Nano-structured complexes of reserpine and quinidine drugs with chloranilic acid based on intermolecular H-bond: Spectral and surface morphology studies

Article abstract of DOI:10.1016/j.saa.2014.02.077

The study of the drug-acceptor interaction may be useful in understanding the drug-receptor interactions and the mechanism of drug action. Here, complexes of reserpine (Res) and quinidine (Qui) drugs with chloranilic acid (CLA) have been synthesized. Then, these complexes were characterized chemically and structurally using CHN elemental analysis, infrared (IR) and electronic absorption spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The stoichiometry of the H-bonded complex was found to have a 1:1 ratio, so these complexes can be formulated as [(Drug)(CLA)]. IR measurements confirmed the presence of intermolecular H-bond. Application of Debye-Scherrer equation indicates that the formed complexes are in the range of nano-size. The Res complex exhibits a remarkable crystalline morphology. It was also found that the particle size of Res complex is 1.533 time higher than that of Qui complex. Interestingly, free Res molecular weight is higher than that of free Qui by the same ratio (precisely; 1.525).

Full text of DOI:10.1016/j.saa.2014.02.077

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Nano-structured complexes of reserpine and quinidine drugs
with chloranilic acid based on intermolecular H-bond: Spectral
and surface morphology studies
⇑
Abdel Majid A. Adam
Department of Chemistry, Faculty of Science, Taif University, Al-Haweiah, P.O. Box 888, 21974 Taif, Saudi Arabia
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
The interesting correlation between molecular weight and particle size of the reported complexes.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Complexes of reserpine and quinidine
with chloranilic acid were obtained.
IR measurements confirmed the
existing of intermolecular H-bond.
Microstructure properties of the
reported complexes were observed.
Debye–Scherrer equation indicates
that complexes are in the nano-range.
One of the complex exhibited a
remarkable morphology feature.
Ratio = 1.533
817.7
533.4
Ratio = 1.525
61
40
Res
Qui
Res
Qui
Molecuar weight (g/mol)
Particle size (nm)
a r t i c l e i n f o
a b s t r a c t
Article history:
The study of the drug-acceptor interaction may be useful in understanding the drug-receptor interactions
and the mechanism of drug action. Here, complexes of reserpine (Res) and quinidine (Qui) drugs with
chloranilic acid (CLA) have been synthesized. Then, these complexes were characterized chemically
and structurally using CHN elemental analysis, infrared (IR) and electronic absorption spectroscopy,
X-ray diffraction (XRD) and scanning electron microscopy (SEM). The stoichiometry of the H-bonded
complex was found to have a 1:1 ratio, so these complexes can be formulated as [(Drug)(CLA)]. IR mea-
surements confirmed the presence of intermolecular H-bond. Application of Debye–Scherrer equation
indicates that the formed complexes are in the range of nano-size. The Res complex exhibits a remarkable
crystalline morphology. It was also found that the particle size of Res complex is 1.533 time higher than
that of Qui complex. Interestingly, free Res molecular weight is higher than that of free Qui by the same
ratio (precisely; 1.525).
Received 20 November 2013
Accepted 13 February 2014
Available online 27 February 2014
Keywords:
Drug-CLA interaction
Hydrogen bonds
XRD
Surface structure
Size determination
Ó 2014 Elsevier B.V. All rights reserved.
Introduction
that result from the reaction between acceptors and drugs or
biological compounds. This is because of the significant physical
Recently, there has been a great deal of interest in the formation
of stable charge-transfer, proton-transfer or H-bonded complexes
and chemical properties of these complexes. The drug-acceptor
complexation is an important technique that is cheaper, simpler,
and more efficient than the methods of drug determination
described in the literature. The study of the drug-acceptor
⇑
Tel.: +966 502099808; fax: +966 563293201.
E-mail address: majidadam@yahoo.com
http://dx.doi.org/10.1016/j.saa.2014.02.077
1386-1425/Ó 2014 Elsevier B.V. All rights reserved.

108
A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
N
N
H
O
H
H
O
CH
3
O
CH
O
3
H
O
O
O
O
O
CH
3
3
HO
Cl
Cl
CH
O
3
2
H
CH CH
O
3
N
N
OH
CH
O
3
CH
OH
Reserpine
Quinidine
Chloranilic Acid
Scheme 1. The chemical structures of Res, Qui and CLA.
