Home Journals Articles Updates About
CN
image
收藏切换
Phenoxazine-based supramolecular tetrahedron as biomimetic lectin for glucosamine recognition
收藏切换
PDF
Yuchao Li, Xuezhao Li*, Lili Li, Bing Xiao, Jinguo Wu, Hechuan Li, Danyang Li, Cheng He*
Chinese Chemical Letters | 2021, 32(2) : 735 - 739
Less
收藏切换
Chinese Chemical Letters | 2021, 32(2): 735-739
• Communication •
Phenoxazine-based supramolecular tetrahedron as biomimetic lectin for glucosamine recognition
Full
Yuchao Li, Xuezhao Li*, Lili Li, Bing Xiao, Jinguo Wu, Hechuan Li, Danyang Li, Cheng He*
Affiliations
  • State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China
Published: 2021-02-15 doi: 10.1016/j.cclet.2020.07.028
Outline
收藏切换

The design and synthesis of a phenoxazine-based metal-organic tetrahedron (Zn4L4) as biomimetic lectin for selectively recognition of glucosamine (GlcN) was reported. Different from the free phenoxazine-based ligand (L), Zn4L4 displayed the highest fluorescent intensity enhancement efficiency toward GlcN over other related natural mono- and disaccharides. Fluorescence titration demonstrated a 1:1 stoichiometric host-guest complex was formed with an association constant about 4.03×104 L/mol. 1H NMR spectroscopic studies confirmed this selectivity resulted from the multiple hydrogen bonding interactions formed between GlcN and Zn4L4. The present results suggested that rational arrangement of recognition sites in the confined space of metal-organic cage is crucial for the selectivity toward target guests.

Glucosamine  /  Phenoxazine  /  Metal-organic cage  /  Fluorescence  /  Host-guest complex
Yuchao Li, Xuezhao Li, Lili Li, Bing Xiao, Jinguo Wu, Hechuan Li, Danyang Li, Cheng He. Phenoxazine-based supramolecular tetrahedron as biomimetic lectin for glucosamine recognition[J]. Chinese Chemical Letters, 2021 , 32 (2) : 735 -739 . DOI: 10.1016/j.cclet.2020.07.028
Full Text
Less
Carbohydrates, as the carriers of energy in life, are essential mediators of a wide range of biological processes including protein folding, cell-cell recognition, infection by pathogens or tumor metastasis [1, 2]. The recognition of carbohydrates with high specificity and sensitivity is biologically important but intrinsically challenging, for both nature and host-guest chemists [3-5]. Saccharides are high hydrophilic, non-charged, subtle variation of the three-dimensional structures, and the only one kind of the recognition units are the hydrogen bonding groups. Even the most common class of natural receptors, lectins, show notably low affinities and modest selectivity [6, 7]. Biomimetic synthetic organic-box-like lectins equipped with multi-hydrogen bonding groups in their inner cavities have been devoted to sensor saccharides operating through non-covalent interactions [8-16]. However, these purely organic hosts [17-21] commonly required lengthy and low-yielding synthetic process. Noted that complexation of saccharides with an organic host receptor was often detected by the 1H NMR chemical-shift changes [22-28], but this method showed a limited sensitivity. Alternatively, the using of fluorescence spectroscopic method to recognize target carbohydrates is highly anticipant. This method possesses excellent signaling properties to modulate the binding process and thus might leave an improved detection sensitivity [29, 30].
On the other hand, self-assembled metal-organic cages (MOCs) with unique hollow cavity environment and rich chemical/physical properties enable them as promising receptors for various compounds recognition [31-33]. The abundant structural configurations and fruitful functionalities can be successfully achieved by rational selection of different metal centers and well-designed ligands. Especially, when amide groups as multiple hydrogen bonding triggers used in nature protein–carbohydrate complexes were incorporated into MOCs, the novel synthetic hosts could be used as efficient receptors for mimicking biological carbohydrate recognition processes [34-38]. The key issues remain how to subtly modulate the distribution of recognition sites, as well as to form appropriate shape and size to encapsulate specific saccharides. Furthermore, fluorescent properties are also desired by integrating emissive ligands and/or coordination complexes into the supramolecular architectures [39] to possess improved signal output properties.
