Pain chemistry: part 1

DAVID MANALLACK: Good day. We’ve seen that Ari Contos needs to take morphine to keep his back pain under control. So what is morphine? In this chemistry module, we will take a detailed look at the chemical structure of morphine. Why is it that this plant derived compound has had such a profound effect on human civilisation? Wars have been fought over this molecule. And yet, it remains an important member of our present day medicines. Down in Tasmania, opium poppy plantations contribute significantly to the world’s supply of both morphine and codeine.

To begin with, we will take a look at the molecular structure of morphine. Despite being isolated in the early 1800s, it wasn’t until 1956 that the structure was fully confirmed, highlighting the complexity of its molecular framework.

The structure of morphine comprises five rings that are joined into a specific scaffold. Let’s build up the structure to show you the five rings. We commence with ring A on the left hand side. This ring is benzene with a hydroxyl group attached. Here, we have added another six-membered ring to build up the scaffold. The third ring, C, has a double bond in the ring and has a hydroxyl group attached as well.

The next ring is labelled D and includes an important basic nitrogen atom or amino group. Finally, ring E, with its ether oxygen, ties the structure together.

The special feature of the molecule is that it is reasonably rigid. And why is this important? Well, it means that the key functional groups that give morphine its biological activity, are held in place in specific positions relative to each other. To understand the placement of key functional groups in space, we need to start considering the structure in three dimensions. Molecular structures, however, are not static, and they can often prove to be quite flexible. Shown here is an animation illustrating the dynamic movements of morphine.

I’d now like to show you a very flexible molecule. Clearly, this compound shows greater movement, while morphine did not change its shape to any considerable extent. Returning now to morphine, we are interested in its overall shape. Rotating the structure gives us an insight into the complexity of the molecule.

We also see in this view the T shape of the molecule.

By applying a surface to the compound, we get a better idea of its three dimensional shape.

The rigid nature of morphine means that the important groups needed for biological activity are always placed specifically in three dimensional space. The following article will compare codeine with morphine before we return to the opioid receptor.