1. ISSN (Print): 2328-3777, ISSN (Online): 2328-3785, ISSN (CD-ROM): 2328-3793
American International Journal of
Research in Formal, Applied
& Natural Sciences
AIJRFANS 14-270; © 2014, AIJRFANS All Rights Reserved Page 130
AIJRFANS is a refereed, indexed, peer-reviewed, multidisciplinary and open access journal published by
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(An Association Unifying the Sciences, Engineering, and Applied Research)
Available online at http://www.iasir.net
Synthesis And Structural Investigation Of Some Trivalent Lanthanide
Complexes Of Cloxacillin
Rajesh Kumar Mishra1
& B.G.Thakur2
1,2
Department Of Chemistry, C.M.Sc. College
L.N.M.U Darbhanga, Bihar-846004
North to Badri Narayan Mandir, New Colony Shubhankarpur, Darbhanga, Bihar-846006
INDIA
I. INTRODUCTION
Cloxacillin (Clox) ,(2S,5R,6R)-6-{[3-(2-chlorophenyl)-5-methyloxazole-4-carbonyl]amino}-3,3-dimethyl-7-
oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid) [Figure-1] is a commonly used biologically important
drug which has been shown to exert pronounced biological effects on various bacterial strains. Cloxacillin is
used against staphylococci that produce beta-lactamase, due to its large R chain, which does not allow the beta-
lactamases to bind.This drug has a weaker antibacterial activity than benzylpenicillin, and is devoid of serious
toxicity except for allergic reactions. Cloxacillin is white crystalline powder, freely soluble in water, methanol
and soluble in alcohol.
N
O
C
O
N
N
S
H
CH3
CH3
O
OH
CH3
O
Cl
Figure-1: Cloxacillin
Most living systems contain metal ions for their proper functioning1-4
. Many studies concerning the biochemical
and pharmaceutical effects of antibiotics when complexed with metal ions have been a subject of great interest
for many scientist5-20
. Based on these observations, we report here the synthesis, characterization and
antimicrobial activity of a few Lanthanide(III)-Cloxacillin complexes.
II. EXPERIMENTAL
Chemicals used for synthesis were of AR grade and used without further purification. Metal salts i.e, LaCl3,
PrCl3,NdCl3, SmCl3, DyCl3,HoCl3 & ErCl3 (of 99.97% Purity) were purchased from Indian Rare Earth Udyog
Mandal, Kerala, India and the ligand i.e, Cloxacillin was purchased from CDH. Molar conductance of the newly
synthesized metal complexes was measured by Systronics Conductivity Meter Model-304 in 1x10-3
M DMF
Solution. Melting points of the complexes were obtained in sealed glass capillary and are still uncorrected.
Magnetic Moment of the complexes were measured Gouys method in Bohr-Magneton unit using
Hg[CO(NCS)4] as the calibrant in INORGANIC RESEARCH LABORATORY, L.N.M.U
Abstract: Complexes of some trivalent lanthanides with Cloxacillin have been synthesized.The complexes
have been formulated as [Ln(Clox)2(H2O)2]Cl Where Ln = La(III), Pr(III), Nd(III), Sm(III), Dy(III), Ho(III)
and Er(III). The ligand and its metal complexes were characterized by their elemental analysis, molar
conductance, magnetic susceptibility, IR and electronic spectral studies. Elemental analysis indicate 1:2
stoichiometry of synthesized complexes. In all the complexes, cloxacillin acts as a tridentate ligand with
coordination involving the carboxylate-O, endocyclic-N of the -Lactam ring and N-of amide. Complexes
are eight coordinated. Finally the complexes have been screened for their antibacterial activity against
E.Coli, K.Pneumoniae, S.Aureus and P.Aeruginosa....etc and found to be more potent against uncomplexed
Cloxacillin.
