Binding properties of polyamidoamine dendrimers

Dendrimers are globular, hyperbranched polymers possessing a high concentration of surface functional groups and internal cavities. These unique features make them good host molecules for small ligands. To reveal relationships between dendrimer size and its encapsulating properties, the interactions of the fourth and the sixth generations of polyamidoamine dendrimers (PAMAM G4 and PAMAM G6) with a fluorescent dye 1‐anilinonaphthalene‐8‐sulfonate (ANS) were studied. Because ANS is a fluorescent molecule and its fluorescence is very sensitive to changes in its microenvironment, it was possible to use spectrofluorometric methods to evaluate the interactions with dendrimers. A double fluorometric titration method was used to estimate a binding constant and the number of binding centers. There were two types of dendrimer binding centers characterized by different affinity towards ANS. For PAMAM G4, the values of K_b and n for low‐affinity and high‐affinity sites equaled to 2.6 × 10⁵, 0.60 and 3.70 × 10⁶, 0.34, respectively, whereas in the case of PAMAM G6, these values equaled to 1.2 × 10⁵, 76.34 and 1.38 × 10⁶, 22.73. It was observed that the size of the dendrimer had a strong impact on the number of ANS molecules that interacted with dendrimers and their location within the macromolecule. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2036–2040, 2007     

Proteolysis of Peptide Dendrimers

Happy tree‐like friends . Using trypsin and α‐chymotrypsin cleavage sites as models, we show that the protease reactivity of peptide dendrimers, such as the structure illustrated in the figure, can be controlled by the degree of branching. Such a control provides a novel possibility to tune the biological properties of peptide dendrimers, and should be generally useful for their employment as functional biomolecule analogues, for example, in drug delivery applications.

     

树枝状大分子用于药物载体的研究进展

树枝状大分子是近年来出现的一类新型合成纳米高分子,具有可控的三维高度支化结构、表面分布着大量的功能基团和单分散等特点,使其在生物医学等领域中日益受到广泛关注。作为一种新型非生物载体,树枝状大分子内部空腔和表面功能基团均可与药物复合,在药物输送和基因转运等方面具有广阔的应用前景。     

Poly(amidoamine), polypropylenimine, and related dendrimers and dendrons possessing different 1 → 2 branching motifs: An overview of the divergent procedures

This review presents an overview of 1 → 2 branched dendrimers and dendrons, created by a divergent procedure, from their synthesis to modern day applications. The first members of this branched class of fractal macromolecules were prepared through a cascade synthesis, which was later replaced by the iterative divergent synthetic approach. Most classes of this 1 → 2 N-, Aryl-, C-, Si-, and P-branched families are included and catalogued by their mode of connectivity. Dendritic macromolecules have had significant impact in the field of material sciences and are one of the major starting points for nanotechnology as a result of the numerous modifications that can be conducted, either on the surface or within their molecular infrastructure, thus taking advantage of their unimolecular micelle properties. These host cavities, maintained by the dendritic branches, allow for the incorporation of nanoparticles as well as metal particles, which make these attractive in catalysis and imaging studies. The solubility of these fractal constructs can be tailored depending on their surface modifications. Highly water-soluble, neutral dendrimers appended with, grown from, or acting as hosts to specific molecules give rise to a wide variety of biomedical applications such as drug delivery systems and MRI imaging agents. The inherent supramolecular or supramacromolecular chemistry has been exploited but the design and construction of uniquely tailored macrostructures have just begun. Laser dyes, as well as electron and energy donor and acceptor functionality, have also been paired with these fractal constructs in order to probe their uses in the field of molecular electronics. With their synthetic control, seemingly limitless modifications and wide variety of potential applications, as well as their now commercial availability, these 1 → 2 branched dendrimers have become an important nanostructured tools for diverse utilitarian applications. This review mainly covers 1 → 2 branched non-chiral dendrimers prepared by a divergent process but selected chiral surfaces are considered as well as metal encapsulation and a few hyperbranched routes to related imperfect dendrimers.     

