Highlight on the Mechanism of Linear Polyamidoamine Degradation in Water

This paper aims at elucidating the degradation mechanism of linear polyamidoamines (PAAs) in water. PAAs are synthesized by the aza-Michael polyaddition of prim-monoamines or bis-sec-amines with bisacrylamides. Many PAAs are water-soluble and warrant potential for biotechnological applications and as flame-retardants. PAAs have long been known to degrade in water at pH 65 7, but their degradation mechanism was never explored in detail. Filling this gap was necessary to assess the suitability of PAAs for the above applications. To this aim, a small library of nine PAAs was expressly synthesized and their degradation mechanism in aqueous solution studied by 1H-NMR in different conditions of pH and temperature. The main degradation mechanism was in all cases the retro-aza-Michael reaction triggered by dilution but, in some cases, hints were detected of concurrent hydrolytic degradation. Most PAAs were stable at pH 4.0; all degraded at pH 7.0 and 9.0. Initially, the degradation rate was faster at pH 9.0 than at pH 7.0, but the percent degradation after 97 days was mostly lower. In most cases, at pH 7.0 the degradation followed first order kinetics. The degradation rates mainly depended on the basicity of the amine monomers. More basic amines acted as better leaving groups

Sericin-based resins from silk degumming wastewater for the removal of heavy metal ions from water

Chromium (VI) is a water pollutant categorized as \u2018likely to be a carcinogen to humans\u2019 compound when orally ingested with estimated cancer potency 0.5 mg/kg/day. The European Directive 2001/59/EC poses a 5 \ub5g/L threshold concentration for Cr(VI) in groundwaters. In this work, a chemical process was devised to obtain heavy metal ion absorbing resins by the polyaddition of bisacrylamides and 1,2-diaminoethane with sericin using as reaction solvent raw waste-water from silk degumming processes. Silk sericin (SS) is a natural globural protein deriving from silk worm Bombyx mori with molecular weight ranging from 10000 to 300000. Following the alkaline degumming process, sericin is degraded to peptides with molecular weight 20000. These peptides contain lysine-deriving residues that participate in the polyaddition leaving to a resin. This resin is a hybrid one in which a substantial portion is constituted by sericin peptides. The rationale of this approach is that the guanidinum ion has the ability to strongly bind oxoanions, due to its geometrical Y-shaped, planar orientation, optimizing charge distribution and hydrogen bonds [1]. SS resins were evaluated for the removal of both positively charged (Cu2+, Co2+, Ni2+, Mn2+) and negatively charged heavy metals oxoanions (CrO42-) from water. Different resins were obtained containing different amounts of sericin. These resins were characterized by elemental analysis and their structure confirmed by FT-IR/ATR spectroscopy. The swelling capacity of the new absorbents in different media and their thermal stability by DSC and TGA techniques were evaluated. The removal properties of resins towards Cu2+, Co2+, Ni2+, Mn2+ and CrO42- ions in aqueous single metal dilute and concentrate solutions were performed in batch absorption experiments and evaluated by EDTA titration in the case of Cu2+, Co2+, Ni2+, Mn2+, and by the UV-VIS spectroscopy in the case of CrO42-. The products showed different absorption capacities depending on the SS content in the resin. Treatment with 0.1 M HCl showed excellent regeneration with maintenance of the resins absorption capacity for 20 regeneration cycles. In conclusion, sericin-based resins, besides being biocompatible, were endowed with environmental friendly preparation process; biodegradability; moderate cost; ability to fast and quantitatively absorb from aqueous solutions even at low pollutant concentration; full reversibility of the absorption process making it economically convenient both for regeneration and metal recovery

Superior flame retardancy of cotton by synergetic effect of cellulose-derived nano-graphene oxide carbon dots and disulphide-containing polyamidoamines

