Aromatic Polyamidines Research Articles

Synthesis of Aromatic Polyamidines by the [2+2]-Cycloaddition Reaction

Synthesis of Aromatic Polyamidines by the [2+2]-Cycloaddition Reaction

Synthesis of Aromatic Polyamidines by the [2+2]-Cycloaddition Reaction

Aromatic polyamidines based on 4,4′-diphenylmethane diisocyanate and bisamides have been synthesized and studied. The one-step reaction of bisamides with diazocyanate according to the [2+2]-cycloaddition mechanism includes a concerted process of the formation of two new σ-bonds in the transition state. The formation of polyamidine occurs as a result of decarboxylation, which completes this reaction. Due to the availability of starting compounds, ease of synthesis, good solubility, and high heat resistance and thermal stability of the resulting polymers, there are wide opportunities for producing new materials by conventional industrial processes. Polyamidines have a sufficiently large set of important technological properties, which suggest their greater potential in relation to applied problems. The resulting film materials and glass-reinforced plastics based on polyamidines show high mechanical properties that are not inferior to those of materials made from commercial polyamides and polybenzimidazoles.

Thermal characteristics and physical and mechanical properties of aromatic polyamidines and materials based on them

Aromatic polyamidines were synthesized by polycondensation of equimolecular amounts of bisimidoyl chlorides with diamines in organic solvents. The obtained polymers are dissolved with organic solvents (N, N'-dimethylacetamide, N-methyl-2-pyrrolidone, etc.), and characterized by a large interval between the temperature of plastic deformation and heat resistance, that is a good possibility of processing polyamidine products with new industrial methods.

Synthesis of aromatic polyamidines on the basis of benzoic acid and diisocyanates

Synthesis of aromatic polyamidines on the basis of benzoic acid and diisocyanates

Preparation of aromatic polyamidines and their transformation in polybenzimidazoles

Polymers with amidine groups -NH-C(=NH)- in main chain were synthesized by two different approaches. The first strategy consists in polyaddition of dinitriles and diamines in acidic ionic liquids (ILs) which act as catalyst and sol- vent, while the second approach is based on polycondensation of 4,4!-oxybis(benzoic acid) diamide and diamines in Eaton's reagent (ER). The resulting polyamidines (PADs) with Mw up to 25 000 g/mol possess thermal stability on air up to 288°C, and good solubility in polar organic solvents. Moreover dehydrocyclization of obtained PADs into polybenzimida- zoles (PBIs) under the action of various oxidants was also studied in this work. The crosslinked films based on PBI and poly(amino imide) resin (PAIR) possess high mechanical characteristics. It has been proved that the crosslinked films based on PBI matrix are perspective materials for design the phosphoric acid electrolyte membranes for the medium temperature fuel cells.

Synthesis of aromatic polyamidines in Eaton’s reagent

Aromatic polyamidines are prepared via the polycondensation of dicarboxamides and diamines in Eaton’s reagent. The polymers are investigated by elemental analysis and IR and NMR spectroscopy. Polyamidines are well soluble in concentrated sulfuric acid and concentrated formic acid and in polar organic solvents, and temperatures corresponding to their 10% weight losses are in the range 245–280°C.

Surface properties of polyamidines

Aromatic and aliphatic polyamidines of the common structure –(R 1–N=C(R 2)–NH) n – were investigated by electrokinetic measurements in dependence on the pH value. It could be evidenced, that all polyamidine surfaces show Brønsted basic behaviour. p K A values of the surfaces between 7 and 11 were calculated. Particularly, the aliphatic polyamidines (R 1, R 2=alkyl) has proven to be strongly basic. The surface properties correlate well with the basic behaviour of the polyamidines in solution. Furthermore, the surface charge density of the different solid substances was determined. It was found that in the case of aromatic polyamidines (R 1=aryl) the charge density is dependent on specific interactions of the amidine groups in the solid phase. Especially, in polyformamidines mutual shielding of the amidine groups by hydrogen bonds resulted in reduced charge densities on the surface.

