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45
CHAPTER IV
46
CHAPTER IV
i. Characterization and biological activity of the carbanionic sigma
complex derived from 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,-6-
(1H,3H,5H)-trione and triethylamine.
Ethanolic solution of 1-chloro-2,4-dinitrobenzene (DNCB) shows wave length
of maximum absorption at 290 nm. When triethylamine is added to the mixture of
DNCB and pyrimidine-2,4,-6-(1H,3H,5H)-trione (barbituric acid) in ethanol, a dark
maroon red colour is obtained, from which maroon red coloured crystals have
been isolated. This maroon red colour product has been identified as carbanionic
sigma complex 26 [triethylammonium 2,4-dinitrophenylbarbiturate, systematic name:
triethylammonium 5-(2,4-dinitrophenyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-
olate)].
N
H NO2
H H H
H
O
O
O
ON
HO O2N
H
N
OH
C N
NC
26b
O
O H
26a
HNO2
H H H
HO
O2N
O
O H N
H3CH2C
CH2CH3CH2CH3CH2CH3
H3CH2C
H3CH2C
CH2CH3CH2CH3CH2CH3
N
C
N
HH
NO2H
N
C
N
Complex 26 (barbiturate)
47
Structure of 26 has been confirmed from visible, IR, PMR, 13
C NMR, COSY, Mass
spectral studies and single crystal X-ray analysis. Elemental analysis and other
qualitative tests have also been performed to throw light on the proposed structure.
The physical data of complex 26 are presented in Table 1. Table 2 reflects the
wavelength of maximum absorption of complex 26 in various solvents of different
polarity. Some important IR spectral data of DNCB, barbituric acid and complex 26
are given in Table 3. PMR spectral data of DNCB, barbituric acid and complex 26
are summarized in Table 4. Figs. 1,2 and 3 are the IR spectra of DNCB, barbituric
acid and complex 26 respectively. Figs. 4,5 and 6 correspond to the PMR spectra of
DNCB, barbituric acid and complex 26. 13
C NMR spectra of DNCB, barbituric acid
and complex 26 are presented in Figs. 7,8 and 9 respectively. Figs 10 and 11 are the
proton-proton COSY and Mass spectrum of complex 26.
The isolated complex 26 is coloured because of the delocalization of charge
over a large area. Qualitative tests197
on complex 26 reveal the presence of nitrogen
atom, nitro groups and the absence of chlorine. In DNCB, a strong sharp absorption
band characteristic of C-Cl stretching mode has been observed at 732 cm-1
, which is
absent in the synthesized complex 26, clearly shows that during the formation of
complex 26, chlorine is removed from DNCB. Since upon the formation of the
complex, the aromatic nitro group is converted to one bearing partial negative charge,
the asymmetric and symmetric absorption frequencies are expected to decrease.17, 48
This has been observed in the present study also (Table 3). The broad band observed
between 2700 – 3400 cm-1
in complex 26 is characteristic of amine salt.198
In the
synthesised complex C=C stretching band appears at 1600 cm-1
. This may be
probably due to stretching of C=C band during delocalization.
In barbituric acid, N-H proton signal appears at 11.09 ppm. During the
formation of complex 26, the negative charge is delocalized over a large area upto the
keto functions nearer the N-H groups and hence the N-H protons are shielded to some
extent and show shift towards upfield. The adjacent ring protons of the nitro moiety
appear as double doublet in DNCB, whereas in the complex it has become a multiplet
supporting the delocalization of the negative charge.
48
Table 1
Physical Data of Complex 26
Data Complex 26
Molecular Formula C16H21N5O7
Molecular Weight 395
Physical State Maroon Red Crystalline Solid.
Stability Stable under ordinary conditions.
Decomposes if heated to high
temperatures.
Melting Point 535-537K (Decomposes at its melting
point).
Solubility Soluble in water (4g/l at 298K), insoluble
in ether.
pH (0.001M solution in water) 6.8
Toxicity (LD50) >1000mg/kg
Yield (pure crystals) 60%
Table 2
max and max of Complex 26 in solvents of different polarity
S.
