Standard molar enthalpy of formation of [(C12H8N2)2Bi(O2NO)3] and its biological activity on Schizosaccharomyces pombe

Article abstract of DOI:10.1007/s10973-017-6104-z

The title complex [(C₁₂H₈N₂)₂Bi(O₂NO)₃] was synthesized by reaction of 1,10-phenanthroline (phen) and Bi(NO₃)₃·5H₂O. The structure of the complex was charac

Full text of DOI:10.1007/s10973-017-6104-z

J Therm Anal Calorim (2017) 128:1743–1751
DOI 10.1007/s10973-017-6104-z
Standard molar enthalpy of formation of [(C12H8N2)2Bi(O2NO)3]
and its biological activity on Schizosaccharomyces pombe
Chuan-Hua Li1 Yong Jiang1 Jian-Hong Jiang1 Xu Li1 Sheng-Xiong Xiao1
•
•
•
•
•
Li-Ming Tao1 Fei-Hong Yao1 Hui Zhang1 Xian-Ming Xia1 Long-Hua Yao1
Hua Zhou1 Ying-Hui Xiang1 Yuan Tian1 Qiang-Guo Li1
•
•
•
•
•
•
•
•
Received: 25 October 2016 / Accepted: 13 January 2017 / Published online: 30 January 2017
´
´
Ó Akademiai Kiado, Budapest, Hungary 2017
Abstract The title complex [(C12H8N2)2Bi(O2NO)3] was
synthesized by reaction of 1,10-phenanthroline (phen) and
Bi(NO3)3Á5H2O. The structure of the complex was char-
acterized by single-crystal X-ray diffraction, IR spec-
troscopy, and elemental analysis. An advanced solution-
reaction isoperibol microcalorimeter was applied to deter-
mine the standard molar enthalpies of formation at
298.15 K of the complex and Bi(NO3)3Á5H2O, giving
microbial infections, such as syphilis, diarrhea, gastritis,
and colitis. In particular, radioisotope 212Bi and 213Bi
compounds exhibited good anticancer activities and could
reduce the side-effects of cisplatin (cis-DDP) in carcinoma
treatment [1, 2]. Bismuth is considered nowadays as a
relatively non-toxic heavy metal. The bismuth(III) atom,
˚
possessing a larger ionic radius (1.16 A) and one inert
electron pair (6s2), can form complexes with higher coor-
dination numbers (from 3 to 10), resulting in producing
some irregular structure of bismuth(III) compounds [3, 4].
The affinity of bismuth(III) for nitrogen donors has been
reported for a range of ligands including glycine and a
number of bidentate nitrogen donors. Among these nitro-
gen-base ligands, 1,10-phenanthroline has gained more
prominence in the coordination chemistry, mainly to have
unusual structural features, such as its rigidity, planarity
and hydrophobicity [5–7]. The two nitrogen atoms are
permanently placed in juxtaposition, ideal for bidentate
binding to metal ions. Owning to its planarity, phen
derivatives and their metal complexes are able to interca-
late with DNA and RNA via aromatic p-stacking [8]. More
importantly, some metal complexes can efficiently cleave
the DNA backbone, especially for the complex
[Cu(phen)2]2? used in molecular biology as DNA cleaving
reagent [9].
–(798.92
5.99) and –(1986.87
0.20) kJ mol-1
,
respectively. The biological effect of the complex was
evaluated by microcalorimetry on the growth of
Schizosaccharomyces pombe (S. pombe). According to
thermogenic curves, the corresponding thermokinetics and
thermodynamic parameters were derived. The complex had
good bioactivity on the growth metabolism of S. pombe,
with the value of IC50 being 2.8 9 10-5 mol L-1
.
Keywords 1,10-Phenanthroline Á Bismuth(III) complex Á
Standard molar enthalpy of formation Á Thermodynamic
parameters Á Microcalorimetry
Introduction
In recent years, much attention has been paid to the design
and construction of bismuth compounds because of their
high effectiveness and low toxicity in the treatment of
Biological microcalorimetry, providing a continuous
measurement of heat production, is very suitable for the
survey of heat–output of slightly exothermic or endothermic
processes, such as the heat production of microbial cells,
organelles, tissues and organs [10–12]. It can provide a
general analytical tool for characterization of cell growth
process and has been extensively used to investigate the
interaction between drug and cultured cell [13]. In this study,
as a part of our continuing studies [14–16], we have pre-
pared a ten-coordinate 1:2 adduct [(C12H8N2)2Bi(O2NO)3]
& Qiang-Guo Li
liqiangguo@163.com
1
Hunan Provincial Key Laboratory of Xiangnan Rare-Precious
Metals Compounds and Applications, Department of
Chemistry and Life Science, Xiangnan University,
Chenzhou 423000, Hunan Province, People’s Republic of
China
123

1744
C.-H. Li et al.
by reacting of Bi(NO3)3Á5H2O and the aromatic bidentate
base 1,10-phenanthroline. The crystal structure of the com-
plex has been reported by Barbour et al. [17]. However, up to
now, the enthalpies of formation of the complex, together
with bismuth nitrate pentahydrate, have not been accurately
determined [18]. As we all know, the thermochemical
parameters are an indispensable part of chemical thermo-
dynamics, which closely relates to fundamental academic
problems together with application development. Therefore,
on the basis of previous work [19], the thermochemical
properties of the complex were planned to be investigated.
