Coordination behaviour of new open chain and macrocyclic peptidomimetic compounds with copper(ii)

Abstract

Two valine-derived bis(amino amides) ligands have been prepared and fully characterized. Both compounds contain additional functionalities that implement their basicity and their water solubility.Besides, compound 1 is an open chain ligand, while 2 is a macrocycle. Their protonation constants as well as their stability constants for the formation of the corresponding Cu 2+ complexes have been determined potentiometrically. Important differences are associated to the macrocyclic effect and to the additional functionalities in the spacer. The presence of an additional amine group and/or the inclusion of a carboxylic side chain in this spacer increase the stabilities of the Cu 2+ complexes, suggesting its participation in the interaction with the metal. Thus, 2 is the first pseudopeptidic cyclophane of this family displaying the ability to form highly stable metal complexes in water. UV-Vis and ESI-MS were used for analyzing the complex species detected in the speciation diagram.

Cu2+, Zn2+, and Ni2+ Complexes of C2-Symmetric Pseudopeptides with an Aromatic Central Spacer

“…The process was accompanied by a change in color from blue to purple for the two Cu 2+ complexes and from green to yellow for the Ni 2+ complexes, while, as could be expected, colorless complexes were formed in the case of Zn 2+ . Moreover, their formation could be followed by FT-IR experiments by a significant shift of the CO band to lower frequencies (i.e., 1551 cm –1 for 9a against 1661 cm –1 for 5 , Figure S10), confirming the deprotonation of the amide group …”

“…For the potentiometric studies in 0.1 M NaCl/CH 3 CN 7/3 v/v, the value used for p K w was determined to be 14.6 . The constants previously obtained in 0.1 M NaCl for the related valine and phenylalanine bis­(amino amides) with an ethylenic central spacer 7 and 8 (Chart ) have also been included for comparison …”

“…This can suggest that, in the nonprotonated compound, for this solvent mixture, the amino nitrogen atoms are involved in strong hydrogen bonding that needs to be broken for the first protonation to occur. As in the case of the pseudopeptides containing an ethylenic spacer, the change in the side chain from isopropyl to benzyl produces a reduction in the overall basicity of 6 relative to 5 . Most likely, this reflects the interference of the aromatic rings of the side chains with the solvation of the ammonium ions.…”

“…Regarding metal complexation, our group has recently studied the coordination ability of some C 2 -symmetrical bis­(amino amides) derived from amino acids with the general structure I and possessing an aliphatic central spacer (−(CH 2 ) n −) toward Cu 2+ and Zn 2+ ions . The obtained results revealed that both the nature of the constituent amino acid (R in I) and the length of the aliphatic spacer ( n in −(CH 2 ) n −) were of importance in determining the complexes formed and their stability.…”

Intracellular Zn(ii) induced turn-on fluorescence of an l-phenylalanine-derived pseudopeptide

“…38,39 Even relatively simple C 2 symmetrical pseudopeptides can represent excellent models for the interaction of peptidic structures with metals, and the formation of coordination complexes with Ni(II), Cu (II), and Zn(II) mainly for valine and phenylalanine derivatives has been studied in detail. [40][41][42][43][44] The incorporation of fluorescent subunits has also allowed the development of pseudopeptidic fluorescence sensors for different species, even intracellularly. 45,46 On the other hand, ligands derived from Schiff bases have been often studied in coordination chemistry, allowing the development of interesting fluorescence sensors for several metal cations, including Zn(II).…”