Construction and regulation of imidazo[1,5-a]pyridines with AIE characteristics via iodine mediated Csp2?H or Csp?H amination

Article abstract of DOI:10.1016/j.cclet.2021.05.018

The widespread applications of aggregation-induced emission luminogens (AIEgens) inspire the creation of AIEgens with novel structures and functionalities. In this work, we focused on the direct and efficient synthesis of a new type of AIEgens, imidazo[1,5-a]pyridicne derivatives, via iodine mediated cascade oxidative Csp²–H or Csp–H amination route from phenylacetylene or styrenes under mild conditions. The resulted compounds showed excellent AIE characteristics with tunable maximum emissions, attractive bioimaging performance, and potential anti-inflammatory activity, which exert broad application prospects in material, biology, medicine, and other relevant areas.

Full text of DOI:10.1016/j.cclet.2021.05.018

ARTICLE IN PRESS
JID: CCLET
[m5G;June 8, 2021;2:57]
Chinese Chemical Letters xxx (xxxx) xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Communication
Construction and regulation of imidazo[1,5-a]pyridines with AIE
characteristics via iodine mediated Csp2−H or Csp−H amination
Jun Zhanga,1, Mengyao Shea,b,1, Lang Liua, Mengdi Liua, Zhaohui Wang a, Hua Liua,
Wei Suna, Xiaogang Liuc, Ping Liua, Shengyong Zhanga, Jianli Lia,∗
a Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest
University, Xi’an 710127, China
b Lab of Tissue Engineering, Provincial Key Laboratory of Biotechnology of Shaanxi, Ministry of Education Key Laboratory of Resource Biology and Modern
Biotechnology, The College of Life Sciences, Faculty of Life and Health Science, Northwest University, Xi’an 710127, China
c Fluorescence Research Group, Singapore University of Technology and Design, Singapore 487372, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
The widespread applications of aggregation-induced emission luminogens (AIEgens) inspire the creation
of AIEgens with novel structures and functionalities. In this work, we focused on the direct and effi-
cient synthesis of a new type of AIEgens, imidazo[1,5-a]pyridicne derivatives, via iodine mediated cas-
cade oxidative Csp2–H or Csp–H amination route from phenylacetylene or styrenes under mild condi-
tions. The resulted compounds showed excellent AIE characteristics with tunable maximum emissions,
attractive bioimaging performance, and potential anti-inflammatory activity, which exert broad applica-
tion prospects in material, biology, medicine, and other relevant areas.
Received 21 February 2021
Revised 7 May 2021
Accepted 13 May 2021
Available online xxx
Keywords:
Aggregation-induced emission (AIE)
Imidazo[1,5-a]pyridicnes
Iodine
© 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia
Medica, Chinese Academy of Medical Sciences.
Bioimaging
Anti-inflammatory
Aggregation-induced emission (AIE) phenomenon has drawn
considerable attention and experienced rapid development since it
was first discovered by Tang and his co-workers in 2001 [1]. The
aggregation-induced emission luminogens (AIEgens) are widely
applied in biosensors, organic light-emitting diodes, photovoltaic
material, and many other areas, displaying remarkable perfor-
mances [2–5]. Recently, an AIE dot based IgM/IgG antibody kit
has been developed and employed in the diagnosis of 2019-nCoV
with high sensitivity and detection speed [6]. Although classical
tetraphenylethylene derivatives possess excellent optical proper-
ties, they are not sufficient to meet the growing demand of mod-
ern materials science during the past decade [7–9]. Many efforts
have been made to develop new types of AIEgens to achieve de-
sired properties, among them many researchers have demonstrated
that introducing heteroatoms into the AIEgen structures could op-
timize the optical properties due to the participation of lone pair
electrons or empty orbits in their electronic structures [10–13].
Many new heterocyclic fluorogens have been successfully de-
veloped during the past decades, among which imidazo[1,5-
a]pyridines exhibited intriguing merits of solid-state luminescence,
long fluorescence lifetime, and large Stokes shifts, which allowed
them to be employed as the signal moiety to construct fluores-
cent sensors for the detection of endogenous cell factors such as
SO2, Cu2+, cysteine [14–17]. However, their optical properties were
still limited by the aggregation caused quenching (ACQ) effect to
a certain extent, the construction of imidazo[1,5-a]pyridines with
excellent AIE characters remains a challenge.
