Journal of Molecular Structure 1179 (2019) 289e296

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Journal of Molecular Structure

journal homepage: http://www.elsevier.com/locate/molstruc

Spectroscopic and quantum chemical study of gossypol imine

derivatives
A.M. Dykun*, V.N. Anishchenko, A.N. Redko, V.I. Rybachenko, K.Y. Chotiy
L.M. Litvinenko Institute of Physical-Organic and Coal Chemistry NAS of Ukraine, 50, Kcharkivske Shose, Kyiv, 02160, Ukraine

a r t i c l e i n f o a b s t r a c t

Article history: The structures and tautomeric equilibria of a number of new gossypol imine derivatives were studied by
Received 5 May 2018 NMR, FT-IR, UVeVis spectroscopy and quantum chemistry methods. Geometry of the molecules and
Received in revised form complete assignment of all signals (13C NMR) and bands in vibrational and electronic absorption spectra
11 October 2018
were established using DFT and TD-DFT calculations. It was shown that gossypol Schiff bases exist in
Accepted 8 November 2018
solution as enamineeenamine tautomer. Shift the equilibrium toward the imine-imine tautomeric form
Available online 9 November 2018
for 3-amino-5-methylisoxazole derivative in highly polar media (DMSO, DMF) was observed. Gossypol
hydrazones exist in solution only as imineeimine tautomer.
Keywords:
Gossypol imine derivative
© 2018 Elsevier B.V. All rights reserved.
Tautomerism
NMR
IR
UVeVis

1. Introduction 2. Experimental

The study of gossypol imine derivatives is very actual and 2.1. Apparatus and materials
important task [1e10]. Interest to this class of compounds is due to
their biological activity. Gossypol imine derivatives are effective All imine derivatives were synthesized and purified as in
antioxidants exhibit antitumor, antiviral activity and posses less Ref. [20]. 1H and 13C NMR spectra were recorded in CDCl3, DMSO-d6
toxicity than the original polyphenol [1e7]. The diversity of the and DMF-d7 solutions on Bruker Avance II (400 MHz) spectrometer
biological properties of gossypol and its derivatives is largely due to at T ¼ 293 K. The spectra were obtained at a base frequency of
their existence in different tautomeric forms. It is known that 100 MHz for 13C and 400 MHz for 1H nuclei. The residual signals of
gossypol imine derivatives can exist in imine-imine and enamine- protons and 13C nuclei of the solvent were used as internal stan-
enamine forms which is analogues of aldehyde-aldehyde and dard. UVeVis spectra were recorded on Shimadzu UV-1650PC
ketol-ketol form of gossypol, respectively [8,9]. Tautomeric equi- spectrometer in cells (layer thickness 1 cm) at T ¼ 293 K. The con-
libria of gossypol Schiff bases and hydrazones are extensively centrations of tested solutions were 2.1$105 e 1.0$104 М. FT-IR
studying by IR, NMR spectroscopy and molecular modeling spectra were recorded on Perkin-Elmer Spectrum BX spectrom-
methods [10e20]. However the factors that determine tautomers eter (resolution 4 cm1) in KBr discs.
ratio in each particular case are not entirely obvious.
In this paper, the structure and tautomeric equilibria of nine 2.2. Computational methods
gossypol imine derivatives (Fig. 1) were studied by 1Н and 13С NMR,
FT-IR, UVeVis spectroscopy and quantum chemistry. The molecular geometries were optimized using the NWChem-
6.1 software package [21]. The vibrational spectra and dipole mo-
ments were calculated using B3LYP/6-31G(d). The scaling factor (l)
was used in order to correct the calculated vibrational frequencies
[22]. Chemical shifts were calculated using the GIAO-B3LYP/6-
31G(d) approach. The excited states energies of enamine-
* Corresponding author. enamine and imine-imine tautomeric forms of GAMI were ob-
E-mail address: [email protected] (A.M. Dykun). tained using the GAMESS-US 12 software package [23] by TD-DFT

https://doi.org/10.1016/j.molstruc.2018.11.028
0022-2860/© 2018 Elsevier B.V. All rights reserved.
290 A.M. Dykun et al. / Journal of Molecular Structure 1179 (2019) 289e296