Table 1
Spectroscopic data for the H-bonded complexes in methanol at room temperature.
Complex
Color
Absorption (nm)
Stoichiometry (Drug-CLA)
K (L molꢁ1
)
emax (L molꢁ1 cmꢁ1
)
[(Res)(CLA)]
[(Qui)(CLA)]
Reddish brown
Dark brown
333
314
1:1
1:1
1.69 ꢂ 104
1.23 ꢂ 104
1.16 ꢂ 107
2.38 ꢂ 104
complexation may be useful in understanding the drug-receptor
interactions and the mechanism of drug action. Furthermore, the
crystalline drug-acceptor complexes have a vital role in biological
systems such as antimicrobial activity and DNA-binding. Further-
more, literature shows that these complexes exhibit potential anti-
microbial properties against Gram-positive and Gram-negative
bacteria as well as fungi [1–11]. Herein, the drug-acceptor interac-
tion between the drug reserpine and quinidine with chloranilic
acid (CLA) acceptor was reported. Reserpine (Res), chemically
2.0
1.5
1.0
0.5
0.0
O
CH
3
CH
2
H
333 nm
N
N
OH
H
O
O
O
Cl
methyl (3b, 6b, 17a, 18b, 20a)-11,17-dimethoxy-18-[(3,4,5-trim-
Cl
OH
ethoxybenzoyl) oxy]yohimban-16-carbox-ylate, the structure of
which is shown in Scheme 1, is an indole alkaloid antipsychotic
and antihypertensive that exists at room temperature as a white
or pale-buff to yellow odorless powder [12]. Res is a biologically
active naturally occurring drug and is now largely used to lower
blood pressure, reduce the heart rate, relief of psychotic symptoms
and as a tranquilizer and sedative in humans [13,14]. Quinidine
(Qui), chemically (9S)-60-methoxycinchonan-9-ol, the structure of
which is shown in Scheme 1, is a pharmaceutical agent that acts
as a class I antiarrhythmic drug in the heart [15]. It is a stereoiso-
mer of quinine, originally derived from the bark of the cinchona
tree. Qui is well-known as medicinally important compound [16].
Based on the interesting results obtained for the complexation
properties of drug-acceptor, in this research herein, as a continua-
tion of my works in this field [17–19], the H-bonded complexes of
Res and Qui with CLA were synthesized and spectroscopically
investigated in both solution and solid state. The complexes have
been structurally characterized via CHN elemental analysis; infra-
red (IR) and electronic absorption spectroscopy; powder X-ray dif-
fraction; and scanning electron microscopy (SEM).
CLA
Res
Complex
300
350
400
450
λ (nm)
314 nm
O
Cl
O
2.0
1.5
1.0
0.5
OH
H
N
N
H
O
Cl
O
O
H
H
O
CH3
O
H
O
O
O
CH3
O
CH3 CH3
O
CH3
CH3
Materials and methods
CLA
Qui
Complex
Reagents and solutions
All reagents and chemicals used throughout this study were of
analytical reagent grade and all solutions were freshly prepared
daily. Methyl (3b, 6b, 17a, 18b, 20a)-11,17-dimethoxy-18-
0.0
250
300
350
400
450
500
λ (nm)
[(3,4,5-trimethoxybenzoyl) oxy]yohimban-16-carbox-ylate (Res;
C
C
33H40N2O9; 608.68) and (9S)-60-methoxycinchonan-9-ol, (Qui;
20H24N2O2; 324.417) were purchased from Merck Chemical
Fig. 1. Electronic absorption spectra of [(Res)(CLA)] and [(Qui)(CLA)] complexes in
methanol solvent.

A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
109
Table 2
The values of Cd, Ca, Cd + Ca and Cd ꢃ Ca/A, for the formed complexes.
