CHAPTER 1
Gas phase ion Chemistry of CrIII(Salen)complex under electrospray
ionization conditions
CHAPTER 2
Proton and alkali metal ion affinities of bidentate bases: spacer chain length effects
CHAPTER 3
Generation of regiospecific carbanions under electrospray ionization conditions and characterization by ion-molecule
reactions with carbon dioxide
Chapter 4
Generation of distonic dehydrophenoxide radical anions under electrospray and atmospheric pressure chemical ionization
conditions
1. Gas phase studies of metal complexes, isomeric carbanions
and distonic radical anions under soft ionization mass
spectral conditions
VIVA OF THE THESIS
Presented to
OSMANIA UNIVERSITY
BY
M. Kiran Kumar
(Mentor: Dr. M. Vairamani)
National Centre for Mass Spectrometry (NCMS)
Indian Institute of Chemical Technology (IICT)
2. CHAPTER 1
Co-ordination chemistry of [Cr(III) Salen] compounds under electrospray
ionization conditions
CHAPTER 2
The effect of spacer chain length on ion binding to α,ω-diamines and
diols: contrasting ordering for H+ and alkali metal ion affinities
CHAPTER 3
Generation of regiospecific carbanions under electrospray ionization
conditions and characterization by ion-molecule reactions with carbon
dioxide
CHAPTER 4
Generation of distonic dehydrophenoxide radical anions under
electrospray and atmospheric pressure chemical ionization conditions
3. Chapter 1: Co-ordination chemistry of [Cr(III) Salen] compounds under
electrospray ionization conditions
• Characterization of the metal complexes and to identify the crucial intermediates
in metal-mediated reactions in order to understand the nature and reactivity of
metal complexes and their reaction pathways.
• The study of metal complex systems using MS (i.e., in the gas phase) is a
rapidly expanding field of research
• Knowledge of the gas-phase structures of metal complexes is important for
analytical applications, as evidenced by several reviews.
• Interest in Salen type complexes intensified in 1990 when the groups of
Jacobsen and Katsuki discovered the enantioselective epoxidation of
unfunctionalised alkenes using chiral MnIII(Salen) complexes as catalysts
4. ► However, there are few reports on the EI
studies on a few metal-Salen complexes. L
► Electrospray ionization (ESI) is a N N
method to study ionic complexes. Cr III
. PF6
O O
► Epoxidation of olefins in solution was
also confirmed in the gas phase by
applying ESI method to [Mn(Salen)]
L
complexes.
► ESI has proven to be a soft ionization method that keeps intact any
weakly bound ligands in a complex ion.
► Axial positions of [M(salen)] are much important will enhance the yield
of the epoxidation reaction.
► Recently the axial interactions with DNA, nucleotides and nucleosides
were studied by this technique.
► We present here axial positions study of [Cr(Salen)] complex using a
primary amine and a series of diamines as ligands.
5. • The positive ion ESI mass spectrum of [CrIII(Salen)]+ complex in
acetonitrile (ACN) shows M+, [M(ACN)]+, [M(ACN)2 ]+ ions.
Abundant ion
10 eV
Low
cone [CrIII(Salen)(ACN)2]+
ESI
CrIII(Salen)
Solvent-ACN
High
[CrIII(Salen)]+ 20 eV
cone
• Significant abundance differences with 30 eV
varying the cone voltage.
The ESI mass spectra of [Cr(Salen)]PF6
in acetonitrile at different cone voltages
6. CONE
Fragmentation
Capillary Voltage : 3-5 kV
Cone: 5-100 V
+ S
+ + +
+++++
S
+ + +
MH+
+ S
S
+
7. • In the presence of propylamine (PA) clearly demonstrates the displacement
of solvent molecules present in the axial positions by the stronger ligand.
