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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Quenching mechanism of PEG emission by pyrimidines and their detections using PEG as fluorescent sensor

Xubao Jiang,Suisui Wang,Xiang Zheng Kong

Pyrimidines, in particular uracil (UL) and 5-fluorouracil (5FU), are well known anticancerogens and widely used against a variety of cancers. An important concerning issue has been their monitoring and detection in order to adequately control their doses and to minimize their health hazards. Among a variety of methods developed, fluorescence sensing is gaining more attention because of its accuracy, easy operation, and straight visuability. However, in most of the reported studies, the sensors are made from transition metals with sophisticated multi-processes; polymers, particularly biopolymers, are hardly available. We demonstrate herein that aqueous solution of poly(ethylene glycol) (PEG), a commonly known biopolymer, is highly emissive under excitation of 280 nm. While the solutions of selected pyrimidines, i.e. UL and 5FU, are non-emissive under the same excitation, their addition to PEG solution, however, brings about a distinct and concentration dependent quenching for PEG emission. PEG was then used as sensor with good stability for UL and 5FU detections in water. The tests were also done by spiking 5FU in tap water, milk and synthetic urine, confirming that 5FU was practically fully recovered in all the cases. The quenching was ascribed to the interaction between PEG clusters and the heteroatoms on pyrimidine molecules through hydrogen bonding, which is supported by multi-technical analyses, including NMR, FTIR and cluster size tests by DLS. This work provides therefore a full green, easy to operate, low-costing, novel and reliable protocol for pyrimidine monitoring and detection, with the quenching mechanism interpreted based on multi-technical characterizations.

CAS / MDL: 51-21-8 66-22-8
研究领域: 生物化学 · 医学检测 · 材料科学
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Nature Communications · 2019 ·Vol. 10 ·期 1 ·1-14 · IF 11.878

ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield

Ou Juanjuan,Peng Yuan,Yang Weiwen,Zhang Yue,Hao Jie,Li Fu,Chen Yanrong,Zhao Yang,Xie Xiong,Wu Shuang,Zha Lin,Luo Xi,Xie Ganfeng,Wang Liting,Sun Wei,Zhou Qi,Li Jianjun,Liang Houjie

The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.

研究领域: 肿瘤学 · 分子生物学 · 药理学
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Materials Chemistry Frontiers · 2024 · IF 6

Two-dimensional covalent organic framework-based hybrid nanosheets for electrochemical detection of 5-fluorouracil and uracil in biofluids

Jia Liu,Zhiyang Wang,Xiaowei Wu,Shanyue Wei,Yiming Xie,Jing Chen,Can-Zhong Lu

Owing to the unique properties of high porosity, outstanding chemical stability, and designable structures, vast applications of covalent organic frameworks (COFs) have been explored in a wide range of areas including energy storage, catalysis, gas separation, etc. Nevertheless, from the perspective of electrochemical sensing, the conductivity of COFs is not satisfactory. Here, a two-dimensional (2D) hybrid nanosheet combining a COF, a supramolecular host, and nanomaterials was constructed by assembling cucurbit[8]uril (CB8) onto the surface of the COF, and achieved in situ growth of uniformly dispersed AuNPs with the aid of the modulation effect of CB8 to synergistically enhance the sensing performance. By taking advantage of the abundant active loading sites and large specific area of the 2D-COF, excellent conductivity of AuNPs, and host–guest binding ability of CB8, the prepared COF/CB8/AuNPs is utilized to modify the glassy carbon electrode (GCE) as an advanced electrochemical sensor for simultaneous detection of structurally similar analytes, e.g. antineoplastic agent 5-fluorouracil (5-FU) and RNA base uracil (U) using differential pulse voltammetry, achieving detection limits down to the nanomolar level (e.g. 0.037 and 0.074 μM for 5-FU and U, respectively) and the physiologically relevant linear detection range within the sub-micromolar window. Impressively, the prepared COF/CB8/AuNPs/GCE sensor is considerably robust in complicated biofluids, allowing for detecting 5-FU and U in unprocessed native synthetic urine (SU) and whole fetal bovine serum (FBS), which remained highly challenging for electrochemical sensors. This study elucidates the integration of COFs with supramolecular host systems, paving the way for the development of advanced electrochemical sensors for rapid and onsite detection in pharmaceutical diagnostic applications.

