Synthesis, structure and luminescence of novel co-crystals based on bispyridyl-substituted α,β-unsaturated ketones with coformers

Article abstract of DOI:10.1016/j.molstruc.2014.09.008

Based on 2,6-bis((pyridin-4-yl)methylene)cyclohexanone (A) and N-methyl-3,5-bis((pyridin-4-yl)methylene)-4-piperidone (B) with coformers, three novel macrocyclic co-crystals, (A)·(resorcinol) (1), (A)·(1,3,5-benzenetriol) (2), (B)₂·(1,3,5-benze

Full text of DOI:10.1016/j.molstruc.2014.09.008

Journal of Molecular Structure 1079 (2015) 414–422
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, structure and luminescence of novel co-crystals based
on bispyridyl-substituted a,b-unsaturated ketones with coformers
⇑
Hong-Juan Li, Lei Wang, Juan-Juan Zhao, Ju-Feng Sun, Ji-Liang Sun, Chun-Hua Wang, Gui-Ge Hou
School of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, PR China
h i g h l i g h t s
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Six novel macrocyclic and chain co-crystals 1–6 were generated.
The ‘‘clip-like’’ resorcinol acts as H-bonding donor and template in 1–3.
They display interesting solid-state luminescent properties.
They are blue-shifted 55–60 nm with decreased emission intensities.
Their luminescence is related to H-bonds, conformations, arranging dispositions.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 May 2014
Received in revised form 15 August 2014
Accepted 3 September 2014
Available online 11 September 2014
Based on 2,6-bis((pyridin-4-yl)methylene)cyclohexanone (A) and N-methyl-3,5-bis((pyridin-4-yl)methy-
lene)-4-piperidone (B) with coformers, three novel macrocyclic co-crystals, (A)Á(resorcinol) (1),
(A)Á(1,3,5-benzenetriol) (2), (B)2Á(1,3,5-benzenetriol)2 (3) and three chain co-crystals, (A)Á(hydroquinone)
(4), (A)Á(isophthalic acid) (5), (B)Á(isophthalic acid) (6) have been synthesized and structurally character-
ized by IR, 1H NMR and X-ray crystal structure analysis. Structural analysis indicates that four-component
macrocycles in 1–3 are generated from ‘‘clip-like’’ resorcinol templates and building blocks, while 4–6
show infinite H-bonding chains. In addition, the luminescent properties of A, B and 1–6 are investigated
primarily in the solid state. Compared with free building blocks, 1–6 are blue-shifted 55–60 nm with
decreasing emission intensities in spite of the enhancement in 6. The change of luminescent properties
might be caused mainly by incorporation of coformers into co-crystals, including H-bonds, molecular
Keywords:
Co-crystals
Crystal structures
Macrocycles
Luminescence properties
conformations, arranging dispositions and
crystal engineering to construct patentable crystals with interesting luminescent properties.
Ó 2014 Elsevier B.V. All rights reserved.
p–p characteristics. It might have potential applications for
Introduction
able co-crystals. Such processes involve designing molecules into
molecular assemblies through noncovalent forces (e.g., hydrogen
Based on Zaworotko’s definition of ‘‘co-crystal’’ [1], co-crystals
are molecular solids composed of at least two types of neutral
chemical species, which are able to offer the aggregation to modify
the physical properties of subset involved without changing chem-
ical species’ structures. During the past few decades, many co-crys-
tals have been reported and shown encouraging potential in
pharmaceutical application [2,3], solid-state organic synthesis [4],
catalysis [5], separation [6] and luminescent materials [7–11].
However, obtaining patentable co-crystals with novel topologies
is a challenge for scientists, such as zero- (0D), one- (1D), two-
(2D), or three-dimensional (3D) frameworks. It is very important
to control the processes of molecular self-assembly to get patent-
bonds, p–p interactions). In addition, template effect could be a
good approach to control the processes of molecular self-assembly
to get desired topologies, especially molecular templates, such as
resorcinol, 1,8-naphthalenedicarboxylic acid (1,8-nap), 2,3-bis(4-
methylenethiopyridyl)naphthalene (2,3-nap) and some derivatives
[4]. Many scientists are utilizing these templates to control molec-
ular self-assembly to get solid materal. For example, MacGillivray
and co-works cocrystallized resorcinol or 1,8-nap with trans-1,2-
bis(4-pyridyl)ethylene or 2,3-nap via four OAHÁ Á ÁN hydrogen
bonds for an intermolecular [2+2] photodimerization [12,13].
Our interests lie in using molecular template to control the pro-
cesses of molecular self-assembly to get patentable co-crystals
[9,14,15]. Specifically, we have shown that co-crystallization of
resorcinol with the asymmetric 5-(4-pyridyl)pyrimidine (5,4-
ppm) or 5-(4-(1-imidazolyl)phenyl)pyrimidine (5,4-ippm) yields
⇑
Corresponding author. Tel.: +86 5356913718.
E-mail address: guigehou@163.com (G.-G. Hou).
http://dx.doi.org/10.1016/j.molstruc.2014.09.008
0022-2860/Ó 2014 Elsevier B.V. All rights reserved.

H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
415
Table 1
Crystallographic data for 1–3.
Compound
1
2
3
Empirical formula
CCDC Deposit No.
