Synthesis of poly(alkyl aryl ether) dendrimers

Poly(alkyl aryl ether) dendrimers of up to four generations composed of a phloroglucinol core, branching components, and pentamethylene spacers are synthesized by a divergent growth methodology. A repetitive synthetic sequence of phenolic O-alkylation and O-benzyl deprotection reactions are adopted for the synthesis of these dendrimers. The peripheries of the dendrimers contain 6, 12, 24, and 48 phenolic hydroxyl groups, either in the protected or unprotected form, for the first, second, third, and fourth generations, respectively. Because of the presence of hydrophilic exterior and relatively hydrophobic interior regions, alkaline aqueous solutions of these dendrimers are able to solubilize an otherwise insoluble pyrene molecule and these supramolecular complexes precipitate upon neutralization of the aqueous solutions.     

Synthesis and characterization of poly(ethyleneimine) dendrimers

Poly(ethyleneimine) (PEI) dendrimers up to the third generation (G3) were prepared by a divergent synthesis method from an ethylenediamine (EDA) core. The amine terminals were bonded with vinylbromide by a Michael addition reaction. Then, the bromide terminals were converted to amine groups using a Gabriel amine synthesis method. PEI dendrimers displayed pH-dependent luminescence, and their emission intensities at pH 6 increased over time. Fluorescence intensities also increased with increasing dendrimer generation from G1 to G3. Air-bubbling in aqueous solutions of dendrimers made to incorporate detectable amount of oxygen in dendrimers. EDA also behaved similarly in luminescence and oxygen incorporation.

Synthesis and pharmacokinetic study of poly(ethylene oxide) triazole dendrimers decorated with aminosteroids as anticancer agent

The use of new aminosteroids has shown increased therapeutic efficiency on multiple cancer cell lines. Those molecules are, however, highly hydrophobic, leading to bad pharmacokinetic properties. Dendrimers are excellent candidates to improve PK, especially for absorption and distribution, since their structure can be designed to be water-soluble. We have the capacity to tailor the particle's size to allow high-loading capacity. In this article, we managed to enhance aqueous solubility of the aminosteroid AH-38 by grafting on three generations of poly(ethylene oxide) triazole dendrimers to reach high drug loading values (w/w %). In vitro and in vivo studies were conducted and showed interesting results, such as increased plasma concentration of the free aminosteroid with G1 and G2 nanocarriers over the AH-38 administrated as a free drug. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020 , 58, 654–661     

Synthesis of carbohydrate‐linked poly(polyoxometalate) poly(amido)amine dendrimers

Mannose‐functionalized and ethoxyethanol‐functionalized poly(amido)amine dendrimers bound multiple vanadate‐substituted polyoxotungstate Wells–Dawson‐type polyoxometalates (POMs). Dendrimers incorporating 10–30 POMs were characterized with NMR, transmission electron microscopy, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry techniques. The number of metal clusters per dendrimer molecule varied according to the dendrimer generation and the nature of the surface functional groups. Efforts aimed at using the poly(polyoxometalate) dendrimers as oxidation catalysts are also described. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3059–3066, 2005     

Synthesis and characterization of fluorescent poly(aromatic amide) dendrimers

The synthesis of a series of poly(aromatic amide) dendrimers up to the second generation is described herein. The AB(2) building block used throughout the synthesis of the dendrimers was the allyl ester of 3,5-diaminocinnamic acid, which has been synthesized from 3,5-dinitrobenzoic acid in good yield with use of a four-step procedure. Dendron synthesis was achieved via a convergent approach with use of a sequence of deprotection/coupling steps. Two commercially available alcohols, L-menthol and citronellol, were coupled to the AB(2) monomer by using an alkyl diacid spacer and two core units; 1,7-diaminoheptane and tris(2-aminoethyl)amine have been used to produce the final dendrimers. Characterization was carried out by NMR and IR spectroscopies, MALDI-TOF mass spectrometry, GPC, and DSC. The novel monomer and dendritic derivatives exhibited a strong fluorescence emission in the visible region (lambda approximately 500 nm) of the spectrum and a weak emission in the near-infrared (lambda approximately 850 nm) upon excitation in the near-UV region. The fluorescence emission characteristics were found to be solvent and dendrimer generation dependent.     

