Supporting Information
Reactions of Micro-Solvated Organic Compounds at Ambient Surfaces: Droplet Velocity, Charge
State and Solvent Effects
Abraham K. Badu-Tawiah, Dahlia I. Campbell and R. Graham Cooks*
Supporting information is summarized in the table below
Topic
Title of Topic
Topic 1
(Figure S1)
Comparison of nanospray-MS of product of Girard T reaction with
androsterone under ambient soft landing conditions with the
corresponding bulk solution-phase product
Topic 2
(Figure S2)
Comparison of nanospray-MS of product of Girard T reaction with
testosterone under ambient soft landing condition with the
corresponding bulk solution-phase product
Topic 3
(Figure S3)
Effect of charge (in a form of applied voltage) on surface reaction
efficiency
Topic 4
(Figure S4)
Ion type (protonated vs. sodiated) soft landed onto the reaction surface
influences the yield of the surface reaction, with protonated ions
reacting more effectively than sodiated and potassiated species
Topic 5
(Figure S5)
Electrospray ionization of keto-steroid predominantly produces sodiated
and potassiated dimers/trimers of the steroid, which when soft-landed
onto a reaction surface generate low product yield compared with when
the dry ketone is exposed to droplets containing the Girard T
Topic 6
(Figure S6)
Effect of solvent evaporation from landed material on reaction yield
even after droplet deposition has ceased
Topic 7
(Figure. S7)
Capture and reaction of vapor-phase analyte using charged
microdroplets
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1
1. Reactive soft landing of androsterone with Girard T reagent at ambient surface and the
comparison with the corresponding bulk solution-phase reaction
(a) DROPLET
345
100% = 1.18E2
100
[3M+Na]+
893
m/z 404
100
Relative Abundance
- N(CH3)3
255
0
160
240
50
[M+Na]+
150
(b) BULK
100
250
450
m/z
320
400
603
404
350
404
[2M+Na]+
[Reaction Product]+
313
0
Relative Abundance
273
132
550
650
m/z
750
850
132
x50
302
0
No Reaction Product
(m/z 404) was Detected
603
50
150
250
399
350
893
450
m/z
550
650
750
850
Figure S1 Nanospray-MS of Girard T and androsterone (M) reaction mixture after 30 min of reaction time (a) at
ambient surface and (b) bulk solution-phase. Spray solvent in a) was 5 µL/min 50 ppm Girard T in acetonitrile
solution, whereas 8 µL (equivalent amount of GT soft landed in 30 min) of the same solution was utilized for the
solution-phase reaction. 2 µL of 100 ppm androsterone was used in (a) and (b). The solution-phase reaction mixture
was allowed to stand at ambient temperature for 30 min. after which 10 µL of methanol/water (1:1, v/v) was added
for MS analysis. Likewise, the surface reaction product was washed using 10 µL of methanol/water (1:1, v/v) after
micro-solvated GT ions were allowed to impinge on the dry androsterone for 30 min. Insert is MS/MS product ion
spectrum of reaction product at m/z 404
2
2. Reactive soft landing of testosterone with Girard T reagent at ambient surface and the
comparison with the corresponding bulk solution-phase reaction
(a)
100
132
Relative Abundance
100
m/z 402
343
100% = 1.69E3
- N(CH3)3
315
[M+Na]+
50
0
311
100
150
250
402
340
400
[2M+Na]+
599
402
(b)
280
m/z
[Reaction Product]+
0
220
350
[3M+Na]+
887
450
m/z 550
650
750
850
132
m/z 402
Relative Abundance
x25
100
401
50
Virtually
No Product
302
270
0
311
343
100% = 3.41E2
140
200
299 314
260
599
0
150
250
350
450
m/z
550
650
750
m/z 320
402
380
440
850
Figure S2 Nanospray-MS of Girard T and testosterone (M) reaction mixture after 30 min of reaction time (a) at
ambient surface and (b) bulk solution-phase. Spray solvent in a) was 5 µL/min 50 ppm Girard T in acetonitrile
solution, whereas 8 µL (equivalent amount of GT soft landed in 30 min) of the same solution was utilized for the
solution-phase reaction. 2 µL of 100 ppm testosterone was used in (a) and (b).. The solution-phase reaction mixture
