Matrix-Free Assisted Laser Desorption Ionization Using Metal-Organic Frameworks

Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique that is widely applied in the characterization of large biomolecules using various mass spectrometry (MS) analyzers, specifically, time-of-flight (TOF) analyzers. The MALDI process involves the deposition of an analyte solution onto a metal substrate before the addition of a matrix. The matrix/analyte dry spot is exposed to a UV laser, and the laser energy that is absorbed by the matrix/analyte is converted into heat energy that initiates charge transfer, which results in the desorption of the matrix and analyte molecules in ionized form. The positive ions are then accelerated through a vacuum into MS analyses.

Representative MOFs including HKUST-1 (named for Hong Kong University of Science and Technology), modified UiO-66 with –COOH and – NH2 functional groups, and poly- coordinated network (PCN)-250 MOFs. The ball embedded in the MOF structures represents the relative pore sizes that are found within the structure of the MOFs. The analytes shown are cytidine, lauric acid, pyridine, and guanine.

The MALDI process, however, lacks guiding systematic principles, which has resulted in mostly empirical work. For example, there is no universal matrix that can be used in the MALDI-MS analysis of biomolecules. Hundreds of compounds were assessed with several analytes and were given qualitative ratings. These variables were the products of differences in charge transfer efficiency between the matrix and analytes because of chemical and structural factors.

This problem represents an urgent analytical need that can advance the MALDI process toward mechanistic understanding. Metal-organic frameworks (MOFs) are an emerging class of porous materials that have been studied in multiple areas, including gas storage, sensing, air purification, and catalysis. MOFs are typically synthesized from metal oxide secondary building units (SBUs) connected by organic linkers to form a reticulated, porous network. MOFs are used because of their versatility and thermal stability.

The unique physical and chemical properties of MOFs provide the potential to serve as MALDI matrixes that are capable of ionizing a wide range of analytes. However, because of their structural complexity, an attempt was made to determine the existence of any interaction between the analytes and the MOFs when they were mixed together. Low-frequency Raman spectroscopy (LFRS) was used to determine the inter- and intramolecular changes between free MOFs. In addition, LFRS was used to investigate the reactions that resulted from mixing analytes in an amorphous environment.

LFRS is a developing technique that concurrently provides vibrational spectra for tested compounds in the terahertz and normal Raman spectral regions, which are indicative of any potential physical and chemical changes in a given analyte. In the case of MOFs, LFRS can be used to investigate the binding properties of MOFs with the analytes of interest and to determine the nature of such binding.

Currently, there are two different mechanisms that explain the ionization process in MALDI-MS analysis. The first mechanism is based on the coupled chemical and physical dynamics model, which involves charge transfer during the excitation stage of a matrix/analyte mixture, resulting from exposure to laser power. The second mechanism is based on a cluster model, which involves a combination of proton and intracluster charge transfer during the desolvation step of the MALDI process. Accordingly, an experimental approach for MOF/analyte interaction during the MALDI process was designed to determine the ionization model that governs the ionization step and determine the basic elements that contribute to the MALDI ionization process of the MOF/analyte mixtures. This base knowledge will aid in the development of efficient matrix-free desorption substrates for MS analyses.

MOF materials have demonstrated superior homogenous and heterogeneous catalysis characteristics that will be transcribed to the MALDI process. Moreover, the diversity of MOFs can be envisioned to act as a selective desorption surface for specific groups of analytes without reliance on the addition of external reagents.

The overall goal of this project was to study the mechanism of ionization and to determine the influence of factors that affect the charge-transfer process during the MALDI-MS ionization. It also addressed the binding affinity issue between MOFs and analytes using the LFRS technique to research inter- and intramolecular changes between the MOF crystalline and amorphous states with different analytes. These analytes were classified as acidic or basic compounds. Once the basic properties of the MOF/analyte mixture are understood, it will be possible to determine how to design MOFs that can enhance the ionization efficiency for a wide range of compounds during MALDI-MS analysis.

This research addressed the potential intra- and intermolecular changes for MOF/analyte mixtures using LFRS and MALDI-MS techniques. The MOFs used in the LFRS technique were UiO-66-COOH and UiO-66-NH2, and the analytes were pyridine, benzoic acid, cytidine, lauric acid, and guanine. More MOFs than those tested by the LFRS technique were used for the MALDI-MS analyses. Most of the MOFs were obtained from internal sources, either through synthesis or by leveraging from already-funded projects that utilize MOFs. The structures for some of the MOFs and analytes are shown in the accompanying figure.

This work was done by Rabih E.Jabbour; Gregory Peterson; Jared DeCoste (ECBC); and Yousef Jabaji (UMBC); for the Army Research, Development and Engineering Command. ARDEC-0005

This Brief includes a Technical Support Package (TSP).
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Matrix-Free Assisted Laser Desorption Ionization Using Metal-Organic Frameworks

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