Synthesis, characterization, crystal structure, and antimicrobial studies of novel thiourea derivative ligands and their platinum complexes

Article abstract of DOI:10.1080/00958972.2018.1427233

N,N-Di-R-N′-(4-chlorobenzoyl)thiourea (Di-R: diethyl, di-n-propyl, di-n-butyl and diphenyl) ligands (HL^1–4) and their Pt(II) complexes (cis-[Pt(L^1–4-S,O)₂]) have been synthesized and structurally characterized by elemental

Full text of DOI:10.1080/00958972.2018.1427233

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
Synthesis, characterization, crystal structure and
antimicrobial studies of novel thiourea derivative
ligands and their platinum complexes
Ummuhan Solmaz, Ilkay Gumus, Gun Binzet, Omer Celik, Gulten Kavak
Balci, Aylin Dogen & Hakan Arslan
To cite this article: Ummuhan Solmaz, Ilkay Gumus, Gun Binzet, Omer Celik, Gulten Kavak Balci,
Aylin Dogen & Hakan Arslan (2018): Synthesis, characterization, crystal structure and antimicrobial
studies of novel thiourea derivative ligands and their platinum complexes, Journal of Coordination
Chemistry, DOI: 10.1080/00958972.2018.1427233
To link to this article: https://doi.org/10.1080/00958972.2018.1427233
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Publisher: Taylor & Francis
Journal: Journal of Coordination Chemistry
DOI: http://doi.org/10.1080/00958972.2018.1427233
Synthesis, characterization, crystal structure and antimicrobial studies of
novel thiourea derivative ligands and their platinum complexes
UMMUHAN SOLMAZ†, ILKAY GUMUS*†, GUN BINZET‡, OMER CELIK§, GULTEN KAVAK BALCI§,
AYLIN DOGEN¶ and HAKAN ARSLAN†
†Department of Chemistry, Faculty of Arts and Science, Mersin University, Mersin, TR 33343, Turkey
‡Department of Chemistry, Faculty of Education, Mersin University, Mersin, TR 33343, Turkey
§Science and Technology Applied and Research Center, Dicle University, Diyarbakır, TR 21280, Turkey
¶Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Mersin University, Mersin, TR 33343, Turkey
N,N-Di-R-N'-(4-chlorobenzoyl)thiourea (Di-R: diethyl, di-n-propyl, di-n-butyl and diphenyl)
ligands (HL1-4) and their Pt(II) complexes (cis-[Pt(L1-4-S,O)2]) have been synthesized and
structurally characterized by elemental analyses, FT-IR and NMR spectroscopy. HL2 ligand and
cis-[Pt(L4-S,O)2] metal complex have been also characterized by a single-crystal X-ray
diffraction study. HL2, C14H19ClN2OS, crystallizes in the monoclinic space group P21/n (no. 14),
with Z = 4, and unit cell parameters, a = 11.1405(16) Å, b = 9.7015(12) Å, c = 14.790(2) Å, β =
106.547(7)°. The cis-[Pt(L4-S,O)2], C40H28Cl2N4O2PtS2: triclinic, space group P-1 (no. 2), a =
8.9919(3) Å, b = 14.7159(6) Å, c = 15.7954(6) Å, α = 113.9317(18)°, β = 97.4490(18)° and γ =
105.0492(16)°. Single crystal analysis of complex, cis-[Pt(L1-4-S,O)2], revealed that a square-
planar coordination geometry is formed around the platinum atom by two sulfur and two oxygen
atoms of the related ligands, which are in a cis configuration. In addition, the thiourea derivative
ligands and their complexes were evaluated for both their in-vitro antibacterial and antifungal
activity. The results have been reported, explained and compared with fluconazole and
ampicillin, used as reference drugs.
Keywords: Benzoyl thiourea; Platinum complex; Antimicrobial activity; Intermolecular
interaction; Crystal structure analysis
1. Introduction
*Corresponding author. Email: ilkay.gumus@mersin.edu.tr
1

Thiourea derivatives are a well-known class of significant ligands and able to bind to metal ions
as neutral, monobasic or dibasic ligands that have three potential donor atoms (N, O and S) in
complexation reactions [1-3]. In particular, benzoyl thioureas react with transition metal centers,
either in monoanionic bidentate form by deprotonation, forming neutral homoleptic complexes
with S, O and N, S coordination, or in neutral form only through S atom [4, 5]. Interest in
thiourea derivatives and their metal complexes has increased due to the diversity of coordination
and varied applications such as in precious metal separation and extraction [6], single source
precursors for nanomaterials [7], plant growth regulator and biological activity, including
antibacterial, anti-fungal, antitubercular, antithyroid, antihelmintic, rodenticidal, insecticidal,
herbicidal, etc. [8-17].
Thiourea ligands, which are selective ligands for the platinum group metals, have a
strong affinity towards the platinum(II) center, which is coming from the sulfur atom. Thiourea
derivatives can be acceptable as convenient sulfur-containing nucleophiles in order to react
relatively fast with platinum(II) species in experiments, such as glutathione, which is present in
biological systems [18, 19]. More recently, there have been efforts to design platinum-
acylthiourea complexes in order to investigate their antifungal activity and inhibitory activities
against viruses [20].
The prominence of such studies is the possibility that thiourea derivatives may be more
effective as antimicrobial agents. However, there is a need for a comprehensive investigation
relating to the structure and activity of thiourea derivatives as well as their stability under
biological conditions. These detailed investigations could be helpful in the design of more potent
antimicrobial agents. Based upon literature research, we could find no synthesis or
characterization of the title compound type thiourea derivative metal complexes. In an effort to
contribute to these studies, here we report the synthesis, characterization and antimicrobial
properties of new N,N-di-R-N'-(4-chlorobenzoyl) thiourea ligands and their platinum metal
complexes.
2. Experimental
2.1. Instrumentation
Melting points were recorded on an Electrothermal model 9200 apparatus. Carbon, hydrogen and
nitrogen analyses were carried out on a Carlo Erba MOD 1106 elemental analyzer. Infrared
2

measurements were recorded from 400-4000 cm−1 on a Perkin Elmer Spectrum 100 series
FT-IR/FIR/NIR Spectrometer Frontier, ATR instrument. The NMR spectra were recorded in
CDCl3 solvent on a Bruker Avance III 400 MHz NaNoBay FT-NMR spectrophotometer using
tetramethylsilane as an internal standard.
The X-ray diffraction data were recorded on a Bruker APEX-II CCD diffractometer. A
suitable crystal was selected and coated with Paratone oil and mounted onto a Nylon loop on a
Bruker APEX-II CCD diffractometer. The crystal was kept at T = 100 K during data collection.
The data were collected with MoKα (λ = 0.71073 Å) radiation at a crystal-to-detector distance of
40 mm. Using Olex2 [21], the structure was solved with the Superflip [22-24] structure solution
program using the Charge Flipping solution method and refined by full-matrix least-squares on
F2 using ShelXL [25] with refinement of F2 against all reflections. Hydrogens were located by
difference maps and were refined isotropically, and all non-hydrogen atoms were refined
anisotropically. Geometric special details: all e.s.d.’s (except the e.s.d. in the dihedral angle
between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.’s are taken
into account individually in the estimation of e.s.d.’s in distances, angles and torsion angles;
correlations between e.s.d.’s in cell parameters are only used when they are defined by crystal
symmetry. An approximate (isotropic) treatment of cell e.s.d.’s is used for estimating e.s.d.’s
involving l.s. planes.
2.2. Reagents
Potassium tetrachloroplatinate(II) was purchased from Sigma Aldrich. 4-Chlorobenzoyl chloride,
potassium thiocyanate, diethylamine, di-n-propylamine, di-n-butylamine and diphenylamine
were purchased from Merck and used as received. All other chemicals and solvents were
obtained from commercial suppliers and used without purification.
2.3. General procedure for the synthesis of ligands
HL1-4 ligands were prepared according to previously published methods [27-29]. A solution of
4-chlorobenzoyl chloride (5 mmol, 0.860 g) in dry acetone (50 mL) was added dropwise to a
suspension of potassium thiocyanate (5 mmol, 0.49 g) in acetone (30 mL). The reaction mixture
was heated under reflux for 30 min and then cooled to room temperature. A solution of
secondary amine (5 mmol, diethylamine: 0.370 g; di-n-propylamine: 0.510 g; di-n-butylamine:
3

