Another core research interest of the MS Resource is the development of room-temperature ionic liquids as matrices for MALDI mass spectrometry. These materials are salts consisting of nitrogen or phosphorus-containing organic cations and large organic or inorganic anions. They have high viscosity, negligible vapor pressure, and high stability. Moreover, they have melting points at or below room temperature, indicating that they are stable liquids under ambient conditions. RTILs are used, for example, as novel solvent systems in organic chemistry, as a new class of stationary phases for gas chromatography, and as solvents for liquid-liquid extraction and electrochemistry.
The properties of RTILs suggest that they can be a successful MALDI matrix. Traditional RTILs (e.g., 1-butyl-3-methylimidazolium chloride), however, are not suitable for MALDI because their anion components do not absorb UV light, and their cation components have no proton to donate to ionize the analyte. Along with Professor Dan Armstrong’s group, we designed RTILs to serve as MALDI matrices by incorporating components of traditional matrices (e.g., α-cyano-4-hydroxycinnamic acid) as the anion component of the salt and organic ammonium ions as the cation (see diagram for synthesis and structure). We designate these new materials as ionic liquid matrices (ILMs).
They form smooth, uniform spots on a MALDI sample plate, unlike traditional solid matrices that give a non uniform surface. The use of ILMs significantly improves shot-to-shot, spot-to-spot signal reproducibility, gives higher peak intensities and longer vacuum persistence as compared to solid matrices, and affords good mass spectra without searching for “sweet or hot spots” that are sometimes sought for productions of good signals when using solid matrices.
The good reproducibility achieved with ILMs suggests that they may be useful in quantification, a difficult problem with MALDI mass spectrometry. Quantification when using solid matrices often requires the use of an internal standard that is similar to the analyte to achieve good results, and even then the dynamic range is small (less than one order of magnitude). When using ILMs, however, good quantification of peptides can be achieved by using a single internal standard (e.g., substance P) for a set of analyte peptides. Good calibrations with high linearity and reproducibility are achievable over a broad concentration range for the many ILMs in spite of their different physical states. Interestingly, the slopes of the calibration curves for a series of polypeptides of similar hydrophobicity correlate with the inverse of the peptide molecular weights, suggesting an opportunity to predict, the relative sensitivities (slopes of calibration plots) for these and related analytes. The quality of the calibration and the linear range are shown in the accompanying plot.
Ionic Liquids as Matrices for Maldi Mass Spectrometry
We are continuing this work by evaluating the use of ILMs in the analysis of glycans and complex phosphor and other lipids. The research has shifted to two new instruments in the lab, namely a Fourier transform MALD and a MALDI tandem TOF.
1. Tu, T., Sauter Jr., A.D., Sauter III, A.D., Gross, M.L. Improving the Signal Intensity and Sensitivity of MALDI Mass Spectrometry by Using Nanoliter Spots Deposited by Induction-Based Fluidics. J. Am. Soc.Mass Spectrom. (2008), 19, 1086-1090.
2. Li, Ying L.; Gross, M.L.; Hsu, F.-F. Ionic-liquid matrices for improved analysis of phospholipids by MALDI-TOF aass spectrometry. J. Am. Soc.Mass Spectrom. (2005), 16, 679-682.
3. Li, Ying L.; Gross, M.L. Ionic-liquid matrices for quantitative analysis by MALDI-TOF mass spectrometry. J. Am. Soc. Mass Spectrom. (2004), 15, 1833-1837.
4. Armstrong, Daniel W.; Zhang, Li-Kang; He, Lingfeng; Gross, Michael L. Ionic liquids as matrixes for matrix-assisted laser desorption/ionization mass spectrometry. Anal. Chem. (2001), 73, 3679-3686.