Then S. pombe was used as an ideal model to evaluate the
biological activity of the complex by microcalorimetry. This
is because that the constitution of human cells are very
complicated, which make them difficult to study. In com-
parison, S. pombe, also called ‘‘fission yeast,’’ which has a
distinct mitotic cycle, have many similar facts with human
cells and are relatively ease to be operated by cytology
technique [20]. Many scientific findings in human cells are
first investigated in yeast cells [21]. In the experiments, we
found that, like the previously reported bismuth(III) complex
[15], the current complex also showed good inhibitory
activity toward S. pombe growth. To fully study the biolog-
ical effect of the complex, some thermodynamics and kinetic
data were derived according to the power–time curves
obtained from the microcalorimeter. The relationship
between the concentration of the complex and the growth of
S. pombe was analyzed by the thermokinetics model.
study was performed on a 3116-2/3239 TAM Air
calorimeter (Thermometric AB, Sweden) [16]. An ele-
mental analyzer (PerkinElmer 2400 II) was used to mea-
sure the C, H, and N contents of the complex. Single-
crystal X-ray diffraction data for the complex were col-
lected on a Bruker SMART CCD diffractometer at
153(2) K using graphite monochromated Mo-Ka radiation
˚
(k = 0.71073 A) and were used to measure cell dimen-
sions and diffraction intensities. The structure was solved
by the direct methods and refined by full-matrix least
squares on F2 using the SHELXTL-97 program.
Synthesis of Bi(NO3)3Á5H2O
Bi2O3 (2 9 10-3 mol, 0.9319 g) was dissolved in HNO3
(8 mol L-1, 5 mL). After continuously stirred for 3 h, the
reaction mixture was filtered, and some colorless crystals
were obtained by slow evaporation of the filtrate. The water
content of the synthetic sample was determined by differ-
ence and thermogravimetric/differential thermogravimetric
(TG–DTG) curves. The TG and DTG curves of the sample,
at a heating rate of 283.15 K min-1 in flowing Ar, were
shown in Fig. 1. When the degradation temperature varies
from 342.05 to 385.55 K, the mass loss is 18.49%, which
roughly coincides with the value of 18.55%, calculated for
the loss of 5 mol of H2O from Bi(NO3)3Á5H2O. These facts
have shown that Bi2O3 can react with HNO3 (8 mol L-1
)
and provide with Bi(NO3)3Á5H2O.
Preparation of the complex [(C12H8N2)2Bi(O2NO)3]
Experimental
In a typical experimental procedure, Bi(NO3)3Á5H2O
(4 9 10-4 mol, 0.194 g) and mannitol (4 9 10-4 mol,
0.0728 g) were ground into a smooth paste in an appro-
priate mortar [15]. To this was added 3 mL deionized water
and 5 mL methanol in turn and stirred until dissolution.
Subsequently, the mixed solution was slowly added
Chemicals and instruments
All chemicals were purchased from commercial sources
and used as received; no further purification was done. The
triply distilled water was used in all the studies. S.pombe
(ACCC 20047) was provided Agricultural Culture Col-
lection of China. The Edinburgh minimal medium (EMM)
culture composition was K2HPO4 3 g, Na2HPO4 2.2 g,
NH4Cl 5 g, and Glucose 20 g. The yeast extract medium
composition was 20 mL and H2O 1000 mL (natural pH).
FTIR spectra were determined in the range of
4000–400 cm-1 on an Avatar 360 (Nicolet, Madison,
USA) spectrophotometer using a KBr pellet with a reso-
lution of 2 cm-1. Absorption spectra were taken with a
Hitachi U-3010 UV/Vis spectrophotometer with 1-cm
quartz, in the range 190–1,100 nm at 298.15 K. The
refractive indexes were done with a S2WA-Z digital Abbe
refractometer. Thermochemical analysis was measured
using a SCR-100 solution-reaction isoperibol calorimeter,
which was constructed by the Thermochemical Laboratory
of Wuhan University, China [22]. The microcalorimetric
6
5
4
3
2
1
0
1
2
3
4
4
2
0
–
–
–
–
–
–
–
2
TG
4
Exothermic
6
DSC
8
–
–
–
–
10
12
14
16
Endothermic
–
100
200
300
400
500
600
700
T/°C
Fig. 1 TG–DTG curves of Bi(NO3)3Á5H2O
123

Standard molar enthalpy of formation of [(C12H8N2)2Bi(O2NO)3] and its biological activity…
1745
dropwise to a stirred methanol solution (25 mL) of 1,10-
phenanthroline monohydrate (4 9 10-4 mol, 0.0792 g) at
60 °C for 30 min. After 2 h of continuously stirring, the
product was collected by filtration after concentration by
rotary evaporation to a small volume and washed with
dichloromethane. Single crystals were obtained by slow
diffusion of diethyl ether into the filtrate for several days. The
solid product was identified as [(C12H8N2)2Bi(O2NO)3].
