Structure fragmentation studies of ring-substituted N-trifluoroacetyl-N-benzylphenethylamines related to the NBOMe drugs

Article abstract of DOI:10.1002/rcm.8593

Rationale: The halogenated derivatives of N-(2-methoxy)benzyl-2,5-dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo analogue (25B-NBOMe) represent a new class of hallucinogenic or psychedelic drugs. The purpose of this study was to determine the role of the electron-donating groups (halogen and dimethoxy) in the pathway of decomposition for the distonic molecular radical cation in the electron ionization mass spectrometry (EI-MS) process of the trifluoroacetamide (TFA) derivatives. Methods: The systematic removal of substituents from the 4-halogenated 2,5-dimethoxyphenethylamine portion of the N-dimethoxybenzyl NBOMe analogues allowed an evaluation of structural effects on the formation of major fragment ions in the EI-MS of the TFA derivatives. All six regioisomeric dimethoxybenzyl-substituted analogues (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethoxy) for the four series of phenethyl aromatic ring substitution patterns were prepared, derivatized and analyzed via gas chromatography coupled with EI-MS. Results: The analogues yield two unique radical cation fragments from the decomposition of the common distonic molecular radical cation. The substituted phenylethene radical cation (m/z 164) is the base peak or second most abundant ion in all six TFA-2,5-dimethoxyphenethylamine isomers. The dimethoxybenzyltrifloroacetamide radical cation (m/z 263) is the base peak or second most abundant ion in the 2- and 3-monomethoxyphenethylamine isomers. However, the 2- and 3-methoxyphenylethene radical cation (m/z 134) is among the five most abundant ions for each of these twelve isomers. Only one isomer in the phenethylamine series yields the corresponding unsubstituted phenylethene radical cation at m/z 104. Conclusions: The decomposition of the hydrogen-rearranged distonic molecular radical cation favors formation of the dimethoxybenzyltrifloroacetamide (m/z 263) species for the less electron-rich phenethyl aromatic rings. The addition of electron-donating groups to the aromatic ring of the phenethyl group as in the NBOMe-type molecules shifts the decomposition of the common distonic molecular radical cation to favor the formation of the electron-rich substituted phenylethene radical cation.

Full text of DOI:10.1002/rcm.8593

Clark C. Randall (Orcid ID: 0000-0002-4063-605X)
Structure Fragmentation Studies for Ring Substituted N-Trifluoroacetyl-N-
Benzylphenethylamines Related to the NBOMe Drugs
1
, 2
1
Ahmad J. Almalki , C. Randall Clark
and Jack DeRuiter1
(
1) Department of Drug Discovery and Development,
Harrison School of Pharmacy, Auburn University,
Auburn, AL 36849, USA
(2) Department of Pharmaceutical Chemistry,
Faculty of Pharmacy, King Abdulaziz University
Jeddah, Saudi Arabia
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differences between this version and the Version of Record. Please cite this article as doi:
10.1002/rcm.8593
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Abstract
Rationale: The halogenated derivatives of N-(2-methoxy)benzyl-2,5-
dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo-analogue (25B-NBOMe)
represent a new class of hallucinogenic or psychedelic drugs. The purpose of this study was
to determine the role of the electron-donating groups (halogen and dimethoxy) on the
pathway of decomposition for the distonic molecular radical cation in the EI-MS of the
trifluoroacetamide (TFA) derivatives.
Methods: The systematic removal of substituents from the 4-halogenated-2,5-dimethoxy-
phenethylamine portion of the N-dimethoxybenzyl NBOMe analogues allowed an evaluation
of structural effects on the formation of major fragment ions in the EI-MS of the TFA
derivatives.
All six regioisomeric dimethoxybenzyl substituted analogs (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-
dimethoxy) for the four series of phenethyl aromatic ring substitution patterns were prepared,
derivatized and analyzed via GC/EI-MS.
Results: The analogues yield two unique radical cation fragments from the decomposition of
the common distonic molecular radical cation. The substituted phenylethene radical cation
(
m/z 164) is the base peak or second most abundant ion in all six TFA-2,5-
dimethoxyphenethylamine isomers. The dimethoxybenzyltrifloroacetamide radical cation
m/z 263) is the base peak or second most abundant ion in the 2- and 3MMPEADMB
(
isomers. However, the 2- and 3-methoxyphenylethene radical cation (m/z 134) is among the
five most abundant ions for each of these twelve isomers. Only one isomer in the PEADMB
series yields the corresponding unsubstituted phenylethene radical cation at m/z 104.
