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Computational approach on architecture and tailoring of organic metal complexes derived from streptomycin and Zn Cd and Pb antimicrobial effectiveness.

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Full Paper
Received: 23 April 2011
Revised: 2 August 2011
Accepted: 2 August 2011
Published online in Wiley Online Library: 7 September 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1838
Computational approach on architecture and
tailoring of organic metal complexes derived
from streptomycin and Zn, Cd and Pb:
antimicrobial effectiveness
Kumar Rajiva,b∗ and Johar Rajnic
Streptomycin has been used to derive organic metal complexes (OMCs) after metallation with ZnCl2 , CdCl2 and PbCl2 and
characterized by elemental analysis, electronic and vibrational spectroscopy, 1 H and 13 C NMR, mass spectroscopy (time-of-flight
MS), magnetic measurement, thermal decomposition analysis (TGA, DTA), molecular modeling and X-ray powder diffraction.
OMCs are monomeric. Crystal system, lattice parameters, unit cell, particle size and volume of crystalline OMCs have been
determined using X-ray powder diffraction pattern analysis. The geometries of complexes were optimized on the basis of
molecular modeling. Kinetic parameters were computed from thermal analysis, confirming first-order kinetics. Molecular models
have been optimized by MM2 calculations. Architecture and tailoring of the rationally designed and synthesized supramolecular
models having covalent bonded oxygen or other molecular contacts extended through Huckel Charge Distribution in highest
c 2011 John Wiley &
occupied molecular orbit (HOMO). Antimicrobial effectiveness of OMCs has been reported. Copyright Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: streptomycin; organic metal complexes (OMCs); thermal decomposition; molecular modeling; XRPD
Introduction
Experimental
Streptomycin, a well-known antibiotic, possesses the property of inhibiting the growth and even destroying microorganisms. Interaction between such drugs and metal ion(s)
has been utilized as a new methodology in design and formation of new class of organometallic complexes.[1,2] Pharmacological activity of such drugs and complexes, in many
cases, is strictly interaction dependent. Because of this, bioorganometallic chemistry and the design of new organometallic
complexes having higher antimicrobial effectiveness are gaining interest. However, synthesis and characterization of such
complexes with streptomycin have not yet been investigated,
except for a neutral Cu(II) complex with Cu–O–bond.[3] Furthermore, there is no consensus in the literature on the
use of streptomycin as a ligand; in particular, for the formation of organometallic complexes with metal–ligand binding
sites.
The molecular architecture is a determining factor that controls
many of the physical properties of ligands and associated
organic metal complexes (OMCs). In order to develop efficient
devices having conductance, sensing and other important
medicinal properties simultaneously, advanced organic synthetic
protocols for a both better architectured formulation and for
medicinal development are in demand. To ascertain metal
binding sites in streptomycin with Zn, Cd and Pb metal ion(s)
(Fig. 1) through solvent accessible surface model (Fig. 2) based
on spectral characterization and molecular modeling of ligand
and derived organometallic complexes (OMCs) are described
herein.
Materials and Instruments
∗
Correspondence to: Kumar Rajiv, Department of Chemistry, University of Delhi,
Delhi 110007, India. E-mail: chemistry rajiv@hotmail.com
This article is dedicated to Prof. David A. Atwood, Editor-in-Chief, Main Group
Chemistry, Department of Chemistry, University of Kentucky, Lexington, KY,
USA, who has inspired the authors to do this research article.
a Department of Chemistry, University of Delhi, Delhi 110007, India
b Department of Chemistry, SC, University of Delhi, New Delhi 110027, India
c Department of Chemistry, Guru Gobind Singh Indraprastha University, New
Delhi 110002, India
c 2011 John Wiley & Sons, Ltd.
