The solid-state structure of the β-blocker metoprolol: a combined experimental and <i>in silico</i> investigation

Rossi, Patrizia; Paoli, Paola; Chelazzi, L.; Conti, Luca; Bencini, Andrea

doi:10.1107/s2053229618017084

Cited by 15 publications

(14 citation statements)

References 36 publications

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“…The intermolecular interactions that build up the crystal packings of BE_IV and BE_I were further studied using the Hirshfeld Surface (HS) analysis. As already evidenced by us [10], identical R2,2(10) motifs were found in the metoprolol (XITNIA refcode) [11], propranolol (PROPRA10 refcode) [38] and a reaction intermediate in an alternative route for the synthesis of atenolol (KAZPOQ refcode) [39].…”

Section: H-bonds and Ch-π Interactions Distance (å)supporting

confidence: 65%

“…Its crystal and molecular structure has been studied by experimental and in silico techniques and compared with the already known solid form (α); thermal data suggest that the two polymorphs are in a monotropic relationship. A similar methodological approach has been used to characterize the solid forms of metoprolol both as free base and as succinate, tartrate and fumarate salts [9][10][11]. In particular X-ray diffraction data and computational results have been used to try to correlate solid-state features to thermal behavior (e.g., isotropic vs. anisotropic thermal expansion).…”

Section: Introductionmentioning

confidence: 99%

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Investigating Differences and Similarities between Betaxolol Polymorphs

et al. 2019

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Betaxolol belongs to the class of β1-adrenergic blocking agent. Several polymorphs of racemic betaxolol have been reported in the literature, but only one of them (BE_I) had the crystal structure determined from single-crystal X-ray diffraction. Here, we present a new crystalline phase of betaxolol (BE_IV). Its solid-state structure has been obtained from single-crystal X-ray diffraction data. The molecular and crystal arrangements of betaxolol in BE_IV have been further investigated by molecular modelling, by Cambridge Structural Database (CSD) surveys and by Hirshfeld surface analysis. A comparison with the solid-state structure of BE_I have been carried out. In the two polymorphs the 2-hydroxy-3-(isopropylamino)-propoxy chain, which is common to other β-blocker drugs, adopts a different conformation. In addition, the rotational isomer found in BE_IV is different with respect to the four already observed in the solid-state structure of analogous compounds. In both the polymorphs, the most significant interaction is due to the H-bonds involving the OH group as donor and the NH as acceptor, while the interaction where OH works as acceptor (NH acts as donor) is definitely less important. The resulting H-bond patterns are however different: Alternate R2,2(10) a > a (OH donors) and R2,2(10) b > b (OH acceptors) in BE_I vs. alternate R4,4 (8) a > b > a > b (OH donors) and R2,2 (10) b > b (OH acceptor) in BE_IV.

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Section: H-bonds and Ch-π Interactions Distance (å)supporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Investigating Differences and Similarities between Betaxolol Polymorphs

et al. 2019

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“…Energies involved in phase transformations, together with the related temperatures, can be measured by DSC; in addition, DSC can be used to distinguish between enantiotropic and monotropic systems (Saunders & Gabbott, 2011). Finally, modelling can provide complementary information, such as, for example, the conformational space and the associated potential energy surface of the molecular species, the role of the environment (vacuum versus mimicked solvent) in driving the 3D arrangement of molecules, the directions and strengths of the intermolecular interactions, together with the related contributions (Rossi et al, 2018(Rossi et al, , 2019.…”

Section: Introductionmentioning

confidence: 99%

A new crystal form of the NSAID dexketoprofen

Rossi

Paoli

Ienco³

et al. 2019

Acta Crystallogr C Struct Chem

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Dexketoprofen [(2S)‐2‐(3‐benzoylphenyl)propanoic acid], C16H14O3, is the S‐enantiomer of ketoprofen, a nonsteroidal anti‐inflammatory drug (NSAID) that has analgesic, antipyretic and anti‐inflammatory properties, and finds applications for the short‐term treatment of mild to moderate pain. A new crystalline phase of dexketoprofen is reported. Its solid‐state structure was determined by single‐crystal X‐ray diffraction (SCXRD). The molecular structure of the two independent molecules found in the asymmetric unit of this new phase (DXKP‐β) were compared to those of the already known crystal form of dexketoprofen (DXKP‐α) and with the S‐enantiomer of the racemic compound. The three different conformers of dexketoprofen found in DXKP‐α and DXKP‐β were then investigated by computational methods. The optimized structures are very close to the corresponding starting geometries and do not differ significantly in energy. The crystal packing of DXKP‐β was studied by means of Hirshfeld surface (HS) analysis; interaction energies were also calculated. A comparison with DXKP‐α shows close similarities between the two crystal forms, i.e. in both cases, molecules assemble through the catemer O—H…O synthon of the carboxylic acid stabilized by additional C—H…O contacts and, accordingly, the interaction energies, as well as the contributions to the HS area, are very similar. Finally, the thermal behaviour of the two polymorphs of dexketoprofen was assessed by means of XRD (both from single crystal and microcrystalline powder) and differential scanning calorimetry (DSC); both crystal forms are stable under the experimental conditions adopted (air, 300–350 K for DXKP‐α and 300–340 K DXKP‐β) and no solid–solid phase transition occurs between the two crystal forms in the investigated temperature range (from 100 K up to ca 350 K).

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“…These interactions are related to van der Waals forces of short and long range. Within these interactions, − C − N … X −, − C − N … H −, − C − H … π , − C − X … π , and − C − N … π are the most relevant [17].…”

Section: Introductionmentioning

confidence: 99%

Experimental and DFT Study of the Photoluminescent Green Emission Band of Halogenated (−F, −Cl, and −Br) Imines

et al. 2019

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The morphological, optical, and structural changes in crystalline chiral imines derived from 2-naphthaldehyde as a result of changing the −F, −Cl, and −Br halogen (−X) atoms are reported. Scanning electron microscopy (SEM), optical absorption, photoluminescence (PL), and powder X-ray diffraction (XRD) studies were performed. Theoretical results of optical and structural properties were calculated using the PBE1PBE hybrid functional and compared with the experimental results. Differences in surface morphology, absorbance, XRD, and PL of crystals were due to the change of halogen atoms in the chiral moiety of the imine. Absorption spectra exhibited the typical bands of the naphthalene chromophore located in the ~200–350 nm range. Observed absorption bands in the UV region are associated with π→π* and n→π* electronic transitions. The band gap energy was calculated using the Tauc model. It showed a shift in the ~3.5–4.5 eV range and the crystals exhibited different electronic transitions associated with the results of absorbance in the UV region. XRD showed the monoclinic→orthorhombic crystalline phase transition. PL spectra displayed broad bands in the visible region and all the samples have an emission band (identified as a green emission band) in the ~400–750 nm range. This was associated with defects produced in the morphology, molecular packing, inductive effect and polarizability, crystalline phase transition, and increase in size of the corresponding halogen atoms; i.e., changes presumably induced by −C−X…X−, −C−X…N−, −C−N…π, and −C−X…π interactions in these crystalline materials were associated with morphological, optical, and structural changes.

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The solid-state structure of the β-blocker metoprolol: a combined experimental and in silico investigation

Cited by 15 publications

References 36 publications

Investigating Differences and Similarities between Betaxolol Polymorphs

Investigating Differences and Similarities between Betaxolol Polymorphs

A new crystal form of the NSAID dexketoprofen

Experimental and DFT Study of the Photoluminescent Green Emission Band of Halogenated (−F, −Cl, and −Br) Imines

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