Conclusions: The decomposition of the hydrogen rearranged distonic molecular radical
cation favors formation of the dimethoxybenzyltrifloroacetamide (m/z 263) species for the
less electron rich phenethyl aromatic rings. The addition of electron-donating groups to the
aromatic ring of the phenethyl group as in the NBOMe-type molecules shifts the
decomposition of the common distonic molecular radical cation to favor the formation of the
electron-rich substituted phenylethene radical cation.
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Introduction
The relative distributions of major fragment ions for trifloroacetyl derivatives of
substituted phenethylamine-type compounds such as 4-iodo- and 4-bromo N-
dimethoxybenzyl-2,5-dimethoxyphenethylamines are described in this report. The four series
of compounds (Figure 1) compared in this study can be viewed as the sequential deletion of
the electron-donating groups on the phenethylamine portion of the 4-halogenated 2,5-
dimethoxyphenethyl-amines. Comparison of the major EI-MS fragment ions and their
abundances for the TFA-derivatives for all six regioisomeric N-dimethoxybenzyl isomers in
all four series of secondary amines will provide additional structure-fragment relationship
data for this series of compounds.
The substituted N-benzyl derivatives of 4-halogenated 2,5-
dimethoxyphenethylamines are examples of the expanding category of drugs of abuse
sometimes referred to as new/novel psychoactive substances (NPS drugs). The 4-iodo- and 4-
bromo-2,5-dimethoxyphenethylamines having a 2-methoxybenzyl substituent on nitrogen are
among the most common hallucinogenic substances referred to as NBOMe drugs. These
drugs have biological activity profiles and potency similar to those of lysergic acid
1
-4
5
diethylamide (LSD) . Casele and Hayes have reported the remarkable analytical similarity
between 2, 3, and 4-methoxybenzyl regioisomers of the same 4-substituted 2,5-
dimethoxyphenethylamine series. While the 4-substituent varies across a variety of NBOMe
drugs6, 7 all these compounds have the 2,5-dimethoxy substitution pattern in the aromatic ring
of the phenethylamine portion of the NBOMe molecules.
Based on the commercial availability of precursor aldehydes the synthesis and
analytical evaluation of the six regioisomeric N-dimethoxybenzyl NBOMe derivatives were
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8
recently described for the 4-bromo-2,5-dimethoxyphenethylamine series . The six isomers in
each series displayed very little analytical uniquenesses and the major EI-MS fragment ions
were essentially equivalent for each isomer.
The acylation of the secondary amine nitrogen in the 4-iodo- and 4-bromo N-
dimethoxybenzyl-2,5-dimethoxyphenethylamines with trifluoroacetyl groups allowed
differentiation of the six isomers based on some unique fragment ions and the relative
8
abundance of other common ions . The purpose of this study was to determine the role of the
electron-donating groups (halogen and dimethoxy) on the pathway of decomposition (Figure
2
) for the distonic molecular radical cation formed by hydrogen radical transfer from the
phenethyl side-chain to the carbonyl of the TFA group.
Experimental
Instrumentation
The GC/MS system consisted of an Agilent Technologies (Santa Clara, CA) 7890A
gas chromatograph and an Agilent 7683B auto injector coupled with a 5975C VL Agilent
mass selective detector. The gas chromatograph was operated in splitless injection mode with
a helium (ultra-high purity, grade 5, 99.999%) flow rate of 0.48 mL/min and an injection
volume of 1 uL. The mass spectrometer was operated in the electron ionization (EI) mode
with an ionization energy of 70 eV, a scan rate of 2.86 scans/s and a source temperature of
2
30°C. The GC injector was maintained at 230°C and the transfer line at 230°C. The GC/MS
chromatographic separations were carried out on a column (30 m ×0.25 mm i.d.) coated with
®
0
.25 μm film of midpolarity Crossbond silarylene phase similar to 50% phenyl, 50%
®
dimethylpolysiloxane (Rxi -17Sil MS) purchased from Restek Corporation (Bellefonte, PA,
USA). The temperature program consisted of an initial hold at 70°C for 1.0 min, ramped up
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to 250°C at 30°C/min followed by a hold at 250°C for 25 min, then increased to 340°C at
5°C/min.