Yield: 0.1495 g, 65.0%. Spectroscopic data of the complex
were given as follows: 3025 cm-1 (s, mC=C–H), 1628 cm-1
(vs, mC=N), 1517 cm-1 (vs, mC=C), 1494 cm-1 (vs, mC=C),
The enthalpy of dilution of (1HNO3 ? 5.119 H2O) was
calculated to be DdHmh [5.119:1 HNO3(aq), 298.15 K] =
- 203.07 kJ mol-1
.
Thermochemical cycle
The complex was synthesized by the following reaction:
BiðNO3Þ3 Á 5H2OðsÞ þ 2C12H8N2 Á H2OðsÞ
! ðC12H8N2Þ2BiðO2NOÞ3ðsÞ þ 7H2Oð1Þ
ð1Þ
Based on Hess’s law, a thermochemical cycle was
designed (as shown in Fig. 3). An ideal mixed calorimetric
solvent S (VDMSO/VHNO (wHNO :20%) = 8:3) was pre-
1382 cm-1 (vs, mNO ), 849 cm-1 (s). Elemental analysis for
À
3
[(C12H8N2)2Bi(O2NO)3], Calc. (Found): C 38.2 (37.8), H 2.1
3
3
pared through testing for many times, which had a good
solubility for all of the relevant samples on the premise of
thermochemical cycle. The standard molar dissolution
enthalpies of the samples were determined successively by
a solution-reaction calorimeter, and the obtained results
were applied to calculate the standard molar enthalpy of
the reaction, so as to further estimate the standard molar
enthalpy of formation of the complex.
(2.2), N 13.0 (12.8) %.
The enthalpy of dilution of nitric acid (8 mol L21
1HNO3 1 5.119 H2O)
,
The prepared nitric acid (8 mol L-1, 1HNO3 ? 5.119
H2O) was obtained by diluting 16 mol L-1 nitric acid
(w = 69.2%, q = 1.42 g mL-1) with water. The prepared
nitric acid (8 mol L-1) is regarded as 1HNO3 in 5.119
H2O. According to the reported literature [18], plot of
dilution enthalpy against the molar amount of water is
shown Fig. 2. Using the Expdec1 curve fitting from data of
the dilution enthalpy ðDdHmh Þ with the molar amount of
water n(H2O), the curve equation was obtained:
To further confirm the feasibility of the thermochemical
cycle, the UV spectra and refractive indexes of solution
B and D were determined, respectively. The experimental
results showed that solution B and D had similar UV
spectrum curves (Fig. 4) and equal refractive indexes
(g25 °C = 1.4130). These facts indicated that solution
B and D had the same thermodynamic state, which
demonstrated that the thermochemical cycle was
reasonable.
DdHmh = ¼ À205:948 þ 28:486 expðnH2O=2:232Þ
¼ À205:948 þ 28:486 expðÀ5:119=2:232Þ
¼ À205:948 þ 28:486 Â 0:10095
¼ À205:948 þ 2:786
Determination of dissolution enthalpies
of the samples
¼ À203:07 kJ molÀ1
The structure of the solution-reaction isoperibol calorime-
ter (SRC-100) has been elucidated in the reported literature
[22]. A Dewar vessel, possessing a 100 mL internal vol-
ume and a twin-blade stirrer, was immersed in the water
thermostat. In the calorimetric experiments, the precision
values of temperature control and temperature measure-
ment were 0.001 and 0.0001 K, respectively. The
temperature, the current, and the resistance of the heater
were 298.15 K, 21.813 mA, and 1212.3 X, respectively.
Before use, the calibration of the calorimeter was per-
formed by measuring the dissolution enthalpies of
tris(hydroxymethyl)aminomethane (THAM; NBS 742a,
USA) in 0.0001 mol mL-1 HCl and KCl (calorimetric
primary standard) in triply distilled water at 298.15 K. In
our experiments, after five parallel measurements, the
mean dissolution enthalpies were (17,588 13) J mol-1
for KCl and [- (29,751 14)] J mol-1 for THAM, in
agreement with published data, (17,536 9) J mol-1 for
–185
–190
–195
–200
–205
0
2
4
6
8
10
n(H2O)
Fig. 2 Relationship between the dilution enthalpy (DdHmh )and the
molar amount of water n(H2O)
123

1746
C.-H. Li et al.
θ
(1a)
ΔrH
m
Bi(NO3)3·5H2O(s)
·
2C12H8N2 H2O(s)
(C12H8N2)2Bi(O2NO)3(s)
+
7H2O(l)
+
+Calorimetric
(2a)
+Calorimetric
solvent S
(4a)
solvent S
Solution C
Solution D
Solution A
Solution B
(3a)
(5a)
Fig. 3 Thermochemical cycle of reaction 1
0.5 mmol [(C12H8N2)2Bi(O2NO)3(s)] ? S ? Solution C
3.5 mmol H2O(l) ? Solution C ? Solution D
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
–0.1
Solution B
Solution D
Five parallel experiments were carried out in each sample,
and the obtained results are shown in Tables 1 and 2.