present in the spectra of hydrazones GDPG and GCTA in DMSO-d6

and CDCl3. С(7)eOH groups protons are involved in a strong
hydrogen bond formed with N(13) nitrogen atoms [18], that leads
to a shift of this protons signals toward a weak field in comparison
with the С(1)eOH and С(6)eOH groups protons signals. It follows
that gossypol hydrazones exist in solution as imine-imine. N(14)eH
groups protons signals are shifted toward a weak field in DMSO-d6
in comparison with the signals of these protons in CDCl3 (Table 2).
This is due to the intermolecular hydrogen bond formation be-
tween these protons and solvent.
In the 1H NMR spectra of all studied compounds in the region of
1.4e1.6 ppm two partially overlapping doublets are observed
(3J(HC, СH) ¼ 6e7 Hz). They were interpreted as signals of the
protons of Me(1) and Me(2) groups and aroused from the diaster-
eotopicity of the methyls in this chiral molecules [17].
Gossypol Schiff bases GDFA, GMTA, GDMTA, GDTA (in DMSO-
d6) and GDBA, GSAP (in solution CDCl3/DMSO-d6 (v:v ¼ 1:5))
exist in enamine-enamine tautomeric form. С(1)eOH and С(6)eOH
groups protons signals shifted toward a weak field compared to
these signals in CDCl3. This is due to the intermolecular hydrogen
bond formation between these protons and DMSO-d6.
The reasons why the most of the gossypol Schiff bases exist
exclusively in eneamine-enamine and hydrazones in imine-imine
tautomeric form are not entirely clear. Presumably the additional
nitrogen atom in hydrazones structure reduces the basisity of the
corresponding imine nitrogen, making it less likely to accept a
proton needed to tautomerize into the enamine form [5]. Also
Fig. 1. The structure of tautomers and numbering of atoms of gossypol imine de-
dienamine tautomer could be stabilized by the hydrogen bond
rivatives (Me ¼ СН3). formed between the proton of С(6)eОН group and the oxygen
atom at C(7) [24,27]. The existence of this hydrogen bonds are
confirmed by the С(6)eОН groups protons signals shifted toward a
B3LYP/6-31 þ G(d,p) method. The solvent (chloroform) effect was weak field in CDCl3 (d ¼ 7.8e8.0 ppm) in the spectra of gossypol
taking into account within the SMD model (Solvation Model Schiff bases GDFA, GDBA, GMTA, GDMTA, GSAP and GDTA. While
Density). for the gossypol [24,27] and hydrazone GDPG this signals are
observed in the range of 6.5e7.0 ppm.
3. Results and discussion Table 1 data shows that the С(6)eOH group proton signal is
slightly shifted toward a strong field for GAMI in CDCl3 compared to
3.1. NMR spectra other studied Schiff bases. This fact indicates that the hydrogen
bond С(6)ОeН···О ¼ С(7) of GAMI is weaker than that of other
Analysis of 1H NMR spectra indicates that all studied gossypol studied Schiff bases. In more polar solvent (DMF-d7, DMSO-d6)
Schiff bases (GDFA, GDBA, GMTA, GDMTA, GAMI, GDTA and GSAP) С(6)eOH group preferentially form intermolecular hydrogen
exist in enamine-enamine tautomeric form in CDCl3. This is bonds with the solvent molecules and the С(6)eOH group proton
confirmed by the presence of N(13)eH groups protons signals in signal shifts toward a weak field. That promotes a shift the equi-
the 1H NMR spectra in region of 13.2e16.2 ppm (Table 1). N(13)eH librium to imine-imine tautomeric form.
1
groups protons are engaged in the N(13)eH···O]C(7) hydrogen H NMR spectra data indicates that in DMSO-d6 and DMF-d7
bond formation that leads to signal shifting towards a weak field. GAMI exists in two tautomeric forms: enamine-enamine and
The 3J(HC, NH) coupling constants in all cases are 10e12 Hz which imine-imine (the content of the enamine-enamine tautomeric form
is typical for compounds in enamine-enamine tautomeric form in DMF-d7 is ~60%, and in DMSO-d6 is ~10% at T ¼ 293 K). The
[24e26]. content of the tautomeric forms was determined from the integral
The signals of the protons of С(7)eOH and N(14)eH groups are intensities ratio of the C(11)eH group proton signal of enamine-

Table 1
1
H NMR chemical shifts (ppm) of gossypol imine derivatives in CDCl3 (numbering according to Fig. 1).

Group of atoms GDFA GDBA GMTA GDMTA GAMI GDTA GSAP GDPG

Me(1) 1.53 1.52 1.54 1.55 1.52 1.52 1.53 1.57

Me(2) 1.55 1.54 1.56 1.57 1.54 1.54 1.55 1.58
Me(3) 2.15 2.15 2.15 2.15 2.12 2.13 2.08 2.14
C(12)H 3.72 3.71 3.74 3.73 3.68 3.70 3.71 3.72
С(1)OH 5.79 5.79 5.77 5.79 5.79 5.21 5.74 5.66
С(6)OH 7.85 7.82 7.91 7.95 7.66 7.89 7.80 6.61
C(4)H 7.63 7.63 7.63 7.63 7.56 7.61 7.55 7.75
C(11)H 10.09 10.10 10.09 10.13 10.02 9.25 11.01 9.64
N(13)H 15.01 14.91 15.09 14.67 14.27 13.41 16.14 e
N(14)H e e e e e e e 3.91
С(7)OH e e e e e e e 13.85
 A.M. Dykun et al. / Journal of Molecular Structure 1179 (2019) 289e296 291

Table 2
1
H NMR chemical shifts (ppm) of gossypol imine derivatives in DMSO-d6 and in solution CDCl3/DMSO-d6 (numbering according to Fig. 1).