Linear polyamidoamines containing disulphide groups (SS-PAAs) were prepared by polyaddition of L-cystine with 2,2-bisacrylamidoacetic acid (B-CYSS), N,N\u2032-methylenebisacrylamide (M-CYSS) and 1,4-bisacryloylpiperazine (BP-CYSS). They were evaluated as flame retardants for cotton, alone or with cellulose-derived nano-graphene oxide (nGO) carbon dots, to assess whether, due to their potential as radical scavengers, the latter would improve the already good performance of SS-PAAs. In vertical flame spread tests (VFST), cotton treated with 1% nGO burned as quickly as cotton, whereas B-CYSS, M-CYSS and BP-CYSS extinguished the flame at add-ons 65 12, 16 and 20%, respectively. Probably, the gaseous products of SS-PAA thermal degradation quenched the radicals involved in oxidation. Cotton treated with 8, 12 and 15%, respectively, of B-CYSS, M-CYSS and BP-CYSS burned completely, but further addition of 1% nGO either inhibited ignition or shortly extinguished the flame, demonstrating synergism between the two components. Synergism was confirmed by assessing the synergism effectiveness parameter for the residual mass fraction (RMF) and by comparing the calculated and experimental TG curves in air for the cotton/SS-PAA-nGO systems. In cone calorimetry tests, the presence of nGO did not improve the already good performances of SS-PAAs, supporting the hypothesis that the action of both takes place in the gas phase

Poly(amidoamine)-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System

A new poly(amidoamine)-cholesterol (PAA-cholesterol) conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step

pH-Dependent Chiral Recognition of D- and L-Arginine Derived Polyamidoamino Acids by Self-assembled Sodium Deoxycholate

D- and L-arginine-based polyamidoamino acids, called D- and L-ARGO7, retain the chirality and acid/base properties of the parent -amino acids and show pH-dependent self-structuring in water. The ability of the ARGO7 chiral isomers to selectively interact with chiral biomolecules and/or surfaces was studied by choosing sodium deoxycholate (NaDC) as a model chiral biomolecule for its ability to self-assembly into globular micelles, showing enantio-selectivity. To this purpose, mixtures of NaDC with D-, L- or D,L-ARGO7, respectively, in water were analysed by circular dichroism (CD) spectroscopy and small-angle neutron scattering (SANS) at different levels of acidity expressed in terms of pD and concentrations. Differences in the CD spectra indicated chiral discrimination for NaDC/ARGO7 mixtures in the gel phase (pD 7.30) but not in the solution phase (pD 9.06). SANS measurements confirmed large scale structural perturbation induced by this chiral discrimination in the gel phase yet no modulation of the structure in the solution phase. Together, these techniques shed light on the mechanism by which ARGO7 stereoisomers modify the morphology of NaDC micelles as a function of pH. This work demonstrates chirality-dependent interactions that drive structural evolution and phase behaviour of NaDC, opening the way for designing novel smart drug delivery systems

Cross-linked polyamidoamine/non-woven fibroin fabric composite hydrogels for tissue engineering applications

Cross-linked polyamidoamines (PAAs) absorb large amounts of water and form hydrogels that can be designed to be biocompatible and biodegradable to nontoxic products. PAA hydrogels were tested as substrates for cell culturing and found adhesive toward different cell types [1-3]. However, PAA hydrogels have poor mechanical properties, and can not be fixed to the surrounding tissues by stitching, but only with fibrin glue. PAA composite hydrogels obtained either by adding inorganic fillers [4] or embedding electrospun PLLA mats were previously investigated [5]. In this work, PAA hydrogels were strengthened by embedding non-woven fibroin fabrics. These composite hydrogels were cured by UV-induced radical polymerization of double bond terminated PAA oligomers obtained from N,N-bis(2-hydroxyethyl)ethylenediamine/1,4-bis(acryloyl)piperazine mixtures with 10% and 20% excess, on a molar basis, bisacrylamide. According to a first procedure, pre-synthesized PAA oligomer solutions containing a radical initiator were used to impregnate the non-woven fibroin fabric within a glass mold. Curing was then obtained by irradiating with a UV lamp. A second procedure relied on the impregnation of the non-woven fabric with the monomer mixture, followed by in situ polymerization and finally by UV-induced curing of the reactive oligomer. Best results were obtained with the second procedure. Slightly milky, soft and pliable hydrogels were obtained, which maintained shape and morphology after several swelling - deswelling cycles, owing to the formation of covalent bonds between the PAA matrix and fibroin. For comparison purposes, the same synthetic procedures were applied for the synthesis of fibroin-embedded poly-4-acryloylmorpholine (PACM) hydrogels with different degrees of crosslinking. Swelling-deswelling tests showed that PACM/fibroin hydrogels had poor strength, likely due to the low PACM-fibroin adhesion. The good PAA/fibroin adhesion was ascribed to the establishing of covalent bonds by surface NH2 of fibroin with the bisacrylamide monomers during PAA formation