Color/shape
Formula weight
Temperature (K)
Crystal system
Space group
a (Å)
C
18H16N2OÁC6H6O2
C18H16N2OÁC6H6O3
983865
Yellow, block
402.44
296(2)
Triclinic
C18H17N3OÁC6H6O3
983870
Yellow, block
417.45
296(2)
Triclinic
983864
Yellow, block
386.44
296(2)
Triclinic
PÀ1
PÀ1
PÀ1
9.192(3)
9.2228(10)
10.0073(11)
11.6429(13)
90.151(2)
93.484(2)
112.015(2)
994.02(19)
2
12.823(2)
13.434(3)
14.297(3)
69.352(3)
86.956(3)
67.952(3)
2127.1(7)
4
b (Å)
c (Å)
10.047(3)
11.495(3)
90.089(4)
94.477(4
112.603(5)
976.5(5)
a
(°)
b (°)
c
(°)
Volume (Å3)
Z
q
l
2
calc. (g/cm3)
(Mo K
) (mmÀ1
1.314
0.08
1.345
0.092
1.304
0.090
a
)
F(000)
408
424
880
Limiting indices
À11 6 h 6 10
À11 6 k 6 12
À13 6 l 6 1
0.20 Â 0.15 Â 0.12
2.20–25.50
98.1%
À11 6 h 6 11
À12 6 k 6 12
À11 6 l 6 14
0.15 Â 0.12 Â 0.10
1.75–25.50
99.2%
À15 6 h 6 15
À16 6 k 6 13
À16 6 l 6 17
0.13 Â 0.10 Â 0.06
1.53–25.50
99.4%
Crystal size (mm)
Theta range for data collection (°)
Completeness to h
Reflections collected
7393
5769
12373
Independent reflections
3561
3673
7869
[R(int) = 0.0462]
3561/0/265
1.051
[R(int) = 0.0177]
3673/0/274
1.039
[R(int) = 0.0243]
7869/0/568
1.022
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R1 = 0.0590
wR2 = 0.1718
R1 = 0.0743
wR2 = 0.1875
0.238 and À0.259
R1 = 0.0471
wR2 = 0.1182
R1 = 0.0648
wR2 = 0.1319
0.231 and À0.264
R1 = 0.0485
wR2 = 0.1120
R1 = 0.0902
wR2 = 0.1342
0.160 and À0.172
R indices (all data)a
Largest diff. peak and hole e ÅÀ3
a
R1
=
R
||Fo| À |Fc||/
R
|Fo|. wR2 = {
R
[w(F2o À F2c)2]/
R .
[w(F2o)2]}1/2
a 3D co-crystal with open hexagonal channels and a four-compo-
nent {(5,4-ippm)2(resorcinol)2} macrocycle through H-bonds. The
results display very interesting tunability of emission intensity
by the incorporation of coformers into the co-crystals [14].
In addition, some 3,5-bis(arylidene)-4-piperidones have been
reported to display good cytotoxic activities and interesting fluo-
rescent properties because of their structural characteristic of dou-
27 FTIR spectrometer. Elemental analyses were performed on a
Perkin–Elmer Model 240c analyzer. 1H NMR data were collected
using a Bruker Avance-300 spectrometer. Chemical shifts were
reported in d relative to TMS. All fluorescence measurements were
carried out on a Cary Eclipse Spectrofluorimeter (Varian, Australia)
equipped with a xenon lamp and quartz carrier at room tempera-
ture. The yields were calculated from the crystalline samples after
removal of the solvent under vacuum and the molar amounts ini-
tially introduced.
ble
bis(arylidene)-4-piperidone derivatives might be potential two-
photon sensitizers because of the donor– -acceptor– -donor
a,b-unsaturated ketone [16–22]. In Short’s report, some 3,5-
p
p
structure in the molecules [19]. We have also reported ten novel
N-substituted-3,5-bis(arylidene)-4-piperidone derivatives with
good cytotoxic activities and fluorescent properties. The results
show the structure–property relationship between fluorescent
properties and cytotoxic activities [22]. In this contribution, 2,6-
bis((pyridin-4-yl)methylene)cyclohexanone (A) and N-methyl-
3,5-bis((pyridin-4-yl)methylene)-4-piperidone (B) are used to get
novel macrocyclic and chain co-crystals by controlling the orienta-
tion of coformers. Three novel macrocyclic co-crystals (A)Á(resor-
cinol) (1), (A)Á(1,3,5-benzenetriol) (2), (B)2Á(1,3,5-benzenetriol)2
(3) and three chain co-crystals (A)Á(hydroquinone) (4), (A)Á(iso-
phthalic acid) (5), (B)Á(isophthalic acid) (6) will be reported. In
addition, the luminescent properties of A, B and 1–6 were investi-
gated primarily in the solid state.
Synthesis of A and B
4-Pyridinecarboxaldehyde (2.14 g, 0.02 mol) was added to a
solution of cyclohexanone (0.98 g, 0.01 mol) or N-methyl-4-piperi-
done (1.13 g, 0.01 mol) and glacial acetic acid (20 mL). Dry hydro-
gen chloride gas was passed through this mixture for 45 min,
during which time a clear solution was obtained. After stirring at
room temperature for about 24 h, the mixture was added into
100 mL water, and then aqueous ammonia was added until the
pH of the system was adjusted to about 7. The system was filtered
and subsequently washed by water to provide a yellow precipitate
A or B.
A: Yield, 75%. IR (KBr Pellet cmÀ1): 3020(m), 2943(m), 1666(m),
1612(s), 1592(s), 1543(m), 1430(s), 1323(m), 1275(s), 1170(s),
1145(s), 971(m), 940(m), 816(s). 1H NMR (300 MHz, DMSO,
25 °C, TMS, ppm): 8.64 (d, J = 5.8, 4H, AC5H4N), 7.54 (s, 2H,
AC@CH), 7.48 (d, J = 5.8, 4H, AC5H4N), 2.90 (t, 4H, ACH2), 1.73
(m, 2H, ACH2). Elemental analysis (%) calcd. for C18H16N2O
(276.33): C 78.23, H 5.83, N 10.13; Found: C 78.43, H 5.89, N 10.02.
B: Yield, 84%. IR (KBr Pellet cmÀ1): 3045(m), 2963(m), 1665(m),
1592(s), 1541(m), 1442(s), 1343(m), 1279(s), 1176(s), 830(m),
Experimental
Materials and methods
Infrared (IR) samples were prepared as KBr pellets, and spectra
were obtained in the 400–4000 cmÀ1 range using a Bruker tensor-

416
H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
Table 2
Crystallographic data for 4–6.
Compound
4
5
6
Empirical formula
CCDC Deposit No.