Group of atoms DMSO-d6 CDCl3/DMSO-d6

GDFA GMTA GDMTA GAMI GDTA GDPG GCTA GDBA GSAP

diimine dienamine

Me(1) 1.45 1.45 1.45 1.41 1.41 1.42 1.47 1.45 1.43 1.43
Me(2) 1.47 1.47 1.47 1.43 1.43 1.44 1.48 1.47 1.45 1.45
Me(3) 1.97 1.99 1.97 2.05 2.05 1.91 1.98 1.95 2.02 1.96
C(12)H 3.74 3.75 3.71 3.71 3.71 3.78 3.90 3.90 3.66 3.71
С(1)OH 8.25 8.18 8.32 7.60 7.41 7.66 8.09 8.36 7.37 7.97
С(6)OH 8.57 8.51 8.68 8.49 8.59 8.33 8.76 8.84 8.08 8.17
C(4)H 7.52 7.52 7.51 7.16 7.16 7.41 7.60 7.60 7.77 7.59
C(11)H 10.31 10.29 10.39 7.20 10.18 9.45 10.47 10.09 10.25 10.88
N(13)H 14.97 15.14 14.61 e 14.42 13.21 e e 14.85 16.18
N(14)H e e e e e e 9.78 13.11 e e
С(7)OH e e e 9.88 e e 13.95 14.25 e e

enamine form (in DMF-d7 d ¼ 10.51 ppm, in DMSO-d6

d ¼ 10.18 ppm) and the C(16)eH group proton signal (in DMF-d7
d ¼ 5.96 ppm, in DMSO-d6 d ¼ 5.70 ppm).
The signal of the proton singlet of С(7)eOH group
(d ¼ 9.88 ppm) in 1H NMR spectrum of GAMI in DMSO-d6 is
observed. The signals at d ¼ 14.42 ppm and at d ¼ 10.18 ppm are
assigned to N(13)eH and C(11)eH groups protons of the enamine-
enamine tautomeric form (3J (HC, NH) ¼ 10.9 Hz). C(11)eH proton
signal of group of the imine-imine tautomeric form is significantly
shifted toward a strong field (d ¼ 7.20 ppm) in comparison to the
signal of this proton of the enamine-enamine form. The tempera-
ture increasing leads to a shift of tautomeric equilibrium toward the
eneamine-enamine form. When the temperature increases from
293 K to 363 K content of the enamine-enamine form increases
from ~10% to ~80% in DMSO-d6.
Joint analysis of experimental and calculated NMR chemical
shifts is a convenient additional procedure for assignment of sig-
nals in the NMR spectra [28]. Calculations within the framework of
Fig. 2. Plot of calculated 13C chemical shifts vs. experimental chemical shifts of
the density functional theory (DFT) in the GIAO (Gauge Including
gossypol Schiff base GSAP (dcalc ¼ 0.94(±0.01)dexper þ 8.8(±1.2), |R| ¼ 0.999, S ¼ 2.44,
Atomic Orbital) approximation ensure an optimum computational n ¼ 26).
cost/accuracy ratio and are most often used [29e34]. To complete
assignment of all signals in 13C NMR spectra the chemical shifts for
all studied gossypol imine derivatives were calculated. To compare DMSO-d6. The signals of the C(1) atoms for Schiff base GAMI and
the calculated and experimental chemical shift values, they should hydrazone GDPG are shifted toward a strong field (d ¼ 146.7 ppm,
be transformed to a unified scale. This was done by performing d ¼ 145.3 ppm) in comparison to the signals of these atoms of other
calculations for the reference compound and the compound under investigated gossypol imine derivatives. However in case of
study using the same method. The final values of the calculated hydrazone GCTA in imine-imine form position of the signal of C(1)
chemical shifts of the compounds under investigation (dcalc) were atom (d ¼ 150.1 ppm) is close to that of Schiff bases in enamine-
determined from the expression [28]: enamine tautomeric form. The signals of C(8) atoms in the
spectra of Schiff bases in enamine-enamine form are slightly shif-
dcalc ¼ d*st e d*sub þ d0st (1) ted toward a strong field in comparison with the analogous signals
of imine derivatives in imine-imine form.
where d*st is the calculated chemical shift of the reference com- In the 13C NMR spectrum of GAMI in DMSO-d6 the signals of the
pound, d*sub is the calculated chemical shift of the substance under C(1), C(6), C(7), C(8) and C(11) atoms of the imine-imine tautomer
study, and d0st is the chemical shift assigned to the reference are observed (d ¼ 146.7 ppm, d ¼ 139.2 ppm, d ¼ 155.5 ppm,
compound (the reference compound was benzene d ¼ 108.4 ppm, and d ¼ 167.9 ppm, respectively). The signals of
d0st ¼ 128.5 ppm) [28]. these atoms of the eneamine-enamine tautomer are registered
Good agreement between experimental and calculated values is with a lower intensity (d ¼ 150.3 ppm, d ¼ 145.8 ppm,
confirmed by high values of correlation coefficients (not lower than d ¼ 175.4 ppm, d ¼ 106.9 ppm and d ¼ 153.7 ppm, respectively).
0.998) (Fig. 2).
13
C NMR data indicate a significant difference between the
chemical shifts of the imine-imine and eneamine-enamine forms of 3.2. UVevis spectra
gossypol imine derivatives which allows them to be easily identi-
fied. The signals of the C(6) and C(7) atoms of imine-imine form are Analysis of UVeVis spectra indicates that the most characteristic
shifted toward the strong field in comparison to the signals of these absorption bands for gossypol Schiff bases (enamine-enamine
atoms of enamine-enamine form (Table 3). Thus imine-imine tautomeric form) in chloroform are located in the range of
tautomeric form is confirmed for GAMI, GDPG and GCTA in 385e480 nm [35e38]. These bands can be assigned to an intra-
molecular charge transfer (CT) interaction [35e38]. The molar
292 A.M. Dykun et al. / Journal of Molecular Structure 1179 (2019) 289e296

