Synthesis, structural properties, DFT studies, antimicrobial activities and DNA binding interactions of two newly synthesized organotin(IV) carboxylates

Article abstract of DOI:10.1016/j.molstruc.2019.04.066

Herein, we report the synthesis, characterization and biological evaluations of two novel organotin(IV) carboxylates (1 and 2). The structures of both complexes are confirmed by single crystal X-rays diffraction analysis. Density functional theory (DFT) s

Full text of DOI:10.1016/j.molstruc.2019.04.066

Accepted Manuscript
Synthesis, structural properties, DFT studies, antimicrobial activities and DNA binding
interactions of two newly synthesized organotin(IV) carboxylates
Arshad Farooq Butt, Muhammad Naeem Ahmed, Moazzam Hussain Bhatti,
Muhammad Aziz Choudhary, Khurshid Ayub, Muhammad Nawaz Tahir, Tariq
Mahmood
PII:
S0022-2860(19)30469-7
DOI:
https://doi.org/10.1016/j.molstruc.2019.04.066
MOLSTR 26438
Reference:
To appear in: Journal of Molecular Structure
Received Date: 21 January 2019
Revised Date: 13 April 2019
Accepted Date: 16 April 2019
Please cite this article as: A.F. Butt, M.N. Ahmed, M.H. Bhatti, M.A. Choudhary, K. Ayub, M.N. Tahir,
T. Mahmood, Synthesis, structural properties, DFT studies, antimicrobial activities and DNA binding
interactions of two newly synthesized organotin(IV) carboxylates, Journal of Molecular Structure (2019),
doi: https://doi.org/10.1016/j.molstruc.2019.04.066.
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Graphical Abstract
Organotin(IV) carboxylates

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Synthesis, structural properties, DFT studies, antimicrobial activities and DNA
binding interactions of two newly synthesized organotin(IV) carboxylates
*
Arshad Farooq Butta,c, Muhammad Naeem Ahmedb, Moazzam Hussain Bhattia , Muhammad Aziz
Choudharyc, Khurshid Ayubd, Muhammad Nawaz Tahire, Tariq Mahmoodd*
a Department of Chemistry, Allama Iqbal Open University Islamabad, Pakistan
b Department of Chemistry, The University of Azad Jammu and Kashmir Muzaffarabad, 13100
Pakistan
c Department of Chemistry Mirpur University of Science and Technology (MUST), Mirpur, Azad
Jammu and Kashmir, Pakistan
d Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, University
Road, Tobe Camp, Abbottabad-22060, Pakistan.
e Department of Physics, University of Sargodha, Sargodha, Pakistan.
*To whom correspondence should be addressed: E-mail: mahmood@cuiatd.edu.pk (T. M) and
moazzam.bhatti@aiou.edu.pk (M. H. B).
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Abstract
Herein, we report the synthesis, characterization and biological evaluations of two novel
organotin(IV) carboxylates (1 and 2). The structures of both complexes are confirmed by single
crystal X-rays diffraction analysis. Density functional theory (DFT) studies are also executed to
compare experimental (X-ray as well as spectroscopic) results with theoretical ones. Excellent
correlation is observed between theoretical and experimental results. Furthermore, organotin(IV)
carboxylates are evaluated against different bacterial stains (E. coli, S. aureus, K. pneumoniae and
B. subtilis) and fungal stains (F. solani, A. fumigatus and A. niger). The complex 1 shows good
antibacterial activity against B. subtilis (17±0.32mm), whereas complex 2 shows good
antibacterial activity against E. coli (18±0.41mm) and B. subtilis (18 ± 0.41mm). The complex 1
shows significant activity against A. fumigatus (28±0.45mm) and 2 shows good activity against A.
fumigatus (16±0.37mm). To determine the interaction of organotin(IV) carboxylates with DNA,
the interaction studies with salmon sperm DNA (SS-DNA) are also carried out through UV-vis
absorption spectroscopy. The Gibbs free energies (ꢀG) (-28.02 KJ/mol for complex 1 and -28.43
KJ/mol for complex 2) and high values of binding constants (K) (8.15 × 104 M-1 for complex 1
and 9.62 × 104 M-1 for complex 2) indicate that strong interactions are developed between
organotin(IV) carboxylates and SS-DNA.