No. Solvent
Concentration
of Complex 26
x 105M
max (nm)
max (mol
-1 l cm
-1)
1 dimethyl sulphoxide 0.50 480 70000
2 water 5.00 395 20000
3 ethanol 5.00 425 27000
4 2-butanol 4.63 435 24840
5 2-methyl-1-propanol 7.00 420 22530
6 methanol 5.00 420 19000
7 glycol 5.00 420 14800
8 1-propanol 5.00 420 11200
9 tert-butylalcohol 10.00 435 10000
10 benzyl alcohol 5.00 440 8400
11 2-butanone 5.00 460 31000
12 acetone 5.00 485 27800
13 acetophenone 0.25 475 10000
14 dioxan 10.00 380 3500
49
Table 3
IR spectral data
Group
1-Chloro 2,4-
dinitrobenzene
(cm-1
)
Barbituric acid
(cm-1
)
Complex 26
(cm-1
)
NO2 asym. str. 1545 (s,sh) - 1516 (m,b)
NO2 sym. str. 1351 (s,sh) - 1343 (s,sh)
C – Cl str. 732 (s,sh) - -
C = O str. - 1716 (s,sh) 1712 (s,sh)
C = C str. - - ~ 1600 (s,sh)
N – H str. - 3479, 3529 (s) 2700-3400 (s,b)
Table 4
PMR spectral data
Molecule Position of
absorption peaks Proton type
1-Chloro-2,4-
dinitrobenzene 8.76 (s,1H)
8.46 (d,1H)
7.92 (d,1H)
Ring proton of nitro moiety
Adjacent ring
protons of nitro moiety
Barbuturic acid 11.09 (s, 2H)
3.39 (s, 2H)
Two N – H protons
H2C – protons
Complex 26 9.66 (s, 2H)
8.36 (s, 1H)
8.15 to 8.25
(m, 2H)
1.15 (t, 9H)
3.08 (q, 6H)
Two N – H protons
Ring protons of nitro moiety
Adjacent ring protons of nitro moiety
–CH3 of HN (CH2CH3)3
–CH2 of HN (CH2CH3)3
50
51
52
Fig.3 IR spectrum of Complex 26
53
54
Fig.4a PMR spectrum of 1-chloro-2,4-dinitrobenzene
55
56
57
58
Fig.7 13
C NMR spectrum of 1-chloro-2,4-dinitrobenzene
59
60
61
Fig.10 Proton-proton COSY of Complex 26
62
Fig.11 Mass spectrum of Complex 26
63
Proton–proton COSY of complex 26 (Fig.10) reveals that 1H –
1H coupling has occurred
between the protons in the cation moiety. 13
C spectrum of barbituric acid exhibits two
signals at 151.7 ppm and 167.8 ppm due to the keto group carbon atoms. Six signals have
been observed in the 13
C spectrum of DNCB. Carbon atom bearing Cl appears at 133.6 ppm.
The synthesized complex 26 exhibits 11 signals in the 13
C spectrum. The absorption peaks at
8.6 ppm and 45.8 ppm are due to the carbon environments of CH3 and CH2 groups
respectively of triethylammonium ion. The absorption peak at 86.6 ppm is not noticed in
DNCB and barbituric acid but only in complex 26 may be due to the newly formed carbon
environment (C=C).199
In FABMS, base peak corresponds to triethylammonium cation (m/z
= 102) is found. Based on spectral observations, Scheme 4 has been proposed for the
formation of complex 26 from DNCB and barbituric acid in the presence of triethylamine.
The structure of complex 26 has been confirmed through single crystal X-ray
analysis.
Crystal data of complex 26
Empirical
formula
C6H16N+. C10H5N4O7
-
Formula weight 395.38
Radiation Mo K Wavelength 0.71073 Å
Volume 3689.20(17)Å3 Temperature 293 K
Crystal system,
space group
Monoclinic, C2/c
Z, Calculated
density
8, 1.424 mg m-3
Unit cell
dimensions
a = 29.7900 (8) Å,
Absorption
coefficient
0.113 mm-1
b = 10.4533 (3) Å, F(000) 1664
c = 11.9606 (3) Å, Crystal size 0.30 x 0.20 x 0.20 mm
alpha = 90.00°
Theta range for
data collection
1.38 to 24.93°
beta = 97.70° R factor 0.0396
gamma = 90.00° CCDC Number 721014
64
Selected bond lengths and bond angles of complex 26 are listed in Table 5. ORTEP view of
complex 26 is shown in Fig.12. The presence of the leaving group (chlorine atom) para
with respect to the nitro group of the starting molecule (1-chloro-2,4-dinitrobenzene)
facilitates the formation of complex 26 in the presence of barbituric acid and triethylamine.