Table 3
13
С NMR chemical shifts (ppm) of gossypol imine derivatives in CDCl3 and DMSO-d6 (numbering according to Fig. 1).

Number of atom DMSO-d6 CDCl3

GDFA GMTA GDMTA GAMI GDTA GDPG GCTA GDBA GSAP

dienamine dienamine dienamine diimine dienamine diimine diimine dienamine dienamine

Me(1e3) 20.3 20.3 20.2 21.0 20.3 20.7 20.6 20.3 20.3
Me(4) e 55.5 e e e e e e e
Me(5) e e 55.6 e e e e e e
Me(6) e e 56.5 e e e e e e
Me(7) e e e 12.1 e e e e e
Me(8) e e e e 25.5 e e e e
Me(9) e e e e 13.5 e e e e
Me(10) e e e e 11.1 e e e e
Me(11) e e e e e e e e 10.6
Me(12) e e e e e e e e 36.3
Me(13e15) e e e e e e 53.6 e e
C(1) 150.2 150.1 150.4 146.7 153.0 145.3 150.1 149.6 149.9
C(2) 127.8 121.0 120.9 115.5 120.0 115.8 116.9 116.6 116.1
C(3) 136.4 132.2 129.1 135.8 131.4 132.6 132.9 133.3 132.4
C(4) 121.2 115.5 115.1 112.6 115.6 129.0 119.0 119.0 118.1
C(5) 128.9 127.7 128.0 125.6 126.9 126.2 128.7 129.4 128.6
C(6) 146.2 146.2 146.5 139.2 146.1 143.8 143.8 147.0 146.5
C(7) 173.7 172.9 174.8 155.5 172.1 151.2 150.9 174.8 171.1
C(8) 105.7 105.3 106.2 108.4 103.3 108.7 107.0 105.5 105.3
C(9) 119.9 117.1 117.1 121.0 116.6 118.1 115.8 118.9 114.7
C(10) 132.5 128.4 128.7 123.8 127.0 126.3 128.4 130.1 129.1
C(11) 153.9 157.4 154.1 167.9 158.7 147.5 154.1 153.6 157.6
C(12) 26.7 26.7 26.6 26.2 26.6 26.6 26.7 27.7 27.6
C(15) 136.4 132.8 132.5 162.7 52.2 144.7 159.6 138.7 111.9
C(16) 117.2 119.4 143.3 94.2 56.6 111.5 63.0 119.7 159.4
C(17) 119.8 115.3 113.3 168.2 161.2 129.5 e 133.1 143.7
C(18) 159.8* 153.8 109.7 e 149.7 119.1 e 114.4 134.2
C(19) 119.8 115.3 150.9 e e 129.5 e 133.1 124.5
C(20) 117.2 119.4 101.5 e e 111.5 e 119.7 129.4
C(21) e e e e e e e e 127.4
C(22) e e e e e e e e 129.4
C(23) e e e e e e e e 124.5
*
e Observing splitting is due to CeF couplings (1J(C,F) ¼ 243 Hz).

