Experimental boundaries of the quantum rotor induced polarization (QRIP) in liquid state NMR Maik Icker, Pascal Fricke, Toni Grell, Julia Hollenbach, Henry Auer and Stefan Berger* The Haupt-effect is a rather seldom used hyperpolarization method. It is based on the interdependence between nuclear spin states and rotational states of nearly free rotating methyl groups having C 3 symmetry. A sudden change in temperature from 4.2 K to room temperature by fast dissolution yields considerably enhanced 13 C and 1 H resonance signals. This phenomenon is now termed quantum rotor induced polarization. More than 40 substances have been studied by this approach in order to identify them as polarizable by the ‘Haupt-effect in the liquid state’. Influencing factors have been analyzed systematically. It could be concluded that substances having a high tunneling frequency, which is due to a small and narrow potential barrier, are most likely to feature quantum rotor induced polarization-enhanced signals. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: Haupt effect; hyperpolarization; quantum rotors Introduction The sensitivity issue of NMR can be addressed by several means such as DNP, [1–3] (photo-)CIDNP, [4,5] optical pumping, [6] and para-H 2 experiments. [7] Recently, we have shown that a simple experimental approach yields a 13 C signal enhancement for the methyl carbon of γ-picoline (1) of about ×100. [8] The signal shape is an antiphase multiplet, which can be manipulated by a spin echo for the purpose of obtaining an in-phase pattern. The latter step is essential to transfer the hyperpolarization efficiently from the methyl group to other carbons within the pyridine ring. [9] We attributed this polarization phenomenon to the Haupt-effect, [10–21] which arises from the inherent interdependence between nuclear spin states and rotational states of nearly free rotating methyl groups having C 3 symmetry. Because of some differences in the mechanism, a more general description of the ‘liquid state Haupt-effect’ with ‘quantum rotor induced polarization’ (QRIP) [21] might be the more appropriate term. Despite a currently missing full theory, this paper aims at giving our complete experimental results that we obtained during our studies of this polarization phenomenon in the liquid state. Results and Discussion Primarily, we have been interested in identifying further substances featuring this extraordinary polarization phenomenon, which simply results from cooling the pure substance in liquid helium (4.2 K) and subsequently dissolving it rapidly with standard NMR solvents and measuring them at room temperature. Methylpyridines The molecule yielding the largest signal enhancement by the use of this procedure is γ-picoline (1) (Scheme 1), which exhibits a polarization factor of up to ε = 200 for the 13 C methyl resonance. Therefore, we investigated different methylpyridine isomers. Remarkably, the α-form (2) and β-form (3) of picoline do not permit any signal polarization. A close analog to γ-picoline (1) is the 1,4-dimethylpyridinium salt 4, but a spectral change after cooling cannot be obtained. However, there is a 20-fold gain in polarization of the 13 C methyl signal of γ-picoline-N-oxide 5 (Fig. 1). These findings nicely illustrate the complex nature in exploring new substances for QRIP as intermolecular interactions (structure within the solid) dominate the probability of the effect instead of the isolated molecular structure alone. Considering lutidines, the 2,6-dimethylpyridine (6) features an interesting effect (Fig. 2). The carbon resonance of 2/6-C yields a significant enhancement by a factor of ε ≈ 14, whereas the methyl group signal only shows a slight influence (ε ≈ 2). In general, an effect on the nearby carbon spins (ipso-C) can also be found for other compounds such as γ-picoline but they typically have a larger methyl group polarization. In contrast, no polarization effect is observed for the isomer 3,5-lutidine (7) as well as for 2,4,6-trimethyl pyridine (8) or 2-methyl quinoline (9) (Scheme 2) Methyl groups in differently hybridized bonds We tried to figure out experimentally if a trend does exist being useful to predict whether a compound is capable of showing the QRIP by simply comparing methyl groups in different intra- molecular environments. sp 3 –sp 3 bonds Methyl group resonances of alkyl chains do not exhibit any change in polarization by pre-cooling at 4.2 K. This is due to the * Correspondence to: Stefan Berger, Institute of Analytical Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig, Germany. E-mail: stberger@rz.uni- leipzig.de Institute of Analytical Chemistry, University of Leipzig, Johannisallee 29, 04103, Leipzig, Germany Magn. Reson. Chem. 2013, 51, 815–820 Copyright © 2013 John Wiley & Sons, Ltd. Research article Received: 15 August 2013 Revised: 14 September 2013 Accepted: 18 September 2013 Published online in Wiley Online Library: 28 October 2013 (wileyonlinelibrary.com) DOI 10.1002/mrc.4021 815