Copyright 791
Appl. Organometal. Chem. 2011, 25, 791–798
All chemicals and solvent used in this study were of analytical
reagent grade and used as procured from Aldrich after drying
over 4 Å molecular sieves. Solvents were purified using standard
procedures.[4]
The stoichiometric analysis (C, H and N) of OMCs was
performed using a Carlo-Ebra 1106 elemental analyzer. Metal
content was estimated on a AA-640-13 Shimadzu flame atomic
absorption spectrometer in a solution prepared by decomposing
the respective complex in hot concentrated HNO3 . IR spectra
were recorded on a PerkinElmer Fourier transform infrered (FTIR)
spectrometer in KBr. The electronic spectra were recorded in
water on a Beckman DU-64 spectrometer with quartz cells. 1 H
and 13 C NMR spectra were recorded at ambient temperatures on
Bruker AMX400 and DRX500 spectrometers with tetramethylsilane
K. Rajiv and J. Rajni
The solution was cooled to room temperature and closed with a
semi-permeable membrane so that methanol could not evaporate
but still maintaining a very slow evaporation. The mixtures were
stored at room temperature for a period of 3–5 weeks. Very small
crystals were filtered off and dried.
Pharmacology: In Vitro Antifungal Assay
Antimicrobial activities (antifungal) of drug along with OMC-1
to OMC-3 were screened against Aspergillus niger by preparing
their stock solutions in DMSO according to the required concentrations for the experiments. To ensure the effect of solvent on
bacterial growth, a control test was performed with test medium
supplemented with DMSO.
Growth of fungus was measured by reading the diameter of
the fungal colony. Screening for antifungal activity was carried
out in vitro against Aspergillus niger, following the procedure
outlined,[5] and relative inhibitory ratios (%) were determined
using the mycelium growth rate method. On completion of
mycelial growth, diameters were measured and inhibition rate
was calculated according to the formula
I=
Figure 1. Stereo-structure of streptomycin ligand.
(DI − Do )
DI
× 100
where I is inhibition rate, DI is average diameter of mycelia in the
blank test and Do is average diameter of mycelia in the presence
of OMC-1 to OMC-3.
X-ray Powder Diffraction (XRPD) Measurements
XRPD patterns were recorded on a vertical-type Philips 1130/00
X-ray diffractometer, operated at 40 kV and 50 mA generator
using a Cu-Kα line at radiation 1.54 source. The sample was
scanned between 5◦ and 70◦ (2θ ) at 25 ◦ C. Crystallographic data
were analyzed using the Crysfire-2000 powder indexing software
package and the space group was found using the CHECK CELL
program. The Debye–Scherer relation was derived with the help
of 100% peak width to determine the particle size. Experimental
density was observed by the Archimedes method.
3D Molecular Modeling
Figure 2. Solvent-accessible surface model of streptomycin.
792
(TMS) as internal reference and D2 O as solvent. Chemical shifts
(δ) were expressed in parts per million (ppm) relative to TMS.
A Rigaku model 8150 thermoanalyzer (Thermaflex) was used for
simultaneous recording of TGA–DTA curves at a heating rate of
10 ◦ C min−1 . For TGA, the instrument was calibrated using calcium
oxalate, whereas for DTA calibration was done using indium metal,
both of which were supplied along with the instrument. A flatbed aluminium crucible was used with α-alumina (99% pure)
as the reference material for DTA. The activation energy and
Arrhenius constant of the degradation process were obtained by
Coats–Redfern method.
The crystals needed for X-ray powder diffraction analysis were
used to produce three-dimensional crystalline models as follows:
1 g bismuth OMC was dissolved at 40 ◦ C in a minimum amount of
methanol. A clear solution was obtained and heated for 4–5 min
under reflux and was then filtered off at a high temperature.
wileyonlinelibrary.com/journal/aoc
The correct sequence of atoms was obtained to obtain reasonable
low-energy molecular models to determine their molecular
representation in three dimensions. Complications of molecular
transformations could be explored using the output obtained. To
gain a better insight into the molecular structure of the ligand and
OMCs, geometric optimization and conformational analysis were
performed using an MM+2 force field.[6]
The potential energy of the molecule was the sum of the
following terms: E = Estr + Eang + Etor + Evdw + Eoop + Eele , where
all Es represent energy values found corresponding to given types
of interaction. The subscripts str, ang, tor, vdw, oop and ele
denote bond stretching, angular bonding, torsion deformation,
van der Waals interactions, out-of-plane bending and electronic
interaction, respectively.
Preparation of OMCs
ZnCl2 (OMC-1)
OMC of ZnCl2 was prepared by dissolving equimolar amounts of
streptomycin (0.2905 g, 0.5 mmol) and ZnCl2 (0.068 g, 0.5 mmol) in
c 2011 John Wiley & Sons, Ltd.