Color/shape
Formula weight
Temperature (K)
Crystal system
Space group
a (Å)
C
18H16N2OÁC6H6O2
C18H16N2OÁC8H6O4
983867
Yellow, block
442.46
296(2)
Monoclinic
P2(1)/c
22.752(2)
14.2803(15)
6.6982(7)
90
C18H17N3OÁC8H6O4
983872
Yellow, block
442.46
296(2)
Monoclinic
P2(1)/c
19.841(5)
7.349(5)
16.433(5)
90
983868
Yellow, block
386.44
296(2)
Monoclinic
P2(1)/c
9.8017(6)
9.0807(5)
22.1860(13)
90
b (Å)
c (Å)
a
(°)
b (°)
91.1280(10)
90
1974.3(2)
4
1.300
0.086
92.557(2)
90
2174.2(4)
4
1.352
0.095
94.520(5)
90
2388.7(19)
2
1.311
0.093
c
(°)
Volume (Å3)
Z
q
l
calc. (g/cm3)
(Mo K
) (mmÀ1
a
)
F(000)
816
928
988
Limiting indices
À11 6 h 6 11
À6 6 k 6 11
À26 6 l 6 24
0.15 Â 0.12 Â 0.12
1.84–25.50
99.9%
À27 6 h 6 27
À11 6 k 6 17
À8 6 l 6 8
0.12 Â 0.12 Â 0.10
0.90–25.50
99.3%
À21 6 h 6 24
À8 6 k 6 8
À19 6 l 6 19
0.15 Â 0.08 Â 0.07
2.06–25.50
99.6%
Crystal size (mm)
Theta range for data collection (°)
Completeness to h
Reflections collected
11120
16503
16919
Independent reflections
3663
4009
4418
[R(int) = 0.0250]
3663/0/265
1.026
[R(int) = 0.0306]
4009/0/301
1.047
[R(int) = 0.0315]
4418/1/319
1.025
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R1 = 0.0358
wR2 = 0.0905
R1 = 0.0457
wR2 = 0.0988
0.160 and À0.115
R1 = 0.0395
wR2 = 0.0974
R1 = 0.0519
wR2 = 0.1054
0.193 and À0.156
R1 = 0.0574
wR2 = 0.1591
R1 = 0.0941
wR2 = 0.1880
0.534 and À0.233
R indices (all data)a
Largest diff. peak and hole e ÅÀ3
a
R1
=
R
||Fo| À |Fc||/
R
|Fo|. wR2 = {
R
[w(F2o À F2c)2]/
R .
[w(F2o)2]}1/2
Table 3
Relevant hydrogen-bonding geometries (Å, °) found in 1–6.
DAHÁ Á ÁA
d(DAH)
d(HÁ Á ÁA)
d(DÁ Á ÁA)
Symmetry code
—(DHA)
1
O(2)AH(2)Á Á ÁN(1)i
0.82
0.82
1.96
1.94
2.782(2)
2.755(2)
174.6
173.4
i: x, y, z À 1
O(3)AH(3)Á Á ÁN(2)ii
ii: Àx, Ày, Àz + 1
2
O(2)AH(2)Á Á ÁN(1)i
O(3)AH(3)Á Á ÁN(3)ii
O(4)AH(4A)Á Á ÁO(1)iii
0.82
0.82
0.82
1.92
1.97
2.41
2.735(2)
2.785(2)
3.106(3)
170.8
175.8
175.8
i: x À 1, y, z
ii: Àx + 1, Ày + 1, Àz
iii: x, y, z + 1
3
O(3)AH(3)Á Á ÁN(1)i
O(5)AH(5A)Á Á ÁN(3)ii
O(6)AH(6A)Á Á ÁN(6)iii
O(8)AH(8)Á Á ÁN(4)iv
O(4)AH(4A)Á Á ÁO(2)v
O(7)AH(7)Á Á ÁO(4)vi
0.82
0.82
0.82
0.82
0.82
0.82
1.92
1.95
1.95
1.97
2.05
2.03
2.736(2)
2.773(2)
2.773(2)
2.783(2)
2.811(2)
2.838(2)
171.3
176.5
175.1
170.7
153.4
166.6
i: Àx + 1, Ày, Àz + 2
ii: x + 1, y À 1, z
iii: Àx + 1, Ày + 2, Àz + 1
iv: x, y, z À 1
v: Àx + 1, Ày + 1, Àz + 1
vi: x, y, z + 1
4
O(3)AH(3)Á Á ÁN(1)i
0.82
0.82
1.93
1.92
2.733(2)
2.730(2)
167.9
168.8
i: Àx + 2, y + 1/2, Àz + 1/2
ii: Àx, Ày + 1, Àz
O(2)AH(2)Á Á ÁN(2)ii
5
O(4)AH(4)Á Á ÁN(1)i
0.82
1.85
2.664(2)
176.0
i: x À 1, y, z
6
O(2)AH(2A)Á Á ÁN(2)i
0.82
0.82
1.81
1.84
2.626(3)
2.617(3)
171.3
157.5
i: Àx, y À 1/2, Àz + 1/2
O(5)AH(5A)Á Á ÁN(1)ii
ii: Àx + 1, y À 1/2, Àz + 3/2
731(m). 1H NMR (300 MHz, DMSO, 25 °C, TMS, ppm): 8.67 (d,
J = 5.9, 4H, AC5H4N), 7.54 (s, 2H, AC@CH), 7.51 (d, J = 5.9, 4H, AC5
H4N), 2.93 (t, 4H, ACH2), 2.49 (s, 3H, ANCH3). Elemental analysis
(%) calcd. for C18H17N3O (291.34): C 74.20, H 5.88, N 14.42; Found:
C 74.35, H 5.81, N 14.48.
Preparation of co-crystals 1–6
Co-crystal 1
A CH2Cl2 and CH3OH solution (10 mL, 1:1, v/v) of A (27.6 mg,
0.1 mmol) with resorcinol (11.0 mg, 0.1 mmol) was kept at room

H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
417
Fig. 1. The ORTEP figures of 1–3 (displacement ellipsoids with 30% probability).
