Synthesis, spectroscopic characterization, crystal structure, antimicrobial and in vitro hemolytic studies of some novel substituted thiourea derivatives

Article abstract of DOI:10.1007/s10870-013-0468-0

A series of N,N′-disubstituted thioureas, [R-CONHCSNH-R′] where (R = thiophenyl, furonyl, phenyl and R′ = 4-sulphonamido phenyl, pyrimidine-2yl, thiazole-2yl, 3-nitro phenyl, 2-nitro-4-chloro phenyl, 2-chloro-4-nitro phenyl, 2-methoxy-4-nitro phenyl, and 6-phenyl-1,3,5-triazinyl were synthesized, characterized and screened for their antimicrobial activities. The structures of synthesized compounds were established by elemental analysis and spectroscopic techniques (FT-IR, ¹H NMR, and ¹³C NMR). Single crystal study on compounds 1a and 1c have been done. The compound 1a crystallizes in monoclinic space group Cc, with a = 15.2974(5) A, b = 11.7766(4) A, c = 8.1059(3) A, α = 90, β = 106.31(3), γ = 90 and Z = 4 molecules per unit cell, where as compound 1c crystallizes in orthorhombic space group Pbca, with a = 7.6307(6) A, b = 11.3895(9) A, c = 24.121(2) A, α = β = γ = 90 and Z = 8 molecules per unit cell. All the compounds were tested for their inhibitory activities against four human pathogen bacteria and three fungal strains. The screening data revealed that five compounds showed moderate to good activity whereas one of the compound 1k displayed excellent activity. In vitro hemolytic activity of the compounds has shown them to be nontoxic in nature. Graphical Abstract: Eleven disubstituted thiourea compounds have been synthesized and characterized by elemental analysis, spectroscopic techniques (FT-IR, ¹H NMR, and ¹³C NMR) and single crystal study on two of compounds has been done to understand the proper structural features of the compounds. All the compounds have been screened for their antimicrobial activity; out of them two have shown promising activity against the bacteria and fungi used.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-013-0468-0

J Chem Crystallogr (2013) 43:610–621
DOI 10.1007/s10870-013-0468-0
ORIGINAL PAPER
Synthesis, Spectroscopic Characterization, Crystal structure,
Antimicrobial and In Vitro Hemolytic Studies of Some Novel
Substituted Thiourea Derivatives
•
Durga Prasad Singh Mayank Gangwar
•
•
Dharmendra Kumar Gopal Nath
•
Seema Pratap
Received: 22 April 2013 / Accepted: 3 September 2013 / Published online: 17 September 2013
Ó Springer Science+Business Media New York 2013
Abstract A series of N,N0-disubstituted thioureas, [R–
CONHCSNH–R0] where (R = thiophenyl, furonyl, phenyl
and R0 = 4-sulphonamido phenyl, pyrimidine-2yl, thiazole-
2yl, 3-nitro phenyl, 2-nitro-4-chloro phenyl, 2-chloro-4-
nitro phenyl, 2-methoxy-4-nitro phenyl, and 6-phenyl-1,3,5-
triazinyl were synthesized, characterized and screened for
their antimicrobial activities. The structures of synthesized
compounds were established by elemental analysis and
spectroscopic techniques (FT-IR, 1H NMR, and 13C NMR).
Single crystal study on compounds 1a and 1c have been
done. The compound 1a crystallizes in monoclinic space
Keywords Thiourea ꢀ Single crystal ꢀ Spectroscopic
techniques ꢀ Antimicrobial screening ꢀ Hemolytic
activity
Introduction
There has always been a great interest in the synthesis of
new substituted thiourea derivatives owing to their diverse
applicability in the pharmaceutical industry, material sci-
ence and analytical chemistry. The coordination chemistry
of substituted thioureas is well documented in literature as
they form complexes with many metal ions which facilitate
them to be used in solvent extraction, pre-concentration,
highly efficient chromatographic separations and fluori-
metric determinations [1, 2]. The hydrogen-bonding ability
of the thiourea moiety has extensively been used in con-
struction of anion receptors [3–5] and in the organocata-
lysts [6]. In particular, thioureas have been successfully
used in environmental control, as ionophores in ion
selective electrodes [7–9]. Thiourea and its derivatives
have also been used as effective corrosion inhibitors
because sulphur atom is easily protonated in acidic solution
[10–12]. Nowadays, these derivatives have been employed
successfully as catalysts in the palladium-catalyzed Suzuki
and Heck reactions because thiourea ligands are thermally
stable and insensitive to air and moisture [13–15]. The
pharmaceutical importance of substituted thioureas is
proved by the wide variety of biological activities exhibited
by them such as antibacterial, antifungal [16], anticancer
[17, 18], anti-tubercular [19] and antiviral [20]. A number
of N,N0-disubstituted carbonyl thioureas have been used
extensively as commercial fungicides, herbicides [21] and
insecticides [22]. The inhibitory activity of some pyrida-
zine derivatives carrying thiourea moiety against
˚
group Cc, with a = 15.2974(5) A, b = 11.7766(4) A,
˚
˚
c = 8.1059(3) A, a = 90°, b = 106.31(3)°, c = 90° and
Z = 4 molecules per unit cell, where as compound 1c
crystallizes in orthorhombic space group Pbca, with
˚
˚
˚
a = 7.6307(6) A, b = 11.3895(9) A, c = 24.121(2) A,
a = b = c = 90° and Z = 8 molecules per unit cell. All the
compounds were tested for their inhibitory activities against
four human pathogen bacteria and three fungal strains. The
screening data revealed that five compounds showed mod-
erate to good activity whereas one of the compound 1k dis-
played excellent activity. In vitro hemolytic activity of the
compounds has shown them to be nontoxic in nature.
D. P. Singh ꢀ S. Pratap (&)
Department of Chemistry, MMV, BHU, Varanasi 221005, India
e-mail: drseemapratap@gmail.com
M. Gangwar ꢀ D. Kumar ꢀ G. Nath
Department of Microbiology, IMS, BHU, Varanasi 221005,
India
M. Gangwar
Department of Pharmacology, IMS, BHU, Varanasi 221005,
India
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J Chem Crystallogr (2013) 43:610–621
611
Staphylococcus aureus, Escherichia coli, and Candida
albicans and C. parapsilosis have been reported [23]. The
insecticidal properties of N-aryl-N0-2,6 dichloro benzoyl
thioureas have been reported and it has also been reported
that these compounds are well tolerated by plants and have
low mammalian toxicity [24]. Measuring hemolytic activ-
ities of compounds is becoming a new area of research
nowadays, as it is being used as an indicator of their cy-
totoxicities. In the light of the above facts we present here
the synthesis, characterization and antimicrobial screening
of a series of substituted thiourea compounds.
of both 1a and 1d at 123 K were measured on an Xcalibur,
Ruby, Gemini X-ray diffractometer equipment (Cu Ka
radiation, k = 1.54184 A). The structure were solved by
direct methods [25] and refined anisotropically by full-
matrix least-squares using SHELXL-97 against F2 using all
data [25]. The non-hydrogen atoms are refined anisotropi-
cally. Hydrogen atoms are refined using the riding model.
