Massimo Benaglia

Poly(glycidyl methacrylate): a highly versatile polymeric building block for post-polymerization modifications

The treatment of poly(glycidyl methacrylate) with nucleophilic agents yielded new linear homo/co-polymers. The materials obtained have different physicochemical properties depending upon the nucleophiles utilized and thus, by this way, water soluble polymers are easily accessible. This approach is also very convenient for the synthesis of amphiphilic block copolymers. Additional chemical modifications can further transform the obtained polymers after the post-polymerization treatment. Starting from RAFT pre-synthesized/pre-functionalized polymers, the described procedures allow us to obtain a wide variety of chemically diverse materials characterized by controlled structure and specific functions.

3,5-Di-tert-butylthiobenzoyltriphenylsilane: A versatile spin trapping agent

Abstract 3,5-Di-tert-butylthiobenzoyltriphenylsilane (DBTBTPS) has been synthesized and tested as a spin trapping agent for electron spin resonance studies. Upon reaction with a variety of radicals of different nature inside the cavity of the ESR spectrometer, DBTBTPS leads to the observation of rather persistent spectra which in nearly all cases allow the unambiguous identification of the trapped species. DBTBTPS is somewhat less stable than thiobenzoyltriphenylsilane (TBTPS), the unsubstituted thiobenzoyltriphenylsilane; yet, as it affords spin adducts whose spectra are characterized by a smaller number of lines, it may prove more useful than TBTPS itself when dealing with radicals leading to species with a large number of magnetically active nuclei interacting with the unpaired electron.

Spin adducts between thioketones and phosphorus centred radicals : Part II. An electron spin resonance study of the addition of phophinyl, phosphonyl and thiophosphonyl radicals to diaryl and dialkyl thioketones

Abstract The paramagnetic adducts between a variety of phosphinyl, phosphonyl or thiophosphonyl radicals and thiobenzophenone, 9,H-xanthen-9-thione, 9, H-thiaxanthen-9-thione, 9, H-selenaxanthen-9-thione and di-tert-butyl thioketone have been generated and studied by means of ESR spectroscopy. Attention has been focused on the variations of a (31P) with the nature of the ligands L in the attacking PLn radicals and with the nature of the thiocarbonylic substrates. In all cases the reactions with the precursors of phosphinyl radicals afforded, beside the expected adducts, additional paramagnetic species, identified as the corresponding phosphonyl and thiophosphonyl adducts: while the formation of the former reflects the high sensitivity of tervalent phosphorus compounds to oxidizing agents, the latter adducts are believed to originate from desulfuration of the thioketones by the starting phosphines.

An Esr Approach To Hypervalent Iodine Induced Iododecarboxylation

Some mechanistic considerations based on the results of an ESR spectroscopic study of the IBDA (iodosobenzene diacetate) induced iododecarboxylation of several aliphatic carboxylic acids are reported. Both acetoxy units in IBDA are replaced by carboxylate groups in the first step of the reaction, forming a hypervalent iodine complex which then undergoes homolytic photodegradation. The R. radicals deriving from decarboxylation of the starting acids have been trapped by means of thiobenzoyl triphenylsilane and identified using ESR spectroscopy.

Drug delivery by polymeric micelles: an in vitro and in vivo study to deliver lipophilic substances to colonocytes and selectively target inflamed colon

UNLABELLED Colitis is the term used for chronic inflammatory bowel diseases at substantially increased risk of developing a form of colorectal cancer (CRC) known as colitis-associated cancer. In our study we synthesized core-shell polymeric micelles obtained by self-assembly of block copolymers for high efficiency delivery of anti-inflammatory and anti-cancer compounds to colonocytes and colon mucosa. We achieved an efficient intracellular delivery of these hydrophobic compounds (prednisone, retinoic acid and doxorubicin) to cultured colonocytes without cellular toxicity. The efficacy of retinoic acid and doxorubicin administration was significantly increased using these nanosized carriers. Moreover, these polymeric micelles have been shown to overcome the multidrug resistance efflux mechanism effectively delivering doxorubicin to multidrug-resistant colon cancer cells. These nanocarriers are also suitable for selective in vivo delivery of lipophilic drugs by enema administration to the inflamed colon tissue, specifically targeting the inflamed mucosa. FROM THE CLINICAL EDITOR This team of investigators studied polymeric micelles as highly efficient drug delivery systems enabling intracellular delivery of hydrophobic compounds (prednisone, retinoic acid, and doxorubicin) to cultured colonocytes without cellular toxicity, also demonstrating beneficial in vivo effects.