1
Synthetic Methods
Precursor materials including the six dimethoxybenzaldehydes were purchased from
Aldrich Chemical Company (Milwaukee, WI, USA) or VWR Chemical Company (Radnor,
PA, USA). The synthesis of 2,5-dimethoxyphenylnitroethene was accomplished using 2,5-
dimethoxybenzaldehyde, nitromethane and anhydrous ammonium acetate heated at reflux.
The excess nitromethane was removed under reduced pressure and the resulting oil dissolved
in isopropyl alcohol and the product isolated as needle shaped crystals by vacuum filtration.
The structure of the product was confirmed by GC/MS and NMR spectroscopy.
The 2,5-dimethoxynitroethene was reduced in a suspension of LiAlH to yield 2,5-
4
dimethoxyphenethylamine and the product oil was converted to the hydrochloride salt via
gaseous HCl. The N-(dimethoxy)benzyl-2,5-dimethoxyphenethylamine final products were
prepared by treating 2,5-dimethoxyphenethylamine HCl with the appropriately substituted
dimethoxybenzaldehyde followed by reduction with NaBH
dimethoxyphenethylamines, N-(dimethoxy)benzyl-3-dimethoxyphenethylamines and N-
dimethoxy)benzyl-phenethylamines were prepared in an analogous manner.
4
. The six N-(dimethoxy)benzyl-2-
(
Results and Discussion
The GC/MS studies in this report are designed to investigate structure-MS
fragmentation relationships in dimethoxybenzyl NBOMe analogs. The compounds shown in
Figure 1 were synthesized to represent the systematic removal of the halogen followed by one
or both of the methoxy groups in the phenethyl aromatic ring of the classic 25XNBOMe
structure. The 2,5-DMPEADMB series represents removal of halogen; 2-MMPEADMB
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derivatives are analogs without the halogen and 5-methoxy group; and the 3-MMPEADMB
derivatives represent analogs where the halogen and 2-methoxy group are removed. In
addition, the ring unsubstituted phenethylamines (PEADMB) derivatives represent analogs
where both the phenethyl ring methoxy groups and the halogen are removed. For each of
these four series of phenethyl aromatic ring substitution patterns all six regioisomeric
dimethoxybenzyl substituted analogs (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethoxy) were
prepared, derivatized and analyzed via GC/MS. These compounds were synthesized by
reductive alkylation reactions with 2,5-dimethoxy-, 2-methoxy, 3-methoxy- or unsubstituted
phenethylamines and the corresponding six regioisomeric dimethoxy benzaldehydes as
8
described in previous reports . The EI mass spectra of the TFA derivatives of each of the 2,5-
DMPEADMB, 2-MMPEADMB, 3-MMPEADMB and PEADMB series are shown in Figures
3
-6 and the relative abundance of fragment ions are summarized in Table 1.
The major fragmentation in the EI-MS spectra for these TFA derivatives appears to be
limited to three pathways yielding the dimethoxybenzyl cation along with the two radical
cations shown in Figure 2. The dimethoxy benzyl cation at m/z 151 and its product ions (m/z
1
21 and m/z 91) can occur following initial radical cation formation at the dimethoxybenzyl
aromatic ring. In addition, the m/z 151 dimethoxybenzyl cation can occur following initial
hydrogen transfer to the carbonyl oxygen as shown for the distonic molecular radical cation
in Figure 2. The fragmentation of this species along pathway “A” would yield the m/z 151
cation. Fragmentation via pathway “B” yields the phenylethene radical cation occurring at
various masses (m/z 164, 134, 104) depending on the methoxy substituents on the phenethyl
group. Decomposition of the common distonic radical cation along pathway “C” results in the
formation of the m/z 263 radical cation (dimethoxybenzyltrifloroacetamide).
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While the m/z 151 cation could occur via several fragmentation pathways, the
substituted phenylethene radical cation and the m/z 263 ion appear to occur from the distonic
8
molecular radical cation. Previous studies have shown that the relative intensities of these
three major fragments can be used to determine the dimethoxy group substitution pattern on
the aromatic ring of the N-benzyl group for TFA-25X-NBOMe compounds. However, all
these observations were made for molecules in which the phenethylamine portion of the
NBOMe structure contained the electron-rich 4-halogen and 2,5-dimethoxyphenyl groups.