Herein, the design and synthesis of a metal-organic tetrahedron (Zn4L4) equipped with four phenoxazinean-based signaling components and a dozen of amide-based hydrogen binding sites as biomimetic lectin for selectively recognition of glucosamine (GlcN) over other related natural mono- and disaccharides was reported (Scheme 1). By contrast, free phenoxazine-based ligand (L) showed no obvious enhancement of the fluorescent intensity towards GlcN. Fluorescence titration and ESI-MS studies demonstrated that the newly obtained biomimetic lectin host could encapsulate one GlcN in the cavity environment of Zn4L4 with high association constant. 1H NMR spectroscopic studies confirmed that the selectivity resulted from the complementary multiple hydrogen bonding interactions between amine, hydroxy groups of GlcN and the amide moieties of Zn4L4. The present results suggested that rational arrangement of recognition sites in the confined space of metal-organic cage is crucial for the selectivity toward target guests, and the supramolecular host-guest species formation between the cage containing hydrogen-bond recognition sites and the encapsulated carbohydrates is responsible for the effective detection process.
As shown in Fig. 1a, ligand L was obtained by connecting phenoxazine-based core (1) and 2,2′-bipyridine chelators through amine-linkages in two steps [40-42]. Acylating of 1 with thionyl chloride, and subsequently reacted with 2 to afford ligand L in 78% yield. The successfully obtained ligand L was confirmed by 1H and 13C NMR spectra (Fig. 1b and Section S2 in Supporting information). The reaction of ligand L (1.0 equiv.) and Zn(OTf)2 (1.0 equiv.) (OTf=trifluoromethanesulfonate) in DMF at 80 ℃ for 12 h resulted in the formation of Zn4L4 as the unique product. The 1H NMR spectra of tetrahedron Zn4L4 displayed only one set of ligand resonances in solution, suggesting the exclusive formation of a discrete structure to be highly symmetrical (Fig. 1c). Diffusion-ordered NMR spectroscopy (DOSY) of the product also showed that the multiple aromatic signals possessed similar diffusion coefficients (D=6.31×10−11 m2/s, Fig. S8 in Supporting information).
The formation of a discrete supramolecular species containing a Zn4L48+ cation was confirmed by electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS). As showed in Fig. 1d, a series of intense peaks at m/z=458.0999, 544.8200, 660.4491, 822.3308, 1065.1522 and 1469.8522 were observed. Comparison of the experimental peaks with these simulated results obtained on the basis of natural isotopic abundance, these peaks were safely assigned to the species [Zn4(L)4]8+ (calcd. 458.1022), [Zn4(L)4+OTf]7+ (calcd. 544.8243), [Zn4(L)4+2OTf]6+ (calcd. 660.4538), [Zn4(L)4+3OTf]5+ (calcd. 822.3351), [Zn4(L)4+4OTf]4+ (calcd. 1065.1570) and [Zn4(L)4+5OTf]3+ (calcd. 1469.8602), respectively. This result demonstrated the Zn-based tetrahedral architecture was successfully assembled with substantially stability in solution.
To confirm the formation of a [4+4] metal-organic cage, UV–vis titration of ligand L (20.0 μmol/L) upon the addition of Zn2+ was further well conducted. As showed in Fig. 2, the ligand L exhibited two broad bands at λ = 310 nm and 390 nm, which assignable to the π–π* and n–π* charge transfer bands. Upon the addition of Zn2+ ions, the band at λ = 310 nm was decreased gradually, while the intensity of new peaks appeared at λ=324 and λ = 432 nm were increasing significantly. These bands remained constant after adding approximately 1.0 equiv. of Zn2+ ions. The presence of sharp isosbestic point at λ = 322 nm indicated that only two species coexisted in the equilibrium system. The almost linear relations between the absorbance at both bands and the concentration of Zn2+ added revealed that the formation of the cage complex was quantitative and the complex exhibited 1:1 stoichiometry. This result demonstrated that the M4L4 cage compound was the only one complexation specie and the association constant of the complexation specie is relatively high.