Ratio (A:D)
Cd (ꢂ10ꢁ4
)
Ca (ꢂ10ꢁ4
)
Cd + Ca (ꢂ10ꢁ6
)
Cd ꢃ Ca (ꢂ10ꢁ8
)
Res-CLA complex
Abs.333 nm
Qui-CLA complex
Abs.314 nm
Cd ꢃ Ca/A (ꢂ10ꢁ8
)
Cd ꢃ Ca/A (ꢂ10ꢁ8
)
0.25
0.50
0.75
1.00
1.50
2.00
2.50
3.00
3.50
4.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
0.25
0.50
0.75
1.00
1.50
2.00
2.50
3.00
3.50
4.00
125
150
175
200
250
300
350
400
450
500
0.25
0.50
0.75
1.00
1.50
2.00
2.50
3.00
3.50
4.00
0.5027
0.6436
0.7971
0.9349
0.9673
1.0056
1.0365
1.0748
1.1036
1.1407
0.4973
0.7769
0.9409
1.0696
1.5507
1.9889
2.4120
2.7912
3.1714
3.5066
1.6046
1.7904
1.9776
2.1816
2.2269
2.1994
2.2453
2.2587
2.2947
2.3124
0.1558
0.2793
0.3792
0.4584
0.6736
0.9093
1.1134
1.3282
1.5253
1.7298
4
3
2
1
2.0
1.5
1.0
0.5
0.0
2.4
1.2
1.0
0.8
0.6
Res complex
Qui complex
2.2
2.0
1.8
1.6
Res complex
Qui complex
0
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
100
200
300
(C +Ca)x10-6
400
500
ml added of CLA
d
Fig. 2. Spectrophotometric titration curves of [(Res)(CLA)] and [(Qui)(CLA)] com-
plexes in methanol measured at 333 and 314 nm, respectively.
Fig. 3. The Benesi–Hildebrand plot of [(Res)(CLA)] and [(Qui)(CLA)] complexes.
Company and were used without further purification. Commer-
cially available spectroscopic grade solvents (supplied from BDH)
were also used as received. Stock solutions of the acceptor and
each drug at a concentration of 5.0 ꢂ 10ꢁ3 M were freshly prepared
prior to each series of measurements by dissolving precisely
weighed quantities in the appropriate volume of the methanol.
The stock solutions were protected from light.
Synthesis of H-bonded complexes
The solid CLA complexes with Res and Qui were prepared by
mixing the saturated solution of the drug donor in pure-grade
methanol (1 mmol in 25 ml) with saturated solution of CLA accep-
tor also in methanol (1 mmol in 25 ml). The solutions were stirred
for approximately 30 min. A change in color developed and the
solution was allowed to evaporate slowly at room temperature
resulting in the precipitation of the solid complexes. The formed
precipitate in each case was filtered off and washed well with
methanol. Then, the complexes were collected and dried under
vacuum over anhydrous calcium chloride for 24 h. The melting
point of the formed H-bonded complexes was found to be 300 °C.
These complexes were characterized spectrophotometrically (IR
and UV–Vis) and elemental analysis.
Characterization of the complexes
Microanalysis for carbon, hydrogen and nitrogen content were
carried out at the Micro analysis unit at Cairo University, Egypt,
on a Perkin–Elmer CHN 2400 (USA). All the electronic absorption
spectral measurements were recorded in methanol over a wave-
length range of 200–800 nm using a Perkin–Elmer Lambda 25
UV/Vis double-beam spectrophotometer at Taif University, Saudi
Arabia. The instrument was fitted with a quartz cell that had a path
length of 1.0 cm. IR spectra, as KBr discs, within the range of
4000–400 cmꢁ1 for the solid CT complexes were acquired at room
temperature using a Shimadzu FT-IR spectrophotometer instru-
ment with 30 scans at 2 cmꢁ1 resolution. The X-ray diffraction
(XRD) scans were recorded using a PANalytical X’Pert PRO X-ray
powder diffractometer in the Central Lab at the Ain Shams Univer-
sity, Egypt. The instrument was equipped with a Ge(III) secondary
monochromator, and a Cu Ka1 as the source of radiation with a
wavelength of 0.154056 nm was employed. Microstructure prop-
erties of the prepared complexes were observed using scanning
electron microscope (SEM) (Quanta FEG 250 instrument). The
instrument was operated at an accelerating voltage of 30 kV.