Low
cone [CrIII(Salen)(PA)2]+
CrIII(Salen) ESI
+ PA
High [CrIII(Salen)(PA)(ACN)]+
cone
Abundant ions
Surrounding
solvent ACN [CrIII(Salen)(ACN)]+
High
cone
[CrIII(Salen)]+
[CrIII(Salen)(PA)2]+ [CrIII(Salen)(ACN)2]+
[CrIII(Salen)PA]+ [CrIII(Salen)PA (ACN)]+
8. 10 eV
A series of primary diamines (DA) studied
to see the effect of chain length and
bidentate nature on the occupation of the
axial positions of CrIII(Salen)]+.
20 eV
H2N-(CH2)n-NH2 n = 2-8.
30 eV
9. 1. S o u r c e e x p e r im e n t s
2. Io n -M o le c u le r e a c t io n s
3. C ID E x p e r im e n t s
1. Source experiments +
NH2
(CH2)n
N N N N
Cr III ESI Cr III
O O . PF6 + H2N (CH2)n NH2 O O
NH2
Depends on the binding strength of the Diamine the abundances of
surrounded solvent adducts will be varied.
Surrounding
High
solvent [CrIII(Salen)(ACN)]+
ACN
cone
[CrIII(Salen)(DA)]+ [CrIII(Salen)]
[CrIII(Salen)(ACN)2]+
10. Propane Diamine
Hexane
Diamine
The order of bidentate nature of the diamines towords [CrIII(Salen)]+ can
be given as
H2N-(CH2)n-NH2 n = 2-8 (1-7). 3 >2 >4 >5 ≈ 8 >7 >6.
11. Relative abundance (%)
Ion
1 2 3 4 5 6 7
[CrIII(Salen)]+
2.9 4.3 10 19 44 34 40
m/z 318
[CrIII(Salen)(ACN)]+
5.8 7.9 20 37 65 61 66
m/z 359
[CrIII(Salen)(ACN)2]+
4.4 7.1 18 35 56 54 48
m/z 400
[CrIII(Salen)(DA)]+ 100 100 100 100 100 100 100
[CrIII(Salen)(DA)(ACN)]+ - - 2.9 5.1 5.1 0.7 0.3
[CrIII(Salen)(DA)2]+ - - 1.5 4.4 5.1 8.7 13
Table 1: Positive ion ESI mass spectra (cone voltage 30 V) of mixtures of [CrIII(Salen)]+ (as the
PF6- salt) with diamines (DA) ligands (1-7) in acetonitrile (ACN) solvent.
12. Ligand-Pickup Experiments:
The ion of interest can be selected by MS1 and allowed to undergo ion-molecule
reactions with the ligand of interest.
Empty axial positions of [CrIII(Salen)]+ ion are occupied by any ligand in collision
cell.
The displacement of weaker ligands in the axial positions by stronger ligands was
also observed this experiments.
Schematic diagram of ESI Mass Spectrometer
13. Ligand-Pickup Experiments:
ions
Cr Se lected
in MS1
PA
ulted S2
Res n M
N i ons
i
Cr
N
ligand-pickup experiments by selecting [Cr(Salen)(PA)]+ and
[Cr(Salen)(hexd)]+ ions using acetonitrile as the collision gas.
14. DA =
Mono [M(DA) L]+
L
[M(DA)] +
Col.Cell
MS1 Bi
[M(DA)]+
MS2
All the diamines(DA) are bidentate in nature with [CrIII (Salen)]+ at its axial
positions.
From these experiments diamines 6,7 and 8 shown to be week in bidentate (not
mono dentate) nature than the other diamines.
15. CID Experiments: (MS/MS)
Ar [Cr(Salen)]+
[Cr(Salen)(DA)]+
Col.Cell
MS1 MS2
Fig: The plot of Pc/Pd ratios ([CrIII(Salen)(DA)]+/ [CrIII(Salen)]+ obtained at collision
energies of 10, 12 and 14 eV from CID of [CrIII(Salen)(DA)]+ ions for ligands (Diamines)
1-7.
16. CID Experiments: (MS/MS)
Ar [Cr(Salen)]+
[Cr(Salen)(DA)]+
Col.Cell
MS1 MS2
Pc/Pd = Relative strength of the Diamines
The order of stabilities of [CrIII(Salen)(DA)]+ complexes for diamines
2-8 can be given as 3 >2 >4 >5 ≈ 8 >7 >6 from Pc/Pd ratios.