Enhancing the three-dimensional steric hindrance and limiting
the intermolecular rotations of fluorophore were widely recognized
as effective strategies for suppressing the ACQ effect [18–20]. To
date, many strategies including multicomponent reaction, denitro-
genative transannulation and cascade Csp3-H amination have sub-
stantially improved the construction of imidazo[1,5-a]pyridicnes,
but the synthetic method for increasing tridimensional features
are still very scarce, and the existing methods were difficult to
achieve one-step synthesis. Furthermore, these works were com-
monly achieved via reaction of aldehyde [21,22], nitrile [23,24],
benzylamine [25–29], amino acid [30,31], methyl ketone [32] with
heteroaryl ketones, alkyl pyridine, and pyridin-2-ylmethyl-amine
derivates, while cyclization of styrene or phenyl derivates to
imidazo[1,5-a]pyridine has not yet been reported. Based on the
previous works and our long-term interests in the construc-
tion of fluorescent molecules [33–35], we hypothesized that
∗
Corresponding author.
E-mail address: lijianli@nwu.edu.cn (J. Li).
1
These authors contributed equally to this work.
https://doi.org/10.1016/j.cclet.2021.05.018
1001-8417/© 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Please cite this article as: J. Zhang, M. She, L. Liu et al., Construction and regulation of imidazo[1,5-a]pyridines with AIE characteristics
via iodine mediated Csp2−H or Csp−H amination, Chinese Chemical Letters, https://doi.org/10.1016/j.cclet.2021.05.018

ARTICLE IN PRESS
JID: CCLET
[m5G;June 8, 2021;2:57]
J. Zhang, M. She, L. Liu et al.
Chinese Chemical Letters xxx (xxxx) xxx
introducing the carbonyl unit to imidazo[1,5-a]pyridicnes could re-
duce the ACQ effect caused by the π-π stacking interaction and
modulating intermolecular rotations, leading to AIEgens with ex-
cellent optical performance (Fig. 1). We further speculated the car-
bonyl unit could be inserted into the skeleton probably via I2-
mediated Kornblum oxidation (from phenylacetylene to phenyl-
glyoxal), then going through subsequently cyclization with proper
synthons to form benzoyl-imidazo[1,5-a]pyridicne.
To verify the above hypotheses, an investigation of optimal
reaction conditions was conducted using the reaction of pheny-
lacetylene (a1) with phenyl(pyridin-2-yl)methanamine (b1) as the
model (Table S1 in Supporting information). At first, the reaction
of a1 (0.5 mmol) with b1 (0.5 mmol) was performed in DMSO
at 100 °C with the addition of 0.5 equiv. of iodine, while only a
trace amount of benzoyl-imidazo[1,5-a]pyridine c1 was detected.
Surprisingly, the reaction efficiency was distinctly enhanced when
treated with oxidants including K2S2O8, TBHP, DTBP, TBPB, and O2.
With the promotion of O2, the mixture smoothly transformed into
c1 with a yield of 42%. Considering the alkylation of pyridine with
intermediated α-iodo acetophenone of a1 may suppress the de-
sired transformation, different acid was introduced into the system
to promote the reaction. As expected, the reaction efficiency was
significantly improved and gave 68% yield of c1 in the presence
of HCl. With further modulation of the iodine catalyst, solvent and
temperature, the reaction achieved a good yield of c1 up to 83%
(Table S1, entry 19). Furthermore, it is surprising that the yield
of c1 could still reach 74% when phenylacetylene was replaced by
styrene.