Highlights in Coupled Electrochemical Flow Cell-Mass Spectrometry,EC/MS

Probing electrochemical processes by mass spectrometry (EC/MS) is a developing field that benefits from the unmatched identification power of mass spectrometry and from the rapid transfer of electrochemical cell products to the mass spectrometer. Most of the current EC/MS efforts are directed towards the development of differential electrochemical mass spectrometry (DEMS) using the electro-ionization source for identification of volatile compounds, and towards the application of electrospray mass spectrometers for determination of semivolatile and nonvolatile products. The challenges in coupling mass spectrometry and electrochemistry are described, and different approaches to using the coupled system for diverse applications are reviewed, with emphasis on electrospray mass spectrometry. Reaction mechanism studies, diagnostic applications, and activity imaging of electrodes are demonstrated based on approaches that were devised in our laboratory.     

Thermo- and pH-sensitive dendrimer derivatives with a shell of poly(N,N-dimethylaminoethyl methacrylate) and study of their controlled drug release behavior

Novel dendrimer derivatives combining the temperature- and pH-sensitivities are synthesized. At first, polyamidoamine (PAMAM) dendrimers with generations 1-5 are synthesized by the reaction of ethylenediamine with methyl acrylate, and then the dendrimers are acylated by chloroacetyl chloride to obtain PAMAM-Cl, which can act as a macroinitiator for further synthesizing functional dendrimers. For fulfilling this goal, the polymers consisting of a dendritic PAMAM core and poly(N,N-dimethylaminoethyl methacrylate) (PDMA) shell are synthesized by atom transfer radical polymerization (ATRP). Their macromolecular structures are characterized by FTIR, ¹H NMR, DSC and particle size analyses, and their aqueous solutions are inspected by UV spectroscopy for understanding their thermo- and pH-sensitivities. The results show that novel dendrimer derivatives exhibit clearly thermo- and pH-respondings in accordance with the change of the environment. Using chlorambucil (CLB) as a model drug, the behaviors of the controlled drug release from polymers with different average graft length of PDMA are studied. The results indicate that the rate of the drug release can be effectively controlled by the pH value.     

Dynamics in complex systems: Dendrimer-polymer blends in electric and mechanical fields

An investigation was carried out on the molecular dynamics of blends composed of poly(amidoamine) (PAMAM) dendrimers with ethylenediamine core and amino surface groups (generations 0 and 3) and three linear polymers: poly(propylene oxide) - PPO and two block copolymers, poly(propylene oxide)/poly(ethylene oxide) - PPO/PEO with different mole ratios: 29/6 (amorphous) and 10/31 (crystalline). The results were generated over a broad range of frequency and temperature by Dielectric Relaxation Spectroscopy (DRS) and Dynamic Mechanical Spectroscopy (DMS). Dielectric spectra of dendrimers in the PPO matrix reveal a decrease in the time scale of normal and segmental relaxation with increasing dendrimer concentration. In the amorphous blends with 29PPO/6PEO matrix, no effect of concentration on the time scale of normal and segmental processes was observed. But in the crystalline blends with 10PPO/31PEO matrix, relaxation time increases with increasing dendrimer concentration. Results acquired by DRS and DMS were contrasted and the obtained relaxation times were found to be in excellent agreement. A detailed analysis of the effect of generation and concentration of dendrimers, hydrophilicity and morphology of the polymer matrix and temperature on the molecular origin, the shape of the relaxation spectra, the dielectric relaxation strength and the frequency location for the maximum loss in dendrimer-polymer blends is provided.     