Numerous efforts for crystallization of Zn4L4 to obtain suitable crystals for the high-quality X-ray diffraction have been unsuccessful. Therefore, in order to understand the three-dimensional structure of Zn4L4 better, we use a MM2 energy-minimized model to simulate the structure of Zn4L4 (Fig. 3). Through the optimized structures, we can more intuitively insight that the Zn4L4 was a twisted tetrahedron structure with a hollow cavity. The four metal atoms occupied the vertices and each of them was coordinated with three ligands. Each ligand was positioned on one of the four faces of the tetrahedron which defined by four metal ions. The Zn⋯Zn distance in the long edges of Zn4L4 was about 19.38(1) Å, and in the short edges was about 18.34(1) Å. The average dihedral angle between the phenyl groups and phenoxazine planes in Zn4L4 was about 74.41(1)°. The structure possessed a confined cavity and contains 12 amide groups, which provides a great possibility for carbohydrate recognition.
The fluorescent nature of ligand L was preserved and transferred to the final cage, which enable the cage Zn4L4 with luminescent recognition process of relative guests (Fig. S10 in Supporting information). Fluorescent emission spectrum of Zn4L4 exhibited a ligand-based broad emission band at λem = 448 nm when excited at λex = 396 nm (5.0 μmol/L in DMF). Subsequently, the potential application of as a fluorescent detector for natural saccharides recognition was explored. Impressively, upon the addition of GlcN (0–10 equiv.) into the DMF solution of Zn4L4 (5 μmol/L), the wavelength of the emission maximum at λem = 448 nm did not change but the luminescence intensity enhanced gradually with the increasing concentration of the guest. When adding of 10.0 equiv. GlcN, the fluorescence intensity of Zn4L4 was dramatically increased around 82%. The hill-plot profile of the fluorescence titration curves at 448 nm demonstrated a 1:1 stoichiometric host-guest complex was formed with an association constant about 4.03×104 L/mol (Fig. 4). The formation of donor-type hydrogen bonds between the amide groups of Zn4L4 and the guest molecules could alter the electronic distribution of the ligand backbone, which suppress the process of photo-induced electron transfer (PET) process, thus leading to the significant luminescence enhancement [36]. Interestingly, the glucose (Glu) only induced negligible emission enhancement of Zn4L4 under the same condition (Fig. 5). The only difference between these two saccharides is that there is one amine group in the skeleton of GlcN. However, the very different recognition ability of Zn4L4 toward them suggested that the amine might played an important role. Under the same condition, when 10.0 equiv. of cyclohexanamine and aniline were added, the fluorescent emission intensity of Zn4L4 was increased around 25% and 29%, respectively (Fig. S13 in Supporting information). Noted that other mono-saccharides including mannose (Man), ribose (Rib) and xylose (Xyl) showed negligible emission enhancement less than 10%. Furthermore, the addition of excess disaccharides including the sucrose (Suc), lactose (Lac), melibiose (Mel), maltose (Mal), and trehalose (Tre) did not cause any obvious spectroscopic changes of Zn4L4 as well (Fig. 5). Combined with the result that free ligand L showed no recognition ability to GlcN, these results suggested that the specific recognition process mainly occurs in the cavity of the cage, and the larger disaccharide could not be encapsulated into the cavity.
The excellent selectivity of Zn4L4 toward GlcN encouraged us to further investigate the interaction detail of the host–guest complexation. As shown in Fig. 6, 1H NMR spectroscopic titration studies on the GlcN confirmed that, as expected, when increasing the concentrations of GlcN (0–10.0 equiv.), the hydrogen signal of the amide groups in Zn4L4 showed upfield shifts (ΔδHa = 0.16 ppm, ΔδHb = 0.16 ppm) that indicated the amide group in Zn4L4 acts as the hydrogen bond receptor, and the hydrogen signal of the GlcN showed downfield shifts (especially, ΔδH1α= 1.50 ppm, ΔδH1β=1.24 ppm), which indicated that the GlcN was encased in the cavity of Zn4L4 and the Zn4L4 and GlcN formed a host–guest complex. In addition, when GlcN (10.0 equiv.) were added into the solution of Zn4L4 in DMF, the electrospray ionization mass spectrometry (ESI-MS) of the mixture exhibited two new peaks at m/z 554.8465 and 672.1405. Compared with the simulation on the basis of natural isotopic abundance, these two peaks can assign to the [GlcN⊂Zn4(L)4-H+CH3CN]7+ and [GlcN⊂Zn4(L)4-H+OTf+CH3CN]6+ (Fig. S21 in Supporting information). The NOESY spectra of the mixture of and GlcN (10.0 equiv.) also gave clear evidence that intermolecular contacts between them were formed (Fig. S22 in Supporting information). Based on the above results, we speculated that the main reason of the specific selectivity was that Zn4L4 with three-dimensional configuration and inner confined environment could encapsulate one GlcN into the cavity, which lead to the formation of complementary multiple hydrogen binding between amine, hydroxy groups of GlcN and the amide moieties of Zn4L4.
