An Ultra-Robust and Crystalline Redeemable Hydrogen-Bonded Organic Framework for Synergistic Chemo-Photodynamic Therapy

Article abstract of DOI:10.1002/anie.201800354

The low structural stability of hydrogen-bonded organic frameworks (HOFs) is a thorny issue retarding the development of HOFs. A rational design approach is now proposed for construction of a stable HOF. The resultant HOF (PFC-1) exhibits high surface area of 2122 m² g^?1 and excellent chemical stability (intact in concentrated HCl for at least 117 days). A new method of acid-assisted crystalline redemption is used to readily cure the thermal damage to PFC-1. With periodic integration of photoactive pyrene in the robust framework, PFC-1 can efficiently encapsulate Doxorubicin (Doxo) for synergistic chemo-photodynamic therapy, showing comparable therapeutic efficacy with the commercial Doxo yet considerably lower cytotoxicity. This work demonstrates the notorious stability issue of HOFs can be properly addressed through rational design, paving a way to develop robust HOFs and offering promising application perspectives.

Full text of DOI:10.1002/anie.201800354

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
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Accepted Article
Title: An Ultra-Robust and Crystalline Redeemable Hydrogen-Bonded
Organic Framework for Synergistic Chemo-Photodynamic
Therapy
Authors: Rong Cao, Tian-Fu Liu, Qi Yin, Zhao Peng, Rong-Jian Sa,
Guang-Cun Chen, and Jian Lü
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201800354
Angew. Chem. 10.1002/ange.201800354
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10.1002/anie.201800354
Angewandte Chemie International Edition
COMMUNICATION
An Ultra-Robust and Crystalline Redeemable Hydrogen-Bonded
Organic Framework for Synergistic Chemo-Photodynamic
Therapy
Qi Yin,[a] Zhao Peng,[b] Rong-Jian Sa,[a] Guang-Cun Chen,[b] Jian Lü,[c] Tian-Fu Liu,*[a] and Rong Cao*[a]
to “create multiple hydrogen bonds”. HOFs are constructed by the
hydrogen bonds between organic building blocks. Therefore, more
numerous intermolecular hydrogen bonds will strengthen the entire
structure. In this sense, multi-topic organic ligands which can
generate more hydrogen bonds would be promising candidates for
constructing stable HOFs. The second approach relies on “taking
advantage of π-π interactions”.[12] While the hydrogen bonding has
employed as an important intermolecular forces for construction of
periodic frameworks, the contribution of π-π interaction is usually
overlooked. Looking carefully into the crystal structures of SOF-7[10c]
and HOF-TCBP[9], which are stable after heating or aqueous
treatments, one can observe that π-π interactions are widespread
throughout the entire structure. This phenomenon has also been
observed in some COF materials.[13] Therefore, choice of planar
organic building blocks with large π-conjugate system would favor a
structure with extensive and strong π-π interactions, and thus a
stable framework. Last but not least, “avoiding the residual hydrogen
donors/acceptors after self-assembly” represents another approach.
It is well known that the unsaturated metal centers are more reactive
and labile than saturated ones.[14] Similarly, the organic building
blocks with unpaired hydrogen donor or acceptor groups are reactive
to involve the intermolecular interactions with solvent molecules,
which would introduce extra stress and tension upon solvent
removal, and thus destroying the integrity of frameworks.
ABSTRACT: The low structural stability of hydrogen-bonded organic
frameworks (HOFs) is a thorny issue retarding the development of
HOFs field. Herein, we proposed a rational design approach for
construction of stable HOF. The resultant HOF (PFC-1) exhibits high
surface area of 2,122 m²/g and excellent chemical stability of being
intact in concentrated HCl for at least 117 days. Moreover, we
demonstrated
a new methodology of acid-assisted crystalline
redemption to readily cure the thermal damage to PFC-1. With
periodic integration of photoactive pyrene in the robust framework,
PFC-1 can efficiently encapsulate Doxorubicin (Doxo) for synergistic
chemo-photodynamic therapy, showing comparable therapeutic
efficacy with the commercial Doxo yet considerably lower cytotoxicity.