0.650 g; diphenylamine: 0.850 g) in acetone (10 mL) was added and the resulting mixture was
stirred for 2 h. Afterwards, the reaction mixture was poured into hydrochloric acid (0.1 M,
300 mL) and the solution filtered. The solid product was washed with water and purified by
recrystallization from an ethanol:dichloromethane mixture (1:1, v:v) (scheme 1).
2.3.1. N,N-Diethyl-N'-(4-chlorobenzoyl)thiourea (HL1). Color: White. Yield: 80% (1.083 g).
M.p.: 153-155 °C. FT-IR (ATR, ν, cm-1): ν(N-H) 3274 (w); ν(C-H) 2979, 2934, 2875 (w);
ν(C=O) 1642 (s); ν(C=S) 1228 (s); ν(C-Cl) 753 (w). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.52
(s, 1H, NH), 7.78 (d, 2H, Ar-H), 7.44 (d, 2H, Ar-H), 4.02 (s, 2H, N-CH2), 3.59 (s, 2H, N-CH2),
1.33 (d, 6H, CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 179.19 (C=S), 163.00 (C=O), 139.27,
130.97 (C-Ar), 129.38 (C-Ar), 129.09 (C-Ar), 47.98 (C-N), 47.68 (C-N), 13.29 (CH3), 11.47
(CH3). Anal. calcd. for C12H15ClN2OS: C, 53.23; H, 5.58; N, 10.35. Found: C, 53.19; H, 5.50; N,
10.25 %.
2.3.2. N,N-Di-n-propyl-N'-(4-chlorobenzoyl)thiourea (HL2). Color: White. Yield: 75%
(1.120 g). M.p.: 98-99°C. FT-IR (ATR, ν, cm-1): ν(N-H) 3270 (w); ν(C-H) 2967, 2932, 2876 (w);
ν(C=O) 1640 (s); ν(C=S) 1212 (s); ν(C-Cl) 753 (w). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.85
(s, 1H, NH), 7.79 (d, 2H, Ar-H), 7.41 (d, 2H, Ar-H), 3.91 (s, 2H, N-CH2), 3.47 (s, 2H, N-CH2),
1.82 (s, 2H, CH2), 1.69 (s, 2H, CH2), 1.01 (s, 3H, CH3), 0.88 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3, δ, ppm): 179.88 (C=S), 162.97 (C=O), 132.02 (C-Ar), 131.41 (C-Ar), 129.55, 127.78 (C-
Ar), 55.02 (C-N), 54.95 (C-N), 21.48 (CH2), 19.75 (CH2), 11.35 (CH3), 11.30 (CH3). Anal.
calcd. for C14H19ClN2OS: C, 56.27; H, 6.41; N, 9.37. Found: C, 56.25; H, 6.39; N, 9.31 %.
2.3.3. N,N-Di-n-butyl-N'-(4-chlorobenzoyl)thiourea (HL3). Color: White. Yield: 80%
(1.310 g). M.p.: 88-89 °C. FT-IR (ATR, ν, cm-1): ν(N-H) 3153 (w); ν(C-H) 2959, 2932,
2871 (w); ν(C=O) 1682 (s); ν(C=S) 1240 (s); ν(C-Cl) 749 (w). 1H NMR (400 MHz, CDCl3, δ,
ppm):8.57 (s, 1H, NH), 7.77 (d, 2H, Ar-H), 7.43 (d, 2H, Ar-H), 3.96 (s, 2H, N-CH2), 3.51 (s, 2H,
N-CH2), 1.78 (s, 2H, CH2), 1.65 (s, 2H, CH2), 1.44 (s, 2H, CH2), 1.28 (s, 2H, CH2), 0.98 (s, 3H,
CH3), 0.90 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 179.62 (C=S), 162.81 (C=O),
139.24 (C-Ar), 130.97 (C-Ar), 129.36 (C-Ar), 129.09 (C-Ar), 53.27 (C-N), 52.98 (C-N), 30.13
(CH2), 28.41 (CH2), 20.05 (CH2), 13.87 (CH2), 13.71 (CH3). Anal. calcd. for C16H23ClN2OS: C,
4

58.79; H, 7.09; N, 8.57. Found: C, 58.71; H, 6.89; N, 8.49 %.
2.3.4. N,N-Diphenyl-N'-(4-chlorobenzoyl)thiourea (HL4). Color: White. Yield: 88% (1.610 g).
M.p.: 161-162 °C. FT-IR (ATR, ν, cm-1): ν(N-H) 3257 (w); ν(C=O) 1645 (w); ν(C=S) 1251 (w);
ν(C-Cl) 757(w). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.72 (s, 1H, NH), 7.53 (t, 3H, Ar-H), 7.33
(m, 10H, Ar-H), 7.25 (d, 2H, Ar-H).13C NMR (100 MHz, CDCl3, δ, ppm): 182.26 (C=S), 161.53
(C=O), 145.62 (C-Ar), 141.89 (C-Ar), 139.52 (C-Ar), 131.82 (C-Ar), 131.07 (C-Ar), 130.42
(C-Ar), 129.35 (C-Ar), 129.16 (C-Ar), 129.12 (C-Ar), 128.86 (C-Ar), 127.58 (C-Ar), 126.84
(C-Ar), 121.01 (C-Ar), 117.83 (C-Ar). Anal. calcd. for C20H15ClN2OS: C, 65.48; H, 4.12; N,
7.64. Found: C, 65.18; H, 4.36; N, 7.44 %.
2.4. General procedure for the synthesis of complexes
A solution of HL1-4 (2.0 mmol, HL1: 0.541 g; HL2: 0.598 g; HL3: 0.654 g; HL4: 0.734 g) in
ethanol (50 mL) at 70 °C was added dropwise to a solution of potassium tetrachloroplatinate(II)
(1.0 mmol, 0.416 g) in water (50 mL) at 70 °C. The reaction mixture was stirred for 30 min and
then cooled to room temperature. A yellow-brown precipitate formed which was filtered off and
recrystallized from ethanol:dichloromethane (2:1, v:v) (scheme 2) [30, 31].
2.4.1. Bis[4-chloro-N-(diethylcarbamothioyl)benzamido-O,S]platinum(II), cis-[Pt(L1-S,O)2].
Color: Yellow. Yield: 81% (0.595 g). FT-IR (ATR, ν, cm-1): ν(C-H) 2975, 2932, 2869 (w);
ν(C-N) 1577 (w); ν(C-O) 1488 (vs); ν(C-S) 1087 (s); ν(C-Cl) 749 (w). 1H NMR (400 MHz,
CDCl3, δ, ppm): 8.16 (d, 4H, Ar-H), 7.39 (d, 4H, Ar-H), 3.82 (q, 4H, N-CH2), 3.77 (q, 4H,
N-CH2), 1.34 (t, 6H, CH3), 1.28 (t, 6H, CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 167.53
(C-S), 167.24 (C-O), 137.67 (C-Ar), 136.14 (C-Ar), 130.67 (C-Ar), 128.38(C-Ar), 47.12(C-N),
46.02 (C-N), 31.58 (CH2), 22.64 (CH2), 13.10 (CH3), 12.40 (CH3). Anal. calcd. for
C24H28Cl2PtN4O2S2: C, 39.2; H, 3.8; N, 7.6. Found: C, 39.0; H, 3.8; N, 7.8 %.
2.4.2. Bis[4-chloro-N-(di-n-propylcarbamothioyl)benzamido-O,S]platinum(II),
cis-[Pt(L2-S,O)2]. Color: Yellow. Yield: 78% (0.623 g). FT-IR (ATR, ν, cm-1): ν(C-H) 2962,
2927, 2868 (w); ν(C-N) 1578 (w); ν(C-O) 1487 (vs), ν(C-S) 1088 (s), ν(C-Cl) 750 (w). 1H NMR
(400 MHz, CDCl3, δ, ppm): 8.15 (d, 4H, Ar-H), 7.39 (d, 4H, Ar-H), 3.72 (q, 4H, N-CH2), 3.65
5

