Gabriele Micheletti

Synthesis and antimicrobial activity of novel structural hybrids of benzofuroxan and benzothiazole derivatives

New compounds containing both benzofuroxan and benzothiazole scaffolds were synthesized through electrophile/nucleophile combination of nitrobenzofuroxan derivatives and 2-mercapto- or 2-aminobenzothiazole derivatives and their biological effect on the natural strain Vibrio genus and different bacterial lux-biosensors was studied. Among all the compounds synthesized, that obtained from 2-mercaptobenzothiazole and 7-chloro-4,6-dinitrobenzofuroxan was toxic for bacterial cells, and also able to activated the 1st type Quorum Sensing system. The reaction between 7-chloro-4,6-dinitrobenzofuroxan and 2-aminobenzothiazole derivatives gave two products, one bearing the benzofuroxan moiety linked to the exocyclic amino nitrogen, and the second derived from the attack of two molecules of electrophile to both the nitrogen atoms of the benzothiazole reagent. Their relative ratio is modifiable by tuning the reagents ratio and the reaction time.

Formaldehyde replacement with glyoxylic acid in semipermanent hair straightening: a new and multidisciplinary investigation

Formaldehyde is an effective and popular semipermanent hair straightener, but the severe consequences for human health due to its toxicity have prompted the search for safer alternatives. Different carbonyl compounds, including glyoxylic acid, have recently been proposed as promising candidates. Despite the interest in this topic, there is a lack of information about the interactions between hair keratin and straightener agents. This study addresses this issue to gain new insights useful in the development of new products for safe, semipermanent hair deformation.

The role played by phosphorus hexacoordination in driving the stereochemical outcome of a phosphination reaction.

Asymmetric alkyl phospholanes have been diastereoselectively synthesized by addition of an unsymmetrical bis-Grignard reagent and of a mono-Grignard reagent to benzothiadiphosphole (1) and isolated as sulfides. The relative cis/trans ratio of the products depends on the steric hindrance of the mono-Grignard used. An accurate analysis of NMR and stereoselective data revealed the fundamental role played by hexacoordinated phosphorus intermediates in driving the stereochemical outcome of the reaction. The particular bicyclic and folded structure of reagent 1 strongly stabilizes hypercoordinated phosphorus species involved in the reaction and favors their formation. Pentacoordinate and metastable hexacoordinate phosphorus species have been detected and their evolution studied through (31)P NMR spectroscopy. The diastereoselective outcome of the reaction between reagent 1 and the couple bis-Grignard reagent 5/mono-Grignard reagent has been explained through a pathway involving hexacoordination of the phosphorus as a key step.

Ring Closure of Azo Compounds to 1,2-Annulated Benzimidazole Derivatives and Further Evidence of Reversibility of the Azo-Coupling Reaction

The reaction between 1,3,5-tris(N,N-dialkylamino)benzene derivatives and 2 equiv of p-substituted benzenediazonium salts gives dicationic species which collapse to new benzimidazole derivatives with expulsion of p-substituted anilines. The presence of electron-withdrawing groups on the benzenediazo moiety of the dicationic species plays a key role in this unexpected ring closure reaction. The observed chemical behavior has been rationalized in terms of the already reported reversibility of azo coupling reactions and provided further evidence for it.

A green synthesis of glycoluril derivatives in aqueous solution with recycle of the waste

Abstract A series of glycoluril derivatives have been synthesized in water at room temperature from urea and 1,2-dicarbonyl compounds in the presence of phosphoric anhydride. The reaction time is about 10 minutes using one mole of 1,2-dicarbonyl compound, three moles of urea, and half mole of P4O10, but the reaction occurs also, even if with longer reaction times, with very small amounts of P4O10 which is recovered at the end of reactions. In fact, several catalytic turnovers can be performed using the same reaction solution obtained after separation by simple filtration of the glycolurils.

The Phosphoenolpyruvate Phosphorylation: A Self-Organized Mechanism with Implications to Understand the RNA Transformations

In this article, we present a study about the non-enzymatic hydrolysis of phosphoenolpyruvate (PEP) by following the reaction course through 31P NMR spectroscopy. We have demonstrated that PEP in water exists mainly as a very stable cyclic pentacoordinate phosphorus compound in equilibrium with other cyclic forms. This explains the PEP stability in water. In contrast, after addition of an alcohol to a PEP aqueous solution, other very unstable cyclic pentacoordinated intermediates are formed, which immediately collapse, giving a feasible phosphorylation of the alcohol. It is known that cyclic pentacoordinated phosphorus intermediates are favored over the corresponding acyclic intermediates by a factor of 106–108, and this preference, found also in this study, might be the “driver mechanism” able to overcome the clutter of abiotic chemistry, thus permitting formation of pre-RNA molecules probably with a “self-organized process.”

The First Flights of a Molecular Shuttle Transporting Elements: Easy One‐pot Formation of Organic Cyclic Arsanes, Stibanes and Bismutanes