The relative binding strength of the
S o u r c e e x p e r im e n t s Diamines towards [Cr(Salen)]+
Io n -M o le c u le r e a c t io n s
C ID E x p e r im e n t s H2N-(CH2)n-NH2 n = 2-8.
3 >2 >4 >5 ≈ 8 >7 >6
Imp: Understanding the Metal complexes under MS conditions
17. Chapter 2: The effect of spacer chain length on ion binding to
bidentate ligands: Contrasting ordering for H+ and Alkali Metal ion
affinities
• Knowledge of accurate H+ and M+ ion binding interactions in poly-functional
macromolecules is an essential step in understanding the biophysical processes.
• The estimation of thermo chemical properties to the mono-functional molecules is
very much straight forward, whereas evaluation to the molecules with two or more
functional groups and chain length are particularly interesting i.e. bi-functional/
poly-functional case, because there will be an internal hydrogen bonding between
the functional groups.
• Protonation of α,ω-diamines has been also extensively studied using other mass
spectrometric methods and computational techniques.
Bidentate Ligands: Diamines and Diols
A
+
H (CH2)n H+
A (CH2)n A
A
A = NH2, OH
18. The Kinetic Method
• The method has been successfully used for the determination of proton
affinities, gas phase acidities, metal, chloride ion affinities, etc.
• This method was developed by Cooks and co-workers, is an effective
method for estimating the relative binding energies of two similar bases that
bind to a central ion, typically a proton/metal ion.
• Basically, the kinetic method consists in relating the ratio of the peak
intensities associated with two competitive dissociation channels
(heterodimer) to a difference in thermo-chemical properties of the
corresponding products.
[L1- - -M+- - -L2] L1 + L2M+ (rate constant = k1) (2)
L2 + L1M+ (rate constant = k2) (3)
ln([L2M+]/[L1M+]) ~ (∆HML2 - ∆HML1)/RTeff ~ ∆ΕΜ/RTeff (6)
19. H2N-(CH2)n-NH2
n = 2-8 (1-7)
Measured ln(ILi+-DA2/ILi+-DA1) values for Li+-bound heterodimers of diamines (1–7). The data presented under the
heading ln(ILi+-DA2/ILi+-DA2) are average cumulative values expressed relative to ethylene diamine (1). The numbers
given in parentheses are estimated errors resulting from the measurement of abundance ratios.
The ln[I(Li+-DA2)/I(Li+-DA1)] values for all pairs are consistent internally with a difference not more than
0.2
20. It is well known that, for chemically similar compounds, the natural logarithm of
intensity (I) ratio values are directly proportional to the binding energy difference
(∆E) (eq 1) between the used diamines with alkali metal ions (M+), where the
entropy term is close to zero.
ln(I(M+- L2) /I (M+- L1)) ~ ∆E /RTeff
• Attempts were made to convert relatve orders into relative alkali metal ion
affinities by measuring the Teff of the dissociating cluster ions.
• We seek to explain the observed contrasting ordering for H+ and Li+ ion
affinities of α, ω-diamines through quantum chemical calculations.
Metal ion affinity (∆H298) = ∆Eele + ∆Ethermal + Τ∆S - BSSE --2
Proton affinity (∆H298) = ∆Eele + ∆Ethermal + 5RT/2 --3
23. Proton and alkali metal ion affinities of α ,ω -
diols:
Spacer chain length effects
• The alkali metal ion affinity orders of α,ω-diamines were compared with their
proton affinity order and found that the affinity orders depend on the size of the
central ion used as well as the spacer chain length of α,ω-diamine.
• It is always ideal to extend such kind of gas phase ion studies to other bifunctional
group molecules for better understanding of their multiple interactions with proton/
metal ions.