extinction coefficients of the CT bands of studied gossypol imine broadened band at lmax ¼ 300 nm. Apparently the intensity
derivatives varies from 16000 l mol1∙cm1to 45000 l mol1 cm1. decreasing of the longest wavelength band in the experimental
In DMSO the CT bands display a red shift and intensity decrease. UVeVis spectrum of GAMI in DMSO is explained by the shifting the
This is due to the intermolecular hydrogen bond formation with the tautomeric equilibrium towards imine-imine form which is in
solvent [35e38]. The longest wavelength bands for the studied agreement with the NMR data.
hydrazones are located in the range of 385e395 nm.
The electronic absorption spectrum of GAMI in chloroform at 3.3. IR spectra
T ¼ 293 K displays three main bands: at lmax ¼ 250 nm, at
lmax ¼ 310 nm and at lmax ¼ 425 nm (ε ¼ 67000 l mol1 cm1, In the IR spectra of all studied compounds strong absorption
ε ¼ 26000 l mol1 cm1 and ε ¼ 30000 l mol1 cm1, respectively). bands in the range of 1600e1620 cm1 are observed. In the spec-
In DMSO all those bands display a shift (lmax ¼ 262 nm, trum of GSAP strong absorption band at 1652 cm1 was assigned to
lmax ¼ 300 nm and lmax ¼ 442 nm, respectively). Furthermore, the the stretching vibrations of C(16) ¼ O. Absorption band at 1691 cm1
longest wavelength band displays significant intensity decrease in the spectrum of hydrazone GCTA was assigned to stretching vi-
(from ε ¼ 30000 l mol1 cm1 to ε ¼ 6200 l mol1 cm1). With ris- brations of C(15) ¼ O. The most noticeable differences in the IR
ing of the temperature from 293 K to 353 K the intensity of this spectra of Schiff bases and hydrazones are observed in the region of
band increases. The intensities of the bands at lmax ¼ 262 and at ОeН and NeН stretching vibrations. In the case of Schiff bases
lmax ¼ 300 nm almost do not change. This may be due to the shift of strong broadened bands corresponding to the stretching vibrations
tautomeric equilibrium toward enamine-enamine form [25]. of ОeН groups (С(1)ОeН and С(6)ОeН groups, respectively) in the
Calculated electronic absorption spectrum of GAMI in enamine- region of 3480 cm1 and 3350 cm1 are observed. Broadened ab-
enamine form in chloroform exhibit band at lmax ¼ 427 nm sorption bands at 3400 cm1 appear in the spectrum of hydrazones.
(2.91 eV). This band is due to the p/p* intramolecular charge Obviously these bands correspond to the stretching vibrations of
transfer transition. Calculated wavelength is in a good agreement ОeН groups at С(7). In the spectra of all studied compounds strong
with the experimental value of 425 nm (2.92 eV). Upon transition to absorption bands in the range of 1500e1600 см1 are observed.
the imine-imine tautomeric form the hydrogen at N(13) is trans- These bands can be assigned to the C]C stretching vibrations. Less
ferred to oxygen at C(7) [26] and the electronic structure of the intense absorption bands are observed in this region in the spectrum
molecule is changed. This leads to a blue shift of the corresponding of hydrazone GCTA. Which is probably due to the absence of C]C
CT band. Calculated electronic absorption spectrum of GAMI in groups in imine fragment of this molecule.
imine-imine form exhibit CT band at lmax ¼ 375 nm (3.31 eV). In IR spectra of enamine-enamine and imine-imine tautomers of
the experimental spectrum of GAMI in DMSO (imine-imine form is GAMI were calculated to determine tautomeric form of this com-
present) this absorption band is overlapped by an intense pound in the solid state. Fig. 3 shows atoms and molecular
 A.M. Dykun et al. / Journal of Molecular Structure 1179 (2019) 289e296 293

fragments numeration used in the analysis of IR spectrum of GAMI

(enamine-enamine).
Experimental spectrum of GAMI is the best consistent with the
calculated IR spectrum of the enamine-enamine form. Good
agreement of the absorption bands corresponding to n(O1,10 eH) and
n(O6,60 eH) are observed (Table 4). In the experimental spectrum at
1605 cm1 strong absorption band is observed. Analogous ab-
sorption band at 1604 cm1 corresponding to the
d(N13,13 eH) þ n(C15,15' ¼ C16,160 ) þ n(C7,7' ¼ O) vibrations is observed
0

in the calculated spectrum. However the contribution of the po-

tential energy of n(C7,7' ¼ O) vibration at 1604 cm1 is only 2.7%. The
largest contribution of the potential energy of n(C7,7' ¼ O) vibration
is observed for the medium band at 1576 cm1 (39.0%). In this case
Fig. 3. Atoms and molecular fragments numeration used in the analysis of IR spectrum
the low frequency n(C7,7' ¼ O) can be due to the formation of 6-
of GAMI (enamine-enamine).
membered ring with the hydrogen bond NeH/O]C and 5-

Table 4
Assignments of fundamental vibrations of GAMI (numbering according to Fig. 3).