研究领域: 材料科学 · 电化学 · 医学诊断
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JOURNAL OF CHEMICAL RESEARCH · 2012 · IF 0.633

Facile Aza-Michael Additions of Uracil Derivatives to Acrylates

Shuguang Zhou,Mingxia Xu,Siyu Ye,Dashuai Li,Jing Xu,Pei Mao,Jing Xiong

24 Aza-Michael adducts were synthesised in moderate to excellent yields by the addition of 5-substituted uracils to acrylates with ethylamine as a catalyst. Many of the adducts were obtained in almost quantitive yield without column chromatography. The procedure provideded an efficient approach to the synthesis of N-1 uracil adducts using acrylates as acceptors. The structures of the compounds were determined by 1H NMR, 13C NMR, mass spectra and X-ray crystallography analyses. The uracil unit is present in DNA and related natural products and has a broad spectrum of biological activity.

研究领域: 有机化学 · 药物化学 · 生物化学
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MOLECULAR PHARMACEUTICS · 2024 · IF 4.5

Drug–Drug Cocrystal Alloy and Nanoformulation of Cytarabine: Optimized Biopharmaceutical Property and Synergistic Antitumor Efficacy

Yue-Ming Yu,Xue-Jie Li,Fan-Zhi Bu,Zhi-Long Zhao,Zhi-Yong Wu,Yan-Tuan Li

An integrated strategy by combining cocrystallization with nanotechnology is developed to optimize in vitro/vivo performances of marine antitumor drug cytarabine (ARA) and further obtain innovative insights into the exploitation of cocrystal alloy nanoformulation. Therein, the optimization of properties and synergistic effects of ARA mainly depends on assembling with uracil (U) and antitumor drug 5-fluorouracil (FU) into the same crystal by cocrystallization technology, while the long-term efficacy is primarily maintained by playing the superiority of nanotechnology. Along this line, the first cocrystal alloy of ARA, viz., ARA-FU-U (0.6:0.4), is successfully obtained and then transformed into a nanocrystal. Single-crystal X-ray diffraction analysis demonstrates that this cocrystal alloy consists of two isomorphic cocrystals of ARA, namely, ARA-FU and ARA-U, in 0.6:0.4 ratio. An R22(8) hydrogen-bonding cyclic system formed by a cytosine fragment of ARA with U or FU can protect and stabilize the amine group on ARA, laying the foundation for regulating its properties. The in vitro/in vivo properties of the cocrystal alloy and its nanocrystals are investigated by theoretical and experimental means. It reveals that both the alloy and nanocrystal can improve physicochemical properties and promote drug absorption, thus bringing to optimized pharmacokinetic behaviors. The nanocrystal produces superior effects than the alloy that helps to extend therapeutic time and action. Particularly, relative to the corresponding binary cocrystal, the synergistic antitumor activity of ARA and FU in the cocrystal alloy is heightened obviously. It may be that U contributes to reducing the degradation of FU, specifically increasing its concentration in tumors to enhance the synergistic effects of FU and ARA. These findings provide new thoughts for the application of cocrystal alloys in the marine drug field and break fresh ground for cocrystal alloy formulations to optimize drug properties.

CAS / MDL: 147-94-4 51-21-8
研究领域: 药学 · 生物医学工程 · 肿瘤学
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RESEARCH ON CHEMICAL INTERMEDIATES · 2012 ·Vol. 38 ·期 7 ·1421-1429 · IF 0.697

Synthesis and characterization of ramose tetralactosyl-lysyl-chitosan-5-fluorouracil and its in vitro release

Li He-ping,Qin Long,Wang Zhou-dong,Li Shan

In order to improve drug loading and achieve a good release effect, this paper adopts the ramose method, choosing chitosan as the carrier and 5-fluorouracil (5-Fu) as a model drug. Ramose chitosan-lysyl-5-Fu(3) and ramose tetralactosyl-lysyl-chitosan-5-Fu(6) were synthesized successfully, then the in vitro release of (6) was researched. The results show that the drug loading of (3) and (6) are 9.17 and 1.63% (w/w), respectively. The in vitro release behavior of (6) in pH 7.4 phosphate buffer solution and pH 1.2 HCl–KCl solution were studied. The zero order release time that (6) maintains in alkaline and acidic media are 64 and 24 h, and the total release by 184 h are 71.97 and 82.34%, respectively. The performance is smooth throughout the whole stage of release, and the concentration of cumulative release is lower in the alkaline environment than in the acidic environment over the same time.