Keywords: Organotin(IV) carboxylate; X-ray; DFT; Antimicrobial; DNA Interaction
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1. Introduction
During last few decades organometallic chemistry has been the subject of great interest of
researchers. Among organometallic compounds, organotin(IV) compounds in general and
organotin(IV) carboxylates in particular, have shown significant biological activities [1–5]. The
organotin carboxylates are the reservoir of many important activities such as fungicidal [6],
bactericidal [7], larvicidal [8], antitumor [9] and anticancer activities [10]. Furthermore, large
number of organotin(IV) carboxylates have been explored as wood preservatives [11],
agrochemicals, biocides, antifouling paints and disinfectants [12]. The biological behavior of
organotin(IV) moieties depend upon the nature of ligand which is helpful for the transportation of
complexes across cell membrane [13]. However, tri-substituted organotin(IV) complexes exhibit
higher toxicity against microorganisms than di-substituted ones, which in turn are more effective
than mono-substituted organotin complexes [14]. Moreover, the order of toxicity is also dependent
on the type of microorganism and stain as well. In addition, inhibitory activities increase in the
order Et < Bu <Ph, which suggest that the toxicity of organotin(IV) complexes also depend upon
hydrophobicity and lipophilicity of attached groups [15,16]. The structures of the complexes
largely depend on the nature of alkyl or aryl group bonded to the central Sn atom and the nature of
carboxylate ion. The carboxylate ions bind with the central atom (Sn) in various modes resulting
in diverse type of structures [17,18].
Organotin carboxylates have been observed to exhibit higher cytotoxicity. Some of the
organotin(IV) carboxylates have shown higher apoptosis inducing cisplatin and carboplatin, both
in vivo and in vitro. As a result of promising various activities of organotin(IV) compounds, large
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number of research groups are synthesizing variety of organotin complexes by altering the type of
donor ligands for improving the solubility and potency [19,20].
By keeping in view, the importance of organotin compounds and in continuation to our previous
work on structural properties and biological activities of various compounds [21–23]. we report
the synthesis, structural properties, DFT studies, antimicrobial activities and DNA binding
interactions of two newly synthesized organotin(IV) carboxylates.
2. Material and methods
2.1 Experimental
Organotin salts and other chemicals of analytical grade are purchased from Aldrich chemical
company (USA). The organic solvents acetone, ethyl acetate, chloroform, dichloromethane,
ethanol, methanol, n-hexane, tetrahydrofuran and toluene are purchased from Merck, Germany.
All solvents are dried by using standard methods. The melting points of synthesized compounds
are determined in capillary using M-560 (BUCHI) electrothermal melting point apparatus. IR
spectra are obtained in the range of 4000-400 cm-1 on Nicollet IS-10 (Thermo Scientific)
spectrophotometer. KBr and solid substrate are used for mid and far IR respectively. UV-vis
spectra are recorded on UV-1700 spectrophotometer, Shimadzu. Elemental analysis for C, H and
N is executed by using instrument Leco True-Spec CHN Determinator. The carrier gas was helium
in 99.99% purity and the pressure was 35 psi ± 10 %. The purity of the oxygen was 99.99% and
1
the pressure was 35 psi ± 10 %. The furnace used for combustion was heated up to 1050 °C. H,
13
and C are recorded at room temperature on 300 MHz and 400 MHz Bruker Advanced Digital
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(Switzerland) instrument using CDCl3 [1H (CDCl3) = 7.28 and 13C (CDCl3) = 77.0 ppm] and
DMSO [1H (DMSO-d6) = 2.50 and 13C (DMSO-d6) = 39.5 ppm] as internal references. Chemical
shifts are given in ppm and coupling constants (J) values are given in Hz. The electron impact
mass spectra (EI-MS) were recorded on MAT 312 mass spectrometer connected to a MASPEEC
system (msw/A091).
2.2 Synthesis
2.2.1 General procedure for the Synthesis of both ligands (HL1) and (HL2)
To synthesize ligands, 1.0 g (10.0 mmol) of aniline for HL1 and 1.47 g (10.0 mmol) of 4-
aminobenzoic acid for HL2 (Scheme 1) were dissolved separately in ethyl acetate. After that the
resulting solution was added drop wise into the solution of (1.07 g, 10.0 mmol) succinic
anhydride with constant stirring. The precipitates formed were filtered and washed with excess
of ethyl acetate to remove unreacted materials. The obtained precipitates were dried at room
temperature and recrystallized in ethanol.
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O
O
O
O
Ethyl acetate
Stirring at room temperature
R NH2
+
O
R NH C
(CH2)2 C OH
Scheme 1: General reaction scheme for the synthesis of both ligands HL1 and HL2
2.2.2 Synthesis of organotin(IV) carboxylates (1 and 2)
Triorganotin(IV) carboxylates are synthesized by refluxing the mixture of triphenyltin hydroxide
1.835g (5 mmol) and ligands HL1 0.965g (5 mmol) or HL2 0.592g (2.5 mmol) in dry ethanol,
acetone (1:1) for eight to ten hours (Scheme 2). The refluxed solutions were cooled to room
temperature and filtered. The solvent was evaporated under reduced pressure. The products
obtained were recrystallized from dichloromethane and n-hexane (4:1).