was allowed to stand at ambient temperature for 30 min. after which 10 µL of methanol/water (1:1, v/v) was added
for MS analysis. Likewise, the surface reaction product was washed using 10 µL of methanol/water (1:1, v/v) after
micro-solvated GT ions were allowed to impinge on the dry testosterone for 30 min. Inserts is MS/MS product ion
spectrum of reaction product at m/z 402
3
3. Effect of applied voltage on Girard T/cortisone reaction efficiency in reactive soft landing
experiment. Positively charged droplets performed better than negatively charged droplets,
which in turn produced more product than when no voltage was applied to the spray
solution
(a)DROPLET +7 kV
Relative Abundance
100% = 9.63E5
100
132
100% = 2.17E5
415
100
[Reaction Product]+
474
m/z 474
[M+H]+
383
50
0
444
387
0
320
160
m/z
400
220
480
280
361
340
400
460
m/z
Relative Abundance
(b)100% = 2.77E5
100
132
383
415
m/z 474
50
0
320
400
0
160
100% = 1.08E5
100
128
220
100% = 9.25E3
100
280
415
474
480
m/z
(c)
Relative Abundance
100% = 4.50E4
100
361
m/z 340
400
460
m/z 474
383
0
50
132
320
400
480
m/z
474
361
0
160
220
280
m/z 340
400
460
Figure S3 Typical nanospray-MS of Girard T and Cortisone (M) ambient surface reaction (30 min of reaction time)
using (a) +7 kV, (b) -7 kV and (c) 0 kV spray voltages. Flow rate 5 µL/min of 50 ppm Girard T in acetonitrile
solution and 2 µL of 100 ppm cortisone was used in all cases. Reaction mixture was washed using 10 µL of
methanol/water (1:1, v/v) after micro-solvated GT ions were allowed to impinge on the dry cortisone for 30 min.
Inserts indicate MS/MS product ion spectrum of reaction product at m/z 474
4
4. Comparison of reaction efficiency when the keto-steroid is soft-landed onto dry Girard
reagent (GT) to the reaction efficiency obtained with GT deposition onto dry keto-steroid.
Here the effect of charge on reaction efficiency is shown in the ion type (protonated vs.
sodiated) deposited onto the reaction surface. Protonated ions reacted more effectively than
sodiated and potassiated species. Evidence of deposition of sodiated and potassiated species
is provided in Figure S5
345 m/z 404
100
Girard Reagent
132
Relative Abundance
255
[M+Na]+
313 Reaction
Product
404
50
300
450
0
220
(c)
273
404
280
340
m/z
[3M+Na]+
893
[3M+K]+
909
[2M+Na]+
603
600
750
100
132
50
900
[M+Na]+
474
387
0
250
383
0
200
400
600
800
150
(b)
m/z 404
100
132
Reaction
Product
50
220
893
345
600
m/z
(d)
750
132
Reaction
Product
404
340
474
400
383
[2M+Na]+
603
404
450
m/z
743
450
50
[M+Na]+
313
273
280
444
350
[3M+Na]+
100
255
300
m/z 474
[3M+Na]+
0
m/z
Relative Abundance
415
100
400
[3M+K]+
415
100
m/z 474
0
[M+H]+
909
0
Relative Abundance
100
Relative Abundance
(a)
361
387
260
340
m/z
444
440
743
0
200
400
600
m/z
800
150
300
450
m/z
600
750
Figure S4 Girard T (GT) reactive soft landing at an ambient surface (30 min.) with androsterone (MW 290) and
cortisone (MW 360). Nanospray-MS of the reaction mixture after positively charged microdroplets containing (a)
androsterone ions deposited onto GT, (b) GT ions deposited onto androsterone, (c) cortisone ions deposited onto
GT, and (d) GT ions deposited onto cortisone. M represents androsterone and cortisone in (a) and (b) and (c) and
(d), respectively. Reaction spot at surface was washed with 10 µL methanol/water (1:1, v/v) solution and analyzed
by nanospray-MS using 1.8 kV spray voltage
5
5. Electrospray of keto-steroids from acetonitrile solution produces mainly dimers and trimers
of sodiated/potassiated ions
Relative Abundance
(a)
[3M+K]+
x20
909
100
[2M+K]+
317
[3M+Na]+
619
[2M+Na]+
603
893
680
0
300
500
700
900
m/z
[3M+K]+
Relative Abundance
(b)
1119
100
[2M+K]+
[M+H]+
759
361
[2M+Na]+
1098
743
0
300
500
700
900
1100
m/z
Figure S5 Positive ion mode ESI-MS of 50 ppm acetonitrile solution of (a) androsterone (MW 290) and (b)
cortisone (MW 360) using a spray voltage of +7 kV. M represents androsterone and cortisone in (a) and (b),
respectively
6
6.
