Novel glucose derived non-ionic gemini surfactants as reverse micellar systems for encapsulation of d- and l-enantiomers of some aromatic α-amino acids in n-hexane

Article abstract of DOI:10.1007/s10847-012-0107-y

Novel glucose-based non-ionic gemini amphiphiles comprising two sugar head groups, two hydrophobic tails having chain length of C₁₂, C ₁₄, and C₁₈ and a -CH₂-Ar-CH₂- spacer have been synthesized. The

Full text of DOI:10.1007/s10847-012-0107-y

J Incl Phenom Macrocycl Chem (2012) 74:251–256
DOI 10.1007/s10847-012-0107-y
ORIGINAL ARTICLE
Novel glucose derived non-ionic gemini surfactants as reverse
micellar systems for encapsulation of D- and L-enantiomers
of some aromatic a-amino acids in n-hexane
•
Lalit Sharma Saroj
Received: 1 November 2010 / Accepted: 4 January 2012 / Published online: 28 January 2012
Ó Springer Science+Business Media B.V. 2012
Abstract Novel glucose-based non-ionic gemini amphi-
philes comprising two sugar head groups, two hydrophobic
tails having chain length of C12, C14, and C18 and a –CH2–
Ar–CH2– spacer have been synthesized. The head groups
of the geminis consist of glucose entities (with reducing
function blocked in cyclic acetal group) connected through
C-6 to tertiary amines. These amphiphiles were explored as
reverse micellar systems, for the encapsulation of D- and
L-enantiomers of ultraviolet-absorbing aromatic a-amino
acids histidine (H), phenylalanine (F), tyrosine (Y) and
tryptophan (W) in n-hexane, without any added water.
Reverse micellar studies revealed that aromatic a-amino
acids were encapsulated in the sequence H [ F [ Y [ W.
In most cases, specifically for F, D-enantiomer was found
better encapsulated than L-enantiomer in the reverse
micellar probes of the gemini surfactants.
cationic, non-ionic or zwitterionic in nature. Different
types of geminis have been synthesized and because of
their unique properties, have opened a new field of research
within surfactant chemistry [5]. Recently, their application
as gene transfection agents have been reviewed [6, 7].
Carbohydrate based non-ionic gemini surfactants are
relatively new comers. Current interest in these amphi-
philes is growing rapidly as besides their proven physical
properties, these are biocompatible and posses broad
spectrum of molecular architecture. Different types of
carbohydrate based non-ionic gemini surfactants have been
reported [8–31].
Herein, we describe the synthesis of some new carbo-
hydrate based tertiary amino non-ionic gemini surfactants
derived from 6-amino-6-deoxy-D-glucose and their use as
reverse micellar systems for the encapsulation of D- and
L-enantiomers of some aromatic a-amino acids histidine
(H), phenylalanine (F), tyrosine (Y), and tryptophan (W) in
n-hexane, without any added water.
Keywords Non-ionic gemini surfactants ꢀ 5,6-Anhydro-
1,2-O-isopropylidene-a-D-glucofuranose ꢀ Amino acids ꢀ
Reverse micelles
Results and discussion
Introduction
Synthesis and characterization
Gemini surfactants or dimeric surfactants are novel class of
amphiphilic molecules, first appearing in literature in 1971
[1]. Geminis possess two hydrophilic head groups and two
hydrophobic alkyl tails linked by a flexible [2] or rigid [3]
spacer, which can be hydrophilic or hydrophobic [4]. The
nature of head group characterizes the geminis as anionic,
Structures of glucose derived non-ionic geminis are given
in Scheme 1. Diamines 2–4 were synthesized by refluxing
terephthaldehyde and appropriate amine in the ratio 1:2 in
ethanol for 3–4 h, followed by reduction of corresponding
Schiff’s base with NaBH4 for 30 h at room temperature.