• The Li+, Na+ and K+ ion affinity order of a series of α,ω-diols (HO-(CH2)n-OH, n=
2-10, 8-16) can be measured by the Kinetic method
H
O
M+
HO (CH2)n OH (CH2)n M+
O
H
24. Measured ln[I(H+-Diol2)/I(H+-Diol1)] values for H+-bound heterodimers of diols (8–16). The data presented
under the heading ln[I(H+-Diol2)/I(H+-14)] are average cumulative values expressed relative to octane diol (14).
25. • The relative affinity order for proton is
8H+<< 9H+<< 14H+ ≈ 13H+< 12H+< 11H+< 10H+< 15H+< 16H+
• where as for alkali metal ions the affinities are in the order of
8M+<< 9M+< 10M+< 11M+< 12M+< 13M+< 14M+< 15M+< 16M+, irrespective of
alkali metal ion used.
• The overall proton/alkali metal ion affinity orders of diols is almost similar to
that obtained for diamines, except some dissimilarities for the Li+ ion affinity
order of diamines.
26. CHAPTER 3
Generation of regiospecific carbanions from aromatic hydroxy acids
and dicarboxylic acids and characterized ion-molecule reactions with
carbon dioxide
؟ Why the study of carbanions in the gas phase is needed?
؟ Will the stable carbanions produce in ESI conditions?
• Carbanions execute a broad and substantial role as reactive intermediates
in organic reaction chemistry
• In the absence of solvation, gas phase studies can reveal the details of
reaction mechanisms and reactivity of ionic and neutral species
• Only three methods are possible to generate the carbanion.
1. Proton Abstraction
2. Fluoro desilylation
3. Decarboxylation
27. 1. Proton abstraction method
Proton abstraction from R–H by use of a strong base B.
Limitations:
The precursor must be sufficiently acidic deprotonation is Limited to molecules
with proton affinities (PA) less than 404 kcal/mol.
2. Fluorodesilylation method
DePuy and co-workers developed fluorodesilylation reactions for the formation
of carbanions and hence it has become popular as the DePuy reaction.
3. Decarboxylation
28. Danikiewicz et al. generated and studied the carbanions under ESI conditions.
The detection of the Carbanions is very easy, because they easily reacts with CO2.
Chou and Kass produced geometrical isomeric vinyl carbanions and studied
differences in the reactivity of these isomers by ion-molecule reactions.
Danikiewicz et al.: Phenide ions from the carboxylate anions by
using high cone voltage.
-
COO
High -
Cone
Ion-Molecule
Rxns with CO2
Benzoate ion Phenide ion
Here we describe the results concerning selective formation of very
unstable regiospecific carbanion from isomeric compounds.
29. O O
H
OH O - -
H
OH OH O
O O O H H
1 m/z 115 1C, m/z 71
O-
O O
H O
HO
-
O - I, m/z 71
OH OH OH
O O O
2 m/z 115 2C, m/z 71
30. -Ve ESI -CO2
M [M-H]- [M-H-CO2]-
-
COO
-
H
Y XH Y X
COOH
3C/6C/10C/13C
Y XH COOH
X = COO, Y = CH, 3
X = COO, Y = N, 6 - -
X = O, Y = CH, 10 Y X Y X
X = O, Y = N, 13 X = COO, Y = CH, II
X = COO, Y = N, III
X = O, Y = CH, IV
X = O, Y = N, V
-
COO -
COOH H
Y XH Y X
4C/7C/11C
COOH
Y XH
X = COO, Y = CH, 4
X = COO, Y = N, 7 II/III/IV
-
X = O, Y = CH, 11 Y X
-
