含磷聚酸酐药物控制释放材料的研究

将二氯磷酸乙酯或苯酯与对羟乙氧基苯甲酸反应，制备了含磷酸酯键的二羧酸，将其转化为混合酸酐并通过熔融缩聚，合成了主链含磷酸酯键的聚酯酐，以含磷酸酯键二羧酸与１，３－双（４－羧基苯氧基）丙烷（ＣＰＰ）熔融共聚，得到一链到酯键的共聚酸酐研究了两类聚酸酐的体外降解，酶促降解，这些聚酸酐的降解过程包含酸酐键的断裂，也包含磷酸酯键断裂，前者比后者更容易断裂，核糖核酸酶和碱性磷酸酶能加速这类聚酸酐的降解，还研究     

聚酯酸酐的合成及其药物释放性能研究

将对羟乙氧基苯甲酸分别与已二酰氯、癸二酰氯和对苯二甲酰氯反应,制备了含酯键的二羧酸.经熔融缩聚,合成了主链含酯键的新型聚酯酸酐.通过¹H NMR、IR及元素分析对单体及聚酯酸酐的结构进行了表征.研究了聚酯酸酐的体外降解和药物释放性能,其降解速率和释药速率次序为:聚4,4'-(已二酰氧二乙氧基)双对苯二甲酸＞聚4,4'-(癸二酰氧二乙氧基)双对苯二甲酸＞聚4,4'-(对苯二甲酰氧二乙氧基)双对苯二甲酸.     

聚γ-(p-二苯膦苯基)丙基硅氧烷钯(Ⅱ)配合物的合成及其催化羰基化性能

对－溴烯丙基苯依次与三乙氧基硅烷加成、二苯膦钾膦化、气相法二氧化硅固载化,再与氯化钯反应,合成了聚γ－（ｐ－二苯膦苯基）丙基硅氧烷钯（Ⅱ）配合物,研究了基催化芳基卤化物的Ｈｅｃｋ羰基化性能。     

4个新型有机磷缩合试剂的合成及其在生物活性肽合成中…

报道了４个新型有机磷化合物：Ｎ－二乙氧基磷酰并恶唑酮（ＤＥＰＢＯ０，Ｎ－（２－氧－１，３，２－二氧杂磷环己烷基）－苯并恶唑酮（ＤＯＰＢＯ），３－（２′－氧－１′，３′，２′－二氧杂磷杂环己烷基）－氧－１，２，３－苯并三嗪－４（３Ｈ）－酮（）ＤＯＰＢＴ）和３－（二乙氧基磷酰基）－氧－１，２，３－苯并三嗪－４（３Ｈ）－酮（ＤＥＰＢＴ）的合成，并研究了它们作为缩合试剂的多肽合成中的应用，研究结果表明，它     

聚酯—酰胺型MRI造影剂的合成及基弛豫性能研究

通过二乙三胺五乙酸双酸酐分别与乙醇胺、L－丝氨酸及其乙酯、L－酪氨酸及其甲酯、苄酯、正辛酯共聚，合成了七种大分子配体，制备了它们的Gd(Ⅲ）配合物，并进行了表征。测试其中五种水溶性配合物的驰豫性能。结果表明它们具有与Gd(DTPA)相当或更强的弛豫性能。     

GC-MS分析水中GB、GD、VX 及其降解产物

甲氟膦酸异丙酯(GB)、甲氟膦酸特己酯(GD)、S-(2-二异丙基氨乙基)甲基硫赶膦酸乙酯(VX)等有机膦酸酯类化合物是毒性大、作用快的致死性化学战剂,而且会严重污染环境(水、泥土、粮食等),对人类和牲畜的生存构成巨大威胁.由于该类化合物在一定条件下易降解,因此对原型化合物及其降解产物的分析鉴定是确定是否被该类化合物污染的最重要指证.本文建立了水中GB等3个原型化合物和其相对应的降解产物甲基异丙氧基膦酸(IMPA)、甲基特乙氧基膦酸(PMPA)、甲基乙氧基膦酸(EMPA)以及它们的二级降解产物甲基磷酸(MPA)的分析鉴定方法.     