(q, 4H, N-CH2), 1.80 (m, 4H, CH2-CH2), 1.71 (m, 4H, CH2-CH2), 0.99 (t,6 H, CH3), 0.94 (t, 6H,
CH3).13C NMR (100 MHz, CDCl3, δ, ppm): 167.71 (C-S), 167.36 (C-O), 137.63 (C-Ar), 136.16
(C-Ar), 130.64 (C-Ar), 128.37 (C-Ar), 54.59 (C-N), 53.49 (C-N), 21.27 (CH2), 20.50 (CH2),
11.40 (CH3). Anal. calcd. for C28H36Cl2PtN4O2S2: C, 42.5; H, 4.6; N, 7.1. Found: C, 41.6; H, 4.6;
N, 7.3 %.
2.4.3. Bis[4-chloro-N-(di-n-butylcarbamothioyl)benzamido-O,S]platinum(II),
cis-[Pt(L3-S,O)2]. Color: Yellow. Yield: 67% (0.567 g). FT-IR (ATR, ν, cm-1): ν(C-H) 2954,
2928, 2869 (w); ν(C-N) 1600 (w); ν(C-O) 1487 (vs); ν(C-S) 1090 (s); ν(C-Cl) 754 (w). 1H NMR
(400 MHz, CDCl3, δ, ppm): 8.16 (d, 4H, Ar-H), 7.38 (d, 4H, Ar-H), 3.76 (q, 4H, N-CH2), 3.68
(q, 4H, N-CH2), 1.41 (m, 4H, CH2-CH2), 1.37 (m,4H, CH2-CH2), 0.98 (t,6H,CH3), 0.94 (t, 6H,
CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 171.51 (C-S), 166.99 (C-O), 137.43 (C-Ar), 136.10
(C-Ar), 130.67 (C-Ar), 128.34 (C-Ar), 52.51 (C-N), 51.51 (C-N), 30.00 (CH2), 29.26 (CH2),
20.33 (CH2), 13.80 (CH3). Anal. calcd. for C32H44Cl2PtN4O2S2: C, 45.4; H, 5.2; N, 6.6. Found:
C, 45.8; H, 5.3; N, 6.8 %.
2.4.4. Bis[4-chloro-N-(diphenylcarbamothioyl)benzamido-O,S]platinum(II),
cis-[Pt(L4-S,O)2]. Color: Brown. Yield: 79% (0.732 g). FT-IR (ATR, ν, cm-1): ν(C-O) 1711,
1588 (s), ν(C-S) 1085 (s), ν(C-Cl) 843, 748 (s). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.94 (d,
2H, Ar-H), 7.88 (d, 2H, Ar-H), 7.64 (t, 4H, Ar-H), 7.58-7.28 (m, 20H, Ar-H).13C NMR (100
MHz, CDCl3, δ, ppm): 167.21 (C-S), 166.83 (C-O), 142.62 (C-Ar), 141.53 (C-Ar), 137.50
(C-Ar), 129.84 (C-Ar), 129.07 (C-Ar), 128.35 (C-Ar), 128.01 (C-Ar), 127.36 (C-Ar), 127.14
(C-Ar), 126.83 (C-Ar), 126.51 (C-Ar), 126.01 (C-Ar), 119.01 (C-Ar), 117.03 (C-Ar). Anal.
calcd. for C40H28N4O2PtS2: C, 51.8; H, 3.0; N, 6.0. Found: C, 50.5; H, 3.2; N, 5.9%.
2.5. Cytotoxicity studies
To evaluate cytotoxicity, HEp-2 human cell line (ATCC CCL23) was selected. In preparation of
the cell cultures, EMEM (Eagle’s minimum essential medium) was used with 10% fetal bovine
serum (Seromed) as growth medium. Incubation of the cells was performed in an atmosphere of
5% carbon dioxide at 37 °C. To determine the effects of the compounds on HEp-2 cells effects of
added compound versus control cells with no added compound were observed. The non-toxic
6

concentration was determined to be up to 1024 µg/mL. We used this limit in all experiments to
test bacterial growth inhibition. In order to test the effects of the compounds on HEp-2 cells,
5×104 cells were seeded into each well of 12-well plates, cultured for 6 h at 28 °C, and allowed
to grow for an additional 48 h in the presence of increasing amounts of compound (0.5, 1, 2, 4, 8,
16, 32, 64, 128, 256, 512, 1024 and 2048 µg/mL). Cytotoxicity of extracts was determined by a
conventional haemocytometer using the trypan blue exclusion method [32-35]. The highest non-
cytocidal (on HEp-2 cells) concentration of the chemical compounds was determined to be
1024 µg/mL. This limit was used for the determination of antimicrobial activities.
2.6. Antimicrobial activity studies
Antimicrobial susceptibility testing was performed by modification microdilution of the
following literature methods [36, 37]. We used the microbial strains Staphylococcus aureus
(ATCC 25923), Streptococcus pneumonia (ATCC 6303), Escherichia coli (ATCC 35218),
Pseudomonas aeruginosa (ATCC 27853), Acinetobacter baumannii (RSHM 2026), Candida
albicans (ATCC 10231) and Candida glabrata (RSHM 40199).
The fungal and bacterial cell inoculums were prepared from the stock culture grown in
Tryptic Soy Agar (TSA) at 28 °C for 24 h and Mueller-Hinton Agar (MHA) 37 °C for 24 h,
respectively. The microorganism suspension concentrations were adjusted according to
McFarland 0.5 turbidity tubes using sterilized saline. A stock solution of the title compound was
prepared in DMSO at 1000 μg/mL. A modified microdilution test was applied for antimicrobial
activity and the experiments were run in duplicates independently.
For antifungal activity testing, 100 μL of Tryptic Soy Broth (TSB) was added to each of
11 wells. 100 μL of chemical derivative solution was added to the first well and 2-fold dilutions
were prepared. Then 5 μL of fungal suspension was added to each tube except the last one,
which acted as a control well.
For antibacterial activity testing, 100 μL of Mueller-Hinton Broth (MHB) was added to
each of 11 wells. 100 μL of chemical derivative solution was added to the first tube and 2-fold
dilutions were prepared. Then 5 μL of the bacterial suspension was added to each tube except the
last control well. Only 5 μL of fungal and bacterial suspension were added in another control
tube without chemical and used as a control for growing. All plates were incubated at 28 °C (for
fungi) and at 37 °C (for bacteria) for 24 h. After the incubation, the minimal inhibitory
7