This work demonstrates the notorious stability issue of HOFs can be
properly addressed through rational design strategy, paving a way
for developing robust HOFs and offering promising application
perspectives.
H
ydrogen bonding plays critical roles in biological systems for both
structure and functionality,[1] which has inspired chemists to use of
hydrogen bonds to construct hydrogen-bonded organic frameworks
(HOFs, also called SOFs, abbreviation of supramolecular organic
frameworks).[2] As with other periodic frameworks for example metal-
organic frameworks,[3] zeolite-imidazolate frameworks (ZIFs),[4] and
covalent organic frameworks (COFs),[5] HOFs possess the merits of
high surface area, predictable structure and tailored pore
size/shape.[6] Beyond that, the hydrogen bonding endows HOFs
unique traits such as mild synthetic conditions,[7] solution
processability,[8] and easy regeneration.[9] More strikingly, HOF
materials exhibit considerable biocompatibility and low toxicity
attributed to their metal-free nature, representing an excellent
candidate for drug delivery and biological application. Despite many
obvious advantages, the field of HOFs is still in its early stage
especially when compared with the impressive success of MOFs,
ZIFs and COFs counterparts. The main limitation lies in the
structural stability of HOFs. A long-standing challenge is the
hydrogen bonds are too weak to stabilize the HOF structure, and the
frameworks usually collapse upon solvent removal. The low stability
issue severely compromises the intrinsic merits of HOFs and
encumbers their wide applications.
Since HOFs are capable of being designed at molecular level, the
strategies mentioned above can be implemented through judiciously
tailoring the organic building blocks. Therefore, in our attempts to
target a robust HOF, we chose 1,3,6,8-tetrakis (p-benzoic acid)
pyrene (H4TBAPy) as a building block which is a planar molecule
with very large π-conjugated system and four carboxylate acid
groups.[15] As expected, the resultant HOF, named PFC-1 (PFC =
Porous materials from FJIRSM, CAS), exhibits high surface area of
2,122 m²/g and excellent chemical stability of being intact in
concentrated HCl (12 M) for at least 117 days. Strikingly, the thermal
damage to PFC-1 can be readily remedied by acid-assisted
crystalline redemption (AACR), a methodology here we observed for
the first time in HOF materials. PFC-1 meets the prerequisites of a
drug carrier including large pore size, high chemical stability,
biocompatibility and low cytotoxicity.[16] Meanwhile, periodic
integration of pyrene, an efficient photosensitizer to generate singlet
oxygen (1O2), makes PFC-1 a promising material for photodynamic
therapy (PDT). [17] The concurrence of permanent void space and
photoactive moiety in structure inspired us to investigate the
synergistic chemo-photodynamic therapy of PFC-1. Herein, we
demonstrated that the size of PFC-1 can be precisely tuned from
micron-scale to nano-scale, and doxorubicin (Doxo) was
successfully encapsulated in Nano-PFC-1 with a high uptake of 26.5
wt%. In vitro PDT studies on Hela cell (human cervical cancer)
shows Doxo@Nano-PFC-1 exhibits synergetic chem-photodynamic
therapy with the merits of considerable biocompatibility, low
cytotoxicity and high therapeutic efficacy.
Despite the efforts of several decades, a very few HOFs have
been reported with permanent porosity in solid state and even fewer
HOFs can survive harsh conditions.[2,9-10] Moreover, strategies to
improve the stability of HOF materials are obscure and the relevant
investigation is rather rare. Learning the lessons from previous
HOFs studies,[6-11] we envision that several approaches can be
employed to construct HOFs with enhanced stability. The first one is
In crystal structure of PFC-1, each H4TBAPy molecule interacts
with four neighboring ones through eight O‒H···O hydrogen bonds
to extend into a two-dimensional (2D) layer. The O‒H···O distance
and angle are 2.597 Å and 176.0o, respectively, falling into strong
hydrogen bond range according to literature 2.49 to 3.15 Å.[1a] Each
2D square layers (sql) interacts with adjacent layers through face-to-
face π-π stacking interactions (interlayer distance 3.338 Å), stacking
as AA mode along 100 direction to form a one-dimensional square
channels of 18 × 23 Å (Figure 1). The activated PFC-1 adsorbs
significant amounts of N2 (606.7 cm3/g) with displaying type-I
isotherm typical of a microporous material (Figure 2b). Fitting the
Brunauuer-Emmett-Teller (BET) equation to the N2 isotherms in the
region of 10-3 < p/po < 0.03 (chosen based on the Rouquerol plot in
Figure S11 in SI) gave a surface area of 2,122 m2/g,[18] which is the
second highest record among the previously reported HOF materials
(Table S2).
