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Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Contents lists available at ScienceDirect

Spectrochimica Acta Part A: Molecular and


Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa

Interaction of vanadium (IV) solvates (L) with second-generation


uoroquinolone antibacterial drug ciprooxacin: Spectroscopic,
structure, thermal analyses, kinetics and biological evaluation
(L = An, DMF, Py and Et3N)
Wael A. Zordok
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
Department of Chemistry, University College of Quanfudha, Umm Al-Qura University, 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

 Synthesis and isolation of some new Four vanadium(IV) complexes with ciprooxacin drugs are synthesized. IR, UVVis, 1HNMR, kinetic study
complexes with ciprooxacin as and thermal analyses techniques are used. Antibacterial behavior is evaluated against Gram-positive and
antibacterial agent. Gram-negative bacterial strains.
 Characterization of the isolated solid
complexes by different spectroscopic
techniques.
 Studying the effect of L on the
antibacterial agent ciprooxacin and
also if it increasing or decreasing the
activity of antibiotic ciprooxacin
inside the human body.
 Kinetic study of all prepared
complexes.

a r t i c l e i n f o a b s t r a c t

Article history: The preparation and characterization of the new solid complexes [VO(CIP)2L]SO4nH2O, where L = aniline
Received 8 December 2013 (An), dimethylformamide (DMF), pyridine (Py) and triethylamine (Et3N) in the reaction of ciprooxacin
Received in revised form 2 February 2014 (CIP) with VO(SO4)22H2O in ethanol. The isolated complexes have been characterized with their melting
Accepted 19 February 2014
points, elemental analysis, IR spectroscopy, magnetic properties, conductance measurements, UVVis.
Available online 15 March 2014
and 1H NMR spectroscopic methods and thermal analyses. The results supported the formation of the
complexes and indicated that ciprooxacin reacts as a bidentate ligand bound to the vanadium ion
Keywords:
through the pyridone oxygen and one carboxylato oxygen. The activation energies, E*; entropies, DS*;
DFT
1
H NMR
enthalpies, DH*; Gibbs free energies, DG*, of the thermal decomposition reactions have been derived from
IR thermo gravimetric (TGA) and differential thermo gravimetric (DTG) curves, using CoatsRedfern and
TGA HorowitzMetzeger methods. The lowest energy model structure of each complex has been proposed
V(IV) by using the density functional theory (DFT) at the B3LYP/CEP-31G level of theory. The ligand and their
Antibacterial activity metal complexes were also evaluated for their antibacterial activity against several bacterial species, such

Address: Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt. Tel.: +20 1006256488.
E-mail address: Wazordok@yahoo.com

http://dx.doi.org/10.1016/j.saa.2014.02.087
1386-1425/ 2014 Elsevier B.V. All rights reserved.
520 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

as Bacillus Subtilis (B. Subtilis), Staphylococcus aureus (S. aureus), Nesseria Gonorrhoeae (N. Gonorrhoeae),
Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli).
2014 Elsevier B.V. All rights reserved.

Introduction and characterization of new V(IV) complexes formed from the


interaction of CIP with vanadium (IV) in ethanol as a solvent and
Ciprooxacin (Scheme 1) with systematic name 1-cyclopropyl- study the effect of change L on the biological activity of ciproox-
6-uoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid was acin drug. The isolated solid complexes were characterized using
rst patented in 1983 by Bayer A.G. and subsequently approved by spectroscopic and thermal analysis techniques. The thermal behav-
the U.S. Food and Drug Administration (FDA) in 1987. Ciprooxacin ior of our complexes was studied and the antibacterial activity was
is marketed worldwide with over three hundred different brand tested against several bacterial species, such as Bacillus Subtilis (B.
names. Ciprooxacin is available as a generic drug under a variety Subtilis), Staphylococcus aureus (S. aureus), Nesseria Gonorrhoeae
of different brand names and is also available for limited use in vet- (N. Gonorrhoeae), Pseudomonas aeruginosa (P. aeruginosa) and Esch-
erinary medicine. Ciprooxacin (INN) is a synthetic chemothera- erichia coli (E. coli).
peutic antibiotic of the uoroquinolone drug class [1,2]. It is a
second-generation uoroquinolone antibacterial. Ciprooxacin is Materials and methods
a broad-spectrum antibiotic active against both Gram-positive
and Gram-negative bacteria. It functions by inhibiting DNA gyrase, Chemicals
a type II topoisomerase, and topoisomerase IV [3], enzymes neces-
sary to separate bacterial DNA, thereby inhibiting cell division. This Ciprooxacin was purchased from Sigma, VOSO4H2O was from
mechanism can also affect mammalian cell replication. In particu- Aldrich Chemical Co., NaOH and all solvents were from Fluka
lar, some congeners of this drug family (for example those that Chemical Co. All the chemicals and solvents were analytical
contain the C-8 uorine) [4], display high activity not only against reagent grade and were used as purchased without further
bacterial topoisomerases but also against eukaryotic topoisome- purication.
rases and are toxic to cultured mammalian cells and in vivo tumor
models [5]. Although quinolones are highly toxic to mammalian Synthesis
cells in culture, its mechanism of cytotoxic action is not known.
The reaction of ciprooxacin with transition metal ions has An ethanolic solution (20 ml) of ciprooxacin hydrochloride
been studied extensively [69], and various metal-ciprooxacin (1 mmol, 0.3675 g) and NaOH (1 mmol, 0.04 g) was added to an
complexes have been isolated and characterized. In these com- ethanolic solution of VOSO4H2O (0.5 mmol, 0.091 g) and the reac-
plexes, ciprooxacin may coordinated via either carbonyl oxygen tion mixture was stirred at room temperature for 1 h and then add-
with carboxylic group or nitrogen atom, depending on the type ing (1 ml) aniline (0.5 mmol, d = 1.025), after that the mixture was
of metal ion [1012]. However, the majority of the evidence sug- stirred at room temperature for 22 h. The solution was left for slow
gests that the carbonyl oxygen atom with oxygen atom of carbox- evaporation, after that a green [VO(CIP)2An]SO49H2O product was
ylic group are preferred coordination site on most of cases studied. deposited. The solid obtained was ltered under vacuum, washed
Infrared spectroscopy has been widely used as a powerful means of with ethanol and dried. In a similar way, the greenish solid com-
distinguishing between these possibilities. plexes [VO(CIP)2DMF]SO415H2O, [VO(CIP)2Py]SO412H2O and
Density functional theory (DFT) was used to compute the cation [VO(CIP)2Et3N]SO42H2O were prepared by using DMF, Py and
type inuence on theoretical parameters of the V(IV) complexes of Et3N instead of aniline. Unfortunately we were not able to obtained
ciprooxacin and detect the exact structure of these complexes appropriate mono-crystals to perform X-ray diffraction analysis.
and show if the two oxygen atoms (Oketo and Ocarboxylic) of cipro- The complexes were characterized by their elemental analysis,
oxacin lie at trans or at cis positions so the two isomers of the infrared, electronic, 1H NMR, thermal analysis as well as density
studied complexes were calculated. Such computational character- functional theory (DFT) at the B3LYP/CEP-31G level of theory.
ization reduces time consuming experiments for biomedical and
pharmaceutical studies of the drugs and its complexes. Proles of Instruments
the optimal set and geometry of these complexes were simulated
by applying the GAUSSIAN 98W package of programs [13] at Elemental C, H, N and halogen analysis was carried out on a Per-
B3LYP/CEP-31G [14] level of theory. kin Elmer CHN 2400. The percentage of the V(IV) was determined
To continue our investigation in the eld of quinolone com- gravimetrically by transforming the solid products into oxide, and
plexes [1524], we reported in the present work, the synthesis also determined by using atomic absorption method. Spectrometer
model PYE-UNICAM SP 1900 tted with the corresponding lamp
was used for this purposed. IR spectra were recorded on FTIR 460
PLUS (KBr discs) in the range from 4000 to 400 cm1, 1H NMR spec-
O O
tra were recorded on Varian Mercury VX-300 NMR Spectrometer
F using DMSO-d6 as solvent. TGA-DTG measurements were carried
OH out under N2 atmosphere within the temperature range from room
temperature to 800 C using TGA-50H Shimadzu. Electronic spectra
+ N N were obtained using UV-3101PC Shimadzu. The solid reection
NH 2 spectra were recorded with KBr pellets. Magnetic measurements
were carried out on a Sherwood scientic magnetic balance using
Cl
Gouy method and Hg[Co(SCN)] as calibrant. Molar conductivities
Scheme 1. Structure of ciprooxacin hydrochloride (CIP), 1-cyclopropyl-6-uoro- of the solution of the ligand and metal complexes in DMSO at
4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid. 5.5  104 M were measured on CONSORT K410. All measurements
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 521

were carried out at ambient temperature with freshly prepared


solution.