Absence of chlorine atom, as indicated by the qualitative test on the synthesized barbiturate
has been supported by the crystallographic data. The title molecule is coloured maroon red
and it has been attributed to the delocalization of negative charge which has also been
substantiated by the bond angles and bond lengths of single crystal X-ray data of 2,4-
dinitrophenyl and barbiturate rings. The bond angles and bond lengths of barbiturate residue
of complex 26 are compatible with that of barbiturate ion 27200
evidencing the delocalization
of negative charge in the barbiturate.
C
N
C
N
C
C
H
O
HH
(1)
(2)
(3)
(4)
(5)
(6)
(2)
1.41Å1.25Å
117.6
1.39Å
125.2
1.37Å
123.6
115.11
117.0
119.9
1.35Å
121.3
1.23Å
125.7
117.1
1.39Å
117.6
1.22Å1.41Å(6)
(4)
O
O
27
Presence of double bond (delocalized) between C3 and C5 atoms fixes the
configuration of the molecule as depicted in Fig.12. The N5–H5…O2 hydrogen bond
between the asymmetric units is the main driving force for the orientation of the
triethylammonium cation (Fig.13). Two inversion related barbiturate anions interact through
a pair of N–H…O=C hydrogen bonds involving N1 – H1 atoms and carbonyl oxygen atom
(O1) forming a R22 (8) ring motif. The same ring motif is also due to a pair of N–H…O
hydrogen bonds involving N2 – H2 atoms and the carbonyl oxygen atom (O3). This motif
is one of the 24 most frequently observed bimolecular cyclic hydrogen – bonded motifs in
organic crystal structures.201
The hydrogen bonds (Table 6) observed in complex 26 are
mainly responsible for its stability. The high solubility of the complex in water (4g/cc at
65
298K) is due to the positively charged triethylammonium cation and negatively charged 2,4-
dinitrophenylbarbiturate anion of the asymmetric unit.
Anticonvulsant activity of complex 26
Complex 26 (barbiturate) is screened for anticonvulsant activity.202
The barbiturate
has been given one hour before the induction of Maximal Electro Shock (150mA / 0.2sec).
The current has been applied on the animals using the corneal electrodes. The barbiturate
shows activity even at low concentration (50mg/kg). The different stages of convulsions such
as tonic flexor, tonic extensor, clonus convulsion, stupor and recovery / death have been
examined. Reduction in extensor phase of convulsion has been noticed for the synthesized
barbiturate (Table 7). This implies that synthesized barbiturate of the present work may be
used as a drug for grand mal type of epilepsy.
Hypnotic activity of complex 26
Complex 26 induces hypnosis in albino mice (Table 8).
Acute toxicity study on complex 26
LD50 of the synthesized barbiturate has been examined as per OECD guidelines
(revised draft 423). The barbiturate falls under class 3 (LD50>1000mg/kg). The animals did
not show any signs of acute toxicity and behavioral changes (Table 9).
66
Scheme 4
Synthetic route of formation of Complex 26
eqn. 3
eqn. 2
NH
H
HNR3+
H
N Cl
O
O
OO
C
C
C N
N
H
O H
O H
O
1-Chloro-2,4-dinitrobenzene
O
O Cl
N
H
R3N
H
H
H
N
OO
O O
O
O
HO
H
C
C
C N
C
N
O
O
N
N
H
R3N
H
H
HHNR3Cl
O O
O
O Cl
N
N
H
R3N
H
H
H
O
NR3+O
HO
H
C
C
C N
N
H
O
O
HO
H
C
C
C N
N
H
(2nd molecule)
amine
Synthesized Barbiturate (Complex 26)
[R = CH2 - CH3]
N
N C
C
C
O + NR3
amine
H O
H
H H
OH
OH
O
N
N C
C
C
HNR3+
O
Barbituric acid
eqn. 1H
(1st molecule)
+
+
67
Table 5
Selected Bond Lengths and Bond Angles of Complex 26 (Å, °)
C1-O1 1.228(2) C5-C10 1.397(3)
C1-N1 1.357(2) C6-N3 1.471(2)
C1-N2 1.357(2) C6-C7 1.377(2)
C2-O2 1.248(2) C7-C8 1.373(3)
C2-N1 1.381(2) C8-C9 1.380(3)
C2-C3 1.412(2) C8-N4 1.464(2)
C3-C4 1.408(2) C9-C10 1.379(3)
C3-C5 1.466(2) N3-O4 1.217(2)
C4-O3 1.242(2) N3-O5 1.223(2)