OOC -
HOOC Y XH
Y XH
5C/8C/12C
HOOC
Y XH
X = COO, Y = CH, 5 II/III/IV
X = COO, Y = N, 8 -
Y X
X = O, Y = CH, 12
-
-
OOC Y XH Y XH
9C/14C
HOOC Y XH
X = COO, Y = N, 9 III/V
-
X = O, Y = N, 14 HOOC Y X
31. -Ve ESI -CO2
M [M-H]- [M-H-CO2]-
CH2COOH CH3
CH2COOH - -
O O
m/z 151 VIa, m/z 107
OH - -
CH2COO CH2
15
H
OH O
m/z 151 15C, m/z 107
CH2COOH CH3
CH2COOH
- -
O O
m/z 151 VIb, m/z 107
- -
CH2COO CH2
OH
16
OH OH
m/z 151 16C, m/z 107
CH2COOH CH3
CH2COOH
- -
O O
m/z 151
VIc, m/z 107
CH2COO- CH2-
OH
17
OH OH
m/z 151 17C, m/z 107
32. At high desolvation temperatures (3000C), instead of 1000C, the relative abundance of
[(M–H)–CO2]- ions and the corresponding CO2 adduct in ion-molecule reaction
experiments increased significantly due to minimization of proton exchange
Source/ Desolvation
Compound % increase in yield
Temp (OC)
100/100
1 8.5
150/300
100/100
3 25.3
150/300
100/100
4 12.9
150/300
100/100
11 17.2
150/300
100/100
12 2
150/300
34. Generation of regiospecific carbanions from Sulfobenzoic acids
• Here we have selected isomeric sulfobenzoic acids and disulfonic acids
COOH COOH COOH
SO3H
SO3H
SO3H
18 19 20
SO3H SO3H
SO3H
SO3H
21 22
35. -
SO3H SO3H SO3
Schemes: COO
-
COOH COOH
-Ve ESI -Ve ESI
m/z 201 m/z 201
- CO2 18 - CO2
- - -
SO3 SO3 SO3
-Ve ESI - CO2 - CO2 -Ve ESI
SO3H COOH SO3H
m/z 201 COOH
I, m/z 157 m/z 201
SO3H SO3H SO3H SO3H
COOH
- CO2 - CO2 COOH
19 20
-Ve ESI
COO
- - -Ve ESI
- -
m/z 201 A, m/z 157 B, m/z 157 COO
m/z 201
Ion-Molecule Reactions SO3H
SO3H with CO2
-
COO COO
-
m/z 201 m/z 201
Schemes 1
-
SO3
- -
-Ve ESI -SO3
-
SO3H SO3 SO3 SO3 SO3H
SO3H SO3H -
-Ve ESI SO3H COO
-Ve ESI
- SO3 - SO3 COOH
SO3H SO3H m/z 201
21 m/z 237 I, m/z 157 m/z 237 22
SO3H
COOH m/z 121
Schemes 2 3 -SO3
-Ve ESI
-
Schemes 3 COO
m/z 201
36. GENERATION OF DISTONIC DEHYDROPHENOXIDE RADICAL
ANIONS UNDER ELECTROSPRAY AND ATMOSPHERIC PRESSURE
CHEMICAL IONIZATION CONDITIONS
General methods for the Preparation of radical anions
2. Electron attachment (dissociative)
N2O e N2 + O-.
2. Electron transfer
3. Ion-molecule reactions
37. DISTONIC RADICAL ANIONS Definition:
Distonic Ions: which possess distinct, spatially separated charged and radical
sites.
OH O- O-
R
OH -
R . Bowie et al.
-R.
R = H/Me/Et/i-Pr m/z 92
Distonic dehdyro phenoxide
radical anions
Squires and co-workers presented several applications of the above
method to generate isomeric distonic radical anions
Si(CH3)3 Si(CH3)3
.
F- F2
Si(CH3)3 - -
- (CH3)3SiF -(CH3)3SiF
-F -, -F . m/z 76
o-, m- and p-
38. Kass et al. recently reported another new method for the generation of distonic radical anions from
aromatic mono and dicarboxylic acids
CO2H CO2-
-
.
EI/ESI -CO2 -NO.
NO2 NO2
SORI-CID
NO2 SORI-CID O-
o-, m- and p- m/z 92
Nitrobenzoic Acid
COOH COO-
. .
F- SORI
- - SORI
COOH COO COO -
HF CO2 -CO2
o-, m- and p-
benzenedicarboxylic acid
39. Characterization of radical anions:
Include isotopic labeling, specific ion-molecule reactions, CID, and collision induced
charge reversal processes
- -
CO2 CO2
-
CO2 NO2
NO2
.