Copyright Appl. Organometal. Chem. 2011, 25, 791–798
Organic metal complexes derived from streptomycin and Zn, Cd and Pb
Table 1. Analytical data (%) of OMCs
Analysis: found (calculated) (%)
OMC
Empirical formula
C
H
N
M
C21 H41 N7 O14 Zn
37.13 (37.03)
6.11 (6.07)
14.41 (14.40)
9.60 (9.60)
C21 H41 N7 O14 Cd
34.61 (34.65)
5.65 (5.68)
13.46 (13.47)
15.42 (15.44)
C21 H41 N7 O14 Pb
30.61 (30.65)
5.11 (5.02)
11.91 (11.92)
25.17 (25.18)
a minimum quantity of CH3 OH (25 mL, absolute) in a 100 mL roundbottomed flask. The mixture was heated for 5 h at ∼81–82 ◦ C on
a water bath to reduce the volume of the solution to ∼12 mL. A
solid mass was separated out on cooling at ∼5 ◦ C and kept in a
refrigerator for better crystallization. It was then filtered, washed
with CH3 OH, and dried over P2 O5 under vacuum. The crystals were
redissolved for recrystallization with warm methanol, resulting in
a clear solution; this was kept undistributed for several weeks
and very small crystals were formed. Various attempts to obtain
single crystals were unsuccessful. XRPD studies indicated the
crystalline nature of the OMCs. The compounds were soluble in
polar solvents.
Infrared Spectra
[Zn(L)(H2 O)2 ]
OMC-1
[Cd(L)(H2 O)2 ]
OMC-2
[Pb(L)(H2 O)2 ]
OMC-3
CdCl2 (OMC-2)
The procedure used for OMC-1 was employed for OMC-2 with
equimolar amounts of streptomycin (0.2905 g, 0.5 mmol) and
CdCl2 (0.092 g, 0.5 mmol).
PbCl2 (OMC-3)
The procedure used for OMC-1 was employed for OMC-3 with
equimolar amounts of streptomycin (0.2905 g, 0.5 mmol) and
PbCl2 (0.139 g, 0.5 mmol).
Results and Discussion
Appl. Organometal. Chem. 2011, 25, 791–798
1 H NMR Spectra
The proton NMR spectra of streptomycin and its diamagnetic
OMCs were recorded in D2 O using TMS as internal standard and
showed well-resolved signals in accordance with their related
resonance and integrated intensities. The chemical shifts of ligand
protons and its diamagnetic OMCs are discussed comparatively.
On comparison, it was concluded that certainly there were some
changes in observed regions of hydroxyl (OH) groups due to
deprotonation. The formation of new bonds (–O–M) between
ligand moiety and metal used was compared.[8] The OH signal
for two protons (O22,38 –H) at δ 2.2 ppm as singlet in the ligand
spectrum completely disappeared in the spectra of OMCs, which
indicated involvement of OH groups in chelation with ZnCl2 , CdCl2
and PbCl2 , followed by displacement of protons. Another new
signal observed at 3.33 ppm in 1 H NMR spectra of diamagnetic
OMCs was absent in 1 H NMR spectra of streptomycin, with an
integration corresponding to four protons assigned to two water
molecules.
1 H NMR of streptomycin (D O): δ 9.72 (s, 1H, OC –H), 5.4 (d,
2
21
1H, J = 9.1 Hz, C10 –H), 5.03 (d, 1H, J = 6.8 Hz, C18 –H), 4.4 (d, 1H,
c 2011 John Wiley & Sons, Ltd.
Copyright wileyonlinelibrary.com/journal/aoc
793
Satisfactory results of elemental analysis have been obtained and
are summarized in Table 1. Their chemical composition confirmed
the purity and stoichiometry of neat and encapsulated OMCs.
Loss of water or other molecules after oligomerization and
polymerization affected the final accuracy of C, H and N analytical
results. In our study all elemental analytical results were linear
without deviation as per oligomerization and polymerization.
Further mass spectra of OMCs supported the same. These studies
revealed that OMC-1, 2, and 3 were of high purity and monomeric in
nature. Various attempts to obtain single crystals have so far been
unsuccessful. XRPD studies of OMCs indicated their crystalline
nature. OMCs were soluble in polar solvents.