All calculations were performed by using the winGX sys-
tem, ver. 1.0.05.
˚
Experimental Procedure for Antimicrobial Activity
Disc Diffusion Method
Experimental Details
Antimicrobial activities of newly synthesized compounds
were evaluated on different gram-positive and gram-neg-
ative human pathogens viz. E. coli ATCC 25323, Pseu-
domonas aeruginosa ATCC 27893, Enterococcus faecalis,
S. aureus ATCC 25323 and on different strains of candida
viz. C. albicans ATCC 90028, C. tropicalis ATCC 750, C.
krusie ATCC 6258 according to the guidelines of National
Committee for Clinical Laboratory Standards (NCCLS)
[26] using the agar disc diffusion method. Briefly, a
24/48 h-old culture of selected bacteria/fungi were mixed
with sterile physiological saline (0.85 %) and the turbidity
was adjusted to the standard inoculums of Mac-Farland
scale 0.5 [*106 colony forming units (CFU) per millilitre].
Petri plates containing 20 ml of Mueller–Hinton agar
(MHA, Hi-Media) were used for all the bacteria tested.
Fungi were cultured in Sabouraud’s dextrose agar (SDA)/
potato dextrose agar (PDA) (Hi-Media) and were purified
by single spore isolation technique [27]. The inoculums
was spread on the surface of the solidified media and
Whatman no. 1 filter paper discs (6 mm in diameter)
impregnated with the test compound (20 ll/disc) were
placed on the plates. Ciprofloxacin (5 lg/disc, Hi-Media)
was used as positive control for bacteria. Fluconazole
(10 lg/disc, Hi-Media), was used as positive control for
fungi. A paper disc impregnated with dimethylsulfoxide
(DMSO) was used as negative control. Plates inoculated
with the bacteria were incubated for 24 h at 37 °C and the
fungal culture was incubated for 72 h at 25 °C. The inhi-
bition zone diameters were measured in millimeters. All
the tests were performed in triplicate.
Materials
Thiopphene-2-carbonyl chloride, furoyl chloride, benzoyl
chloride, ammonium thiocynate, 2-amino thiazole, 2-amino
pyrimidine, sulphanilamide, m-nitro aniline, 2-chloro-4-
nitro aniline, 2-nitro-4-chloro aniline, 2-methoxy-4-nitro
aniline and 2,4-diamino-6-phenyl-1,3,5-triazine were pur-
chased from Sigma Aldrich chemical company (USA),
S.D. Fine (Mumbai), Hi-media (Mumbai) and used without
further purification. Solvents acetone, ethyl acetate, petro-
leum ether and ethanol were obtained from Merck and
Ranchem.
Techniques
Melting points of the synthesized compounds were deter-
mined in open-glass capillaries on Stuart-SMP10 melting
point apparatus. IR absorption spectra were recorded on a
Varian 3100 FT–IR Excalibur series spectrophotometer
using KBr pellets in the range of 4,000–400 cm-1, H and
13C NMR spectra were obtained on a JEOL FT-NMR AL
1
300 MHz spectrometer using tetramethylsilane as the
1
internal standard. The H NMR and 13C NMR chemical
shifts were reported as parts per million (ppm) downfield
from TMS (Me4Si). The splitting patterns are designated as
follows; s, singlet; d, doublet; t, triplet; m, multiplet. Ele-
mental analyses were performed on a CE-440 Exeter
Analytical CHN analyzer. All the new compounds gave C,
H and N analysis within 0.03 % of the theoretical values.
Purity of the compounds was checked by thin layer chro-
matography (TLC), 5 9 20 cm plates coated with silica gel
GF254 type 60 (25–250 mesh) using an ethyl acetate-
petroleum ether mixture (1:2) as solvent.
Determination of MIC
Minimum inhibitory concentration (MIC) of any com-
pound is defined as the lowest concentration which com-
pletely inhibits visible growth (turbidity on liquid media).
MIC values were determined by broth micro dilution
method, according to NCCLS guidelines document M27-A
[26]. Equal volume of tested compounds with different
X-ray Crystal Structure Analysis
Crystal data and details of data collection and refinement
for 1a and 1c are summarized in Table 1. Diffraction data
123

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J Chem Crystallogr (2013) 43:610–621
Table 1 Summary of crystallographic data and structural parameters of the compound 1a and 1c
Compound
1a
1c
Empirical formula
Formula weight
Temperature
C12H11N3O3S3
341.42
C12H9N9O3S2
253.31
123(2) K
122.95(10) K
˚
1.54184 A
˚
1.54184 A
Wavelength
Crystal system
Monoclinic
C c
Orthorhombic
P b c a
Space group
Crystal size (mm3)
Unit cell dimensions
0.50 9 0.14 9 0.06
0.5 9 0.16 9 0.03
˚
˚
a = 15.2974(5) A, a = 90°
a = 7.6307(6) A, a = 90°
˚
˚
b = 11.7766(4) A, b = 106.31(3)°
b = 11.3895(9) A, b = 90°
˚
˚
c = 8.1059(3) A, c = 90°
1,401.50(8)
c = 24.121(2) A, c = 90°
2,096.3(3)
3
˚
Volume (A )
Z
4
8
Density (mg/m3)
Absorption coefficient (mm-3
F(000)
1.618
1.605
)
4.974
4.534
704
1,040
Theta range for data collection
Index ranges
4.81–75.44°
3.66–72.55°
-9 B h B 5
-15 B h B 19
-14 B k B 13
-9 B l B 4
-10 B k B 13
-27 B l B 29
Reflections collected
2,523
4,707
Independent reflections
Absorption correction
Refinement method
1535 [R(int) = 0.0260]
Analytical
Full-matrix least-squares on F2
2018 [R(int) = 0.0,761]
Semi-empirical from equivalents
Full-matrix least-squares on F2
2018/0/154
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2 sigma(I)]
R indices (all data)
1535/4/198
1.024
1.069
R1 = 0.0261, wR2 = 0.0690
R1 = 0.0261, wR2 = 0.0692
-3
R1 = 0.0768, wR2 = 0.1997
R1 = 0.0935, wR2 = 0.2221
-3
˚
˚
Largest diff. peak and hole
0.229 and -0.224 e A
0.662 and -0.516 e A
dilutions and nutrient broth were mixed in wells of micro
titer plate, which were diluted two fold in serial to deter-
mine the MIC. Specifically 0.1 ml with approximately
5 9 105 CFU/ml of actively dividing bacterial/fungal cells
was inoculated in each well. The culture plates were
inoculated for 24 h at 37 °C for bacterial growth and 25 °C
for fungal growth. The standard antibiotic, ciprofloxacin
(5 lg/ml) for bacteria and fluconazole (10 lg/ml) for fungi
were used as positive controls and 100 ll of DMSO used as
a negative control. At the end of the incubation period, the
MIC values were determined.