C4-N2 1.396(2) N4-O6 1.212(2)
C5-C6 1.395(2) N4-O7 1.210(2)
O1-C1-N1 122.11(17)
N2-C4-C3 116.04(15)
O1-C1-N2 122.00 O6-N4-C8 118.64(19)
N1-C1-N2 115.45(16) O7-N4-O6 123.20(18)
C1-N1-C2 125.39
O7-N4-C8 118.14(19)
N1-C2-O2 118.42(15) C10-C5-C3 121.05(17)
N1-C2-C3 116.74(15) C3-C5-C6 122.95(16)
C1-N2-C4 125.53(16) C6-C5-C10 115.80(16)
O2-C2-C3 124.84(16) C7-C6-C5 123.46(16)
O4-N3-O5 123.88(17) C7-C6-N3 114.89(16)
C2-C3-C4 120.71(16) C5-C6-N3 121.64(15)
C4-C3-C5 121.58 (15) C8-C7-C6 117.81(17)
O4-N3-C6 118.73 C9-C8-C7 121.94(16)
O5-N3-C6 117.36(16) C7-C8-N4 117.74(18)
C2-C3-C5 117.63(15) C9-C8-N4 120.34(17)
N2-C4-O3 117.69(16) C10-C9-C8 118.50(17)
C3-C4-N2 116.00 C5-C10-C9 122.44(18)
O3-C4-C3 126.22(16)
68
Table 6
Hydrogen bond geometry (Å, °) of Complex 26
D-H…A d (D-H) d(H…A) d(D…A)
69
Fig. 13 Hydrogen bonding pattern and packing view of Complex 26
70
Table 7
Anticonvulsant activity of Complex 26 against MES
induced convulsion in Albino Rats
S.
No. Treatment
Time (sec) in various phases of convulsion
Flexor Extensor Clonus Stupor Recovery /
Death
1. Control
Normal Saline
(5ml/kg)
3.24
±
0.09
13.30
±
0.25
9.24
±
0.21
137.00
±
8.24
Recovered
2. Complex 26
(25mg/kg)
4.20
±
0.23
13.20
±
0.51
7.20
±
0.31
105.50
±
6.80
Recovered
3. Complex 26
(50mg/kg)
3.10
±
0.05
6.50
±
0.65
5.10
±
0.61
82.20
±
6.10
Recovered
4. Complex 26
(100mg/kg)
2.90
±
0.05
2.00
±
0.00
5.60
±
0.46
85.70
±
6.90
Recovered
5. Phenytoin
(standard)
(25mg/kg)
2.66
±
0.55
0.00
±
0.12
4.60
±
0.38
62.10
±
3.30
Recovered
Table 8
Hypnotic action of Complex 26
S.
No. Treatment
Dose
(mg/kg)
Time of
Admini-
stration
(mins)
(a)
Time of
loss of
reflex
(mins)
(b)
On set
of
action
(mins)
(b-a)
Time of
Recovery
(mins)
(c)
Duration
of action
(mins)
(c-b)
1 Control
Normal
saline
1 ml/kg
0 -- -- -- --
2 Complex 26 100
mg/kg 0
20.6 ±
4.14
20.6 ±
4.14
206.2 ±
2.10
185.6 ±
3.32
3 Phenobarbitone
Standard
20
mg/kg 0
16.4 ±
2.25
16.4 ±
2.25
257.9 ±
3.27
241.50 ±
5.90
71
Table 9
Data showing effect of Complex 26 on behavioural profiles of mice
Responses
Treatment
Score
(Normal Saline)
Score due to
Complex 28
Muscle Tone
Limp tone 4 4
Grip tone 4 4
Body tone 4 4
Abdominal tone 4 4
Reflexes
Pinna 4 4
Corneal 4 4
Writhing 0 0
Autonomic Profile
Urination 0 0
Salivation 0 0
Respiratory rate 4 4
Awareness
Alertness 0 0
Passivity 0 0
Aggression 0 0
Mood
Restlessness 0 0
Fearfulness 0 0
Touch response 4 4
Motor Activity
Pain response 4 4
Twitches 0 0
CNS excitation
Tremors 0 0
Convulsions 0 0
Body posture 4 4
Posture
Limb posture 4 4
72
ii. Characterization and biological activity of the carbanionic sigma
complex derived from 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,-6-
(1H,3H,5H)-trione and tri-n-butylamine
Orange red colour crystals have been isolated from the ethanolic solution of
DNCB, barbituric acid and tri-n-butylamine. Based on physical data (Table 10),
visible spectral data (Table 11), IR data (Table 12; Fig. 14), PMR data (Table 13,
Fig.15), 13
C NMR data (Fig. 16), COSY (Fig. 17), Mass (Fig. 18) and elemental
analysis data – found (calculated) 55.38 (55.11), H 6.53 (6.88), N 14.13 (14.61),
structure 28 has been assigned for the isolated molecule [tri-n-butylammonium 2,4-
dinitrophenylbarbiturate, systematic name: tri-n-butylammonium 5-(2,4-
dinitrophenyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate)]. 13
C NMR spectrum of
complex 28 exhibits 13 signals The absorption peak at 86.69 ppm corresponds to
the newly developed C=C environment. In the mass spectrum base peak corresponds
to tri-n-butylammonium cation (m/z = 186) is found. Single crystal X-ray data
(Tables 14-16, Figs. 19,20) confirm the putative structure.