(Keywords : Ln(III)-Cloxacillin complexes, IR, Electronic, Antibacterial, Disc-Diffusion Method)

2. R. K. Mishra et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 130-
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Darbhanga.Molecular weight of the complexes were determined by Camphor Rast Method. C, H & N were
determined at CDRI Lucknow. Chloride in the complexes was estimated using Volhards Method19
. IR Spectra
of the complexes were recorded by the cortesy of CDRI using KBr Pellets on a Perkin Elmer IR Spectrometer in
the range of 4000-400 cm-1
. Electronic spectra of the complexes were recorded by the courtesy of Dept. of
Chemistry, IIT Delhi in the ranges of (10-35)kk.
III. BIOLOGICAL ACTIVITY
For determining antibacterial activity , the synthesized metal complexes have been screened against E.Coli,
K.Pneumoniae, S.Aureus, P.aeruginosa using Agar-Plate diffusion technique21
. Two to eight hours old bacterial
inoculums containing approximately 104
-106
colony forming units (CFU)/ml were used in these assays. The
wells were dug in the media with the help of a sterile metallic borer with centers at least 24mm. Recommended
concentration (100l) of the test sample (1mg/ml in DMSO) was introduced into the respective wells. Other
wells suplemented with DMSO and reference antibacterial drug, imipenum served as negative and positive
controls respectively. The plates were incubated immediately at 370
C for 20h. Activity was determined by
measuring the diameter of zones (mm) showing complete inhibition. Growth inhibition was compared with the
standard drug. In order to clarify any participating role of DMSO in the biological screening, separate studies
were carried out with the solutions of DMSO alone which showed no activity against any bacterial strains.
IV. PREPARATION OF METAL COMPLEXES
For the preparation of [Ln(Clox)2(H2O)2]Cl Complexes, Cloxacillin(5mmol, 2.1794g) was mixed with 2.5mmol
of Ln(III) chlorides in a mixture of water-ethanol(25ml, 1:1v/v). The pH
of the solution was adjusted to 7-8 with
sodium aceate using digital pH
meter. The mixture was refluxed for 1h on a water bath and concentrated to half
volume. Then on cooling to room temperature, the colored complexes got precipitated slowly, which was
filtered, washed repeatedly with distilled water and ethanol. Now, the complexes were dried over anhydrous
calcium chloride in dessicator.
V. RESULTS AND DISCUSSION
All the Ln(III) complexes were obtained in powder form with characteristic color. All these complexes are non-
hygroscopic. Analytical data, Magnetic moment, %yield, Molar conductance, Decomposition temperature,
Melting points and color of all the seven complexes are reported in Table-1. At room temperature magnetic
moment of the complexes are in good agreement with the theoretical values calculated by Van-Vleck22
.
Complexes are insoluble in common organic solvents, only soluble in DMF and DMSO. All the metal
complexes decomposed above than 3000
C.
VI. IR SPECTRAL STUDIES
IR Spectra of cloxacillin and their Ln(III)-complexes comparing mainly the IR frequencies of free and
complexed cloxacillin are reported in Table-2. The IR Spectra of cloxacillin and their Ln(III) complexes were
recorded in the range of 4000-400cm-1
. The IR Spectra of all the complexes shows band at 3450-3400 cm-1
indicate the involvement of water molecule in the coordination sphere23
. Ligand exhibits strong absorption
bands at 1185 cm-1
, 2988 cm-1
due to C-N(-Lactam) and  (N-H) of Amide stretching vibrations which was shifted in
the range of (1350-1040) cm-1
and (2950-2900) cm-1
respectively. The band at 1748 cm-1
assigned due to C-O
of carboxylic acid of thiazolidine nucleus of cloxacillin which was shifted to lower frequencies in the range of
(1630-1590) cm-1
in the spectra of all the Ln(III) complexes. A comparison of the IR Spectra of free ligand and
complexed ligand provide evidence in support of mode of bonding i.e, Shifting of these bands in all the Ln(III)
complexes indicate that there is a coordinate covalent bonding through endocyclic N of -Lactam, N of Amide ,
carboxylate-O of cloxacillin and ‘O’ of water molecule with Ln(III) central metal ion24,25
. All of the IR–spectral
data confirms coordination number eight of the synthesized metal complexes.
