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The solid-state structure of the β-blocker metoprolol: a combined experimental and in silico investigation
- Source :
- Acta Crystallographica. Section C, Structural Chemistry
- Publication Year :
- 2019
- Publisher :
- International Union of Crystallography, 2019.
-
Abstract
- The metoprolol free base has been characterized in the solid state by X-ray diffaction (both single-crystal and variable-temperature powder diffraction) and differential scanning calorimetry. These studies are supplemented by mol­ecular modelling and Hirshfeld surface analysis. Structural relationships with the strictly related betaxolol are discussed.<br />Metoprolol {systematic name: (RS)-1-iso­propyl­amino-3-[4-(2-meth­oxy­eth­yl)phen­oxy]propan-2-ol}, C15H25NO3, is a cardioselective β1-adrenergic blocking agent that shares part of its mol­ecular skeleton with a large number of other β-blockers. Results from its solid-state characterization by single-crystal and variable-temperature powder X-ray diffraction and differential scanning calorimetry are presented. Its mol­ecular and crystal arrangements have been further investigated by mol­ecular modelling, by a Cambridge Structural Database (CSD) survey and by Hirshfeld surface analysis. In the crystal, the side arm bearing the isopropyl group, which is common to other β-blockers, adopts an all-trans conformation, which is the most stable arrangement from modelling data. The crystal packing of metoprolol is dominated by an O—H⋯N/N⋯H—O pair of hydrogen bonds (as also confirmed by a Hirshfeld surface analysis), which gives rise to chains containing alternating R and S metoprolol mol­ecules extending along the b axis, supplemented by a weaker O⋯H—N/N—H⋯O pair of inter­actions. In addition, within the same stack of mol­ecules, a C—H⋯O contact, partially oriented along the b and c axes, links homochiral mol­ecules. Amongst the solid-state structures of mol­ecules structurally related to metoprolol deposited in the CSD, the β-blocker drug betaxolol shows the closest analogy in terms of three-dimensional arrangement and inter­actions. Notwithstanding their close similarity, the crystal lattices of the two drugs respond differently on increasing temperature: metoprolol expands anisotropically, while for betaxolol, an isotropic thermal expansion is observed.
- Subjects :
- crystal structure
02 engineering and technology
Crystal structure
Molecular Dynamics Simulation
010402 general chemistry
Crystallography, X-Ray
01 natural sciences
Solid state structure
Betaxolol
Inorganic Chemistry
Crystal
Differential scanning calorimetry
Materials Chemistry
medicine
Computer Simulation
Physical and Theoretical Chemistry
Metoprolol
Calorimetry, Differential Scanning
Molecular Structure
Chemistry
Hydrogen bond
Hirshfeld surface
Hydrogen Bonding
021001 nanoscience & nanotechnology
Condensed Matter Physics
Research Papers
metoprolol
Adrenergic beta-1 Receptor Antagonists
0104 chemical sciences
Crystallography
in silico
beta-blocker
anisotropic lattice expansion
0210 nano-technology
Isopropyl
Databases, Chemical
Powder Diffraction
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20532296
- Volume :
- 75
- Issue :
- Pt 2
- Database :
- OpenAIRE
- Journal :
- Acta Crystallographica. Section C, Structural Chemistry
- Accession number :
- edsair.doi.dedup.....ad62713522328f0b166d8424077dbd33