Crystal data of Complex 28
Molecular formula C22 H33 N5 O7
Formula weight 479
Temperature 293(2) K
Radiation MoK
Wavelength 0.71073 Å
Crystal system, space group Monoclinic, C2/c
Unit cell dimensions a = 10.2132(14)Å alpha = 90.00°
b = 14.7146(10)Å beta = 91.674(9)°
c = 34.200(3)Å gamma = 90.00°
Volume 5137.5(9) Å3
73
Z, Calculated density 4, 1.235 mg m-3
F(000) 2032
Theta range for data collection 2.58 to 65.00 deg.
Completeness to theta = 65.00 98.4 %
Final R indices [I >2sigma(I)] R1 = 0.1017, wR2 = 0.2869
R indices (all data) R1 = 0.1829, wR2 = 0.3554
Disorder is observed in the lengthy alkyl chain (C22 is disorder with an occupancy of
45%)
The synthesized barbiturate 28 also has anticonvulsant / hypnotic activities
(Table 17 & 18). The LD50 of barbiturate 28 is > 490 mg/kg. The animals did not
show any signs of acute toxicity and behavioural changes (Table 19). The synthesized
barbiturates of the present investigation (26 & 28) may probably be the potent drugs
in future for grand mal type convulsion because of their extraordinary stability, low
toxicity, high solubility in water and easy method of preparation.
H
O
N
H NO2
H H H
H
O
O
O
ON
HO O2N
HNO
C N
NC
28b
O H
28a
N
C
N
HH
NO2H
N
C
N
NHO
O
O2N
OH
HHH
NO2H
Complex 28 (barbiturate)
74
Table 10
Physical Data of Complex 28
Data Complex 28
Molecular Formula C22H33N5O7
Molecular Weight 479
Physical State Orange Red Crystalline Solid.
Stability Stable under ordinary conditions.
Decomposes if heated to high
temperatures.
Melting Point 521-523K (Decomposes at its
melting point).
Solubility Soluble in water (3.5g/l at 298K),
insoluble in ether.
pH (0.001M solution in water) 6.8
Toxicity >490mg/kg
Yield (pure crystals) 70%
Table 11
max and max of Complex 28 in solvents of different polarities
S.
No. Solvent
Concentration
of Complex 28
x 105M
max (nm)
max (mol
-1 l cm
-1)
1 dimethyl sulphoxide 1.16 465 76388
2 water 1.16 390 34300
3 ethanol 2.70 425 48000
4 methanol 3.80 425 22300
5 1-propanol 3.80 425 17842
6 tert-butylalcohol 3.80 420 19600
7 benzyl alcohol 5.80 400 7000
8 2-butanone 1.90 480 11670
9 acetone 0.78 470 12400
10 acetophenone 2.70 465 14814
11 1-butanol 1.55 380 15748
12 acetonitrile 2.70 450 21060
75
Table 12
IR spectral data
Group
1-Chloro 2,4-
dinitrobenzene
(cm-1
)
Barbituric acid
(cm-1
)
Complex 28
(cm-1
)
NO2 asym. str. 1545 (s,sh) - 1518(m,sh)
NO2 sym. str. 1351 (s,sh) - 1334 (s,sh)
C – Cl str. 732 (s,sh) - -
C = O str. - 1716 (s,sh) 1704(s,sh)