Antimicrobial investigation

Antibacterial activity of the ligand, metal salts and its metal


complexes was investigated by a previously reported modied
method of Beecher and Wong [25], against different bacterial spe-
cies, such as B. Subtilis, S. aureus, N. Gonorrhoeae, P. aeruginosa and
E. coli. The tested microorganisms isolates were isolated from
Egyptian soil and identied according to the standard bacteriolog-
ical keys for identication of bacteria as stock cultures in the
microbiology laboratory, Faculty of Science, Zagazig University.
The Mller-Hington agar (30.0% Beef extract, 1.75% Casein hydroly-
sate, 0.15% Starch and 1.7% Agar) was prepared and then cooled to
47 C and seeded with tested microorganisms. After solidication
5 mm diameter holes were punched by a sterile cork-borer. The
investigated compounds, i.e., ligand, metal salts and their com-
plexes, were introduced in holes (only 100 lL) after being dis-
solved in DMSO at 104 M. These culture plates were then
incubated at 37 C for 20 h. The activity was determined by mea-
suring the diameter of the inhibition zones (in mm). Growth inhi-
bition was calculated with reference to the positive control, i.e.
Ciprooxacin.

Results and discussion

The V(IV) ciprooxacin complexes were characterized by ele-


Fig. 1. Infrared spectra of: (A) ciprooxacin (CIP); (B) [VO(CIP)2An]SO49H2O, (C)
mental analysis, infrared, UVVis and 1H NMR. Elemental analyti-
[VO(CIP)2DMF]SO415H2O, (D) [VO(CIP)2Py]SO412H2O and (E) [VO(CIP)2Et3N]
cal data of the complexes are very close to the theoretical values SO42H2O complexes.
as shown in Table 1. Elemental analysis showed that the metal to
ligand ratio is 1:2 and the composition of V(IV) complexes was
[VO(CIP)2L]SO4nH2O (L = An, DMF, Py and Et3N, n = 9, 15, 12 and IR spectral studies
2, respectively).
Conductance and melting points of the complexes are given in The infrared spectra of the ligand and its complexes were
Table 1, conductance data showed that the V(IV) complexes are shown in Fig. 1 and their bands assignments were listed in Table 2.
electrolyte indicating the sulphate ions is located outside the coor- The infrared spectra of the complexes were compared with those
dination sphere. The magnetic moments are slightly less than, or of the free ligand in order to determine the coordination sites that
slightly more than, the spin-only moment depending on the sign may involved in chelation. There were some guide peaks in the
of k. For V(IV) (d1) ion complexes has k positive (the spinorbit spectra of the ligands, which are of good help for achieving this
coupling constant k a positive sign for d shells less than half lled) goal. These peaks were expected to be involved in chelation. The
and hence leff. < lspin only (1.73) as shown in Table 1. Qualitative position and /or the intensities of these peaks were expected to
reactions revealed the presence of sulphate as counter ions in all be changed upon chelation. New peaks are also guide peaks as well
the complexes (the complexes solutions give white precipitate as water of crystallization.
with an aqueous solution of BaCl2). The infrared spectra and ther- In order to study the binding mode of both the ligands to the
mogravimetric analysis indicated the presence of water molecules metal in complexes, the infrared spectra of the uncomplexes ligand
in all V(IV) complexes. was compared with the spectra of metal complexes. The infrared

Table 1
Elemental analysis and physico-analytical data of metal ciprooxacin complexes.

Complexes (M.Wt.) M.F Yield% mp (C) Color Content (calculated) found K (S cm2 mol1) leffect (BM)
%C %H %N %M
[VO(CIP)2 An]SO49H2O 80.45 410 Green (44.44) (5.64) (9.07) (4.71) 135 1.23
(1079.9) 44.25 5.34 9.01 4.68
C40H61N7O20F2SV
[VO(CIP)2 DMF]SO415H2O 73.65 370 Greenish (38.02) (6.25) (8.39) (4.36) 163 1.18
(1167.9) 37.98 6.15 8.29 4.28
C37H73N7O27F2SV
[VO(CIP)2 Py]SO412H2O 78.95 350 Faint grey (41.79) (5.80) (8.75) (4.55) 164 1.21
(1119.9) 41.68 5.77 8.55 4.46
C39H65N7O23F2SV
[VO(CIP)2 Et3N]SO42H2O 77.85 280 Pale brown (49.90) (5.72) (10.19) (5.29) 157 1.29
(961.9) 49.78 5.70 10.17 5.18
C40H55N7O13F2SV
522 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Table 2
Infrared frequencies cm1 and assignments for (A) ciprooxacin (CIP); (B) [VO(CIP)2An]SO49H2O,(C) [VO(CIP)2DMF]SO415H2O, (D) [VO(CIP)2Py]SO412H2O, and (E)
[VO(CIP)2Et3N]SO42H2O complexes.

A B C D E Assignment
3530vs 3422br 3418br 3414br 3422br m(OAH);COOHH2O
3490vw
3375m
3327vw
3209vw 3017w 3102vw 3112vw 3122vw m(CAH); aromatic
3090ms
3020m
2920ms 2812m 2970vw 2982w 3040w
2837w 2867vw 2878vw 2963m m(CAH); aliphatic
2786vw 2673vw 2812m 2812w 2929vw
2704ms 2488ms 2796vw 2765vw 2851ms
2619ms 2755vw 2714vw 2777w m(ANH+2)
2551vw 2673vw 2650w 2642m
2469m 2492ms 2503ms 2476ms
1705vs m(C@O); COOH
1628vs 1627vs 1628vs 1624vs mas(COO)
1620vs 1578ms 1574s 1574s 1578s m(C@O) phenyl breathing modes and ACH; deformation of ACH2
1489vw 1522vw 1522w 1524m 1539m
1454vs 1481vs 1481vs 1485vs 1485vs
1389s
1381s 1385vs 1385s 1377vs ms(COO)
1344vw 1300ms 1304vs 1304s 1296vs db(ACH2)
1312ms
1269vs 1269m 1269s 1265ms 1256vw m(CAO),
1184m 1178vw 1183vw 1183vw 1184s m(CAN) and
1146m 1139vw 1142s m(CAC)
1107m 1115vs 1119vs 1119vs 1100vw m(SO4 )
1034ms 1034vs 1034s 1034s 1030vs dr(ACH2)
949vs 953vs 953vs 945vs m(V@O)
988ms 895s 903s 903ms 895m ACH bend; phenyl
941ms 834vw 867vw 861vw 833ms
900vw 802w 844vw 822w 783ms
841vw 806m
806w
775w 741s 756ms 745m 783ms db(ACOO)
748w 706vw 706w 700vw 733vs
710ms
667vw 655vw 656vw 621s 644vw m(MAO), ring deformation + m(SO4 )
622vw 621vs 621vs 575w 621s
567vw 575m 579m 544m 567vw
544ms 544m 544m 509w 540s
482s 472vw 505m
470 m(MAN); N of aniline
467vw m(MAN); N of Et3N
422vw m(MAN); N of Py
413s 409s 409s 413s 412ms

