Monte carlo simulation of macromolecular ionization by nanoelectrospray

Abstract

Electrospray ionization (ESI) is commonly used in macromolecular mass spectrometry, yet the dynamics of macromolecules in ESI droplets are not well understood. In this study, a Monte Carlo based model was developed, which can predict the efficiency of electrospray ionization for macromolecules, i.e., the number of macromolecular ions produced per macromolecules electrosprayed. The model takes into account ESI droplet evaporation, macromolecular diffusion within the droplet, droplet fissions, and the statistical nature of the ESI process. Two idealized representations of macromolecular analytes were developed, describing cluster prone, droplet surface inactive macromolecules and droplet surface active macromolecules, respectively. It was found that surface active macromolecules are preferentially ionized over surface inactive cluster prone macromolecules when the initial droplet size is large and the analyte concentration in solution is high. Simulations showed that ESI efficiency decreases with increasing initial droplet size and analyte molecular weight, and is influenced by analyte surface activity, the properties of the solvent, and the variance of the droplet size distribution. Model predictions are qualitatively supported by experimental measurements of macromolecular electrospray ionization made previously. Overall, this study demonstrates the potential capabilities of Monte Carlo based ESI models. Future developments in such models will allow for more accurate predictions of macromolecular ESI intensity. (J Am Soc Mass Spectrom 2008, 19, 1098 -1107) © 2008 American Society for Mass Spectrometry E lectrospray ionization (ESI) allows for the production of gas-phase ions from nonvolatile species in solution, and is particularly useful in the measurement of biological macromolecules with masses in the kDa and MDa ranges. Despite its widespread use, many aspects of the ESI of macromolecules are poorly understood [1]. The efficiency of the ESI process, i.e., the number of gas-phase ions produced per number of analytes electrosprayed, is a fundamental parameter in ESI that is typically unknown [2]. Droplets of the electrosprayed solution are produced in ESI, which have multiple excess charges on their surface [3]. Analytes are ionized from these droplets by one of two mechanisms: the charged residue mechanism [4] or the ion emission mechanism [5,6]. Analyte ionization by the charge residue mechanism requires that analytes be separated from one and other (one analyte per droplet) [7]. This is accomplished by Coulombic fissions of evaporating charged droplets in which unstable droplets emit smaller, charged progeny droplets [8]. Although complete separation of analytes is not necessary in the ion emission mechanism, ESI droplets must have diameters about 10 nm for ion emission to occur [6], and ion emission also occurs only after a series of droplet fission events [9].The parameters governing the ionization of small analytes, which are believed to be ionized by the ion emission mechanism [10], have been examined e...

Charge State Coalescence During Electrospray Ionization Improves Peptide Identification by Tandem Mass Spectrometry

“…Although the charge enhancing phenomena of these reagents correlates well with the Raleigh equation in many measurements, the complex chemical environment at the end of the droplet lifetime produces deviations from theory [24,25]. Factors affecting the observed analyte charging result from the high-boiling supercharging reagent that becomes enriched in the late stage of the desolvating droplet and results in non-spherical droplets [26], and protein chemical and/or thermal denaturation [27].…”

Ion Mobility Measurements of Nondenatured 12–150 kDa Proteins and Protein Multimers by Tandem Differential Mobility Analysis–Mass Spectrometry (DMA-MS)

“…When studying proteins that are less well characterized than those used here, the identification of specific multimeric states may be of interest [65]. It has been argued previously that for multimer ions originating nonspecifically during the electrospray process, the intensity distribution as a function of the degree of aggregation should follow a Poisson distribution [39,66]. Regardless of the exact functional form of the multimer size distribution, nonspecific aggregates would follow a unimodal distribution.…”

“…With these protein concentrations and this droplet size, droplets containing zero, one, or multiple proteins were produced. Although drops underwent coulombic fission prior to complete evaporation, rough calculations show that both single and nonspecific multimeric protein ions were generated under these conditions [39].…”

Quantification and Compensation of Nonspecific Analyte Aggregation in Electrospray Sampling

“…They simulated a Poisson distribution, which was also employed by Lewis et al (1994) and Kaufman et al (1996). Hogan and Biswas (2008a) developed two Monte-Carlo-based models to predict the efficiency of ES ionization for macromolecules and to study the porous film deposition by electrohydrodynamic atomization of nanoparticle sols (Hogan and Biswas 2008b). In their Monte-Carlo-based models, the size distributions of sprayed particles are determined by the convolution of a Poisson distribution within the initial droplet size distribution and the initial ES droplet size distribution is represented by a lognormal distribution function.…”