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Infrared multiple photon dissociation (IRMPD) spectroscopy is a powerful tool used to probe the vibrational modes–and, by extension, the structure—of an ion within an ion trap mass spectrometer. Compared to traditional FTIR spectroscopy, IRMPD spectroscopy has advantages including its sensitivity and its relative ability to handle complex mixtures. While IRMPD has historically been a technique for fundamental analyses, it is increasingly being applied in a more analytical fashion. Notable recent demonstrations pertinent to the clinical laboratory and adjacent interests include analysis of modified amino acids/residues and carbohydrates, structural elucidation (including isomeric differentiation) of metabolites, identification of novel illicit drugs, and structural studies of various biomolecules and pharmaceuticals. Improvements in analysis time, coupling to commercial instruments, and integration with separations methods are all drivers toward the realization of these analytical applications. Additional improvements in these areas, along with advances in benchtop tunable IR sources and increased cross-discipline collaboration, will continue to drive innovation and widespread adoption. The goal of this tutorial article is to briefly present the fundamentals and instrumentation of IRMPD spectroscopy, as an overview of the utility of this technique for helping to answer questions relevant to clinical analysis, and to highlight limitations to widespread adoption, as well as promising directions in which the field may be heading.

OH⋅-induced oxidation products of DNA nucleosides and nucleotides have been structurally characterized by collision-induced dissociation tandem mass spectrometry (CID-MS 2 ) and Infrared Multiple Photon Dissociation (IRMPD) spectroscopy. CID-MS 2 results have shown that the addition of one oxygen atom occurs on the nucleobase moiety. The gas-phase geometries of +16 mass increment products of 2'-deoxyadenosine (dA(O)H + ), 2'-deoxyadenosine 5'-monophosphate (dAMP(O)H + ), 2'-deoxycytidine (dC(O)H + ), and 2'-deoxycytidine 5'-monophosphate (dCMP(O)H + ) are extensively investigated by IRMPD spectroscopy and quantum-chemical calculations. We show that a carbonyl group is formed at the C8 position after oxidation of 2'-deoxyadenosine and its monophosphate derivative. For 2'-deoxycytidine and its monophosphate derivative, the oxygen atom is added to the C5 position to form a C-OH group. IRMPD spectroscopy has been employed for the first time to provide direct structural information on oxidative lesions in DNA model systems., (© 2023 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Abstract: Interactions of halide anions (Cl−, Br−, and I−) with glutamic acid (Glu), histidine (His), and arginine (Arg) and their effects on stabilizing the zwitterionic form of these amino acids were investigated using infrared multiple photon dissociation (IRMPD) spectroscopy between 850 and 1900cm−1 and hybrid density functional theory. The IRMPD spectra of Glu·X− and His·X− each have a diagnostic carbonyl stretching band at ∼1750cm−1 from a carboxylic acid group, indicating that the nonzwitterionic form of these amino acids is most stable. In contrast, a broad band at ∼1625cm−1 for Arg·X−, consisting of the antisymmetric stretch of a carboxylate group and hydrogen bonded NH bends, clearly shows that Arg is zwitterionic in these complexes. There are many similarities between these spectra and those of cationized amino acids, which aid in spectral interpretation. Cl− and Cs+ are of comparable size, and attachment of either ion to these amino acids has little effect on the frequencies of these diagnostic carbonyl stretches. The coordination of cations to these amino acids is different from that of anions, resulting in a favorable alignment of the dipole moment of the carbonyl group with the electric field of ions of either polarity, which causes a redshift in this band, i.e., a Stark effect. There is a slight redshift (∼10cm−1) in the carbonyl stretch band at ∼1750cm−1 for Glu·X− and His·X− with decreasing anion size, consistent with both a Stark effect and with greater carboxylate character for the carboxylic acid group in complexes with the less acidic halide ions. The anion size has little effect on the structures and relative zwitterion stabilities for most of these complexes, which can be attributed to the large size of the halide anions investigated compared to that of the alkali metal cations where size effects are more pronounced. The spectra calculated for the lowest energy structures are generally consistent with the experimental spectra, although no single structure accounts for the many distinct bands in the IRMPD spectra of His·X−. [Copyright &y& Elsevier]

Infrared multiple photon dissociation (IRMPD) spectroscopy is a powerful tool used to probe the vibrational modes-and, by extension, the structure-of an ion within an ion trap mass spectrometer. Compared to traditional FTIR spectroscopy, IRMPD spectroscopy has advantages including its sensitivity and its relative ability to handle complex mixtures. While IRMPD has historically been a technique for fundamental analyses, it is increasingly being applied in a more analytical fashion. Notable recent demonstrations pertinent to the clinical laboratory and adjacent interests include analysis of modified amino acids/residues and carbohydrates, structural elucidation (including isomeric differentiation) of metabolites, identification of novel illicit drugs, and structural studies of various biomolecules and pharmaceuticals. Improvements in analysis time, coupling to commercial instruments, and integration with separations methods are all drivers toward the realization of these analytical applications. Additional improvements in these areas, along with advances in benchtop tunable IR sources and increased cross-discipline collaboration, will continue to drive innovation and widespread adoption. The goal of this tutorial article is to briefly present the fundamentals and instrumentation of IRMPD spectroscopy, as an overview of the utility of this technique for helping to answer questions relevant to clinical analysis, and to highlight limitations to widespread adoption, as well as promising directions in which the field may be heading., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 THE AUTHORS.)

The gas-phase structure of protonated β-methylaminoalanine was investigated using infrared multiple photon dissociation spectroscopy in the C-H, N-H, O-H stretching region (2700-3800 cm -1 ) and the fingerprint region (1000-1900 cm -1 ). Calculations using density functional theory methods show that the lowest energy structures prefer protonation of the secondary amine. Formation of hydrogen bonds between the primary and secondary amine, and the secondary amine and carboxylic oxygen further stabilize the lowest energy structure. The infrared spectrum of the lowest energy structure originating with harmonic density functional theory has features that generally match the positions of the experimental spectra; however, the overall agreement with the experimental spectrum is poor. Molecular dynamics calculations were used to generate a gas-phase infrared spectrum. With these calculations a reasonable match with the experimental spectrum, especially in the high-energy region, was obtained. The results of the molecular dynamics simulation support the density functional theory calculations, with protonation of the secondary amine and the formation of a hydrogen bond between the protonated secondary amine and the primary amine. This work shows the importance of accounting for anharmonic effects in systems with very strong intramolecular hydrogen bonding.