Cross-linked polyamidoamine/non-woven fibroin fabric composite hydrogels for tissue engineering applications

Cross-linked polyamidoamines (PAAs) absorb large amounts of water and form hydrogels that can be designed to be biocompatible and biodegradable to nontoxic products. PAA hydrogels were tested as substrates for cell culturing and found adhesive toward different cell types [1-3]. However, PAA hydrogels have poor mechanical properties, and can not be fixed to the surrounding tissues by stitching, but only with fibrin glue. PAA composite hydrogels obtained either by adding inorganic fillers [4] or embedding electrospun PLLA mats were previously investigated [5]. In this work, PAA hydrogels were strengthened by embedding non-woven fibroin fabrics. These composite hydrogels were cured by UV-induced radical polymerization of double bond terminated PAA oligomers obtained from N,N-bis(2-hydroxyethyl)ethylenediamine/1,4-bis(acryloyl)piperazine mixtures with 10% and 20% excess, on a molar basis, bisacrylamide. According to a first procedure, pre-synthesized PAA oligomer solutions containing a radical initiator were used to impregnate the non-woven fibroin fabric within a glass mold. Curing was then obtained by irradiating with a UV lamp. A second procedure relied on the impregnation of the non-woven fabric with the monomer mixture, followed by in situ polymerization and finally by UV-induced curing of the reactive oligomer. Best results were obtained with the second procedure. Slightly milky, soft and pliable hydrogels were obtained, which maintained shape and morphology after several swelling - deswelling cycles, owing to the formation of covalent bonds between the PAA matrix and fibroin. For comparison purposes, the same synthetic procedures were applied for the synthesis of fibroin-embedded poly-4-acryloylmorpholine (PACM) hydrogels with different degrees of crosslinking. Swelling-deswelling tests showed that PACM/fibroin hydrogels had poor strength, likely due to the low PACM-fibroin adhesion. The good PAA/fibroin adhesion was ascribed to the establishing of covalent bonds by surface NH2 of fibroin with the bisacrylamide monomers during PAA formation

Extra-small gold nanospheres decorated with a thiol-functionalized biodegradable and biocompatible linear polyamidoamine as nanovectors of anticancer molecules

Gold nanoparticles are elective candidate for cancer therapy. Current efforts are devoted to developing innovative methods for their synthesis. Besides, understanding their interaction with cells have become increasingly important for their clinical application. This work aims to describe a simple approach for the synthesis of extra-small gold nanoparticles for breast cancer therapy. In brief, a biocompatible and biodegradable polyamidoamine (named AGMA1-SH), bearing 20%, on a molar basis, thiol-functionalized repeat units, is employed to stabilize and coat extra-small gold nanospheres of different sizes (2.5, 3.5, and 5 nm in gold core), and to generate a nanoplatform for the link with Trastuzumab monoclonal antibody for HER2-positive breast cancer targeting. Dynamic light scattering, transmission electron microscopy, ultraviolet visible spectroscopy, X-ray powder diffraction, circular dichroism, protein quantification assays are used for the characterization. The targeting properties of the nanosystems are explored to achieve enhanced and selective uptake of AGMA1-SH-gold nanoparticles by in vitro studies against HER-2 overexpressing cells, SKBR-3 and compared to HER-2 low expressing cells, MCF-7, and normal fibroblast cell line, NIH-3T3. In vitro physicochemical characterization demonstrates that gold nanoparticles modified with AGMA1-SH are more stable in aqueous solution than the unmodified ones. Additionally, the greater gold nanoparticles size (5-nm) is associated with a higher stability and conjugation efficiency with Trastuzumab, which retains its folding and anticancer activity after the conjugation. In particular, the larger Trastuzumab functionalized nanoparticles displays the highest efficacy (via the pro-apoptotic protein increase, anti-apoptotic components decrease, survival-proliferation pathways downregulation) and internalization (via the activation of the classical clathrin-mediated endocytosis) in HER-2 overexpressing SKBR-3 cells, without eliciting significant effects on the other cell lines. The use of biocompatible AGMA1-SH for producing covalently stabilized gold nanoparticles to achieve selective targeting, cytotoxicity and uptake is completely novel, offering an important advancement for developing new anticancer conjugated-gold nanoparticles