.
• In Chapter 3, we have shown that isomeric carbanions do survive in the ESI
process and selectively react with CO2 when ion-molecule reactions are
performed on these carbanions in the collision cell.
• This encouraged us to extend the same method to study generation of
isomeric dehydrophenoxide radical anions from suitably substituted
nitrobenzoic acids and phenols, and studying their ion-molecule reactions
with CO2 in the collision cell.
40. Nitrobenzoic acids
COOH COOH
COOH
NO2
NO2 NO2
1 2 3
10 ev
Negative ion electrospray ionization
spectra of 3 at different cone voltage 20 ev
values
30 ev
40 ev
41. CID mass spectra of (a) [3-H]‑ (m/z 166) at 20
eV collision energy, (b) [3-H-CO2]‑ (m/z 122)
at 20 eV collision energy.
COOH COO-
- .
NO2 NO2 NO2 O-
-ve ESI
-CO2 -NO.
1 m/z 166 m/z 122 I, m/z 92
COOH COO-
- .
-ve ESI
-CO2 -NO.
Mechanism NO2 NO2 NO2
II, m/z 92
O-
2 m/z 166 m/z 122
COOH COO-
- .
-ve ESI
-CO2 -NO.
NO2 NO2 NO2 O-
3 m/z 166 m/z 122 III, m/z 92
42. OH
OH OH
CH3
CH3
CH3
4 5 6
OH
OH OH
NO2
NO2
NO2
7 8 9
OH
OH OH
CHO
CHO
CHO
10 11 12
43. OH O- O-
R R
. .
-Ve ESI -R
R = -CH3 (4) ; -NO2(7)
OH O- O-
.
-Ve ESI -R
.
R R
R = -CH3 (5) ; -NO2 (8); -CHO(11)
OH O- O-
.
-Ve ESI -R
.
R R
R = -CH3 (6) ; -NO2 (9); -CHO (12)
• The compound 10 does not yield the expected ion at m/z 92, instead it shows the ion at m/z
93 corresponding to the loss of CO from [M-H]- ion due to ortho-effect
44. ESI-high resolution mass spectrum of compound 12.
The Ion-molecule reactions mass spectra of m/z 92, [(12-CHO)-NO]-.
with CO2 in the collision cell
45. Generation of Distonic dehydrophenoxide radical anions from
substituted phenols under atmospheric pressure chemical ionization
conditions.
• Though ESI technique is not amenable to study the isomeric nitrobenzaldehydes
and nitroacetophenones, they can be analyzed under negative ion APCI conditions
• Loss of NO˙ from the molecular ions of nitroaromatic compounds generated under
EI conditions was reported using a tandem sector mass spectrometer.
• In this part, two groups of isomeric substituted nitrobenzenes (13-18), i.e. ortho-,
meta- and para- nitrobenzaldehydes (13-15) and ortho-, meta- and para-
nitroacetophenones (16-18) were selected to study their source fragmentation
under APCI conditions. NO
NO2 2
NO2
CHO
CHO
CHO
13 14 15
NO2
NO2 NO2
COCH3
COCH3
COCH3
16 17 18
46. Generation of Distonic dehydrophenoxide radical anions from
substituted phenols under atmospheric pressure chemical ionization
conditions.
• Under APCI conditions the studied compounds form M-. ion, and upon source
fragmentation/CID they result in [M-NO]- ion.
• Further fragmentation of the [M-NO]- of ortho-isomers specifically show loss
of a neutral (CO or COCH2) to yield the fragment ion at m/z 93.
• The [M-NO]- of meta- and para- isomers further show a radical loss (.CHO
or .COCH3) to generate dehydrophenoxide radical anion (m/z 92).
-.
NO2 NO2 O- O-
-Ve APCI -NO. -CHO.
.
CHO CHO CHO
14 m/z 92
-.
NO2 NO2 O- O-
-Ve APCI -NO. -CHO.
.
CHO CHO CHO m/z 92
15