An ability of the ribbed-functionalized iron(ii) clathrochelates to induce a CD output in interactions with a protein, covalent bonding or supramolecular interactions with a low-molecular-weight chiral inductor, was discovered. The interactions of CD inactive, carboxyl-terminated iron(ii) clathrochelates with serum albumin induced their molecular asymmetry, causing an appearance of strong CD signals in the range of 350-600 nm, whereas methyl ester and amide clathrochelate derivatives remained almost CD inactive. The CD spectra of carboxyl-terminated clathrochelates on supramolecular interactions or covalent bonding with (R)-(+)-1-phenylethylamine gave a substantially lower CD output than with albumin, affected by both the solvent polarity and the isomerism of clathrochelate's ribbed substituents. In supramolecular assemblies, the bands were most intensive for ortho-substituted carboxyl-terminated clathrochelates. The ortho- and meta-phenylethylamide cage complexes in tetrachloromethane inverted the signs of their CD bands compared with those in acetonitrile. It was suggested that the tris-dioximate metal clathrochelates possess a Russian doll-like molecular system. Because of the distorted TP-TAP geometry, their coordination polyhedron had no inversion centre and possessed an inherent chirality together with the equiprobability of its left(Λ)- and right(Δ)-handle twists. The selective fixation of one of these C-distorted conformations resulted in the appearance of the CD signal in the range of their visible metal-to-ligand charge transfer bands. Calculations by DFT methods were used to illustrate the possible conformations of the macrobicyclic molecules, as well as the intramolecular interactions between the cage framework and optically active distal substituents responsible for the chirality induction of the metal-centred coordination polyhedra.
Iron(ii) clathrochelates are protein-sensitive CD reporters able to discriminate proteins of similar structure (HSA and BSA) and reflect the transitions of protein conformation.
Cage metal complexes iron(II) clathrochelates, which are inherently CD silent, were discovered to demonstrate intensive output in induced circular dichroism (ICD) spectra upon their assembly to albumins. With the aim to design clathrochelates as protein-sensitive CD reporters, the approach for the functionalization of one chelate a-dioximate fragment of the clathrochelate framework with two nonequivalent substituents was developed, and constitutional isomers of clathrochelate with two nonequivalent carboxyphenylsulfide groups were synthesized. The interaction of designed iron(II) clathrochelates and their symmetric homologues with globular proteins (serum albumins, lysozyme, blactoglobulin (BLG), trypsin, insulin) was studied by protein fluorescence quenching and CD techniques. A highly-intensive ICD output of the clathrochelates was observed upon their association with albumins and BLG. It was shown that in the presence of BLG, different clathrochelate isomers gave spectra of inverted signs, indicating the stabilization of opposite configurations (L or D) of the clathrochelate framework in the assembly with this protein. So, we suggest that the isomerism of the terminal carboxy group determined preferable configurations of the clathrochelate framework for the fixation in the protein binding site. MALDI TOF results show the formation of BLG-clathrochelate complex with ratio 1 : 1. Based on the docking simulations, the binding of the clathrochelate molecule (all isomers) to the main BLG binding site (calyx) in its open conformation is suggested. The above results point that the variation of the ribbed substituents at the clathrochelate framework is an effective tool to achieve the specificity of clathrochelate ICD reporting properties to the target protein. Scheme 1 Chemical drawings of the isomeric dicarboxyl-terminated iron(II) cage complexes and their dichloroclathrochelate precursor. 24220 | RSC Adv., 2019, 9, 24218-24230 This journal is View Article Online 2.6. Study of the BLG-clathrochelate 3 assembly by MALDI-TOF mass-spectrometry The corresponding spectra were obtained on a Bruker Daltonics MALDI-TOF mass spectrometer. The sample was prepared by mixing 50 ml of BLG solution (2 mg ml À1 in 0.1 M aqueous 24222 | RSC Adv., 2019, 9, 24218-24230 This journal is Scheme 2 Synthesis of the dicarboxyphenylsulfide iron(II) clathrochelates with equivalent (on top) and non-equivalent (on bottom) ribbed substituents. R 1 s R 2 .This journal is
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