The thermal decomposition analysis of OMCs proved the
elimination of two H2 O molecules. In the case of polymerization,
two or more ligands or OMC moieties changed the ratio of water
elimination and the ratio of atoms concerned, i.e. O and H would
differ significantly from the values obtained. Mass spectral findings
further correspond to the monomeric composition nature of OMCs.
Thus the molecular formula of OMCs is [ML(H2 O)2 ], where M = Zn,
Cd or Pb, and L = streptomycin. On the basis of the above findings,
it can be clearly stated that the reported molecular formula and
the presented molecular models are in accordance.
IR spectra of complexes were recorded as KBr disks. In the IR
spectrum of streptomycin, medium to strong absorption bands
were observed at 1750–1050 cm−1 and 1042 cm−1 , indicating
the presence of <C O and –C–O–C–groups. The stretching
frequencies of –OH groups were observed at 3434 cm−1 and
3368 cm−1 in the form of broad vibration bands with a shoulder at
about 3550 cm−1 . Very strong stretching vibration bands appeared
in the IR spectra of streptomycin at 3435–3429 cm−1 , showing the
presence of –NH2 . The same bands appeared for studied OMCs at
the same wave number, ruling out the participation of nitrogen
atoms in coordination.
The conclusion has been drawn that oxygen of the –OH group is
involved in the coordination with metals after comparing the IR of
streptomycin and OMCs. The vibrational bands due to rocking
and wagging modes of water and metal–oxygen stretching
modes were observed at 800–350 cm−1 for OMCs and confirmed
coordinated water molecules.[7] New stretching vibrational bands
of OMCs were observed at 516–315 cm−1 in the far IR region due
to ν(M–O), indicating involvement of oxygen of the –OH group
in new bonds to the metals (–O–M–). The presence of water
molecules was confirmed by the appearance of an intense broad
band centered at 3400 cm−1 in OMCs. IR spectra of OMCs were
complicated and suggestions were made regarding the structural
features of OMCs. Related infrared spectral data are presented in
Table 2.
K. Rajiv and J. Rajni
Table 2. Assignment of relevant IR absorption bands of OMCs
OMCs
ν(<N–H)
ν(OH)
ν(OH)
ν(NH2 )
ν(NH2 )
ν(M–O)
ν(Ph–O–H)
[Zn(L)(H2 O)2 ]
OMC-1
[Cd(L)(H2 O)2 ]
OMC-2
[Pb(L)(H2 O)2 ]
OMC-3
3429 (s, b)
3434, 3368, 1635 (m)
1515 (s)
1215 (m)
695 (s)
516 (s)
1750, 1050
3435 (s, b)
3445, 3419, 1646 (m)
1509 (m)
1217 (w)
696 (s)
514 (s), 420, 365
1745, 1045
3429 (s, b)
3446, 3420, 1622 (m)
1479 (s)
1216 (w)
698 (s)
425 (s), 350, 315
1746, 1042
C9 –H), 4.14–4.20 (m, 2H, C3,12 –H), 3.95 (d, 2H, J = 7 Hz C37 –H),
3.86 (m, 1H, J = 4.5 Hz, C6 –H), 3.88 (m, 1H, J = 6.9 Hz, C14 –H),
3.81 (d, 1H, J = 6.9 Hz, C17 –H), 3.52–3.55 (m, 1H, C2 –H), 3.51 (d,
1H, J = 6.8 Hz, C15 –H), 3.57 (t, 1H, J = 10.2 Hz, C5 –H), 3.53 (m, 1H,
J = 6.1 Hz, C16 –H), 3.57 (m, 1H, J = 7.1 Hz, C4 –H), 2.52–2.58 (m,
1H, C1 –H), 2.10–2.75 (bs, 9H, NH or NH2 , N28,29,32,33,34 –H), 2.55 (s,
3H, C39 –H), 2.4 (s, 2H, O25,35 –H), 2.3 (s, 2H, O23,24 –H), 2.2 (s, 2H,
O22,38 –H), 2.18 (s, 1H, O36 –H), 1,25 (d, 3H, J = 7 Hz, C20 – H).
From the data obtained it was clear that chemical shifts of protonated species were very similar to those of metallic derivatives,
suggesting similar structure and conformation. Change observed
in the region δ 2.2 ppm indicated interaction of streptomycin with
metal ions in competition with protonation in solution.
