EGF受体配基N2S2-Quinazoline的合成

以6-硝基喹唑啉酮为原料,经过氯化亚砜氯化,间碘苯胺连接,氯化亚锡还原,制得6-氨基-4-[(3-碘苯基)氨基]-喹唑啉,再与氯乙酰氯反应,二硫二氮缩合连接,最后与醋酸汞硫化氢反应脱巯基保护基得到标记前体N-[[4-(3-碘苯基)氨基]-喹唑啉-6-基]-2-[N-(2-巯基乙基)-N-[[N-(2-巯基乙基)氨基]甲酰甲基]]乙酰胺,主要产物得到核磁和质谱表征,总收率2.5%。     

Preparation and evaluation of nano-crystalline titania as sorbent for 99Mo/99mTc generator

In the presented work, nano-crystalline titania (TiO₂) was synthesized and evaluated as a novel chromatographic sorbent for the preparation of the medical ⁹⁹Mo/^99mTc generator. TiO₂ was synthesized by dissolving TiCl₄.6H₂O with isopropyl alcohol to form a semisolid mass that was extensively dried and washed. The physicochemical parameters and surface area of the synthesized nano-crystalline TiO₂ were evaluated. TiO₂ was packed as a chromatographic column to study the sorption of ⁹⁹Mo-polymolybdate (VI) anionic solution by dynamic equilibrium. The maximum sorption capacity of ⁹⁹Mo was ~141±2mg Mo/g TiO₂, thereby confirming its suitability for using low specific activity ⁹⁹Mo for the preparation of ⁹⁹Mo/^99mTc generator. The elution performance of the prepared ⁹⁹Mo/^99mTc generator based on Ti-⁹⁹Mo was evaluated. It showed high radiochemical purity (≥ 97% TcO₄^?), high radionuclidic purity (≥ 99.99%^99mTc) and high chemical purity; all of these specifications show the suitability for use in nuclear medicine applications.     

Novel porphyrazines containing peripherally functionalized macrocyclic (N2O2, N2S2) units: Synthesis and characterization

Novel maleonitrile moieties were synthesized by cyclization of 2,3-bis[(2-pyridylmethyl)amino]-2(Z)-butene-1,4-dinitrile with 1,2-bis(2-iodoethoxy)-4-nitrobenzene or o-xylyenebis(1-chloro-3-thiapropane) under conditions of high dilution. A series of novel, free-base, magnesium and zinc porphyrazines bearing macrocyclic substituents in peripheral positions were prepared via Linstead macrocyclization reactions of different maleonitrile derivatives, 12-nitro-4,7-bis(pyridin-2-ylmethyl)-2,3,4,7,8,9-hexahydro-1,10,4,7-benzodioxa-diaza-cyclododecine-5,6-dicarbonitrile or 5,8-bis(pyridin-2-ylmethyl)-1,3,4,5,8,9,10,12-octa-hydro-2,11,5,8-benzodi-thiadiazacyclo-tetradecine-6,7-dicarbonitrile and the corresponding divalent metal salts. Pentanuclear copper(II) complexes were also prepared from the corresponding zinc(II) porphyrazine derivatives. The compounds were characterized by a combination of elemental analysis, FT-IR, UV–vis, ¹H NMR, ¹³C NMR and MS spectral data.     

Synthesis and Evaluation of Bombesin Analogues Conjugated to Two Different Triazolyl‐Derived Chelators for 99mTc Labeling

Overexpression of the gastrin‐releasing peptide receptor (GRPR) in a variety of human carcinomas has provided a means of diagnosis and treatment. Previously we reported a metabolically stable (N^αHis)Ac‐βAla‐βAla‐[Cha¹³,Nle¹⁴]BBS(7–14) analogue with high affinity for the GRPR. We have also shown that the biodistribution pattern of this fairly lipophilic, radiolabeled peptide can be enhanced by glycation, which is easily carried out by Cu^I‐catalyzed cycloaddition. Herein, we further elaborate this “click approach” in the synthesis of a new series of triazole‐based chelating systems as alternatives to the (N^αHis)Ac chelator for labeling with the ^99mTc(CO)₃ core. The bombesin analogues, containing these new chelating systems, were evaluated with regard to their synthesis and in vitro and in vivo properties, and were compared with their (N^αHis)Ac counterparts. The influence of the chelator on biodistribution properties was less than that of glycation, which clearly improved the tumor‐to‐background ratios.     