Gemini amphiphiles 5–7 were synthesized by dry heat-
ing of the appropriate diamine with 5,6-anhydro-1,2-O-
isopropylidene-a-D-glucofuranose (1) at 120–130 °C for
1 h. They possess a tertiary amino group linked to C-6 of
each glucose moiety with its reducing function blocked in a
L. Sharma (&) ꢀ Saroj
Department of Applied Chemistry, SBS College of Engineering
& Technology, Ferozepur 152 004, India
e-mail: s.lalit@lycos.com; srjverma@rediffmail.com
123

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J Incl Phenom Macrocycl Chem (2012) 74:251–256
13C NMR signal assignments are supported by INEPT
data. For diamines 2–4, methyl signals of alkyl chains were
found at d 14.2. Signals for methylene (attached to nitrogen
and to phenyl ring) were found at 49.6 and 53.9, respec-
tively. Aromatic carbons were found at 128.1–128.2 and at
139.2–139.3, respectively. Later signals disappeared in
INEPT spectra to confirm that these were of aromatic
quaternary carbons.
H
H
a
6
R
b
O
b
5
4
N
CH3(CH2)n
O
1
OH
b
O
N
b
(CH2)nCH3
CH3
a
O
3
2
R
a
CH3
a
1
n = 11, R = H
2
O
3 n = 13, R = H
N
4 n = 17, R = H
5 n = 11, R =
OH
H
6
N
H
NH2
H
In 5,6-anhydro-1,2-O-isopropylidene-a-D-glucofuranose
1 and gemini amphiphiles 5–7, the signals for the anomeric
carbon, the isopropylidene-acetal carbon and the isopro-
L-Histidine
OH
5
O
1
a
CH3
CH3
a
OH
3
O
4
O
N
2
O
OH
pylidene-methyl groups were found invariant at
d
N
H
NH2
(104.9 0.1), (111.6 0.0), and (26.5 0.3), respec-
tively. The chemical shifts for sugar carbons C-2, C-3, C-4,
and C-5 were also found constant at (85.2 0.1),
(75.3 0.1), (81.5 0.0), and 66.6 0.2), respectively.
The C-5 and C-6 signals for gemini amphiphiles 5–7 were
found downfield as compared to those in 1. The chemical
shifts for aromatic carbons (except the quaternary carbons)
were found downfield in 5–7 compared to those in 2–4 but
signals due to aromatic quaternary carbons were found
upfield in geminis compared to those in diamines. The
methyl signal of the long alkyl tails was found at 14.2 ppm
and methylene carbons (except the directly attached to
nitrogen) at 22.8–32.0 ppm as multiplets. The methylene
(directly attached to nitrogen) signal was also found
invariant at (55.5 0.1) ppm.
6 n = 13, R = as in 5
7 n = 17, R = as in 5
D-Histidine
O
O
O
OH
OH
NH2
OH
NH
NH2
HO
NH2
L-Tryptophan
O
L-Tyrosine
O
L-Phenylalanine
O
OH
OH
OH
NH2
NH
NH2
HO
NH2
D-Phenylalanine
D-Tryptophan
D-Tyrosine
Scheme 1 Structures of glucose derived gemini surfactants and
aromatic amino acids
cyclic acetal group. Oxirane ring opening of 1 by sec-
ondary amine is expected to proceed by exclusive nucle-
ophilic attack on C-6 and without inversion at C-5 [32].
The NMR signal assignments were based on previous
Synthesis was also confirmed by ESI-MS spectra and
elemental analysis
Solubilization of a-amino acids in apolar media
1
studies by Hall et al. [33] (for H NMR) and Vyas et al.
[34] (for 13C NMR) on O-isopropylidene-D-hexoses. Dia-
mines 2–4 depict nearly identical spectra. In 1H NMR
spectra of diamines, methyl signal was found at d 0.88,
signal due to methylene (directly attached to nitrogen) at
2.60–2.61 and signal due to methylene (directed attached to
phenyl) at 3.76, respectively. Signal due to aromatic pro-
tons was found at 7.26 for all diamines.
Reverse micelles formation by gemini surfactants 5–7 was
studied by solubilization of D- and L-enantiomers of ultra-
violet-absorbing aromatic amino acids H, F, Y, and W in
n-hexane, without any added water, using UV monitoring.
The critical micelle concentrations (cmc’s) of surfactants
are documented in Table 1 and were determined by method
of Gratzer and Beaven [35]. The surfactant concentration
was kept well above cmc for reverse micellar studies.
Solubilization studies for D- and L-enantiomers of aro-
matic amino acids in n-hexane in presence of gemini sur-
factants are documented in Tables 2, and 3, respectively.
