELXS-97 (University of Göttingen, 1997). 2 Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J. App. Cryst. 42, 339-341, (2009). 3 Barbour, L. J. X-Seed - A software tool for supramolecular crystallography. J. Supramol. Chem. 1, 189-191, (2001). 16 NATURE CHEMISTRY www.nature.com/naturechemistry 16