Spectrophotometric measurements
The spectrophotometric titrations of the detectable absorption
bands were performed for the reactions of Res and Qui with CLA
acceptor as follows: 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.50, 3.00, 3.50
or 4.00 ml of a standard solution (5.0 ꢂ 10ꢁ4 M) of the CLA acceptor
in methanol was added to 1.00 ml of 5.0 ꢂ 10ꢁ4 M Res or Qui, which
was also dissolved in the same solvent. The final volume of the mix-
ture was 5 ml. The concentration of Res or Qui (Cd) was maintained
at 5.0 ꢂ 10ꢁ4 M, whereas the concentration of the CLA (Ca) varied
from 0.25 ꢂ 10ꢁ4 M to 4.00 ꢂ 10ꢁ4 M to produce solutions with a
(donor: acceptor) molar ratio that varied from 1:0.25 to 1:4. The
stoichiometry of the formed complexes was obtained from the

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A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
CLA
Res
4000 3500 3000 2500 2000 1500 1000
500
4000 3500 3000 2500 2000 1500 1000
500
Wavenumbers (cm-1)
Wavenumbers (cm-1)
Complex
4000 3500 3000 2500 2000 1500 1000
500
Wavenumbers (cm-1)
Fig. 4. Infrared spectra of CLA, Res and the their complex.
Results and discussion
Table 3
IR spectral data (cmꢁ1) and tentative assignments of donors, acceptor and complexes.
Elemental analysis results
Acceptor Donors
Complexes
Assignmentsa
CLA
Res
Qui
–
2930 3178
– 2940
Res-CLA Qui-CLA
The result of the elemental analyses (C, H, and N) of the formed
H-bonded complexes is given as; [(Res)(CLA)]: C39H42N2O13Cl2;
Mol. wt. = 817.66; Calc.: %C, 57.24; %H, 5.14; %N, 3.42, Found: %C,
57.33; %H, 4.96; %N, 3.48. [(Qui)(CLA)]: C26H26N2O6Cl2; Mol.
wt. = 533.397; Calc.: %C, 58.49; %H, 4.87; %N, 5.25, Found: %C,
58.40; %H, 5.00; %N, 5.28. The resulting elemental analysis values
are in good agreement with the calculated values. Elemental anal-
ysis showed that the Res–CLA and Qui–CLA complexes should be
formulated as [(Drug)(CLA)]. The formation of 1:1 complexes was
strongly supported by spectrophotometric titrations. The Res–
CLA and Qui–CLA complexes have a Reddish brown and dark
brown color, respectively.
–
3230
–
–
–
3430
–
2937
3651
3223
2939
–
m
m
m
m
(NAH); Res
(OH); CLA, Qui
(CAH); aromatic
2838 2869 2835
–
1709
–
s(CAH) + mas(CAH); Res, Qui
–
–
2684
1720
1620
1587
2656
1622
Hydrogen bonding
m
1663
1629
(C@O); Res, CLA, complex
–
–
–
1368
1260
–
1623 1617 1540
1497 1507 1413
–
1522
1479
1425
1290
ddef(NAH); Res, Qui, complex
m
m
m
(CAN); Res, Qui, complex
(C@N); Qui, complex
(CAC) + m(CAO) + m(CAN)
1457
–
1328 1256 1329
1221 1040 1223
1187
1098
945
779
717
CAH in-plane bending
1117
997
–
799
–
1116
996
824
763
763
980
838
–
820
–
772
–
drock, NH; Res, Qui, complex
Electronic spectra
m
(CACl); CLA
CAH out of plane bending
(CACl); CLA
Table 1 shows the spectroscopic data, molar ratio and color of
the formed complexes. Fig. 1 shows the electronic absorption
spectra of the reactants, drug donor (Res and Qui) (5.0 ꢂ 10ꢁ4 M)
and CLA acceptor (5.0 ꢂ 10ꢁ4), along with those of the prepared
complexes. The spectrum of the formed [(Res)(CLA)] complex
revealed the presence of a broad band observed at 333 nm that cor-
respond to the drug-acceptor interaction. Spectrophotometric
titration curve based on the absorption at 333 nm show a reaction
stoichiometry of 1:1 (Res:CLA) as shown in Fig. 2. In the absorption
spectrum of Qui–CLA complex, it is observed that new strong
751
692
m
a
m
, stretching;
m
s, symmetrical stretching; mas, asymmetrical stretching; and d,
bending.
determination of the conventional spectrophotometric molar ratio
according to a literature method [20]. The peak absorbencies that
appeared in the spectra assigned to the formed complexes were
measured for all solutions in each case and plotted as a function
of the donor to acceptor molar ratio (Cd:Ca ratio).

A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
111
Qui
CLA
4000 3500 3000 2500 2000 1500 1000
500
4000 3500 3000 2500 2000 1500 1000
500
Wavenumbers (cm-1)
Wavenumbers (cm-1)
Complex
4000 3500 3000 2500 2000 1500 1000
500
Wavenumbers (cm-1)
Fig. 5. Infrared spectra of CLA, Qui and the their complex.