VII. ELECTRONIC SPECTRAL STUDIES
Electronic spectral data for the solution of Ln(III)-Cloxacillin complexes investigated in CH3CN are reported in
Table-3. For comparison, the spectral data for the corresponding aqueous salt solution are also given in the same
table. Lanthanum(III) has no significant absorption in the UV-Visible region. The absorption bands of the Pr3+
,
Nd3+
, Sm3+
, Dy3+
, Ho3+
, & Er3+
in the visible and near infrared region appears due to the transitions from ground

3. R. K. Mishra et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 130-
135
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state i.e, 3
H4, 4
I9/2, 6
H5/2, 6
H15/2, 5
I8 and 4
I15/2 respectively to the excited states i.e, J-levels of 4fn
-configuration26
.
The Nephlauxetic ratio () has been determined by the method of JØrgensen27
using the relation :
(1-) =
aquo - complex
aquo
The covalence factor (b1/2
), metal – ligand covalency % i.e, sinhas parameter (%) and covalency angular
overlap parameter () have been calculated by using the following relations28
:
b1/2
=
1
2
[(1-)1/2
]  =
(1-)

x 100 
1-1/2
1/2=
The +ve values of (1-) and % supports the evidence of covalent bonding in all the synthesized Ln(III)-
complexes. The spectral profile of hypersensitive bands of Nd(III), Ho(III) and Er(III) complexes closely
resembles that of eight coordinated complexes reported by Karrakar29,30
and is in good agreement with the other
physico-chemical investigations.
VIII. MAGNETIC SUSCEPTIBILITY STUDIES
Except La(III) all the Ln(III) complexes are paramagnetic showing close agreement with the calculated values
except for Sm(III), indicating an insignificant participation of the 4f-electrons in the bonding. Unlike the d-
electrons of the transition metal ions, the f-electrons of the lanthanide ions are almost unaffected by the
chemical environment and the energy levels are same as in the free ion due to very effective shielding by the
overlying 5s2
and 5p6
shells. The relatively high value obtained in the case of samarium(III) complex, which
may be due to small J-J separation, which leads to the thermal population of the higher energy levels and show
susceptibilities due to first order Zeemann effect31
.
IX. BIOLOGICAL EVALUATION
A comparison of the diameter of inhibition zone of complex investigated showed that all the Ln(III) complexes
exhibits higher antibacterial activity than the uncomplexed cloxacillin (Table-4).
Table-1 : Analytical data of “Ln(III)-Cloxacillin” Complex.
%
Obs.(Cal.)
S.No Complex M. Formulae M. Wt
(Obs./Cal.)
C H N Cl Ln
1. Cloxacillin C19H18ClN3O5S 435.88/435 52.47
(52.41)
4.19
(4.13)
9.69
(9.65)
8.07
(8.04)
.........
2. [La(Clox)2
(H2O)2]Cl
C38H36N6O12S2LaCl3 1076.25
(1076)
42.41
(42.37)
3.41
(3.34)
7.84
(7.80)
9.81
(9.75)
12.95
(12.91)
3. [Pr(Clox)2
(H2O)2]Cl
C38H36N6O12S2PrCl3 1078.15
(1078)
42.35
(42.30)
3.35
(3.33)
7.82
(7.79)
9.78
(9.74)
13.12
(13.07)
4. [Nd(Clox)2
(H2O)2]Cl
C38H36N6O12S2NdCl3 1081.23
(1081)
42.24
(42.18)
3.37
(3.33)
7.82
(7.77)
9.78
(9.71)
13.34
(13.32)
5. [Sm(Clox)2
(H2O)2]Cl
C38H36N6O12S2SmCl3 1087.11
(1087)
42.01
(41.95)
3.38
(3.31)
7.74
(7.72)
9.69
(9.65)
13.83
(13.79)
6. [Dy(Clox)2
(H2O)2]Cl
C38H36N6O12S2DyCl3 1099.09
(1099)
41.57
(41.49)
3.32
(3.27)
7.68
(7.64)
9.59
(9.55)
14.82
(14.74)
7. [Ho(Clox)2
(H2O)2]Cl
C38H36N6O12S2HoCl3 1102.21
(1102)
41.40
(41.37)
3.34
(3.26)
7.64
(7.62)
9.54
(9.52)
15.02
(14.97)
8.. [Er(Clox)2
(H2O)2]Cl
C38H36N6O12S2ErCl3 1104.07
(1104)
41.36
(41.30)
3.29
(3.26)
7.65
(7.60)
9.53
(9.51)
15.18
(15.12)
S.No Complex % Yield Color Decomposition
Temp(0
C)
M.Pt
(0
C)
m (Ohm-
1
cm2
mol-1
)
eff.(in B.M.)
