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Synthesis Of Degradable Amphiphilic Organic/Polymeric Compounds Containing Nucleic Bases As Well As Preparation And Properties Of The Aggregates

Posted on:2008-05-16Degree:MasterType:Thesis
Country:ChinaCandidate:W Y XiaoFull Text:PDF
GTID:2121360212997036Subject:Physical chemistry
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It is the new technology in the past thirty years of the microencapsulation and microsphere applied to pharmaceutical.The materials of microencapsulation was the natural or synthetical degradable high molecular material.Adenine and thymine are the bases of nucleic acid,the molecular base of the DNA moleocule forming the spiral structure.If the ademine is introduced to the degradable amphiphilic organic/polymer,self-assembled the aggregates receptor in dilute aqueous solution,the complementary base acts as the substrate.the molecular recognition can do through HLI and the interaction of the receptor and substrate.Through the molecular recognition, interaction of the receptor and substrate in aggregates is strengthened, the function of the receptor drug-loaded and the drug-entrapmented efficiency are inproved , the theoretical and experimental support offered for pharmaceutical preparation.In this paper, ademine and thymine are the major raw materials. monomer (2-(9-Adeninyl)) diethyl succinate was synthesized. Degradable amphiphilic polymer containing nucleic acid base poly(2—(9—Adeninyl))ditetraethylene glycol succinate was synthesized successively by melt polycondensation with monomer (2-(9-Adeninyl)) diethyl succinate and tetraethylene glycol; Amphiphilic small molecular compounds(10—(9—Adeninyl)decyl)trimethylammonium bromide and (10-(1-Thyminyl)decyl)trimethylammonium bromide were also prepared. The structures of the compounds were characterized by the technology of NMR and Elemental Analyzer.By SEM technique, the aggregation of poly(2—(9—Adeninyl)) ditetraethylene glycol succinate was observed as 500-700nm spherical or elliptical nanoparticles,namely constituted with the core hydrophobic segment aggregated coved by shell hydrophilic segment aggregated;The amphiphilic small molecular compounds (10—(9—Adeninyl) decyl) trimethylammonium bromide and (10-(1-Thyminyl)decyl) trimethylammoni-um bromide were about 300nm spherical micelles.In the process of studying the properties of the aggregates , poly(2—(9—Adeninyl)) ditetraethylene glycol succinate acts as the receptor and the thymine acts as the substrate.The solvent water existed in the aggregation aqueous solution of poly (2—(9—Adeninyl))ditetraethylene glycol succinate and the 1:1mixure solution of the receptor poly(2—(9—Adeninyl)) ditetraethylene glycol succinate +the substrate thymine(1:1) was eliminated by freeze-drying technology, the substance left was measured by FTIR with pressing KBr die.Bacause of the aggregates state in their dilute aqueous solutions undestroying ,the results whether the receptor and the substrate molecular- recognized based on hydrogen bond are convincing. Experimental results show that the v (4) - C=0 of the substrate thymine showed red shift from 1677 cm-1 to 1669 cm-1 after mixtured with the receptor poly(2—(9—adeninyl)) ditetraethylene glycol succinate .We note that there came into being hydrogen bond between the receptor poly(2—(9—adeninyl)) ditetraethylene glycol succinate and the substrate thymine,the bond length longer, the bond order decrese, v (σ) moves to lower wave-number.Concurrently amphiphilic small molecular components molecular-recognition systems were also designed : (10—(9—Adeninyl) decyl) trimethylammonium bromide acted as the receptor and thymine acted as the substrate; (10-(1-Thyminyl)decyl) trimethylammonium bromide acted as the receptor and adenine acted as the substrate; (10—(9—Adeninyl) decyl) trimethylammonium bromide acted as the receptor and fluorouracil acted as the substrate. With the same means, we gained the FTIR datas which show the receptor and the substrates of the systems above-mentioned also formed hydrogen bond. Though the study of the FTIR datas ,we discovery that when thymine acts as the substrate , v ( 4 ) - C=O shows red shift;When (10-(1-Thyminyl)decyl) trimethylammonium bromide acts as the substrate, v (2) - C=O shows red shift.ln the system of (10—(9—adeninyl) decyl) trimethylammonium bromide and fluorouracil, v (2) - C=O shows red shift.Tough analyzing,we think that two factors are related possiblely :①the electronegativity effect of atom O of -C=O;②the stability for interspace structure of supramolecular system of the receptor and the substrate formed hydrogen bond.In a word, we designed and synthesized some amphiphilic substances.The core-shellnanoparticles prepared by polymer containing nucleic acid base poly(2—(9—Adeninyl)) ditetraethylene glycol succinate.In dilute aqueous solution, the aggregation receptors core-shell nanoparticles or micelles molecular-recognized all with complementary base.The degradable core-shell nanoparticles provide experimental and theoretical support for preparation drug carriers no mater as self-assembled nanoparticles or for molecular-recognition.
Keywords/Search Tags:Organic/Polymeric
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