Quantifying hydrogen-bonding strength: the measurement of 2hJNN couplings in self-assembled guanosines by solid-state 15N spin-echo MAS NMR

Abstract

^2h J _NN hydrogen-bond mediated J couplings are measured in the solid state for two synthetic deoxyguanosine derivatives by ¹⁵N MAS NMR spin-echo experiments. The use of rotor-synchronised Hahn-echo pulse train (RS-HEPT) ¹H decoupling, with a duty cycle of 6%, allows spin-echo durations out to 200 ms, hence enabling the accurate determination of J couplings as small as 3.8 Hz. A single-crystal X-ray diffraction structure exists for the shorter alkyl chain derivative dG(C₃)₂: the observation of significantly different ^2hJ_NN couplings, 6.2 ± 0.4 and 7.4 ± 0.4 Hz, for the two resolved N7 resonances is to be expected given the NH⋯N hydrogen-bonding distances of 2.91 and 2.83 Å for the two distinct molecules in the asymmetric unit cell. For the longer alkyl chain derivative, dG(C₁₀)₂, for which there is no single-crystal diffraction structure, a ¹⁵N refocused INADEQUATE spectrum (Pham et al., J. Am. Chem. Soc., 2005, 127, 16018–16019) has demonstrated the presence of N2–H⋯N7 intermolecular hydrogen-bonds indicative of a quartet-like structure. The ^2hJ_NN hydrogen-bond mediated J coupling of 5.9 ± 0.2 Hz is at the lower end of the range (5.9–8.2 Hz) of ^2hJ_NN couplings determined from solution-state NMR of guanosine quartets in quadruplex DNA. A full discussion of the determination of error bars on the fitted parameters is given; specifically, error bars determined by a non-linear fitting (using the covariance matrix) or in a Monte-Carlo fashion are found to give effectively identical results.