1. Cloxacillin ........ White ........... ........ .......... .........
2. [La(Clox)2
(H2O)2]Cl
64 Yellowish
White
330 260 10.7 Dia
3. [Pr(Clox)2
(H2O)2]Cl
53 Pale Yellow 335 263 14.3 5.64

4. R. K. Mishra et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 130-
135
AIJRFANS 14-270; © 2014, AIJRFANS All Rights Reserved Page 133
4. [Nd(Clox)2
(H2O)2]Cl
62 Yellow. 332 273 13.4 3.67
5. [Sm(Clox)2
(H2O)2]Cl
59 Deep Yellow. 347 267 10.3 1.63
6. [Dy(Clox)2
(H2O)2]Cl
67 Light Yellow 342 266 17.4 11.5
7. [Ho(Clox)2
(H2O)2]Cl
55 Pale Yellow 377 275 15.9 10.17
8. [Er(Clox)2
(H2O)2]Cl
52 Yellow 384 278 12.8 9.58
Table-2: IR Spectral data (in cm-1
) of ligand and complexes :
Functional Group Ligand
Cloxacillin
Complexes
La(III) Pr(III) Nd(III) Sm(III) Dy(III) Ho(III) Er(III)
N
-Lactam
1185 1182 1178 1072 1317 1329 1105 1038
C
O
OH 1748 1605 1592 1628 1614 1619 1626 1623
-NHAmide 2988 2918 2907 2944 2934 2925 2947 2938
Table-3: Electronic spectral data along with band-assignment (in cm-1
) and related bonding parameters
of “Ln (III)- Cloxacillin” Complex.
Complex Band Assignments Bands of
Ln3+
-
aqua
ions
(in kk)
Bands of
Complex (in
kk)
Calculated Bonding Parameter
(1-) 
b1/2
(%) 
[Pr(Clox)2 (H2O)2]Cl 3
H4 → 3
P2
→ 3
P1
→ 3
P0
→ 1
D2
22.5
21.7
20.8
16.7
22.2
21.3
20.2
16.4
0.0134
0.0185
0.0289
0.0180
0.9866
0.9815
0.9711
0.9820
0.0578
0.0680
0.0850
0.0670
1.3581
1.8848
2.9760
1.8329
0.0068
0.0093
0.0148
0.0091
[Nd(Clox)2
(H2O)2]Cl
4
I9/2→4
G9/2
→4
G5/2,2
G7/2
→4
F9/2
→2
S3/2,4
F7/2
→4
F5/2,4
H9/2
19.3
17.5
14.6
13.8
12.8
18.9
17.1
14.2
13.4
12.3
0.0208
0.0229
0.0274
0.0290
0.0391
0.9792
0.9771
0.9726
0.9710
0.9609
0.0721
0.0756
0.0827
0.0851
0.0988
2.1241
2.3436
2.8171
2.9866
4.0691
0.0106
0.0117
0.0139
0.0149
0.0201
[Sm(Clox)2
(H2O)2]Cl
6
H5/2→7
F5/2
→4
H7/2
→4
I7/2
→4
I15/2
33.8
29.0
26.6
22.7
33.21
28.7
26.1
22.2
0.0175
0.0104
0.0188
0.0221
0.9825
0.9896
0.9812
0.9779
0.0661
0.0509
0.0685
0.0743
1.7811
1.0509
1.9160
2.2599
0.0088
0.0053
0.0095
0.0113
[Dy(Clox)2
(H2O)2]Cl
6
H15/2→6
F5/2
→4
I15/2
→4
G11/2
12.4
22.8
23.6
12.0
22.3
23.1
0.0323
0.0220
0.0212
0.9677
0.9780
0.9788
0.0898
0.0741
0.0728
3.3378
2.2494
2.1659
0.0165
0.0112
0.0108
[Ho(Clox)2
(H2O)2]Cl
5
I8 → 5
G3
→ 5
G5
→ 5
F2
→ 5
F3
→ 5
F4
→ 5
F5
23.87
22.24
21.5
20.8
18.92
15.86
23.6
22.0
21.01
20.5
18.4
15.5
0.0114
0.0108
0.0228
0.0145
0.0275
0.0227
0.9886
0.9892
0.9772
0.9855
0.9725
0.9773
0.0533
0.0519
