Induced CD of iron(ii) clathrochelates: sensing of the structural and conformational alterations of serum albumins

Abstract

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.

Sensing of Proteins by ICD Response of Iron(II) Clathrochelates Functionalized by Carboxyalkylsulfide Groups

“…Recently, it has been discovered that the binding to bovine serum albumin (BSA) makes the optically inactive iron(II) clathrochelates functionalized with carboxyphenylsulfide groups able to induce circular dichroism spectra (ICD) [25]. As an explanation to this phenomenon, we suggested that BSA binding sites are suited to predominant fixation of one of the two (Λ or ∆) trigonal prismatically (TP)-trigonal antiprismatically (TAP)-distorted conformations of the clathrochelate framework [26]. The iron(II) clathrochelate isomers with six carboxyphenylsulfide groups were reported to give a substantially different ICD response upon binding to BSA and to human serum albumin (HSA), thus allowing us to discriminate between these two structurally related proteins [26].…”

“…As an explanation to this phenomenon, we suggested that BSA binding sites are suited to predominant fixation of one of the two (Λ or ∆) trigonal prismatically (TP)-trigonal antiprismatically (TAP)-distorted conformations of the clathrochelate framework [26]. The iron(II) clathrochelate isomers with six carboxyphenylsulfide groups were reported to give a substantially different ICD response upon binding to BSA and to human serum albumin (HSA), thus allowing us to discriminate between these two structurally related proteins [26]. In addition, the clathrochelates with two carboxyphenylsulfide substituents have shown different optical responses upon their supramolecular assembly with globular proteins, permitting to distinguish between albumins and beta-lactoglobulin (BLG) [24].…”

“…Since CD spectra are known to be sensitive to geometrical distortions of the absorbing chromophores, the ability of the clathrochelate framework to adopt left or right TP-TAP twisted conformations makes these cage metal complexes suitable for the detection of the certain elements of protein tertiary structure and discerning between these elements [24]. It should also be mentioned that the intensities and shapes of the clathrochelate CD spectra induced by the presence of the proteins are substantially affected by the constitutional isomerism of the clathrochelates with carboxyphenylsulfide ribbed substituent-i.e., the ortho-, meta-or para-position(s) of their terminal carboxyl group(s) [26,27]. Moreover, the data of isothermal titration calorimetry (ITC) suggest that the clathrochelates-to-protein binding stoichiometry is also affected by this type of isomerism being equal to 1:2 for the para-substituted isomer and to 1:1 for its ortho-and meta-substituted analogs [26].…”

Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents—The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s)

“…Among the earlier-described d-metal monomacrobicyclic complexes (clathrochelates [1,2]) and their bis-cage analogs, shown in Scheme 1 with terminal biorelevant, first of all, carboxyl group(s), compounds 1-5 are reported to be the most prospective bioeffectors, including the so-called "topological drugs" [2,3] and molecular optical probes [4][5][6]. They possess the highest inhibitory activities in the transcription systems of T7 RNA [7,8] and Taq DNA [9] polymerases, the best antifibrillogenic properties [10] and the most intensive CD outputs on their supramolecular binding to albumins [4][5][6] as well. The latter results are explained [4][5][6] by strong supramolecular interactions of the terminal polar and/or H-donor group(s) of a given macrobicyclic "guest" with appropriate aminoacid residues of a suitable protein macromolecule as a "host" upon their non-covalent host-guest clathrochelate-protein self-assembly.…”

“…They possess the highest inhibitory activities in the transcription systems of T7 RNA [7,8] and Taq DNA [9] polymerases, the best antifibrillogenic properties [10] and the most intensive CD outputs on their supramolecular binding to albumins [4][5][6] as well. The latter results are explained [4][5][6] by strong supramolecular interactions of the terminal polar and/or H-donor group(s) of a given macrobicyclic "guest" with appropriate aminoacid residues of a suitable protein macromolecule as a "host" upon their non-covalent host-guest clathrochelate-protein self-assembly. Moreover, very recently, one of the macrobicyclic iron(II) complexes, the molecule that contains one terminal functionalizing carboxyl group, has been found [11] to possess both high in vitro cytotoxicity and selectivity (as compared with normal cells) against the human promyelocytic leukemia cell line.…”