Keys: s = strong, w = weak, v = very, m = medium, br = broad, m = stretching, db = bending.

spectra of free ciprooxacin and [VO(CIP)2L]SO4nH2O (L = An, in the 34223414 cm1 zone conrms the presence of water mol-
DMF, Py and Et3N, n = 9, 15, 12 and 2, respectively). Were mea- ecules in all complexes.
sured as KBr discs. The spectra are shown in Fig. 1 and the full The stretching vibrations m(CAH) of the phenyl groups in these
assignments are given in Table 2. The IR spectra of the ligand show complexes were assigned as a number of bands in the region 3122
a very strong bands at 1705 and 1620 cm1 assignable to the 3017 cm1. The corresponding vibrations m(CAH) of the ACH2 and
stretching vibration of carboxylic m(COOH) and the carbonyl group ACH3 units were observed in the range 29632851 cm1. The
m(C@O), respectively [7,1531]. The absence of the rst band and assignments of all the CAH stretching vibrations agree quite well
the shift of the second band characteristic of the carbonyl group with the expected [32,33]. A group of weak to strong bands lying
m(C@O) to a lower value from 1620 cm1 to average value in the range 12691107 cm1 could be assigned to the m(CAO),
1576 cm1 in V(IV) complexes reveals the deprotonated of the m(CAN) and m(CAC) in all complexes. The data given in Table 2,
ACOOH group on complexation and also indicate coordination of shows that the m(V@O) in these complexes occurs at 949 cm1
CIP through one of the oxygen atoms of the carboxylato group for the An complex and at 953 cm1 for the DMF complex and at
and of the carbonyl group. The asymmetric stretching vibration 953 cm1 for the Py complex and at 945 cm1 for Et3N complex
(mas) of the ligated carboxylato group appear at nearly 1627 cm1 [34]. Comparing between the obtained values for m(V@O) in the
and the symmetric stretching vibration (ms) of our complexes found four complexes, it seems that the ligand (L) has no pronounced
at 1382 cm1 (Table 2). The above description of IR data supports effect on these values.
the bidentate nature of the investigated ligand through the oxygen The IR spectra of the V(IV) complexes also showed some new
atom of the carboxylato group and the oxygen atom of the car- bands with different intensities which are assigned to m(VAO)
bonyl group [12,31]. Also the presence of the broad water bands and m(VAN). The data given in Table 2, shows that m(VAO) in these
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 523

appearance of these bands also for the favor of complexes forma-


tion). For [VO(CIP)2L]SO4nH2O complexes, in order to verify that
the sulphate group is ionic and not coordinate, the complex solu-
tion was tested with an aqueous solution of BaCl2 (a precipitate
was formed). The characteristic bands of anion sulphate (SO 4 ),
belong to high symmetry point group, Td, are shown in Table 2.
This indicates that the sulphate found as counter ion (outside the
complex sphere) [34].

UVVisible spectra

The formation of the V(IV) complexes was also conrmed by


UVVis spectra. Fig. 2 gives the electronic solid reection spectra
of the ligand and its V(IV) complexes in the 200800 nm range.
The free ciprooxacin reected at three distinct absorption bands
Table 3. The rst two at 243 and 298 nm attributed to p ? p* tran-
sition and the third band observed at 338 nm is attributed to
n ? p* electronic transition (these transitions occur in case of
unsaturated hydrocarbons which contain ketone groups) [12,22].
In the spectra of the four V(IV) complexes the absent of the reec-
tion band at 243 nm in all complexes and the shift of the other two
reectance bands kmax to higher values attributed to complexation
behavior of ciprooxacin towards V(IV). Also the complexes of
V(IV) show new bands in the range from 425 to 570 nm, which
may be assigned to the ligand to metal charge-transfer
[6,1619,35].

The 1H NMR spectra

To provide further information on the proposed structures for


the complexes, 1H NMR spectra were carried out. Fig. 3 represents
the 1H NMR spectra of [VO(CIP)2L]SO4nH2O (L = An, DMF, Py and
Et3N) complexes which was carried out in DMSO-d6 as a solvent
and the data listed in Table 4. The absence of the characteristics
signal for H(COOH) at 11.00 ppm in our complexes indicate coordi-
nation of CIP ligand to V(IV) through the deprotonated carboxylic
group [1519,23,24].
The spectra also show characteristic signals for quaternary
nitrogen (A+NH2) at d 2.47, 2.50, 2.49 and 2.492.59 ppm for
V(IV) complexes (Table 4). The signal characteristic for water mol-
ecules was observed at d 3.14, 2.74, 2.89, 2.96, 3.12 and 2.92
3.27 ppm for [VO(CIP)2L]SO4nH2O (L = An, DMF, Py and Et3N,
respectively) which was not found in the free ligand. Also all sig-
nals of the free ligand are present in the spectra of the V(IV) com-
plexes with chemical shift upon binding to the V(IV) [36].

Thermal analyses

Thermo gravimetric analyses (TGA and DTG) of the ligand under


investigation and their complexes were used to get information
about the thermal stability of these new complexes, to decide

Table 3
Electronic reection spectra of (A) ciprooxacin (CIP); (B) [VO(CIP)2An]SO49H2O,
(C) [VO(CIP)2DMF]SO415H2O, (D) [VO(CIP)2Py]SO412H2O and (E) [VO(CIP)2Et3N]
SO42H2O complexes (200800 nm).

Assignments (nm) A B C D E
pp* transitions 243 291 303, 318 251 303
Fig. 2. Electronic reection spectra of: (A) ciprooxacin (CIP), (B) [VO(CIP)2An] 298 311 309
SO49H2O, (C) [VO(CIP)2DMF]SO415H2O, (D) [VO(CIP)2Py]SO412H2O and (E) 318
[VO(CIP)2Et3N]SO42H2O complexes. np* transitions 338 347 355 351 330
384
1 1
complexes occurs at 575, 470 cm for aniline, at 579, 472 cm for Ligandmetal charge transfer 440 425 427 440
DMF, at 575, 509 cm1 for Py and at 540, 505 cm1 for Et3N com- 505 502 501 506
528 528 533 537
plexes which are assigned to m(VAO) stretching vibrations of coor-
568 567 570
dinated carboxylato oxygen atom and carbonyl oxygen atom (the
524 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Fig. 3. 1H NMR spectra of: (A) [VO(CIP)2An]SO49H2O, (B) [VO(CIP)2DMF]SO4


15H2O, (C) [VO(CIP)2Py]SO412H2O and (D) [VO(CIP)2Et3N]SO42H2O complexes.

whether the water molecules (if present) are inside or outside the
inner coordination sphere of the central metal ion and to suggest a
general scheme for thermal decomposition of these chelates. In the
present investigation, heating rates were suitably controlled at
10 C min1 under nitrogen atmosphere and the weight loss is
measured from the ambient temperature up to 1200 C. The
TGA and DTG curves of the ligand and their complexes are shown
in Fig. 4 and the data are listed in Table 5.
The weight losses for each chelate were calculated within the
corresponding temperature ranges. The obtained data strongly
supported the structures proposed for the complexes. The data
obtained indicates that the ciprooxacin is thermally stable in
the temperature range 2550 C. Decomposition of the CIP started
at 50 C and nished at 750 C with two stages. The rst stage of
decomposition occurred at maximum temperature of 132 C and
is accompanied by a weight loss of 7.11%, corresponding exactly Fig. 4. TGA and DTG diagram of: (A) ciprooxacin (CIP), (B) [VO(CIP)2An]SO49H2O,
to the loss of acetylene molecule (C2H2) [22]. The second stage of (C) [VO(CIP)2DMF]SO415H2O, (D) [VO(CIP)2Py]SO412H2O and (E) [VO(CIP)2
Et3N]SO42H2O complexes.
decomposition occurred at two maxima 315 and 382 C

Table 4
1
H NMR values (ppm) and tentative assignments for (A) ciprooxacin (CIP); (B) [VO(CIP)2an]SO49H2O; (C) [VO(CIP)2DMF]SO415H2O; (D) [VO(CIP)2Py]SO412H2O; (E)
[VO(CIP)2Et3N]SO42H2O complexes.

