Computational Insights on the Geometrical Arrangements of Cu(II) with a Mixed-Donor N₃S₃ Macrobicyclic Ligand

Abstract

The macrobicyclic mixed-donor N3S3 cage ligand AMME-N3S3sar (1-methyl-8-amino-3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]eicosane) can form complexes with Cu(II) in which it acts as hexadentate (N3S3) or tetradentate (N2S2) donor. These two complexes are in equilibrium that is strongly influenced by the presence of halide ions (Br(-) and Cl(-)) and the nature of the solvent (DMSO, MeCN, and H2O). In the absence of halides the hexadentate coordination mode of the ligand is preferred and the encapsulated complex ("Cu-in(2+)") is formed. Addition of halide ions in organic solvents (DMSO or MeCN) leads to the tetradentate complex ("Cu-out(+)") in a polyphasic kinetic process, but no Cu-out(+) complex is formed when the reaction is performed in water. Here we applied density functional theory calculations to study the mechanism of this interconversion as well as to understand the changes in the reactivity associated with the presence of water. Calculations were performed at the B3LYP/(SDD,6-31G**) level, in combination with continuum (MeCN) or discrete-continuum (H2O) solvent models. Our results show that formation of Cu-out(+) in organic media is exergonic and involves sequential halide-catalyzed inversion of the configuration of a N-donor of the macrocycle, rapid halide coordination, and inversion of the configuration of a S-donor. In aqueous solution the solvent is found to have an effect on both the thermodynamics and the kinetics of the reaction. Thermodynamically, the process becomes endergonic mainly due to the preferential solvation of halide ions by water, while the kinetics is influenced by formation of a network of H-bonded water molecules that surrounds the complex.

The role of hydroxo-bridged dinuclear species and the influence of “innocent” buffers in the reactivity of cis-[CoIII(cyclen)(H2O)2]3+ and [CoIII(tren)(H2O)2]3+ complexes with biologically relevant ligands at physiological pH

“…3b, bottom), thus showing the typical lack of ΔS ≠ /ΔV ≠ correlation associated with the involvement of mechanistically determinant hydrogen bonding interactions in the transition state of the reaction. 62,[79][80][81][82] This fact fully agrees with the important outer-sphere interactions indicated in the previous paragraphs, not even hampered by the high ionic strength used in the study. 83 Hydrogen bonding seems to be crucial for this process, the fact being a keystone in biologically relevant reactivity; the inherent dissociatively activated Co III substitution mechanisms are severely tuned by associative interactions in the outer-sphere encounter complex.…”

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of CoIII Complexes of Fully Alkylated Cyclen

“…This can be associated with the attachment of a poorer Lewis base (p K a(thymidine) = 9.8) (compared with the aqua ligand), thus leaving a higher positive charge density on the Co III center, making the protonation of the remaining hydroxo ligand more difficult. Although computational methods should potentially improve the understanding of these types of interactions and diffusion-controlled proton transfers, inclusion of specific solvent interactions in the mechanisms of reactions is not a generally solved problem. ,− …”