concentrations (MIC) were noted by controlling the growth inhibition for title compound
(table 1). Fluconazole and ampicillin were used as reference drugs. The results were read
visually and by measuring optical density for 24 h.
3. Results and discussion
3.1. Spectroscopic characterization of the ligand and platinum complexes
Ligands were synthesized in two steps. In the first step, 4-chlorobenzoyl isothiocyanate was
synthesized by reaction of 4-chlorobenzoyl chloride with an equimolar amount of potassium
thiocyanate in dry acetone. In the second step, ligands (HL1-4) were obtained from reaction of
4-chlorobenzoyl isothiocyanate with a secondary amine (diethylamine, di-n-propylamine, di-n-
butylamine and diphenylamine) in dry acetone. Scheme 1 outlines the synthesis of the series of
thiourea derivatives. The ligands were purified by recrystallization from an
ethanol:dichloromethane mixture and characterized by elemental analysis, 1H NMR, 13C NMR
and FT-IR techniques. Data of all synthesized compounds confirm the proposed structures
(figures 1S, 3S, 7S, 9S, 11S, 15S, 17S, 19S, 23S, Supporting Information). The reaction of the
ligands with potassium tetrachloroplatinate(II) at room temperature with an ethanol:water
mixture as solvent yielded the four new complexes cis-[Pt(L1-4-S,O)2] (scheme 2). All the new
metal complexes were recrystallized from an ethanol:dichloromethane mixture and characterized
by elemental analysis, 1H NMR, 13C NMR, COSY, HMQC and FT-IR techniques (figures 2S,
4S, 5S, 6S, 8S, 10S, 12S, 13S, 14S, 16S, 18S, 20S, 21S, 22S and 24S, Supporting Information).
The proposed structures given in schemes 1 and 2 are consistent with the analytical and
spectroscopic data.
IR spectral analysis confirms the presence of characteristic groups in the prepared
compounds. The main vibrational bands of the investigated compounds are given in the
Experimental section. The IR spectra of all prepared ligands showed characteristic bands
approximately at ~3200 cm−1 corresponding to a ν(NH) stretching vibration. This band
disappears upon metal complex formation. The strong ν(C=O) stretching vibration bands for the
free ligands were observed in the range of 1640-1681 cm−1. In the obtained complexes, the
ν(C=O) stretching vibration frequency decreases by ~155-195 cm-1, in agreement with the
literature [38]. A thiocarbonyl ν(C=S) vibration band appeared at 1212-1251 cm−1 for the free
ligands. These bands shifted to lower values (~1085-1090 cm−1) for complex compounds as a
8

result of the coordination via sulfur and oxygen atoms to platinum ions (figures 7S, 8S, 15S, 20S
and 23S, Supporting Information). These results agree with the data supplied in the literature
[38, 39].
The 1H NMR spectra of the ligands were recorded in CDCl3. The 1H NMR data of the
obtained compounds are given in the Experimental section and are consistent with the structural
results. The signals belonging to the NH groups of the ligands were observed the most downfield
as a singlet in the range of δ 8.51-8.85 ppm in the NMR spectra (figures 1S, 9S and 17S,
Supporting Information). But these signals did not appear in the 1H NMR spectrum of the Pt(II)
complexes (figures 2S, 10S and 16S, Supporting Information). The signals for the aromatic
protons in the free ligands were observed at δ ~7-8 ppm; slight variations were observed as a
result of the difference in their environments. After complexation occurred, the aromatic proton
resonance values for protons number 2,2’,4,4’ shifted downfield (Δδ ~0.35 ppm). Protons
number 1,1’,3,3’ are nearly identical (a slight difference in the shift of signals amounting to Δδ
~0.05 ppm). In 1H NMR spectra of the HL1-3 ligands, different 1H resonances are observed for
each of the two ethylene groups of the (S)CN(CH2)2- moiety at room temperature in CDCl3
(δ 4.02 and 3.59 (for HL1); δ 3.91 and 3.47 ppm (for HL2); δ 3.96 and 3.51 ppm (for HL1); δ 4.02
and 3.59 ppm (for HL3)). Since, the resonance in C(O)-NH-C(S)-N part gives the single bond a
double bond character and slows the rotation of the C-N bond [40-45]. For HL1-3 ligands, this
restricted rotation results interestingly in the formation of E/Z configurational isomerism in
solution [43-45]. The coordination of Pt2+ with the ligands does not change the main profile of
the ligands NMR signals of the chemical shifts of the two ethylene groups get closer, indicating
that the anisotropy of the two ethyl groups is less (δ 3.82 and 3.77 (for HL1); δ 3.72 and
3.65 ppm (for cis-[Pt(L1-S,O)2); δ 3.76 and 3.68 ppm (for cis-[Pt(L2-S,O)2); δ 4.02 and 3.59 ppm
(for cis-[Pt(L3-S,O)2)). In other words, a significant consequence of complexation is an increase
of the C-N rotation [43-45]. The most upfield protons in 1H NMR spectra of all the ligands
appear as one sharp triplet between δ 0.85-1.00 ppm which is generated by six protons assigned
to -CH3 groups of ligands. The other aliphatic proton signals (-CH2-CH3, -CH2-CH2 and N-CH2)
of the free ligands are shown relatively in downfield. These resonance values for the complexes
1-3 are almost identical with a slight difference in the shift of signals (figures 1S, 2S, 9S, 10S,
17S and 18S, Supporting Information).
In 13C NMR, the characteristic thiocarbonyl (C=S) and carbonyl (C=O) carbons for all
9