C = C str. - - 1594(s,sh)
N – H str. - 3479, 3529 (s) 2700-3200 (s,b)
Table 13
PMR spectral data
Molecule Position of absorption peaks Proton type
1-Chloro 2,4-
dinitrobenzene
8.76 (s,1H)
8.46 (d,1H)
7.92 (d,1H)
Ring proton of nitro moiety
Adjacent ring
protons of nitro moiety
Barbituric acid
11.09 (s, 2H)
3.39 (s, 2H)
Two N – H protons
–CH2 Protons
Complex 28 9.68 (s, 2H)
8.84 (b, 1H)
8.16 to 8.38 (m, 3H)
3.03 (blurred triplet, 6H)
1.56 (quintet, 6H)
1.31 (sextet, 6H)
0.90 (t, 9H)
N – H protons
HN – of H
N (CH2-CH2-CH2-CH3)3
Ring protons of nitro moiety
–CH2 attached to nitrogen atom of
HN (CH2-CH2-CH2-CH3)3
–CH2 flanked by two methylene
groups of HN (CH2-CH2-CH2-CH3)3
–CH2 nearer to -CH3 of HN
(CH2-CH2-CH2-CH3)3
–CH3 of HN (CH2-CH2-CH2-CH3)3
76
77
Fig.15 PMR spectrum of Complex 28
78
Fig.15a PMR spectrum of Complex 28
79
Fig.15b PMR spectrum of Complex 28
80
Fig.16 13
C NMR spectrum of Complex 28
81
Fig.17 Proton-proton COSY of Complex 28
82
Fig.17a Proton-proton COSY of Complex 28
83
Fig.18 Mass s spectrum of Complex 28
84
Table 14
Selected bond lengths (Å) of Complex 28
C(1)-C(6) 1.344(9) C(13)-C(14) 1.412(14)
C(1)-C(2) 1.381(10) C(13)-H(13A) 0.9700
C(1)-N(1) 1.473(8) C(13)-H(13B) 0.9700
C(2)-C(3) 1.392(8) C(14)-H(14A) 0.9600
C(2)-H(2) 0.9300 C(14)-H(14B) 0.9600
C(3)-C(4) 1.381(8) C(14)-H(14C) 0.9600
C(3)-N(2) 1.500(9) C(15)-C(16) 1.397(14)
C(4)-C(5) 1.412(9) C(15)-H(15A) 0.9700
C(4)-C(7) 1.466(7) C(15)-H(15B) 0.9700
C(5)-C(6) 1.374(8) C(16)-C(17) 1.393(14)
C(5)-H(5) 0.9300 C(16)-H(16A) 0.9700
C(6)-H(6) 0.9300 C(16)-H(16B) 0.9700
C(7)-C(8) 1.408(8) C(17)-C(18) 1.469(17)
C(7)-C(10) 1.416(7) C(17)-H(17A) 0.9700
C(8)-O(5) 1.263(6) C(17)-H(17B) 0.9700
C(8)-N(3) 1.369(6) C(18)-H(18A) 0.9600
C(9)-O(7) 1.229(6) C(18)-H(18B) 0.9600
C(9)-N(4) 1.357(7) C(18)-H(18C) 0.9600
C(9)-N(3) 1.359(6) C(19)-C(20) 1.402(9)
C(10)-O(6) 1.238(6) C(19)-H(19A) 0.9700
C(10)-N(4) 1.397(6) C(19)-H(19B) 0.9700
N(1)-O(1) 1.211(9) C(20)-C(21) 1.524(9)
N(1)-O(2) 1.252(10) C(20)-H(20A) 0.9700
N(2)-O(4) 1.190(6) C(20)-H(20B) 0.9700
N(2)-O(3) 1.221(7) C(21)-C(22) 1.501(10)
N(3)-H(3N) 0.895(10) C(21)-C(22') 1.508(10)
N(4)-H(4N) 0.897(10) C(22)-H(22A) 1.1086
N(5)-C(19) 1.449(10) C(22)-H(22B) 1.1121
N(5)-C(11) 1.454(10) C(22)-H(22C) 1.1116
N(5)-C(15) 1.457(12) C(22')-H(22D) 0.9666
N(5)-H(5A) 0.9100 C(22')-H(22E) 0.9667
C(11)-C(12) 1.352(14) C(22')-H(22F) 0.9669
C(11)-H(11A) 0.9700
C(11)-H(11B) 0.9700
C(12)-C(13) 1.460(12)
C(12)-H(12A) 0.9700
C(12)-H(12B) 0.9700
85
Table 15