times by sterile phosphate buffered saline (PBS) solution
at pH 7.4. Each washing step was carried out by cen-
trifuging the cells at 3,000 rpm, for *7 min at room
temperature, discarding the supernatant after each wash.
The hRBC were resuspended to give a concentration of
5 9 108cells/ml PBS. Cell suspension was used
throughout in the preparation of experimental and control
tubes. The method reported by [28, 29] was followed.
Compounds solution containing 100 lM test compounds
were mixed with 200 ll of hRBC suspension and final
volume was made up to 1 ml with buffer. The reaction
mixture was then incubated at 37 °C for 1 h with con-
tinuous shaking. The controls were 1 % v/v DMSO in
PBS and sterile water, after which the reaction mixture
was, centrifuged (1,300 rpm, 5 min) and absorbance read
at 540 nm. Turbidity was measured by reading absor-
bance at 540 nm using a multi-well plate Bio-Rad
ELISA reader and observing a decrease in optical den-
sity associated with cRBCs lyses.
Determination of Hemolytic Activity of Compounds
on Human Red Blood Cells (hRBC)
Hemolytic assay of Compounds 1a–1k were carried out
and tested for hemolytic activities on human hRBC at a
fixed concentration of 100 lgm/ml. Freshly collected
human red blood cells were taken and washed three
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J Chem Crystallogr (2013) 43:610–621
General Procedure for Synthesis
613
N-[3-(Thiazole-2-yl)]-N0-[2-furoyl] thiourea (1c)
A solution of thiophenoyl chloride (1.065 ml, 0.01 mol
(1.465 g) or furoyl chloride (0.984 ml, 0.01 mol (1.305 g) in
acetone (50 ml) was added drop-wise to a suspension of
ammonium thiocyanate (0.76 g, 0.01 mol) in acetone (30 ml)
and the reaction mixture was refluxed for 45 min. After cooling
to room temperature, a solution of corresponding amine
(0.01 mol) in acetone (25 ml) was added and the resulting
mixture refluxed for 1.5 h. The reaction mixture was poured
into five time its volume of cold water. The desired thioureas
precipitated as solid were washed with water and recrystallized
in ethanol. The light yellow color crystals of two compounds
(1a, 1c) suitable for single crystal study were obtained by slow
evaporation of ethanolic solution of compounds at *30 °C.
Yield: 82 %(2.07 g), m.p.; 172–173 °C. Elemental analy-
ses: calculated for C9H7N3O2S2 (%), C, 42.67; H, 2.78; N,
16.58; Found, C, 42.61; H, 2.78; N, 15.53. IR (KBr, cm-1):
3,244, 3,109 ms (N–H), 3,013 (aromatic C–H), 1,656
(amide-I, C=O), 1,582, (Ph, C=C), 1,521 (thioamide-I),
1,312 (thioamide-II), 1,189 (thioamide-III), 753, 718 (thi-
oamide-IV); The main signals in 1H NMR (300 MHz,
DMSO-d6, 25 °C): d 13.15 (s, 1H, hydrogen bonded-NH),
9.01 (s, 1H, free-NH), 7.56 (d, J(H, H) = 8.1, 2H, furan-
H), 7.41 (t, J1(H, H) = 7.2 Hz, J2(H, H) = 7.6 Hz, 1H,
furan-H), 7.11 (d, J(H, H) = 9.3, 1H, thiazole-H), 6.68 (d,
J(H, H) = 9.3 Hz, 1H, thiazole-H); 13C NMR (75 MHz,
CDCl3, 25 °C): dc 175.46(C=S), 161.65(C=O), 158.36,
138.42, 134.88, 133.54, 131.26, 130.84, 127.44.
N-[4-Sulfonamide phenyl]-N0-[2-thiophenoyl] thiourea
(1a)
N-[3-(Thiazole-2-yl)]-N0-[2-thiophenoyl] thiourea (1d)
Yield: 81 % (2.765 g), m.p.; 210–211 °C. Elemental analy-
ses: calculated for C12H11N3O3S3 (%), C, 32.78; H, 2.56; N,
9.56; Found, C, 32.72; H, 2.50; N, 9.54; IR (KBr, cm-1):
3,337, 3,295, 3,255 ms (N–H), 3,093, 3,014 (aromatic C–H),
1,654 (amide-I, C=O), 1,590 (Ph), 1,535 (thioamide-I), 1,342
(thioamide-II), 1,158 (thioamide-III), 728 (thioamide-IV);
The main signals in 1H NMR (300 MHz, CDCl3, 25 °C): d
13.13 (s, 1H, hydrogen bonded-NH), 9.21 (s, 1H, –NH), 8.79
(d, J(H, H) = 8.1, 1H, thiophene-H), 8.35 (d, J(H,
H) = 7.2 Hz, 1H, thiophene-H), 7.72 (t, J(H,H) = 7.6 Hz,
1H, thiophene-H), 7.49 (d, J(H, H) = 6.9 Hz, 2H, Ar–H),
6.91(s, 2H, –SO2NH2), 6.65 (d, J(H, H) = 6.9 Hz, 2H, Ar–
H); 13C NMR (75 MHz, DMSO-d6, 25 °C): dc 179.30(C=S),
170.12(C=O), 151.86, 145.13, 132.23, 131.68, 131.28,
128.34, 128.95, 127.86.
