Synthesis, spectrophotometric, voltammetric, and density functional theory studies of tetrahydro[3,2-b]indolocarbazoles for sensing small molecules

Article abstract of DOI:10.1002/jhet.4153

Absorption spectra of tetrahydro[3,2-b]indolocarbazoles (THICZs) with respective molecular property and alkyl substituents have been prerecorded in diverse solvents in the scope between 200 and 600 nm for very fewer times in the literary study. The photo-

Full text of DOI:10.1002/jhet.4153

Synthesis, Spectrophotometric, Voltammetric and DFT Studies of THICZs for
sensing small molecules.
Zehbah Ali Al-Ahmed1*, Ibrahim H.I.Habib2, Reham R. Khattab3, Reda M. Abdelhameed2, Mohamed
El-Naggar4, Moursi H. Abu Bieh3, Sergey A. Pisarevd5, Andrey Voronkov6, Mardia T. El Sayed2*
1College of Art and Sciences - Dhahran Aljounb, King Khalid University, Saudi Arabia
2Applied Organic Chemistry Department, Chemical Industries Research Division, National
Research Centre, Dokki, 12311, Egypt.
3Photochemistry Department, Chemical Industries Research Division, National Research Centre,
Dokki, 12311, Egypt.
4Chemistry Department, Faculty of Sciences, University of Sharjah, Sharjah, 27272, UAE.
5Institute of Physiologically Active Compounds, Russian Academy of Sciences,142432 Chernogolovka,
Russian Federation.
6Digital Bio Pharm Ltd., 145-157 St. John Street, London, EC1V 4PW, U.K.
Corresponding authors:
Dr. Mardia El Sayed, mardia.elsayed2016@gmail.com
Dr. Zehbah Ali Ahmed, zehbah.ahmed_999@yahoo.com
Abstract
Absorption spectra of tetrahydro[3,2-b]indolo-carbazoles (THICZs) with respective molecular
property and alkyl substituents have been prerecorded in diverse solvents in the scope between
200 to 600 nm for very fewer times in the literary study. The photo physical behaviour of
liquified THICZs belonging to the existence surroundings. The solvatochromic behaviours of
THICZs and solvent substance physical phenomenon can be analysed by implementation of
linear solvating energy state conception. Compound 4 show excellent properties for sensing
small molecules. The electrochemical behaviour of some THICZs was investigated at carbon
paste electrode where two electrode reactions were involved, irreversible oxidation-one electron
transfer and quasi-reversible redox reactions forming phenolic followed by quinolone moiety
electro active species. The DFT which means (calculated molecular orbital energies (B3LYP/6-
31G) and HOMO-LUMO gap / space for some presented indolocarbazoles have been performed.
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Graphical Abstract
2
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Key words:
Indolocarbazoles, Spectrophotometric, Voltammetric Studies, DFT- calculated molecular
orbitals, Chemical Sensors.
Conclusion
The significance of this article including measuring the dissolving agent actions on
Ultraviolet–visible (UV–vis) absorption spectra of our target THICZs come from its significant
applications in many fields like designing new dyes, engineering light-emitting….etc.
furthermore it can be useful in the fields of photodynamic therapy and molecular imaging.
Solvatochromism, changing the colour of chemical compounds due to a change in solvent
polarity, is important tool for understanding the solvent effects on chemical and biological
processes. In this work, some of THICZs were synthesized and its structures were characterized
by assorted instrumentation of spectral and analytical data. Those have been utilized for
investigating in antithetic solvent for perceptive effects of dissolving agent on the absorption
spectra of these THICZs. In addition, Quantitative classification of solvatochromic behaviours of
targeted THICZs compounds was analyzed via linear salvation energy relationship. The principal
outcome points that there is positive solvatochromism which implement bath chromic shift with
increase in solvent polarizability and solvent bond basicity. This declares stabilization of the
electronic excited state proportional to the ground state. The positive mark of a coefficient for all
THICZs show a hypsochromic shifts with accelerative solvent hydrogen-bond donor acidity.