0.0754
0.0602
0.0829
0.0753
1.1531
1.0917
2.3331
1.4713
2.8277
2.3227
0.0058
0.0055
0.0116
0.0073
0.0140
0.0116
[Er(Clox)2
(H2O)2]Cl
4
I15/2→(2
G,4
F)9/2
→ 4
F7/2
→ 4
H11/2
→ 4
S3/2
→ 4
F9/2
24.6
20.7
19.6
18.5
15.8
24.2
20.5
19.2
18.1
15.2
0.0163
0.0097
0.0205
0.0217
0.0380
0.9837
0.9903
0.9795
0.9783
0.9620
0.0638
0.0492
0.0715
0.0736
0.0974
1.6570
0.9795
2.0929
2.2180
3.9501
0.0082
0.0049
0.0105
0.0111
0.0195
Table-4. Antibacterial activities of the ligand & its Ln(III) complexes [Diameter(mm) of Zones Showing
complete inhibition of growth]
Compound Pseudomonas
Aeruginosa
S. Aureus E. Coli Klebs. Pneumoniae
Cloxacillin 24 22 18 13
[La(Clox)2 (H2O)2]Cl 24 25 19 15
[Pr(Clox)2 (H2O)2]Cl 29 27 23 18
[Nd(Clox)2 (H2O)2]Cl 32 28 22 24
[Sm(Clox)2 (H2O)2]Cl 25 27 25 16
[Dy(Clox)2 (H2O)2]Cl 32 36 24 23

5. R. K. Mishra et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 130-
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AIJRFANS 14-270; © 2014, AIJRFANS All Rights Reserved Page 134
[Ho(Clox)2 (H2O)2]Cl 27 25 27 26
[Er(Clox)2 (H2O)2]Cl 36 29 26 31
X. CONCLUSION
On the basis of above discussion coordination number eight has been assigned for all the Ln(III)-Cloxacillin
complexes. The tentative structure of the synthesized complexes may be as shown in the figure-2.
Figure-2: Proposed structure of Ln(III)-Cloxacillin Complexes..
OH2
OH2
N
O
C
O
N
N
S
H
CH3
CH3
O
O
CH3
O
Cl
N
O
C
O
N
N
S
H
CH3
CH3
O
O
CH3
O
Cl
Ln
.Cl
Where Ln(III)= La(III), Pr(III), Nd(III), Sm(III), Dy(III), Ho(III) and Er(III)
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6. R. K. Mishra et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 130-
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AIJRFANS 14-270; © 2014, AIJRFANS All Rights Reserved Page 135
ACKNOWLEDGEMENT
The authors gratefully acknowledge to Professor L. K. Mishra, Science College, Patna University for providing
valuable suggestions for carrying out this work. Authors also expresses their heartiest thankful to Prof. S. Jha,
University PG Dept. of Chemistry, L.N.M.U Darbhanga for fruitful discussion of the results. For the more
recent work concerning Elemental and Spectral Analysis of ligand & complexes, Courtesy of CDRI &
Department of Chemistry, IIT Delhi is highly acknowledged. One of the author (B.G.Thakur) expresses their
sincere thanks to UGC New Delhi for providing Major Research Project Under XIth
Plan.