TY - JOUR

T1 - Charge Retention/Charge Depletion in ESI-MS

T2 - Theoretical Rationale

AU - Haack, Alexander

AU - Polaczek, Christine

AU - Tsolakis, Manuel

AU - Thinius, Marco

AU - Kersten, Hendrik

AU - Benter, Thorsten

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic experimental study on this topic using Substance P and proposed a charge retention/charge depletion mechanism, explaining different gas- and liquid-phase modifications [Thinius et al. J. Am. Soc. Mass Spec. 2020, 10.1021/jasms.9b00044 ]. In this work, we aim to support this rational by theoretical investigations on the proton transfer processes from (multiply) charged analytes toward solvent clusters. As model systems we use small (di)amines as analytes and methanol (MeOH) and acetonitrile (ACN) as gas phase modifiers. The calculations are supported by a set of experiments using (di)amines, to bridge the gap between the present model system and Substance P used in the preceding study. Upon calculation of the thermochemical stability as well as the proton transfer pathways, we find that both ACN and MeOH form stable adduct clusters at the protonation site. MeOH can form large clusters through a chain of H-bridges, eventually lowering the barriers for proton transfer to an extent that charge transfer from the analyte to the MeOH cluster becomes feasible. ACN, however, cannot form H-bridged structures due to its aprotic nature. Hence, the charge is retained at the original protonation site, i.e., the analyte. The investigation confirms the proposed charge retention/charge depletion model. Thus, adding aprotic solvent vapors to the gas phase of an ESI source more likely yields higher charge states than using protic compounds.

AB - Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic experimental study on this topic using Substance P and proposed a charge retention/charge depletion mechanism, explaining different gas- and liquid-phase modifications [Thinius et al. J. Am. Soc. Mass Spec. 2020, 10.1021/jasms.9b00044 ]. In this work, we aim to support this rational by theoretical investigations on the proton transfer processes from (multiply) charged analytes toward solvent clusters. As model systems we use small (di)amines as analytes and methanol (MeOH) and acetonitrile (ACN) as gas phase modifiers. The calculations are supported by a set of experiments using (di)amines, to bridge the gap between the present model system and Substance P used in the preceding study. Upon calculation of the thermochemical stability as well as the proton transfer pathways, we find that both ACN and MeOH form stable adduct clusters at the protonation site. MeOH can form large clusters through a chain of H-bridges, eventually lowering the barriers for proton transfer to an extent that charge transfer from the analyte to the MeOH cluster becomes feasible. ACN, however, cannot form H-bridged structures due to its aprotic nature. Hence, the charge is retained at the original protonation site, i.e., the analyte. The investigation confirms the proposed charge retention/charge depletion model. Thus, adding aprotic solvent vapors to the gas phase of an ESI source more likely yields higher charge states than using protic compounds.

KW - charge retention

KW - ion-solvent interactions

KW - proton transfer

KW - proton-bound cluster

KW - supercharging

UR - http://www.scopus.com/inward/record.url?scp=85082881525&partnerID=8YFLogxK

U2 - 10.1021/jasms.9b00045

DO - 10.1021/jasms.9b00045

M3 - Article

C2 - 32150409

AN - SCOPUS:85082881525

VL - 31

SP - 785

EP - 795

JO - Journal of the American Society for Mass Spectrometry

JF - Journal of the American Society for Mass Spectrometry

SN - 1044-0305

IS - 4

ER -