This intimate stabilization of the ground state relational to the electronic excited state. Count on
the structure of indolic compounds, cyclic voltammetry established that few indolic compounds
were susceptible to oxidation under certain conditions while others were apparently resisted to
the oxidation. Form the DFT studies we can say that the tris-indole compound 3b its HOMO
generally corresponds to that of the dimeric structure 3a, while LUMO is mostly the
corresponding orbital of the 2-indolyl substituent. The aromatic character of the central ring in
compound 4 does not alter significantly the orbital picture of the non-substituted scaffold. The
energy difference between trans and cis isomers of compound 3d (ca. 0.80 kcal / mol in favor of
the former) could be considered almost negligible in the present investigations context.
List of Abbreviations (if any)
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THICZs : Tetrahydro[3,2-b]indolo-carbazoles
OLEDs : Organic light-emitting diodes
OFETS : Organic field-effect transistors
DSSCs : Dye sensitized solar cells
PSCs : Photovoltaic solar cells
LSER : Linear solvation energy relationship
1. Introduction
5,11-tetrahydroindolo[3,2-b]carbazoles (we will named it THICZs for short) have attracted
overmuch care all over the past decennary because of their prospective electrical and optical
material possession (high charge carrier mobility). It has been demonstrated that it could be
utilized as progressive substantial for organic light-emitting diodes (OLEDs) [1], organic field-
effect transistors (OFETS) [2], organic thin-film transistors [3] and dye sensitized solar cells
(DSSCs) [4] and even photovoltaic solar cells PSCs [5]. Lately, diverse 6,12-diaryl-5,11-
dihydroindolo[3,2-b]carbazoles have been rumored as electrode active materials which modify
the energy density of an electrochemical cell. [6]. Later, a related derivative named 6,12-di(4-
(N,N-diphenylamino)phenyl)-5,11-dihydroindolo[3,2-b]carbazole was planned and synthesized
as a hole-transporting substantial for organic light emitting diodes [7].
Examination of solvent effects on absorption spectra of organic compounds continuing for ample
time period and the individual researchers terminated that the photo-physical action of organic
compounds calculate on the nature of its surroundings, i.e. the intensity, shape, and maximum
absorption wavelength of the absorption band of organic compounds in solution be strongly on
the solvent-solute fundamental interaction and solvent nature [8].The importance of measuring
the solvent personal property on Ultraviolet–visible (UV–vis) absorption spectra come from its
significant applications in many fields like designing new dyes, engineering light-emitting diodes
and building phototropic materials, also can be useful in the fields of photodynamic therapy and
molecular imaging. Solvatochromism, changing the colour of chemical compounds due to a
change in solvent polarity, is important for understanding the solvent effects on chemical and
biological processes [9-13].
The implementation of electrochemical techniques in bio-activity prediction of pharmaceuticals
has increased significantly over the past few years. Cyclic voltammetry studies were used to
explore the electrochemical behaviour of drugs and their mode of action in the human body, such
4
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as metabolism, which is one of the essential track in drug breakthrough. Indole derivatives were
well-known electro active compounds that were ready to oxidize or reduce at various types of
carbon-based electrodes. [14] Theoretical investigations using the density functional theory
(DFT) performings [15] are proven to be the extremely valuable to predict properties of the
various organic compounds including reactive intermediates.
In this work, some of Tetrahydro[3,2-b]indolo-carbazoles (THICZs) were synthesized and its
structures was characterized by assorted implementation of spectral information. All synthesised
organic molecules (THICZs) were investigated in antithetical organic solvent for knowing
personal effects of solvents on the absorption spectrum. In addition, Quantitative classification of
solvatochromic behaviours of target THICZs compounds was investigated using linear salvation
energy relationship. On the other hand, some of synthesised THICZs were selected to study their
electrochemical activities at carbon paste electrode. The DFT measured molecular orbital
energies (B3LYP/6-31G) and HOMO-LUMO gaps for some synthesized indolocarbazoles have
been performed.