free ligands appeared at δ 179-162 ppm range. The C=S and C=O carbon resonance values of the
complexes shifted upfield (Δδ ~12 ppm) and downfield (Δδ ~5 ppm), respectively, when
compared with the free ligand’s resonances. Consequently, the shift of signals in NMR spectra of
complexes, compared with free ligand, is the result of the complexation process.
3.2. Crystal structure description
Suitable crystals for X-ray analysis of HL2 ligand were obtained upon slow diffusion of
dichloromethane into an ethanolic solution of the ligand. HL2 crystallizes in the monoclinic
space group P21/n. The crystallographic data and structure refinement parameters are
summarized in table 2. Figure 1(a) shows an ORTEP III drawing and atom-labeling, figure 1(b) a
packing diagram and figure 1(c) intra- and intermolecular hydrogen bond interactions of the
ligand.
Single crystal analysis of the ligand revealed that the conformation of the HL2 with
respect to the C=S and C=O groups is twisted, as seen by the torsion angles C8-N1-C1-O1 and
C1-N1-C8-S1 of -12.0(2) and -109.53(14)°, forming weak C12-H12A···S1 3.080(2) Å
intramolecular interactions. The dihedral angle between the O1-C1-N1 and S1-C8-N1 planes is
64.99°. The obtained bond lengths and angles for HL2 are typical for thiourea derivatives; both
C8-S1 (1.677(17) Å) and C1-O1 (1.221(2) Å) bonds show a typical double-bond character. Also,
the C-N bond lengths in -C(O)-NH-C(S)-N part (C1-N1 1.385(2), N1-C8 1.414(2) and N2-C8
1.325(2) Å) are shorter than a normal single C-N bond length (1.469 Å), indicating a double
bond character. Thus, hybridization on nitrogen atoms changes from sp3 to sp2. The main bond
lengths of HL2 are within the ranges obtained for similar compounds. These results are
confirmed by bond angles and lengths (table 3). There are no significant differences in the bond
distances and angles comparing with other benzoylthioureas [32-35, 38, 39, 46].
In the ligand molecules, C9-H9A···O1 (D···A: 3.141(2) Å), C12-H12A···S1 (D···A:
3.080(2) Å) intramolecular interactions occur. These intramolecular hydrogen bonds in the
ligand are shown as a light green dashed line in figure 1(c). The molecules of ligand exhibit a
characteristic intermolecular pattern, forming dimers via N-H···S (N1-H1···S1i (D···A:
3.4437(16) Å, (i) 1-x, 1-y, 2-z)) hydrogen bonding to give an eight-membered ring exhibiting an
R2 (8) hydrogen-bonding motif. This intermolecular hydrogen-bonding motif occurs between the
2
thiocarbonyl sulfur atom and the hydrogen of the amide (figure 1(c)). Also, the ligand molecules
10

are connected to each other through intermolecular C6-H6···S1ii (D···A: 3.7859(18) Å, (ii) x,
-1+y, z) hydrogen bonds and π···π stacking (3.721 Å, (i) 1-x, -y, 2-z). In the crystal structure,
these intermolecular hydrogen bond interactions and π···π stacking allows clustering of
molecules.
A yellow block-shaped crystal of cis-[Pt(L1-4-S,O)2] obtained from recrystallization in
dichloromethane:ethanol (1:1, v:v) mixture was selected and the structure of the platinum
complex was confirmed by the result of single crystal X-ray diffraction determination. The
results confirmed the connectivity of the ligand to the metal as 2:1 and a square planar geometry
around the metal center. Single crystal X-ray analysis shows cis-[Pt(L4-S,O)2] belongs to triclinic
crystal system, space group P-1. The details of crystallographic data and structure refinement
parameters are summarized in table 2. Figure 2(a) shows an ORTEPIII drawing and atom-
labeling and figure 2(b) a schematic of selected bond lengths (Å) for the studied complex, which
is a cis form. The Pt ion lies on a crystallographic center of symmetry and has a slightly distorted
square-planar coordination with two S and O atoms at the corners of coordination. The
coordination angle between O1-O2-Pt and Pt-S1-S2 planes is 0.44. The Pt-S1, Pt-S2, Pt-O1 and
Pt-O2 bond lengths are 2.2306(8), 2.2327(9), 2.027(2) and 2.012(2) Å, respectively. The small
differences between the Pt-S1 and Pt-S2 bond lengths (2.2306(8) compared with 2.2327(9) Å) as
well as between the Pt-O1 and Pt-O2 bond lengths (2.027(2) compared with 2.027(2) Å) lead to
difference between the two chelate rings (Pt-S1-C8-N1-C-O1 and Pt-S2-C28-N3-C21-O2).
These small differences are also reflected in the other pertinent bond lengths and angles. The
origin of these small differences may be due to packing effects [47]. The bond angles of
S1-Pt-S2, S1-Pt-O1, S1-Pt-O2, S2-Pt-O1, S2-Pt-O2 and O1-Pt-O2 are 87.66(3), 95.35(7),
177.85(7), 176.98(7), 94.46(7) and 82.53(9), respectively. These structural parameters imply a
slightly distorted square-planar geometry around the platinum center. Other values of bond
angles and torsion angles are given in table 4.
The double bond character of the carbonyl and thiocarbonyl groups when compared to
literature results are weakened (C1-O1 1.273(4) and C21-O2 1.273(4) Å, C8-S1 1.721(3),
C28-S2 1.728(3) Å) due to the donation of electrons to the metal center (figure 2(b)). The bond
lengths of all C-N bonds of synthesized cis-[Pt(L4-S,O)2] complexes (C1-N1 1.334(4), N1-C8
1.328(4), N3-C21 1.326(4) and N3-C28 1.337(4)) are shorter than the normal C-N single bond
(1.48 Å) and longer than normal C=N double bond (1.25 Å). These results are in agreement with
11

expected delocalization in the molecule and confirmed by C1-N1-C8-N2 and C21-N3-C28-N4
angles [30, 31, 46-54]. All other bond lengths are within normal range (table 4).
The molecular geometry of cis-[Pt(L4-S,O)2] was affected by intra- and intermolecular
hydrogen bond interactions. In addition, the crystal structure is further stabilized by C-H∙∙∙Cg and
Cg ∙∙∙Cg (π···π) interactions (tables 5 and 6), where Cg1 is the center of gravity of Pt(1)-S(1)-
C(8)-N(1)-C(1)-O(1), Cg2 is the center of gravity of Pt(1)-S(2)-C(28)-N(3)-C(21)-O(2), Cg3 is
the center of gravity of C2-C7, Cg4 is the center of gravity of C9-C14, Cg5 is the center of
gravity of C15-C20, Cg6 is the center of gravity of C22-C27, Cg7 is the center of gravity of
C29-C34 and Cg8 is the center of gravity of C35-C40. As shown in figure 3, in the complex,
intermolecular C-H···Cl, C-H···S and C-H···N hydrogen bond interactions occurs
(C13-H13···Cl2i 3.572(4) Å; C12-H12···Cl1ii 3.434(3) Å; C11-H11···S1iii 3.903(4) Å;
C31-H31···S1iv 3.757(4) Å; C17-H17···S1v 3.674(4) Å; C17-H17···S2v 3.728(4) Å;
C20-H20···Cl1vi 3.979(4) Å; C6-H6···Cl2vii 3.796(4) Å; C24-H24···Cl2vii 3.778(4) Å;
C30-H30···N1iv 3.569(4) Å; C18-H18···S1v 3.647(4) Å; C26-H26···Cl2viii 3.402(4) Å;
Symmetry codes: (i) -1+x, -1+y, +z; (ii) 3-1-x, -y, 1-z; (iii) -1+x, +y, +z; (iv) 1+x, +y, +z; (v) 1-x,
-y, 2-z; (vi) -x, -y, 1-z; (vii) 1-x, 1-y, 1-z; (viii) 2-x, 1-y, 1-z. Also, the crystal structure of each
complex displays two different types of π···π stacking, edge-to-face of phenyl rings of ligands
with distances in the range of 3.576-3.683 Å (table 5), and slipped face-to-face of two phenyl
rings with distances in the range of 4.097-5.868 Å (table 6). The C-H···π edge-to-face (C38-
H38···Cg7iii) and π···π face-to-face interactions between the centers of gravity (Cg1···Cg3i,
Cg2···Cg3iii, and Cg5···Cg7vi) of the phenyl rings in molecular packing of cis-[Pt(L4-S,O)2] are
shown in figure 3. These stacking interactions direct the packing of the multilayer structure into a
3D structure.
The dihedral angles between Pt1-S1-C8-N1-C1-O1 and Pt1-S2-C28-N3-C21-O2 planes,
C15-C20 and C9-C14 planes are 4.34 and 81.13°, respectively (figure 4). The unit cell and
packing of the compound viewed approximately along the c axis is given in figure 5. It can be
said that there is a charge accumulation in the diagonals of the unit cell. There is intense electron
localization available in the diagonal points. This is suitable for triclinic unit cell.
3.3. Antimicrobial activity studies
Safety tests, including cytotoxicity assays, are required for all products to be used in contact with
12

