04.07.10
Opiates, Opioids and Freebases
Morphine is a painkiller derived from the poppy plant. The naturally derived form of morphine from the poppy plant is what defines it as an opiate. For the last 200 years morphine has been used as one of the most effective painkillers we know of, interacting directly with the central nervous systems pain receptors.
Morphine as a very effective drug, in part because of its shape. Notice in the above figure, all the ring structures involved. There are essentially 5 rings, which all work together to lock the geometry of the molecule in place. This locking is very important, because it closely matches the shape of the pain receptors(which are actually meant to accept endorphins and have a similar structure) , which accept the nitrogen (Its the “N” on the diagram) as a base, effectively breaking its ring.
There has historically been one big problem with morphine. It’s cripplingly addictive. It you have ever had surgery, and been prescribed codeine afterwards, there is a reason for that. Codeine and Percocet are less effective forms of morphine, synthesized artificially, which gives them the classification Opioids. Although they are still very effective painkillers, they are very specifically made to wean people off of the heavy doses of morphine required for surgery.
We have not always been so lucky. In the late 1800s morphine use was on the rise, and people coming out of hospitals were hopelessly addicted. Around 1895 the German company Bayer released a substitute for morphine, that would provide similar effects to morphine, but without the addictive properties. Such a wonderful and heroic drug, could only have one name. Heroin. Of course in the late 1800s there was a lot of guess work as to the final outcome of these things, and we now know that heroin is not only far more potent than morphine, but it is way more addictive.
So whats the difference? It looks like on the picture there is just a couple ‘O’ things tacked on. Well to see the difference we will go over the structure briefly and what it all means. Everywhere there is a line, that is a chemical bond containing 2 electrons. At the end of every line is an implied Carbon atom. We don’t actually write ‘C’ because it would take forever, and we have precious little time. Every where that there is something that is not carbon, there is a letter signifying which atom is there. O=oxygen, N=nitrogen, H=hydrogen. Those are the basic building blocks we are working with here.
Morphine has 2 alcohol groups (OH) on it. It gives the perfect fit for our brain as it requires this acidic group to be activated. If we could just put the morphine directly into our brain then we would be set. But there’s a problem. Our brain absorbs chemicals through a semipermeable membrane called the Blood Brain Barrier. This membrane lets through certain substances and keeps out others. By and large, this membrane prefers to let through hydrophobic (water hating) molecules.
What molecules hate water? Well there is a general rule in chemistry that ‘Like dissolves like’. Water is a polar molecule, which means that it is not electrically balanced. It has a large electronegative oxygen atom and 2 hydrogen atoms projecting out from it in a sort of a triangle. So we want the opposite for a water hating molecule to cross that membrane. We want a nonpolar group.
Well both of these molecules are polar, but one is significantly less polar than the other. The hydrogen molecules attatched to the oxygens on morphine, for reasons I wont go into here, polarize the molecule, making it less hydrophobic, and decreasing the amount that can cross that membrane. Heroin, however, has what is called an ester group in place of the OH, which has no hydrogens-oxygen bonds, and so has a reduced polarity. This makes it perfect for crossing unhindered across the blood brain barrier and into our cerebralspinal fluid en route to the brain.
Once the heroin has crossed that barrier it reacts with chemicals in the cerebralspinal fluid to convert the esters back into alcohol groups, effectively giving us the morphine molecule back again, but in larger doses to the brain. This would have been good to know in the early 1900s when countless people began using it to curb their addictions ranging from alcohol and cocaine to morphine.
One interesting side note, heroin usually comes as a hydrochloride salt, with the name diacetylmorphine hydrochloride. The reason for this is that the Nitrogen molecule often acts as a base because it has 2 lone electrons associated with it. This makes it partially reactive and hard to isolate. In the presence of HCl however, the base attaches to the hydrogen, and balances with the Chloride counter ion. This gives a solid that can be isolated with great amounts of purity. Note that if you pull the hydrogen away from the nitrogen, a cracking sound can be heard (Where crack got its name) as the pure form of the base is freed. In its pure form as in the illustration above, Heroin and morphine are freebases.
Better living through chemistry.