Microcalorimetric measurements
The microcalorimetry was carried out on a TAM air
isothermal microcalorimeter at 32.00 °C. Baselines were
taken before each measurement and the calorimeters were
calibrated electrically. When the system has gained the
stable baseline, 5 mL EMM sterilized culture medium was
added into the sterilized sample ampoules. S. pombe was
inoculated with an initial density of 1 9 106 cells per mL.
The sample at different concentrations was added to the
cell suspension, respectively. Power–time curves for all
measurements were performed at 32.00 °C. All of the
microcalorimetric experiments were repeated three times,
and the obtained results were identical.
200
250
300
350
400
450
500
λ/nm
Fig. 4 UV–Vis spectra of solution B and D
KCl [22] and [- (29,766 31.5)] J mol-1 for THAM
[23]. The dating error was within 0.5%, which indicated
that the calorimeter was reliable.
The content of the prepared complex was determined by
EDTA titration method, which suggested its purity was
greater than 99.0%. All of the solid samples were dried and
ground fully in advance. The volume of calorimetric sol-
vent was 100 mL for each time. When the calorimeter was
adjusted to a constant temperature of (298.150 0.001) K,
the samples were added into the reaction vessel, and their
dissolution enthalpies were determined. The amount and
measurement sequence of the relevant substances of reac-
tion (1) are as follows:
Results and discussion
Crystal structure of the complex
X-ray crystallographic analysis indicated that the complex
crystallized in a monoclinic space group of C2/c symmetry
and its structure along with the atomic numbering scheme was
shown in Fig. 5. Each unit of [(C12H8N2)2Bi(O2NO)3] con-
sisted of one Bi3? ion, two 1,10-phenantroline ligands and
threenitrateions. Thecentralbismuthatomwas10-coordinate
being bound to three bidentate nitrate ions and four nitrogen
atoms from two chelating phen units [17].
1 mmol C12H8N2ÁH2O(s) ? S ? Solution A
0.5 mmol Bi(NO3)3Á5H2O(s) ? Solution A ? Solution B
123

Standard molar enthalpy of formation of [(C12H8N2)2Bi(O2NO)3] and its biological activity…
1747
Table 1 Determination of the reaction enthalpy of [Bi(NO3)3Á5H2O(s)] in 8 mol L-1 HNO3 (100 mL) at 298.15 K
ma/g
tb/s
DrHmh =kJ molÀ1
Reaction
No.
Bi2O3 þ ð6HNO3 þ 30H2OÞ ! 2BiðNO3Þ3 Á 5H2O þ 23H2O
1
2
3
4
5
0.23292
0.23299
0.23304
0.23302
0.23298
121.43
120.87
120.45
120.40
120.56
-151.235
-151.819
-151.101
-151.467
-151.300
DrHmh [Bi(NO3)3Á5H2O (s), 298.15 K] = –(151.38 0.28) kJ mol-1c
a
m mass of Bi2O3
b
t heating period of electrical calibration
c
Uncertainty was estimated as twice the standard deviation of the mean of the results
Table 2 Dissolution enthalpies of [C12H8N2ÁH2O(s)], [Bi(NO3)3Á5H2O(s)], [(C12H8N2)2Bi(O2NO)3(s)], and [H2O(l)] in the calorimetric solvent
S or corresponding solution (100 mL) at 298.15 K
DsHmh =kJ molÀ1
System
No.
ma/g
tb/s
C12H8N2ÁH2O (s) in S
1
2
3
4
5
0.19823
0.19797
0.19804
0.19806
0.19810
14.375
14.328
14.483
14.512
14.390
-15.164
-15.123
-15.148
-15.472
-15.317
DsHmh [C12H8N2ÁH2O (s), 298.15 K] = -(15.24 0.15) kJ mol-1c
Bi(NO3)3Á5H2O(s) in the solution A
1
2
3
4
5
0.24274
0.24251
0.24264
0.24245
0.24245
18.812
18.594
18.453
18.688
18.813
20.061
20.286
20.781
20.289
20.267
DsHmh [Bi(NO3)3Á5H2O(s), 298.15 K] = (20.34 0.27) kJ mol-1
(C12H8N2)2Bi(O2NO)3 (s) in S
1
2
3
4
5
0.28736
0.28748
0.28795
0.28756
0.28774
21.631
21.652
21.631
21.608
21.659
22.782
22.277
22.241
22.632
22.856
DsHmh [(C12H8N2)2Bi (O2NO)3 (s), 298.15 K] = (22.56 0.28) kJ mol-1
H2O(l) in the solution C
1
2
3
4
5
0.03786
0.03790
0.03784
0.03782
0.03789
2.390
2.450
2.421
2.468
2.141
-0.39180
-0.35988
-0.34485
-0.37795
-0.33502
DsHmh [H2O(l), 298.15 K] = -(0.36 0.02) kJ mol-1
a
m mass of sample
b
t heating period of electrical calibration
c
Uncertainty was estimated as twice the standard deviation of the mean of the results
Thermochemistry
Bi2O3 þ ð6HNO3 þ 30H2OÞ ! 2BiðNO3Þ3 Á 5H2O
þ 23H2O
As is shown in Table 1, the reaction enthalpy of Bi
ð2Þ
Standard molar enthalpy of Bi(NO3)3Á5H2O
(NO3)3Á5H2O was estimated to be DrHmh [Bi(NO3)3Á5H2
The reaction enthalpy of Bi(NO3)3Á5H2O was determined
O(s), 298.15 K] = –(151.38 0.28) kJ mol-1
.