From these solubilization studies it was found that both
Gemini amphiphiles 5–7 also show identical spectra. In
1H NMR spectra, the chemical shifts for sugar hydrogen
H-1 (5.91–5.92), H-2 (4.46), and H-3 (4.17–4.18) were
found constant and characteristic of these protons. Signals
for H-4 and H-5 were found overlapping at 3.87–3.93,
respectively. The most prominent shift was found in H-6
signals. The methyl signal for alkyl chain was found at d
0.88 and methylene signals at 1.26–1.36 but merged with
one of sugar isopropylidene signals. The signal at d 1.46
was assigned to other sugar isopropylidene-methyl group.
The position of methylene (directly attached to nitrogen)
could not be assigned due to overlapping signals. Aromatic
protons for gemini amphiphiles were found at 7.25–7.26,
respectively.
Table 1 HLB (hydrophilic–lipophilic balance) values and critical
micelle concentration (cmc) of the surfactants
Surfactant
HLB value
cmc (moles L-1
)
5
6
7
9.2
8.7
7.7
5.0 9 10-4
1.6 9 10-4
5.0 9 10-5
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253
the hydroxyl groups, on sugar surfaces can form contacts
with hydrophobic side chain of the amino acids [36].
The better encapsulation of a particular enantiomer of
aromatic amino acids than its antipode is attributed to a
pronounced shape complementarity with the reverse
micellar phase of surfactant and thus difference in their
structure fit. In such cases, there is more enough ‘chiral
face’ to interact with that enantiomer than its antipode.
Table 2 Solubilization of L-aromatic amino acids in n-hexane with
the help of reverse micelles formed by surfactants
Surfactant Micellar ratio (amino acid:molecules of micelle)
L-Histidine L-Phenylalanine L-Tyrosine L-Tryptophan
5
6
7
1:7.2
1:21.6
1:12.3
1:35.0
1:37.0
1:17.1
1:44.2
1:213.7
1:128.0
1:331.0
1:11.1
1:20.0
Conclusions
Table 3 Solubilization of D-aromatic amino acids in n-hexane with
the help of reverse micelles formed by surfactants
The dissolution of solid aromatic a-amino acids in apolar
media provides valuable means of study amino acids rec-
ognition by carbohydrate derived non-ionic gemini
surfactants. The present investigation shows that glucose
derived non-ionic gemini surfactants (5–7) act as reverse
micellar systems in n-hexane, without any added water.
These amphiphiles also show different propensity towards
encapsulation of D- and L-enantiomers of aromatic a-amino
acids H, F, Y, and W. The propensity was specific in case
of F, thus better encapsulation of D- than L-enantiomer of F
by all these amphiphiles. This study may also lead to
potential applications of reverse micelles in such environ-
ments where the absence of water is required for extremely
aggressive chemistry [38].
Surfactant Micellar ratio (amino acid:molecules of micelle)
D-Histidine D-Phenylalanine D-Tyrosine D-Tryptophan
5
6
7
1:6.7
1:18.1
1:9.0
1:35.7
1:14.9
1:56.0
1:109.4
1:129.0
1:232.5
1:12.7
1:31.0
1:23.2
enantiomers of aromatic amino acids were solubilized in
the order H [ F [ Y [ W. Comparison of Tables 2, and 3
indicate a difference in the encapsulation of D- and
L-enantiomers of aromatic amino acids in reverse micellar
phases of gemini amphiphiles in n-hexane. In most cases,
specifically for F, it was found that D-enantiomer was better
encapsulated than its antipode, i.e., L-enantiomer.
Hydrophilic–lipophilic balance (HLB) values [37] of the
surfactants are documented in Table 1. Hydrophilicity of
the surfactants used in this study is of the order 5 [ 6 [ 7.
Size of the aromatic amino acids is of the order
H \ F \ Y \ W. Tables 2 and 3 clearly show that more
hydrophilic surfactant gives better micellar ratio for
encapsulation of aromatic amino acids which are better
recognized by the reverse micellar phase in order of their
smaller size, i.e., smaller is the amino acid better is its
encapsulation. Thus, H being smallest is best encapsulated
and W being largest is least encapsulated. The high
propensity of H towards encapsulation may also be facili-
tated by its all available nitrogen atoms involved in
hydrogen bond formation with surfactant head groups.