Scheme 2: Scheme for the synthesis of triphenyltin(IV) carboxylates 1 and 2
2.2.2.1 Triphenylstannyl 4-oxo-4-(phenylamino)butanoate (1)
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(Yield: 81.0%). M.p.: 140-141oC. Mol. wt.: 542. Anal. Cal. (%) for C28H25NO3Sn: C, 61.99
(61.90); H, 4.60, (4.57); N, 2.58, (2.62). FT-IR (4000-400 cm-1): ʋ 3330 (NH), 1686 (amide C=O),
1
1496 (OCO)asym, 1307 (OCO)sym, 527 (Sn-C), 453 (Sn-O). HNMR (CDCl3, 300MHz): δ (ppm) =
2.59 (4H, s, CH2), 7.10-7.49 (15H, m, Ar-H), 7.70-7.90 (5H, m, Ar-H), 8.39 (1H, s, NH). 13CNMR
(CDCl3, 75MHz ): δ (ppm) = 30.1, 33.1, 119.8, 128.4, 128.6, 129.5, 130.3, 137.1, 137.3, 138.0,
170.6, 179.5. EI-MS, m/z (%): [C6H5NHCO(CH2)2COOSn(C6H5)2]+ 466 (15.2),
[C6H5NHCO(CH2)2COOSnC6H5]+
389
(2.5),
[Sn(C6H5)3]+
351
(46.8),
[C6H5NHCO(CH2)2COOSn]+ 311 (34.8) , [SnC6H5]+ 274 (7.4), [SnC6H5]+ 197 (37.8),
[C6H5NHCO(CH2)2COO]+ 192 (1.5) , [C6H5NHCO(CH2)2CO]+ 176 (9.0) , [C6H5NHCO(CH2)2]+
148 (1.4) , [C6H5NHCOCH2]+ 134 (3.8) , [Sn]+ 120 (17.5), [C6H5NH]+ 92 (9.0) , [C6H5]+ 77
(26.2).
2.2.2.2 Triphenylstannyl 4-(4-oxo-4-((triphenylstannyl)oxy)butanamido)benzoate (2)
o
(Yield: 74.0 %). M.p.: 187-188 C. Mol. wt.: 935. Anal. Cal. (%) for C47H39NO5Sn2: C, 60.32,
(60.24); H, 4.17, (4.12); N, 1.50 (1.52). FT-IR (4000-400 cm-1): ʋ 3311 (NH), 1678 (amide C=O),
1523 (OCO)asym, 1402 (OCO)sym, 594 ν (Sn-C), 447 (Sn-O). 1HNMR (CDCl3, 300MHz): δ (ppm) =
2.65 (4H, s, CH2), 7.35 - 7.47 (18H, m, Ar-H), 7.53 -7.57 (12H, m, Ar-H), 7.61 (2H, d, J = 6.6Hz
Ar-H), 7.76 (2H, d, J = 8.1Hz, Ar-H), 8.7 (1H, s , NH). 13CNMR (CDCl3, 75MHz): δ (ppm) =
38.5, 34.4, 118.5, 126.1, 130.2, 131.5, 132.5, 133.4, 138.5, 142.8, 170.3, 173.6, 178.4. EI-MS,
m/z
(%):
[(C6H5)3SnOOC(C6H4)NHCO(CH)2COOSn(C6H5)2]+
840
(9.1),
[(C6H5)3SnOOC(C6H4)NHCO(CH)2COOSn]+ 586 (8.4), [Sn(C6H5)3]+ 351 (10.5), [Sn(C6H5]+ 274
(8.3),
[OOC(C6H4)NHCO(CH)2COO]+
235
(18.4),
[SnC6H5]+
197
(33.5),
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[COO(C6H4)NHCO(CH2)2]+ 191 (11.5), [C6H4NHCO(CH2)2]+ 147 (10.2), [C6H4NHCO]+ 133 (
5.1), [Sn]+ 120 ( 12.3 ), [C6H6]+ 78 (100), [C6H5]+ 77 (31.6).
