The interaction of half-sandwich (η5-Cp*)Rh(III) cation with histidine containing peptides and their ternary species with (N,N) bidentate ligands

Abstract

Our goal was to explore the possible interactions of the potential metallodrug (η 5 -Cp*)Rh(III) complexes with histidine containing biomolecules (peptides/proteins) in order to understand the most important thermodynamic factors influencing the biospeciation and biotransformation of (η 5 -Cp*)Rh(III) complexes. To this end, here we report systematic solution thermodynamic and solution structural study on the interaction of (η 5 -Cp*)Rh(III) cation with histidine containing peptides and their constituents ((N-methyl)imidazole, GGA-OH, GGH-OH, histidine-amide, HGG-OH, GHG-NH 2 ), based on extensive 1 H NMR, ESI-MS and potentiometric investigations. The comparative evaluation of our data indicated that (η 5 -Cp*)Rh(III) cation is able to induce the deprotonation of amide nitrogen well below pH 7. Consequently, at physiological pH the peptides are coordinated to Rh(III) by tridentate manner, with the participation of amide nitrogen. At pH 7.4 the (η 5 -Cp*)Rh(III) binding affinity of peptides follow the order GGA-OH < < GGH-OH < < histidine-amide < HGG-OH < GHG-NH 2 , i.e. the observed binding strength essentially depends on the presence and position of histidine within the peptide sequence. We also performed computational study on the possible solution structures of complexes present at near physiological pH. At pH 7.4 all histidine containing peptides form ternary complexes with strongly coordinating (N,N) bidentate ligands (ethylenediamine or bipyridyl), in which the peptides are monodentately coordinated to Rh(III) through their imidazole N 1 -nitrogens. In addition, the strongest chelators histidine-amide, HGG-OH and GHG-NH 2 are also able to displace these powerful bidentate ligands from the coordination sphere of Rh(III).

Organometallic Ru(ii), Rh(iii) and Re(i) complexes of sterane-based bidentate ligands: synthesis, solution speciation, interaction with biomolecules and anticancer activity

“…It was reported that half-sandwich RuCym and RhCp* complexes mostly preferred to bind to the His-imidazole residue of the protein. 54–58…”

“…It was reported that half-sandwich RuCym and RhCp* complexes mostly preferred to bind to the His-imidazole residue of the protein. [54][55][56][57][58] At first, UV-vis spectral changes of the complexes were followed over time in the presence of 10 equiv. MIM (Fig.…”

Diversity in the Interaction of Amino Acid- and Peptide-Based Hydroxamic Acids with Some Platinum Group Metals in Solution

“…(The corresponding stability constants and protonation constants were taken from refs. [53], [92] and [93], except for the (O,O) chelated species at 0.20 M KCl, which were determined in this work and are as follows: [ML] + = 7.08; [MH −1 L]= −1.12). As Figure 4 reveals, in the strongly acidic pH-range (1-3) the stability of the (N,N) 5 chelate is comparable with that of the (O,O) chelate, but upon increasing the pH, the latter becomes the most stable in the whole pH-range.…”

Copper(II) and (η5-Cp*)rhodium(III) complexes of some imidazole and pyridine containing ligands

“…The constants in square brackets are only indicative values, since the systems were non-equilibrated. (taken from [151] Since Rh(III) is diamagnetic (low spin d 6 cation) in all our complexes, NMR is a straightforward method to gain information on the solution structure and also to support the solution speciation. Indeed, all L 5(m) complexes have slow ligand exchange on the NMR timescale, and thus the changes in speciation can be easily followed (Fig.…”

“…4.27A). Considering the difference between the two ligands, the most plausible reason of isomer formation is the metal-promoted deprotonation and coordination of imidazole N 1 H group of L 5 , and the subsequent formation of different oligomers [151]) via imidazolato bridges. This would not be very unusual, since the crystal structure of an imidazolato-bridged (η 5 -Cp*)Rh(III) complex has been already reported in the literature [159].…”