[a]
Q. Yin, Dr. R. J. Sa, Prof. T. F. Liu, and Prof. R. Cao
State Key Laboratory of Structural Chemistry, Fujian Institute of
Research on the Structure of Matter, Chinese Academy of Sciences
Fujian Fuzhou 350002, P. R. China
E-mail: *rcao@fjirsm.ac.cn, *tfliu@fjirsm.ac.cn
Dr. P. Zhao, Dr. G. C. Chen
Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO),
Chinese Academy of Science
Jiangsu Suzhou 215123, P. R. China
[b]
[c]
Prof. J. Lü
College of Resources and Environment, Fujian Agriculture and
Forestry University,
Fuzhou 350002, P.R. China
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201800354
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COMMUNICATION
Figure 1. Crystal structure of PFC-1. a) View of the structure and the
connection of adjacent building blocks. b) Hydrogen bonds Length and Angle.
c) The stacking of 2D layers. d) Face-to-face π-π interactions. e) One-
dimensional (1D) channels. f) Representation of the porous framework.
Previous study shows that as the π system enlarges from
benzene to pentacene, the interaction energy of π-π stacking
significantly increases from -1.563 to -14.908 kcal/mol.[19] In PFC-1,
the large π-conjugated pyrene were further stacking in AA
arrangement along a-axis, and thus the augment of energy would be
more significant. To illustrate the increment, the π-π interaction
energies of PFC-1 dimer and trimer were calculated at the level of
M06-2X/6-31G (d, p). As shown in Table 1, the energy dramatically
increases from -20.351 kcal/mol for PFC-1 dimer to -40.607 kcal/mol
for PFC-1 trimer. These values are much higher than hydrogen
bonding energy of -18.986 kcal/mol, demonstrating a vital role of π-π
stacking for the structural stability. Consequently, PFC-1 exhibits
high chemical stability in acidic condition as shown in Figure. 2a and
2b, wherein the crystallinity and porosity of PFC-1 maintain intact
upon boiling in water for 10 days or with methanol, acetone, and
deionized water for 117 days. More strikingly, even being soaked in
0.1 M and concentrated HCl (12 M) aqueous solutions for 117 days,
PFC-1 well maintained the crystallinity and only showed negligible
disparity on N2 uptake. Such structural robustness has been
unprecedented in HOF materials.
Table 1. Interaction energies (ΔE) and inter monomer distances (R) of
optimized moieties.
System
ΔE (kcal/mol)
R (Å) [a]
Isolated pyrene dimer
PFC-1 dimer
-8.807
-20.351
-40.607
-18.986
3.419
3.748
3.356
PFC-1 trimer
H-bonding of PFC-1 dimer
[a] R is the central benzene ring distance between monomers.
The outstanding thermal stability of PFC-1 was confirmed by
thermogravimetric analysis (TGA) and various temperature powder
X-ray diffraction (VT-PXRD) patterns, which showed that the
o
frameworks maintain crystallinity till 250 C (Figure S2, S4). The N2
isotherms indicated that the gas uptakes of PFC-1 were not
detracted after being heated at 90 oC and 120 oC for 6 hours. Further
increase of the temperature to 150 oC and 210 oC caused a N2
uptake decrease to 415 and 218 cm3/g, respectively. When
immersing the impaired samples in concentrated HCl aqueous
solutions for 12 hours, surprisingly, the gas uptake rose to 581 cm3/g
which is nearly identical to the pristine sample
Figure 2. Structural stability of PFC-1. a) PXRD patterns and b) N2 adsorption
isotherms (77 K) of as-synthesized PFC-1 and samples treated with different
solutions. c) N2 adsorption isotherms (77 K) and d) PXRD of PFC-1 heated at
different temperature for 6 hours, the HCl-redeemed and Regenerated PFC-1.