These electron-donating substituent groups appear to play a role in the ease of formation of
the distonic molecular radical cation and its subsequent decomposition along the perhaps
competing pathways especially the formation of the m/z 263 fragment and the substituted
phenylethene radical cation.
The electron rich substituted phenylethene radical cation fragments from pathway B
are major ions for many of the dimethoxy benzyl substitution patterns in the 4-substituted
(Br, I)-2,5-dimethoxyphenethylamine derivatives (25X-NBOMes). The m/z 263 and the
substituted phenylethene radical cations each form by cleavage of the same chemical bond,
the nitrogen to aliphatic carbon of the phenylethyl group. The heterolytic cleavage of the
bond along Pathway B in Figure 2 yields the substituted phenylethene radical cation and the
neutral substituted benzyl trifluoroacetamide. Breaking the same bond in a homolytic
manner (Pathway C, Figure 2) yields the m/z 263 dimethoxybenzyl trifluoroacetamide radical
cation and the neutral substituted phenylalkene. The substituted phenylethene radical cation
occurs at various masses depending on the nature of the aromatic substituent on the
phenethylamine portion of the structure while the substituted benzyl trifluoroacetamide
radical cation always appears at m/z 263 since all the benzyl group aromatic ring substituents
are dimethoxy. The TFA derivatives of the traditional 25XNBOMe compounds containing
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only monomethoxybenzyl groups (at positions 2, 3 and 4) did not show any equivalent benzyl
trifluoroacetamide radical cation at the expected mass of m/z 233.
The systematic removal of the electron-donating groups from the 4-halogenated-2,5-
dimethoxyphenethylamine structure of 25X-NBOMes to yield the 2,5-dimethoxyphenethyl-
amine, 2-methoxyphenethylamine, 3-methoxyphenethylamine, and phenethylamine allowed
an evaluation of these structural effects on the formation of the phenylethene and m/z 263
radical cations. The EI-MS spectra for these isomers are shown in Figures 3-6. The 2,5-
dimethoxyphenyl series of isomers showed a significant dimethoxybenzyl ion at m/z 151 as
well as a significant peak for the dimethoxyphenylethene radical cation at m/z 164 (Figure 3).
In fact, the phenylethene radical cation is the base peak for three of the six isomers in the
2
5H-NBOMe series and m/z 151 is the base peak for the others, while the m/z 263 fragment is
not a prominent peak in any of the six spectra. However, in both the 2-MMPEADMB (Figure
) and the 3-MMPEADMB (Figure 5) series of isomers containing only one of the electron-
4
donating methoxy groups in the phenethyl aromatic ring, the m/z 263 radical cation becomes
a more prominent fragment ion and the methoxyphenylethene radical cation at m/z 134 is
relatively insignificant (see Table 1). These results suggest that homolytic cleavage of the N-
C bond is the favored pathway leading to the formation of m/z 263 and the neutral 2- or 3-
methoxyphenylethene, rather than the less favored heterolytic bond cleavage that would yield
the methoxyphenylethene radical cation. This is further confirmed by the EI-MS spectra of
the unsubstituted phenethyl PEADMB series (Figure 6) which shows no significant
phenylalkene radical cation at m/z 104. The m/z 151 ion is the base peak in all six spectra of
the PEADMBs and its product ions at m/z 121 and 91 are prominent ions in this series. The
presence of the m/z 263 radical cation shows that the distonic molecular radical cation
continues to form in this unsubstituted phenethylamine series. However, these results suggest
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that the decomposition of this distonic molecular radical cation species strongly favors
formation of the m/z 263 species with the elimination of the neutral phenylethene molecule.
Furthermore, electron-donating groups on the aromatic ring of the phenethyl group appear to
be necessary to allow formation of the substituted phenylethene radical cation. In fact, most
of the spectra of the TFA-PEADMB compounds do not show the phenylethene (m/z 104)
radical cation fragment and instead contain the phenethyl cation fragment at m/z 105 (Figure
6
). Thus, the addition of electron-donating groups to the aromatic ring of the phenethyl group
as in the NBOMe-type molecules shifts the decomposition of the corresponding distonic
molecular radical cation to favor the formation of the electron-rich substituted phenylethene
radical cation.
