Caffeine and glucosamine mobility shifts by adduction with 2‐butanol depended on interaction energy, charge delocalization, and steric hindrance in ion mobility spectrometry

Abstract

Ion mobility spectrometry (IMS) is an analytical technique that separates gas-phase ions drifting under an electric field according to their size to charge ratio. We used electrospray ionization-drift tube IMS coupled to quadrupole mass spectrometry to measure the mobilities of glucosamine (GH ) and caffeine (CH ) ions in pure nitrogen or when the shift reagent (SR) 2-butanol was introduced in the drift gas at 6.9 mmol m . Binding energies of 2-butanol-ion adducts were calculated using Gaussian 09 at the CAMB3LYP/6-311++G(d,p) level of theory. The mobility shifts with the introduction of 2-butanol in the drift gas were -2.4% (GH ) and -1.7% (CH ) and were due to clustering of GH and CH with 2-butanol. The formation of GBH was favored over that of CBH because GBH formed more stable hydrogen bonds (83.3 kJ/mol) than CBH (81.7 kJ/mol) for the reason that the positive charge on CH is less sterically available than on GH and the charge is stabilized by resonance in CH . These results are a confirmation of the arguments used to explain the drift behavior of these ions when ethyl lactate SR was used (Bull Kor Chem Soc 2014, 1023-1028). This study is a step forward to predict IMS separations of overlapping peaks in IMS spectra, simplifying a procedure that is trial and error by now.

Mechanism of atmospheric pressure chemical ionization of morphine, codeine, and thebaine in corona discharge–ion mobility spectrometry: Protonation, ammonium attachment, and carbocation formation

“…In other words, the O‐protomers (isomers b , c , and d ) are less stable than their corresponding N‐protomer (isomers a ). It is in agreement with previous studies reported that nitrogen sites are more basic than the oxygen sites 41,42 . The calculated PAs of the oxygen sites (Table 1) are higher than that of H 2 O (691 kJ mol −1 ), 43 and protonation of these sites in the presence of H 3 O + is thermodynamically favored.…”

“…40 is in agreement with previous studies reported that nitrogen sites are more basic than the oxygen sites. 41,42 The calculated PAs of the oxygen sites (Table 1) Figure S4. With NH 3 dopant, the intensities of peaks M2 and C2 attributed to the carbocations of morphine and codeine decreased and the peaks M1 and C1 were observed as the main peaks.…”

Buffer gas additives (modifiers/shift reagents) in ion mobility spectrometry: Applications, predictions of mobility shifts, and influence of interaction energy and structure

“…Energy interactions have been used to explain the mobility shift behavior of different ions after injecting SRs in the buffer gas. When ethyl lactate (L, 22 mmol m −3 ) or 2‐butanol (B, 6.9 mmol m −3 ) were used as SRs in ESI‐IMS‐QMS at 150°C and humidity ~10 ppm, the mobility of protonated glucosamine, GH + , was more affected than that of protonated caffeine, CH + , because GH + clustered more. Theoretical calculations showed that the GLH + and GBH + clusters were more energetically stable (−26.30 and −19.9 kcal/mol, respectively) than CLH + and CBH + (−24.66 and −19.5 kcal/mol, respectively) possibly because the positive charge in GH + was more sterically accessible than in CH + for adduction and the charge was stabilized by resonance in CH + .…”

“…When dextromethorphan (Dx) and diphenhydramine (Dy) were analyzed with 2‐butanol in the buffer gas, the mobility shift of DxH + was unexpectedly larger than that of DyH + because DxH + showed 2 favorable sites for adduction vs only one in DyH + (see Section 8). Roscioli confirmed that SRs with several interaction sites show the strongest interaction with analyte ions . She found that 2‐ethylhexyl salicylate and ethyl lactate were the SRs producing the largest mobility shifts among 11 SRs including amines, nitriles and nitro groups, and 2‐butanol.…”

“…The ion‐SR noncovalent interaction energies (E I ) may be calculated using E I = E cluster − (E SR + E protonated ion ) and proton affinities subtracting protonated ion energies from molecule energies . Interaction energies of ion‐SR clusters have been calculated using the GAMESS program at the B3LYP/6‐311++G(d,p) level of theory and Gaussian 09 at different levels of theory such as B3LYP, X3LYP/6‐311++(d,p), that accounts for the basis set superposition error, CAMB3LYP/6‐311++G(d,p) . M06‐2X/6‐311++(d,p) and B3LYP‐GD3/6‐311++(d,p) were compared when IHB energies were calculated in dextromethorphan and diphenhydramine to demonstrate IHB effects in their mobilities after introduction of 2‐butanol SR in the buffer gas.…”