Kinetico-mechanistic studies of substitution reactions on cross-bridged cyclen Co^IIIcomplexes with nucleosides and nucleotides

Abstract

Kinetico-mechanistic studies on the substitution reactivity of the [Co{(μ-ET)cyclen}(H2O)2](3+) complex cation at pH values within the 6.0-7.0 range with biologically significant ligands have been carried out. The substitution processes have been found to occur exclusively on the mono-hydroxobridged [(Co{(μ-ET)cyclen}(H2O))2(μ-OH)](5+) species formed after equilibration of the cobalt complex in the relevant medium. The studies conducted on the substitution of the aqua/hydroxo ligands of this dinuclear species are indicative of a dominant role of outer-sphere complexation, involving hydrogen-bonding interactions. The values of the outer-sphere complex formation equilibrium constant are in line with the intervention of both the exiting aqua ligands and the NH groups at the encapsulating {(μ-ET)cyclen} ligand. These complexes result in the preferential formation of O- or N-bonded nucleotides depending on the structure of the base moiety of the ligand. Even the entry of the different donor bonded nucleotides is hampered by the hydrogen-bonding interaction with the dangling moiety of an already coordinated ligand. In general the overall substitution processes occur at a faster rate than those published for the fully alkylated encapsulating {(Me)2(μ-ET)cyclen} ligand derivative, as expected for the still available base-catalysing NH groups in the {(μ-ET)cyclen} ligand.

Kinetico-mechanistic Studies on the Substitution Reactivity on the {RuII(bpy)2} Core with Nucleosides and Nucleotides at Physiological pH

“…Given our previous knowledge of the distinct reactivity patterns of 5′-CMP and 5′-TMP, these ligand molecules were used (Scheme ). , The reactivity with 5′-CMP, followed by UV–vis spectroscopy under pseudo-first-order conditions, agreed with the occurrence of a single step with a bathochromic shift in the position of the maxima. From these changes, the values of 1 k obs could be determined, as indicated in the Experimental Section, and from their limiting [5′-CMP] dependence (see eq 1 ), the values 1 k on , K OS , and 1 k off could be calculated (Figure ).…”

“…As for some cobalt­(III) systems studied with the same aim as that in the present work, ,, the reaction of the complex with chlorides, which may be relevant in in vivo fluids, has been conducted. , Contrary to what had been observed for the cobalt­(III) complexes of the cyclen family, in the present study some water by chloride substitution, under pseudo-first-order conditions, occurs in the 3–6 h time scale at room temperature. The spectral changes obtained indicate, nevertheless, a rather small displacement of the equilibria involved, even at a very large excesses of [Cl – ] [200–1000-fold that of the ruthenium­(II) complex; Figure ].…”

“…A productive orientation 59 by hydrogen bonding of the carbonyl groups on thymidine with the protons of the aqua ligands can be held responsible for this fact, as has already been proposed for the (Co III {μ-ET)cyclen}) system with relatively acidic amine bonds. 11 The thermal and pressure activation parameters determined for this step indicate an associative activation mechanism operating for the first water by thymidine substitution. The breaking of a number of …”

“…Furthermore, the use of complexes that could behave as dead ends, due to excessive inertness, also has to be avoided . This is especially relevant when the appearance of hydroxo-bridged species is inherent with the medium used. , …”

“…We have recently been involved in the substitution reactivity of inert cobalt­(III) complexes, with encapsulating (N) 4 macrocycles and two aqua ligands in the cis position at physiological pH, with nucleotides and nucleosides. ,, Our results have shown that speciation of these complexes in such a medium is a crucial point that has to be considered comprehensively (including the presence of hydroxo-bridged species); furthermore, tuning of the inertness can be easily achieved. The use of equivalent ruthenium­(II) complexes for this type of reactivity represents an obvious and interesting aim, but for ruthenium­(II) complexes, the presence of {HC–NH} units on the ligand is undesirable in aqueous solution at pH values close to 7, which produces ligand oxidation .…”