Selected bond angles (°) of Complex 28
C(6)-C(1)-C(2) 120.9(6) C(9)-N(3)-C(8) 125.7(5)
C(6)-C(1)-N(1) 121.5(8) C(9)-N(3)-H(3N) 115(3)
C(2)-C(1)-N(1) 117.5(7) C(8)-N(3)-H(3N) 120(3)
C(1)-C(2)-C(3) 118.3(6) C(9)-N(4)-C(10) 125.7(4)
C(1)-C(2)-H(2) 120.8 C(9)-N(4)-H(4N) 115(4)
C(3)-C(2)-H(2) 120.9 C(10)-N(4)-H(4N) 119(4)
C(4)-C(3)-C(2) 122.9(7) C(19)-N(5)-C(11) 111.7(8)
C(4)-C(3)-N(2) 121.6(5) C(15)-C(16)-H(16B) 107.5
C(2)-C(3)-N(2) 115.4(6) H(16A)-C(16)-H(16B) 107.0
C(3)-C(4)-C(5) 115.5(5) C(16)-C(17)-C(18) 114.5(13)
C(3)-C(4)-C(7) 124.2(7) C(16)-C(17)-H(17A) 108.6
C(5)-C(4)-C(7) 120.1(5) C(18)-C(17)-H(17A) 108.6
C(6)-C(5)-C(4) 122.0(6) C(16)-C(17)-H(17B) 108.7
C(6)-C(5)-H(5) 119.0 C(18)-C(17)-H(17B) 108.7
C(4)-C(5)-H(5) 119.0 H(17A)-C(17)-H(17B) 107.6
C(1)-C(6)-C(5) 120.3(7) C(17)-C(18)-H(18A) 109.5
C(1)-C(6)-H(6) 119.9 C(17)-C(18)-H(18B) 109.5
C(5)-C(6)-H(6) 119.9 H(18A)-C(18)-H(18B) 109.5
C(8)-C(7)-C(10) 119.8(5) C(17)-C(18)-H(18C) 109.5
C(8)-C(7)-C(4) 119.7(4) H(18A)-C(18)-H(18C) 109.5
C(10)-C(7)-C(4) 120.3(5) H(18B)-C(18)-H(18C) 109.5
O(5)-C(8)-N(3) 118.1(5) C(20)-C(19)-N(5) 120.9(10)
O(5)-C(8)-C(7) 124.2(5) C(20)-C(19)-H(19A) 107.0
N(3)-C(8)-C(7) 117.7(4) N(5)-C(19)-H(19A) 107.1
O(7)-C(9)-N(4) 122.0(4) C(20)-C(19)-H(19B) 107.1
O(7)-C(9)-N(3) 123.0(5) N(5)-C(19)-H(19B) 107.1
N(4)-C(9)-N(3) 115.0(4) H(19A)-C(19)-H(19B) 106.8
O(6)-C(10)-N(4) 117.3(4) C(19)-C(20)-C(21) 113.6(11)
O(6)-C(10)-C(7) 126.5(5) C(19)-N(5)-C(15) 100.5(8)
N(4)-C(10)-C(7) 116.2(5) C(11)-N(5)-C(15) 113.7(8)
O(1)-N(1)-O(2) 125.6(8) C(19)-N(5)-H(5A) 110.3
O(1)-N(1)-C(1) 118.4(9) C(11)-N(5)-H(5A) 110.1
O(2)-N(1)-C(1) 116.0(8) C(15)-N(5)-H(5A) 110.2
O(4)-N(2)-O(3) 126.7(8) C(12)-C(11)-N(5) 125.7(11)
O(4)-N(2)-C(3) 116.8(6) C(12)-C(11)-H(11A) 105.9
O(3)-N(2)-C(3) 116.3(6) N(5)-C(11)-H(11A) 105.9
86
C(12)-C(11)-H(11B) 105.9 H(15A)-C(15)-H(15B) 106.5
N(5)-C(11)-H(11B) 105.9 C(17)-C(16)-C(15) 119.3(13)
H(11A)-C(11)-H(11B) 106.3 C(17)-C(16)-H(16A) 107.5
C(11)-C(12)-C(13) 120.1(11) C(15)-C(16)-H(16A) 107.5
C(11)-C(12)-H(12A) 107.3 C(17)-C(16)-H(16B) 107.5
C(13)-C(12)-H(12A) 107.4 C(19)-C(20)-H(20A) 108.9
C(11)-C(12)-H(12B) 107.3 C(21)-C(20)-H(20A) 108.9
C(13)-C(12)-H(12B) 107.3 C(19)-C(20)-H(20B) 108.8
H(12A)-C(12)-H(12B) 106.9 C(21)-C(20)-H(20B) 108.8
C(14)-C(13)-C(12) 117.1(11) H(20A)-C(20)-H(20B) 107.7
C(14)-C(13)-H(13A) 108.0 C(22)-C(21)-C(22') 89(2)
C(12)-C(13)-H(13A) 108.0 C(22)-C(21)-C(20) 106.3(14)
C(14)-C(13)-H(13B) 108.1 C(22')-C(21)-C(20) 139.7(19)