Structural influences on the properties of aromatic polyamidines

AbstractPolyamidines with both nitrogens in the main chain (‐X‐NH‐CR=N‐) were obtained by polycondensation of diamines with different orthoesters. The thermal properties could be tailored by the choice of diamine and orthoester. Quantitative formation of a cyclic trimer could be observed when 2,6‐diamino‐pyridine was converted with triethyl orthoformate. 1H, 13C and 15N NMR spectroscopic investigations in solution and in solid state showed that the configuration of the amidine group was strongly dependent on the residue R. In polyformamidines, strong interactions caused by hydrogen bonds could be evidenced.

Kupffer cell depletion by liposome-delivered drugs: Comparative activity of intracellular clodronate, propamidine, and ethylenediaminetetraacetic acid

Macrophages such as Kupffer cells in the liver are multifunctional cells. They are involved in host defense mechanisms and have a regulatory role in many biomedical processes. Their selective depletion, using liposome-encapsulated drugs, forms a widely accepted approach to studying their functional aspects in vivo. We have compared the Kupffer cell-depleting activities of liposome-encapsulated clodronate, propamidine, and ethylenediaminetetraacetic acid (EDTA) for this purpose. These molecules represent the drug families of bisphosphonates, diamidines (or aromatic polyamidines), and polyaminopolycarboxylic acid-chelating agents, respectively. The Kupffer cell-depleting activity of the liposome-encapsulated antimicrobial drug propamidine exceeded that of clodronate by about a factor of 10. EDTA appeared to be inefficacious for depletion of Kupffer cells in the rat. (Hepatology 1996 May;23(5):1239-43)

Kupffer cell depletion by liposome-delivered drugs: Comparative activity of intracellular clodronate, propamidine, and ethylenediaminetetraacetic acid

Macrophages such as Kupffer cells in the liver are multifunctional cells. They are involved in host defense mechanisms and have a regulatory role in many biomedical processes. Their selective depletion, using liposome-encapsulated drugs, forms a widely accepted approach to studying their functional aspects in vivo. We have compared the Kupffer cell-depleting activities of liposome-encapsulated clodronate, propamidine, and ethylenediaminetetraacetic acid (EDTA) for this purpose. These molecules represent the drug families of bisphosphonates, diamidines (or aromatic polyamidines), and polyaminopolycarboxylic acid-chelating agents, respectively. The Kupffer cell-depleting activity of the liposome-encapsulated antimicrobial drug propamidine exceeded that of clodronate by about a factor of 10. EDTA appeared to be inefficacious for depletion of Kupffer cells in the rat.

High-Performance Liquid Chromatographic Determination of Aromatic Poly-Amidines: Formulatory and Preclinical Applications

Abstract A high-performance liquid chromatographic procedure has been developed for the simultaneous determination of aromatic poly-amidines (with 2, 3 or 4 benzamidine residues or different 2′-halogen substitutions). A Supelcosil LC-18-DB column with UV detection at 261 nm and an eluent consisting of phosphate buffer (200 mM, pH 3)—rnethanol—tetrahydrofuran—triethylamine (75:25:3:0.5, v/v) were employed. The proposed method was found suitable both in cellular biology/pharmacology studies, for the quantification of aromatic poly-amidines in serum and serum containing cell culture medium, as well as in preformulatory studies for the determination of drug release kinetic from delivery systems as in the case of microspheres.

DNA-binding activity and biological effects of aromatic polyamidines

DNA-binding activity and biological effects of aromatic polyamidines

N1-SUBSTITUTED TETRA-BENZAMIDINES - INHIBITION OF DNA-PROTEIN INTERACTIONS AND INVITRO TUMOR-CELL GROWTH

The pharmacological-mediated inhibition of the interaction between regulatory proteins and target DNA sequences could represent a potential experimental strategy to control growth of neoplastic cells, viral DNA replication and biological life cycle of infectious microorganisms. Aromatic polyamidines are powerful inhibitors of DNA-protein interactions, in vitro proliferation of tumor cell lines and in vivo growth of tumorigenic cells xenografted into nude mice. In order to obtain more detailed information on structure-activity relationships, we have analysed the effects of different aromatic polyamidines on the binding of a recombinant protein, the Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA-1) to the DNA target sequence of EBV, containing the 12 bp palindromic consensus TAGCATATGCTA sequence. The results obtained suggest that aromatic polyamidines differentially inhibit the interactions between DNA-binding proteins and target DNA sequences, leading to differential effects on tumor cell growth.