2.3 Crystal structure determination
The X-ray diffraction data was collected on a Bruker KAPPA APEXII diffractometer with CCD
detector set 40.0 mm from the crystal. The data was collected at room temperature i.e. at 298 K
and intensity measurements were performed using graphite monochromatic Mo-Kα radiation from
a sealed ceramic diffraction tube (SIEMENS). Generator settings were 50 KV/30 mA. The
structures were solved by Patterson method and an extension of the model was accomplished by
the direct method using the program SHELXT. Final refinement on F2 was conducted by full
matrix least squares techniques using SHELXL-2014/7 [24], a modified version of the program
PLUTON (preparation of illustration) and PLATON package [25]. All atoms other than hydrogens
are refined anisotropically with the help of full-matrix least squares methods [24].
CIF files of both organotin(IV) carboxylates 1 and 2 have been assigned CCDC numbers 1473333
and 1473100, respectively, and can be obtained free of charge on demand to CCDC 12 Union
Road, Cambridge CB21 EZ, UK. (Fax: (+44) 1223 336-033: data_request@ccdc.cam.ac.uk).
2.4 Computational methods
DFT studies of both Sn complexes are performed by using Gaussian 09 software [26], where
visualization of geometries and graphics is performed with GaussView 5.0 [27]. The geometries of
both complexes (1 and 2) are optimized by adopting split basis set approach at B3LYP method (6-
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31G(d) for H, C, N and O atoms, Lanl2DZ basis set for Sn) [28,29]. B3LYP functional is quite
reliable for structural properties of compounds due to its nice balance between computational cost
and accuracy [30–32]. The optimized structures are confirmed as true minima through frequency
analysis at the same method (no imaginary frequency is observed). TD-DFT calculations for
absorption studies are performed at CAM-B3LYP method by adopting the split basis set approach
(for C, H, O and N is 6-31G (d) and for Sn is LanL2DZ basis set) in DMSO as solvent using
CPCM model. 20 excited states (10 singlet and 10 triplet) are considered for the calculation of
absorption spectra of both carboxylates. Frontier molecular orbitals (FMOs) and molecular
electrostatic potential (MEP) analyses are computed at the same level of theory as used for
optimization.
2.5 Antibacterial Activity
All the synthesized organotin(IV) carboxylates are screened for antibacterial activity against
Escherichia coli (ATCC-15224), Staphylococcus aureus (ATCC-6538), Klebsiella pneumonia
(ATCC-1705) and Bacillus subtilis (ATCC-6633) by using standard disc diffusion method [33].
Sterile filter paper discs are impregnated with samples (5 ꢁL; 10 mg/mL DMSO) and standards
(2.5 ꢁL; 4 mg/mL DMSO). Impregnated discs are placed on freshly prepared bacterial lawn on
sterile agar plates and incubated at 37 °C for 24 h. Roxithromycin and cefixime are used as
positive controls while DMSO as negative control. After 24 h, average diameter (mm) of the zone
of inhibition (ZOI) around the samples is recorded as the measure of antibacterial activity. The
experiment is run in triplicate.
2.6 Antifungal Activity
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All the synthesized organotin(IV) carboxylates are tested for antifungal activity against different
fungal strain namely, Fusarium solani (FCBP-0291), Aspergillus fumigatus (FCBP-66),
Aspergillus niger (FCBP-0198) and Mucor sp (FCBP-0300) by disc diffusion method [33].
Overnight incubated fungal spores were harvested in Tween 20 (0.02% in water) with turbidity
equivalent to 0.5 McFarland. Sterile filter paper discs impregnated with samples (5 ꢁL; 10 mg/mL
DMSO) and standards (2.5 ꢁL; 4 mg/mL DMSO) were placed on sterile SDA plates swabbed with
100 ꢁL of fungal spores. Clotrimazole and DMSO were used as positive and negative controls
respectively. The plates were incubated at 28°C for 24-48 hours. The average diameter (mm) of
ZOI around the samples and control was recorded. The experiment was run in triplicate.
2.7 DNA binding interaction studies by electronic spectroscopy
Organotin(IV) carboxylates (1 and 2) are studied for interaction with Salmon sperm DNA (SS-
DNA) and kept at 4 °C. SS-DNA (10 mg) is dissolved in deionized water (pH = 7.0) and left for
four hours stirring. Buffer (2 mM Tris-HCl pH = 7.2) is prepared in deionized water. Solution of
SS-DNA in the buffer gave a ratio of UV absorbance at 260 and 280 nm (A260/A280), which shows
that DNA is free from protein. The concentration of SS-DNA is determined by absorption
spectroscopy using the molar coefficient of 6,600 M-1 cm-1 and is found 1.6×10-5. The compounds
are dissolved in 90 % DMSO solution at different concentration separately. The UV absorption
spectra of each complex is measured taking 2 mL of sample, keeping the concentration of complex
fixed and increasing the concentration of SS-DNA solution. Equivalent solution of DNA is added
to the complex and reference to eliminate the absorbance of SS-DNA itself. Complex-DNA
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solution is incubated for 5 minutes before each reading. The absorption spectra are recorded using
cuvettes of 1 cm path length at room temperature (25 °C ± 1).