C(12)-C(13)-H(13B) 108.1 C(21)-C(22)-H(22A) 124.4
H(13A)-C(13)-H(13B) 107.3 C(21)-C(22)-H(22B) 124.8
C(13)-C(14)-H(14A) 109.4 H(22A)-C(22)-H(22B) 90.9
C(13)-C(14)-H(14B) 109.5 C(21)-C(22)-H(22C) 124.8
H(14A)-C(14)-H(14B) 109.5 H(22A)-C(22)-H(22C) 90.8
C(13)-C(14)-H(14C) 109.5 H(22B)-C(22)-H(22C) 90.7
H(14A)-C(14)-H(14C) 109.5 C(21)-C(22')-H(22D) 109.9
H(14B)-C(14)-H(14C) 109.5 C(21)-C(22')-H(22E) 110.0
C(16)-C(15)-N(5) 123.0(11) H(22D)-C(22')-H(22E) 108.8
C(16)-C(15)-H(15A) 106.6 C(21)-C(22')-H(22F) 110.5
N(5)-C(15)-H(15A) 106.6 H(22D)-C(22')-H(22F) 108.8
C(16)-C(15)-H(15B) 106.6 H(22E)-C(22')-H(22F) 108.7
N(5)-C(15)-H(15B) 106.6
Table 16
Hydrogen-bond geometry (Å, °) of Complex 28
D–H…A d(D–H) d(D…H) d(D…A)
87
Fig. 19 ORTEP view of Complex 28
[C22 - disorder with an occupancy of 45%]
Fig. 20 Packing view of Complex 28
88
Table 17
Anticonvulsant activity of Complex 28 against MES
induced convulsion in Albino Rats
S.
No. Treatment
Time (sec) in various phases of convulsion
Flexor Extensor Clonus Stupor Recovery /
Death
1. Control
Normal Saline
(5 ml/kg)
3.24
±
0.09
13.30
±
0.25
9.24
±
0.21
137.00
±
8.24
Recovered
2. Complex 28
(25mg/kg)
8.00
±
1.50
12.00
±
2.40
28.00
±
3.20
43.00
±
1.20
Recovered
3. Complex 28
(50mg/kg)
7.00
±
2.10
10.00
±
2.10
16.00
±
1.40
38.00
±
1.30
Recovered
4. Complex 28
(100mg/kg)
3.50
±
0.08
3.40
±
0.51
4.10
±
0.82
93.20
±
5.80
Recovered
5. Phenytoin
(25mg/kg)
2.66
±
0.55
0.00
±
0.12
4.60
±
0.38
62.10
±
3.30
Recovered
Table 18
Hypnotic action of Complex 28
S.
No. Treatment
Dose
(mg/kg)
Time of
Admini-
stration
(mins)
(a)
Time
of loss
of
reflex
(mins)
(b)
On set
of action
(mins)
(b-a)
Time of
Recovery
(mins)
(c)
Duration
of action
(mins)
(c-b)
1 Control
Normal
saline
1 ml/kg
0 -- -- -- --
2 Complex 28 100 0 28.4 ±
3.35
28.4 ±
3.35
162.8 ±
3.6
134.4 ±
9.16
3 Phenobarbitone
Standard
20
mg/kg 0
16.40 ±
2.25
16.4 ±
2.25
257.9 ±
3.27
241.50 ±
5.90
89
Table 19
Data showing effect of Complex 28 on behavioural profiles of mice
Responses
Treatment
Score
(Normal Saline)
Score due to
Complex 28
Muscle Tone
Limp tone 4 4
Grip tone 4 4
Body tone 4 4
Abdominal tone 4 4
Reflexes
Pinna 4 3
Corneal 4 3
Writhing 0 0
Autonomic Profile
Urination 0 0
Salivation 0 0
Respiratory rate 4 4
Awareness
Alertness 0 0
Passivity 0 0
Aggression 0 0
Mood
Restlessness 0 0
Fearfulness 0 0
Touch response 4 4
Motor Activity
Pain response 4 4
Twitches 0 0
CNS excitation
Tremors 0 0
Convulsions 0 0
Body posture 4 4
Posture
Limb posture 4 4