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10.1002/anie.201800354
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COMMUNICATION
(Figure 2c). This finding demonstrated that the acidic solution
recovery route, which we call “AACR”, can reverse the thermal
impairment to PFC-1. We speculate that high temperature might
destroy hydrogen bonds and induce the deprotonation of carboxylic
acid, while addition of proton causes re-association of hydrogen
bonds and thus recovers the porosity of frameworks. To confirm this
speculation, deuterium chloride was used instead of HCl for the
redemption of PFC-1. If indeed the dissociation/re-association of
hydrogen bonds occur during the heating and AACR process,
addition of deuterium will inevitably generate the O‒D···O bonds in
the redeemed sample. Since 2D has a faster chemical exchange rate
than 1H, substitution of COOH with COOD would give rise to a
sharper peak for the carboxylic acid in 1H-NMR (exchange
broadening).20 As expected, the full width at half maximum (FWHM)
at 13.12 ppm for pristine PFC-1 is 1.25 Hz, while that for the DCl-
redeemed PFC-1 dramatically decrease to 4.06 Hz (width is
inversely proportional to frequency), suggesting the hydrogen bond
re-association mechanism for AACR (Figure S21). Therefore, the
AACR reported here represents for the first time a strategy to readily
cure the thermal damage to HOFs. Besides the ability to redeem the
thermal damage, PFC-1 has the virtue of facile regeneration. Highly
crystalline PFC-1 can be easily regenerated through dissolving the
used samples in DMF and recrystallizing in methanol. The
reprocessed sample exhibits as high N2 uptakes (561 cm3/g) and
BET surface area (2103 m2/g) as the pristine material (Figure 2c, 2d).
Vis absorbance and 1H-NMR spectroscopy (Figure S16, S20).
Remarkably, the crystallinity and morphology of PFC-1 and Nano-
PFC-1 were well preserved throughout the loading process, which
were revealed in PXRD (Figure 4c, S6) and SEM imaging (Figure
S17-S18). The robustness of PFC-1 promises its application in
chemo-photodynamic therapy.
The singlet oxygen generation (SOG) was monitored by chemical
trapping of 1O2 with 9,10-Diphenylanthracene (DPA). As shown in
Figure 4d, irradiation of the DPA solution for 60 minutes with visible
light gave negligible decrease of absorbance at λ = 355 nm. With the
addition of PFC-1 (bulky sample) into DPA solution, the UV-Vis
absorption of DPA evidently decreased along with time, indicating
efficient generation of singlet oxygen. A higher decreasing rate was
observed for Nano-PFC-1, which demonstrates the superiority of
nanomaterials for SOG. Moreover, the incorporation of Doxo does
not detract the SOG efficacy, indicating the possibly synergistic
effect of chemo-photodynamic therapy.
Chemotherapy nowadays is still the most common treatment for
cancer. It, however, has intrinsic limitations including terrible side
effects, poor pharmacokinetics and undesirable bio-distribution,
which encourages the development of combination therapies such
as chemo-photodynamic therapy.[16c] With periodic integration of
photoactive pyrene moiety in framework, PFC-1 is expected to
generate 1O2 upon irradiation for PDT. Meanwhile, the inherent
porosity, chemical stability and metal-free components make PFC-1
an ideal candidate for drug carrier. As
a proof of concept,
Doxorubicin (Doxo), a well-known commercial drug for cancer, was
chosen to incorporate into photoactive PFC-1 for synergetic chemo-
photodynamic therapy.
Figure 4 a) N2 isotherms of Nano-PFC-1 (black) and Doxo@Nano-PFC-1
(red) at 77 K, b) Doxo loading capacity of bulky PFC-1 and nano-PFC-1 under
different conditions, c) PXRD of Doxo@Nano-PFC-1, d) Time-dependent UV-
Vis absorbance of DPA only (black), in the presence of PFC-1 (blue), Nano-
PFC-1 (pink), and Doxo@PFC-1 (red).
Figure 3 Scanning electron microscopy (SEM) images of PFC-1 with
different particle size.