according to the following reaction:
123

1748
C.-H. Li et al.
Standard molar enthalpy of reaction (1)
05
Based on Hess’ law and the dissolution enthalpies of the
tested samples, the standard molar enthalpy of the reaction
was obtained as follows:
N4
04
04A
N3
C1A
03A
03
02
N3A
DrHmh ð1aÞ ¼ 2DsHh ð2aÞ þ DsHmh ð3aÞ À DsHmh ð4aÞ À 7DsHmh ð5aÞ
¼ ½2  ðmÀ15:24Þ þ 20:34 À 22:56 À 7  ðÀ0:36ފ
C1
02A
01A
01
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
C2A
C3A
C4A
C9A
C8A
C2
C3
Bi1
2
2
2
2
N2A
Æ
ð2 Â 0:15Þ þ ð0:27Þ þ ð0:28Þ þ ð7 Â 0:02Þ
N2
N1
C5A
C5
¼ Àð30:18 Æ 0:51Þ kJ molÀ1
N1A
C4
C12
C11
C10
ð4Þ
C6
C7
C6A
C12A
Standard molar enthalpy of formation of the complex
C9
C8
C7A
C11A
According to Hess’ law and the principles of
thermodynamics:
C10A
DrHmh ðlaÞ ¼ DfHmh ½ðC12H8N2Þ2BiðO2NOÞ3ðsÞ; 298:15 KŠ
þ 7DfHmh ½H2OðlÞ; 298:15 KŠ
Fig. 5 SHELXTL diagram of the complex, showing the atom
labeling scheme and 30% probability displacement ellipsoids. All
hydrogen atoms are represented as small spheres of arbitrary radii
À 2DfHmh ½C12H8N2 Á H2OðsÞ; 298:15 KŠ
À DfHmh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ ð5Þ
DrHmh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ
¼ 2DfHmh ½BiðNO3Þ Á 5H2OðsÞ; 298:15 KŠ
þ 23DfHmh ½H2Oð3lÞ; 298:15 KŠ
According to refs [18, 19, 24]
À DfHmh ½Bi2O3ðsÞ; 298:15 KŠ
ð3Þ
À 6DfHmh ½ HNO3ðlÞ; 298:15 KŠ
À 30DfHmh ½H2OðlÞ; 298:15 KŠ
À DdHmh ½5:119 : 1 HNO3ðaqÞ; 298:15 KŠ
According to Ref. [18]
DfHmh ½H2OðlÞ; 298:15 KŠ ¼ Àð285:83 Æ 0:04Þ kJ molÀ1
DfHmh ½Bi2O3ðsÞ; 298:15 KŠ ¼ À573:88 kJ molÀ1
DfHmh ½5:119 : 1 HNO3ðaqÞ; 298:15 KŠ ¼ À203:07 kJ molÀ1
DfHmh ½HNO3ðlÞ; 298:15 KŠ ¼ À174:10 kJ molÀ1
1
DfHmh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ ¼ fDrHmh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ þ DfHmh ½Bi2O3ðsÞ; 298:15 KŠ
2
þ DfHmh ½HNO3ðlÞ; 298:15 KŠ þ 30DfHmh ½H2OðlÞ; 298:15 KŠg
þ DdHmh ½5:119 : 1HNO3ðaqÞ; 298:15 KŠ À 23DfHmh ½H2OðlÞ; 298:15 KŠg
1
¼
¼
fDrHmh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ þ DfHmh ½Bi2O3ðsÞ; 298:15 KŠ
2
þ DfHmh ½HNO3ðlÞ; 298:15 KŠ þ 7DfHmh ½H2OðlÞ; 298:15 KŠ
þ DdHmh ½5:119 : 1HNO3ðaqÞ; 298:15 KŠg
1
½ðÀ151:38Þ þ ðÀ573:88Þ þ 6  ðÀ174:10Þ
2
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ꢀ
ꢁ
ꢀ
ꢁ
2
 0:28 2þ  7  0:040
1
2
1
þ 7  ðÀ285:83Þ þ ðÀ203:07ފ Æ
¼ Àð1986:87 Æ 0:20Þ kJ molÀ1
2
123

Standard molar enthalpy of formation of [(C12H8N2)2Bi(O2NO)3] and its biological activity…
1749
DfHmh ½H2OðlÞ; 298:15 KŠ ¼ Àð285:83 Æ 0:04Þ kJ molÀ1
DfHmh ½C12H8N2 Á H2OðsÞ; 298:15 KŠ ¼ Àð391:34 Æ 2:98Þ kJ molÀ1
DfHmh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ ¼ ðÀ1986:87 Æ 0:20Þ kJ molÀ1
DfHmh ½ðC12H8N2Þ2BiðO2NOÞ3ðsÞ; 298:15 KŠ ¼ DrHmh ð1aÞ À 7DfHmh ½H2OðlÞ; 298:15 KŠ
þ 2DfHmh ½C12H8N2 Á H2OðsÞ; 298:15 KŠ þ DfHh ½BiðNO3Þ3 Á 5H2OðsÞ; 298:15 KŠ
¼ ½ðÀ30:18Þ À 7  ðÀ285:83Þ þ 2  ðÀ391:34Þ mþ ðÀ1986:87ފ