2. Results and Discussion
2.1. Synthesis and structure orientation of THICZs
THICZs (3a-f) were prepared by two different reported synthetic approaches.[16-18] The first is
one-pot synthesis using direct contact of indole with different aromatic aldehydes and the second
is step by step synthesis using dimerization of indole forming bis-indolylmethane (BIMs) (2)
then reacted with the other aldehydes molecule to give the comparable THICZs (3a-f). In the
present study the first method was used for the synthesis of the mixed THICZs 3b. Where the
well-known BIM (2) R=3-indolyl, (that derived from aldol condensation of indole and indole-3-
carboxyaldehyde) and formalin 37 % solution were used in equal molar ratios (1:1). The reaction
mixture has liquified in methanol and with a few drops of conc. H2SO4 were added drop wisly.
Then the mixture was stirring under refluxing for about 1hr. The product was precipitated and
separated from the hot solution giving few quantity of the clean THICZs 3b. Then good amounts
of the compounds could be neutralized, extracted, washed, dried, and purified via column
chromatography eluted by CH2Cl2 of the reaction mixture dropping the second output in
improved yields 80 to 86 % (Scheme 1). Whereas other THICZs (3a, 3c, 3d, 3e, 3f) have been
synthesized by the straightforward approaching of employ the indole itself with the proper
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aldehydes either formaldehyde or aromatic aldehyde. The mixture of indole and aldehyde in
equal molar amount liquified in methanol with a couple of drops of sulphuric acid was reflux for
1hr to afford the THICZs precipitated from the reaction mixture in its pure form. The work up
procedure is the same as mention above. All THICZs (3a-f) were prepared and proved by
implementation of analytical and spectral information. The 6,12-Dihydroindolo(3,2-b)carbazole
(3a), and the THICZs (3e, 3f) are known in the literature and their identities are equivalent to our
synthesized samples [16-18]. Whereas the THICZs (3b, 3c and 3d) novel derivatives were
1
synthesized and confirmed by the means of H- and 13C-NMR, ESI-MS and IR spectra (see
supporting information). The aromatisation of compound 3d to form directly compound 4 has
been performed according to the recently reported method by Sven Van Snick and Wim Dehaen
[19].Where the desired oxidation reaction have been done by I2 in CH3CN under reflux for 14
hours to get pure indolo[3,2-b]carbazole derived compounds (4). Compound 4 was characterized
by its spectral and analytical data see experimental section.
O
MeOH, conc. H SO
R2CHO,
2
4
O
R1
H
N
H
R1
POCl3
CH2Cl2
R2CHO
MeOH, conc. H2SO4
N
R1CHO
N
H
N
N
reflux, 1h
reflux
H
N
H
N
H
R2
H
1
2
O
3a-f
THICZs
Indole
BIMs
O
4
3a: R1= R2=H
3b: R1= 3-indolyl, R2-H
3c: R1=R2= p-Benzyloxy.Ph
3d: R1=R2= m,p-MeO-Ph
3e: R1=R2= m-Benzyloxy-p-MeO.Ph
3f: R1=R2=m-MeO-p-Benzyloxy.Ph
Scheme 1: Synthesis of different types of THICZs
The trans isomer (Figure 1) has reported by Rong Guand et al. [20].
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Figure 1: Confirmed trans-form of diphenyl-tetrahydroindolo[3,2-b]carbazole
1
Our derived function compounds were proved instrumentality by H- and 13C-NMR, ESI-MS
1
and IR spectra. The H-NMR spectra of our synthesized THICZs 3a-f was compared with the
reported one that prepared by iodine catalyst and proved by single crystal x-ray. As we in this
current work have used the method of equimolecular amounts of indoles and aldehydes or
1
13
ketones and we have got the identical H-NMR and identical C-NMR as the reported one by
Rong Guand et al. thus, accordingly we can report that the means of using methanol as solvent
with drops of conc. H2SO4 should afford also the trans isomer similar to the reaction catalyzed
by iodine. Thus we should report that our previous reported structure of THICZs as cis-form
resulted from condensation of BIMs and aldehydes or ketones, should be corrected into its trans
form (Figure 1) [20]. The x-ray crystallography indicated that the spirocyclicindole is in the
trans form. The mechanism of the two possibility formation of both THICZs cis and trans form
has been clearly illustrated in our previously reported articles [16, 18]. That perhaps attributed to
the performing the reaction under vigorous conditions of conc. H2SO4 under reflux leads to a
rearrangement of 3,3-alkylated bisindolylmethane into a 3,2-alkylated bisindolylmethane. This
rearrangement is well known as the Blancher rearrangement [8].