13
C NMR Spectrum of OMCs
In 13 C NMR spectra of streptomycin and OMCs, well-resolved signals were detected. A group of sharp peaks at 165.39–160.11 ppm
were found, confirming the presence of carbon atoms within
azomethine linkages ( C–N> and –N C>). A group of
sharp peaks was also observed at 76.22–65.12 ppm and
44.12–40.33 ppm corresponding to ether (–O–CH2 –) and central methylene (–CH2 –) linkages respectively.[9,10] Another group
of peaks observed was as follows. 13 C NMR (D2 O, ppm): 165–C31 ,
160–C27 , 98–C8 , 95–C10 , 43.9–C6 , 42–C2 , 68.5–C4 , 63.2–C37 ,
65–C5 , 31.6–C39 , 54.0–C17 , 70.8–C16 , 65.8–C15 , 63.1–C1 , 12–C20 ,
62.6–C18 , 61–C3 , 72.5–C14 , 90–C21 , 65–C12 and 75–C9 .
Electronic Spectra
794
Electronic spectra of ligand and OMCs showed transitions at
190–800 nm. A shoulder band was observed at 275 nm in the
spectrum of ligand assigned to n → n∗ transition within –OH group
of hydroxyl moiety in free ligand. A little deviation observed in
OMCs for these transitions appeared for –OH groups in the spectra
of free ligand. It revealed that the involvement of –OH groups in
chelation due to deprotonation confirmed the formation of new
oxygen–metal (–O–M–) bond. Owing to this, new transitions
were observed at 240–280 nm assigned to –O–M(II) as assigned
ligand-to-metal charge transfer (LMCT).[11]
The spectrum is featureless in the visible region, for d10 Cd(II)
ion; however, this complex showed some intense absorptions
in UV, readily assignable to –O–Cd(II) as LMCT.[12] The intensity
of Cd–O–absorption in other isolated sites has been shown
at 240 nm to be roughly consistent with new bond formation
(Cd–O–).[13] Magnetic measurements suggested OMCs of Zn(II),
Cd(II)and Pb(II) to be diamagnetic in nature. On the basis of the
above discussion, the proposed molecular structure for OMCs
(Fig. 3) clears its tetrahedral geometry.
wileyonlinelibrary.com/journal/aoc
Figure 3. Stereo-structure of OMCs (M = Zn, Cd, Pb).
Thermal Decomposition and Kinetics
TGA was used to determine rate-dependent parameters of solid
state non-isothermal decomposition reactions. TGA and DTA
analyses were carried out for OMCs under ambient conditions.
TGA revealed that OMC of Zn(II) lost nearly 15% of total mass
between 65 and 140 ◦ C, followed by considerable decomposition
up to 600 ◦ C, leaving metal oxide (ZnO) as residue. OMCs of
Cd(II) and Pb(II) decomposed to nearly 9% of total mass up to a
temperature of 170 ◦ C, followed by considerable decomposition
of ligand molecule up to 650 ◦ C, leaving metal oxide (CdO and PbO
respectively) as residue. On the basis of thermal decomposition,
the kinetic analysis parameters such as activation energy (E ∗ ),
enthalpy of activation (H∗ ), entropy of activation (S∗ ), and free
energy change of decomposition (G∗ ) were evaluated graphically
by employing the Coats–Redfern relation:[14,15]
log[− log(1 − α)/T 2 ] = log[AR/θ E ∗ (1 − 2RT/E ∗ )] − E ∗ /2.303RT
(1)
where α is mass lost up to temperature T, R is the gas constant,
E ∗ is activation energy in J mol−1 , θ is linear heating rate and the
term (1 − 2RT/E ∗ ) ∼
= 1.
A straight-line plot of the left-hand side of the equation (1) against 1/T gives the value of E ∗ , while its intercept corresponds to A (Arrhenius constant). Coats–Redfern linearization
c 2011 John Wiley & Sons, Ltd.