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
2
2
2
2
Æ
ð0:51Þ þ ð7 Â 0:04Þ þ ð2 Â 2:98Þ þ ð0:20Þ
¼ Àð798:92 Æ 5:99Þ kJ molÀ1
Microcalorimetry
C(the complex) / 10–3 mol L–1
200
180
1
3
5
7
2
0.015
0.023
0.031
0.038
0.000;
Thermogenic curves
0.019; 4
0.027; 6
0.035; 8
The thermogenic curves for growth of S. pombe treated by
different concentrations of the complex were determined
using the ampoule method at 32.00 °C, respectively. All
microcalorimetric experiments were performed in tripli-
cates. The power–time curves are illustrated in Fig. 6.
From Fig. 6, the metabolic process could be divided into
four phases: lag phase, log (exponential) phase, stationary
phase, and decline phase [15, 16].
160
140
120
100
80
1
2
3
4
5
6
7
60
8
40
20
Thermokinetics
0
–200
0
200 400 600 800 1000 1200 1400
During the log phase, the power–time curves obey the
following equation [25]:
t/min
Fig. 6 Metabolically thermogenic curve of S. pombe cells affected by
the complex
ln Pt ¼ ln P0 þ ktÀkt0
ð6Þ
where P0 and Pt stand for the heat–output power at the
beginning of baseline and at time t, respectively; k is the
growth rate constant of S. pombe at specified condition,
whose size represents growth speed. So using the data Pt
and t taken from the power–time curves to fit Eq. (6), the
growth rate constant (k) values of S. pombe at different
concentrations were obtained via linear fitting with the
computer (Table 3). As is shown in Table 3, the growth
rate constant k decreased with the increase in concentration
of the drug. The inhibition ratio of the growth metabolism
of S. pombe by drug is defined as the following:
was gradually increased with the increase in concentration of
the complex, which indicated the growth of S. pombe was
significantly inhibited. Using the logistic curve fitting from
data of the inhibition ratio (I) of S. pombe with concentration
(c) of the complex, the curve equation was obtained:
85:69
À
I ¼ 84:76 À
ð8Þ
B 3.8 9 10-5 mol
Á
5:51
c
0:025
1 þ
(1.5 9 10-5 mol L-1 B C
L-1).
(the complex)
ð
À
Þ
k0 kc
I ¼
 100%
ð7Þ
The correlation coefficient R was 0.9767. Thus, the
k0
inhibition ratio in the range of the above applied amount of
where k0 is the rate constant of the control and kc is the rate the complex on S. pombe could be clearly inferred through
constant under an inhibitor with a concentration of c. The the application of Eq. (8). When the inhibition ratio was
values of (I) were shown in Table 3. Plotting the inhibition 50%, the drug concentration was the half inhibition con-
ratio (I) against the concentration (c) of the complex is shown centration (IC50). The half inhibition concentration (IC50)
Fig. 7. As can be seen from the figure, the inhibition ratio (I) of the complex was found to be 2.8 9 10-5 mol L-1
.
123

1750
C.-H. Li et al.