Fig. 2. The ORTEP figures of 4–6 (displacement ellipsoids with 30% probability).
resorcinol
1, (A)(resorcinol), 0D macrocycle
O
1,3,5-benzenetriol
2, (A)(1,3,5-benzenetriol), macrocycle, 1D chain
N
N
hydroquinone
4, (A)(hydroquinone), 1D chain
A
isophthalic acid
5, (A)(isophthalic acid), 1D chain
O
1,3,5-benzenetriol
3, (B)2(1,3,5-benzenetriol)2, macrocycle, 2D net
N
N
isophthalic acid
N
6, (B)(isophthalic acid), 1D chain
B
Scheme 1. Building modules A, B and co-crystals 1–6.
temperature. Upon slow evaporation of the solvent about 7 days,
yellow crystals 1 were obtained. Yield: 92%. IR (KBr Pellet cmÀ1):
3047(m), 2939(m), 2730(m), 2607(m), 1673(m), 1595(s),
1543(m), 1422(m), 1309(m), 1273(s), 1220(s), 1182(m), 1166(m),
1144(s), 1008(m), 837(m), 763(m). 1H NMR (300 MHz, DMSO,
25 °C, TMS, ppm): 9.12 (s, 2H, AOH), 8.64 (d, J = 5.8, 4H, AC5H4N),

418
H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
Fig. 3. The similiar four-component macrocycles generated from clip-like resorcinol coformer and symmetric building blocks through H-bonding interactions in 1–3
(Symmetry codes in 1: i x, y, z À 1; ii Àx, Ày, Àz + 1; Symmetry codes in 2: i x À 1, y, z; ii Àx + 1, Ày + 1, Àz; iii x, y, z + 1; Symmetry codes in 3: i Àx + 1, Ày, Àz + 2; ii x + 1, y – 1,
z; iii Àx + 1, Ày + 2, Àz + 1; iv x, y, z À 1).
Fig. 4. (a) The
p–p
stacking fashion in co-crystal 1. (b) The double chain through the intermacrocyclic O(4)AH(4A)Á Á ÁO(1)iii hydrogen bonds in co-crystal 2 (Symmetry code:
iii x, y, z + 1). (c) The H-bonded 2D network through the inter-macrocyclic O(4)AH(4A)Á Á ÁO(2)v hydrogen bonds in co-crystal 3 (Symmetry code: v Àx + 1, Ày + 1, Àz + 1).
7.54 (s, 2H, AC@CH), 7.48 (d, J = 5.8, 4H, AC5H4N), 6.89 (m, 1H,
AC6H4), 6.17 (t, 2H, AC6H4), 6.15 (s, 1H, AC6H4), 2.90 (t, 4H,
ACH2), 1.73 (m, 2H, ACH2). Elemental analysis (%) calcd. for
Co-crystal 3
A CH2Cl2 and CH3OH solution (10 mL, 1:1, v/v) of B (29.1 mg,
0.1 mmol) with 1,3,5-benzenetriol (12.6 mg, 0.1 mmol) was kept
at room temperature. Upon slow evaporation of the solvent about
7 days, yellow crystals 3 were obtained. Yield: 86%. IR (KBr Pellet
cmÀ1): 3065(m), 2764(br), 2631(br), 1664(m), 1595(s), 1540(m),
1496(m), 1424(s), 1271(s), 1156(s), 1144(s), 1012(s), 830(s),
731(m). 1H NMR (400 MHz, DMSO, 25 °C, TMS, ppm): 8.91 (s, 3H,
AOH), 8.69 (d, J = 5.9, 4H, AC5H4N), 7.68 (s, 2H, AC@CH), 7.25 (d,
J = 5.9, 4H, AC5H4N), 5.64 (s, 3H, AC6H3), 3.74 (s, 4H, ACH2), 2.47
(s, 3H, ANCH3). Elemental analysis (%) calcd. for C24H23N3O4
(417.45): C 69.05, H 5.55, N 10.06; Found: C 68.95, H 5.61, N 10.12.
C24H22N2O3 (386.44): C 74.59, H 5.74, N 7.25; Found: C 74.43, H
5.81, N 7.19.
Co-crystal 2
A CH2Cl2 and CH3OH solution (10 mL, 1:1, v/v) of A (27.6 mg,
0.1 mmol) with 1,3,5-benzenetriol (12.6 mg, 0.1 mmol) was kept
at room temperature. Upon slow evaporation of the solvent about
4 days, yellow crystals 2 were obtained. Yield: 88%. IR (KBr Pellet
cmÀ1): 3047(m), 2939(br), 2774(br), 2624(br), 1665(m), 1597(s),
1542(m), 1492(m), 1419(s), 1274(s), 1167(s), 1146(s), 1002(s),
824(s), 730(m). 1H NMR (300 MHz, DMSO, 25 °C, TMS, ppm):
8.91 (s, 3H, AOH), 8.64 (d, J = 5.8, 4H, AC5H4N), 7.54 (s, 2H,
AC@CH), 7.48 (d, J = 5.8, 4H, AC5H4N), 5.64 (s, 3H, AC6H3), 2.90
(t, 4H, ACH2), 1.73 (m, 2H, ACH2). Elemental analysis (%) calcd.
for C24H22N2O4 (402.44): C 71.63, H 5.51, N 6.96; Found: C 71.51,
H 5.57, N 6.89.
Co-crystal 4
A CH2Cl2 and CH3OH solution (10 mL, 1:1, v/v) of A (27.6 mg,
0.1 mmol) with hydroquinone (11.0 mg, 0.1 mmol) was kept at
room temperature. Upon slow evaporation of the solvent about
10 days, yellow crystals 4 were obtained. Yield: 75%. IR (KBr Pellet
cmÀ1): 3065(m), 2936(m), 2702(m), 2601(m), 1677(m), 1597(s),
1543(m), 1472(s), 1422(s), 1368(s), 1271(s), 1255(s), 1215(s),

H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
419
Table 4
structures were solved by a combination of direct methods and dif-
ference Fourier syntheses and refined against F2 by the full-matrix
least squares technique. Crystal data, data collection parameters,
and refinement statistics for 1–6 are listed in Table 1 and Table 2.
Relevant hydrogen-bonding geometries for 1–6 are shown in
Table 3.