2.2. Spectrophotometric studies
2.2.1. The solvent actions on the absorption spectra
In this section the solvent effects on the UV/visible absorption spectra of synthesized THICZs
have been described in details. The solvatochromic behaviours of THICZs and solvent solute
interactions can be investigated by methods for instrumentation of linear solvating energy
relationships conception projected by Kamlet and Taft [21].The spectral profiles of the
compounds (3 mg in 10 mL solvent) under investigation were pre-recorded with six organic
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solvents with broad assortment of solvent parameters for instance dielectric constant ε, refractive
index n and solvatochromic parametric quantity α, β and π*. The spectra of THICZs (3a-3f and
4) in diverse organic solvents are bestowed in Figure S1-6, individually. Table (1) shows the
maximum absorptions wavelength of THICZs under different solvents (appearing at 237-310
nm). It is clear that there is appreciable occurrence in absorption visibility of the molecules with
alteration in polarity of the medium. Compound 3a show two main peaks in non-polar solvent
(chloroform), one is maximum wavelength at 244 nm and it is related to π-π* electronic
transitions and the second at 282 nm and it is related to n-π* electronic transitions. The non-polar
solvents have ability to act though polarizability by London fundamental interaction besides
effort a blurring of the vibronic manifold. That can be attributed to the solvent's tendency to
adjust its dipole moment with the dipole moment of the matter. However, in polar aprotic solvent
such dimethylsulfoxide, dimethylformamide and tetrahydrofuran, the maximum wavelength are
shifted to higher wavelength 286, 295 and 302 nm, respectively. This shifts because compound
3a has free hydrogen in its structure, this make it able to forming hydrogen bonding. In contrast,
the wavelength in polar protic solvent such as methanol shifted to lower wavelength (237 nm).
The maximum wavelengths of compound 3b are higher than compound 3a because compound
3b has three unit of indole. Compound 3b in chloroform as solvent show maximum wavelength
at 304 nm (n-π* transitions) rather than 246 nm (π-π* transitions), this is due to the free N-H unit
of compound 3b. The maximum wavelengths of compound 3c and 3d are the same as compound
3a, but in visible region the peak at 412 nm start to be appear due to increasing the number of
benzene ring. The promising results are located on the discussion of compound 3e and 3f, the
two compounds have the same chemical formula but different on substitution position. Stable
molecular conformation of compounds 3e and 3f obtained by running MM2 energy
minimizations in ChemBio 3D 15.1 are presented in Figure S7 and S8. The maximum
wavelength of compound 3e and 3f are the same in non-polar solvent but in the case of polar
solvent such as methanol or DMF the maximum wavelength are completely dissimilar (Figure
2), this may be due to the relatively strong guest–host interaction between the compound 3e and
the methanol environment.
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Compound 3e in CHCl3
Compound 3f in CHCl3
Compound 3e in CH3OH
Compound 3f in CH3OH
200
300
400
500
600
700
Wavelength (nm)
Figure 2: UV/Visible absorption spectra of compound 3e and 3f in solvent chloroform and
methanol.
