Development of Soft-Based Double-Stranded Peptide Chelators which Selectively Separate Europium and Lanthanum Ions Based on the Hardness Concept

Abstract

New double-stranded peptide chelators (1) conjugated Cat (2,3-dihydroxybenzoic acid) were synthesized and formed a molecular complex 1-Eu 3؉ (or 1-Lu 3؉) with Eu 3؉ and Lu 3؉ but not La 3؉. The double-stranded peptide chelator may prove to be useful tools for studying the selective separation of lanthanide ions.Key words double-stranded peptide; soft-based chelator; hardness concept; lanthanide ion; binding constant Many studies have described the determination of luminescence, radiotherapeutic applications, and development of chelators for lanthanide ions (Ln 3ϩ ) in the past several years. [1][2][3] In the application of lanthanide ions for photometry, fluorometry and bioassay, 4,5) or Lu 3ϩ ions, we synthesized target double-stranded amino acid-Cat(OH) (8) and double-stranded peptide-Cat(OH) (9) by conjugation with two 2,3-dihydroxybenzoic acid (Cat,5) at N-terminus of the double-stranded peptide (or amino acid) conjugated with two -Ile-Phe-or -Phe-residues to a spacer. 12,13) In designing the functional chelators we have designed them using absolute hardness (h) and absolute electronegativity (c) based on the hardness concept.14-17) The values of c and h were calculated by Eqs. 1 and 2.14,15)Where E is the electronic energy of a molecule or a atom, N is the number of electrons, and u (r) is the external electrostatic potential. The I p and E a are the ionization energy and the electron affinity (eV), respectively. To analyze the electron structure of lanthanide ions and chelators, the coordinate of the electron structure was defined as r(c, h)ϭ r(Ϫ(∂E/∂N) u (r) , 1/2(∂ 2 E/∂N 2 ) u (r) ). We used c, h, and the diagram r(c, h) in the development of chelators. The coordinate diagram r(c, h) For instance, the r(c, h) values of Eu 3ϩ and La 3ϩ are r(33.809, 8.893) and r(40.561, 20.040), respectively.As the soft-based chelator is favorable to bind the soft-acid metals M nϩ ion according to the hardness concept, we synthesized and chose chelators 8 (r(3.015, 5.635)) and 9 (r(2.810, 5.500)) 19) as soft-based chelators which are a softer chelator than 1 (r(2.495, 8.345)), 2 (r(3.180, 7.500)), and 3 (r(2.370, 5.910)). Because, the s (0.177) of 8 is smaller than that of 1 (0.120), 2 (0.133), and 3 (0.169) since the reciprocal of the h is the global softness (s); sϭ1/h (eV). The s is a measure of chemical softness.The target chelators were synthesized as shown in Fig. 2. Removal of the Boc groups of Boc-protected bis(L-Phe)-1,4-diaminodimethylbenzene (4) by trifluoroacetic acid (TFA) afforded the free compound (6) in good yield.13) Conjugation of 2,3-bis(benzyloxy)benzoic acid, was prepared from 2,3-dihydroxybenzoic acid (5), with N-terminal of 6 afforded by treating CDI in dry CHCl 3 . Deprotection of Bn group in 7 using 5% Pd/C-H 2 gave new functional double-stranded peptide-Cat(OH) chelators (8) (and (9)), in 60-65% yield. All compounds 6, 7, 8 and 9, provided satisfactory analysis by 761-763 (2006) Communications to the Editor a) The data of lanthanide ions was taken from lit. 18)b) At the HF/6-31G* lev...

Superoxide Scavenging Effects of Some Novel Bis-Ligands and Their Solvated Metal Complexes Prepared by the Reaction of Ligands with Aluminum, Copper and Lanthanum Ions

“…We prepared the solvated molecule complexes, 11a –Al 3+ , 11a –Cu 2+ , and 11a –La 3+ , with a molar ratio of 1:1 (= [M n+ ]:[[ 11a ]) according to the method of our previous study based on UV/Vis spectrophotometry [15,16]. Structures were obtained after geometry optimization using the B3LYP method at a molar ratio of 1:1 of M n+ and 11a ; the 6-31G(d) basis set was used for C, H, N, Al 3+ , and Cu 2+ , and the LANL2DZ basis set was used for optimization of the La 3+ ion.…”

“…We previously reported the synthesis and chemical properties of the solved complex of bis(amino acid)catechol derivatives with lanthanoid (Ln 3+ ) ions [11,15,16]. We paid attention to the fact that Al 3+ and Cu 2+/+ ions, besides amyloid β protein misfolding and self-assembly, are causative compounds of Alzheimer’s disease [17,18].…”

Development of New Double-Stranded Phenylalanyl Chelators Using .ETA.-.CHI. Diagrams and Binding Constants for Chelators and Lanthanide Ions

“…Removal of the Boc groups by trifluoroacetic acid (TFA) afforded the free compound (12a) in good yield. 16,19) Conjugated 2,3-bis(benzyloxy)benzoic acid was prepared from 2,3-dihydroxybenzoic acid, 16) with the N-terminal of 12a afforded by treatment with DEPC (phosphorocyanidate) on dry N,N-dimethylformamide (DMF). Deprotection of the Bzl (benzyl) group in 13a using 5% Pd/C-H 2 gave a new peptide chelator (14a) in 65% yield.…”

“…13) The concepts of chemical hardness, absolute hardness [hϭ1/2(∂ 2 E/∂N 2 )] and absolute electronegativity [cϭϪ(∂E/∂N)], 14,15) which have been associated with the theory of chemical reactivity in molecules, are being applied to the design of chelators and chemicals. 16,17) N is the total electron number and E is total electron energy.…”

Design and synthesis of chelating diamide sorbents for the separation of lanthanides

“…Due to the very similar chemical properties of lanthanides (generally trivalent cations with similar in ionic radii [3,13,14]), separating the lanthanides from one another can be quite difficult [14][15][16]. Many efforts have been made in an attempt to achieve these lanthanide separations.…”