Gas-Phase Spectroscopy of Nucleobase Complexes

Gas-phase spectroscopy of nucleobase complexes has emerged as a powerful approach to interrogate the intrinsic structural and electronic properties of DNA and RNA building blocks free from solvent effects. By combining advanced mass spectrometric techniques with laser-based spectroscopies and quantum chemical calculations, researchers can probe protonation, metal‐ion coordination and tautomeric equilibria at the molecular level. Such studies have revealed how metal cations—including alkali, alkaline‐earth and transition metals—alter hydrogen-bonding patterns, induce alternative base-pairing motifs and stabilise noncanonical structures such as i-motifs. Infrared multiple photon dissociation (IRMPD) action spectra in the fingerprint and N–H/O–H regions provide vibrational signatures of specific binding modes, while collision-induced dissociation (CID) experiments yield insights into bond strengths and fragmentation pathways. Complementary density functional theory (DFT) calculations enable unambiguous assignment of observed bands and prediction of low-energy conformers. These combined efforts illuminate fundamental interactions that underlie mutagenesis, nucleic acid catalysis and drug-target recognition, offering a gas-phase benchmark against which solution and biological environments can be compared.

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Gas-Phase Spectroscopy of Nucleobase Complexes publication trend

The graph below shows the total number of articles in gas-phase spectroscopy of nucleobase complexes across all publications each year (not limited to Nature Index journals).

Technical terms

Infrared Multiple Photon Dissociation (IRMPD) Spectroscopy: A technique in which multiple infrared photons are absorbed by mass-selected ions, causing vibrational excitation and subsequent fragmentation, thereby yielding action spectra that reflect molecular vibrations.

Electrospray Ionisation (ESI): A soft ionisation method that transfers molecules from solution to gas phase as charged droplets, enabling the analysis of intact biomolecular complexes by mass spectrometry.

Collision-Induced Dissociation (CID): A process in which accelerated ions collide with inert gas molecules, leading to controlled fragmentation that provides information on bond strengths and structural connectivity.

Density Functional Theory (DFT): A quantum chemical computational approach that describes electronic structure in terms of electron density, allowing prediction of molecular geometries, energies and vibrational spectra.

Tautomer: One of two or more isomeric forms of a molecule that differ only in the position of a proton and the double bond, often leading to distinct hydrogen-bonding and electronic properties.

N-Glycosidic Bond: The covalent linkage between the sugar moiety and the nucleobase in nucleosides and nucleotides, whose stability and cleavage pathways are central to fragmentation studies.

References

1. Interaction of Cu + with cytosine and formation of i-motif-like C–M + –C complexes: alkali versus coinage metals. Physical Chemistry Chemical Physics (2016).
2. Insights into Cisplatin Binding to Uracil and Thiouracils from IRMPD Spectroscopy and Tandem Mass Spectrometry. Journal of The American Society for Mass Spectrometry (2020).
3. Gas-Phase Internal Ribose Residue Loss from Mg-ATP and Mg-ADP Complexes: Experimental and Theoretical Evidence for Phosphate-Mg-Adenine Interaction. Journal of The American Society for Mass Spectrometry (2022).