Table 1. UV/vis spectral data (λmax nm) of some [3,2-b]indolo-carbazolesinvarious solvents
λmax nm/νmax103(cm−1)
Solvent/
compounds
CH3OH
THF
4
3a
3b
3c
3d
3e
3f
207
289
342
241
241
281
48.31 237 42.19 311 32.15 237 42.19 281 35.58 295 33.89 233 42.91
41.49 302 33.11 306 32.67 237 42.19 235 42.55 236 42.37 238 42.01
41.49 295 33.89 305 32.78 282 35.46 284 35.21 284 35.21 270 37.03
29.29 244 40.98 304 32.89 245 40.81 241 41.49 246 40.65 244 40.98
35.59 280 35.71 236 42.37 235 42.55 238 42.01 234 42.73 230 43.47
34.61 286 34.96 310 32.25 286 34.96 286 34.96 282 35.46 286 34.96
DMF
CHCl3
CH2Cl2
DMSO
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2.2.2. Multiple linear regression analysis
The effect of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by
means of linear solvation energy relationship (LSER) using a Kamlet–Taft Eq [21].
νmax=ν0 +aα +bβ +sπ*
Where νmax is maximum absorption wave number of the given compound processed
experimentally, ν0 was calculated by the regression method, the other parameters i.e. the Kamlet-
Taft coefficients a, b and s was also calculated using regression analysis method (Table 2).
Negative values of both s and b (Table 2) indicate that there is positive solvatochromism which
means bathochromic shift with increase in solvent polarizability and solvent bond basicity. This
suggests stabilization of the electronic excited state relative to the ground state. The positive sign
of a coefficient for all compounds indicate a hypochromic shifts with increasing solvent
hydrogen-bond donor acidity. This suggests stabilization of the ground state relative to the
electronic excited state.
Table (2) Regression fits to solvatochromic parameters (Kamlet–Taft Eq.)
Compounds
ν
s
b
a
R2
34.658±0.596
29.377±0.462
49.119±0.816
52.823±0.668
51.396±0.716
48.061±0.972
46.151±0.981
-9.105±0.952
-3.181±0.154
9.291±0.283
4.980±0.551
1.593±0.999
5.829±0.739
7.252±0.353
2.277±0.091
3.517±0.581
0.946
0.984
0.982
0.940
0.957
0.932
0.959
3a
3b
3c
3d
3e
3f
4
11.694±0.754 -9.520±0.333
-11.195±0.467 -3.545±0.842
-12.583±0.799 -7.358±0.631
-9.838±0.101
-9.230±0.661
-8.427±0.222
-3.679±0.930
-10.051 ±0.681 -5.459±0.930
2.2.3. Sensing of organic solvent molecules
To examine the possibility of 4 for sensing of small molecules, the samples (3 mg) of 4 were
soluble in different organic solvents (THF, CHCl3, CH2Cl2, DMF, DMSO and MeOH,
respectively) to form a clear solution for UV/visible absorption studies. As is shown in Figure
3a the absorption intensity of 4 is hugely dependent on the solvent molecules. The order of
quenching effects is THF< CHCl3<CH2Cl2<DMF<DMSO<MeOH as shown in Figure 3b.
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3.0
2.5
2.0
1.5
1.0
0.5
0.0
CH3OH
CHCl3 CH2Cl2
THF
DMF
DMSO
Figure 3: (a) UV-Visible spectrum of aromatic derivatives 4 and (b) Absorbance intensity
(284 nm) of 4 soluble into different organic solvents.
