Role of chelate substituents and cis sigma-effect on the rate of ligand substitution at Pt(N-N-N) and Pt(N-N-C) centres.
Four complexes of the type [Pt(N-N-X)Cl](X = N or C) were tailor synthesized for mechanistic studies in methanol. The terdentate ligands included terpy, 4'-Ph-terpy, 4'-(2"-CF(3)-Ph)-terpy, and 4'-(2"'-CF(3)-Ph)-6-Ph-2,2'-bipy. The rate of substitution of the chloro ligand by thiourea, N,N'-dimethylthiourea, and N,N,N',N'-tetramethylthiourea was studied as a function of nucleophile concentration, temperature and pressure by using a stopped-flow technique. The observed pseudo-first-order rate constants for the substitution reactions obeyed the simple rate law k(obs) = k(2)[Nu]. Second-order kinetics and negative activation entropies and volumes support an associative substitution mechanism. At 298 K, the values of the second-order rate constant show a slight dependence on the nature of the moiety attached to the terpy ligand. Changing from a nitrogen sigma-donor to a carbon sigma-donor in the cis position, results in a deceleration of the substitution rate. The results suggest that the Pt-C bond in the cis position activates the metal centre in a different way than in the trans position.
A kinetic and mechanistic study into the substitution behaviour of platinum(II) polypyridyl complexes with a series of azole ligands.
The kinetics of chloride substitution from a series of square-planar platinum(II) complexes, viz. [Pt(terpyridine)Cl](+), (Pt1), [Pt{2-(2'-pyridyl)-1,10-phenanthroline}Cl]Cl, (Pt2), [Pt{4'-(2'''-CH3-phenyl)-2,2':6',2''-terpyridine}Cl]CF3SO3 (Pt3) and [Pt{4'-(2'''-CH3-phenyl)-6-(3''-isoquinoyl)-2,2'bipyridine}Cl]SbF6 (Pt4) were studied using a series of five-membered heterocyclic neutral nitrogen donor nucleophiles, viz. pyrazole (Pz), triazole (Tz), imidazole (Im), 1-methylimidazole (MIm) and 1,2-dimethylimidazole (DMIm) under pseudo-first-order conditions in methanol using UV/Visible spectrophotometry and conventional stopped-flow techniques. The observed second-order rate constants, k2, followed a two term rate law k(obs) = k2[nucleophile] + k(s) except for DMIm with Pt1, Pt3, Pt4 and Pz, Tz with Pt1. Increasing the π-conjugation in the cis position decreases the rate of chloride substitution by decreasing the π-acceptor property of the terpy moiety. However, increasing the π-conjugation in the cis/trans position increases the rate of substitution by enhancing the π-acceptor property within the ligand framework whereby increasing the reactivity of the metal centre. The observed trend for the reactivity was Pt2 > Pt1 > Pt3 > Pt4. The substitution kinetics was influenced by the basicity of the incoming nucleophiles except for the sterically hindered nucleophile, DMIm. The general trend observed for the reactivity of the nucleophiles is MIm > Im > DMIm > Pz > Tz.
Influence of naloxone on the antinociceptive effects of some antidepressant drugs.
The antinociceptive effects of tricyclic and atypical antidepressants were studied using the rat tail mechanical method. Clomipramine produced analgesia at the doses of 30 and 40 mg/kg, desimipramine at 10, 20 and 40 mg/kg, maprotiline at 20 and 30 mg/kg, mianserin at 30 mg/kg, nomifensine at 1, 2.5 and 5 mg/kg, indalpine at 10, 20 and 40 mg/kg, viloxazine at 60 and 80 mg/kg. Naloxone (0.8 mg/kg) abolished the antinociceptive action of these antidepressant drugs. These results suggest that the antinociceptive activity of these six antidepressant drugs in acute experimental pain could involve opiate mechanisms.