Spin trapping with thiocarbonyl compounds

A wide variety of radicals has been added to three relatively stable thiocarbonyl compounds, namely thiobenzoyltriphenylsilane (TBTPS), 2,4,6-tri-t-butylthiobenzaldehyde (TBTBA), and tris(trimethylsilyl)ethan-ethial or trisylthioaldehyde (TSTA), in order to test their ability to act as radical scavengers and the possibility of using them as spin-trapping agents. Reactions with radicals centred at elements from Groups IV to VI afforded in all cases persistent spin adducts which were studied by e.s.r. spectroscopy. In particular the adducts with TBTPS showed well resolved e.s.r. spectra for which the hyperfine pattern allowed in most cases an unambiguous identification of the trapped radical. The decay of some of the TBTA and TSTA adducts has been monitored, and the rate constants for the process determined. The rate of addition of the t-butoxyl and pivaloyl radicals to TSTA were also measured as (1.2 ± 0.5)× 107 and (1.9 ± 0.5)× 106 dm3 mol–1 s–1, respectively.

Polymeric micelles using pseudo-amphiphilic block copolymers and their cellular uptake

A PS-b-PMA block copolymer bearing a terminal carboxylic group has been synthesized using 3-(benzylsulfanyl thiocarbonylsulfanyl) propionic acid as RAFT agent. When dispersed in methanol, this block copolymer displays pseudo-amphiphilic behaviour providing micelles which can be suspended in water by osmosis. The carboxylic terminations are fundamental during the self-assembling process contributing to the formation of nanosized monodispersed particles. Furthermore, the anionic corona confers the to micelles stability in aqueous media. The core of the micelles was loaded with Nile Red to achieve the intracellular delivery of a lipophilic substance; this was demonstrated by Confocal Laser Scanning Microscopy. The particles, when loaded with doxorubicin, are able to overcome the intrinsic resistance of LoVo-MDR cancer cells. Further stabilization is given to the micelles by covalent shell crosslinking using triethylene glycol diacrylate. Because of the increased intracellular stability of the crosslinked micelles, they stain, when loaded with Nile Red, the aqueous cytosol instead of the lipophilic compartments. The unimers constituting the micelles were covalently labeled with fluorescein to follow their fate once incorporated into the cells.

Hydrogen abstraction ability of different aromatic nitroxides.

Indolinonic aromatic nitroxides have been shown to efficiently inhibit free radical mediated oxidation reactions in biological systems. Since all antioxidants also possess pro-oxidant activity, possibly through a hydrogen abstraction process from suitable substrates, the relative hydrogen abstraction abilities of these compounds were evaluated. Different hydrogen donors were reacted with an indolinic and two indolinonic nitroxides and the rates of hydrogen abstraction were determined using UV–Vis spectroscopy. From the data obtained, a structure–activity relationship was found. In addition, the hydrogen abstraction ability of these compounds was found to be much greater than that of the aliphatic nitroxide TEMPO, despite existing reports indicating that these two classes of compounds show similar antioxidant activities in biological systems.

Phosphoryldithioformates as spin trapping agents and process stabilizers—3

Abstract Five new phosphoryldithioformates bearing different substituents on the phosphoryl group have been synthesised and exploited as spin trapping agents in ESR experiments. While the dilauroxy substituted compound led to the observation of ESR spectra indicating photolability of either the compound as such or of its radical adducts, the three diaryloxy-phosphoryl dithioformates exhibited an excellent spin trapping ability, thus proving an attractive alternative to previously described members of this family. This was also the case for the di(2-menthoxy)phosphoryl derivative which led in all cases to very persistent radical adducts. The low melt-flow index values measured in the extrusion of polypropylene with variable additions of some of the dithioformates investigated in this and in previous studies indicated that the tested compounds have a remarkable ability to act as process stabilisers.

EPR studies on phosphoryldithioformates. Part 2

The addition of a variety of radicals to triphenylmethyl l, allyl 2, benzyl 3 and but-3-enyl (diethoxyphosphoryl)dithioformate 4 has been investigated by EPR spectroscopy. Reactions with the first substrate always led to displacement of the triphenylmethyl radical; release of the allylic or benzylic moieties from 2 and 3 was observed above 243 K under photolytic conditions, while at lower temperatures or in the dark the adducts resulting from thiophilic addition of the radicals were detected. The weak EPR spectra detected when reacting dithioformates 1–4 and methyl(diethoxyphosphono)dithioformate 5 with Grignard reagents are attributed to the radical anions of the starting compounds and to their ion pairs with magnesium cations.