Related Experiment Video
Updated: Jan 16, 2026
06:44
From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding
Published on: March 24, 2018
69.6K
Solid-State NMR Elucidation of Intermolecular Interactions in Venetoclax-Fumaric Acid Cocrystal
Shovik Ray1, Ranadeep Bokalial2, Rahul B Chavan2
1Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore, Karnataka, India.
Magnetic Resonance in Chemistry : MRC
|September 26, 2025
Summary
This study successfully cocrystallized the antileukemia drug venetoclax with fumaric acid, enhancing its properties. Solid-state NMR revealed specific hydrogen bonds driving this cocrystal formation.
Area of Science:
- Pharmaceutical Science
- Solid-State Chemistry
- Drug Delivery
Background:
- Cocrystallization is crucial for improving active pharmaceutical ingredient (API) physicochemical properties like solubility and bioavailability.
- Understanding intermolecular interactions is key for designing cocrystals of complex APIs.
- Venetoclax, an antileukemia drug, presents a complex structure for cocrystallization studies.
Purpose of the Study:
- To investigate the cocrystallization of venetoclax with fumaric acid.
- To confirm the formation of a new cocrystalline phase.
- To elucidate the specific intermolecular interactions governing the cocrystallization process.
Main Methods:
- Powder X-ray Diffraction (PXRD) for phase confirmation.
- Differential Scanning Calorimetry (DSC) for thermal analysis.
- Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy for mechanistic insights.
Main Results:
- A new cocrystalline phase of venetoclax and fumaric acid was successfully formed.
- PXRD and DSC confirmed the formation and thermal properties of the cocrystal.
- Solid-state NMR identified specific hydrogen bonding between venetoclax and fumaric acid.
Conclusions:
- Cocrystallization of venetoclax with fumaric acid is feasible and yields a new phase.
- Specific hydrogen bonds involving aromatic amine, pyrrole, and carboxylic groups are critical for cocrystal formation.
- Complementary techniques like PXRD, DSC, and solid-state NMR are valuable for studying complex pharmaceutical cocrystals.
Related Concept Videos
01:10Recrystallization: Solid–Solution Equilibria
2.5K
Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...
2.5K
02:58Crystal Field Theory - Octahedral Complexes
30.6K
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
30.6K
02:42Valence Bond Theory
11.2K
Coordination compounds and complexes exhibit different colors, geometries, and magnetic behavior, depending on the metal atom/ion and ligands from which they are composed. In an attempt to explain the bonding and structure of coordination complexes, Linus Pauling proposed the valence bond theory, or VBT, using the concepts of hybridization and the overlapping of the atomic orbitals. According to VBT, the central metal atom or ion (Lewis acid) hybridizes to provide empty orbitals of suitable...
11.2K
02:54Molecular and Ionic Solids
19.9K
Crystalline solids are divided into four types: molecular, ionic, metallic, and covalent network based on the type of constituent units and their interparticle interactions.
Molecular Solids
Molecular crystalline solids, such as ice, sucrose (table sugar), and iodine, are solids that are composed of neutral molecules as their constituent units. These molecules are held together by weak intermolecular forces such as London dispersion forces, dipole-dipole interactions, or hydrogen bonds, which...
Molecular Solids
Molecular crystalline solids, such as ice, sucrose (table sugar), and iodine, are solids that are composed of neutral molecules as their constituent units. These molecules are held together by weak intermolecular forces such as London dispersion forces, dipole-dipole interactions, or hydrogen bonds, which...
19.9K
02:46Crystal Field Theory - Tetrahedral and Square Planar Complexes
48.2K
Tetrahedral 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 the dxy,...
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 the dxy,...
48.2K
01:08NMR Spectroscopy: Spin–Spin Coupling
3.0K
The spin state of an NMR-active nucleus can have a slight effect on its immediate electronic environment. This effect propagates through the intervening bonds and affects the electronic environments of NMR-active nuclei up to three bonds away; occasionally, even farther. This phenomenon is called spin–spin coupling or J-coupling. Coupling interactions are mutual and result in small changes in the absorption frequencies of both nuclei involved. While nuclei of the same element are involved...
3.0K