Mono- and Dinuclear Copper(II) and Iron(II) Complexes of a Tetradentate Bispidine-diacetate Ligand

Abstract

The synthesis of a new tetradentate bispidine ligand (LH2 = 2,2′-(1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-3,7-diyl)diacetic acid), containing two tertiary amine and two carboxylic groups, is reported along with the preparation and characterization of the corresponding Cu(ii) and Fe(iii) complexes. The mononuclear [LCu(OH2)]·4H2O (1) complex contains a five-coordinate Cu(ii) centre, which adopt a square pyramidal geometry with the four donor atoms of the ligand (N2O2) occupying the equatorial plane and a water molecule occupying the axial position. An axial electron paramagnetic resonance (EPR) signature is observed for 1 (gx = 2.054, gy = 2.050, gz = 2.234; Ax = 18 × 10–4 cm–1, Ay = 20 × 10–4 cm–1, Az = 188 × 10–4 cm–1) in frozen methanolic solution (0.1 mM). Dimerization of 1 in concentrated solution (10 mM) was observed by EPR spectroscopy (g∥ = 2.24, g⊥ = 2.07, A∥ = 195 × 10–4 cm–1, and A⊥ = 12 × 10–4 cm–1 for each Cu centre). The structure of the dimeric species [LCu(OH2)]2 (1b) was determined by a combination of molecular mechanics with the simulation of the EPR spectrum (MM-EPR). The dimer has each Cu(ii) centre coordinated by the two amines and one carboxylate of one ligand (L), while the other carboxylate bridges to the second Cu(ii) centre; each coordination sphere is completed by an axial water ligand, with the Cu···Cu distance 5.5 Å (relative orientation from EPR simulation: α = 60°, β = 0°, γ = 25°). The aqueous reaction between the tetradentate ligand (L) and Fe(ii) leads to the formation of an oxo-bridged diiron(iii) complex, [LFe-(μ-O)-FeL] (2), with a Fe–O–Fe angle of 180° (dFe···Fe = 3.516 Å), as revealed by X-ray crystallography. The Mössbauer spectrum of 2 consists of one quadrupole doublet with an isomer shift (δ) of 0.37 mm s–1 and a quadrupole splitting (ΔEQ) of 0.73 mm s–1, which is consistent with S = 5/2 Fe(iii) centres. Variable-temperature magnetic susceptibility measurements show the presence of intramolecular antiferromagnetic interactions between the two Fe(iii) centres, with an exchange coupling constant J of –91(3) cm–1 (H = –2JS1·S2).

Elucidation of Binding Site and Chiral Specificity of Oxidovanadium Drugs with Lysozyme through Theoretical Calculations

“…When thinking about paramagnetic vanadium­(IV) compounds, one of the spectroscopic approaches to decode metallodrug–protein interactions is electron paramagnetic resonance (EPR). Over the last years, several studies that combined EPR and computational methods, such as molecular mechanics (MM), quantum mechanics/molecular mechanics (QM/MM), molecular dynamics (MD), and density functional theory (DFT), were published. − For V IV the value of the hyperfine coupling constant, A iso or A z , can be correlated with the type and number of atoms that coordinate V IV O 2+ ion in the equatorial plane by using either the empirical “additivity rule” or comparative quantum mechanical calculations . EPR spectroscopy provided strong experimental evidence of the interaction of V IV O compounds with proteins, such as apo-transferrin (apo-hTf), holo-transferrin (holo-hTf), albumin (HSA), immunoglobulin G (IgG), and hemoglobin (Hb) .…”

Copper–Bispidine Complexes: Synthesis and Complex Stability Study

“…To overcome this problem, we used a known synthetic procedure for separation, which includes precipitation of the barium salt of the target compound and exclusion of the barium cation using diluted sulfuric acid. 30 The overall yield of the alkylation step is quite moderate (30–50%). Considering the alkylation efficiency (by means of NMR) and efficiency of barium precipitation as barium sulfate (100%), one can conclude that the maximum loss of target ligands 2 and 3 occurred at the barium salt precipitation stage.…”

“…The presence of binuclear cations in the mass spectra coincides with the structure proposed by Comba et al for complex 2a with copper(II) on the basis of quantum chemical calculations and ESP spectroscopy study. 30…”

“…Recently, 30 single crystals of Cu-2d have been characterized, indicative of the formation of a 1:1 stoichiometry, whereas by electron paramagnetic resonance spectroscopy and molecular mechanic structure optimization, the formation of dinuclear complexes with a 2:2 stoichiometry has been suggested. Our results, that is, 1:1 complexation of copper with 2a–c , 3b , and 3c , are in line with those obtained from single-crystal X-ray data in ref (30) and from the complexation study in ref (62). On the other hand, for ligands having carboxylic groups as part of their structures, complex CuL is stable over a wide pH range (Figure 10b).…”

“…This could be achieved at the ligand-design stage, which includes the choice of the central diazacore, the nature (Q’s) and length (k’s) of the pendant arms, and that of the cyclizing bridge (n’s). In the context of this challenge, we noted with interest complexes of tetradentate bispidine-based ligands, studied mostly by Comba et al. − Recently, bispidines themselves proved to be privileged structures in medicinal chemistry . The rigid framework of bispidines in double-chair conformation allows them to be used to study the binding of small cations for a long time .…”