The main driving force for encapsulation of aromatic
amino acids by surfactants 5–7 is the electrostatic inter-
actions between aromatic amino acids and glucose head
groups of the gemini surfactants at the reverse micellar
interface. A glucose hydroxyl can interact with aromatic
amino acid both as hydrogen bond donor as well as
acceptor. As donor it possesses added advantage of having
rotational freedom about C–OH torsional angle, thus
enabling it to attain the best possible linear bond with
amino acid, which is important in imparting specificity.
Hydrophobic portions, created due to steric disposition of
Experimental
Melting point determinations were performed in capillaries
and are uncorrected. NMR spectra were recorded on a
Bruker Avance II 400 Spectrometer with SiMe4 as an
internal reference. J-values are given in Hz. UV spectra
were recorded with an EC 5704 SS spectrophotometer.
ESI-MS spectra were measured on a Waters Micromass
Q-Tof micro mass spectrometer coupled with Waters 2795
HPLC system. Optical rotations were measured with a
JASCO DIP-360 digital polarimeter in a 1 dm cell. Specific
rotations are reported in degrees. Elemental analyses were
performed by Perkin Elmer 2400 CHN elemental analyser.
Materials
Column chromatography was performed on silica gel
(60–120 mesh) and TLC plates were coated with silica G.
The spots were developed in iodine and/or charring with
1% sulfuric acid in water. Doubly distilled water and
analytical grade n-hexane were used for spectroscopy.
Distilled solvents were used for column chromatography.
Other chemicals were of AR grade and used without fur-
ther purification.
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J Incl Phenom Macrocycl Chem (2012) 74:251–256
ESI-mass m/z 551.4 (M ? Na)?. Anal. calcd. for
C36H68N2: C 81.75, H 12.96, N 5.30; found C 82.03, H
13.18, N 5.62.
Preparation of 5,6-anhydro-1,2-O-isopropylidene-a-D-
glucofuranose (1)
The compound was synthesized as described in literature
[39], m.p. 133 °C. 1H NMR (400 MHz, CDCl3): d 1.32 and
1.48 (s, 3H, CH3-a), 2.87 (dd, 1H, J = 2.9, 2.8, H-6a), 2.99
(dd, 1H, H-6b), 3.24 (s, 1H, OH), 3.42 (m, 1H, H-5), 4.00
(dd, 1H, H-4), 4.27 (dd, 1H, H-3), 4.52 (d, 1H, J = 3.6,
H-2), 5.99 (d, 1H, J = 3.6, H-1); 13C NMR (100 MHz,
CDCl3): d 26.2 and 26.8 (CH3-a), 46.1 (C-6), 50.2 (H-5),
75.2 (C-3), 79.6 (C-4), 85.1 (C-2), 105.0 (C-1),
111.9 (Me2C); Inept: d 26.2, 26.8 (?ve), 46.1 (-ve), 50.2,
75.2, 79.5, 85.1, 105.0 (?ve). ESI-mass m/z 224.7
(M - H ? Na)?.
N,N0-Di(octadecyl)-p-phenylenediamine (4)
1
Colorless solid in 81% yield (2.60 g); m.p. 75–77 °C. H
NMR (400 MHz, CDCl3): d 0.88 (t, 6H, CH3), 1.25
(s, 54H, CH2 and NH), 1.49 (br, 4H, CH2CH2N), 2.61
(t, 4H, NCH2CH2), 3.76 (s, 4H, CH2Ph), 7.27 (s, 4H,
Ar–H); 13C NMR (100 MHz, CDCl3): d 14.1 (CH3),
22.7–32.0 (CH2), 49.6 (CH2CH2N), 53.9 (CH2Ph), 128.1
(Ar–C), 139.2 (Ar–C); Inept: 14.1 (?ve), 22.7, 27.4, 29.4,
29.5, 29.6, 29.7, 30.2, 32.0 (-ve), 49.6 (-ve), 53.9 (-ve),
128.1 (?ve). ESI-mass m/z 640.4 (M)?, 683.5 (M ? 2H ?
Na ? H2O)?. Anal. calcd. for C44H84N2: C 82.43, H 13.21,
N 4.37; found C 82.52, H 13.42, N 4.62.