In summary, we reported a supramolecular tetrahedron as biomimetic lectin for GlcN recognition with high specificity and sensitivity over other related natural mono- and disaccharides. The Zn4L4 displayed phenoxazine-based broad fluorescent emission property, and equipment of 12 amide groups in the skeleton. The formation of a 1:1 host-guest complexes has been characterized by fluorescence titration spectroscopy and ESI-MS. 1H NMR spectroscopic titration studies and NOESY spectra confirmed that the hydrogen bonding interactions between GlcN and receptor Zn4L4, resulting a stronger host-guest binding affinity. The present results demonstrated that the rational distribution of amide groups and luminescent ligands into the 3D metal-organic cage structure not only provides a recognizable hydrogen-bonding functional site for the guest molecule, which facilitates the formation of the host-guest complex, but also provides a way to convert identification information into effective communicator for optical signals. Accordingly, changing the topology and the arrangement of hydrogen binding sites in the confined space of host, the selectivity toward other target guests could be expected.
Declaration of competing interest
Less
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
Less
We appreciate the National Natural Science Foundation of China (Nos. 21701019 and 21861132004) and Doctoral Scientific Research Launching Fund Project of Liaoning province (No. 2019-BS-050).
Appendix A. Supplementary data
Less
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.cclet.2020.07.028.
References
Less
[1]
T.K. Lindhorst, Essentials of Carbohydrates Chemistry and Biochemistry, Wiley-VCH, Weinheim, 2000.
[2]
A. Varki, R. Cummings, J. Esko, et al., Essentials of Glycobiology, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1999.
[3]
A.P. Davis, R.S. Wareham, Angew. Chem. Int. Ed. 38 (1999) 2978-2996.
[4]
M. Mazik, Chem. Soc. Rev. 38 (2009) 935-956.
[5]
W. Lin, T. Cen, S. Wang, et al., Chin. Chem. Lett. 29 (2018) 1372-1374.
[6]
H. Lis, N. Sharon, Chem. Rev. 98 (1998) 637-674.
[7]
M. Ambrosi, N.R. Cameron, B.G. Davis, Org. Biomol. Chem. 3 (2005) 1593-1608.
[8]
S. Anderson, U. Neidlein, V. Gramlich, et al., Angew. Chem. Int. Ed. 34 (1995) 1596-1600.
[9]
G. Lecollinet, A.P. Dominey, T. Velasco, et al., Angew. Chem. Int. Ed. 41 (2002) 4093-4096.
[10]
E. Klein, M.P. Crump, A.P. Davis, Angew. Chem. Int. Ed. 44 (2005) 298-302.
[11]
O. Francesconi, A. Ienco, G. Moneti, et al., Angew. Chem. Int. Ed. 45 (2006) 6693-6696.
[12]
Y. Ferrand, M.P. Crump, A.P. Davis, Science 318 (2007) 619-622.
[13]
O. Perraud, A. Martinez, J. Dutasta, Chem. Commun. 47 (2011) 5861-5863.
[14]
H. Destecroix, C.M. Renney, T.J. Mooibroek, et al., Angew. Chem. Int. Ed. 54 (2015) 2057-2061.
[15]
T.J. Mooibroek, J.M. Casas-Solvas, R.L. Harniman, et al., Nat. Chem. 8 (2016) 69-74.
[16]
P. Rios, T.J. Mooibroek, T.S. Carter, et al., Chem. Sci. 8 (2017) 4056-4061.
[17]
U. Neidlein, F. Diederich, Chem. Commun. (1996) 1493-1494.
[18]
N.P. Barwell, M.P. Crump, A.P. Davis, Angew. Chem. Int. Ed. 121 (2009) 7809-7812.
