NMR crystallography of 2-acylamino-6-[1H]-pyridones: Solid-state NMR, GIPAW computational, and single crystal X-ray diffraction studies

Ośmiałowski, Borys; Kolehmainen, Erkki; Ikonen, Satu; Ahonen, Kari; Löfman, Miika

doi:10.1016/j.molstruc.2011.10.034

Cited by 12 publications

(10 citation statements)

References 47 publications

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“…The synthesis of studied compounds is described in detail elsewhere. 40 Their purity and structure was confirmed by melting point measurements, elemental analysis, 1 H, 13 C and 15 N NMR spectra both in solution and in solid state. The liquid state 1 H and 13 C NMR and 2 D PFG 1 H, 1 H COSY, PFG 1 H, 13 C HMQC and PFG 1 H,X (X = 13 C and 15 N) HMBC spectra were recorded with NMR spectrometer equipped with an inverse detection probehead and a z-gradient accessory for structure verification and chemical shift assignments.…”

Section: ■ Experimental Sectionmentioning

confidence: 91%

“…This is in agreement with the X-ray determined geometry. 40 Since dimer formation alone did not explain the chemical shift behavior upon dilution, calculations also taking trimer into account were included. Due to the large computational cost, other higher associates were not considered, which also can be justified by entropy reasons.…”

Section: Calculated Values (See Supporting Information For Chart and ...mentioning

confidence: 99%

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2-Acylamino-6-pyridones: Breaking of an Intramolecular Hydrogen Bond by Self-association and Complexation with Double and Triple Hydrogen Bonding Counterparts. Uncommon Steric Effect on Intermolecular Interactions

2012

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2-Acylamino-6-pyridones (acyl = RCO, where R = Me, Et, i-Pr, t-Bu, and 1-adamantyl) were previously characterized by X-ray diffractometry and solid-state NMR techniques by us. One of these compounds was used recently in organocatalysis. The series is now studied in solution and by computational methods recommended for noncovalent interactions (DFT/M05). These compounds showed interesting behavior during dilution and titration experiments monitored by (1)H NMR. 2-Acylamino-6-pyridones change their conformation at higher concentrations, forming double hydrogen-bonded dimers and trimers in which an uncommon steric effect is observed. To the best of our knowledge, this is the first example of such behavior of hydrogen-bonded molecules. Heterocomplexation of the studied compounds happens via double or triple hydrogen bonding, depending on the properties of the counterpart. The computation data support and explain the effects observed experimentally, including the tautomeric, closed/open form equilibrium and intermolecular interaction preferences.

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Section: ■ Experimental Sectionmentioning

confidence: 91%

Section: Calculated Values (See Supporting Information For Chart and ...mentioning

confidence: 99%

2-Acylamino-6-pyridones: Breaking of an Intramolecular Hydrogen Bond by Self-association and Complexation with Double and Triple Hydrogen Bonding Counterparts. Uncommon Steric Effect on Intermolecular Interactions

2012

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“…The recording of NMR spectra and solution of the solid-state structures by X-ray diffractometry were performed as described in our previous papers.…”

Section: Methodsmentioning

confidence: 99%

2-Acylamino- and 2,4-Bis(acylamino)pyrimidines as Supramolecular Synthons Analyzed by Multiple Noncovalent Interactions. DFT, X-ray Diffraction, and NMR Spectral Studies

et al. 2012

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Intermolecular interactions of ten 2-acylamino and 2,4-bis(acylamino)pyrimidines (7 of which are previously unknown) have been investigated by X-ray structural, quantum chemical (DFT), and NMR spectral methods. Especially the concentration dependencies of the (1)H NMR chemical shifts and titrations with other molecules capable of multiple hydrogen bonding provided useful information regarding their association via triple or quadruple hydrogen bonding, which is controlled by the conformational preferences of 2-acylamino- and 2,4-bis(acylamino)pyrimidines. On comparison of the properties of 2-acylamino- and 2,4-bis(acylamino)pyrimidines with the corresponding pyridines, an additional nitrogen in the heterocyclic ring is the crucial factor in explaining the stability of various conformers and dimers of pyrimidines. Computational modeling of their dimerization (self-association) and heteroassociation supports the experimental findings. The substituent effects in 2-acylamino- and 2,4-bis(acylamino)pyrimidines are discussed via inter- and intramolecular terms. The subtle balance between several structural factors and their influence on the aggregation of studied pyrimidines was confirmed also by variable-temperature NMR and NOE experiments. X-ray structures of 2-methyl- and 2-adamantyl-CONH-pyrimidines revealed very different intermolecular interactions, showing the importance of the substituent size on the self-assembly process. As a whole NMR spectral, X-ray structural, and computational data of 2-acylamino- and 2,4-bis(acylamino)pyrimidines can be interpreted in terms of multiple intra-/intermolecular interactions.

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“…A number of spectacular applications of NMR crystallography in structural studies of small molecules, mostly pharmaceuticals, have been published thus far by Emsley, Brown, Harris − and others. − In our recent paper, we demonstrated the power of this methodology in the analysis of the N-terminal sequence of dermorphin, which belongs to a group of opioid peptides that interact with G-protein-coupled receptors (GPCRs) …”

Section: Introductionmentioning

confidence: 99%

Fine Refinement of Solid-State Molecular Structures of Leu- and Met-Enkephalins by NMR Crystallography

Pawlak

Potrzebowski

2014

J. Phys. Chem. B

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This paper presents a methodology that allows the fine refinement of the crystal and molecular structure for compounds for which the data deposited in the crystallographic bases are of poor quality. Such species belong to the group of samples with molecular disorder. In the Cambridge Crystallographic Data Center (CCDC), there are approximately 22,000 deposited structures with an R-factor over 10. The powerful methodology we present employs crystal data for Leu-enkephalin (two crystallographic forms) with R-factor values of 14.0 and 8.9 and for Met-enkephalin (one form) with an R-factor of 10.5. NMR crystallography was employed in testing the X-ray data and the quality of the structure refinement. The GIPAW (gauge invariant projector augmented wave) method was used to optimize the coordinates of the enkephalins and to compute NMR parameters. As we reveal, this complementary approach makes it possible to generate a reasonable set of new coordinates that better correlate to real samples. This methodology is general and can be employed in the study of each compound possessing magnetically active nuclei.

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NMR crystallography of 2-acylamino-6-[1H]-pyridones: Solid-state NMR, GIPAW computational, and single crystal X-ray diffraction studies

Cited by 12 publications

References 47 publications

2-Acylamino-6-pyridones: Breaking of an Intramolecular Hydrogen Bond by Self-association and Complexation with Double and Triple Hydrogen Bonding Counterparts. Uncommon Steric Effect on Intermolecular Interactions

2-Acylamino-6-pyridones: Breaking of an Intramolecular Hydrogen Bond by Self-association and Complexation with Double and Triple Hydrogen Bonding Counterparts. Uncommon Steric Effect on Intermolecular Interactions

2-Acylamino- and 2,4-Bis(acylamino)pyrimidines as Supramolecular Synthons Analyzed by Multiple Noncovalent Interactions. DFT, X-ray Diffraction, and NMR Spectral Studies

Fine Refinement of Solid-State Molecular Structures of Leu- and Met-Enkephalins by NMR Crystallography

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