3. Results and discussion
3.1 Molecular structure
The ORTEP plots of both organotin(IV) carboxylates (1-2) are given in the Fig. 1, and the
structural refinement parameters are narrated in Table 1. The molecular formulae of both
carboxylate Sn complexes are [C28H25NO3Sn] (1) and [C47H41NO6Sn2] (2), respectively. The
compound (1) crystallized in triclinic crystal system having space group P-1, whereas 2
crystalized in monoclinic crystal system having P21/c space group.
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Fig. 1: The ORTEP plots of 1 and 2 drawn at 50 % probability level
The structure of the complex 1, is analyzed to distinguish between distorted trigonal bipyramidal
and distorted tetragonal pyramid. This concept has been extensively analyzed and presented by
Meutterties and coworkers [34]. In this process, the angles defining the edges are analyzed. The
angles defining the edges for a pure trigonal bipyramidal structure are ideally all 53.1 degrees. On
the other hand, the angles defining the edges in tetragonal pyramid are 0.0, 75.7 and 75.7 degrees.
For the complex 2, the angles defining the edges are 53.54, 53.68 and 54.16 degrees. These angles
are very much comparable to 53.8, 53.8 and 53.8 for CdCl53- reported in the literature as very
close to ideal trigonal bipyramidal with very little distortion [35]. Therefore, we can confidently
say that the structures reported here is close to an ideal trigonal bipyramidal with very little
distortion rather than being close to a tetragonal pyramid (Fig. 1).
The molecules are dimerized due to N-H…O bonding having distance 2.17Å, with
ring
motifs. The dimers are further interlinked due to C-H…O hydrogen bonding having distance
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2.30Å, with
ring motifs as shown in packing diagram (Fig. 2). In the asymmetric unit the
phenyl rings A (C1-C6) and B (C7-C12) are planar with r. m. s. deviation of 0.0019 and 0.0015 Å,
respectively. The dihedral angle between rings A/B is 79.67 (12)°. The third phenyl ring is
disordered over two set of sites with occupancy ratio of 0.571(4): 0.429(4). Both disordered rings
are refined as regular phenyl rings having all C-atoms as equal thermal parameters. The dihedral
angle between C (C13A-C18A) and D (C13B-C18B) is 44.0 (4)°. In the ligand acetate part E
(C19/C20/ O1/O2) and N-phenyl acetamide moiety F (O3/N1/C21-C28) are planar with r. m. s.
deviation of 0.0026 and 0.0338 Å, respectively. The dihedral angle between E/F is 70.78 (15)°.
There exist π-π interactions between various benzene rings in the range of 3.136(3) - 3.728(2) Å.
The coordination of Sn1 center in 2, directly attached with carboxylate adjacent to benzene has
distorted trigonal bipyramid geometry, consisting of three C-atoms from three phenyl rings and O-
atom of carbonyl adjacent to imine. The range of Sn-C and Sn-O bond distance are 2.123(4)-
2.136(4) Å and 2.116(3)- 2.621(3) Å, respectively. The coordination sphere of Sn2 center attached
to carboxyl through O-atom of 4-amino-4-oxobutanoic acid is distorted trigonal bypyramid
consisting of three C-atoms from three phenyl rings and O-atom of terminating water. The Sn-C
and Sn-O bond distances are in the range of 2.116(4)-2.141(4) Å and 2.104(3)-2.621(3) Å,
respectively. In the asymmetric unit the phenyl rings A (C12-C17), B (C18-C23) and C (C24-C29)
are planar with r. m. s. deviation of 0.0045, 0.0078 and 0.0034 Å, respectively. The dihedral angle
between A/B, A/C and B/C are 55.33 (17)°, 70.58 (14)° and 60.56 (17)°, respectively. Similarly,
the phenyl rings D (C30-C35), E (C36-C41) and F (C42-C47) are planar with r. m. s. deviation of
0.0058, 0.0111and 0.0061 Å, respectively. The dihedral angle between D/E, D/F and E/F is 63.16
(23)°, 78.02 (19)° and 89.39 (18)°, respectively. In the ligand there exist N-H…O bonding to
complete S(7) loop ( Fig. 2). There is also a C-H…O interaction which helps in the formation of S
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(5) ring. There exist π-π interactions between various benzene rings in the range of 2.895(3)-
4.049(2) Å.