聚氧乙烯链封端的聚酰胺-胺树状聚合物的合成与表征

采用酰氯法,用丙烯酰氯和不同相对分子质量的聚乙二醇为原料,制备出一系列具有丙烯酰端基的聚氧乙烯大单体(PEO-A)。实验证明,较佳的原料摩尔比n(PEG)∶n(CH2CHCOCl)∶n〔(CH3CH2)3N〕=2∶1∶1。然后以聚氧乙烯大单体为端基改性剂,在氮气保护下50℃四氢呋喃溶液中分别与G1.0～G4.0聚酰胺-胺树状聚合物进行Michael加成反应96h,合成出了聚氧乙烯(PEO)链封端的非离子型聚酰胺-胺树状聚合物,并用傅立叶变换红外光谱(FTIR)、核磁共振波谱(1HNMR,13CNMR)对其组成和结构进行了表征。     

聚氧乙烯链封端的聚酰胺-胺树状聚合物的性质与应用

研究了聚氧乙烯链封端的非离子型聚酰胺-胺树状聚合物的热稳定性以及在造纸助留和催化剂载体上的应用。结果表明,该类树状聚合物具有较好的热稳定性,温度低于300℃无明显热分解行为,最大的热分解温度均为400℃。助留性能测试表明,M4.0G与P44复配双元助留体系(摩尔比1∶23.22),造纸助留率为89.2%,比空白造纸助留率分别提高了18.3%。纸样的物理机械特性:撕裂指数、撕裂强度、耐破指数、耐破强度和抗张指数比空白纸样分别提高了8.6%、1.5%、35.5%、29.6%和4.3%。TEM测试表明:以聚氧乙烯大单体(PEO-A)链封端的聚酰胺-胺树状聚合物样品封装的钯金属纳米粒子单分散性较好,粒径分布在0.75～2.4nm。     

Poly(amidoamine) Dendrimers as Nanocarriers for 5-Fluorouracil: Effectiveness of Complex Formation and Cytotoxicity Studies

Two generations of positively charged poly(amidoamine) dendrimers (PAMAMs) were selected for study as potential carriers for the anticancer drug 5-fluorouracil (5FU), a drug primarily used in the treatment of colorectal cancer. Analytical techniques, such as UV-Vis spectrophotometry, NMR Spectroscopy and Laser Doppler Velocimetry (LDV), have shown that the most critical factor determining the formation of a PAMAM–5FU complex is the starting components’ protonation degree. The tests confirmed the system’s ability to attach about 20 5FU molecules per one dendrimer molecule for the G4PAMAM dendrimer and about 25 molecules for the G6PAMAM dendrimer, which gives a system yield of 16% for the fourth generation and 5% for sixth generation dendrimers. Additionally, using the QCM-D method, the adsorption efficiency and the number of drug molecules immobilized in the dendrimer structure were determined. A new aspect in our study was the determination of the change in zeta potential (ζ) induced by the immobilization of 5FU molecules on the dendrimer’s outer shell and the importance of this effect in the direct contact of the carrier with cells. Cytotoxicity tests (resazurin reduction and MTS tests) showed no toxicity of dendrimers against mouse fibroblast cells (L929) and a significant decrease in cell viability in the case of four human malignant cell lines: malignant melanoma (A375), glioblastoma (SNB-19), prostate cancer (Du-145) and colon adenocarcinoma (HT-29) during incubation with PAMAM–5FU complexes. The purpose of our work was to investigate the correlation between the physicochemical properties of the carrier and active substance and the system efficiency and optimizing conditions for the formation of an efficient system based on PAMAM dendrimers as nanocarriers for 5-fluorouracil. An additional aspect was to identify potential application properties of the complexes, as demonstrated by cytotoxicity tests.     

树形高分子增强的高分子磁性颗粒的制备与表征

利用化学共沉淀法制备Fe3O4磁性纳米粒子;悬浮聚合的方法制备带有酰胺基的聚苯乙烯-丙烯酰胺磁性颗粒(NMP);发散法制备聚酰胺胺树形高分子(PAMAM)并与酰胺修饰聚苯乙烯磁性颗粒结合,得到树形高分子增强的磁性微粒。并对NMP和PAMAM-NMP的颗粒基质晶体结构、饱和磁化强度、表面官能团和微观结构以及各元素的百分含量进行表征。结果显示,Fe3O4磁核晶形完整,平均粒径为9 nm;PAMAM-NMP的红外图谱在3478 cm-1和3 300 cm-1处有吸收峰,证明存在胺基;经PAMAM增强后氮元素百分含量由0.225%增加到0.992%,证明PAMAM为NMP提供了更多的活性基团;在有无磁场存在时的沉淀时间分别为16 h和2112 h,证明PAMAM-NMP有良好的磁响应性和悬浮性。     

