In case of IR data of Compound K it is seen that the IR frequencies are
found to be formed at 744.52(CSstr),1166.93,1444.68(CNstr)1510.26(C=CStr),1625.99(C=Nstr),1728.22(C=Ostr),3082.25,2916.37(Ar-Hstr)
indicating the presence of C-S, C-N, C=C, C=N,C=O and Ar-H in the compound as expected
and similarly the IR data of inclusion complexes of Compound K show characteristics
absorption at 752.24(C-Sstr),937.40(N-C-Sstr)1442.75(C=Cstr),1612.49(C=N
str),1658.78(C=Ostr),2920.23(Ar-H str),3267.41(N-H str) indicating the presence
O, Ar-H and N-H in the compounds.
Similarly the IR data of compounds L ,M,N and their inclusion complexes are
found to be absorbed at the suitable characteristic frequency as shown in the Table
-2. In case of IR data for all compounds, it is seen that the IR frequencies of
the compounds changed after the formation of inclusion complexes. All these changes noticeably demonstrate
transference of compounds into the cavity of ?-cyclodextrin and development of
weak interaction like H-bonding, van der Waals forces, hydrophobic interactions
in between the host and guest molecules 22. It can be concluded that the ? values of the
inclusion complexes are having low value as compare to their respective
compounds. This means PMR signals are shifted towards up field in the inclusion
complex which could be attributed to encapsulation induced shielding within the
cavity of ?-cyclodextrin.
From the aqueous phase
solubility studies, it was found that the aqueous phase solubility plots of the
compounds within ?-cyclodextrin solution exhibited a linear increase in
solubility of these compounds with increasing concentration of ?-cyclodextrin(Fig
.1). Since the slopes of all the plots were less than unity, the stoichiometry
of these complexes may be 1:1. The thermodynamic stability constants (KT)
of inclusion complexes were determined by using Benesi-Hilderband relation 20.
= 1/ ?? +
1/ KT Guest o??.
Where ?A is change in
absorbance, ?? is
change in molar extension coefficient, Guesto is concentration of
compound in incl usion
complex and ?-CDo
is molar concentration of ?-CD.
Fig-1: Variation of absorption with concentration
Variation of 1/ absorption with 1/concentration
Good linear correlations
were obtained for a plot of 1/?A verses ?- CDo for compounds as
shown compounds in fig.2 . The values of KT for all the complexes
were calculated using the relation. KT = Intercept/Slope .The KT
values of the inclusion complexes of compounds with ?- Cyclodextrin were found
to be 526.13, 399.66 and 533.94 M-1
respectively (Table -3). The data obtained were within 100 to 1000 M-1 (ideal
values) indicating appreciable stabilities for the inclusion complexes through
host-guest interaction like van der Waal’s force, hydrophobic interaction etc.
The value of ?G was
calculated at 298 K using the equation:
= -2.303RT log K
of free energy of activation has been calculated and found to be -15.627,
-14.941and -15.756 kJ/mole (Table -3) for the inclusion complexes of Compound A, B
and C respectively. The negative value of free energy change indicates that the
inclusion complex formation is a thermodynamically allowed process.
3:Equlibrium constant and free energy change of inclusion complexes
Inclusion complex of Compound
The data obtained from the antibacterial
studies conforms that the diameter of the zone of inhibition obtained ( Fig-3,4
and 5) of the compounds and their corresponding inclusion complexes against three
bacterial strains E. coli, S. aureus and P.vulgaris visibly recommend that inclusion complex formation
increases the antibacterial activities significantly. Among the tested
substances the inclusion complex of compound-C exhibited maximum activity against
S.aureus than that of other complexes
whereas compound-B shows maximum activity against E. coli and P.Vulgaris with
respect to other complexes. This increase
of antibacterial activity of the inclusion complexes may be due to the enhance
of solubility of the compounds which makes the compounds more bioaccasessible
to specific tissues leading to increased drug activity. The radical scavenging
activity of the compound increases significantly after the formation of
inclusion complex as shown in Table-4. This can be correlated to the higher
solubility of the compounds due to inclusion complex formation there by
increasing the bioaccessibility. Higher the bioaccessibility of the compounds,
more is the ability of compounds to trap the reactive oxygen species or free
radicals, thereby increasing antioxidant activity of the compounds 26.
activity of the compound and inclusion complex against S.aureus
Fig-4: Antibacterial activity of the tested
compounds and their inclusions against E.Coli
Fig-5:Antibacterial activity of
the compound and inclusion complex against P.Vulgaris
Antioxidant activity of synthesized compounds and their inclusions
The formation of inclusion
complexes are thermodynamically allowed and have high stability. Thus, by the formation of inclusion complexes
bioaccessibility of the drug is found to be increased .The study further proves
that, there is a considerable increase in antibacterial and anti-oxidant
activities of the inclusion complexes.
The authors are thankful to Dr. J.R. Panda, Department
of Pharmaceutical science, Roland institute of pharmaceutical sciences, Berhampur,
Odisha, India for doing antibacterial
and antioxidant study.
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