Experimental frequencies, Theoretical frequencies, Approximate assignments

cm1 cm1

3491 3483 n(O1,10 -H)

3327 3327 n(O6,60 -H)
3134 3151 n(C11,110 eH) þ n(N13,130 -H)
3107 3114 n(N13,130 eH) þ n(C11,110 -H)
3100 n(C4,40 eH) þ n(C12,120 -H)
2963 3029 n (CeH)Me1,1' þ nas(CeH)Me2,2' þ n(C12,120 -H)
as

3009 nas(CeH)Me3,30
2992 nas(CeH)Me1,1' þ nas(CeH)Me2,2' þ nas(CeH)Me4,40
2981 nas(CeH)Me3,3' þ n(C12, 120 -H)
2928 2933 ns(CeH)Me4,40
2924 ns(CeH)Me1,1' þ ns(CeH)Me2,20
2921 ns(CeH)Me1,1' þ ns(CeH)Me2,20
2919 ns(CeH)Me3,30
1624 1634 n(C5,5' ¼ C6,60 ) þ d(N13,130 -H)
1625 d(N13,130 eH) þ d(C11,110 eH) þ n(C15,15' ¼ C16,160 )
1605 1604 d(N13,130 eH) þ n(C15,15' ¼ C16,160 ) þ n(C7,7' ¼ O)
1599 n(RI,I0 ) þ n(RII,II0 )
1553 1576 n(C7,7' ¼ O) þ d(N13,130 -H)
1512 1518 n(C8,8' ¼ C11,110 ) þ d(N13,130 eH) þ n(C]N)RIII,III0
1513 n(C2,2' ¼ C3,30 ) þ d(CeH)Me3,30
1485 1489 d(O1,10 eH) þ d(O6,60 eH) þ n(C]N)RIII,III' þ d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 -H)
1486 n(C7,7' ¼ C8,80 ) þ d(O1,10 eH) þ d(O6,60 eH) þ n(C]
N)RIII,III' þ d(C4,40 eH) þ d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ n(C16,160 -CMe4,40 )
1462 1473 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ d(C11,110 eH) þ n(C14,14' ¼ C15,150 )
1468 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(CeH)Me4,4' þ d(O1,10 eH) þ n(C14,14' ¼ C15,150 ) þ d(C11,110 -H)
1462 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(CeH)Me4,4' þ d(O1,10 eH) þ n(C14,14' ¼ C15,150 ) þ d(C11,110 eH) þ d(C15,150 -H)
1454 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 -H)
1449 d(CeH)Me3,3' þ n(C1,1' ¼ C9,90 )
1423 1436 d(CeH)Me4,4' þ d(CeH)Me3,30
1433 d(CeH)Me3,30
1427 d(CeH)Me4,40
1424 d(CeH)Me3,3' þ d(C12,120 eH) þ d(O1,10 eH) þ d(O6,60 eH) þ d(CeH)Me4,40
1423 d(CeH)Me3,3' þ d(C12,120 eH) þ d(C4,40 eH) þ d(O1,10 eH) þ d(O6,60 eH) þ d(CeH)Me4,4' þ n(C6,60 -C7,70 )
1411 d(CeH)Me3,3' þ n(C1,10 -C9,90 ) þ n(C2eC20 )
1383 1396 n(C2,20 -C3,30 ) þ d(C4,40 eH) þ d(CeH)Me3,3' þ d(O6,60 -H)
1375 d(CeH)Me3,3' þ d(C12,120 eH) þ d(C4,40 -H)
1367 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(CeH)Me3,3' þ d(O6,60 -H)
1365 d(CeH)Me3,3' þ d(CeH)Me4,4' þ d(C12,120 eH) þ n(C7,70 -C8,80 ) þ d(O6,60 eH) þ d(C15,150 eH) þ d(C11,110 -H)
1319 1348 d(CeH)Me1,1' þ d(CeH)Me2,20
1339 d(C12,120 eH) þ d(C4,40 eH) þ n(C5,50 -C12,120 )þ d(O1,10 eH) þ d(O6,60 -H)
1331 d(O1,10 eH) þ d(O6,60 eH) þ d(CeH)Me3,3' þ d(C11,110 eH) þ d(N13,130 eH) þ n(C1,10 -O)
1318 d(C12,120 eH) þ n(C9,90 -C10,100 ) þ d(O1,10 eH) þ d(O6,60 eH) þ d(C11,110 eH) þ d(N13,130 eH) þ d(C15,150 eH) þ d(CeH)Me4,40
1313 d(C11,110 eH) þ d(O6,60 eH) þ d(C15,150 -H)
1311 d(C11,110 eH) þ d(O6,60 eH) þ d(C12,120 eH) þ n(C7,70 -C8,80 ) þ n(C9,90 -C10,100 )
1309 d(C12,120 eH) þ n(C9,90 -C10,100 ) þ n(C1,10 -C2,20 )
1290 d(C11,110 eH) þ d(O1,10 eH) þ d(C12,120 eH) þ n(C8,80 -C9,90 ) þ n(C5,50 -C10,100 ) þ n(C2eC20 )
1287 n(C11,110 -N13,130 ) þ n(C5,50 -C10,100 ) þ n(C3,30 -CMe3,30 )
1286 n(C16,160 -O)RV,V' þ n(C11,110 -N13,130 ) þ d(O6,60 eH) þ n(C5,50 -C12,120 )
1273 d(C11,110 eH) þ d(O6,60 eH) þ n(C6,60 eO) þ n(C6,60 -C7,70 ) þ n(C8,80 -C9,90 ) þ d(C12,120 -H)
1244 1259 n(C16,160 -O)RV,V' þ n(C14,140 -C15,150 ) þ d(C11,110 eH) þ n(C6,60 eO) þ d(CeH)Me4,40
1252 d(O1,10 eH) þ n(C2eC20 ) þ d(C4,40 eH) þ n(C8,80 -C9,90 )
1245 d(CeH)Me4,4' þ d(O1,10 eH) þ d(N13,130 eH) þ
(continued on next page)
294 A.M. Dykun et al. / Journal of Molecular Structure 1179 (2019) 289e296

