14N ultra-wideline (UW), 1H{15N} indirectly-detected HETCOR (idHETCOR) and 15N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of 14N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. A case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes. For most of the APIs, it was possible to acquire frequency-stepped UW 14N SSNMR spectra of stationary samples, which display powder patterns corresponding to pseudo-tetrahedral (i.e., RR′R′′NH+ and RR′NH2+) or other (i.e., RNH2 and RNO2) nitrogen environments. Directly-excited 14N NMR spectra were acquired using the WURST-CPMG pulse sequence, which incorporates WURST (wideband, uniform rate, and smooth truncation) pulses and a CPMG (Carr-Purcell Meiboom-Gill) refocusing protocol. In certain cases, spectra were acquired using 1H → 14N broadband cross-polarization, via the BRAIN-CP (broadband adiabatic inversion – cross polarization) pulse sequence. These spectra provide 14N electric field gradient (EFG) tensor parameters and orientations that are particularly sensitive to variations in local structure and intermolecular hydrogen-bonding interactions. The 1H{15N} idHETCOR spectra, acquired under conditions of fast magic-angle spinning (MAS), used CP transfers to provide 1H–15N chemical shift correlations for all nitrogen environments, except for two sites in acebutolol and nicardipine. One of these two sites (RR′NH2+ in acebutolol) was successfully detected using the DNP-enhanced 15N{1H} CP/MAS measurement, and one (RNO2 in nicardipine) remained elusive due to the absence of nearby protons. This exploratory study suggests that this combination of techniques has great potential for the characterization of solid APIs and numerous other organic, biological, and inorganic systems.

/pdf/natural-abundance-14n-and-15n-solid-state-nmr-of-1njdrbdltj.pdf

Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs

14N-NQR based device for detection of explosives in landmines

https://bilder.buecher.de/zusatz/20/20830/20830285_lese_1.pdf

Nuclear quadrupole resonance spectroscopy

A series of transition-metal organometallic complexes with commonly occurring metal-chlorine bonding motifs were characterized using (35)Cl solid-state NMR (SSNMR) spectroscopy, (35)Cl nuclear quadrupole resonance (NQR) spectroscopy, and first-principles density functional theory (DFT) calculations of NMR interaction tensors. Static (35)Cl ultra-wideline NMR spectra were acquired in a piecewise manner at standard (9.4 T) and high (21.1 T) magnetic field strengths using the WURST-QCPMG pulse sequence. The (35)Cl electric field gradient (EFG) and chemical shielding (CS) tensor parameters were readily extracted from analytical simulations of the spectra; in particular, the quadrupolar parameters are shown to be very sensitive to structural differences, and can easily differentiate between chlorine atoms in bridging and terminal bonding environments. (35)Cl NQR spectra were acquired for many of the complexes, which aided in resolving structurally similar, yet crystallographically distinct and magnetically inequivalent chlorine sites, and with the interpretation and assignment of (35)Cl SSNMR spectra. (35)Cl EFG tensors obtained from first-principles DFT calculations are consistently in good agreement with experiment, highlighting the importance of using a combined approach of theoretical and experimental methods for structural characterization. Finally, a preliminary example of a (35)Cl SSNMR spectrum of a transition-metal species (TiCl4) diluted and supported on non-porous silica is presented. The combination of (35)Cl SSNMR and (35)Cl NQR spectroscopy and DFT calculations is shown to be a promising and simple methodology for the characterization of all manner of chlorine-containing transition-metal complexes, in pure, impure bulk and supported forms.

A study of transition-metal organometallic complexes combining 35Cl solid-state NMR spectroscopy and 35Cl NQR spectroscopy and first-principles DFT calculations.

Nuclear quadrupole resonance (NQR) is a solid-state radio frequency (RF) spectroscopic technique that allows for the detection of many narcotics and highly explosive substances. Unfortunately, the practical use of NQR is often restricted by the presence of strong RF interference (RFI). In this letter, extending our recent work on stochastic NQR (sNQR), we propose acquiring signal-of-interest free samples, containing only corrupting signals, and exploiting them to reduce the effects of RFI on conventional NQR (cNQR) measurements. Similar to the sNQR case, the presented detectors are able to substantially outperform previous cNQR detectors when RFI is present.

Countering Radio Frequency Interference in Single-Sensor Quadrupole Resonance

Theoretical and practical aspects of using multi-pulse spin-locking and the “strong off-resonant comb” (SORC) sequence for detecting nitrogenated substances by the nuclear quadrupole resonance method were studied. A number of optimum correlations between the parameters of multi-pulse sequences and the relaxation characteristics of the substances under investigation were determined. The obtained relations were used for the fast detection of α-trinitrotoluene (TNT). Relaxation parameters and temperature coefficients for twelve 14N lines of the orthorhombic phase of TNT measured at room temperature are also presented. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

On the NQR detection of nitrogenated substances by multi‐pulse sequences

A number of methods for cancelling magnetoacoustic and piezoelectric ringing signals in the spectroscopy of the nuclear quadrupole resonance are presented. The suggested methods include using the sequence (ϕ0)ϕ-(τ-ϕx-2τ-ϕ
 y
 -2τ-ϕ−x
 -2τ-ϕ−y
 -τ)
 n
 and a multipulse analog of the two-pulse Hahn sequence with the first pulse replaced by a short steady-state sequence. Another method presented is the method of orthogonal effective fields for a fast saturation of the quadrupole spin system which can be used for subtracting the magnetoacoustic and piezoelectric components from the signal. The suggested methods can be used for the practical purposes of detecting explosive substances and narcotics.

Multipulse sequences for explosives detection by NQR under conditions of magnetoacoustic and piezoelectric ringing

Modification of the steady-state free precession (SSFP) multipulse technique for the effective detection of nuclear quadrupole resonance (NQR) signals was studied. This modification is based on the use of the preparatory pulse in the SSFP pulse sequences. It was shown that under certain conditions the total intensity of accumulated NQR signal can be increased. Experimental results of applying the proposed technique to nitrogen-14 NQR in the sample of sodium nitrite (NaNO2) are presented and convincingly demonstrate the technique’s effectiveness.

T.N. Rudakov

Papers

On the NQR detection of nitrogenated substances by multi‐pulse sequences

Multipulse sequences for explosives detection by NQR under conditions of magnetoacoustic and piezoelectric ringing

Modified multipulse technique for the effective detection of pure nuclear quadrupole resonance

Optimised NQR pulse technique for the effective detection of Heroin Base.

Modified steady-state free precession pulse sequences for the detection of pure nuclear quadrupole resonance.