Relevant torsion angles (°) found in 1–6.
Torsion angle
Value (°)
Torsion angle
Value (°)
28.7
1
C2AC3AC6AC7
À36.0
C9AC13AC14AC17
C9AC13AC14AC17
2
C4AC3AC6AC7
À29.4
35.4
3
Results and discussion
C4AC3AC6AC7
C22AC21AC24AC25
À22.6
À25.8
C9AC13AC14AC18
C28AC31AC32AC36
26.6
28.0
Structural analysis
4
C4AC3AC6AC7
24.4
À39.0
À22.9
C9AC13AC14AC17
C9AC13AC14AC17
C9AC13AC14AC18
À25.7
38.5
As described in the experimental section, co-crystals 1–6 were
prepared by direct assembly in CH2Cl2 and CH3OH solution under
the ambient condition and crystallization via solvent evaporation.
1H NMR spectra of the solution were collected on crystalline sam-
ples of 1–6. 1H NMR spectra indicated that the chemical shift val-
ues were completely identical to that of the original materials,
indicating the formation of the neutral and discrete molecules in
solution. In addition, solubility of A, B and 1–6 were investigated
at room temperature. Building blocks A and B are almost insoluble
in water but can freely soluble in some organic solvent, such as
alcohol, chloroform and dimethyl sulfoxide (DMSO). Except being
freely soluble in above-mentioned organic solvent, the power of
co-crystals can slightly soluble in water or 20 mM PBS buffer sys-
tem (pH 7.4). The solubilities of 1–6 are approximately 3.6, 4.2,
2.5, 1.2, 4.7, 1.7 mg mLÀ1 in water and 4.0, 4.9, 2.7, 1.3, 5.8,
2.2 mg mLÀ1 in PBS buffer system, respectively. The results dis-
played the solubility of all co-crystals were distinctly improved.
Single-crystal structure reveals that co-crystals 1–6 exhibit an
1:1 stoichiometric ratio of components. The asymmetric units of
co-crystals 1–6 are shown in Fig. 1 and Fig. 2. They contain one
building block and one coformer, while 3 contains two B and two
1,3,5-benzenetriol templates. The results are corresponding to
the formulas in Scheme 1, which is basically identical to those of
1H NMR spectra data.
As shown in Fig. 3, the bent resorcinol template as the hydrogen
bonding donor looks like an ‘‘organic clip’’ [24,25] with two group
OAHÁ Á ÁN hydrogen bonds from two pyridine groups in co-crystal
1–3. Relevant hydrogen-bonding geometries are given in Table 3.
Interestingly, two clip-like resorcinol templates link two building
blocks into similiar four-component {(A)2Á(resorcinol)2}, {(A)2Á
(1,3,5-benzenetriol)2} and {(B)2Á(1,3,5-benzenetriol)2} macrocycles
with an R44 (40) motif [26]. It is noteworthy that two building
blocks are almost vertical with the resorcinol templates, proved
by the dihedral angles between pyridine and resorcinol plane
(83.6° and 84.2° in 1, 85.0° and 84.3° in 2, 59.5° and 69.4°, 59.5°
and 65.7° in 3, respectively). In addition, due to the structure char-
5
C4AC3AC6AC7
6
C2AC3AC6AC7
23.2
1168(s), 1144(s), 1009(s), 856(s), 830(s), 763(m). 1H NMR
(400 MHz, DMSO, 25 °C, TMS, ppm): 8.64 (d, J = 5.8, 4H, AC5H4N),
8.60 (s, 2H, C6H6O2), 7.54 (s, 2H, AC@CH), 7.48 (d, J = 5.8, 4H, AC5-
H4N), 6.54 (s, 4H, C6H6O2), 2.90 (t, 4H, ACH2), 1.73 (m, 2H,
ACH2).8.91 (s, 3H, AOH), 8.67 (d, J = 5.9, 4H, AC5H4N), 7.54 (s,
2H, AC@CH), 7.51 (d, J = 5.9, 4H, AC5H4N), 5.64 (s, 3H, AC6H3),
2.93 (t, 4H, ACH2), 2.49 (s, 3H, ANCH3). Elemental analysis (%)
calcd. for C24H22N2O3 (386.44): C 74.59, H 5.74, N 7.25; Found: C
74.38, H 5.84, N 7.14.
Co-crystal 5
A CH2Cl2 and CH3OH solution (10 mL, 1:1, v/v) of A (27.6 mg,
0.1 mmol) with isophthalic acid (16.6 mg, 0.1 mmol) was kept at
room temperature. Upon slow evaporation of the solvent about
10 days, yellow crystals 5 were obtained. Yield: 81%. IR (KBr Pellet
cmÀ1): 2948(m), 1928(br), 1687(s), 1599(s), 1417(m), 1316(s),
1272(s), 1241(s), 1163(s), 1141(s), 1014(s), 968(s), 839(m),
735(m). 1H NMR (400 MHz, DMSO, 25 °C, TMS, ppm): 13.26 (s,
2H, ACOOH), 8.64 (d, J = 5.8, 4H, AC5H4N), 8.48 (s, 1H, AC6H4),
8.17 (d, 2H, AC6H4), 7.64 (m, 1H, AC6H4), 7.54 (s, 2H, AC@CH),
7.48 (d, J = 5.8, 4H, AC5H4N), 2.90 (t, 4H, ACH2), 1.73 (m, 2H,
ACH2). Elemental analysis (%) calcd. for C26H22N2O5 (442.46): C
70.57, H 5.01, N 6.33; Found: C 70.76, H 5.06, N 6.12.
