Amedea Manfredi

Polyamidoamine hydrogels prepared by the radical post-polymerization of α,ω-bisacrylamide-terminated M-AGM oligomers, in turn obtained by the polyaddition of 4-aminobutylguanidine with N,N’-methylenebisacrylamide, were reinforced with raw silk fibers, which can establish covalent bonds with the polyamidoamine matrix via reaction of the amine groups in the lysine residues with the acrylamide terminals of the M-AGM oligomer. Silk/M-AGM membranes were prepared by impregnating silk mats with M-AGM aqueous solutions and subsequent crosslinking by UV irradiation. The guanidine pendants of the M-AGM units imparted the ability to form strong but reversible interactions with oxyanions, including the highly toxic chromate ions. The potential of the silk/M-AGM membranes to purify Cr(VI)-contaminated water down to the drinkability level, that is, below 50 ppb, was tested by performing sorption experiments both in static (Cr(VI) concentration 20–2.5 ppm) and flow conditions (Cr(VI) concentration 10–1 ppm). After static sorption experiments, the Cr(VI)-loaded silk/M-AGM membranes could easily be regenerated via treatment with a 1 M sodium hydroxide solution. Dynamic tests performed using two stacked membranes and a 1 ppm Cr(VI) aqueous solution reduced Cr(VI) concentration down to 4 ppb. Remarkably, the use of renewable sources, the environmentally friendly preparation process, and the goal achieved meet eco-design requirements.

A novel polyamidoamine (M-PCASS) bearing a disulfide group and two phosphonate groups per repeat unit was obtained by reacting N,N′-methylenebisacrylamide with a purposely designed bis-sec-amine monomer, namely, tetraethyl(((disulfanediylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethane-2,1-diyl))bis(phosphonate) (PCASS). The aim was to ascertain whether the introduction of phosphonate groups, well-known for inducing cotton charring in the repeat unit of a disulfide-containing PAA, increased its already remarkable flame retardant efficacy for cotton. The performance of M-PCASS was evaluated by different combustion tests, choosing M-CYSS, a polyamidoamine containing a disulfide group but no phosphonate groups, as a benchmark. In horizontal flame spread tests (HFSTs), M-PCASS was a more effective flame retardant than M-CYSS at lower add-ons with no afterglow. In vertical flame spread tests, the only effect was afterglow suppression with no self-extinguishment even at add-ons higher than in HFSTs. In oxygen-consumption cone calorimetry tests, M-PCASS decreased the heat release rate peak of cotton by 16%, the CO₂ emission by 50%, and the smoke release by 83%, leaving a 10% residue to be compared with a negligible residue for untreated cotton. Overall, the set of results obtained envisage that the newly synthesized phosphonate-containing PAA M-PCASS may be suitable for specific applications as flame retardant, where smoke suppression or reduction of total gas released is a key requirement.

Linear amphoteric polyamidoamines (PAAs) are usually water-soluble, biodegradable and biocompatible. Crosslinked PAAs form in water hydrogels, retaining most of the favorable properties of their linear counterparts. The hydrogels prepared by the radical post-polymerization of the oligo-α,ω-bisacrylamido-terminated PAA called AGMA1, obtained by the polyaddition of 4-aminobutylguanidine (agmatine) with 2,2-bis(acrylamido)acetic acid, exhibit excellent cell-adhesion properties both in vitro and in vivo. However, due to their low mechanical strength, AGMA1 hydrogels cannot be sewn to biological tissues and need to be reinforced with fibrous materials. In this work, short silk fibers gave excellent results in this sense, proving capable of establishing covalent bonds with the PAA matrix, thanks to their lysine content, which provided amino groups capable of reacting with the terminal acrylamide groups of the AGMA1 precursor in the final crosslinking phase. Morphological analyses demonstrated that the AGMA1 matrix was intimately interconnected and adherent to the silk fibers, with neither visible holes nor empty volumes. The silk/H-AGMA1 composites were still reversibly swellable in water. In the swollen state, they could be sewn and showed no detachment between fibers and matrix and exhibited significantly improved mechanical properties compared with the plain hydrogels, particularly as regards their Young’s modulus and elongation at break.

