Electron Density Analyses of Opioids: A Comparative Study

The electron densities of five morphine related molecules (codeine, diprenorphine, naltrexone in the neutral
and protonated states, and dextromethorphan) were determined from high-resolution X-ray diffraction
experiments (Mo Kα and synchrotron primary radiation) at low temperature and CCD area detection techniques.
Bond topological analyses were applied, and a partitioning of the molecules into atomic regions making use
of Bader's zero flux surfaces yielded atomic volumes and charges. The obtained atom and bonding properties
were compared to the results of a previous experimental study of morphine and to theoretical calculations.
Experimental and theoretical properties for all chemically equivalent bonds agree within an uncertainty range
as is otherwise seen for different theoretical calculations. Hence, the transferability of chemically equivalent
submolecular properties, being a key issue of the atoms in molecules (AIM) theory, has been verified
experimentally in this class of chemically related molecules. On the other hand, topological differences could
clearly be verified in regions with different chemical environments. Electron density differences between the
two forms of naltrexone were examined and made visible in an extendend region around the nitrogen atom
which is once in a neutral state and once in a positively charged state.