A B C D E Assignments
1.13 1.02, 1.13 1.07, 1.18, 1.32 1.17, 1.29 1.011.32 dH, ACH2;of cycloproban ring
2.00 dH, ANH; piperazine
2.47 2.50 2.49 2.492.59 d H, A+NH2
3.14 2.74, 2.89, 2.96 3.12 2.923.27 d H, H2O
2.78, 3.10, 3.46 3.37 3.38 3.41 3.373.47 d H, ACH3ACH2 aliphatic
6.04, 8.01, 8.66 6.50, 6.95, 7.87, 8.62 7.95, 8.67 7.55, 7.89, 8.65 7.527.54, 7.857.89, 8.65 d H, ACH2 aromatic
11.00 d H, ACOOH
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 525

Table 5
The maximum temperature Tmax/C and weight loss values of the decomposition stages for ciprooxacin complexes.

Compounds Decomposition steps Tmax/C Weight loss (%) Lost species


Calc. Found
CIP First step 132 7.07 7.11 C2H2
(C17H19N3O3FCl) Second step 315, 76.60 76.54 4C2H2 + C2H4 + 3 NO + HF + HCl + 1.5H2
Total loss, Residue 382 83.67, 16.33 83.65, 16.35
[VO(CIP)2 An]SO49H2O First step 83 15.00 14.91 9H2O
C40H61N7O20F2SV Second step 347,439 71.40 71.23 20C2H2 + 7NO + 2HF + 0.5H2
Total loss, Residue 86.40, 13.60 86.14, 13.86
[VO(CIP)2DMF]SO415H2O First step 70 23.10 23.01 15H2O
C37H73N7O27F2SV Second step 361 60.22 60.19 13C2H2 + 3C2H4 + 6NO + CO2 + NH3 + 2HF
Total loss, Residue 83.32, 16.68 83.20, 16.80
[VO(CIP)2 Py]SO412H2O First step 54 19.30 19.20 12H2O
C39H65N7O23F2SV Second step 378,476 61.16 61.54 16C2H2 + CH4 + 7NO + HF + 1.5H2
Total loss, Residue 80.46, 19.54 80.74, 19.26
[VO(CIP)2 Et3N]SO42H2O First step 120 3.70 3.61 2H2O
C40H55N7O13F2SV Second step 325,486 69.07 68.96 9C2H2 + 3CH4 + 4C2H4 + CO + 6NO + NH3 + 2HF
Total loss, Residue 72.77, 27.23 72.57, 27.43

60 C
accompanied by a weight loss of 76.54%, corresponding to the loss (ii) VOCIP2 PySO4  12H2 O !VOCIP2 PySO4 12H2 O
of 4C2H2 + C2H4 + 3NO + HF + HCl + 1.5H2. The actual weight loss of
378;476 C
these stages is equal to 83.65%, and this is very closer to calculated VOCIP2 PySO4 ! VSO4 6C 16C2 H2 CH4 7NO
value 83.67%.
HF 1:5H2
Thermal degradation for the complex [VO(CIP)2An]SO49H2O
exhibited two main degradation steps. The rst occurred at 83 C, 120 C
(iii) VOCIP2 Et3 NSO4  2H2 O !VOCIP2 Et3 NSO4 2H2 O
accompanied by weight loss of 14.91% corresponding to the loss
of nine water molecules [37]. Theoretically, the loss of these mol- 325;486 C
ecules corresponds to a weight loss of 15.00%. The second decom- VOCIP2 Et3 NSO4 ! VSO4 10C 9C2 H2 3CH4
position step occurs at two different temperatures; 347 and 439 C. 4C2 H4 CO 6NO NH3 2HF
These are attributed to the rupture of the VAN and VAO bonds N
and O of aniline and CIP [33]. The weight loss associated with these
stages is 71.23% due to the loss of 20C2H2 + 7NO + 2HF + 0.5H2 The kinetics parameters
molecules in agreement with the theoretical weight loss value of
71.40%, giving the nal product VSO4. The infrared spectrum of Coats Redfern [38] and Horowitz-Metzger [39] are the two
the nal product of the thermal analysis supports these conclu- methods mentioned in the literature related to decomposition
sions. Accordingly, the mechanism for the thermal decomposition kinetics studies. The thermodynamic activation parameters of
of the complex, [VO(CIP)2An]SO49H2O, is as follows decomposition processes of complexes namely of [VO(CIP)2An]
SO49H2O, [VO(CIP)2DMF]SO415H2O, [VO(CIP)2Py]SO412H2O and
VOCIP2 AnSO4  9H2 O ! VOCIP2 AnSO4 9H2 O [VO(CIP)2Et3N]SO42H2O, the activation energies, E*, pre-exponential
factor, A, entropies, DS*, enthalpies, DH* and Gibbs free energies,
347;439 C DG*, were calculated graphically by employing the Coats Redfern
VOCIP2 AnSO4 ! VSO4 20C2 H2 7NO 2HF 0:5H2
relation. The entropy of activation, DS*, enthalpy of activation,
Thermal decomposition of the other three complexes DH* and the free energy change of activation, DG*, were calculated
[VO(CIP)2L]SO4nH2O (L = DMF, Py and Et3N) also exhibit two main using the following equations:
degradation steps. The rst step of decomposition occurred at 70, DS 2:303logAh=KTR
60 and 120 C, respectively, accompanied by a weight loss of
23.01%, 19.20% and 3.61%, corresponding to the loss of 15, 12 DH E  RT
and 2 water molecules, respectively, in agreement with the
theoretical values of 23.10%, 19.30% and 3.70%. The second decom- DG DH  TDS
position stage occurred at one maximum temperature 361 C for
[VO(CIP)2DMF]SO4 complex and at two maxima as expected for The linearization curves of Coats Redfern and HorowitzMetzger
[VO(CIP)2Py]SO4 and [VO(CIP)2Et3N]SO4 since the two ligands methods are shown in Fig. 5 and all calculations are summarized
coordinates with vanadium through two different donor atoms in Table 6. The entropy of activation was found to have negative val-
(N and O). The infrared spectra of the nal product of the thermal ues in the two complexes which indicate that the decomposition
analysis and also the qualitative reactions revealed the presence reactions proceed with a lower rate than normal ones. The correla-
of sulphate in all the nal product (the solutions give white tion coefcients of the Arrhenius plots (r) of the thermal decompo-
precipitate with an aqueous solution of barium chloride) for all sition steps were found to lie in the range 0.92390.9840, showing a
above complexes supported these conclusions. The mechanisms for good t with linear function. It is clear that the thermal decompo-
the thermal decompositions of the three complexes are as follows sition process of the complexes is non-spontaneous, i.e., the com-
plexes are thermally stable.
70 C
(i) VOCIP2 DMFSO4  15H2 O !VOCIP2 DMFSO4 15H2 O The negative values of the entropies DS* in these complexes
indicate that the activated complex has more ordered structure
361 C
VOCIP2 DMFSO4 ! VSO4 4C 13C2 H2 3C2 H4 than the reactants and that the reactions are slower than normal
[40]. The higher values of the activation energies reect the ther-
6NO CO2 NH3 2HF
mal stability of complexes and also indicate that the processes
526 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Fig. 5. The diagrams of kinetic parameters of Ciprooxacin (CIP), [VO(CIP)2Et3N]SO42H2O, [VO(CIP)2Py]SO412H2O, [VO(CIP)2DMF]SO415H2O, and [VO(CIP)2An]SO49H2O
complexes.