General method for the synthesis of long tailed
diamines (2–4)
Terephthaldehyde (670 mg, 5 mmol) and appropriate long
chain amine (10 mmol) were dissolved in EtOH (30 mL)
and refluxed for 4 h. The mixture was cooled to room
temperature and NaBH4 (570 mg, 15 mmol) was added
during 10 min. The mixture was stirred for additional 24 h
at room temperature. Excess NaBH4 was decomposed with
water and the solvent evaporated under diminished pres-
sure. The residue was recrystallized from ethanol. The
yields and spectroscopic data for resulted compounds are
given below:
General method for the synthesis of glucose derived
non-ionic gemini surfactants (5–7)
Appropriate diamine 2–4 (2 mmol) was heated to 100 °C
and to this was added 1 (808 mg, 4 mmol). The temperature
was raised to 120–130 °C and kept for 1 h. Purification of the
residue by column chromatography on silica gel (1:2
EtOAc–CH2Cl2) resulted desired product. The yields and
spectroscopic data for resulted surfactants are given below:
[6,60-(N,N0-Di(dodecadecyl)-p-phenylenediamino)]
N,N0-Di(dodecyl)-p-phenylenediamine (2)
bis(6-deoxy-1,2-O-isopropylidene-a-D-glucofuranose) (5)
1
Syrup in 84% yield (1.47 g); 1H NMR (400 MHz, CDCl3):
d 0.88 (t, 6H, CH3-b), 1.26–1.34 (m, 46H, CH2 and CH3-a),
1.46 (s, 6H, CH3-a), 1.52 (br, 4H, OH), 2.52–2.62 (m, 6H,
NCH2 and H-6b), 2.74 (dd, 2H, J = 4.2, 4.6 Hz, H-6a),
3.57–3.69 (AB system, 4H, J = 3.3 Hz, CH2Ph),
3.87–3.93 (m, 4H, H-5 and H-4), 4.18 (d, 2H, J = 2.4 Hz,
H-3), 4.46 (d, 2H, J = 3.7, H-2), 5.91 (d, 3.7, H-1), 7.25
(s, 4H, Ar–H); 13C NMR (100 MHz, CDCl3): d 14.2 (CH3-b),
22.7–31.9 (CH2 and CH3-a), 55.4(NCH2CH2), 57.4(CH2Ph),
58.8 (C-6), 66.4 (C-5), 75.2 (C-3), 81.5 (C-4), 85.2 (C-2),
105.0 (C-1), 111.6 (Me2C), 129.7 (Ar–C), 137.1 (Ar–C),
Inept: 14.2 (?ve), 22.8 (-ve), 26.2, 26.8 (?ve), 26.4, 27.3,
29.4, 29.6, 29.7, 32.0, 55.4, 57.4, 58.8 (-ve), 66.3, 75.1, 81.5,
85.2, 105.0, 129.7 (?ve); ESI-mass m/z 898.1 (M–H ? Na)?.
Colorless solid in 81% yield (1.91 g); m.p. 49–50 °C. H
NMR (400 MHz, CDCl3): d 0.88 (t, 6H, CH3), 1.25
(s, 36H, CH2), 1.48 (br, 4H, CH2CH2N), 1.65 (brs, 2H,
NH), 2.60 (t, 4H, NCH2CH2), 3.76 (s, 4H, CH2Ph), 7.26 (s,
4H, Ar–H); 13C NMR (100 MHz, CDCl3): d 14.2 (CH3),
22.8–32.0 (CH2), 49.6 (CH2CH2N), 53.9 (CH2Ph), 128.2
(Ar–C), 139.3 (Ar–C); Inept: d 14.2 (?ve), 22.8, 27.4, 29.4,
29.7, 30.2, 32.0 (-ve), 49.6 (-ve), 53.9 (-ve), 128.2
(?ve). ESI-mass m/z 473.2 (M ? H)?, 511.2 (M ? K)?.
Anal. calc. for C32H60N2: C 81.29, H 12.39, N 5.92; found
C 80.73, H 12.63, N 5.98.