With the optimal conditions, phenylacetylenes with alkyl,
alkoxy and halide were successfully screened and transform into
the desired products with yields from 75% to 81% (c2−c6, c8,
c9), while valuable cyano substituted phenylacetylene is well com-
patible to giving c7 with a yield of 72% (Scheme 1). It was no-
table that the electron-donating groups on the ortho-position of
phenylacetylenes would suppress the reaction while the electron-
withdrawing group exerted no significant influences on the yields
of the desirable products (c11, c12). Furthermore, poly-substituted
phenylacetylenes were also suitable for affording the target com-
pounds (c13, c14) with satisfactory yields up to 78%. Besides, this
new catalytic system is also applicable to hetero and aliphatic sub-
stituted alkynes leading to c16 and c17 with acceptable yields of
71% and 44%, respectively. Similar to the reaction from styrene
to c1, other styrene derivates were also applicable to the current
system, leading to corresponding products in good yield such as
c4, c10, c12 and c15. Besides, the substituent group on the ben-
zene ring of R2 exhibited good compatibility, whether electron-
withdrawing or electron-donating (c18−c24). The effect of substi-
tutes on the pyridine ring was also investigated and exhibited no
significant influence on the transformation (c25, c26). When the
substituents on R1 and R2 were changed simultaneously, the re-
action would still proceed smoothly even for N,N-diphenyl substi-
tuted substrate (c27−c34). Furthermore, the reaction can also be
extended to more complicated imidazo[1,5-a]pyrimidines in good
yields (c35, c36)
Scheme 1. The extension of the scope of the reaction substrates. Conditions:
a
(0.5 mmol), b (0.6 mmol), I2 (0.1 mmol), and HCl (1 equiv.) were stirred in DMSO
α
with an O2 balloon at 100 °C. All the yields are isolated yields. Reaction was per-
formed with corresponding styrenes.
Fig. 1. Proposed imidazo[1,5-a]pyridine based AIE dyes by inhibiting the in-
tramolecular rotation.
electron-donating group, would substantially promote the AIE ef-
fect of the corresponding products (c3, c4, c8 and c10) (Figs. S24-
S27 in Supporting information). In these compounds, c10, the tri-
fluoromethyl substituted compound displayed a more prominent
enhancement of quantum yield (0.4% to 6.4%) and bathochromic
shift in peak emission wavelengths. Similar effects were also ob-
served when the electronic effect of R2 was changed (c19, c20 and
c22) (Figs. S28–S30 in Supporting information). However, the emis-
sion and quantum yield did not improve when R2 was changed to
a large and steric group, which may be caused by the inhibited
aggregation behaviors (c23). Moreover, substitutes on the pyridine
ring did not exhibit significant promotion of AIE performance (c25
and c26) (Figs. S32 and S33 in Supporting information). Based on
these results and previous literature [36,37], the AIE properties of
these compounds could be ascribed to the formation of the donor-
π-acceptor (D-π-A) structure among R1, R2, and heterocycle. Thus,
Intriguingly, all the synthesized compounds presented strong
solid-state fluorescence under the illumination of 370 nm with
large Stokes shifts. To verify the AIE characters and establish the
structure-property relationship, 19 compounds with different sub-
stitutions were selected to analyze the detailed optical perfor-
mance (Table 1). The representative compound c1 emitted weak
yellow-green fluorescence at the peak emission wavelengths of
510 nm with a relatively low quantum yield (ꢀf) of 1.6% in THF.
Along with the gradually increased water fraction from 0% to 99%,
a red-shift of the maximum wavelength to 517 nm and a higher
quantum yield (4.2%) was observed (Fig. S23 in Supporting infor-
mation). The substitution of R1, both by electron-withdrawing and
2

ARTICLE IN PRESS
JID: CCLET
[m5G;June 8, 2021;2:57]
J. Zhang, M. She, L. Liu et al.
Chinese Chemical Letters xxx (xxxx) xxx
Table 1
The optical properties of selected compounds.
a
b
c
d
e
λab (nm) λem,sol (nm) λem,agg (nm) Ia/I0
Фs (%) Фa (%)
c1
c3
c4
c8
376
400
408
398
510
485
503
511
513
468
533
512
504
465
498
498
513
497
504
491
494
525
530
517
509
512
524
547
521
549
524
500
505
511
529
540
554
569
528
527
550
558
2.1
4.3
20
1.6
2.9
2.2
1.8
4.2
7.3
6.2
5.6
6.4
6.0
5.7
5.9
1.7
3.4
2.0
7.7
7.1
3.3
8.2
4.5
5.1
10.9
12.6
3.6
c10 375
c19 400
c20 354
c22 390
c23 395
c25 370
c26 372
c27 405
c28 406
c29 406
c30 406
c31 399
c32 377
c33 397
c34 397
30.3 0.4
2.9
3.0
3.6
1.8
14
1.0
1.9
2.2
0.2
0.7
2.3
6.8
1.7
1.6
4.0
1.3
2.7
3.6
6.5
0.7
1.1
3.1
1.5
3.2
3.0
1.9
6.3
3.0
Fig. 3. (a) Fluorescent spectra of c34. (b) Emission spectra of c34 in H2O/THF so-
lution. (c) SEM image of c34 in H2O/THF (99/1, v/v). (d) Fluorescent image of HeLa
cells stained with c34 (20 μmol) for 20 min. (e) The bright-field image of cells. (f)
The overlaid image of d and e.