2-氰基-3-[1-(4-取代苯氧基苯基)乙胺基]烯酸乙氧乙酯的合成及除草活性

以取代苯酚4和对氟苯乙酮(5)为原料,经4步反应合成关键中间体1-(4-取代苯氧苯基)乙胺(9),再与3种中间体2-氰基-3-乙氧基-2-戊烯酸乙氧乙酯(1)、2-氰基-3,3-二甲硫基丙烯酸乙氧乙酯(2)和2-氰基-3-氯-4,4,4-三氟丁烯酸乙氧乙酯(3)分别发生缩合反应,合成了3个系列共35个新2-氰基-3-[1-(4-取代苯氧基苯基)乙胺基]烯酸乙氧乙酯类化合物(10,11和12).所有新化合物的结构均经过1H NMR,13C NMR,19F NMR和HRMS的确证,并测试了目标化合物的除草活性,部分化合物在剂量为93.75 g/ha时,对双子叶植物油菜和苋菜的抑制率为100%.     

两亲性聚酯配体及其钆（Ⅲ）配合物的合成和弛豫性能研究

通过二乙三胺五乙酸二酐（ＤＴＰＡＡ）分别与Ｌ－Ｎ，Ｎ－双（２－羟乙基）取代的丙氨酸、苯丙氨酸、缬氨酸、亮氨酸、异亮氨酸和Ｎ，Ｎ－双（２－羟乙基）甘氨酸共聚，制备了六个大分子聚酯配体及其轧（Ⅲ）配合物。对所合成的配体和钆配合物进行了表征，并测试了部分钆配合物的弛豫性能。     

含5—氟尿嘧啶生物可降解聚磷酰胺的合成及其抗肿瘤活性研究

通过Ｌ－赖氨酸（Ｎ＾１－５－氟尿嘧啶）烷基酯双盐酸盐与二氯磷酸乙酯，二氯膦甲酸乙酯，二氯膦乙酸乙酯共聚，合成了三类１２种侧链含５－氟尿嘧啶的聚磷酰胺。聚合物的结构经ＵＶ，ＩＲ，ＨＮＭＲ及元纱分析鉴定。聚合物用微量细胞培养四氮唑实验方法（ＭＴＴ法）进行了对人肝癌细胞系Ｂｅｌ－７４０２细胞的微量培养实验。     

用气相色谱-原子发射光谱法检测VX、Bz及其降解产物

应用气相色谱－原子发射光谱（ＧＣ－ＡＥＤ）同时检测Ｓ－（２－二异丙基氨乙基）甲基硫直膦酸乙酯（ＶＸ）、二苯羟乙酸－３－喹咛环酯（ＢＺ）战剂及其降解产物等５种化合物,得取了Ｃ、Ｈ、Ｓ、Ｎ、Ｏ、Ｐ６种元素色谱图,通过选择合适的检测元素,其检出限ＶＸ为１５．６ｍｇ／Ｌ,Ｂｚ为１６．７９ｍｇ／Ｌ,二异基氨基乙太醇为３．０２ｍｇ／Ｌ,３－羟基喹咛为２８．４０ｍｇ／Ｌ,二苯羟乙酸甲酯为３１．７８ｍｇ／Ｌ,定量     

Degradable polymer blends. I. Screening of miscible polymers

Blends of biodegradable polymers having properties distinct from the individual polymer components, and that are suitable for use as carriers of pharmaceutically active agents, were prepared from two or more polyanhydrides, polyesters, and mixtures of polyanhydrides and low molecular weight polyesters. The blends have different properties than the original polymers, providing a mean for altering the characteristics of the polymeric matrix without altering the chemical structure of the component polymers. Aliphatic, aromatic, and copolymers of polyanhydrides were miscible in each other and formed less crystalline compositions with a single melting point which was lower than the melting point of the starting polymers. The polyesters: poly(lactide-glycolide), poly(caprolactone), and poly(hydroxybutyric acid) presented some miscibility in each other. However, the polyanhydrides were immiscible with the polyesters resulting in a complete phase separation both in solution or in melt mixing. Only low molecular weight polyesters (in the range of 2000) of lactide and glycolide, mandelic acid, propylenefumarate, and caprolactone presented some miscibility with polyanhydrides. Similarly, poly(orthoester) and hydroxybutyric acid polymers formed a uniform mixture with the anhydride polymers which had the two melting points of the original polymers. Drug release from polymer blends composed of poly(hydroxybutyric acid) or low molecular weight poly(lactic acid) with poly(sebacic anhydride) (PSA) showed a constant release of drug for periods from 2 weeks to several months as a function of the PSA content in the blend. Increasing the content of PSA, a fast degrading polymer, increases the release rate from the blend. © 1993 John Wiley & Sons, Inc.     