聚酰胺-胺的合成及在水处理中的应用

聚酰胺-胺(PAMAM)树枝状大分子作为一类三维的、分子尺寸和构型高度可控的高分子聚合物,因其具有无毒高效、易于修饰等优点,已在工业水处理领域引起了广泛的关注。本文介绍了PAMAM的主要合成路线及工艺优缺点,综述了近年来PAMAM及其改性衍生物在工业水处理中应用研究进展,分析其作用机理及影响因素,最后对未来的研究方向作以展望。     

Polymers with platinum drugs and other macromolecular metal complexes for cancer treatment

Metal-based anticancer drugs, in particular platinum-drugs, have been investigated for the treatment of cancer for the last 40 years. A small set of platinum-based drugs have meanwhile received FDA approval for the treatment of various cancer. Cisplatin and its relatives are currently one of the most widely used anticancer drugs. The use is however associated with significant side effects and rising drug resistance. To combat these problems, drug delivery carriers have been developed to increase the protection of the drug and increase efficacy. Metal-based drugs represent a rather unique drug delivery challenge. Most anticancer drugs are either physically encapsulated into a polymer matrix or they can be conjugated to the polymer via a degradable linker. While both pathways are possible for metal-based drugs, the conjugation to the polymer can be carried via labile or permanent ligands. In addition, the prodrug strategy using the drug in the higher oxidation state is a common approach that has been widely tested for platinum drug. The delivery of platinum drugs is now a mature field and the various conjugation techniques have been combined with a range of drug carriers including dendrimers, micelles and solid polymer nanoparticles. Hybrids of macromolecular metal complexes with inorganic nanoparticles have been tested in recent years to combine the ability to deliver the drug with imaging properties. An emerging trend is the surface decoration of the polymeric nanoparticles with targeting ligands such as folates. The advanced state of this field is evident by the fact that some macromolecular platinum drugs even advanced to the clinic. While the delivery of platinum drugs has been well explored, the delivery of other metal-based drugs based on gold, ruthenium or cobalt is still in their infancy.     

Studies on the complexation between generation‐4.5 methyl ester‐terminated poly(amidoamine) dendrimer and Pd2+ ions in methanol

Poly(amidoamine) (PAMAM) dendrimers have attracted attention because of their well‐defined molecule structures and chemical versatility, which also complicate the mechanism of interactions between metal ions and PAMAM dendrimers. To further understand the complexation of dendrimers with metal ions, the interactions between Pd²⁺ ions and G4.5‐COOCH₃ PAMAM dendrimers were investigated by UV‐vis and FTIR spectrophotometric method. The results show that the addition of K₂PdCl₄ results in covalent attachment of the PdCl alcoholysis product of this complex to tertiary amines within the dendrimers under the appropriate conditions. This process was also supported by X‐ray photoelectron spectroscopy data of the new complex which indicated a 1 : 3 Pd/Cl ratio. The maximum loading of 80 Pd²⁺ ions within the G4.5‐COOCH₃ dendrimers and the best pH value of 8.3 for complexation system are also obtained. Details regarding the Pd species present in solution of different chemical environments are reported. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

A structure/function study of polyaminoamide dendrimers as silica scale growth inhibitors