Table 4 (continued )

Experimental frequencies, Theoretical frequencies, Approximate assignments

cm1 cm1

1242 d(O1,10 eH) þ d(O6,60 eH) þ d(C11,110 eH) þ d(C4,40 eH) þ d(C12,120 eH) þ n(C5,50 -C10,100 ) þ n(C8,80 -C9,90 )
1237 d(C4,40 eH) þ n(C5,50 -C10,100 ) þ n(C5,50 -C12,120 )
1171 1197 d(O1,10 eH) þ d(C4,40 eH) þ d(C11,110 eH) þ d(N13,130 eH) þ n(C1,10 -C9,90 ) þ n(C6,60 -O)
1160 d(C12,120 eH) þ d(C4,40 eH) þ d(C15,150 eH) þ d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C6,60 -C7,70 )
1156 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(O1,10 eH) þ d(C11,110 eH) þ n(C6,60 -O)
1138 1134 d(C15,150 eH) þ d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ d(C4,40 eH) þ d(C5,50 -C12,120 ) þ d(C12,120 -Me1,10 ) þ d(C12,120 -
Me2,20 )
1115 d(C15,150 eH) þ d(N13,130 -H)
1105 1089 d(C15,150 eH) þ d(C4,40 eH) þ d(C12,120 eH) þ d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(CeH)Me3,30
1062 1071 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ d(O6,60 eH) þ d(C11,110 eH) þ d(N13,130 -H)
1062 d(C15,150 eH) þ n(OeN)RIII,III' þ d(C12,120 eH) þ d(C4,40 eH) þ d(N13,130 -H)
1036 1056 n(OeN)RIII,III' þ d(C15,150 -H)
1005 1011 d(CeH)Me3,3' þ n(C5,50 -C10,100 )
996 d(CeH)Me4,4' þ d(C15,150 -H)
976 973 dop(N13,130 eH) þ dop(C11,110 -H)
953 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ d(N13,130 eH) þ d(C11,110 eH) þ d(C8,8' ¼ C11,110 ) þ d(C1,1' ¼ C9,90 )
926 928 d(CeH)Me4,4' þ d(C15,150 eH) þ n(OeN)RIII,III0
925 d(CeH)Me1,1' þ d(CeH)Me2,20
839 843 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ d(C5,50 -C12,120 ) þ d(C12,120 -Me1,10 ) þ d(C12,120 -Me2,20 )
830 dop(N13,130 -H)
804 dop(C4,40 eH) þ d(C11,110 -N13,130 )
779 780 d(C11,110 -N13,130 ) þ d(N13,130 eH) þ d(C11,110 eH) þ d(C16eO)RIII,III0
760 759 dop(C15,150 -H)
747 d(CeH)Me1,1' þ d(CeH)Me2,2' þ d(C12,120 eH) þ d(C4,40 -C10,100 ) þ d(C9,90 -C10,100 ) þ d(C11,110 -N13,130 )
708 727 dop(N13,130 eH) þ dop(O6,60 eH) þ dop(RI,I0 ) þ dop(RII,II0 ) þ d(C2eC20 )
682 677 dop(O6,60 eH) þ dop(C4,40 -H)
578 578 dop(O1,10 -H)
505 511 dop(O1,10 -H)
495 d(C8,8' ¼ C11,110 ) þ d(C15,150 eH) þ d(C14,140 -N13,130 )
Abbreviations: R e ring; Me e methyl; n e stretching; d e deformation; as e asymmetric; s e symmetric; op e out of plane bending.
Calculated frequencies obtained using B3LYP/6-31G(d) and l ¼ 0.9613.