Copyright Appl. Organometal. Chem. 2011, 25, 791–798
Organic metal complexes derived from streptomycin and Zn, Cd and Pb
Table 3. Thermodynamic activation parameters of OMCs
OMCs
[Zn(L)(H2 O)2 ]
OMC-1
[Cd(L)(H2 O)2 ]
OMC-2
[Pb(L)(H2 O)2 ]
OMC-3
Order/n
Steps
E∗ (J mol−1 )
A (s−1 )
S∗ (J K−1 mol−1 )
1
I
II
I
II
I
II
34.09
39.75
9.814
6.76
39.18
67.82
8.27 × 105
2.16 × 105
2.501 × 105
1.71 × 104
2.28 × 106
1.42 × 106
−25.096
−146.69
−1.641
−1.611
−11.083
−12.431
1
1
plots confirmed the first-order kinetics for the decomposition
process. The calculated values of thermodynamic activation parameters for decomposition steps of OMCs have been reported in
Table 3.
According to the kinetic data obtained from TG curves,
activation energy is related to thermal stability of OMCs. Among
metal complexes, activation energy increases as OMC-2 < OMC-1
and OMC-3, and the same trends have been obtained for thermal
stability curves of OMCs.[16] All these OMCs have negative entropy,
which clearly indicates spontaneous formation of these complexes.
The negative value of entropy indicated a more ordered
activated state that may be possible through chemisorption of
oxygen and other decomposition products. The negative values
of entropy of activation were compensated by values of enthalpies
of activation, leading to almost the same values for free energy of
activation.
Time-of-Flight (TOF) Mass Spectra
Appl. Organometal. Chem. 2011, 25, 791–798
84.10
1205.89
218.76
52.691
709.35
25.1077
G∗ (kJ mol−1 )
96.62
106.53
5.801
2.348
3.566
10.547
corresponding to metals, i.e. Cd(II) and Pb(II) with ligand fragments.
On the basis of the above discussion, a mononuclear nature of
studied OMCs has been proved and may be assigned as [M+
(ligand fragments)].
In the mass spectra of OMC-2 and OMC-3, molecular ion peaks
(ligand + metal) were observed at 730.1101 and 824.4311 (m/z)
respectively, which represented the final molecular ion peak (m/z)
for reported compounds. (Scanned graphs of TOF mass spectra
of OMC-2 and OMC-3 were added and are presented as online
supporting information in supplementary graphs S-1 and S-2
respectively).
XRPD Analysis
XRPD is a powerful technique in structural determination of
molecular solids. While single crystal methodologies (direct
methods and Patterson synthesis) have proved successful in
solving structures from XRPD data, the systematic or accidental
overlap of diffraction peaks leads to inevitable problems in
attempting to extract intensities of individual reflections.
In the absence of single crystals, XRPD data are especially
useful and are used to deduce accurate cell parameters of studied
solid compounds. The diffraction patterns revealed the crystalline
nature of OMCs. The indexing procedure was performed using
(CCP4 , UK) the Crysfire program,[18,19] giving different crystal
systems with varying space group. Merit of fitness and particle
size of OMCs have been calculated from XRPD spectra of OMC-2
(scanned graph given in supplementary graph S-3 for Cd(II)SM. The cell dimensions and other related parameters of OMCs
obtained are shown in Table 4.
Molecular Modeling of OMCs
It is good to see simple mechanical models presented here.
The current models, therefore, are proposed as a standard
by which specific interactions in real molecules might be
judged. If deviations in distances, angles or torsion are in
evidence, then specific electronic interactions should perhaps
be pursued. In order to ascertain structural features and other
related preferences to confirm observed spectral reports about
coordination behavior of streptomycin with metal ion(s) under
study, molecular mechanics calculations have been done for the
same. The energy minimization values for optimized structures of
studied OMCs-1, 2 and 3 were determined and found to be 35.12,
25.31 and 38.24 kcal mol−1 respectively. Selected bond lengths
and bond angles of OMCs between metal ion(s) and –O–atom of
hydroxyl are illustrated in Table 5.
However, the following structural features inspire continued
research: (a) has two hydroxyl groups that may be completely
dependent on certain conditions; (b) these groups may induce
c 2011 John Wiley & Sons, Ltd.
Copyright wileyonlinelibrary.com/journal/aoc
795
MS has been successfully used to investigate molecular ion species
[M]+ and various other peaks corresponding to fragmentation
patterns of OMCs in solution. The patterns of the mass spectrum
give a clear impression of successive degradation of target
compound, with series of peaks corresponding to various
fragments. The intensity of a corresponding peak is directly related
to the stability of corresponding fragments. In the mass spectra of
OMCs, molecular ion peaks corresponding to fragments (ligand or
fragments of the ligand with metal or metal + ligand) have been
observed, which further confirmed their molecular formula.[17]
In initial peaks, it can be easily observed that the ligand
used degraded and broke down into various fragments such
as [C8 H15 NO5 ], showing a molecular ion peak at 196.4797 (m/z
values) with low intensity and many more similar fragments.
