In press, in Chemical Physics Letters (CPL). Yes, the blog has taken a bit of a turn, from high explosives to illicit drugs. I expect my google rating to rise sharply with this post. The protonated form of the 3,4-methylene-dioxymethamphetamine (Ecstasy, but I'll keep the post legit, so it is herein referred to as MDMA) molecule (herein referred to as MDMA:H+) and MDMA:H+ in its crystal cell with a chloride ion (Cl–, the crystal form herein referred to as MDMA:HCl) is shown below in yet another fantastic NanoEngineer-1 rendering (if I do say so myself).
This CPL article is, to some extent, a response to those in the terahertz community who continue to attempt spectral assignments of crystalline and poly-crystalline samples using isolated-molecule quantum chemical calculations. The MDMA:HCl sample and MDMA molecule, as a pair, are a very interesting case study of theory and experiment for reasons detailed below. The spectra, shown below from a previous version of the paper (but the same spectra), show quite a bit of detail that will make sense shortly.
Panel A shows the isolated-molecule calculation for the neutral MDMA molecule at a B3LYP/6-31G(d) level of theory (in red). You will note that this simulated spectrum is in very good agreement with experiment (in black), reproducing all of the major features and showing a number of smaller features that account for shoulders. This agreement was the basis for the assignment of the MDMA:HCl spectrum reported in: G Wang, J Shen, Y Jia. "Vibrational spectra of ketamine hydrochloride and 3,4-methylenedioxymethamphetamine in terahertz range." Journal of Applied Physics 102 (2007) 013106/1-06/4.
The new theoretical analysis reported in the CPL article was instigated by this assignment in this previous publication. Relevant to the measured sample and the previously reported assignment, two points arise that require address.
1. The previous calculation, as reported, was of the neutral MDMA molecule and is reasonably close to the MDMA spectrum shown above (in red. This calculation was redone for the CPL article for comparative purposes). As the experimental THz sample was of solid-state MDMA:HCl, the appropriate form of the molecule to run is not the neutral MDMA molecule, but the protonated form, MDMA:H+. The protonated form has a different vibrational spectrum (shown in green in Panel A) than the isolated molecule form. At the very least, the isolated-molecule to consider for the MDMA:HCl sample must be the protonated form. Interestingly, the re-calculation at B3LYP/6-31G(d) reported for the CPL article predicts a fifth vibrational mode at 48.0 cm-1 that was not reported in the previous study. We do not know if the previous group missed that peak in the write-up, decided that (since it is a low-intensity mode) it was not worth reporting, or if their starting molecular geometry was somehow different so that the other four modes were predicted to be in the same region and this mode was somehow turned off.
2. The solid-state spectrum shown in Panel B at a BP/DNP level of theory does not agree as well as the isolated-molecule MDMA B3LYP/6-31G(d) calculation. That being said, THAT IS NOT THE POINT. The goal of a simulated spectrum IS NOT to obtain the closest spectral agreement with experiment. The goal IS to explain the solid-state spectrum with the best theoretical model possible that, hopefully, is as close to the experimental result as possible. In this case, the solid-state BP/DNP spectrum contains a finite number of vibrational modes that do group according to features in the THz spectrum, making the assignment reasonably straightforward. Interestingly, the two most intense modes in the solid-state BP/DNP calculations involve the motions of the Cl–…H+-N chains, which CANNOT be accounted for in an isolated-molecule calculation of either the neutral MDMA molecule or the protonated MDMA:H+.
In summary, as taken from the CPL paper:
With all of these considerations taken into account in this re-examination of the MDMA.HCl THz spectrum, it is found that this system serves as a fortuitous example of one whose THz spectrum is predicted quite precisely by two very different approaches, but is only described accurately by one that considers the crystal environment and the actual state of the molecule in its solid-state form.
Abstract: The terahertz (THz, far-infrared) spectrum of 3,4-methylene-dioxymethamphetamine hydrochloride (Ecstasy) is simulated using solid-state density functional theory. While a previously reported isolated-molecule calculation is noteworthy for the precision of its solid-state THz reproduction, the solid-state calculation predicts that the isolated-molecule modes account for only half of the spectral features in the THz region, with the remaining structure arising from lattice vibrations that cannot be predicted without solid-state molecular modeling. The molecular origins of the internal mode contributions to the solid-state THz spectrum, as well as the proper consideration of the protonation state of the molecule, are also considered.