CAS / MDL: 79-08-3 1122-58-3
研究领域: 药剂学 · 生物材料学
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2020 ·Vol. 32 ·期 3 ·1176-1186 · IF 2.578

One-step treated wood by using natural source phytic acid and uracil for enhanced mechanical properties and flame retardancy

Lichen Zhang,Deqi Yi,Jianwei Hao,Ming Gao

Wood has always maintained an important position in construction engineering and decoration due to its unique excellent characteristics, but its flammability has limited various application. In this study, phytic acid (PA) derived from plant seeds and uracil (U) derived from ribonucleic acid (RNA) were prepared as water solution, and natural wood just through physical infiltration in the water solution to obtain wood/PA/uracil (flame retardant [FR] wood), which was environmentally friendly, high strength and fire-resistant. The three-point bending test performance was basically unchanged, compressive strength was increased by 15.3%. The peak heat release rate, total heat release, smoke production rate, and total smoke production of FR wood were reduced up to 41%, 30%, 61%, 56%, respectively, compared with the natural wood. Limiting oxygen index value of FR wood can reach 31.8%, and UL-94 V-0 rating can be reached. These results suggested that wood/PA/uracil could be promising green construction applications.

CAS / MDL: 66-22-8 7664-38-2
研究领域: 材料科学 · 林业工程 · 环境科学
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DESALINATION · 2012 · IF 2.59

Synthesis of polyaspartic acid/5-aminoorotic acid graft copolymer and evaluation of its scale inhibition and corrosion inhibition performance

Ying Xu,Ben Zhang,Linlin Zhao,Yuanchen Cui

Polyaspartic acid/5-aminoorotic acid graft copolymer (PASP/5-AOA) was synthesized by the reaction of maleic anhydride , urea and 5-aminoorotic acid (5-AOA). The graft copolymer (PASP/5-AOA) was characterized by FT-IR and UV–VIS analyses. Its performance was evaluated by static scale inhibition method and dynamic corrosion testing . The results showed that PASP/5-AOA possessed super scale inhibition property against CaCO 3 and Ca 3 (PO 4 ) 2 as well as good corrosion inhibition property. Inhibition efficiency of PASP/5-AOA was close to 100% against CaCO 3 when the dosage was 1   mg/L in the simulation experiment. Corrosion inhibition efficiency was close to 60% and scale inhibition efficiency was close to 100% against Ca 3 (PO 4 ) 2 when the dosage was 12   mg/L in the simulation experiment. When PASP/5-AOA was added to the solution, CaCO 3 and Ca 3 (PO 4 ) 2 deposits show flower and cascade patterns with floppy accumulation by scanning electron microscopy (SEM).

CAS / MDL: 7164-43-4
研究领域: 化学工程 · 材料科学
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Polymer Chemistry · 2018 ·Vol. 9 ·期 36 ·4535-4542 · IF 4.927

Anti-fatigue adhesive and tough hydrogels regulated by adenine and uracil

Xin Liu,Qin Zhang,Yanchao Qiao,Lijie Duan,Guanghui Gao

Hydrogels generally possess either high strength or excellent adhesive behavior but not both, which limits their applications. Here, we present anti-fatigue, adhesive and tough hydrogels through introducing nucleobase pairs of adenine–uracil (A–U) and chemical crosslinkers of N,N′-methylene bis-acrylamide (MBA) into polyacrylamide hydrogels. The synergetic interaction of A–U and MBA endowed hydrogels with high mechanical performance and excellent adhesive behavior via the tunable balance of cohesion and adhesion. The hydrogels exhibited a tensile strength of 120 kPa, a superior stretchability of 2700%, and remarkable adhesive behavior for various materials and biological tissues, including wood, steel, copper, polytetrafluoroethylene, plastics, glass, rubber, silica rubber, spleen, liver and fat. For example, the adhesion strength of hydrogels at the surface of polytetrafluoroethylene was 190 N m−1. More importantly, the hydrogels exhibited excellent anti-fatigue compressive toughness and adhesiveness. It was envisioned that the nucleobase-tackified chemical crosslinking hydrogels with excellent anti-fatigue, tough and adhesive behavior would be widely applied in wound dressings, human wearable devices and biomedical sensors and electrodes.