O
O
CH
Cl
3
O
OH
H
N
CH
2
N
H
O
H
Cl
O
O
H
H
O
N
CH
N
3
O
H
O
OH
H
O
O
O
O
CH
3
Cl
O
3
CH CH
O
3
O
3
CH
Cl
OH
3
CH
Scheme 2. Proposed structure of the [(Res)(CLA)] complex.
Scheme 3. Proposed structure of the [(Qui)(CLA)] complex.
absorption band appear in the UV region. The spectrum of CLA
acceptor has a kmax at 303 nm, while that of the Qui drug is
303 nm. When CLA and Qui are mixed together, a new strong broad
band appears at 314 nm. This strong broad band is indicative of the
formation of the H-bonded complex. The spectrophotometric
measurements based on this characterized absorption band was
performed in order to determine the reaction stoichiometry
(Fig. 2). The results showed that the Qui:CLA molar ratio was found
to be 1:1. So, this complex can be formulated as [(Qui)(CLA)].
coefficient;
on the 1:1 Benesi–Hildebrand equation:
e
(L molꢁ1 cmꢁ1) of the H-bonded complexes based
ðCaCdÞ=A ¼ 1=K
e
þ ðCa þ CdÞ=
e
ð1Þ
where Ca and Cd are the initial concentrations of the acceptor (CLA)
and the drug donor (Res or Qui), respectively, while A is the absor-
bance at the mentioned absorption band. By plotting the values of
(Ca ꢃ Cd)/A as a function of the corresponding values of (Ca + Cd), a
straight line was obtained, which supports the formation of a 1:1
Determination of K and
e
complex. In the plot, the slope and intercept equal 1/e and 1/Ke,
The spectrophotometric data were used to calculate both the
formation constant; and the molar extinction
(L molꢁ1
respectively. The Benesi–Hildebrand plots are shown in Fig. 3, and
the values of Cd, Ca, (Cd + Ca) and (Cd ꢃ Ca)/A are listed in Table 2. It
K
)

112
A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
20.3535o
[(Res)(CLA)] complex
3000
2500
2000
1500
1000
3000
2500
2000
1500
1000
500
20.3535o
[(Res)(CLA)] complex
500
0
20.0
20.2
20.4
20.6
20.8
21.0
0
10
20
30
40
50
60
70
80
2θ
2θ (degrees)
[(Qui)(CLA)] complex
4.81o
1800
1500
1200
900
1800
1500
1200
900
600
300
0
4.81o
[(Qui)(CLA)] complex
600
4.2
4.4
4.6
4.8
5.0
0
10
20
30
40
50
60
70
80
2θ
2θ (degrees)
Fig. 7. The highest intensity XRD line of the [(Res)(CLA)] and [(Qui)(CLA)]
Fig. 6. X-ray diffraction patterns of [(Res)(CLA)] and [(Qui)(CLA)] complexes.
complexes.
was observed that the correlation coefficient (r) value for
the straight line was found to be 0.999. The values of the K for the
[(Res)(CLA)] and [(Qui)(CLA)] complexes are found to be
1.69 ꢂ 104, and 1.16 ꢂ 107 L molꢁ1, respectively. The corresponding
gen atom of the (CAN) group in hydrogen bonding with CLA. This
bonding is confirmed by the appearance of a weak absorption band
at 2684 cmꢁ1, representing the H-bonded OH group. Furthermore,
the carbonyl stretching vibration bands; m(C@O) appeared at 1620
and 1587, slightly shifted with respect to those of CLA (1663 and
e
values are 1.23 ꢂ 104 and 2.38 ꢂ 104 L molꢁ1 cmꢁ1, respectively.
These results indicate that Res complex exhibits a high K value com-
pared with that of Qui complex, which indicates a strong interaction
between the Res–CLA pairs and confirms a high stability of the Res
complex as a result of the higher donation power of Res drug.
Accordingly, the donation from drug to CLA acceptor in decreasing
order is as follows: Res > Qui. The results also revealed that the
1629); this is probably due to intermolecular H-bond with Res.
Concerning
m(CACl) vibrational bands, they are recorded at 824
and 761 cmꢁ1 in the complex spectrum compared with 838 and
751 cmꢁ1 for CLA alone. All these observations clearly indicate
the formation of intermolecular H-bond between the (CAN) group
in the Res drug and the (AOH) group in the CLA acceptor [24–27].