Owing to degradation, another fragment pattern appeared at
163.3124/196.4797/206.3986 (m/z) (OMC-1, OMC-3, OMC-2) with
different intensity, and a very strong peak was also observed
at 263/264/284 with 100% intensity separately, which has a
correlation with the fragmentation patterns of streptomycin
(OS) and OMC-3, OMC-1 and OMC-2 respectively. The results
obtained represented the degradation and demetallation patterns
of reported OMCs.
In TOF mass spectra of OMC-2 and OMC-3, initial fragmentation
patterns were found similar to the ligand and also showed an
additional peak indicating mass loss of two water molecules and
degradation of double bonded nitrogen fragments >N–C NH
from parent molecule of streptomycin observed at 690.0010
and 687.7129 (ligand fragments + metal) for these complexes
respectively. Mass degradation patterns provide most important
information about fragmentations of a particular compound in
the studied spectra and proved the presence of an isotropic ratio
H∗ (J mol−1 )
K. Rajiv and J. Rajni
Table 4. Crystallographic data of OMCs
OMC-1
Formula
FW
Temp. (K)
Wavelength
Crystal system
Space group
OMC-2
OMC-3
C21 H41 N7 O14 Zn C21 H41 N7 O14 Cd C21 H41 N7 O14 Pb
679.20
729.17
823.25
293
293
293
1.54056
1.54056
1.54056
Monoclinic
Triclinic
Monoclinic
P 2/M
P1
P 2/M
Unit cell dimensions
a (Å)
14.1937
b (Å)
10.5175
c (Å)
9.26918
α
90.0000
β
110.8413
γ
90.000
Volume (Å 3 )
1293.19
θ range (◦ )
13.811-61.987
Limiting indices
−6 ≤ h ≤ 4
0≤k≤7
0≤l≤4
Particle size (nm)
80.82
Intensity (%)
5.9–100
R indices
0.0000615
Density
1.7437
Z
2
6.709547
9.231634
8.685700
118.1240
97.8563
49.1991
347.14
10-65
−3 ≤ h ≤ 1
−4 ≤ k ≤ 4
0≤l≤4
55.99
4.5–100
0.0000754
1.034
1
12.961
13.184
7.224
90
106.36
90
1184.36
12-67
−7 ≤ h ≤ 5
0≤k≤8
0≤l≤5
10.92
3.4–100
0.0000362
1.151
1
core aggregation via versatile bridging abilities (c) hydroxyl is a
good tool for construction of novel organometallic complexes;
because of this, active groups could bind central metal ion(s) and
form a –O–M–bond, confirming the stability of main group OMCs.
Data analysis for bond lengths and angles of studied compounds
reveals the following remarks.
Selected bond lengths of OMC-1, OMC-2, and OMC-3 between
–O–and metal ion(s) were as follows: O(23)–Zn(39), 1.8896;
O(23)–Cd(39), 2.1200; and O(23)–Pb(39), 2.1102 respectively.
This variation indicates that all the OMCs have different
metal ion(s). The bond angles of OMC-1, OMC-2, and OMC3 metal to donor atom moiety were altered somewhat
upon coordination; bonds angles O(41)–Zn(39)–O(23), 130.888;
O(25)–Cd(39)–O(23), 120.0647; and O(25)-Pb(39)-O(23), 109.4584
respectively.
All active groups taking part in coordination had bonds longer
than that already existing in the ligand (like –O–and <O → M–).
Coordination significantly shortens for O(23)–Zn(39), which was
1.8896, as compared to O(23)–Cd(39), which was 2.1200. This is
because bond lengths between donor atoms and metal ion(s) are
probably affected by variation in the atomic size of metal ion(s).
There was a large variation in bond lengths on complexation. It
becomes slightly longer as coordination takes place via the O atom
of <O → M–.
Taking account of the above factors, in this paper we reported a
novel three-dimensional structure with their topological networks
separately represented by a common molecular structure for
OMCs. The optimized structure of OMC-3 as a molecular modeling
model is presented in Fig. 4. The process to determine energy
minimization was repeated several times to find the global
minimum minimization energy.[20,21] The optimized structures
of OMC-1, OMC-2, and OMC-3 showed respective tetrahedral
geometry.
