The chirality of chemical compounds is of undisputed importance in science and technology. In particular with respect to pharmacological application most molecules of interest cannot be accessed by the powerful techniques developed in recent years for gas phase analytes. Here, we demonstrate that the combination of electrospray ionization (ESI) with the detection of photoelectron circular dichroism (PECD) provides access to chirality information applicable to molecular materials with negligible vapor pressure, for example, amino acids. To this end, glutamic acid and 3,4-dihydroxyphenylalanine (DOPA) have been electrosprayed into the source of a chirality spectrometer, where photodetachment is enforced and the PECD is detected. The technique can be expected to be conceptually applicable to all chemical systems with chirality based on molecular properties.

A major obstacle to the gas-phase study of larger (bio)molecular systems is the vaporisation step, that is, the introduction of intact sample molecules into the gas-phase. A promising approach is the use of laser-induced acoustic desorption (LIAD) sources, which have been demonstrated using both nanosecond pulsed and continuous desorption lasers. We directly compare here both approaches for the first time under otherwise identical conditions using adenine as a prototypical biological molecule, and study the produced molecular plumes using femtosecond multiphoton ionisation. We observe different desorption mechanisms at play for the two different desorption laser sources; however, we find no evidence in either case that the desorption process leads to fragmentation of the target molecule unless excessive desorption energy is applied. This makes LIAD a powerful approach for techniques that require high density and high purity samples in the gas-phase, such as ultrafast dynamics studies or diffraction experiments. Graphic abstract

Many sophisticated approaches for analyzing properties of chiral matter have been developed in recent years. But in general, the available chiroptical methods are limited to either solvated or small gaseous molecules. Studying the chirality of large biopolymers in the gas phase, including aspects of the secondary structure, becomes accessible by combining the electrospray ionization technique with chiroptical detection protocols. Here, laser-induced photodetachment from gramicidin anions, a peptide consisting of 15 amino acids has been investigated. The angular distribution of photoelectrons is demonstrated to be sensitive to the substitution of protons by cesium ions, which is accompanied by a conformational change. The photoelectron circular dichroism (PECD) is −0.5% for bare gramicidin, whereas gramicidin with several Cs+ ions attached exhibits a PECD of +0.5%. The results are complemented and supported by ion mobility studies. The presented approach offers the prospect of studying chirality and the secondary structure of various biopolymers.

High-throughput photofragmentation studies of thymine and guanine were performed at 257 and 343 nm and for a wide range of ionisation laser intensities. Combining a continuous laser-based thermal desorption source...