involving in translational, rotational, vibrational states and The test solutions were prepared in DMSO-d6 and the results
changes in mechanical potential energy of complexes [18]. are presented in Table 7. The synthesized compounds were
found to have remarkable bactericidal. Fig. 6 shows the statisti-
Antibacterial activities cal representation for biological activity of ciprooxacin (CIP)
and its metal complexes. These activities showed that all the
The susceptibility of certain strains of bacterium towards cip- complexes of V(IV) became less potentially resistance to Bacillus
rooxacin and its complexes was judged by measuring the size subtilis, N. gonorrhoeae, P. aeruginosa and E. coli compared to the
of inhibition zone diameter. Antibacterial activities of ciprooxa- sole ligand but they were more biologically active as compared
cin and its complexes have been carried out with two to free ciprooxacin against Staphylococcus aureus. The chela-
Gram-positive bacteria such as B. Subtilis, S. aureus and three tion made ciprooxacin a more powerful bacteriostatic agent
Gram-negative species N. gonorrhoeae, P. aeruginosa and E. coli. [41,42]. Chelation considerably reduced the polarity of the metal
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 527

Fig. 5 (continued)

ion because of the partial sharing of its positive charge with the ation through the lipid layer of cell membrane [42,43]. This
donor groups and possible p-electron delocalization over the increased lipophilicity enhances the penetration of the com-
chelate ring. Such chelation increased the lipophilic character plexes into the lipid membranes and blocks the metal binding
of the central metal ion, which subsequently favors the perme- sites in enzymes of microorganisms [44,45].
528 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Fig. 5 (continued)

Table 6
Thermal behavior and kinetic parameters determined using CautsRedfern (CR) and HorpwitzMatger (HM) operated for ciprooxacin and complexes.

Compounds Decomposition Ts Method Parameter Ra


range (K) (K) 4 1 * 2 * 4 * 5
E  10 A (s ) DS  10 DH  10 DG  10
(J mol1) (J mol1K1) (J mol1) (J mol1)
CIP (C17H19N3O3FCl) 323490 405 CR 8.202 18.08  108 0.702 7.866 1.0708 0.9575
HM 8.112 83.09  108 0.576 7.776 1.0105 0.9544
577754 588 CR 8.545 1.03  106 1.354 8.057 1.6015 0.9470
HM 8.257 2.97  106 1.266 7.769 1.5209 0.9349
[VO(CIP)2 An]SO49H2O 318660 356 CR 9.799 1.26  105 1.487 0.684 0.597 0.9239
C40H61N7O20F2SV HM 10.602 1.72  105 1.461 0.764 0.596 0.9532
660756 620 CR 13.875 1.19  107 1.155 0.872 0.803 0.9691
HM 14.391 1.80  107 1.121 0.924 0.787 0.9840
[VO(CIP)2DMF]SO415H2O 307612 343 CR 12.401 1.39  105 1.475 0.955 0.602 0.9724
C37H73N7O27F2SV HM 13.549 1.59  105 1.464 1.069 0.609 0.9771
612656 634 CR 15.788 13.87  108 0.762 1.052 0.588 0.9332
HM 17.664 21.68  108 0.724 1.239 0.583 0.9524
[VO(CIP)2 Py]SO412H2O 310634 327 CR 7.368 0.98  105 1.501 0.465 0.537 0.9381
C39H65N7O23F2SV HM 7.942 1.11  105 1.491 0.522 0.539 0.9824
634798 553 CR 10.947 0.26  105 1.671 0.635 0.987 0.9287
HM 11.444 0.23  105 1.666 0.685 0.989 0.9309
[VO(CIP)2 Et3N]SO42H2O 325613 393 CR 9.856 1.31  105 1.492 0.659 0.652 0.9268
C40H55N7O13F2SV HM 11.674 2.03  105 1.456 0.840 0.656 0.9790
613913 598 CR 13.473 1.09  105 1.542 0.850 1.007 0.9464
HM 14.946 1.44  105 1.527 0.953 1.091 0.9703
a
Correlation coefcient of the Arrhenius plots.

Computational details to detect the energies at a highly accurate level. The atomic charges
were computed using the natural atomic orbital populations. The
Computational method B3LYP is the keyword for the hybrid functional [46], which is a lin-
ear combination of the gradient functionals proposed by Becke [47]
The geometric parameters and energies were computed by den- and Lee, Yang and Parr [48], together with the HartreeFock local
sity functional theory at the B3LYP/CEP-31G level of theory, using exchange function [49]. The aim to present a molecular model
the GAUSSIAN 98W package of the programs, on geometries that for each new complex that is unbiased by the starting structure,
were optimized at CEP-31G basis set. The high basis set was chosen DFT method with B3LYP/CEP-31G have been used. The mean total
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 529

Table 7
The inhibition diameter zone values (nm) for CIP and there complexes as [VO(CIP)2 (L)]SO4xH2O.

Compound Bactria species


E. coli N. gonorrhoeae P. aeruginosa S. aureus B. Subtilis
CIP 27 20 23 26 34
0.3 0.4 0.3 0.3 0.3
V(IV) / CIP / An 28NS 28+1 31+2 35+2 38+1
0.3 0.3 0.3 0.3 0.3
V(IV) / CIP / DMF 29NS 28+1 28+1 37+3 38+1
0.3 0.3 0.3 0.4 0.3
V(IV) / CIP / Py 28NS 28+1 30+2 33+1 38+1
0.3 0.3 0.3 0.3 0.3
V(IV) / CIP / Et3N 28NS 28+1 27+1 35+2 38+1
0.3 0.2 0.2 0.4 0.3
VOSO4.2H2O 0 0 0 0 0
Control (DMSO) 0 0 0 0 0
Standard Moxioxacin 22 16 22 40 36
1.7 0.1 0.3 0.5 1.2
Lomeoxacin 17 19 13 24 25
0.1 0.1 0.3 0.2 0.5

Statistical signicance
NS
Not signicance, p > 0.05;
+1
Signicant, p < 0.05;
+2
Highly signicant, p < 0.01;
+3
Very highly signicant, p < 0.001; students t-test.

Fig. 6. Statistical representation for biological activity of ciprooxacin (CIP) and its metal complexes.

energy of an ensemble of structures guides the selection of most length C4AO23 is 1.28 [52], there is a double bond between
favorable conguration for each complex. Starting structures are C14 and O22 atoms 1.26 , whereas C14AO21 is a single bond
cis- and tras-forms as ligand L (aniline (An), dimethylformamide 1.29 [52]. Detailed analysis of corresponding bond lengths in var-
(DMF), pyridine (Py) and triethyl amine (Et3N)) molecule lying ious quinolone molecules was given elsewhere [53]. The lengths
axial position with respect to oxygen atom of M@O while the and angles between the atoms of the rigid quinolone ring system
two oxygen atoms Oketo or two oxygen atoms Ocarboxylic for and those of the piperazine ring are similar appearance described
ciprooxacin lying in the same face (cis-conformer) or lying in earlier [26,50,51].
opposite face (trans-conformer), the cis-isomer is more steric The biological activity of quinolones (ciprooxacin) is mainly
while, trans-isomer is less steric. determined by its ne structure, the Ciprooxacin has many char-
acteristic structural features. The molecule is a highly sterically-
Structural parameters and model of drug ligand ciprooxacin hindered, the cyclopropyl ring not laying in the same plane of
quinolone ring the dihedral angles C10N1C11C13 and
A role of the quinolone molecule in the structure is similar to C10N1C11C12 are 73.47 and 134.95, respectively, also the
the ionic compounds reported so far [26,50,51], it is protonated piperazine group out of plane of the molecule. This observation
at a terminal nitrogen atom of piperazine ring N18. The bond is supported by the values of calculated dihedral angles:
530 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Fig. 7. Optimized geometrical structure of ciprooxacin by using B3LYP/CEP-31G.

