Lorella Izzo

Modulating antimicrobial activity by synthesis: dendritic copolymers based on nonquaternized 2-(dimethylamino)ethyl methacrylate by Cu-mediated ATRP.

The synthesis of novel star-like heteroarms polymers A(BC)(n) containing m-PEG (block A), methylmethacrylate (MMA), and nonquaternized 2-(dimethylamino)ethyl methacrylate (DMAEMA) (blocks BC) is here reported. We demonstrated that copolymer films with comparable amounts of DMAEMA have antimicrobial properties strongly depending on the topological structure (i.e., the number of arms) of the composing copolymers. We interpret the highest antimicrobial activity of A(BC)(2) with respect to A(BC)(4) and linear copolymers (respectively, A(BC)(2) ≥ A(BC)(4) > A(BC)) as probably due to the formation of strong hydrogen bonds between close amino-ammonium groups in the A(BC)(2) film. Strong hydrogen bonds seem to be somewhat disfavored in the case of the linear species by the difference in both polymer architecture and film morphology compared with the A(BC)(2) and A(BC)(4) architectures.

The Role of Charge Density and Hydrophobicity on the Biocidal Properties of Self-Protonable Polymeric Materials

Intrinsic antimicrobial thermoplastic A(BC)n copolymers (n = 1, 2, 4), where A was poly(ethylene glycol) (PEG), BC was a random chain of methylmethacrylate (MMA), and alkyl-aminoethyl methacrylate (AAEMA), were synthesized and the antimicrobial activity and hemolyticity were evaluated on plaques obtained by casting as a function of the architecture, the N-substituent groups of the AAEMAs (methyl, ethyl, isopropyl, and tert-butyl groups) and the hydrophobic/charge density balance. Antimicrobial effectiveness and efficiency is controlled by the surface charge density and by the influence of N-alkyl groups on the surface morphology. Also interestingly, it is the absence of hemolitytic activity in all copolymers. In presence of Escherichia coli, the A(BC)2 copolymer with 40% of N-methyl groups is the most efficient, killing 91% of the bacteria already after 1.5 h.

Low molecular mass model compounds of alternating ethylene-styrene copolymers

The stereochemistry of alternating ethylene-styrene copolymers has been investigated by comparison of their NMR spectra with those of purposely synthesised model compounds. The results seem to confirm the isotactic structure of the stereoregular copolymers prepared in the presence of a variety of catalytic systems.

Dicopper(II) MozobilTM: a dinuclear receptor for the pyrophosphate anion in aqueous solution

Abstract In this work, we investigated the dicopper(II) complex of MozobilTM as a potential receptor for anions in MeOH and MeOH/water mixture. The results were compared with those obtained for the mononuclear complex, copper(II) benzyl-cyclam as a model system. Experimental investigations were also supported by computational studies on both the dinuclear and the mononuclear species. Among the investigated anionic guests, the dicopper complex showed an outstanding affinity for the pyrophosphate anion, leading to the formation of a stable adduct in MeOH solution. Our computational studies strongly suggested a 2:2 stoichiometry for the adduct. At least in MeOH, this dimeric structure, with two pyrophosphate anions sandwiched between two dicopper MozobilTM units, is stabilized by H-bonding interactions between the receptor and pyrophosphate. In MeOH:water mixture, beside the strong competition of solvent, the affinity toward the anion was preserved. We exploited this property to develop a novel indicator displacement assay (IDA) for pyrophosphate in aqueous solution, using Pyrocatechol Violet (PV) as the indicator.

pH-sensitive polymersomes: controlling swelling via copolymer structure and chemical composition

Abstract pH-sensitive vesicles used as drug delivery systems (DDSs) are generally composed of protonable copolymers. The disaggregation of these nanoparticles (NPs) during drug release implies the dispersion of positively charged cytotoxic polyelectrolytes in the human body. To alleviate such issue, we synthesised A(BC)n amphiphilic block copolymers with linear (n = 1) and branched (n = 2) architectures to obtain pH-sensitive vesicles capable of releasing drugs in acidic conditions via controlled swelling instead of disaggregation. We obtained this feature by fine-tuning the relative amount of pH-sensitive and hydrophobic monomers. We studied pH-driven swelling by measuring NPs size in neutral and acidic conditions, the latter typical of tumours or inflamed tissues (pH∼6) and lysosomes (pH∼4.5). Dynamic light scattering (DLS) and zeta potential data provided useful indications about the influence of architecture and chemical composition on NPs swelling, stability and polycation release. Results demonstrated that vesicles made of linear copolymers with ∼22–28% in mol of protonable monomers in the ‘BC’ block swelled more than other species following a pH change from pH 7.4 to pH 4.5. We finally evaluated the cytotoxicity of vesicles composed of linear species, and paclitaxel (PTX) release from the latter in both cancer and normal cells.

Effect of Molecular Architecture on Physical Properties of Tree-Shaped and Star-Shaped Poly(Methyl Methacrylate)-Based Copolymers

The synthesis of star-like A(B)n copolymers based on the hydrophilic poly(ethylene glycol) monomethyl ether (m-PEG, block A) and the hydrophobic poly(methyl methacrylate) (PMMA, blocks B) is reported. We obtained copolymers made of one m-PEG chain and 2 or 4 PMMA blocks using a combined “arm first”—“core first” approach. Such structures were called tree-shaped copolymers where the m-PEG was considered as the trunk and PMMA arms as the branches. Star-like copolymers (B)nA-A(B)n built by two tree-shaped fragments with a poly(propylene oxide) (PPO) as the central junction, were also synthesized according to a previously reported procedure. The latter were called star-shaped structures and the synthesis was performed to obtain architectures different from the tree-shaped one but characterized by a similar length of the PMMA arms. Microstructural analysis was carried out through 1H-NMR and GPC, and the thermal and transport properties (sorption and diffusion) to liquid water were investigated and correlated to the molecular architecture of the two classes of copolymers.

Impact of intermolecular drug-copolymer interactions on size and drug release kinetics from pH-responsive polymersomes

Abstract pH-sensitive polymersomes are produced from amphiphilic copolymers of the type mPEG-b-(PMMA-ran-PDMAEMA) obtained via ATRP, so that mPEG with molecular masses of 2k and 5kDa forms the corona of a hydrophobic double layer with 22–28% molar content in protonable DMAEMA. Vesicles obtained via dialysis were loaded with curcumin, 2-naphthole, paclitaxel (PTX) and ampicillin sodium salt, and the release kinetics of the latter studied via UV-vis spectrometry as a function of pH. Overall, the release profiles clearly indicated a dopant-sensitive kinetics and, likely, mechanism depending on molecule-copolymer interactions. Infrared spectrometry highlighted the formation of hydrogen bonds and salt bridges that may be responsible for these findings; support for the formation of the latter are obtained comparing the IR spectrum for ampicillin doped-vesicles with the anharmonic vibrational transition of model salt bridges. Importantly, DLS data indicated that our vesicles appeared to remain stable even at pH 4.4 after 48 h and completely releasing ampicillin. The release profiles of co-loaded curcumin/PTX with ampicillin also suggest that desorption rates of water-soluble species can be modulated by the presence of hydrophobic molecules in the double layer, at least at pH 7.4 and 6.4.