Fig. 2: Packing diagrams of both 1 and 2
3.2 DFT Optimized geometries
The geometries of both Sn complexes 1 and 2 have been optimized (Fig. 3) through DFT method
in order to compare geometric parameters (bond lengths and bond angles) with those obtained
from X-ray diffraction results. The comparison of important X-ray and theoretical geometric
parameters is given in Tables 2-3 (bond lengths Table 2 and bond angles Table 3). The computed
geometric parameters are in strong agreement with the experimental results.
The X-ray values of important bond lengths involving hetero atoms such as Sn1—O1, Sn1—C7,
Sn1—C1, O1—C19, O2—C19, O3—C22, N1—C22 and N1—C23 (atomic labelling is in
accordance with Fig. 1) in complex 1 are 2.07, 2.11, 2.12, 1.30, 1.22, 1.22, 1.34 and 1.40Å,
respectively. The theoretical values for the same bonds are 2.04, 2.13, 2.13, 1.31, 1.23, 1.22, 1.37
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and 1.40Å, respectively. In complex 2, the important bonds such as Sn1—O1, Sn1—C18, Sn1—
C24, Sn1—C12, Sn2—O5, Sn2—C36, Sn2—C30, Sn2—C42, O1—C1, O2—C1, O3—C8, O4—
C11, O5—C11, N1—C8 and N1—C5 experimentally are 2.11, 2.12, 2.12, 2.13, 2.10, 2.11, 2.12,
2.14, 1.29, 1.22, 1.23, 1.22, 1.35 and 1.40Å, respectively. The simulated values of respective
bonds are 2.06, 2.14, 2.14, 2.13, 2.05, 2.14, 2.14, 2.14, 1.30, 1.23, 1.22, 1.24, 1.31, 1.37 and
1.40Å, respectively.
The experimental and computed values of prominent bond angles of both complexes (1 and 2) are
narrated in Table 3. Excellent correlation exists among experimental and theoretical values of
important bond angles of both complexes. In 1, the experimental values of important bond angles
such as O1—Sn1—C7, C6—C1—Sn1, C2—C1—Sn1, O1—Sn1—C1, C7—Sn1—C1, O2—
C19—O1, O2—C19—C20, O1—C19—C20, C12—C7—Sn1, C19—O1—Sn1, C22—N1—C23,
O3—C22—N1, O3—C22—C21 and N1—C22—C21 are 107.7, 121.2, 120.5, 114.1, 112.1,
121.4, 123.0, 115.6, 118.1, 111.1, 129.4, 124.0, 121.4 and 114.6o, respectively. The theoretical
values of same bond angles are 110.6, 121.4, 120.4, 110.6, 110.1, 121.6, 123.6, 123.9, 114.4,
118.7, 112.4, 130.0, 124.8, 122.2 and 115.5o, respectively. Similarly, the prominent experimental
and theoretical bonds angles of complex 2, corroborated nicely (Table 3).
Fig. 3: Optimized geometries of both carboxylates 1 and 2
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3.3 Absorption studies and frontier molecular orbitals (FMOs) analyses
The experimental absorption spectra of both organotin (IV) carboxylates are recorded in dimethyl
sulfoxide (DMSO). The simulated absorption spectra are computed by using time dependent (TD)
calculation at CAM-B3LYP method. The experimental and theoretical absorption spectra of both
carboxylates are shown in Fig. 4. The both complexes have almost similar structural similarity
with respect to the chromophoric groups, therefore similar kind of trend is expected for absorption
of light. The experimental absorption maxim of respective organotin(IV) carboxylates (1 and 2)
are 273 nm and 294 nm, respectively. Theoretically measured absorption maxima of both
carboxylates 1 and 2 are 227 and 259 nm, respectively which correlated nicely with the
experimental results. The minute difference of absorption maxima is may be due to the difference
of medium of experimental and theoretical conditions.
1
40000
Complex 1
35000
Complex 2
30000
Complex 1
Complex 2
25000
20000
15000
10000
5000
0
0
250
300
350
400
200
300
400
Wavelength (nm)
Wavelength (nm)
Fig. 4: Experimental (left) and theoretical (right) absorption maxima of both organotin (IV)
carboxylates 1 and 2 measured in DMSO.
