Synthesis and characterization of a 13-member macrocycle functionalized by tyramine arms: Complexation with Cu2+ and antioxidant capacity
Por:
López-Martínez, L.M., Santacruz-Ortega, H., Navarro, R.E., Inoue, M., Sugich-Miranda, R., Hernández-Paredes, J., Castillo, I., Sotelo-Mundo, R.R.
Publicada:
8 may 2017
Resumen:
A new macrocycle bearing tyramine arms through amide linkages,
2,2'-(2,9-dioxo-1,4,7,10-tetraazacyclotridecane-4,7-diyl)bis(N-(4-hydrox
yphenethyl)acetamide) abbreviated as L13Tyra, has been synthesized with
amide-coupling agents in a microwave reactor. This macrocycle involves
two potential metal-coordinating and bioactive sites, i.e., the
tetraaza-macrocyclic ring (with a low basicity of the amino nitrogen)
and the pendant phenol arms (with a small pK(a) 8.6). The Cu2+ complex
has different compositions in solid and in solution. An X-ray crystal
study shows that a mononuclear complex [Cu (L13Tyra 2H)](0) is formed
with a square coordination of two deprotonated amide nitrogen and two
amino nitrogen atoms of the macrocyclic ring; a carbonyl oxygen atom
from a pendant arm occupies an axial site to construct a square pyramid.
UV-Vis spectrometric titrations in aqueous solutions indicate the
formation of a binuclear complex [Cu-2(L13Tyra-4H)(H2O)(x)](0) in
which phenolate oxygen atoms of the tyramine arms coordinate a Cu2+ ion
in addition to the coordination of the macrocyclic chelate; such a
binuclear structure is maintained only in solution. The uncoordinated
ligand has a high antioxidant capacity with a TEAC (Trolox equivalent
antioxidant capacity) assay comparable to that of ascorbic acid, thanks
to the phenolic OH of the tyramine arms. Copper(II) ion works as an
inhibitor against the activity; the TEAC assay of the binuclear complex
is as small as one-twentieth that of the uncoordinated ligand.
Antiproliferative and cytotoxic assays with normal and cancer cell lines
show no toxicity for both the ligand and its Cu2+ complex. (C) 2016
Elsevier Ltd. All rights reserved.
Filiaciones:
Departamento de Investigación en Polímeros y Materiales (DIPM), Universidad de Sonora, Calle Rosales y Blvd. Luis Encinas s/n, Col. Centro, Hermosillo, Sonora 83000, Mexico
Departamento de Ciencias Químico-Biológicas, Universidad de Sonora, Calle Rosales y Blvd. Luis Encinas s/n, Col. Centro, Hermosillo, Sonora 83000, Mexico
Departamento de Física, Universidad de Sonora, Calle Rosales y Blvd. Luis Encinas s/n, Col. Centro, Hermosillo, Sonora 83000, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, México, D. F. 04510, Mexico
Laboratorio de Estructura Biomolecular, Centro de Investigación en Alimentación y Desarrollo (CIAD), A.C., Carretera a Ejido La Victoria Km 0.6, Hermosillo, Sonora 83304, Mexico
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