a
Maximum UV absorption wavelength in THF.
Maximum emission wavelength in THF.
b
c
Maximum emission wavelength in H2O/THF (99/1, v/v).
Absolute quantum yield calculated in THF solution.
Absolute quantum yield calculated in H2O/THF (99/1, v/v).
characteristics before and after the replacement of the nitrogen α-
H on pyridine with chloride atom. As shown in Fig. 2c, c3 solu-
tion (THF) exhibited a significant change in the maximum emission
wavelength (485–510 nm) and quantum yield (2.9%–7.3%) when
the water fraction was raised from 0% to 99%. In contrast, when
the α-H was substituted by chloride (c37, Fig. S43 in Supporting
information), although an obvious red-shift of the maximum wave-
length could be observed, the fluorescence quantum yield did not
change significantly. These results confirmed that the formation of
O–H interaction indeed played an important role in promoting the
AIE character.
d
e
To perform the biological imaging experiment, c34 was cho-
sen as a representative AIEgen due to the good AIE performance,
the relevant long emission at 558 nm, and the highest quantum
yield of 12.6% in the aggregation state among these obtained com-
pounds (Figs. 3a and b). Moreover, the SEM image revealed c34
would aggregate into spherical nanoparticles with a size range of
200−400 nm in the solution with high water content, which is
suitable for biological applications (Fig. 3c). Furthermore, the MTT
assay showed excellent viability of cells even when the concen-
tration of c34 reached 100 μmol/L (Fig. S44 in Supporting infor-
mation). As illustrated in Figs. 3d–f, c34 (20 μmol/L) showed effi-
cient and ultrafast uptake by Hela cell within 20 min and exhib-
ited strong orange fluorescence signals in the cytoplasm, suggest-
ing that c34 could serve as a potential AIEgen for mapping impor-
tant biological analytes in living cells.
Fig. 2. (a, b) Crystal structures and packing patterns of c3. (c) Control experiment
to illustrate the effect of the intramolecular hydrogen bond.
the fluorescence regulating effect of synchronously changing R1
and R2 were further investigated to generate c27–c34 (Figs. S34–
S41 in Supporting information). It is worth noting that when R1
was 4-fluorine benzene, the quantum yields of the compounds in
the aggregation state could reach 10.9% and 12.6% with methoxy
(c33) and N,N-diphenyl (c34) on R2, respectively.
Afterwards, the biological activity of the obtained compounds
was investigated using c27-c36 as examples beginning with virtual
screening (Table S8 in Supporting information). To our delight, all
the selected compounds exhibited high affinity for cannabinoid-
2 (CB2) receptor which is closely associated with inflammatory
pathways [38,39]. Due to the lack of enough investigation of
imidazo[1,5-a]pyrimidines derivates upon the anti-inflammatory
effect, we have chosen c36 as the representative to assess the
anti-inflammation activity via animal models (docking score of
c36 is better than c35. Then, arachidonic acid (AA) induced ear
swelling test was performed to evaluate its anti-inflammatory ef-
fect (Fig. 4a). All the experimental protocols were approved by the
Institutional Animal Experimental Ethics Committee of Northwest
University (ethic code: NWU-AWC-20190202R). The results showed
that c36 could effectively prevent the ear swelling with an inhi-
bition rate of 35.69% via intragastric administration (50 mg/kg),
which is weaker than that of dexamethasone (DEX) (Fig. 4b).