SYNTHESIS OF MONO-, DI-, AND POLYNITROXIDES. CLASSIFICATION OF ESRSPECTRA OF FLEXIBLE DINITROXIDES DISSOLVED IN LIQUIDS AND GLASSES

The synthesis of flexible biradical strain-gauges which could be anchored onto two sites of a deformable biological structure had been attempted. Qualitative relationships between the possible conformations of the biradicals and the observed ESR spectra provide guidelines for further synthetic work. Some of the nitroxides synthesized and characterized are: R-CO-R{sub 1}-N-(CH{sub 2}){sub n}-R{sub 2}-N-CO-R, where R is 1-oxyl-2,2,6,6-tetramethyl pyrroline bonded at the 3-position, n = 2,3 and R{sub 1,2} = -H; -C{sub 18}{sub 37}; -CH{sub 2}COOH; -CH{sub 2}COOC{sub 2}H{sub 5}; -CH{sub 2}CONH(CH{sub 2}){sub 2}N(CH{sub 3}){sub 2}; -CH{sub 2}CONH(CH{sub 2}){sub 2}N{sup +}(CH{sub 3}) -CH{sub 2}CO-imidazolide

Molecular weight-controlled synthesis of polyamidoamines

Polyamidoamines (PAAs) are biocompatibile and biodegradable synthetic polymers obtained by Michael-type stepwise polyaddition of prim- or sec-amines to bisacrylamides. They can be used, for instance, as drug and protein intracellular carriers, transfection promoters, antiviral and antimalarial agents. The PAA synthesis is simple and environment friendly, but leads to highly polydisperse products. A process leading to monodisperse PAAs would be much welcome. The first attempts to synthesize a controlled molecular weight PAA by polyaddition of 2-methylpiperazine (2-MeP) with 1,4-bisacryloylpiperazine (BP) failed. Amino-functionalized polystyrene resins were used as solid supports for the controlled synthesis of a typical PAA by polyaddition of 2-MeP with BP. Bisacryloylcystine (BaCy) was covalently attached to the resin by reaction with of its amine groups. 2-MeP was then added, followed by BP. The double 2-MeP/BP addition was repeated three more times performing all steps at rt in water for 24 h. After each step the resin was exhaustively washed with water. Finally, a large excess of mercaptoethanol in water was added to cleave the BaCy disulphide bond and recover the product. However, the oligomer was not obtained, since the steric hindrance and hydrophobicity of the support biased the first addition steps and, possibly, the cleavage reaction. Then, a soluble support (bis-imidazolyl polyethyleneglycol MW 8000) was used and reacted with excess cystamine (NH2-Cyst-NH2). After each single step, the product was purified by ultrafiltration. The double-addition step was repeated three times, then N,N-dimethylacrylamide (DMA) was added to end-cap the residual amine terminals. The product was purified by ultrafiltration. The disulphide bond of the cystamine moiety connecting BP-2MeP to PEG was then reductively cleaved with excess 2-mercaptoethanol, the exhausted matrix separated by ultrafiltration through a membrane with cut-off 5000, a further amount of DMA added to the passed-through solution, which was then ultrafiltered through a membrane with cut-off 1000. The expected oligomer was recovered by lyophilizing the retained fraction. The NMR spectrum was consistent with the expected structure. MALDI-TOF analysis revealed an average MW 1945 (expected 2138) with polydispersity index 1.01, thus demonstrating that the PAA controlled synthesis is feasible