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Several new molecules with different thio-scaffolds were designed, synthesised, and evaluated biologically as inhibitors of Carbonic Anhydrases (CAIs). The structure-activity relationship analysis identified thioether derivatives, here reported, as a potent and selective CAIs against hCA II and hCA IX. High resolution X-ray structure of inhibitor bound hCA II revealed extensive interactions with the hydrophobic pocket of active site and provided molecular insight into the binding properties of these new inhibitors.

The effect of eight potassium salts (KF, K3PO4, KOCN, K2CO3, KCl, K2SO4, KBr and KI) on glycerol carbonate (GC) is studied through NMR, DSC, solubility and ATR-FTIR experiments. From the solubility data, the main thermodynamic functions of solution and solvation are estimated, and the mean molal activity coefficients are calculated. The results suggest that the capability of an anion to establish hydrogen bonds with the solvent molecules (or behave as a base, as in the case of fluoride, phosphate, cyanate and carbonate) is the most important structural feature that determines its effects on the solvent structure. On the other hand potassium iodide behaves in an anomalous way, due to the large polarizability of the anion that can form non-electrostatic, van der Waals dispersive intermolecular interactions.

A series of tellurides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) carbonic anhydrase isoforms hCA I, II, IV, VII and IX, involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors. These compounds, which are the first tellurium-containing derivatives acting as inhibitors of carbonic anhydrase enzymes, showed effective inhibition against all isoforms investigated and some of them were selective for inhibiting the cytosolic or the membrane-bound CAs. Thus, these carbonic anhydrase inhibitors are interesting leads for the development of isoform-selective inhibitors.

Differently substituted β-hydroxy- and β-amino dialkyl and alkyl-aryl tellurides and selenides have been prepared through ring-opening reactions of epoxides and aziridines with selenium- or tellurium-centered nucleophiles. The antioxidant properties and the cytotoxicity of such compounds have been investigated on normal human dermal fibroblasts. Most of the studied compounds exhibited a low cytotoxicity and a number of them proved to be non-toxic, not showing any effect on cell viability even at the highest concentration used (100 μM). The obtained results showed a significant antioxidant potential of the selected organotellurium compounds, particularly evident under conditions of exogenously induced oxidative stress. The antioxidant activity of selenium-containing analogues of active tellurides has also been evaluated on cells, highlighting that the replacement of Se with Te brought about a significant increase in the peroxidase activity.

Functionalised aliphatic selenols, straightforwardly obtained through ring-opening reaction of strained heterocycles, represent a new chemotype acting as carbonic anhydrase inhibitors (CAIs). These compounds showed pronounced selectivity towards the cytosolic human (h) isoforms such as the hCA I, II and VII rather than the membrane tumor associate hCA IX. In addition, we reported for the first time the X-ray crystal structure of an aliphatic selenol bound to the hCA I zinc ion, and that afforded the opportunity to decipher in detail the inhibition mechanism underpinning such a new class of CAIs. In this context selenols are interesting leads worth developing for the obtainment of novel and efficient selective CAIs potentially useful for the management of a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy and arthritis.

A method for the synthesis of β3-amino acids starting from α-amino acids is described. This conversion can be effected by an eight-step procedure which involves the transformation of the carboxylic group into an alkyne followed by a selenium-mediated conversion of the carbon–carbon triple bond to a Se-phenyl selenocarboxylate intermediate. The reactive Se-phenyl selenocarboxylate intermediates can be trapped with water, alcohols or the amine of an amino acid derivative to give β3-amino acids, β3-amino esters or mixed peptides, respectively. The whole transformations of the carboxylic group into an alkyne and of the alkyne group into β3-amino acids may not require purification of the intermediate products but a work-up and isolation procedure of crude materials.

Two soils developed over 21 years on a homogeneous mine spoil bank — one under a pure plantation of Quercus robur L., the other under a mixed plantation Q. robur L. and N-fixer Alnus cordata Loisel. — were compared and contrasted in terms of quantity and quality of organic matter. The amount of both organic C and N are significantly higher in the mixed stand, with the differences confined to the mineral topsoil. Soil organic matter (SOM) was extracted by alkali and fractionated on a molecular weight basis. In terms of C, the extracted SOM amounted to about half of the total and the fraction 50,000 Da in the organo-mineral aggregates from the forest floor while the two fractions were equivalent in the mineral soil. In the mixed stand, the soil sampled under the oak canopy and that sampled under the alder canopy were processed separately. The whole extracted SOM and the soil residue were analysed for C/N ratio and spectroscopic properties (CP/MAS 13 C NMR). The qualitative differences are less evident than the quantitative ones, and often hardly interpretable. Nonetheless, some of the differences are clear and, together with morphological features, such as the presence only in the mixed stand of patches of a darker A material, indicate an effective role of the N-fixer species on both pedogenic processes and C cycle in this human-made environment.

