We report for first time the presence of functional delta-, kappa-, and mu-opioid receptors in human sperm membranes. These findings are indicative of a role for the opioid system in the regulation of sperm physiology.

Thirteen N,N‐diazolylmethanes, including derivatives of pyrazole, imidazole, 1,2,4‐triazole, benzimidazole and indazole were prepared by reaction of azoles with methylene chloride under phase transfer catalysis conditions. The relative amounts of isomeric mixtures obtained with ‘asymmetric’ azoles or with equimolar mixtures of azoles are compared with literature results on monoalkylation of azoles. Proton and carbon‐13 nmr spectra of the N,N'‐diazolylmethanes are discussed.

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The interaction with Cu2+ and dopamine of three polyazacyclophanes containing pyrazole fragments as spacers is described. Formation of mixed complexes Cu2+−macrocycle−dopamine has been studied by potentiometric methods in aqueous solution. The crystal structures of the complexes [Cu2(L 1)(H2O)2](ClO4)4·2H2O (4) (L 1 = 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.111,14]octacosa-1(27),11,14(28),24-tetraene) and [Cu2(H- 1 L 3)](HClO4)(ClO4)2·2H2O (6) (L 3 = 1,4,7,8,11,14,17,20,21,24,29,32,33,36-tetradecaazapentacyclo[12.12.12.16,9.119,22.131,34]hentetraconta-6,9(41),19(40),21,31,34(39)-hexaene) are presented. In the first one (4), each Cu2+ coordination site is made up by the three nitrogens of the polyamine bridge, a sp2 pyrazole nitrogen and one water molecule that occupies the axial position of a square pyramid. The distance between the copper ions is 6.788(2) Å. In the crystal structure of 6, the coordination geometry around each Cu2+ is square pyramidal with its base being formed by two secondary nitrogens of the bridge and two nitrogen atoms of two different pyrazolate units which act as exobidentate ligands. The axial positions are occupied by the bridgehead nitrogen atoms; the elongation is more pronounced in one of the two sites [Cu(1)−N(1), 2.29(2) Å; Cu(2)−N(6), 2.40(1) Å]. The Cu−N distances involving the deprotonated pyrazole moieties are significantly shorter than those of the secondary nitrogens. The Cu(1)···Cu(2) distance is 3.960(3) Å. The pyrazole in the noncoordinating bridge does not deprotonate and lies to one side of the macrocyclic cavity. One of the aliphatic nitrogens of this bridge is protonated and hydrogen bonded to a water molecule, which is further connected to the sp2 nitrogen of the pyrazole moiety through a hydrogen bond. The solution studies reveal a ready deprotonation of the pyrazole units induced by coordination to Cu2+. In the case of L 2 (L 2 = 3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.111,14]octacosa-1(27),11,14(28),24-tetraene), deprotonation of both pyrazole subunits is already observed at pH ca. 4 for 2:1 Cu2+:L 2 molar ratios. All three free receptors interact with dopamine in aqueous solution. L 3 is a receptor particularly interesting with respect to the values of the interaction constants over five logarithmic units at neutral pH, which might suggest an encapsulation of dopamine in the macrocyclic cage. All three receptors form mixed complexes Cu2+−L−dopamine. The affinity for the formation of ternary dopamine complexes is particularly high in the case of the binuclear Cu2+ complexes of the 1-benzyl derivative L 1.

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Opioid peptides have been reported to have important functions in human reproduction. Indeed, very high concentrations of enkephalins and their degrading enzymes have been reported in human semen. In the present paper, we compare the activity of two enkephalin-degrading enzymes, aminopeptidase N and neutral endopeptidase 24.11, in different fractions of semen from normozoospermic, fertile men and from subfertile patients with different abnormalities revealed by spermiogram analysis (asthenozoospermia, necrozoospermia, and teratozoospermia). High levels of activity of aminopeptidase N were found in the soluble and particulate sperm fractions of semen from patients presenting asthenozoospermia with necrozoospermia. In contrast, lower aminopeptidase N activity was measured in the soluble sperm fraction of asthenozoospermic semen. The percentage of dead spermatozoa was positively correlated with aminopeptidase N activity in both soluble and particulate sperm fractions. In contrast, the percentage of immobile spermatozoa was negatively correlated with aminopeptidase activity in soluble and particulate sperm, and in prostasome fractions. Levels of activity of neutral endopeptidase were found to be unaltered among the different conditions. In summary, the results of the present study indicate that alterations in the activity of aminopeptidase N may be one of the molecular components that contribute to male human subfertility.