Synthesis of large generation poly(propyl ether imine) (PETIM) dendrimers

Large generation poly(propyl ether imine) (PETIM) dendrimers are synthesized in iterative synthetic cycles of two reductions and two Michael addition reactions. Dendrimers up to sixth generation, containing up to 128 peripheral functionalities, are synthesized. Growth of the PETIM dendrimers, possessing a tertiary amine as the branch juncture and an ether as the linker component, is assessed systematically by routine spectroscopic methods. The peripheries of these dendrimers possess either alcohols, amines, carboxylic acids, esters, or nitriles, thereby opening up possibilities for varied studies involving PETIM dendrimers.     

Synthesis of new poly(ethylene glycol)-block-poly(ester sulfide) dendrimers

The design and synthesis of novel copolymers that consist of a linear polyoxyethylene block and a dendrimeric poly(ester-sulfide) block with potential applications in drug delivery are described. The dendrimers bear hydroxyl or acrylate functional groups and were prepared via a divergent approach using readily available methoxypoly(ethylene glycol) (mPEG), acryloyl chloride, and 1-thioglycerol as building blocks. All reactions involved occurred efficiently and purification steps consisted of washing the reaction mixture with aqueous solutions and precipitation of the product in diethyl ether.     

Water-soluble poly(aryl ether) dendrimers as a potential fluorescent detergent to form micelles at very low CMC

The self-assembly of amphiphilic pyrene-cored poly(aryl ether) dendrimers has been studied. Pyrene excimer emission at 500 nm from the higher generation 6 is observed in KOH aqueous solution at the concentration as low as 1.8 × 10⁻⁵ M, while the excimer emission from lower generation 5 could not be detected at 3.5 × 10⁻⁵ M. The results indicate that the self-aggregation in higher generation dendrimer takes place more efficiently than in lower generation in aqueous solution.     

Synthesis of new soluble dendrimers on poly(ethylene glycole) sublayer

Russian Journal of Organic Chemistry - A rational method of synthesis was developed for new soluble dendrimers on poly(ethylene glycole) sublayer with a high density of functional groups applying...     

Conformational and vibrational study of platinum(II) anticancer drugs: cis-diamminedichloro-platinum(II) as a case study

A conformational and vibrational analysis of cisplatin [cis-diamminedichloro-platinum(II)] (cDDP) is reported. Several theory methods (from Hartree-Fock to Moller-Plesset and density functional theory) combined with different all-electron basis sets are evaluated, in view of determining the best suited strategy for accurately representing this molecule. This choice is based on the best compromise between accuracy and computational requirements. Different scaling models of the cDDP vibrational modes were tested for obtaining the best scaling factors to be used in this type of inorganic systems. The structural parameters and vibrational results predicted by the calculations are compared with the corresponding experimental data, namely, x-ray structure, and Raman and inelastic neutron scattering spectra. Finally, a complete assignment of the cDDP vibrational spectra is presented.     

Synthesis and reactivity profiles of phosphinated poly(alkyl aryl ether) dendrimers

Poly(alkyl aryl ether) dendrimers were utilized to synthesize a series of new triphenylphosphine functionalized dendrimers. Zero, first, second and third generation dendrimers, carrying 3, 6, 12 and 24 triphenylphosphine units, were prepared and characterized. The new triphenylphosphine containing dendrimers were assessed for their reactivity profiles and in this instance, the dendrimers were used as reagents to mediate Mitsunobu etherification reaction between phenol and various primary, secondary and benzylic alcohols. In addition, dendritic poly-phenols were also tested in an O-benzylation reaction. A monomeric methoxy group attached triphenylphosphine acted as a control for comparison of reactivity profiles of dendrimers. It was observed that the etherification reaction was mediated efficiently by the dendritic reagent, and in addition, the dendritic phosphine oxide reagents could be recovered quantitatively by precipitation methods. The recovered dendritic phosphine oxides were reduced subsequently to the corresponding phosphines and used as reagents for the Mitsunobu reaction, repetitively.     