Co-crystal 6
A CH2Cl2 and CH3OH solution (10 mL, 1:1, v/v) of B (29.1 mg,
0.1 mmol) with isophthalic acid (16.6 mg, 0.1 mmol) was kept at
room temperature. Upon slow evaporation of the solvent about
12 days, yellow crystals 6 were obtained. Yield: 78%. IR (KBr Pellet
cmÀ1): 3065(m), 2778(br), 1709(m), 1595(s), 1417(s), 1277(s),
1174(m), 1061(m), 922(m), 829(m), 733(s). 1H NMR (400 MHz,
DMSO, 25 °C, TMS, ppm): 13.26 (s, 2H, ACOOH), 8.69 (d, J = 5.0,
4H, AC5H4N), 8.48 (s, 1H, AC6H4), 8.17 (d, 2H, AC6H4), 7.68 (s,
2H, AC@CH), 7.64 (m, 1H, AC6H4), 7.25 (d, J = 5.0, 4H, AC5H4N),
3.74 (s, 4H, ACH2), 2.47 (s, 3H, ANCH3). Elemental analysis (%)
calcd. for C26H22N2O5 (442.46): C 70.57, H 5.01, N 6.33; Found: C
70.23, H 5.08, N 6.41.
acteristic of bis(arylidene)-a,b-unsaturated ketone, two building
blocks in the same macrocycle are closer each other through
p–p
interaction (the centroid–centroid distances, 3.52–3.61 Å).
However, two cyclohexanones in 1, 2 or two 4-piperidones in 3
are located on the opposite directions in head-to-tail fashion [27].
Unfortunately, the head-to-tail fashion leads to olefin misalign-
ment [24], and the olefins adopt an antiparallel orientation
(Fig. 3), such that the double bonds could not conform to Schmidt’s
alignment criterion for [2+2] photoreaction [28].
Single-crystal structure determination
In the solid state, all the four-component macrocycles have
potential in constructing novel frameworks by hydrogen bonds
Suitable single crystals 1–6 were selected and mounted in air
onto thin glass fibers. X-ray intensity data of 1–6 were measured
at 296 K on a Bruker SMART APEX CCD-based diffractometer (Mo
or intermolecular
orcinol)2} macrocycles link each other through intermolecular
p
–
p
interactions. As shown in Fig. 4a, {(A)2Á(res-
p–p
interactions between two adjacent pyridine groups into 1D chain
along the crystallographic c axes. The centroid–centroid distances
are ca. 3.50 Å, which is shorter than that of intra-macrocyclic cen-
troid–centroid distance (ca. 3.60 Å). In 2, these {(A)2Á(1,3,5-benze-
netriol)2} macrocycles connect each other into an 1D ladder-like
Ka radiation, k = 0.71073 Å). The raw frame data for 1–6 were inte-
grated into SHELX-format reflection files and corrected for Lorentz
and polarization effects using SAINT [23]. None of the crystals
showed evidence of crystal decay during data collection. All

420
H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
Fig. 5. The infinite H-bonding chains of 4–6 (Symmetry codes in 4: i Àx + 2, y + 1/2, Àz + 1/2; ii Àx, Ày + 1, Àz; Symmetry codes in 5: i x À 1, y, z; Symmetry codes in 6: i Àx,
y À 1/2, Àz + 1/2; ii Àx + 1, y À 1/2, Àz + 3/2).
chain (Fig. 4b). In 3, two 1,3,5-benzenetriol molecules are grouped
together through O(7)AH(7)Á Á ÁO(4) bond from third OAH of 1,3,5-
benzenetriol. Meantime, it is similar with
2 that desired
O(4)AH(4A)Á Á ÁO(2) bonds are formed by 1,3,5-benzenetriol and
ketone from two {(B)2Á(1,3,5-benzenetriol)2} macrocycles resulting
in a 2D network (Fig. 4c). Relevant hydrogen-bonding geometries
are given in Table 3.
It is well-known that many organic hydroxybenzene, aniline
and aromatic carboxylic acids have been widely used in construct
co-crystals systems as hydrogen-bond donors [29–32]. The differ-
ent functional groups and orientations will profoundly influence
the structural assemblies and luminescent properties because of
their different hydrogen bonding capability and steric/electronic
effect. In this contribution, the bent resorcinol and 1,3,5-benzenet-
riol are used as ‘‘organic clip’’ templates in 1–3, meanwhile, hydro-
quinone and isophthalic acid are used as for linear templates for
synthesis of novel co-crystals 4–6, as below. In co-crystal 5 and
6, all carboxy-H atoms on isophthalic acid were located in the dif-
ference Fourier map and included as riding atoms with OAH = 0.82
Å (Table 4) and Uiso(H) = 1.5 ⁄ Ueq(O).
Fig. 6. Solid-state photoinduced emission spectra of A, B and 1–6 (excitation
480 nm) at room temperature.
Single-crystal structures reveal that the symmetric building
module A or B links hydroquinone or isophthalic acid templates
to generate simple infinite zigzag chains through intermolecular
H-bonding interactions. As shown in Fig. 5, they exhibit C22(21)
motif in 4, C22(22) motif in 5 and C22(22) motif [26] in 6, respec-
tively. Relevant hydrogen-bonding geometries are given in Table 3.
In addition, the –ABAB– alternate arranging disposition between
building modules and templates in co-crystals can be found. What
is important is that pyridyl groups and templates are not fully
coplanar. For example, the dihedral angles between pyridyl groups
and hydroquinone are approximately 70.2° and 50.4°, which illus-
trates an almost vertical arranging disposition. In 5, the dihedral
angles are only 35.9° and 40.1°. However, compared with that of
4 and 5, the isophthalic acid planes are almost coplanar from pyr-
idyl groups, proved by the dihedral angles ca. 6.5° and 10.8° in 6.
erties because of their different hydrogen bonding capability and
steric/electronic effect [7–11,14,15]. The exploration of the synthe-
sis of new and patentable co-crystals, furthermore their lumines-
cent properties are very significant. In this study, the solid-state
emission spectra of A, B and 1–6 with approximate 25 mg crystal-
line samples, respectively, were investigated primarily at room
temperature. Fig. 6 presents the comparison of the emission spec-
tra of co-crystals 1–6 with A and B.
Upon excitation at k = 480 nm, building module A exhibits an
emission maximum at 586 nm, while B provides a blue-shifted
emission band at 567 nm. In the solid state, co-crystals 1, 2, 4, 5
exhibits emission maximum at ca. 525 nm as well as 512 nm of
3, 6 upon excitation at k = 480 nm. Compared to emission maxima
of A or B, the emission maxima are not only blue-shifted 55–
60 nm, but also emission intensities of 1–5 distinctly decrease.