Yield: 83 %(2.23 g), m.p.; 143–144 °C. Elemental analy-
ses: calculated for C9H7N3OS3 (%), C, 40.12; H, 2.61; N,
15.51; Found, C, 40.15; H, 2.66; N, 15.54; IR (KBr, cm-1):
3,219, 3,088 ms (N–H), 3,008 (aromatic C–H), 1,654
(amide-I, C=O), 1,588, (Ph, C=C), 1,542 (thioamide-I),
1,308 (thioamide-II), 1,197 (thioamide-III), 736 (thioam-
1
ide-IV); The main signals in H NMR (300 MHz, CDCl3,
25 °C): d 13.60 (s, 1H, hydrogen bonded-NH), 9.26 (s, 1H,
free-NH), 7.62 (d, J = 8.3, 2H, thiophene-H), 7.44 (t, J1(H,
H) = 7.2 Hz, J2(H, H) = 7.8 Hz, 1H, thiophene-H), 7.03
(d, J(H, H) = 9.3, 1H, thiazole-H), 6.66 (d,
J(H,H) = 9.0 Hz, 1H, thiazole-H); 13C NMR (75 MHz,
CDCl3, 25 °C): dc 174.52(C = S), 160.81(C=O), 159.46,
138.50, 134.78, 132.54, 131.21, 130.04, 128.27.
N-[m-Nitro phenyl]-N0-[2-thiophenoyl] thiourea (1e)
N-[Pyrimidine-2-yl]-N0-[2-thiophenoyl] thiourea (1b)
Yield: 81 %(2.37 g), m.p.; 204–205 °C. Elemental analy-
ses: calculated for C12H9N2O3S2 (%), C, 46.85; H, 2.92; N,
13.66; Found, C, 46.79; H, 2.96; N, 13.69; IR (KBr, cm-1):
3,373, 3,097 ms (N–H), 3,012 (aromatic C–H), 1,658
(amide-I, C=O), 1,600, 1,562 (Ph, C=C), 1,519 (thioamide-
I), 1,345 (thioamide-II), 1,145 (thioamide-III), 716 (thio-
amide-IV); The main signals in 1H NMR (300 MHz,
DMSO-d6, 25 °C): d 12.55 (s, 1H, hydrogen bonded-NH),
11.78 (s, 1H, free-NH), 8.75 (d, J(H, H) = 7.6, 1H, thio-
phene-H), 8.38 (d, J(H, H) = 7.8 Hz, 1H, thiophene-H),
8.05 (t, J(H, H) = 6.8 Hz, 1H, thiophene-H), 7.69 (s, J(H,
H) = 7.2 Hz, 1H, Ar–H), 7.26 (m, 3H, Ar–H); 13C NMR
(75 MHz, CDCl3, 25 °C): dc 179.45 (C=S), 161.84 (C=O),
147.50, 139.23, 136.57, 135.55, 132.87, 131.10, 129.97,
128.80, 120.86, 119.02.
Yield: 76 % (2.006), m.p.; 182–183 °C. Elemental analyses:
calculated for C10H8N4OS2 (MW = 264.32) in wt%, C,
45.43; H, 3.05; N, 21.19; Found C, 45.49; H, 3.11; N, 21.29;
IR (KBr, cm-1): 3,373, 3,097 ms (N–H), 3,020 (Ar–H), 1,658
(amide-I, C=O), 1,600, 1,564 (Ph), 1,504 (thioamide-I), 1,321
(thioamide-II), 1,155 (thioamide-III), 745 (thioamide-IV);
The main signals in 1H NMR (300 MHz, DMSO-d6, 25 °C):
d13.58(s, 1H, hydrogenbonded-NH), 12.10(s, 1H, free-NH),
8.79 (d, J(H,H) = 7.5 Hz, 2H, pyrimidine-H), 8.05 (d, J(H,
H) = 7.2 Hz, 1H thiophene-H), 7.47 (d, J(H, H) = 7.4, 1H,
thiophene-H), 7.28 (t, J1(H, H) = 7.8 Hz, J2(H,H) = 7.6 Hz,
1H, thiophene-H), 7.10 (t, J1(H, H) = 7.2 Hz, J2(H,
H) = 7.4 Hz, 1H, PYrimidine-H); 13C NMR (75 MHz,
DMSO-d6, 25 °C): dc 176.45(C=S), 158.24(C=O), 156.16,
154.23, 146.57, 143.55, 116.87, 115.42, 112.02.
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J Chem Crystallogr (2013) 43:610–621
N-[2-cl-4-Nitro phenyl]-N0-[2-furoyl] thiourea (1f)
N-[2-cl-4-Nitro phenyl]-N0-[2-thiophenoyl] thiourea (1i)
Yield: 81 %(2.63 g), m.p.; 173–174 °C. 42 Elemental anal-
yses: calculated for C12H8N3O4S1Cl (%), C, 44.24; H, 2.48;
N, 12.91; Found, C, 44.18; H, 2.42; N, 12.87; IR (KBr, cm-1):
3,373, 3,097ms (N–H), 3,020 (aromatic C–H), 1,658 (amide-I,
C=O), 1,600, 1,564 (Ph), 1,504 (thioamide-I), 1,321 (thio-
amide-II), 1,155 (thioamide-III), 745 (thioamide-IV); The
main signals in 1H NMR (300 MHz, CDCl3, 25 °C): d 13.10
(s, 1H, hydrogen bonded-NH), 9.11 (s, 1H, free-NH), 8.72 (d,
J = 9.1 Hz, 1H, furon-H), 8.36 (s, 1H, Ar CH), 8.12 (d, J(H,
H) = 8.2 Hz, 1H, thiophene-H), 7.67 (t, J1(H, H) = 7.1 Hz,
J2(H, H) = 7.8 Hz, 1H, thiophene-H), 7.74 (d,
J(H,H) = 8.2 Hz, 1H, Ar–H), 6.70 (d, J(H, H) = 7.6 Hz, 1H,
Ar–H); 13C NMR (75 MHz, CDCl3, 25 °C): dc 179.67 (C=S),
170.04 (C=O), 146.45, 139.24, 137.53, 134.64, 131.87,
130.69, 129.46, 128.80, 124.25, 122.42.