Fig. 5 shows the IR spectra of the Qui, CLA and their solid com-
plex, and Table 3 presents their characteristic band assignments.
As expected, the characteristic IR bands of the Qui and CLA in the
complex exhibit small changes in the band intensities and fre-
quency values. The IR spectrum of this complex is characterized
by a broad absorption band that appears at 2656 cmꢁ1, which does
not appear in the spectra of the free Qui or CLA acceptor. This
broadened band is attributed to the stretching vibration of the
intermolecular H-bond formed between the acidic center on the
CLA acceptor with the basic center of the Qui donor (lone pair of
electrons on the non-aromatic nitrogen atom) [24–27]. Further-
more, C@O stretching band is shifted to 1622 cmꢁ1 for the complex
compared with 1663 cmꢁ1 for CLA alone. Accordingly, the pro-
posed structures of the formed H-bonded complexes are repre-
sented in Schemes 2 and 3
Qui complex exhibits a higher
complex.
e value compared with that of Res
IR spectra
The infrared absorption spectra of the Res, CLA and their solid
complex are shown in Fig. 4, and their characteristic band assign-
ments are provided in Table 3. The observation of the main IR
bands of Res complex with small shift in both intensities and
wavenumber values from those of the free molecules supports
the formation of the complex. The situation could be interpreted
based on the expected electronic structure change upon complex-
ation. The characteristic band of
1497 cmꢁ1 in the free Res drug [21–23], is shifted to 1413 cmꢁ1
in the complex. The outlined changes in (CAN) in the Res drug
upon complexation clearly confirm the involvement of the nitro-
m(CAN) group observed at
m

A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
113
Table 4
XRD spectral data for the formed complexes.
Complex
Position 2h (°)
d-Spacing value (Å)
Relative intensity (%)
b FWHM
Particle size (nm)
[(Res)(CLA)]
[(Qui)(CLA)]
20.3535
4.81
4.36333
18.3719
100.0
100.0
0.2766
0.4124
60.984
40.294
Table 5
Characteristic XRD lines for the formed complexes.
[(Res)(CLA)] complex
[(Qui)(CLA)] complex
Pos. (2h°)
d-Spacing (Å)
Rel. int. (%)
FWHM
Position (2h°)
d-Spacing (Å)
Rel. int. (%)
FWHM
5.0132
9.2811
17.62784
9.52900
8.48178
7.34489
6.22420
5.84824
5.24331
4.79362
4.36333
4.16188
3.85204
3.52126
3.38944
3.21905
2.93003
2.85342
2.70407
2.47805
2.41834
2.10490
1.94079
59.53
27.84
20.02
71.49
40.82
41.10
37.86
33.87
100.00
38.14
70.65
66.78
29.62
33.42
16.96
15.85
16.18
14.54
12.36
6.82
0.2854
0.2906
0.0010
0.0010
0.3138
0.0010
0.0010
0.6518
0.2766
0.0010
0.6612
0.3565
0.3334
0.1894
0.0010
0.3837
0.0558
0.0444
0.1361
0.0900
0.0900
4.8100
9.4766
18.37190
9.33283
7.19033
6.19618
4.71278
4.13889
3.64077
3.49453
3.36235
3.19550
3.01701
2.88613
2.73076
2.60782
2.49280
2.43536
2.32270
2.20824
2.00737
100.00
13.18
19.46
13.31
8.24
69.73
29.15
21.46
17.55
14.72
6.80
6.97
5.04
1.77
1.05
1.50
4.97
5.87
1.32
0.4124
0.0010
0.4786
0.4039
0.0010
0.1074
0.0010
0.0010
0.0010
0.3631
0.0010
0.2851
0.1742
0.0900
0.0900
0.0900
0.0010
0.1794
0.0900
10.4300
12.0500
14.2300
15.1500
16.9100
18.5096
20.3535
21.3500
23.0900
25.2933
26.2943
27.7131
30.5100
31.3500
33.1300
36.2518
37.1793
42.9700
46.8100
12.3100
14.2947
18.8300
21.4700
24.4500
25.4900
26.5100
27.9215
29.6100
30.9856
32.7970
34.3900
36.0300
36.9100
38.7700
40.8669
45.1700
5.61
patterns of the [(Res)(CLA)] and [(Qui)(CLA)] complexes are shown
in Fig. 6. The mean particle size of the synthesized complexes
based on the highest intensity line (Fig. 7) was calculated using
the Debye–Scherrer formula as [28]
Ratio = 1.533
817.7
D ¼ 0:94k=b cos h
ð2Þ
where D is the mean particle size of the grains, 0.94 in the Scherrer
constant; k is the wavelength of the incident X-ray (Cu Ka;
533.4
Ratio = 1.525
1.5406 Å), h is the position of the selected diffraction peak (Bragg
diffraction angle) and b is the full-width at half-maximum (FWHM)
of the selected diffraction peak in radians. Table 4 presents the XRD
spectral data (i.e., 2h, b, d (the interplanar spacing between atoms)