Thermal degradation studies of polystyrene sulfonic and polyacrylic carboxylic cationites

The thermal degradation of polyacrylic carboxylic and polystyrene sulfonic cationites was investigated using thermal analysis (TG) combined with Scanning Electron Microscopy (SEM). Fourier Transform Infrared Spectroscopy (FTIR) was used to characterize the resins degradation steps. The carboxylic cationite undergoes degradation through dehydration forming polyanhydrides, decomposition of polyanhydrides through decarboxylation with elimination of CO₂ and CO. The sulfonic cationite undergoes degradation through dehydration, followed by decomposition of sulfonic acid functional groups liberating SO₂. It was observed that strong acid (−SO₃H⁺) cationite shows small mass loss of 55%, as against 88% mass loss shown by low-acidity carboxylic cationite. The possible reason for small mass loss of sulfonic cationite is discussed. The text was submitted by the authors in English.     

Synthesis and erosion properties of PEG-containing polyanhydrides

To tailor the erosion rate of polyanhydrides while retaining their surface erosion characteristics, new three-component polyanhydrides of sebacic acid, 1,3-bis(p-carboxyphenoxy)propane and poly(ethylene glycol) were synthesized. The hydrophilicity of the polymer increased and its mechanical strength decreased with increasing PEG content. Correspondingly, the erosion rate increases with increasing PEG content, whereas it decreases with increasing specimen thickness. This indicates that the incorporation of poly(ethylene glycol) into traditional two-component polyanhydrides retains their surface erosion properties while making the erosion rate tunable. The new polyanhydrides hold potential for drug delivery applications.     

Synthesis,characterization, and degradation of poly(anhydride‐co‐amide)s and their blends with polylactide

In attempt to improve the properties of polyanhydrides based on aliphatic anhydrides, we synthesized novel polyanhydrides containing amide groups in the main chains. In this work, N,N′‐bis(L ‐alanine)‐sebacoylamide (BSAM) was prepared from natural amino acid and sebacic acid (SA) and characterized by IR and ¹H NMR. In addition, polymers of PBSAM, P[1,6‐bis(P‐carboxyphenoxy) hexane (CPH)‐BSAM], and P(CPH‐SA), blends of P(CPH‐SA)/polylactide (PLA), P(CPH‐BSAM)/PLA were also prepared and characterized by IR, gel permeation chromatography, and differential scanning calorimetry. The hydrolytic degradation of polyanhydrides and their blends with PLA (number‐average molecular weight = 2.90 × 10⁵) was evaluated in 0.1 M phosphate buffer pH 7.4 at 37 °C. The results indicate that the existence of amide, aromatic, and ester bonds in the main chain of polymers slows down the degradation rate, and the tendency becomes clearer with the increasing amount of them, and the copolymers and their blends with PLA possess excellent physical and mechanical properties. These can make them more widely used in drug delivery and nerve regeneration. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4311–4317, 2004     

Synthesis of Poly(Adipic Anhydride) by Use of Ketene

Polyadipic anhydrides were prepared (a) from the mixed anhydride of adipic acid and acetic acid, (b) from the mixed anhydride of adipic acid and ketene in tetrahydrofurane solution (0°C), (c) by melt polycondensation of adipic acid with ketene, and (d) from the seven-membered ring adipic anhydride. The polymers were characterized by means of NMR, IR, DSC, and GPC. The polymer with the highest melting temperature was obtained by melt polycondensation of adipic acid with ketene (T _peak 76°C). The heat of fusion was approximately 40 J/g in all four methods. The number-average and weight-average molecular weights of the polyanhydrides were 2000 and 3000, respectively.     

