Quantitative electrospray ionization efficiency scale: 10 years after

Abstract

Rationale The first comprehensive quantitative scale of the efficiency of electrospray ionization (ESI) in the positive mode by monoprotonation, containing 62 compounds, was published in 2010. Several trends were found between the compound structure and ionization efficiency (IE) but, possibly because of the limited diversity of the compounds, some questions remained. This work undertakes to align the new data with the originally published IE scale and carry out statistical analysis of the resulting more extensive and diverse data set to derive more grounded relationships and offer a possibility of predicting logIE values. Methods Recently, several new IE studies with numerous compounds have been conducted. In several of them, more detailed investigations of the influence of compound structure, solvent properties, or instrument settings have been conducted. IE data from these studies and results from this work were combined, and the multilinear regression method was applied to relate IE to various compound parameters. Results The most comprehensive IE scale available, containing 334 compounds of highly diverse chemical nature and spanning 6 orders of magnitude of IE, has been compiled. Several useful trends were revealed. Conclusions The ESI ionization efficiency of a compound by protonation is mainly affected by three factors: basicity (expressed by pKaH in water), molecular size (expressed by molar volume or surface area), and hydrophobicity of the ion (expressed by charge delocalization in the ion or its partition coefficient between a water–acetonitrile mixture and hexane). The presented models can be used for tentative prediction of logIE of new compounds (under the used conditions) from parameters that can be computed using commercially available software. The root mean square error of prediction is in the range of 0.7–0.8 log units.

Nonempirical Prediction of the Relative Electrospray Ionization Efficiencies of Nitroanilines by Combined CBS-QB3 and SCC-DFTB Calculations

“…The ionization efficiencies (logIE) for isomers of nitroanilines reported by Oss et al for positive ion mode are 2.26, 3.29, and 2.72 for ortho-, meta-, and para-nitroaniline, respectively. The experimental data we use for validation of our model were measured in positive ion mode (ionization by monoprotonation) using an Agilent XCT ion trap mass spectrometer in solvent composition (20/80 v/v of 0.1% formic acid and acetonitrile). In principle, a larger value of IE (or RIE) means that a larger proportion of the analyte present in the analyzed solution will reach the detector and generate the signal. , Comparison of the experimental IE ordering (ortho < para < meta) does not coincide with either the gas-phase (meta < ortho < para) or droplet (ortho < meta < para) stability ordering calculated for nitroanilines by us.…”

“…The ability to obtain quantitative information from LC/ESI/MS is currently limited by the availability of standard substances, as different compounds ionize to different extents in an electrospray source. The response of the compounds in LC/ESI/MS is influenced by the properties of the compound, eluent composition, and instrument and usually described by ionization efficiency (IE) or relative IE (RIE). − In principle, a bigger value of the IE (or RIE) means that a larger proportion of the analyte present in the analyzed solution will reach the detector and generate the signal.…”

“…Many groups have examined ionization efficiencies in the electrospray sources to gain the understanding on factors contributing to the ionization efficiencies. ,− The findings have generally been similar: larger, more hydrophobic and basic compounds possess a higher IE. , However, those studies mostly contain only a limited number of compounds studied under the same conditions or do not result in a model explicitly describing the compounds’ ionization in the ESI source (under fixed conditions) via the compounds’ physicochemical properties. An extensive study by Oss et al proposes three different models, able to predict logIE values within 0.7–0.8 units based on different properties of the molecules, part of which should be calculated with only commercially available software. Still, even those models are often unable to predict IE values for very similar compounds like isomers of nitroanilines.…”

Selected Ion Monitoring Using Low-Cost Mass Spectrum Detectors Provides a Rapid, General, and Accurate Method for Enantiomeric Excess Determination in High-Throughput Experimentation

“…A short 3 min isocratic method using chiral RP-HPLC was developed for this analysis. 28 As previously reported, ee values were measured using the crude product with both UV/vis and SIM detection; the product was then purified using RP-HPLC, and actual ee values of the purified products were determined using HPLC-UV/vis analysis. Figure 4b shows the correlation between the ee values determined on the crude samples using UV/vis detection (xaxis) compared to the actual ee values measured on the purified material (y-axis).…”

“…Although this increased sensitivity is undoubtedly substrate-dependent, it is notable as it might allow for SIM detection to readily translate to HTE formats using smaller well sizes, which would likely involve reactions on an even smaller scale. The structural dependencies on electrospray ionization efficiencies of various compounds have been discussed previously in the literature …”