Yield: 76 %(2.59 g), m.p.; 173–174 °C. Elemental analy-
ses: calculated for C12H8N3O3S2Cl (%), C, 42.16; H, 2.36;
N, 12.29; Found, C, 42.24; H, 2.38; N, 12.35; IR (KBr,
cm-1): 3,373, 3,097 ms (N–H), 3,020 (aromatic C–H),
1,658 (amide-I, C=O), 1,600, 1,564 (Ph), 1,504 (thiourei-
do-I), 1,321 (thioureido-II), 1,155 (thioureido-III), 745
1
(thioureido-IV); The main signals in H NMR (300 MHz,
CDCl3, 25 °C): d 13.07 (s, 1H, hydrogen bonded-NH), 8.98
(s, 1H, free-NH), 9.05 (d, J(H, H) = 9.0 Hz, 1H, thio-
phene-H), 8.35 (s, 1H, Ar CH), 8.18 (d, J(H, H) = 8.4 Hz,
1H, thiophene-H), 7.97 (t, J1(H, H) = 7.2 Hz, J2(H,
H) = 7.8 Hz, 1H, thiophene-H), 7.76 (d, J(H, H) = 8.1,
1H, Ar–H), 6.72 (d, J(H, H) = 7.2, 1H, Ar–H); 13C NMR
(75 MHz, CDCl3, 25 °C): dc 179.45(C=S), 169.74(C=O),
146.50, 142.23, 137.57, 136.54, 131.87, 130.39, 129.67,
128.80, 124.50, 122.32.
N-[Pyridine-2-yl]-N0-[2-thiophenoyl] thiourea (1g)
N-[4-Chloro-2-nitro phenyl]-N0-[2-thiophenoyl] thiourea
Yield: 78 %(2.05 g), m.p.; 242–243 °C. Elemental analy-
ses: calculated for C11H9N3O1S2 (%), C, 50.17; H, 3.44; N,
15.95; Found, C, 50.24; H, 3.48; N, 15.98; IR (KBr, cm-1):
3,373, 3,097 ms (N–H), 3,020 (aromatic-H), 1,658 (amide-I,
C=O), 1,600, 1,564 (Ph), 1,504 (thioamide-I), 1,321 (thi-
oamide-II), 1,155 (thioamide-III), 745 (thioamide-IV); The
main signals in 1H NMR (300 MHz, CDCl3, 25 °C): d
12.90 (s, 1H, hydrogen bonded-NH), 8.88 (s, 1H, free-NH),
8.78 (d, J(H, H) = 8.1 Hz, 1H, thiophene-H), 8.44 (t, J1(H,
H) = 7.7 Hz, J2(H, H) = 7.2 Hz, 1H thiophene-H), 7.77
(d, J(H, H) = 7.8 Hz, 1H thiophene-H), 7.23 (m, 4H, Py-
H); 13C NMR (75 MHz, CDCl3, 25 °C): dc 177.65 (C=S),
169.12 (C=O), 154.04, 148.52, 138.23, 137.87, 132.58,
131.27, 129.14, 118.07, 113.68.
(1j)
Yield: 75 %(2.56 g), m.p.; 145–147 °C. Elemental analy-
ses: calculated for C12H8N3O3S2Cl (%),C, 42.16; H, 2.36;
N, 12.29; Found, C, 42.22; H, 2.39; N, 12.34; IR (KBr,
cm-1): 3,373, 3,097 ms (N–H), 3,012 (aromatic C–H),
1,658 (amide-I, C=O), 1,600, 1,562 (Ph, C=C), 1,519
(thioamide-I), 1,345 (thioamide-II), 1,145 (thioamide-III),
716 (thioamide-IV); The main signals in 1H NMR
(300 MHz, DMSO-d6, 25 °C): d 12.39 (s, 1H, hydrogen
bonded-NH), 11.77 (s, 1H, free-NH), 8.37 (d, J = 7.8 Hz,
1H, thiophene-H), 8.15 (d, J(H, H) = 7.8 Hz, 1H thio-
phene-H), 8.09 (s, 1H, Ar–H), 7.65 (d, J(H, H) = 7.2, 1H,
Ar–H), 7.28 (d, J(H, H) = 7.8, 1H, thiophene-H), 6.85 (d,
J1(H, H) = 7.2, Hz, J2(H, H) = 6.9 Hz, 1H Ar–H); 13C
NMR (75 MHz, CDCl3, 25 °C): dc 179.64 (C=S), 169.80
(C=O), 149.56, 137.62, 135.26, 134.64, 132.55, 130.81,
129.6, 128.94, 128.80, 126.86.
N-[2-Methoxy-4-nitro phenyl]-N0-[2-furoyl] thiourea (1h)
Yield: 78 %(2.63 g), m.p.; 183–184 °C. Elemental analy-
ses: calculated for C13H11N3O4S2 (%), C, 46.28; H, 3.28;
N, 12.45; Found, C, 46.36; H, 3.32; N, 12.49; IR (KBr,
cm-1): 3,373, 3,097 ms (N–H), 3,020 (aromatic C–H),
1,658 (amide-I, C=O), 1,600, 1,564 (Ph), 1,504 (thiourei-
do-I), 1,321 (thioureido-II), 1,155 (thioureido-III), 745
N-[6-Phenyl-1,3,5-triazinyl]-N0-benzoyl thiourea (1k)
Yield: 70 %(3.59 g), m.p.; 162–164 °C. Elemental analy-
ses: calculated for C25H19N7O2S2 (%), C, 58.46; H, 3.72;
N, 19.09; Found, C, 58.58; H, 3.76; N, 19.18; IR (KBr,
cm-1): 3,325, 3,135 ms (N–H), 3,052 (aromatic C–H),
1,656 (amide-I, C=O), 1,610, 1,568 (Ph, C=C), 1,526
(thioamide-I), 1,348 (thioamide-II), 1,141 (thioamide-III),
726 (thioamide-IV); The main signals in 1H NMR
(300 MHz, DMSO-d6, 25 °C): d 13.10 (s, 2H, hydrogen
bonded-NH), 11.66 (s, 2H, free-NH), 8.24 (d, J(H,
H) = 7.2 Hz, 2H, aromatic-H), 8.09(d, J(H, H) = 7.6 Hz,
4H aromatic-H), 7.98–6.96 (m, 9H, Ar–H); 13C NMR
(75 MHz, DMSO-d6, 25 °C): dc 178.14 (C=S), 167.52
1
(thioureido-IV); The main signals in H NMR (300 MHz,
CDCl3, 25 °C): d 13.01 (s, 1H, hydrogen bonded-NH), 9.26
(s, 1H, free-NH), 9.21 (d, J(H, H) = 5.7, 1H, thiophene-H),
7.92 (d, J(H, H) = 9.0 Hz, 1H, thiophene-H), 7.79 (s, 1H,
Ar–H), 7.63 (d, J(H, H) = 7.2 Hz, 1H, Ar–H), 7.35(t, J1(H,
H) = 7.6 Hz, J2(H, H) = 7.2 Hz, 1H thiophene-H) 6.86 (d,
J(H, H) = 9.0, 1H, Ar–H) 3.98(s, 3H, OCH3); 13C NMR
(75 MHz, CDCl3, 25 °C): dc 179.48 (C=S), 169.64 (C=O),
159.88, 145.50, 138.23, 132.57, 131.55, 130.87, 129.10,
120.37, 116.80, 105.86, 55.98.
