Analysis of isomeric mixtures by molecular rotational resonance spectroscopy

Abstract

Recent developments in molecular rotational resonance (MRR) spectroscopy that have enabled its use as an analytical technique for the precise determination of molecular structure are reviewed. In particular, its use in the differentiation of isomeric compounds—including regioisomers, stereoisomers and isotopic variants—is discussed. When a mixture of isomers, such as resulting from a chemical reaction, is analyzed, it is highly desired to be able to unambiguously identify the structures of each of the components present, as well as quantify them, without requiring complex sample preparation or reference standards. MRR offers unique capabilities for addressing this analytical challenge, owing to two factors: its high sensitivity to a molecule's structure and its high spectral resolution, allowing mixtures to be resolved without separation of components. This review introduces core theoretical principles, an introduction to MRR instrumentation and the methods by which spectra can be interpreted with the aid of computational chemistry to correlate the observed patterns to molecular structures. Recent articles are discussed in which this technique was applied to help chemists complete challenging isomer analyses. Developments in the use of MRR for chiral analysis and in the measurement of isotopically labeled compounds are also highlighted.

Application of Laser-Induced Acoustic Desorption for Molecular Rotational Resonance Spectroscopy

“…As MRR data sets have an exceptionally high spectral resolution (Figure 4), 3,4 MRR can be used to directly analyze complex mixtures of organic compounds with minimal spectral overlap. 30 In order to test the mixture analysis capabilities of LIAD/MRR, spectra were measured for an equimolar mixture of vanillin and coumarin in methanol (49 μmol of each, 3.17 mg of mixture deposited on foil). The specific transition frequencies mentioned above for these compounds were monitored after translating the laser beam twice in different locations across the width of a titanium foil coated with the mixture.…”

“…It also decomposes upon heating, thus making it a thermally labile compound and an ideal LIAD/MRR target. l -Alanine has previously been investigated using laser ablation with MRR; the limitations of that technique have been discussed above. ,, Coumarin and vanillin were chosen because they are nonvolatile (boiling points of 301 and 285 °C, respectively) but have low melting points (71 and 81 °C, respectively). The isomeric compounds vanillin, o-vanillin, and isovanillin were selected to demonstrate the ability to differentiate between isomers.…”

“…Neon gas efficiently cools gas-phase molecules during supersonic expansion and minimizes clustering, which results in high resolution and sensitivity. 30 The transfer line was a Swagelokfitted stainless-steel tube (OD 1/4 in., length 3.5 in). The LIAD chamber and transfer line were heated to a constant temperature that was maintained using a Proportional− Integral−Derivative (PID) controller, with temperatures ranging from 100 up to 170 °C.…”

“…Neon gas (research grade, Praxair) was used as the carrier gas to transfer the volatilized analytes into the vacuum chamber of the MRR through a pulsed valve. Neon gas efficiently cools gas-phase molecules during supersonic expansion and minimizes clustering, which results in high resolution and sensitivity . The transfer line was a Swagelok-fitted stainless-steel tube (OD 1/4 in., length 3.5 in).…”

An Automated, Highly Selective Reaction Monitoring Instrument Using Molecular Rotational Resonance Spectroscopy

“…Molecular rotational resonance (MRR) spectroscopy is a gas-phase spectroscopic technique with the ability to directly identify and quantify individual components out of reaction mixtures without the need for chromatographic separation, 19 making it an attractive technique for online reaction monitoring. MRR resolves compounds directly through measurement of their rotational angular momentum transitions, which are directly tied to the molecule's structure through its three-dimensional moments of inertia.…”