Hydrogen bonding interactions in α-substituted cinnamic acid ester derivatives studied by FT–IR spectroscopy and calculations

Intermolecular hydrogen bonding interactions in stereoisomeric α-substituted cinnamic acid methyl esters (methyl 2,3-diphenylpropenoate, methyl 2-phenyl-3-(2′-methoxyphenyl)-propenoate, methyl 2-(2′-methoxyphenyl)-3-phenylpropenoate and methyl-2,3-bis(2′-methoxyphenyl)-propenoate) were studied by FT–IR spectroscopy and model calculations at the semi-empirical quantum chemical level of theory. Intermolecular hydrogen bonds of C–H…O types were found to be general in the solid state, but rare in solution. In this hydrogen bond the carbon may be part of either aromatic ring or the olefinic bond. The hydrogen bond acceptor may be the carbonyl oxygen or the oxygen in the methoxy substituent. Modeling helped in determining probable hydrogen bonding sites and their positions and provided with approximate geometric parameters (bond lengths and angles). Pointing out differences between the stereoisomers was also possible.     

Amino acids and peptides. LIII. Synthesis and biological activities of some pseudo-peptide analogs of PKSI-527, a plasma kallikrein selective inhibitor: the importance of the peptide backbone.

Pseudo-peptide analogs of trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-4-aminopheny l acetic acid (PKSI-527, plasma kallikrein selective inhibitor), in which an amide bond (peptide bond) has been replaced by a CH2-NH bond, i.e., trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (I), trans-4-aminomethylcyclohexanecarbonyl-psi (CH2-NH)-L-phenylalanyl-4-aminophenyl acetic acid (II) and trans-4-aminomethylcyclohexanecarbonyl-D-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (III) were synthesized. These pseudo-peptide analogs did not exhibit any detectable inhibitory activity against plasma kallikrein (PK), plasmin (PL), urokinase (UK), thrombine (TH) or trypsin (TRY). These results indicate that both carbonyl groups in the PKSI-527 are important for the manifestation of potent inhibitory activity against plasma kallikrein.     

Biodegradable polymers derived from natural fatty acids

A new class of polyanhydrides synthesized from nonlinear hydrophobic fatty acid esters, based on ricinoleic, maleic acid, and sebacic acid, possessed desired physico-chemical and mechanical properties for use as drug carriers. The polymers were synthesized by melt condensation to yield film-forming polymers with molecular weights exceeding 100,000. Their rate of elimination from rats in the course of about 2 months was faster than that found for similar polyanhydrides previously tested. In vitro studies showed that these polymers underwent rapid degradation in the first 10 days. The drug release followed first-order kinetics, showing a rapid drug release rate in the first 10 days which correlated with the degradation of the polymers. The fatty acid ester monomers underwent in vitro enzymatic degradation to the natural starting acids. Tests in rats demonstrated their toxicological inertness and biodegradability. © 1995 John Wiley & Sons, Inc.     

Energetics of hydroxybenzoic acids and of the corresponding carboxyphenoxyl radicals. Intramolecular hydrogen bonding in 2-hydroxybenzoic acid