We first set out to prepare nano-sized PFC-1 for applying in
biological system. Through adjusting solvent polarity and synthetic
condition, the HOFs materials can be prepared with controlled
particle sizes with the minimum size about 100 nm × 300 nm
(denoted as Nano-PFC-1 hereafter) (Figure 3d). The N2 adsorption
of Nano-PFC-1 preserved the type-I isotherm with a relative lower
BET surface area of 1,144 m²/g and an obvious up-tail appeared at
high P/Po, which are probably caused by the stacking of the
nanoparticles (Figure 4a).[21] Doxo loading capacity of bulky PFC-1
was 16.6 wt% in aqueous solution (denoted as Doxo@PFC-1
hereafter). The acidic environment (with 0.001 mmol/mL HCl in Doxo
solution) and the scaled-down particle size result in an optimized
loading capacity of 26.5 wt% (denoted as Doxo@Nano-PFC-1
hereafter) (Figure 4b, Figure S12-S14). The successful incorporation
of Doxo in PFC-1 and Nano-PFC-1 was confirmed by solid state UV-
Figure 5. In vitro a) cytotoxicity and b) PDT efficacy of Doxo (blue), Nano-
PFC-1 (red), and Doxo@Nano-PFC-1 (green) at various concentrations in
Hela cells.
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10.1002/anie.201800354
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C. B. Knobler, M. O'Keeffe, O. M. Yaghi, Acc. Chem. Res. 2010, 43, 58-
67.
a) A. P. Cote, A. I. Benin, N. W. Ockwig, M. O'Keeffe, A. J. Matzger, O.
M. Yaghi, Science 2005, 310, 1166-1170; b) X. Feng, X. Ding, D. Jiang,
Chem. Soc. Rev. 2012, 41, 6010-6022; c) S. Y. Ding, W. Wang, Chem.
Soc. Rev. 2013, 42, 548-568.
a) M. Mastalerz, I. M. Oppel, Angew. Chem. Int. Ed. 2012, 51, 5252-
5255; b) Z.-B. Han, Z.-Z. Xiao, M. Hao, D.-Q. Yuan, L. Liu, N. Wei, H.-
M. Yao, M. Zhou, Cryst. Growth Des. 2015, 15, 531-533; c) I. Hisaki, S.
Nakagawa, N. Ikenaka, Y. Imamura, M. Katouda, M. Tashiro, H.
Tsuchida, T. Ogoshi, H. Sato, N. Tohnai, M. Miyata, J. Am. Chem. Soc.
2016, 138, 6617-6628.
a) Y. He, S. Xiang, B. Chen, J. Am. Chem. Soc. 2011, 133, 14570-
14573; b) P. Li, Y. He, Y. Zhao, L. Weng, H. Wang, R. Krishna, H. Wu,
W. Zhou, M. O'Keeffe, Y. Han, B. Chen, Angew. Chem. Int. Ed. 2015,
54, 574-577; c) C. A. Zentner, H. W. Lai, J. T. Greenfield, R. A.
Wiscons, M. Zeller, C. F. Campana, O. Talu, S. A. FitzGerald, J. L.
Rowsell, Chem. Commun. 2015, 51, 11642-11645.
Doxo, Nano-PFC-1 and Doxo@Nano-PFC-1 were incubated with
Hela cells to investigate the cooperative therapeutic effects in vitro.
As shown in Figure S24, the resulting cells exhibited blue
fluorescence from HOFs and red fluorescence from Doxo, indicating
efficient internalization of materials. Figure 5a shows that the cell
viability drop to 10% for the Doxo group at the concentration of 10
μg/mL. Compared with Doxo drug group alone, Nano-PFC-1 and
Doxo@Nano-PFC-1 show much lower cytotoxicity, demonstrating
their outstanding biocompatibility. Under the exposure of 400 nm
light for 30 minutes, Doxo@Nano-PFC-1 causes the fraction of
surviving cell dropped to ca. 20.4%, delivering higher therapeutic
efficacy than Nano-PFC-1 (31.9% cell survival) and comparable
efficacy as commercial Doxo drug (18.3% cell survival) (Figure 5b).
These results indicate that PFC-1 would be a promising delivery
system for combinational therapy with the advantages of low toxicity
and high efficacy.