humans. Cytotoxicity tests using culture cells have been accepted as a first step in identifying
active compounds and for biosafety testing. Samples were placed in contact with a monolayer of
HEp-2 cells and incubated. The cells were then scored for cytopathic effects [34, 35]. In the
cytotoxicity assay, concentrations up to 1024 µg/mL of the compounds were not toxic for the
replication HEp-2 cells. Thus, lower concentrations of all compounds (1000 µg/mL) were used
for the experiments.
The in vitro biological activity of the four benzoyl thiourea derivative ligands (HL1-4) and
their Pt(II) complexes, cis-[Pt(L1-4-S,O)2], were tested towards five type of bacteria and two
types of fungal. The organisms used in the present investigations included S. aureus and
S. pneumoniae (as Gram positive bacteria), E. coli, P. aeruginosa and A. baumannii (as Gram
negative bacteria) and C. albicans and C. glabrata (as fungal). The results of the biological
activity of the synthesized compounds are recorded and compared with fluconazole (for fungal)
and ampicillin (for bacteria) reference drugs. MIC values of the ligands and their Pt(II)
complexes are listed in table 1.
All free ligands and their Pt(II) complexes inhibited the growth of bacteria strains with
MIC values ranging between 3.90-62.50 μg/mL (table 1). When the synthesized Pt(II) metal
complexes compared with ampicillin, which is used as a reference drug, the synthesized
complexes demonstrated lower activity against S. aureus, S. pneumonia (as Gram positive
bacteria) and A. baumannii (as Gram negative bacteria). In contrast, the synthesized complexes
showed mostly better activity than ampicillin against E. coli and P. aeruginosa (as Gram
negative bacteria). This may be explained by the differences between structures of bacterial cells
[12, 55].
HL1 ligand displayed better activity than ampicillin used as reference drug against E. coli
and P. aeruginosa bacteria with MIC values at 15.62 μg/mL. HL2 ligand and its Pt(II) complex,
cis-[Pt(L2-S,O)2], showed maximum inhibitory action against P. aeruginosa bacterium with MIC
values at 7.80 and 3.90 μg/mL, respectively. They showed better activity than ampicillin, used as
reference drug, against P. aeruginosa bacterium. HL3 ligand exhibited the lowest activities
against E. coli bacterium with MIC values at 125.00 μg/mL but its Pt(II) complex,
cis-[Pt(L3-S,O)2], as effective as ampicillin used as reference drug against E. coli bacterium.
HL4 ligand and its Pt(II) complex, cis-[Pt(L4-S,O)2], are as effective as ampicillin
reference drug against E. coli and P. aeruginosa bacteria with MIC values at 31.25 μg/mL.
13

Among all the complexes, the cis-[Pt(L2-S,O)2] complex showed maximum inhibitory action
against all bacterial strains with MIC values ranging between 3.90 and 15.62 μg/mL (table 1).
All free ligands and their Pt(II) complexes inhibited the growth of fungal strains with
MIC values ranging between 15.62 and 250.00 μg/mL but they are not as effective as
fluconazole used as reference drug against all fungal strains. While all free ligands showed same
activity against fungal with MIC values at 31.25 μg/mL, the cis-[Pt(L1-S,O)2] and
cis-[Pt(L3-S,O)2] complexes exhibited best activity against C. albicans fungal with MIC values at
15.62 μg/mL.
According to data generated from this study, ligands and their Pt(II) complexes are
observed to have different antimicrobial activity despite having similar structures. This is due to
the fact that the zone of inhibition depends on both the diffusion of a compound into the agar
medium and the solubility of compound. When the solubility is low, the diffusion is limited,
resulting in the small zone, even for highly active derivatives presenting low MICs. On the other
hand, high inhibition zone correlated with relatively high MIC could be explained by
precipitation of a compound in the liquid medium and the changing of its real concentration [56].
Ligand HL2 showed excellent inhibition against some bacteria species compared to other ligands.
The structures of HL1 through HL3 vary gradually by increasing one carbon atom each.
However, the antimicrobial results show significant different values for HL2. In comparison to
HL1 and HL2, HL3, which has the longest carbon chain, could have imitated the molecule in the
lipid bilayer of organism and afforded less disruption in the bacteria membrane. Also, it is
known that binding affinities (binding free energy) of compounds to microorganisms through
intermolecular interactions are effective on antimicrobial activity [57]. The increase of carbon
chain in ligands can give rise to lesser binding affinity. Looking at the results obtained, we think
that the binding affinity of HL3 ligand to microorganisms may be lower than that of the other two
ligands [58].
Moreover, antibacterial efficiency is higher than antifungal activity. Antimicrobial
activity against bacteria may be due to the difference between cell structures of bacteria and
fungi. While the cell walls of fungi contain chitin, the cell walls of bacteria contain murein [55].
The cell walls of fungi contain chitin, which enhance the rigidity and structural support. In
addition, fungi contain ergosterol in cell membrane instead of cholesterol in the cell membrane
of animals [9, 54, 60].
14

4. Conclusion
N,N-Di-R-N'-(4-chlorobenzoyl)thiourea type ligands and their Pt(II) complexes have been
synthesized and characterized by elemental analysis, FTIR, 1H, 13C, COSY and HMQC NMR
studies. HL2 ligand and cis-[Pt(L4-S,O)2] metal complex have been also characterized by a
single-crystal X-ray diffraction study. The crystal data reveal that HL2 crystallizes in space group
P21/n of the monoclinic crystal system while the cis-[Pt(L4-S,O)2] complex crystallizes in space
group P-1 of the triclinic crystal system. The central Pt(II) atom is coordinated in cis form by two
S and O donor atoms. The Pt(II) ion in complex has a a slightly distorted square-planar
geometry. The analysis of crystal structures shows that intermolecular interactions have effective
role in stabilization of crystal structure of both compounds. Synthesized compounds were tested
in vitro against Gram positive and Gram negative bacteria and fungi. The evaluation of in vitro
antimicrobial activities of compounds against various bacteria and fungi revealed that the HL2
ligand and its platinum metal complex showed excellent inhibition against some bacteria species
compared to other ligands and complexes. HL2 and its platinum metal complex show best
antimicrobial activity against S. pneumoniae as Gram positive bacteria, P. aeruginosa and
A. baumannii as Gram negative bacteria. The activity of HL2 became more pronounced when
coordinated with the platinum ion. Hence, from all these observations, it was concluded that the
cis-[Pt(L2-S,O)2] complex could be exploited for the design of novel antimicrobial drugs.
Supplementary material
Crystallographic data for the structures reported in this paper have been deposited at the
Cambridge Crystallographic Data Centre (CCDC) with quotation number CCDC-1532704 for
HL2 and CCDC-1532706 for cis-[Pt(L4-S,O)2], and can be obtained free of charge on application
to CCDC 12 Union Road, Cambridge CB2 1EZ, UK [Fax: (internat.) +44(1223)336-033, E-mail:
deposit@ccdc.cam.ac.uk].
Acknowledgements
This work was supported by the Mersin University Research Fund [Project No: 2015-AP4-
1162]. We thank Dicle University Science and Technology Applied and Research Center
(DUPTAM) for X-ray data collection. This academic work was linguistically supported by the
15