Moreover, c36 could occupy a binding pocket mainly through
hydrophobic interactions with the Phe87, Phe91, Ile110, Val113,
To better understand the AIE mechanism of these compounds,
we selected the crystal structure of c3 as an example to analyze
the structure-function relationship. As illustrated in Fig. 2, c3 dis-
played a propeller-like shape, the dihedral angle between the het-
erocycle plane and the benzoyl plane was measured to be 45.7° as
well as a dihedral angle of 34.2° between the heterocycle and ben-
zene plane. Therefore, the C–C single bond between the conjugate
planes became highly rotatable in the dissolved state and cause
energy loss through a series of non-radiative transitions, which
would be weakened in the aggregation or solid-state, resulting in
excellent AIE performance. Also, strong O–H interaction was also
observed in molecular packing diagrams, which could also effec-
tively restrain the intramolecular motions (Fig. 2b). To verify the
effect of this special intramolecular hydrogen bond, a control ex-
periment was conducted to compare the respective luminescence
3

ARTICLE IN PRESS
JID: CCLET
[m5G;June 8, 2021;2:57]
J. Zhang, M. She, L. Liu et al.
Chinese Chemical Letters xxx (xxxx) xxx
Science and Technology Project (Nos. 2019218214GXRC018CG019-
GXYD18.4 and 2020KJRC0115). We thank the support from
COVID-19 Prophylaxis and Treatment Emergency Research Special
Projects of Northwest University.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.cclet.2021.05.018.
References
[1] J. Luo, Z. Xie, J.W.Y. Lam, et al., Chem. Commun. (2001) 1740–1741.
[2] Q. Gao, L.H. Xiong, T. Han, et al., J. Am. Chem. Soc. 141 (2019) 14712–14719.
[3] W. Chen, F. Song, Chin. Chem. Lett. 30 (2019) 1717–1730.
[4] C. Wang, Z. Liu, M. Li, et al., Chem. Sci. 8 (2017) 3750–3758.
[5] J.D. Zhang, Z. Yan, S. Wang, et al., Dyes Pigm. 150 (2018) 112–120.
[6] D. Ding, G. Zhang, B.Z. Tang, L. Zheng, B. Situ, Patent, CN111239391 (A), 2020.
[7] D.D. La, S.V. Bhosale, L.A. Jones, S.V. Bhosale, ACS Appl. Mater. Interfaces 10
(2018) 12189–12216.
Fig. 4. (a) The arachidonic acid-induced ear swelling. (b) The activity of c36 against
the ear swelling. (c) The binding mode of c36 and CRA1 with CB2.
[8] J. Mei, N.L.C. Leung, R.T.K. Kwok, J.W.Y. Lam, B.Z. Tang, Chem. Rev. 115 (2015)
11718–11940.
Thr114, Phe183, Ile186, Leu191, Met265 amino acids (Fig. 4c), which
is consistent with the bind mode of reference CB2 agonist CRA1
[40]. These results indicated that c36 could influence CB2’s rele-
vant anti-inflammatory signal path, and its modification is signifi-
cant for the development of anti-inflammatory agents.
[9] Y. Zhang, Y. Wang, J. Wang, X.J. Liang, Mater. Horiz. 5 (2018) 799–812.
[10] P. Shen, Z. Zhuang, Z. Zhao, B.Z. Tang, J. Mater. Chem. C 6 (2018) 11835–11852.
[11] Y. Yu, J. Chen, S. Tan, et al., J. Mater. Chem. C 9 (2021) 888–893.
[12] L. Zhang, Y.F. Wang, M. Li, Q.Y. Gao, C.F. Chen, Chin. Chem. Lett. 32 (2021)
740–744.
[13] W. Chi, J. Chen, W. Liu, et al., J. Am. Chem. Soc. 142 (2020) 6777–6785.
[14] S. Chen, H. Li, P. Hou, Anal. Chim. Acta 993 (2017) 63–70.
[15] Y. Ge, R. Ji, S. Shen, X. Cao, F. Li, Sens. Actuators B 245 (2017) 875–881.
[16] S.L. Shen, X.Q. Huang, X.H. Lin, X.Q. Cao, Anal. Chim. Acta 1052 (2019) 124–130.