membered ring with the hydrogen bond OeH/O]C. In the case of

imine-imine form of GAMI no absorption bands of C]O vibrations
were observed in calculated spectra, but there are three OeH vi-
brations, one of which (at C7,7’) shifts to 3000 cm1 due to the
hydrogen bond formation (C7,7’OeH/N). Strong absorption band at
1564 cm1 corresponding to n(С ¼ N) þ n(С ¼ С) arises. Thus a
comparison of experimental and calculated IR spectra of GAMI in-
dicates that this compound exists as enamine-eneamine tautomer
in the solid state.
The observed FT-IR wavenumbers, corresponding calculated
harmonic frequencies of GAMI (enamine-enamine) and the pro-
posed vibrational assignments are summarized in Table 4.
Fig. 4 shows experimental and calculated (enamine-enamine) IR
spectra of GAMI.

3.4. Theoretical calculations of tautomers structure

Calculated energies and dipole moments of different tautomers

of GAMI indicate that the enamine-enamine tautomeric form is
more stable in the gas phase which is in agreement with data
[20,25]. Thus dipole moment for enamine-eneamine form is 3.1 D
and for imine-imine form is 0.6 D. Energy difference between
imine-imine and enamine-enamine forms is 133.6 kJ mol1.
Table 5 shows calculated structural characteristics of studied
gossypol imine derivatives.
Geometries of the most stable tautomeric forms were optimized
and their structural characteristics were obtained. The relaxed
potential energy surface (PES) scans along dihedral angle C(1)e
C(2)eC(2’)eC(1’) for dienamine and diimine tautomeric forms of
GAMI were performed (Fig. 5). There are two minima for each
tautomeric form corresponded to dihedral angle C(1)eC(2)eC(2’)e
C(1’) of ±102.0 and ± 101.8 respectively. Calculations confirm
presence of intramolecular hydrogen bond N(13)$$$HeOC(7) in Fig. 4. Experimental (a) and calculated (b) (enamine-enamine) IR spectra of GAMI.
 A.M. Dykun et al. / Journal of Molecular Structure 1179 (2019) 289e296 295

Table 5
Structural characteristics of gossypol imine derivatives (numbering according to Fig. 1).

Compound Hydrogen bond Hydrogen bond length, Å Bond angle, Dihedral angle C(1)eC(2)eC(20 )eC(10 ), 

GDFA (dienamine) С(7)O/HeN(13) 1.73 137.0 100.8

С(7)O/HeОС(6) 1.87 122.4
GDBA (dienamine) С(7)O/HeN(13) 1.75 135.6 98.7
С(7)O/HeОС(6) 1.90 120.5
GMTA (dienamine) С(7)O/HeN(13) 1.73 137.2 101.0
С(7)O/HeОС(6) 1.87 122.7
GDMTA (dienamine) С(7)O/HeN(13) 1.77 133.9 101.3
С(7)O/HeОС(6) 1.86 123.0
GAMI (dienamine) С(7)O/HeN(13) 1.72 135.8 102.0
С(7)O/HeОС(6) 1.88 122.2
GDTA (dienamine) С(7)O/HeN(13) 1.74 135.4 100.5
С(7)O/HeОС(6) 1.87 122.7
GSAP (dienamine) С(7)O/HeN(13) 1.67 140.1 102.6
С(7)O/HeОС(6) 1.86 123.0
GDPG (diimine) N(13)$$$НeОС(7) 1.67 145.6 100.0
С(7)O/HeОС(6) 1.95 118.3
GCTA (diimine) N(13)$$$НeОС(7) 1.66 149.5 105.9
С(7)O/HeОС(6) 1.96 116.7

4. Conclusions

The structure of a number of gossypol imine derivatives has

been established in the paper by the methods of molecular spec-
troscopy and quantum chemistry. It has been found that gossypol
Schiff bases GDFA, GDBA, GMTA, GDMTA, GDTA and GSAP exist in
solution as the enamineeenamine tautomer irrespective of solvent.
Hydrazones GDPG and GCTA exist in solution only as the imine-
eimine. Gossypol Schiff base GAMI exists as an enamine-enamine
tautomer in chloroform and as a mixture of two tautomeric forms
in DMSO and DMF. It has been shown that the longest wavelength
band in the electronic absorption spectrum of GAMI is character-
istic for gossypol Schiff bases in enamine-enamine tautomeric form
and corresponds to intramolecular charge transfer interaction. The
intensity of this band significantly decreases at the transition from
enamine-enamine to imine-imine form. This compound exists as
enamine-eneamine tautomer in the solid state.

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