Backbone conformation affects duplex initiation and duplex propagation in hybridisation of synthetic H-bonding oligomers

Forming the first intramolecular H-bond is straightforward, but forming subsequent intramolecular interactions is difficult, because the backbone imposes more severe constraints.


Synthesis of 9 1
A mixture of 8 (3.8 g, 14 mmol), ethane-1,2-diol (0.08 ml, 14 mmol) and a catalytic amount of p-toluenesulfonic acid in toluene (80 ml) was refluxed for 12 h under nitrogen. After cooling to room temperature, the solution was washed with water (3 x 100 mL) and brine (1 x 100 ml), dried with MgSO 4 , and the solvent was removed under reduced pressure. The crude product was then purified by column chromatography on silica eluting with hexane /DCM from 0 to 20% DCM. The product was isolated as a yellow oil (1.87 g, 44%).

Binding studies
All binding constants were measured by means of NMR titrations. A known concentration of host solution (0.5-1 mM) in deuterated toluene or chloroform was prepared. A fraction of the host stock solution (0.45-0.6 ml) was transferred to a NMR tube. The guest solution (1-10 mM) was then prepared by dissolving it in the host stock solution. In this way the concentration of host is maintained constant throughout the titration. 31 P NMR spectra were recorded after successive additions of aliquots of guest solution. The observed changes in chemical shift were analysed using a purpose-written fitting program in Microsoft Excel.
Errors are quoted as two times the standard deviation.
Figure S1 a) 31 P NMR chemical shift as a function of guest concentration for addition of 5a to 5b. The line represents the best fit to a 1:1 binding isotherm; b) 162 MHz 31 P NMR titration data for addition of 5a to 5b in toluene-d8 at 298 K; c) 31 P NMR chemical shift as a function

Molecular mechanic calculations 2
Molecular mechanic calculations were performed using MacroModel version 9.8 (Schrödinger Inc.). All structures were minimized first and the minimized structures were then used as the starting molecular structures for all MacroModel conformational searches.
The force field used was MMFFs as implemented in this software. The charges were defined by the force field library and no cut off were used for non-covalent interaction. H-bonds were fixed by constraining the distance between the phenolic hydroxyl and phosphine oxide functionalities to 2 ± 1 Å. A Polak-Ribiere Conjugate Gradient (PRCG) was used and each structure was subjected to 10000 iterations. The minima converged on a gradient with a threshold of 0.01. Conformational search was performed from previously minimized structures using 10000 steps. Only the structures in a 5 kJ·mol -1 windows from the global minimum were analysed.

X-ray structure of the AA 2-mer of backbone N8
Pure compound (3 mg) was dissolved in MeCN (1 mL) in an NMR tube, resulting in crystallization after 3 days at room temperature. Crystals suitable for X-ray crystallography were selected using an optical microscope and examined at 100 K on a Bruker SMART APEX-II CCD diffractometer operating with a Cu Kα sealed tube X-ray source. The structures were solved using SHELXL-97 and refined using WinGX V1.64.05.23.24. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were placed in idealised position. Figure S3. X-ray structure of derivative AA 2-mer (backbone N8) in ORTEP view (ellipsoids are drawn at 50% probability level).