Applications of nuclear quadrupole resonance spectroscopy in drug development

Latosinńska, Jolanta N

doi:10.1517/17460441.2.2.225

Cited by 20 publications

(22 citation statements)

References 112 publications

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“…A combination of experimental and theoretical techniques has certainly much to offer for the studies of drugs or potential drugs in early phases of drug research. Their capabilities in particular when applied to the known drugs, have been well documented in literature [92,99,101,104,105,148,[156][157][158][159][160][161][184][185][186][187][188][189]. Although in some fields the NMR or NQR are not competitive to IR, UV or XRD the examples of combined studies given above show that both techniques have a potential to elicit structural and physico-chemical information about a molecule of dug, target or the interaction drug-target.…”

Section: Discussionmentioning

confidence: 99%

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

Latosińska¹,

Latosińska²

2011

Drug Discovery and Development - Present and Future

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Section: Discussionmentioning

confidence: 99%

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

Latosińska¹,

Latosińska²

2011

Drug Discovery and Development - Present and Future

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“…NQRS has been suggested for the investigation of polymorphic powder samples in different application fields. As reviewed in References [6] and [7] the identification and selection of the right polymorphic form of the active compound of a drug can have significant impact on its stability and bioavailability and is this an important issue in the quality control of pharmaceutics. Typical quadrupolar target nuclei are 35 Cl and 14 N. The latter, however, is more difficult to measure with standard NQRS equipment due to its typically low transition frequencies and, consequently, low SNR which require advanced sampling techniques as presented in References [8,9].…”

Section: Introductionmentioning

confidence: 99%

Tris(2-Methoxyphenyl)Bismuthine Polymorphism Characterized by Nuclear Quadrupole Resonance Spectroscopy

et al. 2019

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Based on the previous identification of metastable polymorphs in crystalline triphenylbismuth by nuclear quadrupole resonance spectroscopy (NQRS), the potential formation of similar phases was studied in Tris(2-Methoxyphenyl)Bismuthine. To this end, commercial samples with known NQRS properties were molten and re-crystallized at different speeds (shock freezing in different coolants versus slow cooling inside of a heater). In all recrystallization products we have identified a new crystal phase which has not been observed after synthesis from a solution. The new crystallographic structure has been confirmed by X-ray diffraction (XRD). The newly isolated polymorph crystallizes in the monoclinic space group P2(1)/c with only one molecule in the asymmetric unit and consequently only one 5/2-7/2 transition is observed at 88.75 MHz at 310 K. In contrast, the two transitions at 89.38 and 89.29 MHz for the well-known trigonal polymorph originate from two crystallographically distinct molecules of Tris(2-methoxy-Phenyl)Bismuthine in the asymmetric unit. Additional relaxometric NQRS shows distinctly different T2 relaxation times for the new polymorph when compared to the original samples. Additional phase transitions could not be observed during temperature sweeps between 153K and 323K.

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“…The failure to detect some nanocrystals, e.g., smaller ones, but not the larger ones can have serious consequences for the interpretation of otherwise simple 14 N NQR spectra and could undermine the reputation of NQR as non-sensitive to the physical form of the sample. This problem has become relevant for 14 N NQR spectroscopy only recently, when pharmaceutical substances, which are often nitrogen containing molecular crystals and can be studied with 14 N NQR, 8,11,16,17 became increasingly more often prepared as nanocrystals embedded in some sort of matrix. Nanocrystals are here preferred due to their large surface area, which increases the dissolution rates, and are of particular importance for poorly water soluble molecules.…”

Section: Introductionmentioning

confidence: 99%

14N NQR lineshape in nanocrystals: An ab initio investigation of urea

Gregorovič

2017

The Journal of Chemical Physics

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N nuclear quadrupole resonance (NQR) lineshapes mostly contain information of low interest, although in nanocrystals they may display some unexpected behaviour. In this work, we present an ab initio computational study of the N NQR lineshapes in urea nanocrystals as a function of the nanocrystal size and geometry, focusing on the surface induced broadening of the lineshapes. The lineshapes were obtained through a calculation of the electric field gradient for each nitrogen site in the nanocrystal separately, taking into account the individual crystal field by embedding the molecule of interest in a suitable lattice of point multipoles representing other urea molecules in the nanocrystal. The small influence of distant molecules is found with a series expansion, using the in-crystal Sternheimer shieldings which we also calculated ab initio. We have considered nanocrystals with two geometries: a sphere and a cube, with characteristic sizes between 5 and 100 nm. Our calculations suggest that there is a dramatic difference between the linewidths for the two geometries. For spheres, we find a steep drop in linewidths at ∼10 nm; at 5 nm the linewidth is ∼11 kHz, whereas for sizes above 20 nm the linewidth is practically negligible (<100 Hz). For cubes, on the other hand, we find a steady 1/size decrease, from 12 kHz at 10 nm to 1.2 kHz at 100 nm. This analysis is important for N NQR spectroscopy of crystalline pharmaceuticals, where nanoparticles are increasingly more often embedded in some sort of matrix. Although this is only a theoretical analysis, we believe that this work can serve as a guidance for the forthcoming experimental analysis.

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Applications of nuclear quadrupole resonance spectroscopy in drug development

Cited by 20 publications

References 112 publications

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

Tris(2-Methoxyphenyl)Bismuthine Polymorphism Characterized by Nuclear Quadrupole Resonance Spectroscopy

14N NQR lineshape in nanocrystals: An ab initio investigation of urea

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