and D in nm) for the obtained complexes, whereas Table 5 lists all
the characteristic XRD lines with their d-spacing, FWHM and rela-
tive intensity. The primary characteristic scattering peak of the
[(Res)(CLA)] and [(Qui)(CLA)] complex occurred at 20.3535° and
4.81° in the diffraction pattern, respectively. The particle size values
of the complexes were found to be ꢄ61 and ꢄ40 nm for the
[(Res)(CLA)] and [(Qui)(CLA)] complexes, respectively. Application
of Debye–Scherrer equation indicates that the formed complexes
are in the range of nano-size. It was also found that the particle size
of Res complex is 1.533 time higher than that of Qui complex. Inter-
estingly, free Res molecular weight is higher than that of free Qui by
the same ratio (precisely; 1.525) as illustrated in Fig. 8. This finding
may indicate that the mean particles dimensions increase with
increasing the molecular weight.
61
40
Res
Qui
Res
Qui
Molecuar weight (g/mol)
Particle size (nm)
Fig. 8. The interesting correlation between molecular weight and particle size of
the reported complexes.
Structural analysis
Characterization of both shape and size of drug-acceptor com-
plexes is important in the development of these materials and as
a means to control the quality of the synthesis. X-ray diffraction
(XRD) and scanning electron microscopy (SEM) techniques were
convincingly used to reveal the complexes structural features
and characteristics.
Morphology analysis
Scanning electron microscopy (SEM) was employed to observe
the morphology and particle size of the prepared complexes. The
surface micrographs obtained with the SEM technique provide
general information regarding the microstructure, surface mor-
phology, particle size, chemical composition, and porous structures
of the surfaces. The morphological phases of the formed H-bonded
XRD analysis
The X-ray diffraction (XRD) patterns were recorded for 2h = 5–80°
at
a scanning speed of 3°/min using a PANalytical model
X’PERT-PRO X-ray powder diffractometer system. The XRD

114
A.M.A. Adam / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 127 (2014) 107–114
Fig. 9. SEM micrographs of [(Res)(CLA)] complex at different magnifications.
Fig. 10. SEM micrographs of [(Qui)(CLA)] complex.
[3] H.H. Eldaroti, S.A. Gadir, M.S. Refat, A.M.A. Adam, Spectrochim. Acta A 109
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(2013) 5774.
complexes showed a uniform matrix in the SEM micrographs
indicating the formation of a homogeneous material. Visible mor-
phological change is observed between Res and Qui complexes.
Res complex shows a higher degree of crystallinity than that of
Qui complex. The size of the particles differed substantially for
each drugs. Fig. 9 shows the SEM surface morphology of the
nano-scale Res complex at different magnifications. The complex-
ation of Res with CLA leads to a very interesting morphology. The
micrographs of this complex show a densely packed fiber-like-
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shaped morphology with
a particle of size 30 lm. Such a
microstructure offers large surface area. A further magnified SEM
micrographs at a high magnification (5000ꢂ) shows a highly
well-defined microstructure. This clear image displays that the
fibers have a beveled head. Fig. 10 illustrates the surface morphol-
ogy of the nano-scale Qui complex. The micrographs indicate that,
this complex has different shapes and some single phase formation
with well defined structure was observed. The particles of the Qui
complex have a crushed flake-shaped morphology, where most of
the particles exhibit angular shapes with estimated particle size of
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ꢄ5
lm. Also some particles with sheet-like structure were
observed too. The surface of this complex is smoother than the
surface of the Res complex. Comparing the morphology of Res
complex with that of Qui complex, one can see they are quite
different in microstructure.
References
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