Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen

Abstract

The solution chemistry of complex [Co{(Me)2(μ-ET)cyclen}(H2O)2](3+) containing a fully substituted tetraammine ligand designed for the avoidance of base-conjugated substitution mechanisms in the 6-8 pH range has been studied. The study should shed some light on the possible involvement of such Co(III) skeleton in inert interactions with biomolecules. The reactivity and speciation of the complex has been found similar to that of the parent cyclen derivative with the presence of mono- and bis-hydroxo-bridged species; at pH < 7.1, all reactivity has been found to be related to the aqua/hydroxo monomeric complexes. Under these pH conditions, the substitution reactions of the aqua/hydroxo ligands by chloride, inorganic phosphate, thymidine, cytidine 5'-monophosphate (5'-CMP), and thymidine-5'-monophosphate (5'-TMP) have been studied at varying conditions; ionic strength has been kept at 1.0 NaClO4 due to the high concentration of 2-(N-morpholino)ethanesulfonic acid (MES) or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) used to ensure buffering. Except for chloride, the process occurs neatly in a one or two step process, showing dissociatively activated substitution mechanisms, having in general large ΔH(⧧), positive ΔS(⧧), and values of ΔV(⧧) close to those corresponding to the liberation of an aqua ligand to the reaction medium. The actuation of noticeable encounter-complex formation equilibrium constants has been found to be the determinant for the reactions with nucleosides and nucleotides, a clear indication of the relevance of hydrogen-bonding interactions in the reactivity of these molecules, even in this highly ionic strength medium. For the substitution of the active aqua/hydroxo ligands with 5'-TMP, the first substitution reaction produces an Nthymine-bound 5'-TMP complex that evolves to a bis-5'-TMP with an Nthymine,Ophosphate-bonding structure. The formation of outer-sphere complexes between the dangling phosphate group of the Nthymine-bound 5'-TMP and the thymine moiety of another entering 5'-TMP has been found to be responsible for this fact, which leaves only the phosphate group for coordination available.

Kinetico-mechanistic studies of substitution reactions on cross-bridged cyclen CoIIIcomplexes with nucleosides and nucleotides

“…S1 †), and show the two-step sequence indicated above. The time-scale of these processes (10 plus 70 minutes at 17 °C) is clearly intermediate between those observed for the parent cyclen 9 and those found for the fully substituted {(Me) 2 (μ-ET)-cyclen} 22 analogous derivatives. This trend is in line with the residual presence of two slightly acidic NH axial groups attached to the Co III centre in the present compound, still capable of induced base-catalysed substitution reactivity.…”

“…33 Effectively, for this nucleoside the value of KOS is an order of magnitude larger than for the not-containing NH group analogue systems studied. 22 As for the entry of the second thymidine ligand, the value of the outer-sphere association equilibrium constant has definitively decreased in a way that a simple linear dependence between the value of kobs2 and [thymidine] is obtained (Fig. 3b).…”

“…Summarising, the behaviour of the [Co{(μ-ET)cyclen}-(H 2 O) 2 ] 3+ system has intermediate features between those of the parent cyclen 9 and {(Me) 2 (μ-ET)cyclen} 22 derivatives. The polymerisation equilibria indicated in Scheme 2 are at pH values higher than 7.5 (after 30 minutes at room temperature, see below) significantly displaced to the formation of a dimeric dead-end bis-hydroxo [(Co{(μ-ET)cyclen}) 2 (μ-OH) 2 ] 4+ complex.…”

“…18 Even some Co alkyne complexes have shown promising activity associated with their capability to target specific enzymes. 19,20 The use of complexes of type cis-[Co(N) 4 (H 2 O) 2 ] 3+ , with (N) 4 being tren, cyclen or fully alkylated {(Me) 2 (μ-ET)cyclen} has already been explored by us 9,21,22 by studying their substitution processes with some nucleosides and nucleotides at physiological pH. In this respect there has been an important increase in the use of cross-bridged cyclen and cyclam ligands, both for their promising properties and the robustness of their structure containing five-and six-membered macrocyclic full encapsulation.…”

Redox‐Assisted Self‐Assembly of a Water‐Soluble Cyanido‐Bridged Mixed Valence {CoIII/FeII}2 Square

“…Thep resence of signals in the 2000-2200 cm À1 IR range are associatedw ith three types of cyanidol igandsi nt he complex:a xial (2051 cm À1 ), trans to bridge (2128 cm À1 ), and bridging (2146 cm À1 ). [28,39] In the same context, 13 CNMR of the sample in aqueous solution showed the signals corresponding to the ligand (56.9, 66.4, 67.1, and 71.5 ppm) [63] plus three signals associated with the axial (175.6 ppm), trans to bridge (176.9 ppm), and bridging (185.1 ppm) cyanidog roups (Figure S1 in the Supporting Information). [4,28] The presence of large amounts of NaClO 4 ,o riginated from the preparative procedure, and the high solubility of the complexi nw ater prevented the crystallization of the analytically pure species, which prompted us to optimize its structure using DFT calculations.…”