Table 3 Thermokinetics parameters of S. pombe growth affected by the inhibitor at different concentrations
Inhibitors
Ca/(10-3 mol L-1
)
Kb/min-1
Ic/ %
ICd50/mol L-1
Qtotal/J
The complex
0.000
0.015
0.019
0.023
0.027
0.031
0.035
0.038
6.18 9 10-5 2.69 9 10-8 e
6.12 9 10-5 2.06 9 10-8
5.21 9 10-5 2.72 9 10-8
4.13 9 10-5 3.35 9 10-8
3.52 9 10-5 1.87 9 10-8
1.97 9 10-5 1.47 9 10-8
1.68 9 10-5 1.03 9 10-8
1.61 9 10-5 1.89 9 10-8
0
2.8 9 10-5
84.89
71.17
55.45
47.38
37.52
29.55
26.03
22.57
0.97
15.6
33.2
43.0
68.1
72.8
73.9
a
The concentration
b
The growth rate constant of S. pombe
The inhibitive ratio
c
d
e
The half inhibition concentration
Mean SD; n = 3
90
80
70
60
50
40
30
20
80
70
60
50
40
30
20
10
0
–0.005 0.000 0.005 0.010 0.015 0.020 0.025 0.030 0.035 0.040
–10
C/(10–3 mol L–1)
–0.005 0.000 0.005 0.010 0.015 0.020 0.025 0.030 0.035 0.040
C/(10–3 mol L–1)
Fig. 8 Total thermal effects (Qtotal) of S. pombe with different
concentrations of the complex
Fig. 7 Relationship between the concentration of the complex and
the growth inhibition rate (I) of S. pombe
Thermodynamics
The correlation coefficient R was 0.9949. Thus, the
total thermal effects in the range of the above applied
amount of the complex on S. pombe could be clearly
inferred through the application of Eq. (9). From Fig. 8,
it could be seen that the total thermal effects (Qtotal) of
S. pombe growth decreased with increase in the con-
centration of the complex, which indicated that the
complex significantly inhibited the growth of S. pombe
cell. This is mainly because after addition of the drug
into the S. pombe suspension, some cells were inhibited
or killed, but the survivors continue to metabolize
which maintain a lower level of the heat production
rate, and this level is directly depending on the drug
concentration.
The total thermal effects (Qtotal) value can be calculated by
the area under the power–time curves, and listed in Table 3.
Drawing the total thermal effects (Qtotal) of S. pombe
growth against concentration(c), the curve was shown in
Fig. 8. Using the logistic curve fitting from data of the total
thermal effects (Qtotal) of S. pombe growth with the con-
centration of the complex, the curve equation was obtained:
71:30
À
Qtotal ¼ 13:82 þ
ð9Þ
Á
3:49
c
0:022
1 þ
(1.5 9 10-5 mol L-1 B C
L-1).
B 3.8 9 10-5 mol
(the complex)
123

Standard molar enthalpy of formation of [(C12H8N2)2Bi(O2NO)3] and its biological activity…
1751
8. Kaplanis M, Stamatakis G, Papakonstantinou VD, Paravatou-
Petsotas M, Demopoulos CA, Mitsopoulou CA. Re(I) tricarbonyl
complex of 1,10-phenanthroline-5,6-dione: DNA binding, cyto-
toxicity, anti-inflammatory and anti-coagulant effects towards
platelet activating factor. J Inorg Biochem. 2014;135:1–9.
9. Sigman DS, Landgraf R, Perrin DM, Pearson L. In: Sigel A, Sigel
H, editors. Metal ions in biological systems, vol. 33 (Probing of
Nucleic Acids by Metal Ion Complexes of Small Molecules),
New York: Marcel Dekker; 1996, p. 485–514.
10. Braissant O, Bonkat G, Wirz D, Bachmann A. Microbial growth
and isothermal microcalorimetry: growth models and their
application to microcalorimetric data. Thermochim Acta. 2013;
555:64–71.
11. Wu YW, Gao WY, Xiao XH, Liu Y. Calorimetric investigation of
the effect of hydroxyanthraquinones in Rheum officinale Baill on
Staphylococcus aureus growth. Thermochim Acta. 2005;429:
167–70.
12. Kong WJ, Zhao YL, Xing XY, Ma XP, Sun XJ, Yang MH, Xiao
XH. Antibacterial evaluation of flavonoid compounds against
E. coli by microcalorimetry and chemometrics. Appl Microbiol
Biotechnol. 2015;99:6049–58.
13. Braissant O, Bachmann A, Bonkat G. Microcalorimetric assays
for measuring cell growth and metabolic activity: methodology
and applications. Methods. 2015;76:27–34.
14. Li CH, Tao X, Jiang JH, Li X, Xiao SX, Tao LM, Zhou JF, Zhang
H, Xie MA, Zhu Y, Xia Z, Tang SM, Yuan HM, Li QG. Syn-
thesis, crystal structure and spectroscopic studies of bismuth(III)
complex with 2-substituted benzimidazole ligands. Spectrochim
Acta A. 2016;166:56–61.
15. Li CH, Jiang JH, Li X, Tao LM, Xiao SX, Gu HW, Zhang H,
Jiang C, Xie JQ, Peng MN, Pan LL, Xia XM, Li QG. Synthesis,
crystal structure and biological properties of a bismuth(III)
Schiff-base complex. RSC Adv. 2015;5:94267–75.
Conclusions
In this work, a bismuth(III) complex [(C12H8N2)2-
Bi(O2NO)3] was prepared and characterized. According to
the principles of thermodynamics, the standard molar
enthalpies of formation of the complex and Bi(NO3)3Á5H2O
were estimated to be DfHmh [(C12H8N2)2Bi(O2NO)3] =
–(798.92 5.99) kJ mol-1 and DfHmh [Bi(NO3)3Á5H2O] =
–(1986.87 0.20) kJ mol-1, respectively. The microcalori
metric method was used to study the influence of synthetic
complex on the growth of S. pombe. The thermokinetic
parameters of growth, such as growth rate constants k, the
inhibition ratio I and half inhibition concentration IC50 were
obtained. The quantitative relationships of the I and Q values
of S. pombe with concentrations of the complex were dis-
cussed. IC50 value of the complex was found to be
2.8 9 10-5 mol L-1, which indicated that the complex had
good bioactivity on the growth metabolism of S. pombe [15].