The mass spectra of the 2,3-dimethoxybenzyl isomer of 2,5-DMPEADMB, 2-
MMPEADMB, 3-MMPEADMB and PEADMB (as well as the TFA derivatives for each
series) each contain a m/z 136 fragment ion which is not present in the mass spectra of the
other five N-(dimethoxy)benzyl regioisomers in each series. The m/z 136 ion is also a
significant fragment in the 2,3-dimethoxybenzyl isomer for 25I- and 25B-NBOMe and their
TFA derivatives. This unique ion appears to form in a fragmentation process resulting from
loss of a methyl radical from one of the methoxy groups on the benzyl aromatic ring. The m/z
1
2
36 radical cation probably forms via methyl radical migration from a methoxy group of the
,3-dimethoxybenzyl group to the initial molecular radical cation site on the oxygen of the
carbonyl group to yield the distonic molecular radical cation. Direct heterolytic bond
cleavage of this rearranged molecular radical cation would yield the unique m/z 136
fragment. For the underivatized NBOMe compounds, the m/z 136 ion can occur via migration
of the methyl radical to the radical cation site on nitrogen followed by the analogous
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fragmentation process. An equivalent fragment appears as the base peak in the EI mass
spectra of the vicinal isomers 2,3- and 3,4-dimethoxybenzylamine.9
In the 2,3-dimethoxybenzyl 25X-NBOMe series (where X is 4-H, 4=Br or 4-I), the
m/z 136 ion is the third most abundant after the substituted phenylethene radical cation (most
abundant) and dimethoxybenzyl cation (second most abundant). For the 2,3-dimethoxy
isomers of the 2- and 3-MMPEADMB series, the m/z 136 ion is less abundant than the TFA
amide radical cation (m/z 263) and dimethoxybenzyl cation (m/z 151). However, in the mass
spectra of the 2,3-dimethoxy isomer of the PEADMB series only the dimethoxybenzyl cation
(m/z 151) is more abundant than the m/z 136 ion and the TFA amide radical cation (m/z 263)
is formed in relatively low abundance.
Each of the methyl groups of the 2,3-dimethoxybenzyl portion of the molecule was
1
3
individually labeled with C in an effort to determine which of the methyl groups is
eliminated during the formation of the m/z 136 fragment. The m/z 130 to m/z 140 mass
1
3
regions of the EI-MS spectra for both C-labeled compounds are shown in Figures 7A and
1
3
7
B. These results indicate that the C methyl group was neither completely conserved nor
completely eliminated for either of the labeled analogues in this set of experiments. However,
both spectra support a slight preference for the migration and elimination of the methyl from
the 3-methoxy group of the 2,3-dimethoxybenzyl isomer. Figure 7A shows the m/z 136 and
1
3
1
1
37 region for the labeled analogue having the C at the 2-methoxy group, and the ion at m/z
1
3
37 is the more intense of the two ions. The analogue having the C at the 3-methoxy group
13
yields a fragment ion pattern (Figure 7B) indicating a more intense m/z 136. Thus, both C-
labeled compounds consistently support a slight preference for the migration and elimination
1
3
of the methyl group from the 3-methoxy substituent. The two C-labeled compounds used to
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obtain the spectra in Figures 7A and 7B were prepared via reductive amination of the
1
3
appropriately labeled 2,3-dimethoxybenzaldehydes. The C-labeled 2,3-
1
3
dimethoxybenzaldehydes were obtained by C-methyl iodide treatment of 2-hydroxy-3-
methoxybenzaldehyde or 2-methoxy-3-hydroxybenzaldehyde under basic conditions.