123

J Chem Crystallogr (2013) 43:610–621
615
(C=O), 152.86, 144.72, 135.54, 133.89, 132.45, 131.60,
130.65, 129.46, 128.64, 127.24, 121.23.
compound 1a and 1c are shorter than the normal C–N
˚
single-bond length of about 1.48 A. The above can be
Note: [thioamide-I; d (N2–H), thioamide-II; mas (N–C–
N), thioamide-III; ms (N–C–N), thioamide-IV; m (C=S).
explained on the basis of existence of resonance in this part
of the molecule. In 1a the thiophene ring (C4/C3/C2/C1/
S1) is inclined 6.91(0.16)° with respect to the plane formed
by the thiourea moiety (N1–C6–S2–N2), while the phenyl
ring (C7/C8/C9/C10/C11/C12) is inclined 13.58(0.14)°
with thiourea moiety. The thiophene ring (C4/C3/C2/C1/
S1) is inclined 10.53(0.14)° with respect to the plane
formed by the phenyl ring (C7/C8/C9/C10/C11/C12). In 1c
the furan ring (O1/C1/C2/C3/C4/C5) are inclined
4.37(0.28)° with respect to the plane formed by the thio-
urea moiety (N1–C6–S1–N2), while the thiazole ring (S2/
C7/N3/C8/C9) is inclined 3.69(0.25)° with respect to the
plane formed by thiourea moiety. The angle between plane
formed by furan ring (O1/C1/C2/C3/C4/C5) and thiazole
ring (S2/C7/N3/C8/C9) is 1.20(0.29). The trans–cis
geometry in the thiourea moiety is stabilized by the N2–
H2ꢀꢀꢀO1(O2) intramolecular hydrogen bonding which also
locks the –CONHCSNHR– unit into a stable planar six-
membered ring structure (Figs. 1, 2; Tables 4, 5). It has
been reported that such strong interactions are maintained
in solutions also [33]. In S-shaped conformation between
the C=O and C=S groups (two donors sites rich in electron
density), the O–S distance is maximum, contributing to a
minimum conformational energy of the molecule as a
whole [34]. In the crystal structure of 1a, symmetry related
molecules are linked by three different N–HꢀꢀꢀO interac-
tions and one C–HꢀꢀꢀO interaction to form one dimensional
supramolecular chain along b-axis (Fig. 3a, b), while in 1c
symmetry related molecules are linked by N1–H1ꢀꢀꢀN3
interaction to form one dimensional supramolecular chain
along a-axis (Fig. 4a, b; Tables 3, 4, 5).
Result and Discussion
Synthesis and Characterization
The general synthetic route for the target compounds is
outlined in scheme 1. The target compounds were syn-
thesized by slight modification of the reported literature
procedure [30]. On the basis of elemental analysis and
spectral studies the structures of the compounds have been
1
proposed. In the H NMR spectra of all the compounds in
CDCl3 the signal appearing at *9.00 ppm is due to O=C–
N1H proton. These peaks suffer a downfield shift of
*3 ppm when the spectra are recorded in DMSO-d6. This
is due to polarity effect of solvent. Since DMSO is highly
polar solvent hence upon addition of DMSO-d6, a dipole–
dipole interaction occurs between the oxygen atom of
DMSO-d6 and H-atom of O=C–N1H group. The S=C–
N2H peak in all the above compounds appeared in range
12.53–14.09 ppm. The high d value of this peak in com-
parison to N1H proton is due to strong intramolecular
(C=OꢀꢀꢀN2H) hydrogen bonding resulting in formation of
pseudo six-member ring as shown in Fig. 1. Since
intramolecular hydrogen bonding is unaffected by polarity
of solvent, so this peak appears nearly in same region in
DMSO. In the 13C NMR spectra of the compounds the
peaks at *179 and *165 ppm may be attributed to C=S
and C=O group carbons respectively. The rest of the peaks
are due to ring carbons. Absorption bands appearing at
*3,300 and *3,100 cm-1 in the IR spectra of compounds
are due to free –NH and associated –NH group respec-
tively. The band appearing at *1,655 cm-1 due to amide
group (C=O–NH), is lower than normal amide group
absorption (1,680 cm-1) which may be attributed to the
formation of hydrogen bonding explained above.
Antimicrobial Activity
All the synthesized thiourea derivatives (1a–1k) were
checked for their antibacterial and antifungal activities,
quantitatively and qualitatively. The inhibitory activity was
quantified by the occurrence of a growth inhibition zone
and MIC values (Tables 6, 7, 8, 9). The results of the
antibacterial screening revealed that six of the tested
compounds inhibited the growth of bacterial colonies.