Mersin Technology Transfer Office Academic Writing Center of Mersin University.
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Table 1. MIC values (μg/mL) of the ligands and metal complexes tested against the Gram positive,
Gram negative bacteria and fungal and cytotoxicity values (μg/mL) against the HEp-2 human cell
line*.
Gram positive
bacteria
Gram negative bacteria
Fungal
Cytotoxicit
y
(µg/mL)
HEp-2
Compound
S.
S.
A.
P.
C.
C.
E.
aureu pneumonia baumanni
aeruginos albican glabrat
a
coli
s
e
i
s
a
HL1
HL2
HL3
62.50 15.62
62.50 7.80
31.25 31.25
15.62
7.80
31.25
15.62 15.62
62.50 7.80
125.0 31.25
0
31.25
31.25
31.25
31.25
31.25
31.25
1024
1024
2048
HL4
cis-[Pt(L1-
31.25 31.25
62.50 62.50
31.25
31.25
31.25 31.25
31.25 31.25
31.25
15.62
31.25
31.25
1024
2048
S,O)2]
cis-[Pt(L2-
S,O)2]
cis-[Pt(L3-
S,O)2]
cis-[Pt(L4-
S,O)2]
15.62 3.90
62.50 62.50
62.50 62.50
3.90
15.62 3.90
31.25 31.25
31.25 31.25
62.50
15.62
125.00
-
62.50
31.25
250.00
-
2048
1024
2048
31.25
15.62
Fluconazol
e
Ampicillin
K2PtCl4
-
-
-
31.25 31.25
250
250
62.5
125
125
125
62.5
* “-”: Effective in all concentrations used.
19

Table 2. Crystal data and details of the structure refinement for HL2 and cis-[Pt(L4-S,O)2].
Parameters/compound
HL2
cis-[Pt(L4-S,O)2]
Crystal formula
Formula weight
Crystal dimensions (mm)
Temperature (K)
Crystal system
Space group
a (Å)
C14H19ClN2OS
298.82
C40H28Cl2N4O2PtS2
926.77
0.26 × 0.22 × 0.22
100
0.23 × 0.1 × 0.04
100
Monoclinic
P21/n
Triclinic
P-1
11.1405(16)
9.7015(12)
14.790(2)
90
8.9919(3)
14.7159(6)
15.7954(6)
113.9317(18)
97.4490(18)
105.0492(16)
2
b (Å)
c (Å)
α ()
106.547(7)
90
β ()
γ ()
Z
4
Dcalc (g.cm-1)
Range of θ ()
μ (mm-1)
1.295
1.731
6.834 - 63.444
0.380
5.546 - 61.26
4.256
Reflections collected
Index ranges
26237
72763
-15 ≤ h ≤ 14,
14 ≤ k ≤ 12,
-21 ≤ l ≤ 21
-12 ≤ h ≤ 12,
-21 ≤ k ≤ 20,
-22 ≤ l ≤ 22
Reflections used in refinement
No. of refined parameters
Final R indexes [I≥2σ(I)]
4990
194
10913
460
R1 = 0.0494,
wR2 = 0.0918
R1 = 0.0407,
wR2 = 0.0559
Final R indexes [all data]
R1 = 0.0915,
wR2 = 0.1051
R1 = 0.0702,
wR2 = 0.0616
GOF
1.031
1.039
()min-()max (e Å-3)
0.67, -0.70
1.10, -1.53
20

Table 3. Selected bond lengths (Å), bond angles and torsion angles (°) for HL2.
Distance (Å)
Bond angle (°)
Torsion angle (°)
Cl1-C5
S1-C8
1.7392(17)
1.6773(17)
1.221(2)
1.385(2)
1.414(2)
1.325(2)
1.473(2)
1.465(2)
1.487(2)
1.389(2)
1.396(2)
1.387(2)
1.383(2)
1.386(2)
1.382(2)
1.518(2)
1.521(3)
1.583(4)
1.455(6)
1.514(4)
C1-N1-C8
C8-N2-C9
C8-N2-C12
C12-N2-C9
O1-C1-N1
O1-C1-C2
N1-C1-C2
C3-C2-C1
C3-C2-C7
C7-C2-C1
C4-C3-C2
C5-C4-C3
C4-C5-Cl1
N1-C8-S1
N2-C8-S1
N2-C8-N1
N2-C9-C10
C9-C10-C11
N2-C12-C13
119.29(13)
123.31(14)
121.41(14)
115.25(13)
122.22(15)
121.92(14)
115.85(13)
122.61(14)
119.78(15)
117.56(15)
120.21(15)
118.95(16)
119.63(14)
118.93(11)
125.45(13)
115.61(14)
110.51(13)
111.55(15)
104.82(16)
Cl1-C5-C6-C7
O1-C1-C2-C3
O1-C1-C2-C7
N1-C1-C2-C3
N1-C1-C2-C7
N2-C9-C10-C11
N2-C12-C13-C14
N2-C12-C13A-C14A
C1-N1-C8-S1
C1-N1-C8-N2
C1-C2-C3-C4
C1-C2-C7-C6
C2-C3-C4-C5
C3-C2-C7-C6
C3-C4-C5-Cl1
C3-C4-C5-C6
C8-N1-C1-O1
C8-N1-C1-C2
C8-N2-C9-C10
C8-N2-C12-C13
C8-N2-C12-C13A
-178.22(12)
-145.18(17)
32.2(2)
O1-C1
N1-C1
N1-C8
N2-C8
N2-C9
N2-C12
C1-C2
C2-C3
C2-C7
C3-C4
C4-C5
34.0(2)
-148.63(15)
-179.52(15)
-177.13(19)
56.2(5)
-109.53(14)
69.86(19)
177.20(15)
-178.92(14)
1.8(2)
C5-C6
C6-C7
-1.5(2)
176.65(13)
-1.9(3)
C9-C10
C10-C11
C12-C13
C12-C13A
C13-C14
-12.0(2)
168.83(14)
86.65(18)
95.85(19)
69.4(4)
C13A-C12-N2 125.2(3)
C14-C13-C12
C13A-C14A 1.528(10)
110.3(2)
21