2.3.Voltammetric Studies
The Met Rohm model 693 VA processor and 694 VA stand equipped with three electrodes were
employed. The electrodes were Ag/AgCl- 3M KCl a reference electrode and a platinum counter
electrode. The carbon paste electrode CPE was used as a working electrode for electrochemical
measurements and was prepared by mixing 200 µL paraffin oil and 250 mg synthetic carbon
powder 1-2 micron in agate mortar for at least 20 min. The paste was then packed into the tip of
a 1 mL insulin plastic syringe and a copper wire was inserted to obtain the external electric
contact. Electrochemical detection was performed by cyclic voltammetry, scanning between -0.1
and 1.3 V in a 10 mL working solution. Two stock solutions of 3d and 4 were prepared by
dissolving 25 mg in 50 ml acetonitrile “ACN“. Working solution was prepared by transferring
aliquot of the stock solution to 10 ml aqueous acetonitrile solution (90 % ACN). No peaks were
observed by the cited compounds (3d or 4) in Britton-Robinson buffer solution and at different
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pH values. This was as a result of salting out effect, but on increasing the proportion of organic
phase in the working solution up to 90 %, the peaks were developed. As depicted in Figure 4,
two peaks were generated by the compound 3d at sweep rate 250 mV/s, the first peak was at
oxidation potential around 0.9 V corresponding to irreversible one electron transfer [22]. This
electrochemical oxidation reaction may be attributed to chemical deprotonating of nitrogen
leading finally to hydroxylation of benzene ring in the indole derivatives (scheme 2) [23]. The
second peak was at about 0.55 V and is due to reduction of phenolic indole forming quinone [24,
25]. The peaks heights were proportional to the concentrations of the 3d species. The
electrochemical reaction may be ascribed as a quasi-reversible reaction which was confirmed by
appearing a reduction peak on scanning first from high to low potentials (reduction direction)
then by oxidation scan. This was indicated also by potential shift on increasing the scan rate from
10 to 500 mV/s and on repeating cyclic voltammetry measurements as shown in Figures 5 and 6,
respectively. It is worth mentioning that white particles apparently were shown on repeating the
electrolysis most likely due to the formation of dimers or trimmers [26]. The electrochemical
behaviour of compound 4, on the other hand, was released an irreversible cyclic voltammogram
with a tiny and broad peak at oxidation potential of about 0.75 V in the same medium of 90 %
CAN and at scan rate 500 mV/s (Figure 7). This phenomenon may be explained by the
delocalization of the free electron along the neighbouring aromatic rings after deprotonating
indolic nitrogen. The expected electrochemical oxidation reaction of compound 3d is presented
in Scheme 2.
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3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
0.252 mM
0.199 mM
0.122 mM
0.088 mM
0.048 mM
blank
0.0
0.2
0.4
0.6
0.8
1.0
1.2
potential, V
Figure 4: Cyclic voltammogram of 3d at carbon paste electrode in acetonitrile with scan rate 250
mV/s.
4
3
2
500 mV/s
250 mV/s
100 mV/s
10 mV/s
1
n
o
ti
a
d
i
n
x
o
o
cti
0
u
d
e
r
-1
-2
-0.1 0.0
0.2
0.4
0.6
0.8
1.0
1.2
potential, V
Figure 5: Cyclic voltammetric measurements of 3d in acetonitrile at different scan rates.
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O
O
O
O
O
O
O
O
O
H
N
H
N
H
N
H
N
-1e, -1H+
-1e, -1H+
-1e, -1H+
H2O
N
O
O
N
H
N
HO
N
H
H
O
O
O
O
O
O
O
3d
Scheme 2: Expected electrochemical oxidation reaction of compound 3d.
4
3
2
1
on
i
dat
i
ox
0
-1
-2
eduction
r
1
2
0.0
0.2
0.4
0.6
potential, V
0.8
1.0
1.2
Figure 6: Repeated cyclic voltammograms of 0.9 mM 3d compound repeated 5 times at scan
rate 500 mV/s in 90% CAN.
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4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
-2.0
0.2 M 4d
blank
0.0
0.2
0.4
0.6
0.8
1.0
1.2
potential, V
Figure 7: Cyclic voltammogram of 4 at carbon paste electrode in acetonitrile at scan rate 500
mV/s in 90 % CAN.
2.4.Theoretical DFT studies
The DFT studies for several molecules were performed using the B3LYP [27, 28] functional in
the 6-31G (d) Pople polarized basis set. Calculations were performed using the version 4 of the
ORCA quantum chemistry program package [29]. The sketch map of the subjected structures for
DFT studies are illustrated in Figure 8. The values of total energy and frontier orbital levels are
presented in the Table 3.