The energetics of the phenolic O-H bond in the three hydroxybenzoic acid isomers and of the intramolecular hydrogen O-H- - -O-C bond in 2-hydroxybenzoic acid, 2-OHBA, were investigated by using a combination of experimental and theoretical methods. The standard molar enthalpies of formation of monoclinic 3- and 4-hydroxybenzoic acids, at 298.15 K, were determined as Delta(f)(3-OHBA, cr) = -593.9 +/- 2.0 kJ x mol(-1) and Delta(f)(4-OHBA, cr) = -597.2 +/- 1.4 kJ x mol(-1), by combustion calorimetry. Calvet drop-sublimation calorimetric measurements on monoclinic samples of 2-, 3-, and 4-OHBA, led to the following enthalpy of sublimation values at 298.15 K: Delta(sub)(2-OHBA) = 94.4 +/- 0.4 kJ x mol(-1), Delta(sub)(3-OHBA) = 118.3 +/- 1.1 kJ x mol(-1), and Delta(sub)(4-OHBA) = 117.0 +/- 0.5 kJ x mol(-1). From the obtained Delta(f)(cr) and Delta(sub) values and the previously reported enthalpy of formation of monoclinic 2-OHBA (-591.7 +/- 1.3 kJ x mol(-1)), it was possible to derive Delta(f)(2-OHBA, g) = -497.3 +/- 1.4 kJ x mol(-1), Delta(f)(3-OHBA, g) = -475.6 +/- 2.3 kJ x mol(-1), and Delta(f)(4-OHBA, cr) = -480.2 +/- 1.5 kJ x mol(-1). These values, together with the enthalpies of isodesmic and isogyric gas-phase reactions predicted by density functional theory (B3PW91/aug-cc-pVDZ, MPW1PW91/aug-cc-pVDZ, and MPW1PW91/aug-cc-pVTZ) and the CBS-QMPW1 methods, were used to derive the enthalpies of formation of the gaseous 2-, 3-, and 4-carboxyphenoxyl radicals as (2-HOOCC(6)H(4)O(*), g) = -322.5 +/- 3.0 kJ.mol(-1) Delta(f)(3-HOOCC(6)H(4)O(*), g) = -310.0 +/- 3.0 kJ x mol(-1), and Delta(f)(4-HOOCC(6)H(4)O(*), g) = -318.2 +/- 3.0 kJ x mol(-1). The O-H bond dissociation enthalpies in 2-OHBA, 3-OHBA, and 4-OHBA were 392.8 +/- 3.3, 383.6 +/- 3.8, and 380.0 +/- 3.4 kJ x mol(-1), respectively. Finally, by using the ortho-para method, it was found that the H- - -O intramolecular hydrogen bond in the 2-carboxyphenoxyl radical is 25.7 kJ x mol(-1), which is ca. 6-9 kJ x mol(-1) above the one estimated in its parent (2-OHBA), viz. 20.2 kJ x mol(-1) (theoretical) or 17.1 +/- 2.1 kJ x mol(-1) (experimental).     

tert-Butylphosphonic acid: from the bulk to the gas phase

The structure of tert-butylphosphonic acid in the solid, in solution, and in the gas phase was studied by single-crystal X-ray diffraction, (1)H and (31)P NMR spectroscopic studies in solution, solid-state (31)P NMR spectroscopy, and electrospray ionization mass spectrometry. In addition, density functional theory (DFT) calculations at the B3LYP/6-31G*, B3LYP/6-31+G*, and B3LYP/6-311+G* level of theory for a large number of H-bonded aggregates of the type (tBuPO(3)H(2))(n) (C(n), P(n); n=1-7) support the experimental work. Crystallization of tBuPO(3)H(2) from polar solvents such as CH(3)CN or THF gives the H-bonded one-dimensional polymer 2, whereas crystallization from the less polar solvent CDCl(3) favors the formation of the H-bonded cluster (tBuPO(3)H(2))(6).CDCl(3) (1). In CDCl(3) the hexamer (tBuPO(3)H(2))(6) (C(6)) is replaced by smaller aggregates down to the monomer with decreasing concentration. DFT calculations and natural bond orbital (NBO) analyses for the clusters C(1)-C(7) and the linear arrays P(1)-P(7) reveal the hexamer C(6) to be the energetically favored structure resulting from cooperative strengthening of the hydrogen bonds in the H-bonded framework. However, the average hydrogen bond strengths calculated for C(6) and P(2) do not differ significantly (42-43 kJ mol(-1)). The average distances r(O.O), r(Obond;H), r(Pdbond;O), and r(Pbond;OH) in C(1)-C(7) and P(1)-P(7) are closely related to the hydrogen bond strength. Electrospray ionization mass spectrometry shows the presence of different anionic species of the type [(tBuPO(3)H(2))(n)-H](-) (A(1)-A(7), n=1-7) depending on the instrumental conditions. DFT calculations at the B3LYP/6-31G* level of theory were carried out for A(1)-A(6). We suggest the dimer [(tBuPO(3)H(2))(2)-H](-) (A(2)) and the trimer [(tBuPO(3)H(2))(3)-H](-) (A(3)) are the energetically favored anionic structures. A hydrogen bond energy of approximately 83 kJ mol(-1) was calculated for A(2). Electrospray ionization mass spectrometry is not suitable to study the assembling process of neutral H-bonded tert-butylphosphonic acid since the removal of a proton from the neutral aggregates has a large influence on the hydrogen bond strength and the cluster structure.