The aza-Michael polyaddition of L-arginine and N,N′-methylene-bis-acrylamide gives the biocompatible and easily cell-internalized polyamidoamine ARGO7. By controlled synthesis, two ARGO7 oligomers, namely a trimer and a pentamer, bearing acrylamide terminal units, were obtained as precursors of the β-cyclodextrin-end-terminated oligomers P3 and P5, which have been shown to encapsulate curcumin at both pH 7.4 and 4.5. After lyophilization, P3- and P5-curcumin complexes gave stable water solutions. The apparent solubility of encapsulated curcumin was in the range 20–51 μg mL⁻¹, that is, three orders of magnitude higher than the water solubility of free curcumin (0.011 μg mL⁻¹). The drug release profiles showed induction periods both at pH levels 4.5 and 7.4, suggesting a diffusive release mechanism, as confirmed by kinetic studies. The release rate of curcumin was higher at pH 7.4 than at pH 4.5 and, in both cases, it was higher for the P5 complex. Encapsulated curcumin was more photostable than the free drug. Molecular mechanics and molecular dynamics simulations explain at atomistic level the formation of aggregates due to favorable van der Waals interactions. The drug molecules interact with the external surface of carriers or form inclusion complexes with the β-cyclodextrin cavities. The aggregate stability is higher at pH 4.5.

A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV–Vis and NMR spectroscopies. The pK_a values of the ionizable groups of the repeat unit were estimated by potentiometric titration, using a purposely synthesized molecular ligand (Agly-EDDS) mimicking the structure of the BAC-EDDS repeat unit. Dynamic light scattering (DLS) and ζ-potential analyses revealed the propensity of BAC-EDDS to form stable nanoaggregates with a diameter of approximately 150 nm at pH 5 and a net negative charge at physiological pH, in line with an isoelectric point r₁) and transverse (r₂) relaxivities as a function of the externally applied static magnetic field were investigated and compared to the ones of commercial contrast agents. Furthermore, a model derived from the Solomon–Bloembergen–Morgan theory for the field dependence of the NMR relaxivity curves was applied and allowed us to evaluate the rotational correlation time of the complex (τ = 0.66 ns). This relatively high value is due to the dimensions of Gd-BAC-EDDS, and the associated rotational motion causes a peak in the longitudinal relaxivity at ca. 75 MHz, which is close to the frequencies used in clinics. The good performances of Gd-BAC-EDDS as a contrast agent were also confirmed through in vitro magnetic resonance imaging experiments with a 0.2 T magnetic field.

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 have potential for biotechnological applications and as flame-retardants. PAAs have long been known to degrade in water at pH ≥ 7, but their degradation mechanism has never been 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.

This paper reports on synthesis, acid–base properties, and self-structuring in water of a chiral polyamidoamino acid, M-l-Gln, obtained from the polyaddition of N,N′-methylenebisacrylamide with l-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-l-Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents. The NMR diffusion studies were consistent with a population of unimolecular nanoparticles thus excluding aggregation. The M-l-Gln had the highest molecular weight and hydrodynamic radius among all polyamidoamino acids described. Possibly, transient hydrogen bonds between l-glutamine molecules and M-l-Gln growing chains facilitated the polyaddition reaction. Theoretical modeling showed that M-l-Gln assumed pH-dependent self-ordered coil conformations with main chain transoid arrangements reminiscent of the protein hairpin motif owing to intramolecular dipole moments and hydrogen bonds. The latter were most numerous at the isoelectric point (pH 4.5), where they mainly involved even topologically distant main chain amide N–H and side chain amide C=O brought to proximity by structuring. Hydrogen bonds at pH 4.5 were also suggested by variable temperature NMR. The 2D NOESY experiments at pH 4.5 confirmed the formation of compact structures through the analysis of the main chain/side chain hydrogen contacts, in line with MD simulations.

Polyamidoamino acids (PAACs) are synthetic polymers prepared by the polyaddition of bisacrylamides with natural α-amino acids, which in the process maintain both their chirality and their amphoteric nature. This polymerization process is slow, but has the merits of taking place in water and of neither involving protection/de-protection steps nor releasing by-products. However, it leads to polydisperse polymers and, using α-amino acids mixtures, random copolymers. This paper presents a step-by-step polyaddition process leading to homo- and copolymeric PAACs with controlled sequences and controlled molecular weights. It exploits the much different rates of the two Michael addition steps of NH₂ of α-amino acids with acrylamides, and the low solubility in organic solvents of the α-amino acid addition products. As a proof of principle, the controlled synthesis of the PAAC from l-arginine and N,N′-methylenebisacrylamide was performed up to a monodisperse product with 11 monomeric units and molecular weight 1840. This synthetic procedure was also tested with l-alanine. All intermediates were isolated and characterized. Noticeably, all of them were α,ω-difunctionalized with either acrylamides or sec-amines and were, in fact, building blocks with potential for preparing complex macromolecular architectures. In a first instance, copolymers with controlled sequences of amidoamine- and amidoamino acid units were prepared.