Use of effective core potential calculations for the conformational and vibrational study of platinum(II) anticancer drugs. cis-Diamminedichloroplatinum(II) as a case study

In the light of the recognized anticancer properties of cisplatin-type inorganic systems, the exact knowledge of their conformational preferences is of the utmost importance for understanding their biological activity. The present study reports the use of theoretical (quantum mechanical) calculations for achieving this goal. An alternative calculation method to the use of the AE basis sets, both accurate and computationally feasible, was presently tested for the conformational and vibrational study of cis-diamminedichloroplatinum(II). Effective core potentials (ECPs) were used, within the HF methodology and, within the B3LYP and mPW1PW DFT protocols. The DFT methods (particularly mPW1PW) were found to be the best choice for describing cDDP (as compared to the HF methodology).     

Synthesis of poly(amino)ester dendrimers via active cyanomethyl ester intermediates

A novel strategy for the synthesis of poly(amino)ester dendrimers was developed on the basis of active cyanomethyl ester intermediates and an iteration of four consecutive steps of deprotection, activation, transesterification, and scavenging.     

Thermodynamics of hard poly(phenylene-pyridyl) dendrimers

The temperature dependences of heat capacity C ^○ _p = f(T) of hard poly(phenylene-pyridyl) dendrimers of the first and the second generations based on 1,3,5-triethynylbenzene were studied over the temperature range from 7–180 to 455–470 K for the first time. Over the range 290–350 K, the relaxation transition supposedly caused by sample devitrification was detected and characterized for the dendrimer of the first generation. The experimental results were used to calculate the standard thermodynamic functions, namely, heat capacity, enthalpy, entropy, and change in the Gibbs energy on heating. The standard entropy of formation of the compounds under study was determined at T = 298.15 K. The qualitative and quantitative dependences of the thermodynamic properties of the poly(phenylene-pyridyl) dendrimers on their composition and structure were revealed by comparison of the determined parameters with similar data for the earlier studied dendrimers of this series.     

水溶性超支化共聚(酯-胺)的分子设计及合成

超支化聚酯是超支化聚合物中的一大类 [1～ 4 ] ,由于酯结构能在自然环境下降解 ,因而引起了许多研究者的兴趣 .Hult[1,5] ,Voit[6 ,7] 和 Kricheldorf等 [8] 在合成超支化聚酯方面做出了卓有成效的贡献 .他们用带羧基和羟基的 AB2 型单体在催化剂作用下缩合反应制得超支化聚酯 ;或先将羟基保护起来 ,再把羧基酰氯化 ,得到带酰氯的 AB2 型单体 ,经进一步缩聚得到超支化聚酯 .但用这种传统方法合成的超支化聚酯一般不溶于水 ,因而在某些领域的应用受到了限制 .本文提出了一种合成水溶性超支化聚酯的新策略 ,超支化聚酯并不是用酸与醇直接…     

Cationic poly(amidoamine) dendrimers as additives for capillary electroseparation and detection of proteins

We examine the influence of cationic poly(amidoamine) (PAMAM) dendrimers on capillary electroseparation–UV analysis of proteins. PAMAMs adsorbing to the capillary surface suppressed the wall‐adsorption of proteins; meanwhile, PAMAMs added to the buffer exhibited selectivity toward proteins. Presence of 3×10^?4 g/mL PAMAM generation one (G 1.0) in 30 mM phosphate, at pH 2.6, rendered significant enhancement in separation efficiency; the merged peaks of myoglobin and trypsin inhibitor were separated. Moreover, the protein–dendrimer interactions changed the inherent UV absorbance profiles of proteins. UV–Vis study showed that the absorbance of cytochrome C and transferrin increased at the detection wavelength of 214 nm; their detection sensitivity enhanced by 2.44 and 2.01‐folds, respectively, with addition of 5×10^?4 g/mL PAMAM G 1.0.     

