Related Experiment Video
Updated: May 9, 2025
Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae
Published on: January 10, 2018
Unraveling the Crystal Structures of Picolinic Acid Derivatives: Synthesis, Packing, Interactions, and Conformational
Sara Camorali1, Lorenzo Tei1, Marco Milanesio1
1Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121, Alessandria, Italy.
None:
Picolinic acid and its derivatives are widely used as pendant arms in ligands for metal ion complexation, with possible biomedical applications, when exploited in the preparation of magnetic resonance imaging contrast agents and radioisotope labeling for α- and β-therapy. Its structural and electronic characteristics make picolinic acid versatile and able to form stable complexes with various metal ions. The present study reports the synthesis of four picolinic acid derivatives useful for both coordination and bioconjugation, featuring a benzyl-protected hydroxy group removable via palladium-catalyzed hydrogenolysis. Chromatography and magnetic resonance assessed the purity, identity, and structural features of the synthesized compounds, ensuring their suitability for the said applications. Single-crystal X-ray diffraction was exploited for structure solution of three of them, revealing that the introduction of specific substituents induces changes in both the molecular structure and the crystal packing, driven by a balance between π-stacking and weak nonbonding contacts. Small changes in the pyridine substituents can induce conformational changes in the opposite benzyl ring orientation, spanning from a planar to a perpendicular orientation. The structural analysis, including Hirshfeld surfaces and energetic frameworks calculations, clarified intermolecular interactions contributing to a better understanding of the solid state behavior of the title compounds.
Related Concept Videos
01:28Structures of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the...
02:42Ionic Crystal Structures
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
02:34Molecular Structure and Acidity
The size effect explains the change in atomic size on acidity. When comparing the acids formed from elements that belong to the same column in the periodic table, their atomic sizes...
02:11Conformations of Cyclohexane
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
02:46Crystal Field Theory - Tetrahedral and Square Planar Complexes
Crystal field theory (CFT) is applicable to molecules in geometries other than octahedral. In octahedral complexes, the lobes of the dx2−y2 and dz2 orbitals point directly at the ligands. For tetrahedral complexes, the d orbitals remain in place, but with only four ligands located between the axes. None of the orbitals points directly at the tetrahedral ligands. However, the dx2−y2 and dz2 orbitals (along the Cartesian axes) overlap with the ligands less than...
02:18Fischer Projections