Vol. 32, No. 1 (2020)
Inclusion Complexes of Some Substituted 4-Thiazolidinones with Activating and Deactivating Group 135
duced with the help of micropipette and the plates were placed
at 8-10 ºC for right diffusion of drug into the media.After 2 h of
cold incubation, the petri plates were transferred to incubator
placed at 37 ºC for 18-24 h.
cyclodextrin . After the formation of inclusion complexes, UV
spectra of the compounds are found to be increased. The δ
values of inclusion complexes are found to be less as compared
to the parent compound. This indicates that PMR signals are
shifted towards upfield in the inclusion complex on account of
notable shielding factor which arises through encapsulation
within the cavity of β-cyclodextrin.
RESULTS AND DISCUSSION
Thiazolidinone derivatives exhibit less pharmacological
activities on account of their less solubility in polar solvents.
The formation of inclusion complex of thiazolidinone makes
the augmentation of solubility and therapeutic potential in a
noticeable amount. In an encapsulation of compound with β-
cyclodextrins, its solubility and therapeutic activity can be
enhanced significantly. Table-1 provides the analytical data
of synthesized compounds and their inclusions. Analysis of the
spectral characteristics and elemental analysis evidences forma-
tion of compounds and their inclusion complexes (Table-2).
The changes in melting points of inclusion complexes with
their respective compounds indicates its inclusion complex
formation with β-cyclodextrin. This accounts that some excess
thermal energy is essential to bring the molecules out of the
hollow space of β-cyclodextrin.
The IR data of inclusion complexes of compound K show
characteristics absorption at 750, 1246, 1597, 1730, 2962 and
3315 cm-1 indicating the presence of C-S, C-C, C-N, C=O, C-
H and N-H bonds, respectively in the compounds. Likewise
compounds L and M with their inclusion complexes are found
to be absorbed at the proper characteristic frequency (Table-
2). The develop-ment of weak interaction like H-bonding, van
der Waals forces, hydrophobic interactions in between the host
and guest molecules [25] leads to all these changes evidently
demonstrate transference of compounds into the cavity of β-
With increasing concentration of β-cyclodextrin, the solu-
bility of these compounds increase linearly which can be deter-
mined from aqueous phase solubility study. The slopes of all
the plots were not as much of as unity because of stoichiometry
of these complexes are 1:1. By using Benesi-Hilderband relation
[21], thermodynamic stability constants (KT) of inclusion
complexes were determined. Good linear correlations were
obtained for a plot of inverse of ∆A versus inverse of [β-CD]o
for compounds. Subsequently, the KT values of inclusion
complexes of comp-ounds with β-cyclodextrin were found to
be 313,295 and 276 M-1, respectively (Table-3), which were
remained within 100 to 1000 M-1 (ideal values) representing
substantial stabilities for the inclusion complexes through host-
guest interaction like van der Waal′s force, hydrophobic inter-
action, etc. [26-28]. The interaction of the compound with β-
cyclodextrin for 1:1 stoichiometry were calculated by deter-
mining stability constant (KT values) with the help of thermo-
dynamic parameter at different temperatures. With increase
in temperature, KT values were found to be decreasing.
The value of diameter of zone of inhibition formed by
the compounds and their corresponding inclusion complexes
against E. coli, S. aureus and P. vulgaris are shown in Table-4.
Thus, it is found that inclusion complex formation increases
the antibacterial activities considerably extent. Compound
TABLE-1
PHYSICAL DATA OF THE COMPOUNDS AND THEIR INCLUSION COMPLEXES
Compound/Complex
Compound K
Inclusion complex of compound K
Compound L
Inclusion complex of compound L
Compound M
Inclusion complex of compound M
Ar.
Phenyl
Colour
Brownish red
Light yellowish
Deep Yellow
Brownish yellow
Dull brown
m.p. (°C)
202
208
161
168
Yield (%)
59
40
65
41
55
45
o-ClPh
p-ClPh
135
144
Pale yellow
TABLE-2
SPECTRAL DATA OF THE COMPOUNDS AND THEIR INCLUSION COMPLEXES
Compound/
Complexes
1H NMR
UVλ
IR (KBr, νmax, cm–1)
max
1H NMR (CDCl3): δ 7.28 (s, 1H, N-H), 7.50 (s, 1H,
C-NH), 7.30 (s, 1H, C-H), 7.32-7.48 (m, 8H, Ar-H)
748.38 (C-S str.), 1494.83 (C=C str.), 1595.13 (C=N
str.), 1728.22 (C=O str.), 3111.18, 2960.73 (N-H str.)
267
Compound K
1H NMR (CDCl3): δ 7.30 (s, 1H, N-H), 7.48 (s, 1H,
Compound K
with β-CD
750.31 (C-S str.), 1456.26, 1496.76 (C=C str.), 1597.06
(C=N str.), 3315.63, 2962.66 (N-H str.)
273
277
281
278
285
C-NH), 7.39 (s, 1H, C-H), 7.28-7.50 (m, 8H, Ar-H)
667.37 (C-Cl str.), 748.38 (C-S str.), 1494.83 (C=C str.),
1595.13 (C=N str.), 1730 (C=O str.), 3111.18, 3037.89
(N-H str.)
1H NMR (CDCl3): δ 7.28 (s, 1H, N-H), 7.74 (s, 1H,
C-NH), 7.31 (s, 1H, C-H), 7.53-7.73 (m, 6H, Ar-H)
Compound L
1H NMR (CDCl3): δ 7.29 (s, 1H, N-H), 7.50 (s, 1H,
C-NH), 7.48 (s, 1H, C-H), 7.28-7.41 (m, 13H, Ar-H)
Compound L with
β-CD
667 (C-Cl str.), 748 (C-S str.), 1496 (C=C str.), 1597
(C=N str.), 1732 (C=O str.), 3280, 3111, (N-H str.)
667 (C-Cl str.)), 748. (C-S str.), 850.61, 1338.60 (N=O
str.), 1494 (C=C str.), 1595 (C=N str.), 1732 (C=O str.),
2916.37 (Ar-H str.), 3112, 3037 (N-H str.)
1H NMR (CDCl3): δ 7.28 (s, 1H, N-H), 7.74 (s, 1H,
C-NH), 7.32 (s, 1H, C-H), 7.36-7.73 (m, 8H, Ar-H)
Compound M
1H NMR (CDCl3): δ 7.29 (s, 1H, N-H), 7.74 (s, 1H,
C-NH), 7.73 (s, 1H, C-H), 7.30-7.72 (m, 14H, Ar-H)
Compound M
with β-CD
667 (C-Cl str.), 750 (C-S str.), 1128 (C-N str.), 1494
(C=C str.), 1670 (C=N str.), 3159 (N-H str.)