A novel lipophilic zinc(II) complex with 1-hexadecyl-1,4,7,10-tetrazacyclododecane (hexadecylcyclen, L) has been synthesized, which is almost insoluble in water, but becomes soluble in the presence of Triton X-100 surfactant. Analysis of the potentiometric pH titration of ZnII−hexadecylcyclen (1 mM) in the presence of Triton X-100 (10 mM) disclosed monodeprotonation of the ZnII-bound H2O, yielding an OH--bridged complex (ZnL)2OH- (pK d = −log([(ZnL)2OH-]a H + /[ZnL]2) = 3.92 ± 0.05) and a monomeric ZnII−OH- complex ZnL−OH- (pK a = −log([ZnL−OH-]a H + /[ZnL]) = 7.56 ± 0.05) at 25 °C with I = 0.10 (NaNO3). The zinc(II) complex (ZnL) possesses higher catalytic activity than the parent zinc(II) complex of 1,4,7,10-tetrazacyclododecane (cyclen, L‘) in hydrolysis of 4-nitrophenyl acetate (NA), bis(4-nitrophenyl) phosphate (BNP-), and tris(4-nitrophenyl) phosphate (TNP) in aqueous comicellar solution with 10 mM Triton X-100. The NA hydrolysis activity of ZnII−hexadecylcyclen increased with the pH and leveled off at pH > 10 and 25 °C, from which the active species was estimated to be a ZnL−OH- complex. The second-order rate (first-order in [NA] and [ZnL−OH-]) of NA hydrolysis (k NA = 5.0 ± 0.2 M-1 s-1) in the presence of 10 mM Triton X-100 is 50 times greater than that with a reference ZnL‘−OH- in 10% (v/v) CH3CN aqueous solution. Hydrolysis of TNP in 10% (v/v) MeOH aqueous solution with ZnL−OH- and 10 mM Triton X-100 (k TNP = (1.1 ± 0.1) × 103 M-1 s-1) is 290 times more efficient than with ZnL‘−OH- (3.8 ± 0.2 M-1 s-1) at 25 °C. The higher effective molarity of the lipophilic substrate coexisting with ZnL−OH- in the micelles accounts for the extraordinary catalytic activity. From comparison with previously reported metal catalysts, the present lipophilic zinc(II) complex with hexadecylcyclen is probably one of the best candidate catalyst for detoxification of poisonous phosphotriesters.

The functionality of human erythrocyte nucleoside transporter ENT1 was examined at ice-cold temperatures (ICT; measured temperature, 0.5-0.7 degrees C) using rightside-out membrane vesicles (ROVs). The uptake of uridine, an ENT1 substrate, showed saturation kinetics and was inhibited by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), a specific ENT1 inhibitor, at both 23 degrees C and ICT. [3H]Uridine uptake was markedly trans-stimulated by preloading ROVs with unlabeled uridine or ribavirin, another ENT1 substrate, and the overshoot phenomenon was observed at ICT. Similarly, [3H]ribavirin uptake was markedly trans-stimulated by unlabeled ribavirin or uridine at ICT. The trans-stimulated uptake of [3H]uridine at ICT was inhibited by ENT1 inhibitors/substrates such as NBMPR, dipyridamole, adenosine, and ribavirin in a concentration-dependent manner. The inhibition of [3H]uridine uptake by NBMPR and dipyridamole at ICT was also observed in intact red blood cells. Like uridine uptake, [3H]D-glucose uptake by ROVs, which is mediated by facilitative glucose transporter GLUT1, was trans-stimulated by unlabeled D-glucose at ICT, and the overshoot phenomenon was observed. In contrast, the ability of ATP-dependent transport of 5-(and-6)-carboxy-2',7'-dichlorofluorescein via multidrug resistance-associated protein 5 in inside-out membrane vesicles disappeared at ICT. These results clearly indicate that human erythrocyte transporters such as ENT1 function even at very low temperatures near 0 degrees C. The significance of these findings in transporter research is discussed.

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ChemInform Abstract ((III) and (IV); protonation constants; stability constant of (Vc) 2.5 ±0.2; EPR data for all (V); UV data and half-wave potentials of complexes (V) and (VI)).

198 ChemInform Abstract The 12-membered macrocyclic triamine (III) is synthesized from coumarin (I) and the triamine (II). Reaction of methyl cinnamate (IV) with (II) gives the macrocycle (V), a homologue of some macrocyclic spermidine alkaloids. The 1:1 complexation constants of (III) with Cu2+, Zn2+, Ni2+ and Co2+ are determined.