Di(ethylene glycol) methyl ether methacrylate (DEGMA) gels align small organic molecules in metanol.

MANUELA E. GARCÍA; SHANNON R. WOODRUFF; ERICH HELLEMANN; NICOLAY V. TSAREVSKY; ROBERTO R. GIL.

Atlanta Georgia

Congreso; SMASH 2014, Small Molecules Are Still Hot NMR Conference; 2014

SMASH Organization

Di(ethylene glycol) methyl ether methacrylate (DEGMA) gels align small organic molecules in methanol Manuela E. García,1,2 Shannon R. Woodruff,3 Erich Hellemann,1 Nicolay V. Tsarevsky,3 and Roberto R. Gil. Residual dipolar couplings (RDCs) analysis has been successfully applied to the constitutional, configurational and conformational analysis of small organic molecules within the last 10 years. [ , , ] This approach is particularly useful for structural problems, in which conventional NMR experiments such as NOE and 3J coupling constant analysis fail to provide a unique solution. The measurement of RDCs relies on the partial orientation of the molecule of interest, for which a so called alignment medium is necessary. While a series of adequate alignment media exists for aqueous solutions and apolar organic solvents, only few orienting media are reported for polar organic solvents, such as DMSO or methanol [ , ] and the compressed gels method developed in our group has been limited to the use of PMMA gels swollen in CDCl3 and CD2Cl2. One of the objectives of this work was to develop an orienting gel that would exhibit good alignment properties in methanol-d (CD3OD) since it is a solvent for sugars and peptides, which are an important class of molecules that are insoluble in other organic solvents. Herein we propose the use of compressed DEGMA (di(ethylene glycol) methyl ether methacrylate) gels for partial orientation of molecules dissolved in methanol. Some characteristics of these gels are their low cost and ease of preparation, their chemical structure without aromatic rings to minimize chemical shift perturbation, and flexibility to have reversible compression. Briefly, gels rods were prepared in disposable NMR tubes by polymerizing di(ethylene glicol) monomethyl ether methacrylate (DEGMA) in the presence of various amounts of the cross-linker ethylene glycoldimethacrylate (EGDMA), initiated by V-70 (2,2´-azobis(2,4-dimethyl-4-methoxyvaleronitrile) at 50 °C, for 6 hrs. After confirming gelation, gels were let to dry. Then, gels were swollen in CH3OH to wash the remaining monomer. Subsequent, they were let to dry again, cut in 2.5 cm rod and finally swollen in CD3OD inside a 5mm NMR tube. Retrorsine, a member of the natural pyrrolizidine alkaloids family was used to test the alignment capabilities of our gel. This molecule has four stereocenters, and its configuration is well established as RRRS (see below). Retrorsine (3 mg) was dissolved in CD3OD (200 µL), poured into the NMR tube containing the swollen gel, and the gel was gently compressed and decompressed several times (pumping action) with a Shigemi plunger. A 1D 2H NMR spectrum was collected to measure the 2H quadrupolar splitting of the solvent signal, in order the evaluate the degree of alignment. A small quadrupolar splitting value small values for the ?OD signal (~7 Hz) with the gel fully compressed. Pure-shift J-Scaled BIRD HSQC spectra (See Erich Hellemann et al. poster abstract for SMASH 2014) were acquired in both isotropic and anisotropic conditions. Due to the low viscosity of methanol and to the low degree of alignment, the resolution of both, isotropic and anisotropic spectra was very similar. 1DCH RDCs were extracted as the difference between the corresponding couplings measured. Fitting of the RDC data to all possible configurations/conformation combinations, alignment tensor determination, back computation of RDC values, and calculation of quality factors Q were performed using MSpin. The goodness of fit between experimental and back computed RDCs was expressed in terms of the Cornilescu quality factor Q.