The hydrogen bond continuum in solid isonicotinic acid

Blahut, Jan; Štoček, Jakub Radek; Šála, Michal; Dračínský, Martin

doi:10.1016/j.jmr.2022.107334

Cited by 6 publications

(2 citation statements)

References 51 publications

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“…57 This proves important for predicting salt or co-crystal formation corresponding to the transfer or not of a proton, as evidenced by the 1 H chemical shift. 58,59 Dracinsky has investigated geometry optimisation using the hybrid functional B3LYP or the meta-GGA functional rSCAN 60 and observe improved agreement compared to experiment for 1 H chemical shifts, though there is not clear improvement for 13 C chemical shifts. 61 This analysis has been extended to NMR crystallography of amino acids.…”

Section: A Review Of Applications Of Nmr Crystallography To Pharmaceu...mentioning

confidence: 99%

Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls

Rehman,

Lubay,

Franks

et al. 2025

Faraday Discuss.

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Section: A Review Of Applications Of Nmr Crystallography To Pharmaceu...mentioning

confidence: 99%

Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls

Rehman,

Lubay,

Franks

et al. 2025

Faraday Discuss.

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“…34 While potentially appealing, the reliability of this transformation seemed questionable, as further implementation showcased an extremely narrow synthetic application. 35,36,37,38 In addition, a series of pitfalls were identified: i) the need for a long reaction time, incompatible for applications with short-lived 13 N; ii) the inherent two-step nature of the procedure; iii) the wellestablished intolerance of the Zincke reaction towards pyridine substitution. 39 , 40 After preliminary investigations (see SI), we confirmed the narrow synthetic scope of the Zincke strategy and decided to move toward a more convenient approach.…”

Section: Reaction Design and Optimizationmentioning

confidence: 99%

Pyridine-based Strategy towards Nitrogen Isotope Exchange

Feng,

Norlöff,

Guichard

et al. 2023

Preprint

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Isotopic labeling is at the core of health and life science applications such as nuclear imaging, pharmacokinetics and bio-distribution studies and plays a central role in drug development. The rapid access to isotopically labeled organic molecules is a sine qua non condition to support these societally vital areas of research. Despite the relevance of pyridine as a biologically active scaffold, the nitrogen-13 labeling of this scaffold remains elusive and an almost prohibited challenge for radio-labelling (+ emitter, T1/2 9.97 min), despite its relevance in positron emission tomography. Based on a rationally driven approach, this study presents an innovative solution to access labeled pyridines by a nitrogen isotope exchange reaction based on a Zincke activation strategy. The technology conceptualizes a new opportunity in the field of nitrogen isotope labeling. 15N-labeling of pyridine and other heterocycles such as pyrimidines and isoquinolines was provided on a large set of derivatives including structurally elaborated pharmaceuticals. Using [13N]NH3 as the primary nitrogen-13 source, proof-of-concept was provided to achieve examples of 13N-labeling of pyridines. We believe this method will play a fundamental role for future developments of 13N-based PET radiotracers.

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The Hydrogen‐Bond Continuum in the Salt/Cocrystal Systems of Quinoline and Chloro‐Nitrobenzoic Acids

Radek Štoček,

Blahut,

Chalupná

et al. 2024

Chemistry A European J

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This study investigates the hydrogen‐bond geometry in six two‐component solid systems composed of quinoline and chloro‐nitrobenzoic acids. New X‐ray diffraction studies were conducted using both the conventional independent‐atom model and the more recent Hirshfeld atom‐refinement method, with the latter providing precise hydrogen‐atom positions. The systems can be divided into salts (the hydrogen atom transferred to the quinoline nitrogen), cocrystals (the hydrogen atom retained by the acid), and intermediate structures. Solid‐state NMR experiments corroborated the X‐ray diffraction‐derived H–N distances. DFT calculations, using five functionals including hybrid B3LYP and PBE0, showed varying energy profiles for the hydrogen bonds, with notable differences across functionals. These calculations revealed different preferences for salt or cocrystal structures, depending on the functional used. Path‐integral molecular dynamics simulations incorporating nuclear quantum effects demonstrated significant hydrogen‐atom delocalization, forming a hydrogen‐bond continuum, and provided average N–H distances in excellent agreement with experimental results. This comprehensive experimental and theoretical approach highlights the complexity of multicomponent solids. The study emphasizes that the classification into salts or cocrystals is frequently inadequate, as the hydrogen atom is often significantly delocalized in the hydrogen bond. This insight is crucial for understanding and predicting the behavior of such systems in pharmaceutical applications.

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The hydrogen bond continuum in solid isonicotinic acid

Cited by 6 publications

References 51 publications

Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls

Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls

Pyridine-based Strategy towards Nitrogen Isotope Exchange

The Hydrogen‐Bond Continuum in the Salt/Cocrystal Systems of Quinoline and Chloro‐Nitrobenzoic Acids

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