Conclusions
The EI-MS spectra for the trifloroacetamides of the N-dimethoxybenzyl NBOMe
analogues yield two unique radical cation fragments from the decomposition of the common
distonic molecular radical cation. The systematic removal of the electron-donating groups
from the 4-halogenated-2,5-dimethoxyphenethylamine portion of the N-dimethoxybenzyl
NBOMe analogues to yield the 2,5-dimethoxyphenethylamine, 2-methoxyphenethylamine, 3-
methoxyphenethylamine, and unsubstituted phenethylamine allowed an evaluation of these
structural effects on the formation of the substituted phenylethene (m/z 164, 134, 104) and
m/z 263 dimethoxybenzyltrifloro-acetamide radical cations. The decomposition of this
hydrogen-rearranged distonic molecular radical cation species favors formation of the
dimethoxybenzyltrifloroacetamide (m/z 263) species with the elimination of the neutral
phenylethene molecule, and the addition of electron-donating groups on the aromatic ring of
the phenethyl group appear to be necessary to allow formation of the substituted
phenylethene radical cation. The unique m/z 136 benzylic radical cation formed exclusively
in the 2,3-dimethoxybenzyl regioisomer was unaffected by the nature of the substituent
groups in the phenethylamine aromatic ring.
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Acknowledgements
This project was supported by Award No. 2016-DN-BX-K0175, awarded by the
National Institute of Justice, Office of Justice Programs, U.S. Department of Justice. The
opinions, findings, and conclusions or recommendations expressed in this publication are
those of the author(s) and do not necessarily reflect those of the Department of Justice.
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7] Zuba D, Sekuła K. Analytical characterization of three hallucinogenic N-(2-
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Figure 1. Substituted phenethylamines based on systematic removal of electron-donating
groups.
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Figure 2. Major fragmentation pathways in the TFA-NBOMe analogues.
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Figure 3. EI-MS of the 2,5-DMPEADMB regioisomers.
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Figure 4 EI-MS of the 2MMPEADMB regioisomers.
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Figure 5 EI-MS of the 3MMPEADMB regioisomers.
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Figure 6 EI-MS of the PEADMB regioisomers.
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A
B
1
3
Figure 7. The m/z 136 and m/z 137 region of the EI-MS for N-(2- C-methoxy-3-
1
3
methoxybenzyl)-2,5-dimethoxyphenylamine (7A) and N-(2-methoxy-3- C-methoxybenzyl)-
2
,5-dimethoxyphenylamines (7B).
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Table 1 Relative abundance of fragment ions in the EI-MS of TFA-2,5-DMPEADMBs,
TFA-2-MMPEADMBs, TFA-3-MMPEADMBs and TFA-PEADMBs.
2
,5DMPEADMB Base
2nd Most
Abundant
Ion
151
164
151
164
164
151
3rd Most
Abundant
Ion
136
121
121
91
121
121
4th Most
Abundant
Ion
91
91
91
121
91
5th Most
Abundant
Ion
121
77
263 = 77
77
77
Regioisomers
Peak
2
2
2
2
3
3
,3-Isomer
,4-Isomer
,5-Isomer
,6-Isomer
,4-Isomer
,5-Isomer
164
151
164
151
151
164
91
77
2
MMPEADMB Base
2nd Most
Abundant
Ion
3rd Most
Abundant
Ion
4th Most
Abundant
Ion
5th Most
Abundant
Ion
Regioisomers
Peak
2
2
2
2
3
3
,3-Isomer
,4-Isomer
,5-Isomer
,6-Isomer
,4-Isomer
,5-Isomer
263
151
151
151
151
263
151
263
263
91
263
151
91
121
121
134
91
91
136
91
91
263
121
121
134
134
134
121
134
134
3
MMPEADMB Base
2nd Most
Abundant
Ion
151
263
263
263
263
151
3rd Most
Abundant
Ion
136
121
121
91
134
134
4th Most
Abundant
Ion
91
91
91
134
91
5th Most
Abundant
Ion
134
134
134
121
121
121
Regioisomers
Peak
2
2
2
2
3
3
,3-Isomer
,4-Isomer
,5-Isomer
,6-Isomer
,4-Isomer
,5-Isomer
263
151
151
151
151
263
91
PEADMB
Regioisomers
Base
Peak
2nd Most
Abundant
Ion
3rd Most
Abundant
Ion
4th Most
Abundant
Ion
5th Most
Abundant
Ion
2
2
2
2
3
3
,3-Isomer
,4-Isomer
,5-Isomer
,6-Isomer
,4-Isomer
,5-Isomer
151
151
151
151
151
151
136
121
121
91
263
263
91
263
263
263
104
91
263
91
91
105
91
105
105
105
105
121
121
121
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