TY - JOUR
T1 - Ab initio design of chelating ligands relevant to Alzheimer's disease: Influence of metalloaromaticity
AU - Rimola, Albert
AU - Alí-Torres, Jorge
AU - Rodríguez-Rodríguez, Cristina
AU - Poater, Jordi
AU - Matito, Eduard
AU - Solà, Miquel
AU - Sodupe, Mariona
PY - 2011/11/17
Y1 - 2011/11/17
N2 - Evidence supporting the role of metal ions in Alzheimer's disease (AD) has rendered metal ion chelation as a promising therapeutic treatment. The rational design of efficient chelating ligands requires, however, a good knowledge of the electronic and molecular structure of the complexes formed. In the present work, the coordinative properties of a set of chelating ligands toward Cu(II) have been analyzed by means of DFT(B3LYP) calculations. Special attention has been paid to the aromatic behavior of the metalated rings of the complex and its influence on the chelating ability of the ligand. Ligands considered have identical metal binding sites (through N/O coordination) and only differ on the kind and size of the aromatic moieties. Results indicate that there is a good correlation between the stability constants (log β 2) and the degree of metalloaromaticity determined through the I NG and HOMA indices; that is, the higher the metalloaromaticity, the larger the log β 2 value. MOs and aromaticity descriptors confirm that present complexes exhibit Möbius metalloaromaticity. Detailed analysis of the nature of the Cu(II)-ligand bonding, performed through an energy decomposition analysis, indicates that ligands with less aromatic moieties have the negative charge more localized in the metalated ring, thus increasing their σ-donor character and the metalloaromaticity of the complexes they form. © 2011 American Chemical Society.
AB - Evidence supporting the role of metal ions in Alzheimer's disease (AD) has rendered metal ion chelation as a promising therapeutic treatment. The rational design of efficient chelating ligands requires, however, a good knowledge of the electronic and molecular structure of the complexes formed. In the present work, the coordinative properties of a set of chelating ligands toward Cu(II) have been analyzed by means of DFT(B3LYP) calculations. Special attention has been paid to the aromatic behavior of the metalated rings of the complex and its influence on the chelating ability of the ligand. Ligands considered have identical metal binding sites (through N/O coordination) and only differ on the kind and size of the aromatic moieties. Results indicate that there is a good correlation between the stability constants (log β 2) and the degree of metalloaromaticity determined through the I NG and HOMA indices; that is, the higher the metalloaromaticity, the larger the log β 2 value. MOs and aromaticity descriptors confirm that present complexes exhibit Möbius metalloaromaticity. Detailed analysis of the nature of the Cu(II)-ligand bonding, performed through an energy decomposition analysis, indicates that ligands with less aromatic moieties have the negative charge more localized in the metalated ring, thus increasing their σ-donor character and the metalloaromaticity of the complexes they form. © 2011 American Chemical Society.
U2 - https://doi.org/10.1021/jp203465h
DO - https://doi.org/10.1021/jp203465h
M3 - Article
VL - 115
SP - 12659
EP - 12666
JO - Journal of Physical Chemistry A
JF - Journal of Physical Chemistry A
SN - 1089-5639
ER -