Ethynyl silyl ketone 1 proved to be a very efficient Michael acceptor in carbocupration and metallocupration reactions. In particular, when using carbocuprates, a smooth entry to polyenals can be obtained, while, when using metallocuprates, silyl- and stannylpropenoyl silanes may be obtained, very powerful intermediates in organic synthesis.

Non racemic t-Boc protected aminoalkyl ketones have been obtained starting from γ-stannylated (E)-allylamines through a high yielding two step procedure consisting of a Stille coupling and a subsequent Wacker oxidation. These compounds are useful intermediates for obtaining 2,6-disubstituted piperidines.

A new class of differently protected chiral γ-amino acetylenic esters have been synthesized using natural occurring amino acids as chiral source. Enantiomerically enriched propargylamines or vinyldibromides have been treated with BuLi at low temperature affording, after carboxylation, enantiomerically enriched derivatives of alkynologous amino esters.

4-Tributylstannyl-5-substituted-pyrrolin-2-ones are prepared through the addition of tributylstannyl cyano cuprate to enantiomerically enriched N-protected γ-amino acetylenic esters. The regio- and stereoselectivity of the addition is discussed as a function of the substrates and of the reaction conditions. Cyclization of the ( E )-isomers to the corresponding 4-stannylated pyrrolin-2-ones is reported.

Reaction of trithiocarbonates with meta-chloroperoxybenzoic acid in CH2Cl2 at 0°C affords the corresponding S-oxides. These sulfines are relatively stable compounds which can be purified by chromatography. They react readily with organolithiums in THF at −78°C in a thiophilic manner to give carbanions which are stabilized by three sulfur groups. Hydrolysis affords trithioorthoester oxides. The thermal behaviour of these hindered products has been investigated and new rearrangement processes have been evidenced. The former carbanions are soft nucleophiles: 1,4-addition of these intermediates to α-enones was achieved selectively to lead to β-oxo ketenedithioacetals, which are easily transformed into 4-oxoalkanethioates. This “Umpolung” route allows the formal use of the (alkylthio)carbonyl anion. A thiophilic addition was also observed with allylsilanes in the presence of n-Bu4NF furnishing allyl sulfoxides.

Reaction of several azido compounds with acetylenic silyl ketone affords a simple and direct entry to triazolylacylsilanes and, alter desilylation to the corresponding functionalized triazolylaldehydes

4-Tributylstannyl,2-(5H)-furanone and pyrrolone have been prepared in good yields by addition of mixed stannylcuprate reagent on γ-amino and γ-hydroxy acetylenic esters. The use of these compounds as useful intermediates for the selective functionalization of these heterocyclic rings is discussed.

Reaction of dithioesters and trithiocarbonates with silylated nucleophiles under fluoride ion conditions affords a novel example of silyl mediated regiochemical control in the thiophilic functionalization.

The silylcupration of N-phenyl-N-ethynyl-aniline, occurs regioselectively leading to silylation at the β-carbon atom. Subsequent reaction of the resulting vinyl copper adduct with electrophiles, opens a new flexible route to functionalized enamines.

A wide range of thioketones may be conveniently obtained by silyl triflate promoted bis(trimethylsilyl)sulfide thionation of ketones.

2-Trimethylsilyl-1,3-dithiolane, easily obtainable through transthioacetalization of corresponding silylated acetals, can be efficiently reacted, under fluoride-ion catalysis, with different organic electrophiles, leading to a general and mild functionalization protocol. This reactivity discloses the ability of compound 3 to act as a masked dithiolane anion.

(E)-3-iodo propenoyltriphenylsilane 2 undergoes smooth coupling reactions with a variety of unsaturated organostannanes to afford polyunsaturated acylsilanes.

Reaction of [bis(trimethylsilyl)methyl]amine with aldehydes, leads to Schiff bases with unexpected remarkable stability.

Acetylenic silyl ketone 1 undergoes smooth Michael addition reaction with different silylated nucleophines to afford β-functionalized propenoylsilanes.

The highly reactive unsubstituted propenoylstannanes 3a–c have been prepared, and the reactivity of propenoyltrimethylstannane toward different silylated nucleophiles evaluated.

The reaction of bis(trimethylsilyl)sulphide with thiosulphinates and thiosulphonates in an inert solvent under neutral and mild conditions gives symmetrical alkyl- or aryl-trisulphides.

Unsymmetrical aryl- and alkyl- disulphides are prepared from silylsulphides and thiosulphinates or thiosulphonates. Silyl sulphinic esters are also obtained in the reaction of the thiosulphonates.