Mass-resolved electronic circular dichroism ion spectroscopy

Circular dichroism spectroscopy is widely used to distinguish between nonidentical mirror-image molecules. The technique relies on differential absorption of left versus right circularly polarized light and therefore tends to require solution-phase samples for adequate sensitivity. Daly et al. now report gas-phase circular dichroism spectra of DNA oligonucleotides based on detection of photodetached electrons rather than transmitted light (see the Perspective by Barran). The salient spectral features matched those in solution. Pairing the technique with mass spectrometry enables prior mass selection of particular molecules for analysis. Science , this issue p. 1465 ; see also p. 1426 Electron ejection by left versus right circularly polarized light tracks configurations of gas-phase DNA oligonucleotides. DNA and proteins are chiral: Their three-dimensional structures cannot be superimposed with their mirror images. Circular dichroism spectroscopy is widely used to characterize chiral compounds, but data interpretation is difficult in the case of mixtures. We recorded the electronic circular dichroism spectra of DNA helices separated in a mass spectrometer. We studied guanine-rich strands having various secondary structures, electrosprayed them as negative ions, irradiated them with an ultraviolet nanosecond optical parametric oscillator laser, and measured the difference in electron photodetachment efficiency between left and right circularly polarized light. The reconstructed circular dichroism ion spectra resembled those of their solution-phase counterparts, thereby allowing us to assign the DNA helical topology. The ability to measure circular dichroism directly on biomolecular ions expands the capabilities of mass spectrometry for structural analysis.