[5]
[6]
[7]
[8]
[9]
H. Wang, B. Li, H. Wu, T. L. Hu, Z. Yao, W. Zhou, S. Xiang, B. Chen, J.
Am. Chem. Soc. 2015, 137, 9963-9970.
F. Hu, C. Liu, M. Wu, J. Pang, F. Jiang, D. Yuan, M. Hong, Angew.
Chem. Int. Ed. 2017, 56, 2101-2104.
In summary, an ultra-robust hydrogen-bonded organic framework
PFC-1 has been synthesized. The high chemical stability of PFC-1
was attributed to the introduction of multiple hydrogen bonding, the
strong π-π interactions and the avoidance of unpaired hydrogen
donors/acceptors. We believe that these design principles pave a
way for developing robust HOF materials. Moreover, the acid-
assistant crystalline redemption discovered in this work offers an
inexpensive and facile method to recover the depressed surface
area and porosity of HOFs. As a proof of concept, we demonstrated
that the photoactive PFC-1 is an excellent drug carrier for synergetic
chemo-photodynamic therapy with the merit of low cytotoxicity and
high efficacy, representing the first example of HOF materials for
multiple therapeutics for cancer.
[10] a) S. Nandi, D. Chakraborty, R. Vaidhyanathan, Chem. Commun. 2016,
52, 7249-7252; b) W. Yang, A. Greenaway, X. Lin, R. Matsuda, A. J.
Blake, C. Wilson, W. Lewis, P. Hubberstey, S. Kitagawa, N. R.
Champness, M. Schroder, J. Am. Chem. Soc. 2010, 132, 14457-14469.
c) J. Lu, C. Perez-Krap, M. Suyetin, N. H. Alsmail, Y. Yan, S. Yang, W.
Lewis, E. Bichoutskaia, C. C. Tang, A. J. Blake, R. Cao, M. Schroder, J.
Am. Chem. Soc. 2014, 136, 12828-12831; d) T. H. Chen, I. Popov, W.
Kaveevivitchai, Y. C. Chuang, Y. S. Chen, O. Daugulis, A. J. Jacobson
and O. Š. Miljanić, Nat. Commum, 2014, 5, 5131.
[11] a) P. Li, Y. He, J. Guang, L. Weng, J. C. Zhao, S. Xiang, B. Chen, J.
Am. Chem. Soc. 2014, 136, 547-549; b) Yasuhiro Aoyama, Masumi
Asakawa, Y. Matsui, H. Ogoshi, J. Am. Chem. Soc. 1991, 113, 6233-
6240; d) G. R. Desiraju, Angew. Chem. Int. Ed. 1995, 34, 2311-2327; c)
K. D. Zhang, J. Tian, D. Hanifi, Y. Zhang, A. C. Sue, T. Y. Zhou, L.
Zhang, X. Zhao, Y. Liu, Z. T. Li, J. Am. Chem. Soc. 2013, 135, 17913-
17918; d) G. R. Desiraju, J. Am. Chem. Soc. 2013, 135, 9952-9967; e)
R. S. Patil, D. Banerjee, C. Zhang, P. K. Thallapally, J. L. Atwood,
Angew. Chem. Int. Ed. 2016, 55, 4523-4526.
Acknowledgements
R. C. thanks the National Natural Science Foundation of China
(NSFC, Grant 21520102001, 21521061, 21331006, 9162214),
Key Research Program of Frontier Science, CAS (QYZDJ-SSW-
SLH045). T.-F. L thanks “Strategic Priority Research Program”
of the Chinese Academy of Sciences (Grant No. XDB20000000)
and NSFC (Grant 21441008). The authors also thank Suzhou
NIR-Optics Technology Co. Ltd. for its instrumental and
technical supports on the fluorescence imaging and photo-
dynamic therapy.
[12] a) B. Kohl, F. Rominger, M. Mastalerz, Org. Lett. 2014, 16, 704-707; b)
B. Kohl, M. V. Bohnwagner, F. Rominger, H. Wadepohl, A. Dreuw, M.
Mastalerz, Chem.Eur. J. 2016, 22, 646-655.