Synthesis of new bicarbazole-linked triazoles as non-cytotoxic reactive oxygen species (ROS) inhibitors

Abstract

Carbazole analogs 3 and 4 and a new library of bicarbazole-linked triazoles 6–11 were prepared via new synthetic methodology. Metal-catalyzed oxidative coupling reaction was utilized for the synthesis of bicarbazole acetylene 4 and different metals (Zn⁺², Co⁺², Fe⁺³, Ni⁺², Cu⁺², Mn⁺²) as catalyst were screened. Only Fe-catalyzed reaction was found to be excellent and gave homocoupled product 4. Cu-catalyzed 1,3-dipolar cycloaddition was also utilized to install triazole moiety for the synthesis of hybrid molecules 6–11. Based on reported anti-inflammatory activity of carbazole and triazole scaffolds, all compounds were screened for their reactive oxygen species (ROS) inhibitory potential. Results from these studies revealed triazole 9 as most active compound (IC₅₀ value of 7.6?±?0.1?µg/mL on human whole blood and 2.7?±?0.09?µg/mL on isolated neutrophils) using ibuprofen as a standard. Therefore, class described herein can serve as attractive structural element for further studies on ROS inhibition.     

Synthesis and catalytic activities of Pd-phosphine complexes modified poly(ether imine) dendrimers

In this paper, we report synthesis of new alkyldiphenyl phosphine ligand modified poly(ether imine) dendrimers up to the third generation. The phosphinated dendrimers were obtained by functional group transformations of the alcohols present at the periphery of the dendrimers to chloride, followed by phosphination using LiPPh₂. The modification at the peripheries of the dendrimers was performed successfully to obtain up to 16 alkyl diphenylphosphines in the case of a third generation dendrimer, in good yields for each individual step. After phosphination, dendritic ligands were complexed with Pd(COD)Cl₂ to give dendritic phosphine-Pd^II complexes. Both the ligands and the metal complexes were characterized by spectroscopic and spectrometric techniques including high-resolution mass spectral analysis for the lower generations. Evaluation of the catalytic efficacies of the dendrimer-Pd^II metal complexes in mediating a prototypical C-C bond forming reaction, namely the Heck reaction, was performed using various olefin substrates. While the substrate conversion lowered with catalyst in the order from monomer to third generation dendrimer, the second and third generation dendrimers themselves were found to exhibit significantly better catalytic activities than the monomer and the first generation dendrimer.     

Synthesis and properties of new thiourea-functionalized poly(propylene imine) dendrimers and their role as hosts for urea functionalized guests

Five generations of poly(propylene imine) dendrimers have been modified by palmityl and adamantyl endgroups via a thiourea linkage. The synthesis of the thiourea dendrimers DAB-dendr-(NHCSNHAd)(n) and DAB-dendr-(NHCSNHC(16)H(33))(n) (n = 4, 8, 16, 32, 64) proceeds smoothly via the amino-terminated DAB dendrimer and the adamantyl and palmityl isothiocyanates, respectively. The properties of the thiourea dendrimers have been studied by IR and (1)H NMR, including relaxation (T1, T2) measurements. The thiourea dendrimers are used as multivalent hosts for a number of guest molecules containing a terminal urea-glycine unit in organic solvents. The host-guest interactions have been investigated using 1D- and NOESY-NMR. These investigations show that the guest molecules bind to the dendritic host via thiourea (host)-urea (guest) hydrogen bonding, and ionic bonding between the terminal guest carboxylate moiety and the outer shell tertiary amines of the dendrimer. The ability to bind guest molecules of the adamantyl- and palmitylthiourea dendrimers has been compared with their respective urea containing dendrimer analogues, by NMR-titration, and competition experiments. Upon complexation, the thiourea dendrimer hosts show a larger downfield NH shift than the corresponding urea dendrimer hosts, indicative of stronger hydrogen bonding in the complexed state. Furthermore, microcalorimetry has been used to determine binding constants for formation of the host-guest complexes; the binding constants are typically in the order of 10(4) M(-1). Both NMR and microcalorimetric studies show that the thiourea dendrimers bind the urea containing guests with somewhat higher affinity than the corresponding urea dendrimers.