Natural Abundance 14N and 15N Solid-State NMR Studies of Organic, Biochemical, and Pharmaceutical Systems

Nitrogen is an important element in all areas of chemistry, biology, and materials science. However, it is challenging to probe directly with solid-state nuclear magnetic resonance (SSNMR). The commonly studied isotope, 15N (nuclear spin, I, = ½), has a low natural abundance (0.36%); therefore, 15N NMR experiments often require isotopically enriched samples. 14N (I = 1) has a high natural abundance (99.64%) but is a quadrupolar nucleus. 14N SSNMR spectra are generally very broad due to the moderate quadrupole moment of 14N. Ultra-wideline (UW) 14N SSNMR spectra have very low signal-to-noise, which complicates their acquisition; however, they are useful probes of molecular-level structure and dynamics, and do not require isotopic enrichment for their acquisition

Ultra-wideline 14N solid-state NMR as a method for differentiating polymorphs: glycine as a case study

Nitrogen-14 solid-state NMR (SSNMR) is utilized to differentiate three polymorphic forms and a hydrochloride (HCl) salt of the amino acid glycine. Frequency-swept Wideband, Uniform Rate, Smooth Truncated (WURST) pulses were used in conjunction with Carr-Purcell Meiboom-Gill refocusing, in the form of the WURST-CPMG pulse sequence, for all spectral acquisitions. The 14N quadrupolar interaction is shown to be very sensitive to variations in the local electric field gradients (EFGs) about the 14N nucleus; hence, differentiation of the samples is accomplished through determination of the quadrupolar parameters CQ and ηQ, which are obtained from analytical simulations of the 14N SSNMR powder patterns of stationary samples (i.e., static NMR spectra). Additionally, differentiation of the polymorphs is also possible via the measurement of 14N effective transverse relaxation time constants, Teff2(14N). Plane-wave density functional theory (DFT) calculations, which exploit the periodicity of crystal lattices, are utilized to confirm the experimentally determined quadrupolar parameters as well as to determine the orientation of the 14N EFG tensors in the molecular frames. Several signal-enhancement techniques are also discussed to help improve the sensitivity of the 14N SSNMR acquisition method, including the use of selective deuteration, the application of the BRoadband Adiabatic INversion Cross-Polarization (BRAIN-CP) technique, and the use of variable-temperature (VT) experiments. Finally, we examine several cases where 14N VT experiments employing Carr-Purcell-Meiboom-Gill (CPMG) refocusing are used to approximate the rotational energy barriers for RNH3+ groups

(14) N solid-state NMR spectroscopy of amino acids

(14) N ultra-wideline solid-state NMR (SSNMR) spectra were obtained for 16 naturally occurring amino acids and four related derivatives by using the WURST-CPMG (wideband, uniform rate, and smooth truncation Carr-Purcell-Meiboom-Gill) pulse sequence and frequency-stepped techniques. The (14) N quadrupolar parameters were measured for the sp(3) nitrogen moieties (quadrupolar coupling constant, CQ , values ranged from 0.8 to 1.5 MHz). With the aid of plane-wave DFT calculations of the (14) N electric-field gradient tensor parameters and orientations, the moieties were grouped into three categories according to the values of the quadrupolar asymmetry parameter, ηQ : low (≤0.3), intermediate (0.31-0.7), and high (≥0.71). For RNH3(+) moieties, greater variation in N-H bond lengths was observed for systems with intermediate ηQ values than for those with low ηQ values (this variation arose from different intermolecular hydrogen-bonding arrangements). Strategies for increasing the efficiency of (14) N SSNMR spectroscopy experiments were discussed, including the use of sample deuteration, high-power (1) H decoupling, processing strategies, high magnetic fields, and broadband cross-polarization (BRAIN-CP). The temperature-dependent rotations of the NH3 groups and their influence on (14) N transverse relaxation rates were examined. Finally, (14) N SSNMR spectroscopy was used to differentiate two polymorphs of l-histidine through their quadrupolar parameters and transverse relaxation time constants. The strategies outlined herein permitted the rapid acquisition of directly detected (14) N SSNMR spectra that to date was not matched by other proposed methods