[13] a) A. P. Cote, H. M. El-Kaderi, H. Furukawa, J. R. Hunt, O. M. Yaghi, J.
Am. Chem. Soc. 2007, 129, 12914-12915; b) S. Wan, J. Guo, J. Kim,
H. Ihee, D. Jiang, Angew. Chem. Int. Ed. 2009, 48, 5439-5442.
[14] R. H. Holm, P. Kennepohl, E. I. Solomon, Chem. Rev. 1996, 96, 2239-
2314.
[15] a) K. C. Stylianou, R. Heck, S. Y. Chong, J. Bacsa, J. T. Jones, Y. Z.
Khimyak, D. Bradshaw, M. J. Rosseinsky, J. Am. Chem. Soc. 2010,
132, 4119-4130; b) J. E. Mondloch, W. Bury, D. Fairen-Jimenez, S.
Kwon, E. J. DeMarco, M. H. Weston, A. A. Sarjeant, S. T. Nguyen, P.
C. Stair, R. Q. Snurr, O. K. Farha, J. T. Hupp, J. Am. Chem. Soc. 2013,
135, 10294-10297.
[16] a) M. X. Wu, Y. W. Yang, Adv. Mater. 2017, 29; b) C. Song, Y. Zhang,
C. Li, G. Chen, X. Kang, Q. Wang, Adv. Funct. Mater. 2016, 26, 4192-
4200; c) R. Ruiz-González, P. Milán, R. Bresolí-Obach, J. Stockert, A.
Villanueva, M. Cañete, S. Nonell, Cancers 2017, 9, 18.
[17] a) J. Kagan, Organic Photochemistry: Principles and Applications, San
Diego: Academic press, 1993; b) Y. Liu, C. T. Buru, A. J. Howarth, J. J.
Mahle, J. H. Buchanan, J. B. DeCoste, J. T. Hupp, O. K. Farha, J.
Mater. Chem. A 2016, 4, 13809-13813.
[18] K. S. Walton, R. Q. Snurr, J. Am. Chem. Soc. 2007, 129, 8552-8556.
[19] N. J. Silva, F. B. Machado, H. Lischka, A. J. Aquino, Phys. Chem.
Chem. Phys. 2016, 18, 22300-22310.
[20] a) J. Kaplan, J. Chem. Phys. 1958, 28, 278-282; b) D. Lankhorst, J.
Schriever, J. C. Leyte, Chem. Phys. 1983, 77, 319-340.
Keywords: Hydrogen-Bonded Organic Frameworks • Structural
Stability • π-Stacking Interactions • Singlet Oxygen Generation •
Chemo-Photodynamic Therapy.
[1]
a) T. Steiner, G. R. Desiraju, The weak hydrogen bond in structural
chemistry and biology; OUP: Oxford, 1999,pp 108-113; b) A. Bitra, A.
Biswas, R. Anand, Biochemistry, 2013, 52, 8106−8114.
[2]
[3]
J. Lu, R. Cao, Angew. Chem. Int. Ed. 2016, 55, 9474-9480.
a) H. Li, M. Eddaoudi, M. O'Keeffe, O. M. Yaghi, Nature 1999, 402,
276-279; b) S. L. James, Chem. Soc. Rev. 2003, 32, 276−288; c) H. C.
Zhou, J. R. Long, O. M. Yaghi, Chem. Rev. 2012, 112, 673-674; d) J.
Bae, J. W. Jung, H. Y. Park, C. H. Cho, J. Park, Chem. Commun. 2017,
53, 12100-12103. e) X.-D. Zhu, K. Zhang, Y. Wang, W.-W. Long, R.-J.
Sa, T.-F. Liu, and J. Lü, Inorg. Chem. 2018, 57, 1060–1065.
[21] J. Zhang, L. Sun, F. Xu, F. Li, H. Y. Zhou, Y. L. Liu, Z. Gabelica, C.
Schick, Chem. Commun. 2012, 48, 759-761.
[4]
a) X. C. Huang, Y. Y. Lin, J. P. Zhang, X. M. Chen, Angew. Chem. Int.
Ed. 2006, 45, 1557-1559; b) A. Phan, C. J. Doonan, F. J. Uribe-Romo,
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