N,N0-Di(tetradecyl)-p-phenylenediamine (3)
1
Colorless solid in 80% yield (2.11 g); m.p. 65–67 °C. H
[6,60-(N,N0-Di(tetradecyl)-p-phenylenediamino)]
NMR (400 MHz, CDCl3): d 0.88 (t, 6H, CH3), 1.25 (s,
46H, CH2 and NH), 1.50 (br, 4H, CH2CH2N), 2.61 (t, 4H,
NCH2CH2), 3.76 (s, 4H, CH2Ph), 7.27 (s, 4H, Ar–H); 13C
NMR (100 MHz, CDCl3): d 14.1 (CH3), 22.7–31.9 (CH2),
49.6 (CH2CH2N), 53.9 (CH2Ph), 128.1 (Ar–C), 139.2
(Ar–C); Inept: d 14.1 (?ve), 22.7, 27.4, 29.4, 29.6, 29.7,
30.1, 31.9 (-ve), 49.6 (-ve), 53.9 (-ve), 128.1 (?ve).
bis(6-deoxy-1,2-O-isopropylidene-a-D-glucofuranose) (6)
Syrup in 82% yield (1.53 g); [a]2D7 = -1.4° (c 0.6, CHCl3).
1H NMR (400 MHz, CDCl3): d 0.88 (t, 6H, CH3-b),
1.26–1.34 (m, 54H, CH2 and CH3-a), 1.46 (s, 6H, CH3-a),
1.53 (br, 4H, OH), 2.52–2.62 (m, 6H, NCH2 and H-6b),
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J Incl Phenom Macrocycl Chem (2012) 74:251–256
255
2.75 (dd, 2H, J = 4.2, 4.6 Hz, H-6a), 3.55–3.69 (AB sys-
tem, 4H, J = 3.3 Hz, CH2Ph), 3.87–3.92 (m, 4H, H-5 and
H-4), 4.18 (d, 2H, J = 2.4 Hz, H-3), 4.46 (d, 2H, J = 3.6,
H-2), 5.92 (d, 3.6, H-1), 7.26 (s, 4H, Ar–H); 13C NMR
(100 MHz, CDCl3): d 14.2 (CH3-b), 22.8–32.0 (CH2 and
CH3-a), 55.4 (NCH2CH2), 57.3 (CH2Ph), 58.8 (C-6), 66.4
(C-5), 75.2 (C-3), 81.5 (C-4), 85.1 (C-2), 105.0 (C-1),
111.6 (Me2C), 129.6 (Ar–C), 137.1 (Ar–C), Inept: 14.2
(?ve), 22.8 (-ve), 26.2, 26.8 (?ve), 26.4, 27.3, 29.4, 29.6,
29.7, 32.0, 55.4, 57.3, 58.8 (-ve), 66.4, 75.2, 81.5, 85.1,
105.0, 129.6 (?ve); ESI-mass m/z 934.1 (M ? H)?, 956.0
(M ? Na)?, 972 (M ? K)?.
determined by electronic absorption spectroscopy (211 for
H, 257 for F, 274 for Y and 280 nm for W). Solubilities
thus obtained were corrected for the solubilities of aromatic
amino acids in n-hexane without surfactant found in the
same way.
Acknowledgments The financial support of this work (Grant
SERC/OC-17/2006) and research fellowship to Srj from the Depart-
ment of Science and Technology, Government of India, New Delhi
was gratefully acknowledged. Spectroscopic analysis by SAIF, Pan-
jab University, Chandigarh is highly appreciated.
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Colorless solid in 82% yield (1.71 g); m.p. 61–62 °C.
[a]2D7 = ? 21.3° (c 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3): d 0.88 (t, 6H, CH3-b), 1.26–1.36 (m, 70H, CH2
and CH3-a), 1.46 (s, 6H, CH3-a), 1.52 (br, 4H, OH),
2.52–2.62 (m, 6H, NCH2 and H-6b), 2.76 (dd, 2H, J = 4.4,
4.7 Hz, H-6a), 3.54–3.69 (AB system, 4H, CH2Ph),
3.87–3.93 (m, 4H, H-5 and H-4), 4.17 (d, 2H, J = 2.4 Hz,
H-3), 4.46 (d, 2H, J = 3.6, H-2), 5.92 (d, 3.6, H-1), 7.24
(s, 4H, Ar–H); 13C NMR (100 MHz, CDCl3): d 14.2 (CH3-
b), 22.8–32.0 (CH2 and CH3-a), 55.6 (NCH2CH2), 57.4
(CH2Ph), 58.9 (C-6), 66.8 (C-5), 75.4 (C-3), 81.5 (C-4),
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66.8, 75.4, 81.5, 85.3, 104.9, 129.4 (?ve); ESI-mass m/
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