Gradual evaporation of solvent from charged droplets at surface causes modest increase in the
product yield. Normalized product ion intensity also increases with reaction time (black trace, Fig.
S6b). Solvent from neutral droplets generated via drop-casting also affords product (red trace, Fig
S6b) faster than bulk solution-phase conditions conducted using the same quantities of reagents (data
not shown). However, due to charge/pH effects, charged droplets performed better than the neutral
big droplets.
Normalized Product
Ion
ProductIon
Normalized
(m/z
Intensity
474)Intensity
(m/z474)
(a) (a)
0.8
(b) (b)
0.6
Dry Environ.
ES Droplet (+ve) Landing
Open Air
Pipette Droplet Casting
0.6
0.4
0.4
0.2
0.2
0
0
10
Delay
Time
(min)
Time
(min.)
20
30
0
10
20
30
Reaction
(min)
TimeTime
(min.)
Figure S6 (a) Effect of delay time on product yield during the 30 min. period after deposition of positively charged
microdroplets containing Girard T (50 ppm) sprayed at 5 µL/min onto dry cortisone (2 µL of 100 ppm), and (b)
comparison of positively charged (black trace) vs. neutral (red trace) droplet/surface reaction as a function of
reaction time. Neutral droplets were generated at the surface by drop-casting 2 µL of Girard T (50 ppm) and
cortisone (100 ppm) in each case. Normalized product ion intensity was calculated based on the ratio: I P/[IP+IGT+IM],
where IP, IGT and IM represent product (m/z 474), GT (m/z 132) and sodiated cortisone (m/z 383) ion intensities,
respectively
7
7. Mass spectra of the products collected from the vapor analyte capture and reaction with
charged droplet experiment. Products were collected in small quantities but MS/MS
product ion spectra of the collected materials provide confirmation of their presence.
100
132
393
Relative Abundance
50
140
(b)
Relative Abundance
200
390
260
133
62
55
430
m/z
380
100 100% = 6.23E2
0
m/z 215
171
197 215
100
140
m/z 180
220
244
215
(c)
60
100
140
74
100
62
50
133
0
60
100
140
420
440
50
103
340
444
m/z
320
m/z
260
470
Reaction Product
0
Relative Abundance
387
350
m/z 474
50
0
74
100
50
Reaction
Product
474
50
0
0
415
100 100% = 4.54E2
180
m/z
Relative Abundance
Relative Abundance
100
Relative Abundance
(a)
220
240
100% = 2.15E1
100
183
m/z 240
196
222
50
139
0
130
170
m/z
210
250
244 256
m/z 180
220
260
Figure S7 Vapor-phase analyte capture and reaction by charged droplets in the open laboratory environment.
Droplets and their content were transferred to a surface and collected for mass analysis. (a) Full mass spectrum of
reaction products of Girard T reagent with vapor-phase cortisone. Full mass spectrum of the reaction product of
ethanolamine with (b) 4-phenylpyridine N-oxide and (c) 2-phenylacetophenone vapors. Nitrogen gas pressure of 80
psi was used as the nebulizing/carrier gas for these droplet/vapor reactions the yields of which are low. Product
identification by MS/MS product ion spectra of the collected materials are given as inserts
8