However, emission intensity of 6 distinctly enhances as well as
blue-shifted 57 nm. The change of their luminescent properties
might be caused mainly by their incorporation of their coformers
into the co-crystals.
Luminescent properties of A, B, 1–6
Co-crystals are molecular solids composed of at least two types
of neutral chemical species. Incorporation of different coformers
with the different functional groups and orientations maybe pro-
foundly influence the structural assemblies and luminescent prop-
Firstly, single-crystal structures of all co-crystals show the E, E
stereochemistry of the olefinic double bond and pyridyl group

H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
421
Fig. 7. View of the characteristic of intermolecular p–p stacking interactions in co-crystals 1–6, respectively.
[22,33,34]. The point can be characterized by the torsion angle
value between pyridyl groups and central cyclohexanone or 4-pip-
eridone, which can influence the molecular conformations, further
influencing the fluorescent property. As shown in Table 4, all the
torsion angle values are within the range of 22.0–39.0°. It is worth
pointing out that the torsion angle values of co-crystal 3, 4, 6 look
relatively small, and less than 28.0°, especially for co-crystal 6, in
which h(C2AC3AC6AC7) = À22.9° and h(C9AC13AC14AC18) = 23.2°. Their
relatively small torsion angles may be conducive to intramolecular
interactions are listed in Fig. 7. For 1 and 2, four-component {(A)2-
Á(coformer)2} macrocycles are parallel packing in –AA– stacking
fashion with the vertical distances ca. 3.50–3.65 Å (Fig. 7a and b).
For 4, the –AA– alternate disposition of chains only through simple
p–p
interactions can be found (Fig. 7d). But in 5, the H-bonding
chains stack in -ABCD- fashion with simple interactions in
pairs (Fig. 7e). Unfortunately, all chains are not linked each other
by interactions resulting in segregative
and p⁄ electron-
p–p
p–p
p
transport of components. So the emission intensity of 5 distinctly
decreases compared with that of 1, 2 and 4. For 6, chains are linked
p
and p⁄ electron-transport, further influencing the fluorescent
property.
Secondly, the different intermolecular arranging disposition
each other by
p
–
p
interactions to generate a 2D network (Fig. 7f),
and p⁄
which help co-crystal contribute to more opportunities to
p
between building modules and their coformers badly influences
the intermolecular electron-transport in their co-crystals. In co-
crystals 1–5, coformers are hardly planar with the hydrogen-bond-
ing pyridine groups. The corresponding dihedral angles are ca.
84.3° and 83.6° in 1, ca. 85.1° and 84.3° in 2, ca. 59.5°, 69.4°,
65.7° and 59.5° in 3, ca. 70.2° and 50.4° in 4, 35.9° and 40.1° in 5,
respectively. By comparing the data, we can conclude that the
interplanar dihedral angles between building modules and their
coformers are close to intermolecular vertical forms in 1–4, result-
ing in poor conjugated effect, further decreasing their emission
intensities compared with free building modules. Therefore, by
introduction of the coformers, 1–4 displays distinctly weak emis-
sion intensity than A, B in the solid state. Interestingly, the emis-
sion intensity of 6 distinctly increases compared with that of B
and 3 (Fig. 6). The main reason may be that co-crystal 6 shows
smaller dihedral angles (ca. 6.6° and 10.8°) between pyridine group
and isophthalic acid resulting in the better coplanarity.
electron-transport of components. Added to the better coplanarity
described above, co-crystal 6 shows stronger emission intensity
than co-crystal 3.
In addition, temperature and particle size of crystalline samples
also can influence the solid-state luminescent properties of co-
crystals. Although we cannot give further explanations for the rela-
tionship between the solid-state luminescent properties and
hydrogen bonding interactions, molecular conformations, intermo-
lecular arranging disposition, intermolecular p–p contacting char-
acteristic, it is clear that the structure–property relationship of
these co-crystal systems are basically related to the introduction
of the coformers. Notably, all co-crystals display more interesting
luminescent properties. The strategy provides a facile way to
design and develop new types of solid fluorescent materials.
Conclusions
Thirdly, their different intermolecular
p–p contacting charac-
teristic can influence
p
and p⁄ electron-transport of components.
In this study, three novel macrocyclic co-crystals 1–3 and three
chain co-crystals 4–6 were generated based on two bispyridyl-
It is one of the critical factors that determine the solid state emis-
sion colors and emission intensity [9,35]. The parallel stack and the
substituted
a,b-unsaturated ketones A and B with ‘‘clip-like’’ resor-
vertical distance of components through the intermolecular
p–p
cinol, 1,3,5-benzenetriol and hydroquinone, isophthalic acid

422
H.-J. Li et al. / Journal of Molecular Structure 1079 (2015) 414–422
[4] L.R. Macgillivray, G.S. Papaefstathiou, T. Frišcꢀic´, T.D. Hamilton, D.K. Bucꢀar, Q.
Chu, D.B. Vareshney, I.G. Georgiev 41 (2008) p. 280.
[5] J. Rebek, Angew. Chem. Int. Ed. 44 (2005) 2068.
[6] D.S. Lawrence, T. Jiang, M. Levett, Chem. Rev. 95 (1995) 2229.
[7] T. Lee, P.Y. Wang, Cryst. Growth Des. 10 (2010) 1419.
[8] A.D.G.D. Mauro, M. Carotenuto, V. Venditto, V. Petraccone, M. Scoponi, G.
Guerra, Chem. Mater. 19 (2007) 6041.