Liposome mediated delivery of retinoids and aromatic polyamidines: Effects on growth of tumor cell lines

This paper describes the increase of antiproliferative activity toward tumor cell lines of liposome-delivered retinoids and aromatic polyamidines.

Tumor Cell Growth Inhibition by Liposome-Encapsulated Aromatic Polyamidines

Apart from its antiproteinase activity, the aromatic polyamidine TAPP-Br [the bromo derivative of 1,3-di-(p-amidinophenoxy)-2,2-bis-(p-amidinophenoxymethyl)propane (TAPP-H)] is able to inhibit the in vitro growth of a variety of tumor cell lines, including human melanoma, and breast and kidney carcinoma. We have now shown that TAPP-Br can efficiently be encapsulated into egg phosphatidylcholine vesicles. When incorporated into these liposomes, the inhibitory effect of TAPP-Br is significantly enhanced compared with that of the free drug. Based on these promising results, a proposal is made for the delivery of this antiproliferative agent to tumor cells by using liposomes as the vehicle.

Induction of murine erythroleukemia cell differentiation by proteinases is inhibited by aromatic poly-amidines

The effects of the tetra benzamidine serine-proteinase inhibitor 1,3-di-(p-amidinophenoxy) -2,2- bis- (p-amidinophenoxymethyl)propane (TAPP-H) and related compounds, including halo-derivatives, were determined on the erythroid differentiation of murine erythroleukemic cells induced by trypsin and kallikrein. These aromatic poly-amidines and their halo derivatives were found to be strong inhibitors of both trypsin and kallikrein mediated induction of commitment of MEL cells to erythroid differentiation, hemoglobin synthesis and accumulation, globin mRNA production. No inhibitory effects were detected by treating proteinase-induced MEL cells with benzamidine. Only slight inhibitory activity was found after treatment of trypsin-induced MEL cells with other antiproteinase compounds widely used in the control of proteinase-dependent functions, including leupeptin, antipain and Bowman-Birk proteinase inhibitor. MEL cells induced to erythroid differentiation by proteinases could be proposed as an experimental system to test the biological activity of proteinase inhibitors.

Inhibition of 'in vitro' tumor cell growth by aromatic polyamidines exhibiting antiproteinase activity.

Aromatic polyamidines containing two, three or four benzamidine residues inhibit proteinase activity and proliferation of different human tumor cell lines, including leukemic (K562, HEL), melanoma (Colo 38) and B-lymphoid (WI-L2) cell lines. In addition, the benzamidine derivatives analysed in the present study inhibit cell growth of the Chinese hamster FHO6T1-1 cell line, obtained after transfection of primary lung cells with the activated human T24-Ha-ras-1 oncogene. After treatment of FHO6T1-1 cells with benzamidine derivatives, a sharp decrease of the content of Ha-ras-1 mRNA was found, but not of transferrin receptor mRNA. We found that inhibition of cell proliferation by tetra-benzamidine derivatives is not restricted to tumor cells, but concerns also non-tumorigenic cell lines as well as normal primary fibroblasts. Therefore, our analysis was extended to di- and tri-benzamidine derivatives, which could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors. The data obtained demonstrate that these latter compounds and their halo-derivatives also exhibit strong antiproliferative effects on in vitro cultured cells.

Direct synthesis of new aromatic polyamidines from aromatic diamines and benzoic acids by using poly(trimethylsilylphosphate)

Autopolycondensation. Influence de la concentration du monomere sur la viscosite du polymere