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O
O
O
O
HN
H
N
H
H
N
N
H
N
N
H
N
N
N
H
H
H
N
H
O
O
O
O
1
3a
3b
3d
4
Figure 8: The sketch map of requested structures for DFT studies
Table 3: The values of total energy and frontier orbital levels of requested compounds.
Structure
-Etot, hartree
E(HOMO),
eV
E(LUMO), eV
1 (2,3-dimethylindole)
442.1589377
803.3587383
(#38) -4.992
-5.201
(#67) -5.139
-5.367
-5.194
(#97) -5.023
-5.184
(#66) -4.820
-5.390
-5.269
(#139) -5.088
-5.391
(#39) 0.126
(#68) -0.016
0.082
(#98) -0.243
0.024
0.160
(#67) -0.906
0.365
(#140) -0.118
0.032
0.151
(#140) -0.116
0.028
0.124
(#139) -0.922
0.059
3a
1165.7488387
802.1784877
3b
4
Trans-3d
Cis-3d
4
1722.9889549
1722.9876875
1721.8175255
-5.237
(#139) -5.064
-5.461
-5.079
(#138) -4.602
0.209
Diagrams of the frontier orbitals plotted at the ±0.025 is contours (Figure 9 and 10)
reveal that for the dimeric compound 3a they are formed by the corresponding frontier orbitals of
the monomeric indole fragments as calculated in 1 (2,3-dimethylindole derivative). For the tris-
indole compound 3b the HOMO generally corresponds to that of the dimeric structure 3a, while
LUMO is mostly the corresponding orbital of the 2-indolyl substituent. The aromatic character of
the central ring in 4 does not alter significantly the orbital picture of the non-substituted scaffold.
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The similar picture observed for the bis-[3,4-bis-(methoxy)-phenyl] derivatives 3d, 4
(Figure 10). The energy difference between trans and cis isomers of 3d (ca. 0.80 kcal / mol in
favor of the former) could be considered almost negligible in the present investigations context.
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LUMO
HOMO
1
3a
3b
3a
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Figure 9: represented diagrams of the frontier orbitals HOMO and LOMO plotted at the±0.025
of compounds 1 (2,3-dimethylindole derivative), 3a and 3b.
HOMO
LUMO
Cis-3d
Trans-3d
4
Figure 10: Represented diagrams of the frontier orbitals HOMO and LOMO plotted at
the±0.025 of compounds 3d (cis/trans) and 4.
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Conflict of Interest
Authors declare no conflicts of interest
Acknowledgements
This work was financially supported by the National Research Centre, Egypt. The NMR and
Mass Spec service were carried out in The Central Unit for Analysis and Scientific Services
(CUASS) at the National Research Centre, Egypt. The Digital Bio Pharm LTD Company
(London, UK) (R25GM067122) is greatly acknowledged.
Experimental section
General information
The melting points were measured on a Boetius-Mikroheiztisch the company VEB weighing,
Rapido Radebeul/VEB NAGEMA measured and are uncorrected. The carbon, hydrogen and
nitrogen content of the substances were performed on a CHNS-932 automatic analyzer of the
company LECO Corporation in the automatic Micro chemical determined. The reactions were
followed up using thin layer chromatography on aluminium foil fluorescent indicator from
Merck KGaA (silica gel 60 F254, layer thickness 0.2 mm). The separations were with column
chromatography at atmospheric pressure on silica gel 60 (Grain size from 0.063 to 0.200 mm)
from Merck KGaA. The NMR spectra were recorded on a Gemini 2000 (400/100 MHz). The
ATR spectra were recorded on an FT-IR spectrometer IFS 28 by Bruker, the KBr spectra on an
FT-IR Spectrometer Spectrum BX the Company Perkine Elmer measured. The ESI mass spectra
were recorded on a Finnigan LCQ Classic by thermal Electron measured the sample was injected
directly. Optical spectra of the samples were determined on a JASCO UV 3100 spectrometer.
The chemical and physical data of new compounds along with their spectra have been presented
in the supporting information file.
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