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Frontier molecular orbital (FMOs) analysis is very useful tool for explaining the molecular
transitions and reactivity of compounds [36,37]. The frontier molecular orbital analysis of both
organotin(IV) carboxylates is performed for understanding the reactivities and surfaces are shown
in the Fig. 5. In complex (1), the EHOMO and ELUMO are -5.71 eV and -0.88 eV, respectively. The
H-Lg is 4.83 eV, which corresponds to 256 nm and corelated nicely with the experimental UV-vis
spectra. In (2), the EHOMO and ELUMO are -5.78 eV and -0.89 eV, respectively. The H-LEg is 4.89
eV, which corresponds to transitions at 253 nm. The absorption maxima of both carboxylates
reflect that the electronic transitions are due to π to π* transitions. The HUMO and LUMO
surfaces of both reflect the different kind of behavior. In HOMO of 1, the electronic density is
concentrated on the amide and phenyl ring attached to that, where as in the LUMO the isodensity
is totally shifted toward the Sn and phenyl rings there. In complex 2, the again the isodensity in
both HOMO and LUMOs is concentrated on the carboxylate and amide moieties present between
the both Sn atoms.
HOMO (1)
LUMO (1)
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HOMO (2)
LUMO (2)
Fig. 5: HOMO and LUMO surfaces of both Sn carboxylates 1 and 2
3.5 Molecular electrostatic potential (MEP) analysis
MEP analysis of both carboxylates Sn complexes (1 and 2) is performed and MEP surfaces are
given in the Fig. 6. It is observed from MEP surfaces that overall the both complexes (1 and 2)
appears as neutral (no red or blue region is observed over the entire surface). The dispersion of
electrostatic potential in complex 1 is ranged from -0.11 to 0.11 esu, whereas in 2 is from -0.102
to 0.102 esu, respectively. The dispersion of potential also reflects that both complexes are very
less polar in nature [38].
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Fig. 6: The MEP surfaces of both Sn complexes 1 and 2
3.6 Antimicrobial activities
In the present study screened organotin(IV) carboxylates and their associated ligands for
antibacterial and antifungal activities. It is observed that the ligands themselve did not show
activity against any Gram-positive or Gram-negative bacterial stain. On the contrary, it is observed
that attachment of the ligand with triphenyltin moiety provided the antibacterial profile to the final
compound. Complex 1 showed moderate activity against K. pneumoniae while against B. subtilis,
it was comparable to that of roxithromycine. Whereas, complex 2 is more active against all strains
of bacteria with effect almost equivalent to roxithromycine but lower than cefixime (Table 4). The
triphenyltinbenzoate
derivatives
show
antibacterial
activity
against
Escherichia
coli, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa [3].
Likewise, triphenutin with benzamidoalanine also demonstrated significant antibacterial activity
[39]. Antibacterial agents work by targeting vital microbial functions including cell wall and
nucleic synthesis [2]. Different compounds may act depending upon the type of interaction based
their molecular structure. This it is possible that both complex 1 and 2 have targeted one or more
of the above proteins rendering the bacteria non-viable. However, this needs to be further studied
in detail.
Besides, similar pattern was observed in case of antifungal activity where the ligands did not show
any response while the compounds were cytotoxic to selected fungal strains. Complex 1 is highly
effective against F. solani and A. fumigatus with their antifungal activity either greater than or
equivalent to clotrimazole. On the other hand, 2 is moderately active against F. solani, A.
fumigatus and A. niger (Table 5). This variation is based on the structural differences and the
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capacity of compound to interact with fungal biomolecules. The Literature shows that triphenyltin
(IV) dithiocarbamate compounds were also good antifungal agents [40]. Similarly, other
derivatives were also active against yeast-like and filamentous fungi [7].
3.7 DNA binding interactions
Electronic spectroscopy is used for studying the interaction of both organotin(IV) carboxylates
with SS-DNA. The results of interaction of both organotin(IV) carboxylates with various SS-DNA
concentrations are shown in the Figs. 7 and 8. The absorption maxim of respective organotin(IV)
carboxylates (1 and 2) are 270-275 nm and 290-296 nm, respectively. The absorptions bands are
due to π-π* interaction of organotin(IV) carboxylates with SS-DNA. With increasing
concentration of DNA, intensity of peaks decreases gradually, and wavelengths have a minor red
shift (1-6 nm). Long and Barton observed that when a molecule interacts with DNA, shifting of
peak gives clue for the mode of binding interactions. They pointed out that if, bathochromic effect
(red shift) is observed due to interaction of compound with DNA along with hypochromic effect,
an intercalative mode of binding will be there. The intercalation is mainly due the stacking
between chromophore and the base pairs of DNA. The intercalating surfaces are sandwiched
between π orbitals of the compounds and heterocyclic base pairs, which are stabilized in the helix
through π-π stacking and dipole-dipole interactions. In intercalation, there is a structural overlap
between the intercalator and base pair. The intercalator become tightly held and oriented with the
planner moiety perpendicular to the axis of helical of DNA. Therefore, the interaction between
organotin(IV) carboxylate and SS-DNA could be non-covalent intercalative binding [41,42]. After
intercalating, the π* orbital of the intercalated organotin(IV) carboxylate could couple with π
orbital of base pair, thus decreasing the energy, which results bathochromism. Furthermore, the
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coupling of π orbital with partially filled π orbitals of DNA decreases the transition probabilities
resulting hypochromic effect. Since, bathochromic shift may be observed when DNA duplex is
stabilized while hypochromic shift is due to π-π* stacking interaction, which occur in intercalative
binding mode.