Pharmaceutical Effectiveness of OMCs
Pharmaceutical effectiveness of OMC-1, OMC-2, and OMC-3
depends on the connectivity of ligand to metal ion(s). Moreover,
coordination reduces polarity of used positively charged metal
ion(s) and negatively charged donor atoms in drug used as ligand.
Antifungal activity of drug formed metal complexes (OMC-1, OMC2 and OMC-3) and was performed by agar plate technique against
Aspergillusniger; results obtained are displayed graphically in Fig. 5.
OMC-1, OMC-2, and OMC-3 were directly mixed in a medium of
different concentrations. The fungus was positioned in medium
with the help of an inoculum needle.[22] Petri dishes wrapped in
polythene sheets containing some drops of C2 H5 OH were placed
in an incubator at 30 ± 3 ◦ C for 70–90 h. Enlargement of the fungal
colony was measured by its diameter.
Table 5. Selected bond lengths (Å) and bond angles (◦ ) of OMCs
OMCs
Selected bond lengths
Selected bond angles
C21 H41 N7 O14 Zn
Zn(39)–O(41)
Zn(39)–O(40)
O(25)–Zn(39)
O(23)–Zn(39)
1.8
1.8
1.8
1.8
C21 H41 N7 O14 Cd
Cd(39)–O(43)
Cd(39)–O(40)
O(25)–Cd(39)
O(23)–Cd(39)
2.1
2.1
2.1
2.1
C21 H41 N7 O14 Pb
Pb(39)–O(43)
Pb(39)–O(40)
O(25)–Pb(39)
O(23)–Pb(39)
2.1
2.1
2.1
2.1
796
wileyonlinelibrary.com/journal/aoc
c 2011 John Wiley & Sons, Ltd.
Copyright O(41)–Zn(39)–O(25)
O(41)–Zn(39)–O(23)
O(40)–Zn(39)–O(25)
O(40)–Zn(39)–O(23)
O(25)–Zn(39)–O(23)
O(43)–Cd(39)–O(25)
O(43)–Cd(39)–O(23)
O(40)–Cd(39)–O(25)
O(40)–Cd(39)–O(23)
O(25)–Cd(39)–O(23)
O(43)–Pb(39)–O(40)
O(43)–Pb(39)–O(25)
O(43)–Pb(39)–O(23)
O(40)–Pb(39)–O(25)
O(40)–Pb(39)–O(23)
O(25)–Pb(39)–O(23)
99.50
130.8
120.0
120.0
119.9
111.5
122.9
119.9
119.9
120.0
109.4
109.4
109.4
109.4
109.4
109.4
Appl. Organometal. Chem. 2011, 25, 791–798
Organic metal complexes derived from streptomycin and Zn, Cd and Pb
Figure 4. Optimized molecular model of Pb(II)-OMC (color code: C, blackish gray; N, blue; O, red; yellowish gray, Pb).
Figure 5. Comparative aspects of antifungal findings.
Antifungal activity significantly increased after complexation
with metal ion(s) because it is strictly interaction dependent and
so new bonds (O–M) in OMCs inhibit enzymatic activity. This is
well known that enzymes required certain group for enhancing
concerned activity. It was thus susceptible to deactivation by metal
ion(s) on coordination.[23] Results indicated that OMC-1, OMC-2,
and OMC-3 had the potential to generate a novel antimicrobial
agent by displaying moderate to high affinities for most of the
receptors, particularly in the case of Zn-OMC-1.
Conclusions
Acknowledgments
One of the authors (Rajiv Kumar) gratefully acknowledges his
younger brother Bitto for motivation. Special thanks to papa
(Mohan Pal Singh) for helping and interpretation of 1 H and 13 C
NMR spectra. The authors acknowledge CSL Delhi University Delhi
for providing computer facilities, DRDO, New Delhi for financial
assistance, IIT Bombay and IIT Delhi for recording EPR and 1 H and
13 C NMR spectra, respectively.
Supporting information
Supporting information may be found in the online version of this
article.
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Appl. Organometal. Chem. 2011, 25, 791–798
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c 2011 John Wiley & Sons, Ltd.
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