Compound 1b inhibited the growth of S. aureus (MIC
*300 lg/ml) whereas compound 1d inhibited the growth
of E. coli only with MIC values 300 and 150 lg/ml
respectively. Compounds 1d and 1e inhibited the growth of
both S. aureus and E. coli with MIC values 75 and 300 lg/
ml respectively. Compound 1k exhibited excellent activity
against all the bacterial strains used, with the MIC values
even lower than the control drug except for P. aeruginosa
(Table 7). The results of the antifungal screening showed
The Crystal Structure
The molecular structure of compounds 1a and 1c have been
depicted in Figs. 1 and 2 respectively. Selected bond
lengths and bond angles are listed in Table 2. The main
bond lengths are within the range obtained for similar
˚
compounds [31, 32]. The bond lengths S2–C6, 1.656 A;
˚
˚
˚
S1–C6, 1.648 A; O1–C5, 1.234 A and O2–C5, 1.231 A
show usual double bond character. However, for the C–N
bonds, bond lengths N1–C5, N1–C6 and N2–C6 in both
123

616
J Chem Crystallogr (2013) 43:610–621
Scheme 1 Synthetic rout of
compounds from 1a to 1k
Fig. 1 Single-crystal X-ray structure of N-[4-sulphonamide phenyl]-
N0-[2-thiophenoyl] thiourea (1a) with the atom labeling scheme and
50 % displacement ellipsoids. The dashed line shows intermolecular
and intramolecular hydrogen bonds
Fig. 2 Single-crystal X-ray structure of N-[3-(thiazole-2-yl]-N0-[2-
furoyl] thiourea (1c), with the atom labeling scheme and 50 %
displacement ellipsoids
123

J Chem Crystallogr (2013) 43:610–621
617
Table 2 Bond length and bond angles of 1a and 1c
Table 3 Torsion angles [°] of 1a and 1c
Torsion angles (°)
1a
Torsion angles (°)
1c
1a
1c
˚
Bond length (A)
C(6)–N(1)–C(5)–O(1)
C(6)–N(1)–C(5)–C(4)
C(7)–N(2)–C(6)–N(1)
C(7)–N(2)–C(6)–S(2)
C(5)–N(1)–C(6)–N(2)
C(5)–N(1)–C(6)–S(2)
C(6)–N(2)–C(7)–C(8)
C(6)–N(2)–C(7)–C(12)
5.4(4)
C(6)–N(1)–C(5)–O(2)
C(6)–N(1)–C(5)–C(4)
C(7)–N(2)–C(6)–N(1)
C(7)–N(2)–C(6)–S(1)
O(1)–C(4)–C(5)–O(2)
C(3)–C(4)–C(5)–N(1)
C(6)–N(2)–C(7)–N(3)
C(6)–N(2)–C(7)–S(2)
0.5(7)
-173.9(2)
-171.9(2)
8.9(4)
-178.7(4)
-176.5(4)
4.9(7)
S(2)–C(6)
1.656(2)
1.234(3)
1.372(3)
1.410(3)
1.344(3)
1.404(3)
1.466(3)
S(1)–C(6)
O(2)–C(5)
N(1)–C(5)
N(1)–C(6)
N(2)–C(6)
N(2)–C(7)
C(4)–C(5)
1.648(4)
1.231(5)
1.374(5)
1.410(5)
1.357(5)
1.384(5)
1.463(6)
O(1)–C(5)
N(1)–C(5)
-8.8(3)
170.5(2)
5.4(5)
-179.9(4)
-179.2(4)
175.1(4)
-6.6(7)
N(1)–C(6)
N(2)–C(6)
N(2)–C(7)
-178.4(3)
C(4)–C(5)
Bond angles (°)
C(5)–N(1)–C(6)
C(6)–N(2)–C(7)
C(5)–C(4)–S(1)
O(1)–C(5)–N(1)
O(1)–C(5)–C(4)
N(1)–C(5)–C(4)
N(2)–C(6)–N(1)
N(2)–C(6)–S(2)
N(1)–C(6)–S(2)
C(8)–C(7)–N(2)
C(12)–C(7)–N(2)
128.0(2)
C(5)–N(1)–C(6)
C(6)–N(2)–C(7)
C(3)–C(4)–C(5)
O(2)–C(5)–N(1)
O(2)–C(5)–C(4)
N(1)–C(5)–C(4)
N(2)–C(6)–N(1)
N(2)–C(6)–S(1)
N(1)–C(6)–S(1)
N(2)–C(7)–S(2)
N(3)–C(7)–N(2)
126.8(4)
132.2(2)
117.32(19)
122.9(2)
120.5(2)
116.6(2)
113.3(2)
129.00(19)
117.66(18)
126.6(2)
113.5(2)
127.4(4)
130.2(4)
124.0(4)
119.3(4)
116.8(4)
114.8(4)
125.4(3)
119.8(3)
125.6(3)
118.6(4)
˚
Table 4 Hydrogen bonds for 1a [A and °]
D–HꢀꢀꢀA
d(D–H)
d(HꢀꢀꢀA) d(DꢀꢀꢀA) \(DHA)
N(1)–H(1B)ꢀꢀꢀO(3)#1
N(2)–H(2B)ꢀꢀꢀO(1)
0.78(4)
0.82(4)
2.14(4)
1.87(4)
2.883(3) 160(4)
2.602(3) 147(4)
2.958(3) 165(4)
2.962(3) 166(5)
N(3)–H(3N1)ꢀꢀꢀO(1)#2 0.859(19) 2.12(2)
N(3)–H(3N2)ꢀꢀꢀO(2)#3 0.84(2)
2.14(2)
Symmetry transformations used to generate equivalent atoms: #1
x - 1/2, y - 1/2, z - 1 #2 x ? 1/2, -y ? 3/2, z ? 1/2 #3 x, -
y ? 1, z - 1/2
Fig. 3 a, b Illustrates the
packing pattern of N-[4-
sulphonamide phenyl]-N0-[2-
thiophenoyl] thiourea (1a) along
b axis, the dashed lines
represent the intermolecular and
intramolecular hydrogen bonds
Fig. 4 a, b Illustrates the
packing pattern of N-[3-
(thiazole-2-yl]-N0-[2-furoyl]
thiourea (1c) along a axis, the
dashed lines represent the
intermolecular and
intramolecular hydrogen bonds
123

618
J Chem Crystallogr (2013) 43:610–621
that the compounds 1c and 1g displayed activity against C.
allicans and C. tropicalis only whereas compounds 1d and
1k inhibited the growth of all the tested fungal strains.
Compound 1j inhibited the growth of C. albicans and 1e of
C. krusie only with MIC value 150 lg/ml (Tables 8, 9).
These results are depicted well for both bacteria and fungus
in Figs. 5, 6, 7, 8, 9. The difference in the bioactivity of the
compounds can be correlated to the lipophilic behavior of
the compounds. It has been observed that the compounds
having high lipophilic tendency show good inhibitory
activity [35, 36]. The presence of a heterocyclic ring
together with the thioamide group in a compound probably
enhances its lipophillic nature, which results in a higher
capability to penetrate the micro-organisms through the
lipid layer of the cell membrane [35, 36].