研究领域: 材料科学 · 生物医学工程
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CRYSTENGCOMM · 2021 ·Vol. 23 ·期 46 ·8027-8032 · IF 3.545

Polymorph control of 5-fluorouracil during a ball milling process

Fenghua Chen,Jie Fan,Xiuzhi Chen,Yanping Li,Chengfeng Liang,Shizhao Ren,Rongrong Xue

Polymorph control of 5-fluorouracil (5-FU) was achieved by ball milling. Form II was synthesized through one-step neat grinding of raw 5-FU (RFU), and Form III (a new polymorph) was obtained by neat grinding RFU twice. Forms II and III of 5-FU were prepared separately through ball milling with different amounts of ethanol as an additive at the same period without influencing each other.

CAS / MDL: 51-21-8
研究领域: 药物化学 · 制药工程
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VIBRATIONAL SPECTROSCOPY · 2024 · IF 2.7

Preparation and characterization of 5-fluorouracil drug cocrystal and its dynamic monitoring of cocrystallization process via SERS spectroscopy

Fan Yang,Jing Zhao,Zhengang Wu,Yingna Wei,Hengyong Wei,Jingwu Li,Bo Li

Cocrystal is a new class of pharmaceutical crystal form, which could improve the physical and chemical properties of drug substance without affecting the internal structure of drug substance. Therefore, the cocrystals show a great deal of potential in the development and research of drugs. 5-Fluorouracil (5-FU) is one of the most widely used anti-pyrimidine drugs. However, its solubility is poor and its oral bioavailability is low. In this work, the cocrystal of 5-FU with nicotinamide was prepared by the solvent evaporation method. The cocrystal structure was confirmed by infrared spectroscopy (IR), X-ray diffraction (XRD) and Raman spectroscopy. The X-ray diffraction and infrared spectroscopy presented that there were significantly different peaks between the raw drug and the cocrystal. Raman spectral results also indicated the differences of such cocrystal compared with the raw drug. In addition, TiN-Ag composite SERS substrate was used to study the formation of 5-FU cocrystal drugs and the formation process was dynamically monitored, and the interaction between molecules during the cocrystal reaction was deeply understood. The cocrystal reaction process was tracked, it can be found that the peak intensity of the raw drug and cocrystal changes with the reaction, indicating that the TiN-Ag composite substrate can monitor the cocrystal transformation process.

研究领域: 药学 · 分析化学
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ACS Synthetic Biology · 2024 · IF 3.7

Systematic Engineering of Escherichia coli for Efficient Production of Pseudouridine from Glucose and Uracil

Chi Zhang,Guoguang Wei,Ning Zhou,Yingying Wang,Jia Feng,Xin Wang,Alei Zhang,Kequan Chen

In this study, we proposed a biological approach to efficiently produce pseudouridine (Ψ) from glucose and uracil in vivo using engineered Escherichia coli. By screening host strains and core enzymes, E. coli MG1655 overexpressing Ψ monophosphate (ΨMP) glycosidase and ΨMP phosphatase was obtained, which displayed the highest Ψ concentration. Then, optimization of the RBS sequences, enhancement of ribose 5-phosphate supply in the cells, and overexpression of the membrane transport protein UraA were investigated. Finally, fed-batch fermentation of Ψ in a 5 L fermentor can reach 27.5 g/L with a yield of 89.2 mol % toward uracil and 25.6 mol % toward glucose within 48 h, both of which are the highest to date. In addition, the Ψ product with a high purity of 99.8% can be purified from the fermentation broth after crystallization. This work provides an efficient and environmentally friendly protocol for allowing for the possibility of Ψ bioproduction on an industrial scale.

CAS / MDL: 10102-40-6
研究领域: 合成生物学 · 微生物工程
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