Table 8 O O
Equilibrium geometric parameters bond lengths (), bond angles (), dihedral angles
() and charge density of Ciprooxacine ligand by using DFT/B3LYP/Cep-31G. L Oc L Ok
Bond length ()
C4AO23 1.28 (1.30) [52] C3AC14 1.51 (1.47) [52] M M
C4AC3 1.47 (1.41) C14AO22 1.26 (1.23)
C2AC3 1.38 (1.38) C14AO21 1.29 (1.29)
C10AN1 1.41 (1.40) C11AN1 1.46 (1.46)
Ok Ok Ok Oc
Bond angle ()
Oc Oc
C7N15C20 115.08 O23C4C3 124.89
C7N15C16 114.66 O21C14C3 114.95
cisOk
N15C7C8 121.97 O22C14C3 114.92 transOk
N15C7C6 120.17 O21C14O22 129.98
C4C3C14 123.67 C2N1C11 120.36
Dihedral angles () O O
O23C4C3C2 177.90 C10N1C11C13 73.47
L Ok L
C16N15C7C8 69.70 C11N1C2C3 177.40 Oc
C20N15C7C8 65.70 O23C4C3C14 0.00
C10N1C11C12 143.95 O22C14C3C4 145.45
O21C14C8C4 38.5
M M
Charges
Oc Oc Oc Ok
N1 0.178 O23 0.133
N15 0.098 O21 0.356
N18 0.279 O22 0.369 Ok Ok
C14 0.018 C2 0.305
C4 0.386 C3 0.187
cisOc transOc
Total energy/au 207.81236
Total dipole moment/D 24.5
Scheme 2. The diastereoisomers of [VO(CIP)2(L)] complexes employed in theoret-
ical calculations. Oc and Ok are the carboxylate and the pyridone oxygen atoms,
respectively, of the ciprooxacin ligand, and L = aniline, dimethyl formamide,
pyridine and triethylamine.
C20N15C7C8 and C16N15C7C8 are 65.7 and 69.7, respectively,
where the values are neither zero nor 180. Fig. 7, shows the opti- result was obtained with C4 and C14. The values of bond distances
mized geometrical structure of ciprooxacin molecule, the dihe- are compared nicely with that obtained from X-ray data [52].
dral angles O23C4C3C14 and O21C14C3C4 are 0.0 and 38.5, Charge distribution on the optimized geometry of ciprooxacin
respectively, also, O22C14C3C4 is 145.45 which conrms that is given in Table 8. There is a signicant built up of charge density
the O23 and O21 lying in the same direction. The C4O23 bond is on the oxygen atoms which distributed over all molecule, charge
laying in the same plane of C14O21 bond while O23 and O22 are on O21 of carboxylate group 0.356 and O23 of ketone 0.133,
lying in the opposite direction to each other so, the C4O11 not in so ciprooxacin molecule behaves as bi-dentate ligand (Oketo and
the same plane of C14O22. Table 8 gives the optimized geometry Ocarboxylic atoms) and the molecule is a highly dipole l = 24.5D.
of ciprooxacin as obtained from B3LYP/Cep-31G calculations.
These data are drowning to give the optimized geometry of mole- The electronic structure of the complexes with molecular modeling
cule. The bond distance of C14AO21 and C14AO22 are 1.28 and
1.26 while, C4AO23 is 1.28 . The value of bond angle The V(IV) may be chelated with two molecules of ciprooxacin
C4C3C14 is 123.67 reected on sp2 hybridization of C8, the same through four coordinate bonds via oxygen atom of carboxylic
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 531

group and oxygen atom of pyridine group (Ocarboxylic and Oketo


atoms) from each molecule. The experimental data set that the
result complex is six-coordinate and the complex consists of four
coordinate bonds with two ciprooxacin molecules and one coor-
dinated bond with other molecule as aniline, dimethyl formamide,
pyridine or triethylamine molecule beside oxygen atom of VO ion.
In this part we study theoretically the all structures can be
obtained [VO(CIP)2An]2+, [VO(CIP)2DMF]2+, [VO(CIP)2Py]2+ and
[VO(CIP)2Et3N]2+. The two isomers cis and trans of theses com-
plexes have been constructed as starting models. The two oxygen
atoms of ciprooxacin ligand can be either at trans or at cis posi-
tions. Each of these complexes has eight diastereoisomers as
shown in Scheme 2, the most stable structures were obtained
and detected through the value of energy.
The structure of these complexes did not determine by X-ray
crystallography. In order to present a model for the complex, only
the enantiomers having the two oxygen atoms can lie either at
trans [53,54] or at cis [55,56] positions, so this complex has eight
diasterioisomers as shown in Scheme 3. The total energy for the
two enantiomers were calculated theoretically by using DFT
method combine with B3LYP/CEP-31G as basis set to determine
the most stable isomer.

Description of the structure of [VO(CIP)2An]2+


Table 8 lists selected inter atomic distances and angles. The
structure of complex with atomic numbering schema is shown in
Fig. 8. The complex consists of two units of ciprooxacin molecule
and one aniline molecule with metal ion VO ion. The complex is
six-coordinate with distorted octahedral environment around the
Scheme 3. The coordination mode of V(IV) with ciprooxacin and L = aniline (An), metal ion. The metal ion V(IV) of VO is coordinated to one Oketo
dimethyl formamide (DMF), pyridine (Py) and triethylamine (Et3N). atom and one Ocarboxylate atom of ciprooxacin ligand and NAn atom
for aniline molecule. The VAO21a and VAO21b bond lengths are

Fig. 8. Optimized geometrical structure of trans-isomer of [VO(CIP)2An]2+ complex by using B3LYP/CEP-31G.


532 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Table 9
Equilibrium geometric parameters bond lengths (), bond angles () and charge density of [VO(CIP)2(An)]2+ by using DFT/B3LYP/Cep-31G.

Bond length ()
VAO23b 1.856 (1.93) [58] C14bAO21b 1.349
VAO21b 1.847 (1.93) [58] C14bAO22b 1.211
VAO23a 1.851 (1.93) [58] C4bAO23b 1.213
VAO21a 1.845 (1.93) [58] C14aAO21a 1.349
VAO 1.788 (1.57) [58] C14aAO22a 1.211
VANAn 1.938 (2.04) [58] C4aAO23a 1.210
Bond angle ()
O21bAVAO23b 93.13 (97.23) [59] O21bAVANAn 87.15
O23aAVAO23b 85.35 (89.84) [59] O21bAVAO 90.12 (89.84) [59]
O21aAVAO23b 85.91 (86.82) [59] O21aAVAO23a 94.82 (98.01) [59]
O23bAVANAn 177.01 O23aAVAO 172.48
O23aAVAO21b 85.11 (86.82) [59] O21aAVANAn 93.80
O21aAVAO 89.85 (89.84) [59] OAVANAn 87.94
O23bAVAO 89.08 (89.84) [59] O23aAVANAn 97.65
Dihedral angle ()
O21bAVANAnACBenzen 109.62 O21aAVANAnACBenzen 70.45
O23aAVANAnACBenzen 24.95 OAVANAnACBenzen 160.16
O23bAVAO21aAC14a 84.32 O23aAVAO21bAC14b 56.87
NAnAVAO21bAC14b 154.79 NAnAVAO23aAC4a 92.16
OAVAO21aAC14a 173.41 OAVAO21bAC14b 117.27
Charges
V 0.558 O23a 0.490 O 0.317 O22a 0.357
O21a 0.461 O21b 0.489 NAn 0.154 O22b 0.366
O23b 0.496
Total energy/au 551.42668
Total dipole moment/D 32.48

Table 10
Equilibrium geometric parameters bond lengths (), bond angles () and charge density of [VO(CIP)2(DMF)]2+ by using DFT/B3LYP/Cep-31G.

