Solution to doubling spectroscopy challenge

Analytical and Bioanalytical Chemistry, Feb 2016

Reinhard Meusinger

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Solution to doubling spectroscopy challenge

The winner of the doubling spectroscopy challenge (published in Solution to doubling spectroscopy challenge Reinhard Meusinger 0 1 0 Institute of Organic Chemistry and Biochemistry, University of Technology Darmstadt , Alarich-Weiss-Str. 4, 64287 Darmstadt , Germany 1 Reinhard Meusinger However, the phase of these cross-peaks (red color) is opposite to that of the other NOESY cross-peaks (blue color). This indicates that there is a slow exchange process between both amino protons during the 700-ms continuous mixing time at room temperature. The energy barrier for this exchange process can be calculated using the experimentally determined coalescence temperature Tc and the frequency difference Δν between the separate signals of the amino-group protons. Both of these parameters were determined twice at different magnetic field strengths: - Solution The reason for the signal doubling of the H-6 hydrogen signal in the 1H-NMR spectrum of dexelvucitabine (DFC) is the presence of the fluorine at position 5 (Fig. 1). Fluorine has only one isotope, 19F, with a spin ½ nucleus. Since both 1H-6 and 19F-5 are connected in DFC by a vicinal coupling 3JH6,F5, the NMR signal of each 1H-6 nucleus is split by the interaction with the 19F-5 nucleus and vice versa. Therefore, no cross-peak will be observed for the H-6 doublet in the H,H-COSY spectrum. As expected, noticeable crosspeaks were observed in the NOESY spectrum for interactions between H-6, H-2′, H-5′, and –OH protons, indicating correct signal assignment (Fig. 2). Considerable cross-peaks were also observed between the pair of twin amino proton signals in the NOESY spectrum. T c;300 MHz ¼ 314 K Δν300 MHz ¼ 73:5 Hz T c; 500 MHz ¼ 322 K Δν500 MHz ¼ 123 Hz By using the Boltzmann constant kB, the Planck constant h, and the universal gas constant R, the H-5’ F-5 H-6 H-2’ Fig. 1 Three-dimensional structure of DFC with observed NOEs for proton H-6 (black arrows) Fig. 2 Two-dimensional 1Hcorrelated double quantum filtered COSY spectrum (left) and NOESY spectrum (right) of DFC. The phase of the NOE crosspeaks (blue) is opposite to that of the diagonal peaks (red). The redcolored cross-peaks between both amino protons relate to the intramolecular exchange process 4‘ OH 2‘ 3‘ 1‘ NH2 6 6 6 NH2 1‘ energy of activation can be calculated as the Gibbs energy G# ¼ RTcln ffiffi p 2kBTc πhv G# ¼ 8:314 J K−1 mol−1⋅Tcln 22:96 K−1 s−1⋅Tc=v : T h i s y i e l d s Δ G 3# 0 0 M H z = 6 3 . 7 k J m o l − 1 a n d ΔG500 MHz = 64.0 kJ mol–1. # Accounting for small experimental deviations, a very similar result of 64 kJ mol−1 was obtained in both experiments. 5 '

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Reinhard Meusinger. Solution to doubling spectroscopy challenge, Analytical and Bioanalytical Chemistry, 2016, 1723-1724, DOI: 10.1007/s00216-015-9267-0