N2,N2,N6,N6-四乙基-4-醛基吡啶-2,6-二甲酰胺的合成

以2,6-二甲基吡啶为原料,经KMnO4氧化、二乙胺酰胺化、吡啶环自由基亲核取代反应得到N2,N2,N6,N6-四乙基-4-羟甲基吡啶-2,6-二甲酰胺,然后用Sarret试剂氧化得到标题化合物并探讨了氧化反应的最佳条件,产物结构经1HNMR、IR和MS得到表征.该产物是合成新型吡啶类有机配体的重要中间体.     

氮气气氛下铁铝尖晶石的合成

烧结法合成铁铝尖晶石需要控制适当的气氛,以保证氧化亚铁(FeO)处在其稳定存在温度与氧分压条件下.以往通过对不同氧分压下Fe2O3-Al2O3相图以及1 500℃时FeO-Fe2O3-Al2O3三元系统等温截面图的分析,说明氧分压越低越有利于铁铝尖晶石的合成,而且Fe3O4与FeAl2O4的固溶度随着氧分压降低以及铁铝...     

N2·9-二乙酰基鸟嘌呤的合成

对N2*9-二乙酰基鸟嘌呤合成反应的动力学关系式的进行分析,得出影响反应的因素为反应温度、反应时间、溶剂用量和乙酰试剂用量.V(乙酸)∶V(乙酐)=2∶1;反应温度为135 ℃;反应时间为7.5 h,N2·9-二乙酰基鸟嘌呤的收率达到96%,用红外光谱,核磁共振,元素分析以及质谱对所得产品结构进行了分析,证明所得产物即为目标产物.     

N2·9-二乙酰基鸟嘌呤的合成

介绍了用N,N-二甲基吡啶(DMAP)为催化剂合成N2@9-二乙酰基鸟嘌呤的新方法,并对催化剂及其他因素的影响进行了研究.方法操作简便,反应时间短,产品收率达76%.     

Separation of Carrier-Free 99mTc from 99Mo and 144Pr from 144Ce over a Column of Zirconium Arsenate

Abstract

Carrier-free ^99mTc and ¹⁴⁴Pr activities were separated from ⁹⁹Mo and ¹⁴⁴Ce, respectively, by using simple chemical procedures and a column of zirconium arsenate. A crystalline variety of zirconium arsenate was prepared by mixing a proportionate quantity of sodium arsenate solution in water with a solution of zirconium oxychloride in 2N HCl at 70°C. The ratio of zirconium:arsenate was 1:2. γ-Ray spectra of the separated ^99mTc, and β-decay studies of ¹⁴⁴Pr showed that both were of high radionuclidic purity. The overall separation processes were simple, clean, and in each case required less than half an hour, with quantitative yield. After separation, the daughter activities were allowed to form in the column, so that it was possible to obtain these freshly formed species by eluting the column with suitable reagents.     

Induction of DNA-double-strand breaks by auger electrons from 99mTc complexes with DNA-binding ligands

The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including 111In, 125I, and 123I, to induce DNA double-strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for 99mTc, which, besides the well-known gamma radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster-Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic 99mTcI-tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X-ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1 x 10(6) M(-1), while the analogous complex with anthraquinone interacts with DNA in a groove-binding mode and has an affinity value of K=8.9 x 10(4) M(-1). We showed with phiX174 double-stranded DNA that the corresponding 99mTc complexes induce a significant amount of dsb, whereas non-DNA-binding [TcO4]- and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter 99mTc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with 99mTc complexes.