[9] G.G. Hou, J.P. Ma, L. Wang, P. Wang, Y.B. Dong, R.Q. Huang, CrystEngComm 12
(2010) 4287.
coformers, respectively. In 1–3, the ‘‘clip-like’’ resorcinol or 1,3,5-
benzenetriol coformers as the hydrogen bonding donors and tem-
plates link two building modules to generate four-component
macrocycles, {(A)2Á(resorcinol)2}, {(A)2Á(1,3,5-benzenetriol)2} and
{(B)2Á(1,3,5-benzenetriol)2}. The study provides a facile way to
design and generate novel four-component macrocyclic com-
pounds through template effect. In 4–6, infinite H-bonding chains
can be found from building blocks and coformers through H-bond-
ing interactions. In addition, A, B and 1–6 display the interesting
solid-state luminescent properties. Compared to free building
blocks, emission maxima of 1–5 are not only blue-shifted 55–
60 nm, but also emission intensities distinctly decrease in spite
of enhancement of emission intensity in 6. Their luminescent prop-
erties might be caused mainly by their incorporation of their
coformers into the co-crystals. The structure–property relationship
of these co-crystal systems may be dependent on hydrogen bonds,
[10] S. D’Agostino, F. Grepioni, D. Braga, D. Moreschi, V. Fattori, F. Delchiaro, S.D.
Motta, F. Negri, CrystEngComm 15 (2013) 10470.
ˇ
[11] D. Yan, D.K. Bucar, A. Delori, B. Patel, G.O. Lloyd, W. Jones, X. Duan, Chem. Eur.
J. 19 (2013) 8213.
[12] L.R. MacGillivray, J.L. Reid, J.A. Ripmeester, J. Am. Chem. Soc. 122 (2000) 7817.
ˇ ´
[13] T. Frišcic, L.R. MacGillivray, Chem. Commun. 46 (2005) 5748.
[14] G.G. Hou, H.J. Zhao, J.F. Sun, D. Lin, X.P. Dai, J.T. Han, H. Zhao, CrystEngComm
15 (2013) 577.
[15] X.P. Dai, G.G. Hou, J.F. Sun, D. Lin, J.T. Han, J. Mol. Struct. 1035 (2013) 203.
[16] J.R. Dimmock, M.P. Padmanilayam, R.N. Puthucode, A.J. Nazarali, N.L.
Motaganahalli, G.A. Zello, J. Wilson Quail, E.O. Oloo, H.B. Kraatz, J.S. Prisciak,
T.M. Allen, C.L. Santos, J. Balzarini, E.D. Clercq, E.K. Manavathu, J. Med. Chem.
44 (2001) p. 586.
[17] H.I. El-Subbagh, S.M. Abu-Zaid, M.A. Mahran, F.A. Badria, A.M. Al-Obaid, J. Med.
Chem. 43 (2000) 2915.
[18] V.N. Nesterov, T.V. Timofeeva, S.S. Sarkisov, A. Leyderman, C.Y.C. Lee, M.Y. Acta
Cryst. C59 (2003) p. o605.
molecular conformations, arranging disposition,
p–p contacting
characteristic, and so on. It might have potential applications for
the organic crystal engineering to construct patentable crystals
with interesting luminescent properties.
[19] K.W. Short, T.L. Kinnibrugh, D.M. Sammeth, T.V. Timofeeva, Proc. SPIE 7164
(2009) 716411.
Supplementary material
[20] M.V. Makarov, E.S. Leonova, E.Y. Rybalkina, V.N. Khrustalev, N.E. Shepel, G.V.
Roschenthaler, T.V. Timofeeva, I.L. Odinets, Arch. Pharm. Chem. Life Sci. 345
(2012) 349.
[21] V.N. Nesterov, Acta Cryst. C60 (2004) o806.
[22] J.F. Sun, S.P. Zhang, C. Yu, G.G. Hou, X.F. Zhang, K.K. Li, F. Zhao, Chem. Biol. Drug
Des. 83 (2014) 392.
[23] Bruker Analytical X-ray Systems Inc., Madison, WI, 1998.
[24] L.R. MacGillivray, J.L. Reid, J.A. Ripmeester, G.S. Papaefstathiou, Ind. Eng. Chem.
Res. 41 (2002) 4494.
CCDC 983864 (1), 983865 (2), 983870 (3), 983868 (4), 983867
(5) and 983872 (6) contain the supplementary crystallographic
data for this paper. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (fax: +44 1223 336 033; e-mail: deposit@ccdc.cam.ac.uk).
[25] Y.B. Dong, T. Sun, J.P. Ma, X.X. Zhao, R.Q. Huang, Inorg. Chem. 45 (2006) 10613.
[26] M.C. Etter, Acc. Chem. Res. 23 (1990) 120.
Acknowledgements
[27] G.K. Kole, G.K. Tan, J.J. Vittal, Org. Lett. 12 (2010) 128.
[28] G.M.J. Schmidt, Pure Appl. Chem. 27 (1971) 647.
´
[29] M. Sowa, K. Slepokura, E. Matczak-Jon, J. Mol. Struct. 1058 (2014) 114.
We are grateful for financial support from the Foundation of
Shandong province (Nos. ZR2013BM022, J11LF27), the Foundation
of Yantai (Nos. 2013ZH095) and the Foundation of Binzhou
Medical University (No. BY2013KJ81).
[30] L. Brammer, Chem. Soc. Rev. 33 (2004) 476.
[31] M. Du, X.J. Jiang, X. Tan, Z.H. Zhang, H. Cai, CrystEngComm 11 (2009) 454.
[32] B. Sandhu, M.S. Fonari, K. Sawyer, T.V. Timofeeva, J. Mol. Struct. 1052 (2013)
125.
[33] S. Das, U. Das, H. Sakagami, K. Hashimoto, M. Kawase, D.K.J. Gorecki, J.R.
Dimmock, Bioorg. Med. Chem. Lett. 20 (2010) 6464.
[34] G.L. Patrick, An Introduction to Medicinal Chemistry, Oxford University Press,
Oxford, 1995. p. 130.
References
[1] M.J. Zaworotko, Cryst. Growth Des. 7 (2007) 4.
[2] A.A. Najar, Y. Azim, J. Indian Inst. Sci. 94 (2014) 45.
[3] M.K. Stanton, A. Bak, Cryst. Growth Des. 8 (2008) 3856.
[35] Y. Fan, Y.F. Zhao, L. Ye, B. Li, G.D. Yang, Y. Wang, Cryst. Growth Des. 9 (2009)
1421.