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Journal of Materials Chemistry C Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/materialsC Page 1 of 8 Journal of Materials Chemistry C Journal Name RSC Publishing ARTICLE The 2-Phenylbenzimidazole-5-sulfonate/layered double hydroxides co-intercalation composites and its Cite this: DOI: 10.1039/x0xx00000x luminescence response for nucleotides Shufang Zheng, Jun Lu *,Wu Li,Yumei Qin, Dongpeng Yan, David G Evans, and Manuscript Received 00th January 2012, Xue Duan Accepted 00th January 2012 DOI: 10.1039/x0xx00000x The fluorescence sensing for nucleotides is an important topic for biosensor and fluorescence materials. In this paper, a cheap UV light absorber, 2-Phenylbenzimidazole- www.rsc.org/ 5-sulfonate(PBS) was immobiled into the interlayers of Zn 2Al layered double hydroxides(LDHs) by co-intercalating with 1-decane sulfonate (DES) anions. The fluorescence dependance on the molar concentration (x%) of PBS was investigated and the PBS(15%)-DES/LDH composite exhibited the optimal violet luminescence at 402 nm, compared with that of PBS solution with luminescence at 342 nm. The PBS(15%)- Accepted DES/LDH composite thin films were fabricated by solvent evaporation method on quartz substrate. Moreover, the composite thin film exhibited the remarkable PBS luminescence C transformation (violet to UV light) for nucleotides triphosphate (ATP, GTP, CTP and UTP), compared with their diphosphate and monophosphate counterparts (ADP, AMP and etc.), which is expected to be prospective for sensing the nucleotide molecules at the simulated physiological conditions. The origin of the luminescence enhancement was investigated and attributed to the extensive hydrogen bonding interaction between the intercalated PBS and nucleotides. Introduction key building blocks for RNA synthesis, were widespread in living cells and featured in various biological events. 12 In recent years, the development of molecular- The recognition and sensing of nucleotides like ATP has recognition and sensing systems for biologically important been an active research focus for academic research and 1-8 Chemistry anions has received considerable attention. As one of applications. the nucleotides, adenosine triphosphate (ATP) molecules Up to now, many methods have been developed for the play an indispensable role in the biochemical process, detection of nucleotides, among which the fluorescence which was not only a universal energy source in the sensing progressed rapidly due to the advantage of high biochemical reactions, but also an extracellular signaling sensitivity, lossless determination, fast, low cost, easy to 9 mediator in many biological processes. Guanosine operate. For example, Yoon et al . 7 investigated a pincer- trisphosphate (GTP) was involved in RNA synthesis, citric like benzene-bridged sensor with a pyrene excimer as a acid cycle, and acts as an energy source for protein signal source and imidazolium as a phosphate anion 10 synthesis. Moreover, other nucleoside poly-phosphates, receptor for ATP sensing. Ones such as azacrown, amide such as adenosine monophosphate (AMP), adenosine and urea derivatives were found to detect nucleotides Materials diphosphate (ADP) and guanosine monophosphate (GMP), based on hydrogen bond interactions. In 2006, Bazzicalupi also play pivotal roles in various physiological events. For and Bencini et al. reported a new phenanthroline- of example, AMP and ADP were vital in bioenergetics, containing macrocycle which could selectively recognize metabolism, and transfer of genetic information, and GMP and sense ATP among triphosphate nucleotides at pH 6. 13 acts as an intermediate in the synthesis of nucleic acids and One also use the metal complexes like zinc (Zn 2+ ) ， has a crucial role to perform in several metabolic 3+ 2+ 3+ 11 ytterbium (Yb ), ruthenium (Ru ), europium (Eu ), processes. CDP and CTP is also a kind of energetic terbium (Tb 3+ ), yttrium (Y 3+ ), manganese(Mn 2+ ) or cobalt compounds, which take part in the biological phospholipid (Co 2+ ) as the binding motif to detect nucleotides,. 8 Even metabolism in the body. On the other hand, uridine more, polymers or mesoporous materials can be used as triphosphate (UTP) and uridine diphosphate (UDP), the nucleotides sensors. Shinkai’s group 14 reported a water- Journal This journal is © The Royal Society of Chemistry 2013 J. Name ., 2013, 00 , 1-3 | 1 Journal of Materials Chemistry C Page 2 of 8 ARTICLE Journal Name soluble cationic polythiophene derivative which displayed (C10 H21 O3SNa, DES), 5'-adenosinetriphosphate disodium colorimetric and fluorescent responses to ATP through salt (C 10 H14 N5O13 P3Na 2, ATP), 5'-adenyldiphosphate electrostatic and hydrophobic cooperative interactions. All disodium salt (C 10 H13 N5O10 P2Na 2, ADP), adenosine-5'- of the methods were rather complex, expensive and/or one- monophosphate disodium salt (C 10 H12 N5O7PNa 2, AMP), off for sensing. The repeatable and high performance uridine-5'-triphosphate trisodium salt dihydrate （ devices detection is needed for practical nucleotides probe. C9H12 N2O15 P3Na 3⋅2H 2O, UTP), uridine-5'-diphosphate Furthermore, it is still a challenge for these sensor sodium salt (C9H14 N2O12 P2Na 2⋅2H 2O, UDP), Uuridine-5'- materials to discriminate a certain nucleotide triphosphate monophosphate disodium salt (C9H11 N2O9PNa 2⋅xH2O, among others. UMP), cytidine 5'-triphosphate disodium salt Recently, considerable interest has been focused on (C9H14 N3O14 P3Na 2, CTP), cytidine 5'-diphosphate the fabrication of 2D ordered organic-inorganic thin film trisodium salt hydrate (C9H12 N3O11 P2Na 3⋅xH2O, CDP), materials, for they may show novel functionalities (such as cytidine 5'-monophosphate disodium salt enhanced photo-, thermal-, and mechanical-stability) (C H N O PNa , CMP), Guanosine 5-triphosphate compared with their individual components alone.15,16 In 9 14 3 8 2 Manuscript disodium salt (C 10 H14 N5O14 P3Na 2, GTP), guanosine 5′- this sense, layered double hydroxides (LDHs), whose diphosphate sodium salt(C H N O P Na, GDP), structure can be generally expressed as the general formula 10 14 5 11 2 II III z+ n- . II III guanosine 5'-monophosphate disodium salt [M 1-xM x(OH) 2] A z/n yH 2O(M and M are divalent (C H N O PNa , GMP) and (2-[4-(2-hydroxyethyl)-1- and trivalent metals respectively, A n- is the guest anion), 10 12 5 8 2 pipera-zinyl] ethane sulfonic acid) (C 8H18 N2O4S, HEPES) were one type of important layered matrixes with the were purchased from J&K Chemical Co. Ltd. Analytical various interlayer anions, and the adJustable interlayer 17-21 grade Zn(NO 3)2·6H 2O, Al(NO 3)3·9H 2O, and NaOH were spacing. Various negative-charged species including purchased from BeiJing Chemical Co. Ltd. All other DNA and nucleotides have been intercalated into the 22,23 chemicals were analytical grade and used as received LDHs . without further purification. Deionized water was used Accepted The 2-Phenylbenzimidazole-5-sulfonic acid (PBS) is an throughout the experimental process. kind of ultraviolet light absorber due to its outstanding UV C 24 light absorption ability , and it has extensive applications Preparation of PBS( x%)-DES/LDH composites in cosmetics and rubber industry. Its π-conJungated electon The PBS(x%)-DES/LDH powder was synthesized by system involving benzene ring and imidazole group made 25 it well blue fluorophore, and the PBS powder and solution the co-precipitation method reported previously. luminesces at 450 nm and 340 nm, respectively, which no Zn(NO 3)3·6H 2O(0.01mol) and Al(NO 3)2·9H 2O(0.005mol) attention was paid to being a sensor for biomolecules. were dissolved in ethanol-deionized/deCO 2 water (v/v 1:1) Herein, PBS anions were introduced into the interlayers mixture as solution A, PBS (a mol), DES ( b mol in which a + b = 0.005 mol, x % = a /( a + b ), x % = 10, 15, 20, 25, of Zn 2Al-LDHs by co-intercalating with decane-1- sulfonate (DES) anions to form the PBS(x%)-DES/LDHs 30, 50, 75, and 100 %, respectively) and NaOH (0.03 mol) composite system . The strongest fluorescence was found were dissolved in ethanol-deionized/deCO 2 water (v/v, Chemistry to be PBS(15%)-DES/LDHs at 402 nm, with a blue shift of 1:1) mixture as solution B. Then the solution B was added about 50 nm compared with PBS powder. The PBS(15%)- into solution A with the dropping rate of 10 d/min by using DES/LDHs composite thin film on quartz substrates was the seal funnel under the protection of N 2 atmosphere. The fabricated by the drop-casting method, which show the 402 product then was aged in 100 ml PTFE-lined autoclave at nm luminescence on-off switch response for the ATP 100 °C for 20 h. Then the white powder product was physiological solution with concentration range from 10 -3 obtained by centrifugation, washing and drying. to 10 -7 M. Furthermore, accompanied with the quenching of 402 nm luminescence, the strong 342 nm UV Fabrication of PBS(15%)-DES/LDHs thin films and its detection luminsecence appears, which is more obvious for sensing of nucleotides ATP than ADP/AMP, and is held for other nucleotides The PBS(15%)-DES/LDH composite thin film was Materials (CXP, GXP, and UXP).
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  • On the Action of Fluorouracil on Leukemia Cells1

    On the Action of Fluorouracil on Leukemia Cells1

    [CANCER RESEARCH 26 Part 1, 1611-1615,August 1966] On the Action of Fluorouracil on Leukemia Cells1 ALLAN R. GOLDBERG, JOHN H. MACHLEDT, JR., AND ARTHUR B. PARDEE Department of Biology, Princeton University, Princeton, New Jersey Summary In the present study the lymphoid leukemia L1210 of the mouse and a FU-resistant line were investigated. The problem The uptake and metabolism of radioactive uracil, uridine, posed was to discover a site of FU inhibition in the sensitive phosphate, and 5-fluorouracil by the mouse L1210 leukemic cells. The results suggest that the "salvage" pathway of pyrimi leukocytes and a fluorouracil-resistant variant were investigated. dine synthesis (see Chart 1) is sensitive to FU, with a resulting The dual aims of the research were to locate a metabolic differ inhibition of nucleic acid synthesis in the sensitive cells. The re ence responsible for resistance, and to define the site of action of the inhibitor. The resistant cells possess a much less active "sal sistant cells do not depend on this pathway, and hence are not vage" pathway, from uracil to nucleic acids, owing to a weaker susceptible to the inhibitor. uridine phosphorylase activity. They depend on the de novo pathway for a supply of pyrimidine nucleotides. Also, the con Materials and Methods version of fluorouracil to phosphorylated derivatives and its Uracil-3H and uridine-3H were obtained from the New Eng incorporation into RNA is somewhat reduced. Fluorouracil is land Nuclear Corporation, 5-FU-3H from Schwarz BioResearch, postulated to be less effective against these cells because its main Inc., and Na2H32PO4from Volk Radiochemical Co.