Hydrogen/Deuterium-Isotope Effects on NMR Chemical Shifts and Symmetry of Homoconjugated Hydrogen-Bonded Ions in Polar Solution

The understanding of the relation between the NMR parameters and the nature of strong or low-barrier hydrogen bonds in polar but aprotic environments is crucial for the elucidation of enzymatic reaction pathways using NMR spectroscopy. 1 Of special interest are homoconjugated symmetric ions where the loss of the molecular symmetry induced by intermolecular interactions can be probed by measuring H/D-isotope effects on the NMR chemical shifts without complications arising from equilibrium isotope effects. Furthermore, systems with intermolecular hydrogen bonds are not exposed to steric strain as systems with intramolecular hydrogen bonds and are, therefore, better models of interactions of flexible amino acid side chains. The development of solvents which allow one to obtain NMR spectra at low temperatures has improved the requirement of this method to reach the slow hydrogen bond exchange regime even for small model systems. For example, the Freon mixture CDF 3/CDF2Cl (1:2) is liquid down to 90 K, 2 and its dielectric constant increases from about 20 at 170 K to about 40 at 100 K 2e which provides a convenient way to vary the solvent polarity. Using this methodology we have been able to measure the H/Disotope effects on multinuclear NMR chemical shifts of tetranbutylammonium (TBA) hydrogen diacetate and of bis-2,4,6trimethyl pyridinium (bis-collidinium) tetrafluoroborate as models for the interactions of the side chains of aspartic acid and histidine. The choice of these ions was motivated by the analogy to interacting amino acid side chains such as aspartic acid or histidine in active sites of enzymes. 3 For comparison we have reexamined also the [FHF] and the hydrogen maleate anion with TBA as counterion, for which low-temperature data have not yet been reported. To facilitate the discussion we summarize in Scheme 1 the expected H/D-isotope effects on the geometry of linear symmetric hydrogen bonded systems. We remind that these effects arise from zero-point vibrations, whereas equilibrium geometries are isotopeindependent within the Born -Oppenheimer approximation. Case (a) depicts the symmetric single-well potential where the deuteron is more confined to the hydrogen bond center than the proton due to a smaller amplitude of the zero-point stretching vibration. This effect leads to a small contraction of the heavy atom distance upon deuteration, as was demonstrated theoretically 4a and experimentally4b,c for [FHF]-. Case (b) corresponds to a symmetric double-well potential with delocalized protons and deuterons oscillating between the two wells with the tunnel frequency ν. In other words, the proton and or deuteron eigenstates are delocalized eigenstates of the vibrational Hamiltonian. As compared to the proton, the deuteron is shifted away from the hydrogen bond center. 5a,b,dIn addition, the heavy atom distance of the deuterated bridge is larger than in the protonated bridge. The geometric isotope effects in case (c) are similar, but now intraand intermolecular interactions have destroyed the symmetry of the proton potential leading to a proton localization in either the left or the right well. Both forms interconvert via a rate process characterized by a rate constant k. In Figure 1a the low-temperature NMR signals of [FHF] and [FDF]are depicted. As expected, they are split by scalar coupling with a normal ratio of JFH/JFD. A primary low-field shift p∆(H/D) ≡ δ(FDF) δ(FHF) ) 0.32 ppm and a secondary high field fluorine shift 2∆F(D) ≡ δ(FDF) δ(FHF) ) -0.37 ppm are observed. These values are independent of temperature in the range between 110 and 170 K, and they are almost identical to those obtained previously 5a,c for acetonitrile between 250 and 300 K. The new information obtained here is then that geometry of [FHF]is almost independent of the solvent polarity and temperature and that the symmetry of the ion is only slightly perturbed by intermolecular interactions. This finding is in agreement with a single well potential as depicted in case (a). The main source of the observed H/D-isotope effects on the 1H and 19F chemical shifts is that the deuteron is more effectively confined to the hydrogen bond center as compared to the proton, as indicated by the double arrow in Scheme 1a. This interpretation is in agreement with our recent findings of the dependence of 1H and 19F chemical shifts of (FH) nF clusters upon the hydrogen bond geometry 5d and with the discussion of single well potentials in intramolecular hydrogen bonds by Forsen et al.5a,b,e In the case of the maleate anion (Figure 1b) we observe a primary isotope effect of p∆(H/D) ) δ(ODO) δ(OHO) ) 0.08 ppm, which is slightly larger than the value of +0.03 ppm reported in ref 5a (-55 °C, CD2Cl2) and a vanishing value in ref 6a ( +25 °C, CDCl3). The secondary and tertiary isotope effects on the carbon chemical shifts are found to be 2∆C(D) ) -0.07 ppm for C1, and3DC(D) ) -0.05 ppm for the C2 (signal not shown), which exceed the experimental error of about 0.01 ppm. These results have been also explained 6 in terms of case (a), but the solvent and temperature conditions start now to play a role.