It is safe to assume that a large number of forum members are familiar with a concept of enantiomers, substances that have the same molecular formula and connectivity but differ in their three-dimensional arrangement. The root of the reason why D-meth is better than L-meth or why R-modafinil is stronger than a racemic (mixed enantiomers) form of modafinil. Stereometry is a well-understood area of organic chemistry, but there is another dimension in identical materials science which is far less understood and is utterly fascinating. It falls under nucleonic crystallography. Chemical compounds that form crystals can exist in multiple forms. Cocoa butter, for example, has six polymorphic crystal forms. The shiny one that you get from the store, which makes a satisfying crunchy sound is one of them. But let it rest for a while, and it will turn into another polymorph - I am sure you've seen. And once it does, good luck trying to get it back to the original form! Just like radio isotopes of radioactive elements can be more or less stable, some crystal lattice formations of the same polymorphic molecule can be more stable than others. A truly uncanny aspect of polymorph formation is that sometimes once a more stable form of the same material occurs in nature, it can poison the global environment and forever (at least as we know today) prevent the previously dominant, but now less stable form from coming into existence ever again. Note that I said sometimes, which is why we still have six polymorphs of cocoa butter.
One of the most famous cases when this impacted humanity on a great scale is what happened with an anti-HIV drug Ritonavir. Abbott pharmaceuticals introduced the drug in 1996 and in that time it was critical to keeping millions of people alive. Then at some point in 1998 without any warning over a course of a few weeks at a US production facility Ritonavir mutated from an easily soluble pharmaceutically desirable Form I into a far less soluble Form 2, which made the drug far less effective. All process steps in the American facility have been scrutinized to no avail. Nothing has been changed in the pharmaceutical workflow, no new equipment introduced, no sabotage has been discovered, but any Form 1 Ritonavir produced at the lab would quickly undergo phase transformation into Form 2. Luckily, Abbott pharmaceuticals had another lab in Italy which continued to produce Ritonavir in its original up until that point Form 1. A team from US visited the italian facility and compared production steps. Everything proved to be identical and puzzled Abbot scientists returned to the US. But this was not the end of the story. In a few weeks that followed the visit, the italian production facility reported that their lab seemed to have been infected. They could no longer produce Form 1 of Ritonavir. Now this was no chocolate - millions of lives depended on this drug. At that time the industry has not yet developed the many alternatives which we have today to keep HIV patients alive. But all efforts to produce the original Form were fruitless. Abbot has lost $250 million as a result of the incident. It was hypothesized that the visiting US team has brought tiny particles of Form 2 imbedded in either their clothes or, think of pharmaceutical clean room standards - in their own bodies and that was enough to vanquish Form 1 for good.
And this is not the only case. The same problem plagues both chemical and pharmaceutical industry. It can come out of nowhere. We have neither knowledge to predict when this might happen, nor the technology to counter it. If you are a and aspiring chemist, it makes crystallography, the Walter White's choice a promising field. If you could only put away your other experiments...
There is a famous statement by the renowned crystallographer Jack Dunitz who captured the frustration and unpredictability of the field with this observation: "The most stable crystal form of a substance is the one that has yet to be discovered."
Dunitz’s point was that just because you have been using "Form A" for twenty years doesn't mean "Form B" doesn't exist. It just means the conditions (the "seed") to trigger Form B haven't happened yet.
And that brings me to my take on why post-ban mephedrone might never again "feel like the real thing".
One of the most famous cases when this impacted humanity on a great scale is what happened with an anti-HIV drug Ritonavir. Abbott pharmaceuticals introduced the drug in 1996 and in that time it was critical to keeping millions of people alive. Then at some point in 1998 without any warning over a course of a few weeks at a US production facility Ritonavir mutated from an easily soluble pharmaceutically desirable Form I into a far less soluble Form 2, which made the drug far less effective. All process steps in the American facility have been scrutinized to no avail. Nothing has been changed in the pharmaceutical workflow, no new equipment introduced, no sabotage has been discovered, but any Form 1 Ritonavir produced at the lab would quickly undergo phase transformation into Form 2. Luckily, Abbott pharmaceuticals had another lab in Italy which continued to produce Ritonavir in its original up until that point Form 1. A team from US visited the italian facility and compared production steps. Everything proved to be identical and puzzled Abbot scientists returned to the US. But this was not the end of the story. In a few weeks that followed the visit, the italian production facility reported that their lab seemed to have been infected. They could no longer produce Form 1 of Ritonavir. Now this was no chocolate - millions of lives depended on this drug. At that time the industry has not yet developed the many alternatives which we have today to keep HIV patients alive. But all efforts to produce the original Form were fruitless. Abbot has lost $250 million as a result of the incident. It was hypothesized that the visiting US team has brought tiny particles of Form 2 imbedded in either their clothes or, think of pharmaceutical clean room standards - in their own bodies and that was enough to vanquish Form 1 for good.
And this is not the only case. The same problem plagues both chemical and pharmaceutical industry. It can come out of nowhere. We have neither knowledge to predict when this might happen, nor the technology to counter it. If you are a and aspiring chemist, it makes crystallography, the Walter White's choice a promising field. If you could only put away your other experiments...
There is a famous statement by the renowned crystallographer Jack Dunitz who captured the frustration and unpredictability of the field with this observation: "The most stable crystal form of a substance is the one that has yet to be discovered."
Dunitz’s point was that just because you have been using "Form A" for twenty years doesn't mean "Form B" doesn't exist. It just means the conditions (the "seed") to trigger Form B haven't happened yet.
And that brings me to my take on why post-ban mephedrone might never again "feel like the real thing".