˚
Table 5 Hydrogen bonds for 1c [A and °]
D–HꢀꢀꢀA
N(1)–H(1N1)ꢀꢀꢀN(3)#1 0.91(5)
N(2)–H(2N2)ꢀꢀꢀO(2) 0.79(5)
d(D–H) d(HꢀꢀꢀA) d(DꢀꢀꢀA) \(DHA)
2.18(6)
1.93(5)
3.092(5) 178(6)
2.612(5) 144(5)
Symmetry transformations used to generate equivalent atoms:
#1 -x ? 3/2, y - 1/2, z
Table 6 Antibacterial activity
Zone of inhibition (in mm)
of compounds against the
various human pathogens
Compounds
Gram (?ve) bacteria
Gram (-ve) bacteria
S. aureus
(ATCC 25323)
P. aeruginosa
(ATCC 27853)
E. faecalis
(Clinical isolate)
E. coli
(ATCC 35218)
1a
–
–
–
–
1b
9.70 0.40
–
–
–
1c
–
–
–
10.60 0.55
1d
9.76 0.66
–
–
12.80 0.36
1e
10.86 0.35
–
–
12.60 0.55
1f
–
–
–
–
1g
–
–
–
–
1h
–
–
–
–
1i
–
–
–
–
1j
–
–
–
–
1k
22.36 0.30
29.87 0.49
–
16.50 0.40
23.34 0.80
–
15.80 0.36
28.88 0.46
–
11.46 0.28
33.45 0.73
–
Ciprofloxacin
DMSO
Table 7 Antibacterial activity
of compounds against the
various human pathogens
MIC (lg/ml)
Compounds
Gram (?ve) bacteria
Gram (-ve) bacteria
S. aureus
(ATCC 25323)
P. aeruginosa
(ATCC 27853)
E. faecalis
(Clinical isolate)
E. coli
(ATCC 35218)
1a
–
–
–
–
1b
300
–
–
–
–
1c
–
–
150
75
75
–
1d
300
300
–
–
–
1e
–
–
1f
–
–
1g
–
–
–
–
1h
–
–
–
–
1i
–
–
–
–
1j
–
–
–
–
1k
1.20
6.25
–
9.7
3.12
–
2.4
3.2
–
4.8
6.25
–
Ciprofloxacin
DMSO
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J Chem Crystallogr (2013) 43:610–621
619
Table 8 Antifungal activity of compounds against the various human
pathogens
Zone of inhibition (in mm)
Compounds Candida
albicans
Candida
tropicalis
(ATCC 750)
Candida
krusie
(ATCC 6258)
(ATCC 90028)
1a
1b
1c
1d
1e
1f
–
–
–
–
–
–
9.60 0.50
10.36 0.25
–
11.60 0.26
10.53 0.51
13.7 0.45
–
–
11.60 0.26
–
–
–
1g
1h
1i
10.46 0.40
9.85 0.35
–
Fig. 5 Zone of inhibition of compounds against S. aureus
–
–
–
–
–
–
1j
10.63 0.25
14.50 0.51
–
–
1k
12.70 0.43
16.66 0.65
–
15.60 0.43
20.70 0.43
–
Fluconazole 21.80 0.30
DMSO
–
Table 9 Antifungal activity of compounds against the various human
pathogens
MIC (lg/ml)
Compounds Candida
albicans
Candida
tropicalis
(ATCC 750)
Candida
krusie
(ATCC 6258)
(ATCC 90028)
1a
1b
1c
1d
1e
1f
–
–
–
–
–
–
300
150
–
300
300
–
–
Fig. 6 Zone of inhibition of compounds against E. coli
150
300
–
–
–
1g
1h
1i
150
–
150
–
–
–
–
–
–
1j
150
75
–
–
1k
75
3.12
–
37.5
25
–
Fluconazole 6.25
DMSO
–
Hemolytic Activity
The results of the in vitro hemolytic study of the com-
pounds have been shown in Fig. 10 and represent as bar
graph in Table 10. Almost all the tested compounds
exhibited moderate to low hemolysis, which indicated
their low toxicity. Especially the compounds with very
good antimicrobial activity showed negligible level of
toxicity.
Fig. 7 Zone of inhibition of compounds against Candida albicans
123

620
J Chem Crystallogr (2013) 43:610–621
Table 10 Hemolytic activity of compounds (1a–1k)
Compounds
% Hemolysis
1a
1b
1c
1d
1e
1f
15.85
17.04
26.52
19.48
7.54
21.56
29.67
12.45
9.67
1g
1h
1i
1j
7.83
1k
11.87
Fig. 8 Zone of inhibition of compounds against Candida tropicalis
Conclusion
Twelve novel N,N0-disubstituted thiourea compounds have
been synthesized by the reaction of aroyl chloride with
substituted aromatic and hetrocyclic amines. These com-
pounds have been characterized by elemental analysis, FT–
IR, 1H and 13C NMR spectroscopy and single crystal study
for 1a and 1c. The single crystal structures of the com-
pounds revealed S-shaped conformation between C=O and
C=S groups and presence of intramolecular hydrogen
bonding between N2H proton and oxygen of C=O group.
The results of antibacterial screening revealed that among
all the compounds screened, compound 1b–1e showed mod-
erate to good anti-bacterial activity when compared with cip-
rofloxacin used as standard while the compound 1k exhibited
the highest activity against all the bacterial strains tested (zone
of inhibition up to 11–22 mm at concentrations of
4.8–1.20 lg/ml). Other compounds having electron with-
drawing group on phenyl ring did not show any inhibition
activity. The results of antifungal screening showed that
compound 1c–1g have moderate to good activity while com-
pound 1k exhibited very promising activity especially against
C. krusie with MIC value 37.5 lg/ml and zone of inhibition
15 mm when compared with the standard drug fluconazole.
On the basis of screening result obtained for compounds, the
antimicrobial screening results reveal that the compounds
containing a heterocyclic ring with two or three hetero atoms
exhibited good to excellent activity. The low cytotoxicity of the
compounds can be inferred on the basis of their moderate to low
hemolytic activity. The findings of our study suggest thatfew of
the tested compounds are worth of further investigations.
Fig. 9 Zone of inhibition of compounds against Candida krusie
Supplementary Material
CCDC 880462, 880463 contains the supplementary crys-
tallographic data for compound 1a and 1d respectively.
Fig. 10 Hemolysis of compounds (1a–1k)
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J Chem Crystallogr (2013) 43:610–621
621
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These data can be obtained free of charge via http://www.
ccdc.cam.ac.uk/conts/retrieving.html, or from Cambridge
Crystallographic Data Center, 12 Union Road, Cambridge
CB2 1EZ, UK; fax (?44) 1223 336 033; or email:
deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk
Acknowledgments The authors sincerely thanks to Prof. Ray J.
Butcher, Department of Chemistry, Howard University, 525 College
Street NW, Washington, DC 20059, USA, for X-ray data collection.
The author Durga Prasad Singh is grateful to BHU for providing
UGC-research fellowships. Mr. Mayank Gangwar and Mr. Dhar-
mendra Kumar is thankful to CSIR-New Delhi for providing senior
research fellowship.
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