Bond length ()
VAO23b 1.939 (1.93) [58] C14bAO21b 1.266
VAO21b 1.895 (1.93) [58] C14bAO22b 1.326
VAO23a 1.941 (1.93) [58] C4bAO23b 1.316
VAO21a 1.891 (1.93) [58] C14aAO21a 1.278
VAO 1.713 (1.57) [58] C14aAO22a 1.327
VAODMF 1.882 (1.95) [60] C4aAO23a 1.363
Bond angle ()
O21bAVAO23b 91.46 (97.23) [59] O21bAVAODMF 91.46
O23aAVAO23b 81.43 (89.84) [59] O21bAVAO 101.31 (89.84) [59]
O21aAVAO23b 79.97 (86.82) [59] O21aAVAO23a 97.03 (98.01) [59]
O23bAVAODMF 81.68 O23aAVAO 84.95 (89.84) [59]
O23aAVAO21b 84.55 (86.82) [59] O21aAVAODMF 84.37
O21aAVAO 87.75 (89.84) [59] OAVAODMF 112.51
O23bAVAO 160.35 O23aAVAODMF 162.54
Dihedral angle ()
O21bAVAO23aAC4a 156.89 O21aAVAO23bAC4b 155.23
O23bAVAO23aAC4a 64.59 O23aAVAO23bAC4b 105.99
O23bAVAO21aAC14a 62.53 O23aAVAO21bAC14b 111.79
ODMFAVAO21bAC14b 51.16 ODMFAVAO23aAC4a 79.49
OAVAO21aAC14a 102.07 OAVAO21bAC14b 164.48
Charges
V 0.468 O23a 0.409 O 0.378 O22a 0.356
O21a 0.379 O21b 0.395 ODMF 0.458 O22b 0.358
O23b 0.413
Total energy/au 550.5071
Total dipole moment/D 36.54

1.845 and 1.847 , respectively, are shorter than VAO23a and the benzene ring of aniline not linear with VANAn and parallel
VAO23b 1.851 and 1.856 , respectively, and the bond distance to one molecule of ciprooxacin at which the dihedral angle
between VANAn is 1.938 [57]. Also the angles around the central CbenzeneANAnAVAO23a is 24.95 and the benzene ring of aniline
metal ion V(IV) with surrounding oxygen atoms and nitrogen atom molecule is lying in outside respect to the oxygen atom of
of aniline vary from 85.11 to 97.65; these values not differ largely VO-ion, the dihedral angle CbenzeneANAnAVAO23a is 160.17.
from these expected for a regular octahedron. The distances and The difference between the average total energy of trans and cis
angles in the quinolone ring system are similar to those found in isomers is 7.42 au and the obtained trans-isomer is trans Oc isomer
reported structure of free ciprooxacin and ciprooxacin com- is more stable since it exhibit the lowest energy as shown in
pounds [26]. The angle between VANAnACbenzene is 112.10 so Scheme 3. For the trans Oc model with the lowest energy and
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 533

Fig. 9. Optimized geometrical structure of trans-isomer of [VO(CIP)2DMF]2+ complex by using B3LYP/CEP-31G.

Fig. 10. Optimized geometrical structure of trans-isomer of [VO(CIP)2Py]2+ complex by using B3LYP/CEP-31G.

making corrections of geometry by minimizing the energy of respectively, and charges on nitrogen atom of aniline molecule is
complex once again, the structure of the predicted most stable 0.154 as shown in Table 9.
isomer a trans Oc isomer has been obtained as shown in Fig. 8.
The energy of the most stable trans-isomer of this complex is
Description of the structure of [VO(CIP)2DMF]2+
551.427 au while the dipole moment is greater 32.48D while,
The two isomers of this complex employed in the theoretical
the dipole moment of the cis-isomer of this complex is 14.32D,
calculations. The total energy for the two enantiomers is obtained
so the cis-isomer of this complex is less stable than trans-isomer.
by using density functional theory combined with B3LYP/CEP-31G
The charge accumulated on V(IV) in this complex is 0.558 while
as basis set. The difference between the average total energy of
the charges over donating ketonic oxygen atoms O23a and O23b
trans and cis-isomers is 11.498 au with the trans enantiomer
are 0.490 and 0.496, respectively, while the charges over car-
more stable since it exhibit the lowest energy. The energy of
boxylic oxygen atoms O21a and O21b are 0.461 and 0.489,
the trans form is more negative than other complex 550.5071
534 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

Table 11
Equilibrium geometric parameters bond lengths (), bond angles () and charge density of [VO(CIP)2(Py)]2+ by using DFT/B3LYP/Cep-31G.

Bond length ()
VAO23b 1.861 (1.93) [58] C14bAO21b 1.350
VAO21b 1.849 (1.93) [58] C14bAO22b 1.210
VAO23a 1.851 (1.93) [58] C4bAO23b 1.212
VAO21a 1.843 (1.93) [58] C14aAO21a 1.350
VAO 1.790 (1.57) [58] C14aAO22a 1.210
VANPy 1.929 (2.07) [65] C4aAO23a 1.210
Bond angle ()
O21bAVAO23b 91.88 (97.23) [59] O21bAVANPy 175.99
O23aAVAO23b 88.44 (89.84) [59] O21bAVAO 87.43 (89.84) [59]
O21aAVAO23b 177.62 O21aAVAO23a 93.86 (98.01) [59]
O23bAVANPy 90.57 O23aAVAO 170.11 (172.70) [62]
O23aAVAO21b 83.59 (86.82) [59] O21aAVANPy 89.95
O21aAVAO 89.93 (89.84) [59] OAVANPy 95.83
O23bAVAO 87.70 (89.84) [59] O23aAVANPy 93.32
Dihedral angle ()
O21aAVAO21bAO14b 149.72 O23aAVAO21bAC14b 55.58
O21aAVAO23aAO4a 0.66 O21bAVAO23aAC4a 86.61
O23bAVAO21aAC14a 169.16 O23aAVAO23bAC4b 58.09
NPyAVAO23aAC4a 90.84 NPyAVAO21aAC14a 88.13
OAVAO21aAC14a 176.04 OAVAO21bAC14b 120.25
Charges
V 0.696 O23a 0.369 O O22a 0.488
O21a 0.459 O21b 0.487 NPy 0.483 O22b 0.521
0.228 O23b 0.380
Total energy/au 544.5512
Total dipole moment/D 26.11

Fig. 11. Optimized geometrical structure of trans-isomer of [VO(CIP)2Et3N]2+ complex by using B3LYP/CEP-31G.