[17] H. Sheng, Y. Hu, Y. Zhou, et al., Dyes Pigments 160 (2019) 48–57.
[18] K. Tajima, N. Fukui, H. Shinokubo, Org. Lett. 21 (2019) 9516–
9520.
In summary, we have presented a series of twisted imidazo[1,5-
a]pyridines via iodine-mediated Kornblum oxidation and cascade
dual C–N bond coupling from phenylacetylenes or styrenes. Com-
paring with previous imidazo[1,5-a]pyridine based fluorophores,
the optimized structures have overcome the adverse π–π stacking
effect and enhanced the intermolecular rotation, leading to excel-
lent AIE characters. The maximum emission could be easily modu-
lated to achieve the desired performance to meet the requirement
of bioimaging via regulating the electronic and steric effects. More-
over, compound c36 was proven to be an anti-inflammation agent
via the activation of the CB2 receptor. This promising synthetic
method will be beneficial to the development of new AIEgens and
lead compounds.
[19] K. Sun, X.L. Chen, S.J. Li, et al., J. Org. Chem. 83 (2018) 14419–14430.
[20] M. Liu, S. Ma, M.Y. She, et al., Chin. Chem. Lett. 30 (2019) 1815–1824.
[21] F. Shibahara, R. Sugiura, E. Yamaguchi, A. Kitagawa, T. Murai, J. Org. Chem. 74
(2009) 3566–3568.
[22] Z. Xie, J. Peng, Q. Zhu, Org. Chem. Front. 3 (2016) 82–86.
[23] S. Chuprakov, F.W. Hwang, V. Gevorgyan, Angew. Chem. Int. Ed. 46 (2007)
4757–4759.
[24] A. Joshi, D.C. Mohan, S. Adimurthy, J. Org. Chem. 81 (2016) 9461–9469.
[25] A. Joshi, D.C. Mohan, S. Adimurthy, Org. Lett. 18 (2016) 464–467.
[26] H. Wang, W. Xu, Z. Wang, L. Yu, K. Xu, J. Org. Chem. 80 (2015) 2431–2435.
[27] M. Li, Y. Xie, Y. Ye, et al., Org. Lett. 16 (2014) 6232–6235.
[28] C.T. Feng, H.J. Wei, J. Li, Y. Peng, K. Xu, Adv. Synth. Catal. 360 (2018) 4726–4730.
[29] P. Qian, Z. Zhou, K. Hu, et al., Org. Lett. 21 (2019) 6403–6407.
[30] H. Wang, W. Xu, L. Xin, et al., J. Org. Chem. 81 (2016) 3681–3687.
[31] P. Qian, Z. Yan, Z. Zhou, et al., Org. Lett. 20 (2018) 6359–6363.
[32] Y.D. Wu, X. Geng, Q. Gao, et al., Org. Chem. Front. 3 (2016) 1430–1434.
[33] H. Wu, X. Guo, C. Yu, et al., Dyes Pigments 176 (2020) 108209.
[34] Y. Zhang, B. He, J. Liu, et al., Phys. Chem. Chem. Phys. 20 (2018) 9922–9929.
[35] M.Y. She, Z. Wang, T. Luo, et al., Chem. Sci. 9 (2018) 8065–8070.
[36] M. Yang, J. Deng, H. Su, et al., Mater. Chem. Front. 5 (2021) 406–417.
[37] J. Li, S. Zhang, H. Zou, Org. Chem. Front. 7 (2020) 1218–1223.
[38] S. Han, J. Thatte, D.J. Buzard, et al., J. Med. Chem. 56 (2013) 8224–8256.
[39] X. Li, T. Hua, K. Vemuri, et al., Cell 176 (2019) 459–467.
[40] B.W. Trotter, K.K. Nand, C.S. Burgey, et al., Bioorg. Med. Chem. Lett. 21 (2011)
2354–2358.
Declaration of competing interest
The authors declare that they have no conflict of interests.
Acknowledgments
This work was financially supported by the National Nat-
ural Science Foundation of China (Nos. 22077099, 21807087
and 21673173), Key Research and Development Plan in Shaanxi
Province of China (No. 2019KWZ-07), the Technology Innovation
Leading Program of Shaanxi (No. 2020TG-031), the Xi’an City
4