The synthesis of the new alcohol-pendant macrocycle 4-(2-hydroxyethyl)-1,4,7,16,19,22-hexaaza-10,13,25,28-tetraoxacyclotriacontane (L2) is reported. This ligand contains two different triamine moieties, one of them bearing an ethanolic sidearm. L2 binds two Zn(II) ions in aqueous solution. The stability constants of the L2 complexes have been determined at 298.1 and 308.1 K by means of potentiometric measurements. Besides a [Zn2 L2]4+ species, a deprotonated [Zn2(L2-H)]3+ complex and a hydroxo [Zn2(L2-H)(OH)]2+ complex are formed in aqueous solution. Zn(II)-assisted deprotonation of the alcoholic group takes place at neutral pH, giving the [Zn2(L2-H)]3+ complex. In [Zn2(L2-H)]3+, the deprotonated R−O- function bridges the two metals, as shown by the crystal structure of [Zn2(L2-H)Br2]BPh4·MeOH. The hydroxo species [Zn2(L2-H)(OH)]2+ is formed at slightly alkaline pH's. This complex contains both a Zn(II)-bound alkoxide and a Zn(II)−OH nucleophilic function. Therefore, it may provide a simple model system for alkaline phosphatases, where both a deprotonated serine and a Zn−OH function are involved in phosphate ester hydrolysis. Indeed, this complex promotes the hydrolysis of the carboxy ester p-nitrophenyl acetate (NA) as well as the cleavage of phosphate ester bis(p-nitrophenyl) phosphate (BNP). The kinetics of promoted hydrolysis of NA and BNP were studied by means of UV and 1H and 31P NMR measurements. In NA hydrolysis, the R−O-−Zn(II) function acts as nucleophile in the first step of the hydrolytic mechanism, to give an acetyl derivative, which is subsequently hydrolyzed to acetate by a Zn−OH group. Similarly, in BNP cleavage, the nucleophilic attack of alkoxide on phosphorus gives a pendant-alcohol phosphorylated intermediate, which undergoes subsequent intramolecular nucleophilic attack of a Zn(II)-bound hydroxide to yield a phosphomonoester product.

The dihydroxo complexes [Zn2L(OH)2]2+ (L = dinucleating ligands containing two polyamine units separated by polyoxa chains) promote both p-nitrophenyl acetate and bis(p-nitrophenyl) phosphate hydrolysis. In NA cleavage, the hydrolytic properties depend mainly on the nucleophilicity of the Zn(II)−OH functions, while in BNP hydrolysis, the activity is modulated by the interaction of the phosphate ester with the two metal centers.

The syntheses of four new, differently O-substituted 3-hydroxypyrroline N-oxides and the first 3-amino analogue have been performed by the use of a strategy involving double nucleophilic displacement of the corresponding dimesylates by hydroxylamine and oxidation of the resulting 1-hydroxypyrrolidines. The regioselectivity data of the oxidation reactions nicely confirm the mechanistic hypothesis, which explains the dependence on the electronic nature of the substituent. The trend of the regioselectivity ratio has useful predictive value. Practical complete regioselection has been obtained by substitution with a benzoyloxy functionality. The O-allyl-substituted nitrone is not stable in the reaction conditions, undergoing immediately an intramolecular cycloaddition reaction with complete stereocontrol and inversion of regio- and stereoselectivity with respect to the intermolecular case.

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