au and highly dipole 36.54D. The structure of the predicted most molecule. The VAO21b and VAO21a bond lengths are (1.895 and
stable isomer a transOc isomer has been obtained as shown in 1.891 , respectively) are shorter than that VAO23b and VAO23a
Fig. 8, the bond angle between O23aVODMF is 162.54 and also (1.939 and 1.941 , respectively) and the bond distance between
the angle between O23bVO is 160.35 so the two ciprooxacin VAODMF is 1.882 [59,60]. Also the angles around the central
molecules are not lying in the same plane they are perpendicular metal ion V(IV) with surrounding oxygen atoms vary from 79.97
respect to each other with angle equal 90 at which the angles to 101.31; these values agree with these expected for a distorted
between O23bVO21a and O23bVO23a are 79.97 and 81.43, octahedron.
respectively. The charge accumulated on Ocarboxylate (O21a and O21b) are
Table 10 lists selected inter atomic distances and angles. The 0.395 and 0.379, respectively, and Oketo (O23a and O23b) are
structure of complex with atomic numbering scheme is shown in 0.409 and 0.413, respectively, and the charge accumulated on
Fig. 9. The complex consists of two units of ciprooxacin molecule V(IV) is 0.468 while, the charge on ODMF is 0.458.
and one DMF molecule with metal ion VO ion. The complex is six-
coordinate with distorted octahedral environment around the Description of the structure of [VO(CIP)2Py]2+
metal ion. The metal ion V(IV) of VO is coordinated to one Oketo The V(IV) chelated with two molecules of ciprooxacin through
atom and one Ocarboxylate atom of ciprooxacin ligand and DMF four coordinate bonds (Oketo and Ocarboxylic atoms) from each
W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536 535

Table 12
Equilibrium geometric parameters bond lengths (), bond angles () and charge density of [VO(CIP)2(Et3N)]2+ by using DFT/B3LYP/Cep-31G.

Bond length ()
VAO23b 1.880 (1.93) [58] C14bAO21b 1.350
VAO21b 1.850 (1.93) [58] C14bAO22b 1.210
VAO23a 1.860 (1.93) [58] C4bAO23b 1.210
VAO21a 1.851 (1.93) [58] C14aAO21a 1.350
VAO 1.790 (1.57) [58] C14aAO22a 1.210
VANTEA 1.980 (2.10) [66] C4aAO23a 1.210
Bond angle ()
O21bAVAO23b 90.69 (97.23) [59] O21bAVANTEA 92.61
O23aAVAO23b 78.32 (89.84) [59] O21bAVAO 82.91 (89.84) [59]
O21aAVAO23b 79.08 O21aAVAO23a 94.39 (98.01) [59]
O23bAVANTEA 176.64 O23aAVAO 156.25 (172.70) [62]
O23aAVAO21b 90.86 (86.82) [59] O21aAVANTEA 97.56
O21aAVAO 87.69 (89.84) [59] OAVANTEA 100.91
O23bAVAO 78.87 (89.84) [59] O23aAVANTEA 102.26
Dihedral angle ()
O21aAVAO21bAO14b 64.67 O23aAVAO21bAC14b 49.81
O21aAVAO23aAO4a 7.76 O21bAVAO23aAC4a 160.66
O23bAVAO21aAC14a 66.19 O23aAVAO23bAC4b 66.49
NTEAAVAO23aAC4a 160.94 NTEAAVAO21aAC14a 113.99
OAVAO21aAC14a 145.30 OAVAO21bAC14b 107.21
Charges
V 0.578 O23a 0.303 O O22a 0.486
O21a 0.467 O21b 0.498 NTEA 0.465 O22b 0.384
0.072 O23b 0.516
Total energy/au 539.7426
Total dipole moment/D 39.86

molecule. The experimental data set that the result complex is six- exhibit the lowest energy value and the lowest energy model
coordinate so, the complex consists of four coordinate bonds with structure found for the trans-isomer is present in Fig. 11.
two ciprooxacin molecules and one coordinated bond with pyri- Table 12 lists selected inter atomic distances and angles. The
dine molecule beside oxygen atom of VO ion. The difference structure of complex with atomic numbering scheme is shown in
between the average total energy of trans and cis-isomers is Fig. 11. The complex consists of two units of ciprooxacin molecule
68.689 au with the trans enantiomer more stable since it exhibit and one water molecule with metal ion VO ion. The complex is
the lowest energy. The energy of the trans form is more negative than six-coordinate with distorted octahedral environment around the
other complex 544.551 au and highly dipole 26.54D. The structure metal ion. The V(IV) of is coordinated to one Oketo atom and one
of the predicted most stable isomer a transOc isomer has been Ocarboxylate atom of ciprooxacin ligand and nitrogen atom of tri-
obtained as shown in Fig. 10. Table 11 lists selected inter atomic dis- ethyl amine molecule. The VAO21a and VAO21b bond lengths
tances and angles. The structure of complex with atomic numbering are 1.851 and 1.85 , respectively, are shorter than that VAO23a
scheme is shown in Fig. 10. The complex consists of two units of cip- and VAO23b 1.86 and 1.88 , respectively, and the bond distance
rooxacin molecule and one pyridine molecule with metal ion VO between VAOEt3N is 1.98 [65]. Also the angles around the central
ion. The complex is six-coordinate with a regular octahedral envi- metal ion V(IV) with surrounding oxygen atoms vary from 78.32
ronment around the metal ion. The angles around center metal ion to 100.91; these values agree with these expected for a distorted
varied between 87.70 and 95.83, also the angles between octahedron. The triethyl amine molecule occupies a cis position
O23bVO21a and O21bVNpy are 177.62 and 175.99, respectively, with respect to the V@O, in accordance with the experimental
and the angle OVO23a is 170.11 [62], these values agree nicely with results and as in similar in vanadyl complexes [63,64]. The trans
a regular octahedral structure [59]. The V(IV) of is coordinated to one isomer is more stable and present as trans Oc as shown in
Oketo atom and one Ocarboxylate atom of ciprooxacin ligand and nitro- Scheme 2.
gen atom of pyridine ring. The VAO21a and VAO21b bond lengths The charge on V(IV) in this complex is 0.578 and on nitrogen
are (1.84 and 1.85 , respectively) are shorter than that VAO23a atom of Et3N is 0.072 while, on the oxygen atoms around the cen-
and VAO23b (1.85 and 1.86 , respectively) and the bond distance tral metal ion O21a, O21b, O23a and O23b are 0.467, 0.498,
between VANpy is 1.92 [61]. The pyridine ring occupies a cis posi- 0.303 and 0.516, respectively, and the charge on oxygen atom
tion with respect to the V@O, in accordance with the experimental of VO is 0.465 as shown in Table 12.
results and as in similar in vanadyl complexes [63,64]. The resultant
model of [VO(CIP)2 Py]2+ isomer is trans-isomer present as trans Oc
Conclusions
as shown in Scheme 2.
The charge accumulated on V(IV) in this complex is 0.696 while
The synthesis and characterization of four complexes of the sec-
the charge on atoms around metal ion O21a, O21b, O23a, O23b are
ond-generation quinolone antibacterial drug ciprooxacin with
0.487, 0.459, 0.369 and 0.380, respectively, while the charge
V(IV) has been achieved with physicochemical and spectroscopic
on oxygen atom of VO is 0.483 and charge on NPyridine is 0.228
methods. In the resultant complexes, ciprooxacin is bound to the
as shown in Table 11.
V(IV) via the carboxylato and ketone oxygen. The V(IV) is six-coordi-
nate with a distorted octahedral geometry. The lowest energy model
Description of the structure of [VO(CIP)2Et3N]2+ structure of each complex has been proposed with molecular mod-
The energy of the isomers is almost equal as expected [65] and eling calculated. The aniline complex [VO(CIP)2An]SO49H2O is more
since the energy difference is very low (1.54 au), it is difcult to dis- stable than other studied complexes for some reasons (i) Bonds
tinguish between trans or cis isomers. Nevertheless, the trans-isomer between V(IV) with surrounded oxygen atoms are slightly shorter
536 W.A. Zordok / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 519536

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