[19]
A. Schmitt, O. Perraud, E. Payet, et al., Org. Biomol. Chem. 12 (2014) 4211-4217.
[20]
O. Francesconi, M. Gentili, C. Nativi, et al., Chem. Eur. J. 20 (2014) 6081-6091.
[21]
O. Francesconi, M. Martinucci, L. Badii, et al., Chem. Eur. J. 24 (2018) 6828-6836.
[22]
M. Mazik, H. Cavga, P.G. Jones, J. Am. Chem. Soc. 127 (2005) 9045-9052.
[23]
E. Klein, Y. Ferrand, E.K. Auty, et al., Chem. Commun. (2007) 2390-2392.
[24]
Y. Ferrand, E. Klein, N.P. Barwell, et al., Angew. Chem. Int. Ed. 48 (2009) 1775-1779.
[25]
C. Ke, H. Destecroix, M.P. Crump, et al., Nat. Chem. 4 (2012) 718-723.
[26]
O. Francesconi, M. Gentili, S. Roelens, J. Org. Chem. 77 (2012) 7548-7554.
[27]
K. Palanichamy, M.F. Bravo, M.A. Shlain, et al., Chem. Eur. J. 24 (2018) 13971-13982.
[28]
R.A. Tromans, T.S. Carter, L. Chabanne, et al., Nat. Chem. 11 (2019) 52-56.
[29]
J. Fang, S. Selvi, J. Liao, et al., J. Am. Chem. Soc. 126 (2004) 3559-3566.
[30]
Y. Wang, R. Rong, H. Chen, et al., Chin. Chem. Lett. 28 (2017) 1262-1267.
[31]
S. Tashiro, M. Tominaga, M. Kawano, et al., J. Am. Chem. Soc. 127 (2005) 4546-4547.
[32]
C. Liu, R. Zhang, C. Lin, et al., J. Am. Chem. Soc. 139 (2017) 12474-12479.
[33]
T. Feng, X. Li, J. Wu, et al., Chin. Chem. Lett. 31 (2020) 95-98.
[34]
C. He, Z. Lin, Z. He, et al., Angew. Chem. Int. Ed. 47 (2008) 877-881.
[35]
Y. Liu, X. Wu, C. He, et al., Chem. Commun. 45 (2009) 7554-7556.
[36]
L. Zhao, S. Qu, C. He, et al., Chem. Commun. 47 (2011) 9387-9389.
[37]
Y. Jiao, J. Zhang, L. Zhang, et al., Chem. Commun. 48 (2012) 6022-6024.
[38]
J. Zhang, C. He, C. Duan, Inorg. Chem. Commun 49 (2014) 140-142.
[39]
P.D. Frischmann, V. Kunz, F. Würthner, Angew. Chem. Int. Ed. 54 (2015) 7285-7289.
[40]
B. Zhang, R. Breslow, J. Am. Chem. Soc. 119 (1997) 1676-1681.
[41]
X. Guo, Z. Zhou, C. Chen, et al., ACS Appl. Mater. Inter. 8 (2016) 31746-31756.
[42]
R. Zou, P. Li, Y. Zeng, et al., Small 12 (2016) 2334-2343.
Appendix
Less
Year 2021 volume 32 Issue 2
PDF
49
27
Cite this Article
BibTeX
Article Info
doi: 10.1016/j.cclet.2020.07.028
  • Receive Date：2020-06-22
  • Online Date：2026-01-04
  • Published：2021-02-15
Article Data
Affiliations
History
  • Received：2020-06-22
  • Revised：2020-07-02
  • Accepted：2020-07-14
Affiliations
    State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China
References
Share
https://castjournals.cast.org.cn/joweb/ccl/EN/10.1016/j.cclet.2020.07.028
Share to
QR

Scan QR to access full text

Cite this article
BibTeX
Citations
表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
  • BibTeX
  • EndNote
  • RefWorks
  • TxT
Links
Articles
Latest Articles
Most Read
Collections
Updates
Events
News
Multimedia
About
About Us
Contact
No. 86 Xueyuan South Road, Haidian District, Beijing
100081
010-62199257
qkjq@cast.org.cn

Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House