Dendrimers have attracted immense attention during the last decade due to their interesting properties both from a basic and an applied research viewpoint. Encapsulation of metal nanoparticles for catalysis, drug delivery and light harvesting are only some applications of dendrimers that are breaking new ground. A novel application of dendrimer technology is described in the present paper that relates to industrial water treatment. Industrial water systems often suffer from undesirable inorganic deposits. These can form either in the bulk or on metallic surfaces, such as heat exchangers or pipelines. Silica (SiO₂) scale formation and deposition is a major problem in high‐silica‐containing cooling waters. Scale prevention rather than removal is highly desired. In this paper, benchtop screening tests on various silica inhibition chemistries are reported, with emphasis on materials with a dendrimeric structure. Specifically, the inhibition properties of commercially available STARBURST^® polyaminoamide (PAMAM) dendrimers generations 0.5, 1, 1.5, 2, and 2.5 are investigated in detail together with other commonly‐used scale inhibitors. Experimental results show that inhibition efficiency largely depends on structural features of PAMAM dendrimers such as generation number and nature of the end groups. PAMAM dendrimers are effective inhibitors of silica scale growth at 40 ppm dosage levels. PAMAM dendrimers also act as silica nucleators, forming SiO₂–PAMAM composites. This occurs because the SiO₂ formed by incomplete inhibition interacts with cationic PAMAM‐1 and ‐2. The general scope of silica formation and inhibition in industrial waters is also discussed. Copyright © 2005 Society of Chemical Industry     

Synthesis of G0 aminopolyol and aminosugar dendrimers,controlled by NMR and MALDI TOF mass spectrometry

Organic compounds designed to serve as stable dendrimer cores were developed. A series of aminosugar and amino polyol containing G0 dendrimers were synthesized. The reaction mixture composition was checked by MALDI TOF mass spectrometry, while that of purified products – by ¹H and ¹³C NMR combined with 2D NMR spectroscopy as well as MALDI TOF MSMS mass spectra. Mass spectrometric fragmentation experiments were performed in positive ion mode in order to determine common fragmentation patterns of [M+H]⁺ ions.     

Novel developments in the multidimensional characterization of segmented copolymers

Controlled radical polymerization (CRP) provides the polymer chemist with the ability to produce tailor-made polymers with controlled molar masses, molar mass distributions, chemical compositions and macromolecular architectures. Segmented copolymers can be synthesized having polymer segments arranged in a linear fashion (linear block copolymers), however, polymer segments can also be attached to pre-synthesized macromolecules or to multifunctional core molecules to produce branched (graft) copolymers, polymer stars or dendrimers. Although there are many ways to control the chain growth and the architecture of the target macromolecules, side reactions cannot be completely avoided. Accordingly, even with CRP, obtained products exhibit chemical composition and topology distributions along with the molar mass distribution.     

A method to crystallize substances that oil out

A new approach to crystallize oily substances is described. The tendency for liquid–liquid phase separation (LLPS) is reduced by decreasing the kinetics of self-association via the formation of an intermediate amorphous network. The path to initial crystal formation followed a sequence of first freeze-drying an emulsion of solute in the solvent system followed by suspending the dried solid in water to obtain a hydrated crystalline form. This new procedure was applied successfully to a pharmaceutical organic substance that was previously isolated only as a viscous oil. Once isolated, crystals of the drug were utilized as seeds to allow the successful transformation of an emulsion of the substance into a suspension of crystalline drug solid thus avoiding the freeze-drying step. The isolated crystalline solid retained its physical and chemical purity at room temperature for at least 3 months.     

Dendrimer‐Based Signal Amplification of Click‐Labelled DNA in Situ

The in vivo incorporation of alkyne‐modified bases into the genome of cells is today the basis for the efficient detection of cell proliferation. Cells are grown in the presence of ethinyl‐dU (EdU), fixed and permeabilised. The incorporated alkynes are then efficiently detected by using azide‐containing fluorophores and the Cu^I‐catalysed alkyne–azide click reaction. For a world in which constant improvement in the sensitivity of a given method is driving diagnostic advancement, we developed azide‐ and alkyne‐modified dendrimers that allow the establishment of sandwich‐type detection assays that show significantly improved signal intensities and signal‐to‐noise ratios far beyond that which is currently possible.