The values of binding constant (K) for organotin(IV) carboxylates with SS-DNA are calculated
using Bensi-Heldibrand,s equation [43].
Ao / A-Ao = (ƐG / ƐH-G ̶ ƐG) + (ƐG / ƐH-G ̶ ƐG) x (1/K[DNA])
Where Ao and A are absorbance, ƐG and ƐH-G are the absorption coefficient of the organotin(IV)
carboxylate and its complex with DNA. K is the binding constant and its value can be obtained
from the intercept/sloop ratio of Ao / A-Ao vs 1/[DNA] plot. The Gibb,s free energy (ꢀG) of all the
secerned organotin(IV) carboxylate was calculated from the equation:
ꢀG = -RT lnK
Where R is a gas constant (8.314 JK-1 mol-1) and T is the temperature (298 K).
The values of binding constants (K) of screened organotin(IV) carboxylates are in the range of
8.15 × 104 (complex 1) to 9.62 × 104 (complex 2). The high values of binding constant K indicates
that strong interactions are developed between organotin(IV) carboxylates and SS-DNA. All the
complexes show negative values of Gibb,s free energy (ꢀG = -28.02 and -28.43 kJ mol-1 for 1 and
2, respectively) which suggests that interactions were spontaneous. Most of the anticancer drugs
interact with DNA and proteins either in reversible or irreversible mode suggesting a direct
relationship between interactions with specific target and leading to the therapeutic effect. From
the interaction studies of organotin(IV) carboxylates with SS-DNA, it is proposed to pursue the
said compounds in future studies as potential anticancer drug candidates.
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Fig. 7: (A) UV spectra of complex 1 (0.1 mM concentration) with different concentrations of SS-
DNA and (B) plot of A0/A-A0 vs. 1/[DNA]
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Fig. 8: (A) UV spectra of complex 2 (0.1 mM concentration) with different concentrations of SS-
DNA and (B) plot of A0/A-A0 vs. 1/[DNA]
4. Conclusions
Two new organotin(IV) carboxylates are synthesized in very good yields. Characterization of final
structures are made with help of different spectroscopic and single crystal X-ray diffraction
analyses. DFT calculations show excellent correlation with the geometric parameters obtained
through X-ray results. The FMOs analysis proved that the electronic transitions in both
carboxylates are mainly due to π to π* transitions. The relatively high band gap reflects the kinetic
stability of both carboxylates. The ESP analysis showed that both (1 and 2) are neutral in nature.
Complex 1 showed the moderate activity against K. pneumoniae while against B. subtilis,
Whereas, complex 2 is proven more active against all tested strains of bacteria with (almost
equivalent to standard drug roxithromycine). Both organotin(IV) carboxylates are also proved very
effective against F. solani and A. fumigatus stains with their antifungal activity either greater than
or equivalent to clotrimazole. The high binding constant values of both organotin(IV) carboxylates
against the SS-DNA (8.15 × 104 for 1 and 9.62 × 104 for 2) are observed. Both complexes showed
negative values of Gibb,s free energies (ꢀG = -28.02 and -28.43 kJ mol-1 for 1 and 2, respectively)
which suggests that interactions with SS-DNA are favorable and exothermic.
Acknowledgements
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The authors highly acknowledge Higher Education Commission of Pakistan (NRPU grant # 3013),
COMSATS University Islamabad, Abbottabad Campus and University of Azad Jammu and
Kashmir for financial support.
Supplementary material
Cartesian co-ordinates of optimized geometries and cif files of both complexes (1 and 2) are
1
provided in supporting information. Experimental H-NMRs are also pasted in supporting
information as Fig. S1-S2. Supplementary data associated with this article can be found, in the
online version, at http://dx.doi.org/
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