The structure of Rimonabant in the solid state and in solution: an experimental and theoretical study

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Solid-State Chemistry

Background:

• Rimonabant is a selective cannabinoid receptor 1 antagonist.
• Understanding the molecular structure and conformation is crucial for drug design and activity.
• Solvation can influence crystal packing and molecular properties.

Purpose of the Study:

• To elucidate the X-ray molecular structure of Rimonabant methanol solvate.
• To investigate the conformational landscape of Rimonabant using computational methods.
• To correlate theoretical calculations with experimental spectroscopic data.

Main Methods:

• X-ray crystallography was employed to determine the solid-state structure.
• Nuclear Magnetic Resonance (NMR) spectroscopy ((1)H, (13)C, (15)N) was used to analyze the molecule in solution.
• Density Functional Theory (DFT) calculations (B3YP/6-311++G(d,p)) were performed to find minimum energy conformations.
• Gauge-Independent Atomic Orbital (GIAO) calculations were conducted to predict chemical shifts.

Main Results:

• The precise X-ray molecular structure of Rimonabant methanol solvate was determined.
• Two low-energy conformations of Rimonabant were identified through computational modeling.
• Calculated absolute shieldings from GIAO correlated well with experimental NMR chemical shifts.
• The study provides insights into Rimonabant's structural behavior in both solid and solution states.

Conclusions:

• The combined crystallographic and computational approach provides a comprehensive understanding of Rimonabant's structure.
• The agreement between calculated and experimental data validates the chosen computational methods.
• This structural and conformational information can aid in the development of Rimonabant analogs.