The increasing role of organic derivatives of arsenic, antimony, and bismuth in many fields of chemistry is due to their versatility as ligands, their use in materials science and their applications in the pharmacological field. Despite this, few methods of synthesis of triorganoderivatives of these elements have been reported to date and they all involve multi-step procedures giving products in very low overall yields. Moreover, the toxicity of these derivatives requires that their preparation must be carried out with strong attention and adequate precautions in their handling. For these reasons, to find synthetic one-pot procedures that permit the manipulation of these compounds to be minimised represents an interesting challenge. Here we report a very simple synthesis of new arsenic-, antimonyand bismuth-donor reagents and their use in the one-pot synthesis of cyclic arsanes, stibanes and bismutanes, respectively, through a procedure in which the simultaneous formation of three C As, C Sb or C Bi bonds is achieved. Recently, we reported (Scheme 1) a new synthesis of tertiary cyclic phosphanes 2 and 3 in 60–70 % yields by addition of a bis ACHTUNGTRENNUNG(Grignard) reagent and a Grignard reagent to an unusual phosphorus-donor reagent, the benzothiadiphosphole 1 a, called by us a “butterfly reagent” owing to its particular folded structure. At the end of the reaction the starting reagent 1 a was quantitatively regenerated by addition of one equivalent amount of PCl3 to the end-product 4, which is the remainder of 1 a obtained after quenching the reaction mixture with water (Scheme 1). More recently, we found that tertiary phosphanes are formed spontaneously in the reaction mixture, and that the quantitative regeneration of the reagent 1 a can be accomplished by simple addition of one equivalent amount of PCl3 to the crude reaction mixture. Taking these findings into consideration, together with the fact that as As, Sb and Bi, belong to the same group of P they could show similar behaviour, we decided to try a transport process for these elements, in order to find a new protocol for obtaining cyclic organoarsanes, organostibanes and organobismutanes, which, to date, have been synthesised with multi-step procedures and in very low overall yields. For this purpose, firstly we tried the synthesis of new heterocycles 1 b–d (Scheme 2), by reaction between compound 4 and AsCl3, SbCl3, and BiCl3, respectively. [10] With this reaction benzothiaphospharsole (1 b), benzothiaphosphastibole (1 c), and benzothiaphosphabismole (1 d ; Scheme 2) were isolated in almost quantitative yields (95–98 %) and characterised. It is worth noting that mass spectra of 1 a–d showed the same peak (m/z= 243), originating by the loss from the molecular ion of the fragment PS, AsS, SbS and BiS, respectively. At the same time, the P NMR spectra showed a regular decrease of the chemical shifts on going from 1 b (d= 78.6 ppm) to 1 c (d= 52.7 ppm), to 1 d (d=35.0 ppm) in [D8]THF, as a result both of the decrease in electronegativi[a] Prof. G. Baccolini, Dr. C. Boga, Dr. M. Mazzacurati, Dr. G. Micheletti Department of Organic Chemistry “A. Mangini” ALMA MATER STUDIORUM—Universit di Bologna Viale Risorgimento, 4 40136 Bologna (Italy) Fax: (+39) 051 2093654 E-mail : baccolin@ms.fci.unibo.it boga@ms.fci.unibo.it Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200802007. Scheme 1. One-pot synthesis of tertiary phosphanes.

(9R)-9-Hydroxystearate-Functionalized Hydroxyapatite as Antiproliferative and Cytotoxic Agent toward Osteosarcoma Cells.

The possibility to functionalize calcium phosphates with bioactive agents is a promising strategy to design innovative biomaterials for bone repair able to couple the bioactive properties of the inorganic compounds with the therapeutic effect of the functionalizing agent. The R enantiomer of the 9-hydroxystearic acid, (9R)-9-HSA, produced from Dimorphotheca sinuata L. seeds, has proven to act as a natural negative regulator of tumor cell proliferation. On this basis, hydroxyapatite was synthesized with increasing contents of (9R)-9-hydroxystearate, up to ∼8.6 wt %. The incorporation of HSA in the composite nanocrystals induces a reduction of the crystal mean dimensions and of the length of the coherently scattering crystalline domains, which suggest a preferential adsorption onto the hydroxyapatite crystal faces parallel to the c-axis direction. The composite nanocrystals were designed so that their cytostatic and cytotoxic effects toward osteosarcoma cells were modulated by hydroxystearate content. In fact, results of in vitro tests show that the presence of HSA in the composite nanocrystals provokes a significant decrease in SaOS2 osteosarcoma cells proliferation and viability as well as an increase in lactate dehydrogenase, tumor necrosis factor α, and caspase 3 levels, with a cytotoxic effect increasing with HSA content in the nanocrystals.

Wittig Reaction: Role of Steric Effects in Explaining the Prevalent Formation of Z Olefin from Nonstabilized Ylides

Abstract For understanding the mechanism involved in the Wittig reaction, it is important to know the factors which influence the stability of 1,2-oxaphosphetane intermediates with pentacoordinate phosphorus; in these intermediates, the steric factor plays a predominant role. Studying the Wittig reaction between nonstabilized ylides and different aldehydes, we noted that the stereochemical outcome driving toward Z-olefin formation was influenced only by different steric factors. The proposed mechanism differs from those previously reported because it underlines the fundamental role of the two cis/trans oxaphosphetane intermediates with the oxygen atom in equatorial position. GRAPHICAL ABSTRACT

A Fast Catalytic Process of Transfer of a Phosphorus Atom: How Folding of the Reagent is Related to its Catalytic Activity. A Possible Correlation with Rna Behavior

Abstract A simple and very fast process of transfer of a phosphorus atom, performed by a simple molecule acting as catalyst in an almost infinite catalytic cycle is described. The catalyst donates a P atom to a mixture of two different Grignard reagents giving, in a very fast and in a highly selective manner, only one phosphorus-containing compound with an enormous rate enhancement with respect to the corresponding no-catalyzed reaction which gives a final cluttered mixture of many organophosphorus products. The focal factor to explain this highly selective process of P transport lies in the folded structure of the reagent with particular angles around the phosphorus atom which can facilitate the formation of cyclic trigonal bipyramidal pentacoordinated species and then its catalytic activity. In a similar manner, RNA can adopt, in a precise position, a particular three-dimensional structure that might facilitate the formation of pentacoordinated species leading to the catalytic function. GRAPHICAL ABSTRACT