Moreover, the present work has also demonstrated that
microcalorimetry is a valuable tool to evaluate the biological
activity of drugs because it could provide important
thermokinetics and thermodynamic information that cannot
be obtained from conventional biological techniques [13]. In
conclusion, this work provides some important reference
data, which may benefit the research of bismuth complexes.
Acknowledgements The authors thank the National Natural Science
Foundation of China (No. 21273190), The Project of Scientific
Research of Hunan Provincial Education Department (15A175,
15A176, 14A134, 15C1272 and 16C1492), Science and Technology
Plan Projects of Hunan Province (2014FJ3011, 2011TP4016-1 and
2012TP4021-5), and Science and Technology Plan Project of Chen-
zhou city (CKJ2016020) for financial support.
16. Li X, Jiang JH, Chen QQ, Xiao SX, Li CH, Gu HW, Zhang H, Hu
JL, Yao FH, Li QG. Synthesis of nordihydroguaiaretic acid
derivatives and their bioactivities on S. pombe and K562 cell
lines. Eur J Med Chem. 2013;62:605–13.
17. Barbour LJ, Belfield SJ, Junk PC, Smith MK. Bidentate nitrogen
base adducts of bismuth(III) Nitrate. Aust J Chem. 1998;51:337–42.
18. Weast RC. CRC handbook of chemistry and physics. 69th ed.
Boca Raton: CRC Press Inc; 1988/1989, p. D–121.
19. Xiao SX, Zheng XF, Li WJ, Li CH, Jiang SL, Lu L, Li X, Han
BX, Li QG. Synthesis, crystal structure and thermochemical
study on a novel ternary coordination compound [Bi(C7H5O3)3-
C12H8N2]. J Therm Anal Calorim. 2015;120:1859–65.
References
´
1. Li HY, Sun HZ. Recent advances in bioinorganic chemistry of
bismuth. Curr Opin Chem Biol. 2012;16:74–83.
20. Cortes JC, Carnero E, Ishiguro J, Sanchez Y, Duran A, Ribas JC.
The novel fission yeast (1,3)beta-D-glucan synthase catalytic
subunit Bgs4p is essential during both cytokinesis and polarized
growth. J Cell Sci. 2005;118:157–74.
2. Kondo Y, Himeno S, Satoh M, Naganuma A, Nishimura T, Imura
N. Citrate enhances the protective effect of orally administered
bismuth subnitrate against the nephrotoxicity of cisdi-
amminedichloroplatinum. Cancer Chemother Pharmacol.
2004;53:33–8.
3. Cotton FA, Wilkinson G, Murillo CA, Bochmann M. Advanced
inorganic chemistry. 6th ed. New York: Wiley; 1999.
4. Levason W, Reid G. in Comprehensive coordination chemistry II:
coordination chemistry of the S, P, and F Metals, edn. Lever
A.B.P, vol. 3. Amsterdam: Elsevier Pergamon; 2004. p. 465–
544.
5. Luman CR, Castellano FN. ‘‘Phenanthroline Ligands’’ in com-
prehensive coordination chemistry II, 2003, Elsevier. ISBN
978-0-08-043748-4.
6. Bencini A, Lippolis V. 1,10-Phenanthroline: a versatile building
block for the construction of ligands for various purposes. Coord
Chem Rev. 2010;254:2096–180.
21. Drgonova J, Drgon T, Tanaka K, Kollar R, Chen GC, Ford RA,
Chan CSM, Takai Y, Cabib E. Rho1p, a yeast protein at the
interface between cell polarization and morphogenesis. Science.
1996;272:277–9.
22. Yu HG, Liu Y, Tan ZC, Dong JX, Zou TJ, Huang XM, Qu SS. A
solution–reaction isoperibol calorimeter and standard-molar
enthalpies of formation of Ln(hq)2Ac (Ln = La, Pr). Ther-
mochim Acta. 2003;401:217–24.
23. Rychly R, Pekarek V. The use of potassium chloride and
tris(hydroxymethyl)aminomethane as standard substances for
solution calorimetry. J Chem Thermodyn. 1977;9:391–6.
24. Cox JD, Wagman DD, Medvedev VA. CODATA key values for
thermodynamics. Chapter 1, New York: Hemisphere Publishing
Corp.; 1984.
25. Xie CL, Tang HK, Song ZH, Qu SS, Liao YT, Liu HS.
Microcalorimetric study of bacterial growth. Thermochim Acta.
1988;123:33–41.
7. Sammes PG, Yahioglu G. 1,10-Phenanthroline: a versatile ligand.
Chem Soc Rev. 1994;23:327–34.
123