Table 4. Selected bond lengths (Å), bond angles and torsion angles (°) for cis-[Pt(L4-S,O)2].
Distance (Å)
Bond angle (°)
Torsion angle (°)
Pt1-S1
Pt1-S2
Pt1-O2
Pt1-O1
S1-C8
2.2306(8)
2.2327(9)
2.012(2)
2.027(2)
1.721(3)
1.728(3)
1.737(3)
1.744(4)
1.273(4)
1.273(4)
1.337(4)
1.326(4)
1.328(4)
1.334(4)
1.364(4)
1.440(4)
1.446(4)
1.354(4)
1.385(5)
S1-Pt1-S2
O2-Pt1-S1
O2-Pt1-S2
O2-Pt1-O1
O1-Pt1-S1
O1-Pt1-S2
C8-S1-Pt1
C28-S2-Pt1
C21-O2-Pt1
C1-O1-Pt1
C21-N3-C28
C8-N1-C1
C8-N2-C9
C8-N2-C15
C9-N2-C15
N1-C8-S1
N1-C8-N2
N2-C8-S1
N3-C28-S2
87.66(3)
177.85(7)
94.46(7)
82.53(9)
95.35(7)
176.98(7)
107.49(11)
107.89(12)
129.6(2)
128.8(2)
126.5(3)
127.5(3)
122.4(3)
122.3(3)
115.4(2)
130.7(2)
114.4(3)
114.8(2)
130.1(3)
Pt1-S1-C8-N1
Pt1-S1-C8-N2
Pt1-S2-C28-N3
Pt1-S2-C28-N4
Pt1-O2-C21-N3
Pt1-O2-C21-C22
Pt1-O1-C1-N1
Pt1-O1-C1-C2
S2-C28-N4-C35
S2-C28-N4-C29
Cl1-C5-C4-C3
N3-C28-N4-C35
N3-C28-N4-C29
N2-C9-C14-C13
N2-C9-C10-C11
C8-N1-C1-O1
C8-N1-C1-C2
C8-N2-C9-C14
C8-N2-C9-C10
-4.8(4)
178.0(2)
-8.4(4)
172.9(2)
-4.4(6)
S2-C28
Cl1-C5
Cl2-C25
O2-C21
O1-C1
N3-C28
N3-C21
N1-C8
N1-C1
N2-C8
N2-C9
N2-C15
C28-N4
C9-C14
176.2(2)
-4.2(5)
174.6(2)
166.2(2)
-1.7(4)
178.3(3)
-12.7(5)
179.5(3)
177.7(3)
-179.0(3)
1.7(6)
-177.2(3)
124.4(3)
-58.7(5)
Table 5. Geometrical parameters of C-H/Cl⋯π interactions for cis-[Pt(L4-S,O)2] (Å, °).
D-H···Cg
d(D-H)
d(H···A)
d(D···A)
d(H···Cg)
(D-H···A)
C30-H30···Cg(1)i
C32-H32···Cg(4)ii
C38-H38···Cg(7)iii
2.72
2.76
2.88
2.68
2.71
2.74
9.67
150
160
143
3.576(4)
3.668(5)
3.683(4)
10.71
17.75
D-Cl···Cg
D-H
H···A
D···A
D—H···A
Cl···Cg
3.690(4)
C5-Cl1···Cg(1)iv
3.8215(15) -3.688
15.18
72.43(15)
Symmetry codes: (i) 1+x, y, z; (ii) 1-x, -y, 2-z; (iii) 3-x, 1-y, 2-z; (iv) -x, -y, 1-z
22

Table 6. Geometrical parameters of the π-stacking moieties involved in the π···π interaction for the cis-[Pt(L4-S,O)2]
(Å, °).
Cg(I) a···Cg(J)
Distance
α b
γ c
Cg(1···Cg(3)i
4.1148(19)
4.8916(19)
5.201(2)
4.0970(19)
5.600(2)
5.358(2)
5.2282(19)
4.1150(19)
4.0970(19)
4.291(2)
5.111(3)
5.603(2)
5.714(3)
5.662(2)
5.020(3)
4.694(2)
5.520(2)
4.516(2)
4.417(2)
5.111(3)
5.241(3)
5.481(2)
5.600(2)
5.682(2)
4.417(2)
5.481(2)
4.645(3)
4.948(2)
5.201(2)
5.358(2)
5.497(3)
5.947(2)
4.645(3)
5.868(2)
13
68
65
17
73
63
63
13
17
0
16
67
65
65
87
81
81
0
13
16
70
71
73
87
13
71
87
87
65
63
89
55
87
87
27.6
83.7
43.7
30.0
45.2
37.4
82.8
33.2
14.1
34.6
37.4
89.3
81.6
61.6
87.8
62.3
61.3
27.5
46.0
45.1
81.9
59.7
37.0
75.7
32.8
33.4
56.4
78.0
35.0
34.5
63.8
86.0
59.0
83.2
Cg(1)···Cg(7)ii
Cg(1)···Cg(8)ii
Cg(2)···Cg(3)iii
Cg(2)···Cg(7)iv
Cg(2)···Cg(8)ii
Cg(2)···Cg(8)iv
Cg(3)···Cg(1)i
Cg(3)···Cg(2)ii
Cg(3)···Cg(3)i
Cg(3)···Cg(6)ii
Cg(3)···Cg(8)ii
Cg(4)···Cg(3)v
Cg(4)···Cg(3)i
Cg(4)···Cg(7)vi
Cg(5)···Cg(4)v
Cg(5)···Cg(4)iii
Cg(5)···Cg(5)vi
Cg(5)···Cg(7)vi
Cg(6)···Cg(3)iii
Cg(6)···Cg(4)vii
Cg(6)···Cg(7)iv
Cg(7)···Cg(2)iv
Cg(7)···Cg(4)iii
Cg(7)···Cg(5)vi
Cg(7)···Cg(6)iv
Cg(7)···Cg(8)v
Cg(7)···Cg(8)viii
Cg(8)···Cg(1)iii
Cg(8)···Cg(2)iii
Cg(8)···Cg(5)vii
Cg(8)···Cg(6)v
Cg(8)···Cg(7)v
Cg(8)···Cg(7)iv
Cg(1): Pt(1)-S(1)-C(8)-N(1)-C(1)-O(1)
Cg(2): Pt(1)-S(2)-C(28)-N(3)-C(21)-O(2)
Cg(3): C(2)-C(3)-C(4)-C(5)-C(6)-C(7)
Cg(4): C(9)-C(10)-C(11)-C(12)-C(13)-C(14)
Cg(5): C(15)-C(16)-C(17)-C(18)-C(19)-C(20)
Cg(6): C(22)-C(23)-C(24)-C(25)-C(26)-C(27)
Cg(7): C(29)-C(30)-C(31)-C(32)-C(33)-C(34)
Cg(8): C(35)-C(36)-C(37)-C(38)-C(39)-C(40)
Symmetry codes: (i) -x, -y, 1-z; (ii) -1+x, y, z; (iii) 1+x, y, z; (iv) 2-x, 1-y, 2-z; (v) x, y, z, (vi) 1-x, -y, 2-z; (vii) 1+x,
1+y, z; (viii) 3-x, 1-y, 2-z.
a Cg(I): Center of gravity of ring I (= ring number in ( ) above),
23

b Dihedral angle between planes I and J.
c Angle Cg(I)···Cg(J) vector and normal to plane J.
Figure captions
Figure 1. (a) ORTEP view of HL2. (b) The crystal packing of HL2. (c) The intramolecular
hydrogen bond interactions (left), intermolecular hydrogen bond and π···π stacking interactions
(right) are shown as green dashed lines in crystal packing of HL2.
Figure 2. (a) ORTEP view of cis-[Pt(L4-S,O)2] with the atom numbering scheme. Displacement
ellipsoids are shown at the 50% probability level. (b) Schematic of selected bond lengths (Å) in
cis-[Pt(L4-S,O)2] complex.
Figure 3. The molecular packing of cis-[Pt(L4-S,O)2] with the intermolecular interactions. The
Cg-Cg (π···π) and C-H···π (Cg) interactions (Symmetry codes: (i) -x, -y, 1-z; (iii) 1+x, y, z;
(vii) 1+x, 1+y, z) are shown as green dashed lines.
Figure 4. The dihedral angle between (a) Pt1-S1-C8-N1-C1-O1 and Pt1-S2-C28-N3-C21-O2 (b)
C15-C20 and C9-C14 planes.
Figure 5. The unit cell and packing of cis-[Pt(L4-S,O)2] viewed approximately along the c axis.
24

25

26

27

28

29