Coordination to Imidazole Ring Switches on Phosphorescence of Platinum Cyclometalated Complexes: The Route to Selective Labeling of Peptides and Proteins via Histidine Residues

Abstract

In this study, we have shown that substitution of chloride ligand for imidazole (Im) ring in the cyclometalated platinum complex Pt(phpy)(PPh)Cl (1; phpy, 2-phenylpyridine; PPh, triphenylphosphine), which is nonemissive in solution, switches on phosphorescence of the resulting compound. Crystallographic and nuclear magnetic resonance (NMR) spectroscopic studies of the substitution product showed that the luminescence ignition is a result of Im coordination to give the [Pt(phpy)(Im)(PPh)]Cl complex. The other imidazole-containing biomolecules, such as histidine and histidine-containing peptides and proteins, also trigger luminescence of the substitution products. The complex 1 proved to be highly selective toward the imidazole ring coordination that allows site-specific labeling of peptides and proteins with 1 using the route, which is orthogonal to the common bioconjugation schemes via lysine, aspartic and glutamic acids, or cysteine and does not require any preliminary modification of a biomolecule. The utility of this approach was demonstrated on (i) site-specific modification of the ubiquitin, a small protein that contains only one His residue in its sequence, and (ii) preparation of nonaggregated HSA-based Pt phosphorescent probe. The latter particles easily internalize into the live HeLa cells and display a high potential for live-cell phosphorescence lifetime imaging (PLIM) as well as for advanced correlation PLIM and FLIM experiments.

Pt-ttpy, a G-quadruplex binding platinum complex, induces telomere dysfunction and G-rich regions DNA damage

“…The discrepancy of the three complexes in anti-proliferative activity between both cell lines might result from their difference in cellular uptake and/or genomic DNA binding efficiency, since platinum DNA-adducts have been recognized as the ultimate event generated in cells [39,50]. At the stage, we want to point out that contrary to other platinum complexes, our complexes are not luminescent [51].…”

Building up PtII−Thiosemicarbazone−Lysine−sC18 Conjugates

“…However, although promising, metal complexes are generally only less developed as pharmaceutics owing to their poor water solubility and limited cellular uptake [30] . One way to overcome these issues is the combination of metal complexes with bioactive peptides, which has gained considerable attention during the last decade [31–41] . In this context, so‐called cell‐penetrating peptides (CPPs) are promising tools to deliver metal complexes into various types of cells [41–49] .…”

Reactions of Cyclometalated Platinum(II) [Pt(N∧C)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules: Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design

“…21,22,26 Recently, we published the study on the reactions of [Pt(ppy)(PPh 3 )Cl] (ppy-2-phenilpyridine) complex with imidazole (Im), histidine, and histidine-containing proteins (human serum albumin (HSA) and ubiquitin (Ubq)). 27 The study revealed that the reaction of this complex with imidazole and imidazole function of histidine results in substitution of the chloride ligand to give the cationic complexes of the following composition [Pt(ppy)(PPh 3 )(Im)] + . In contrast to nonluminescent starting compound, the substituted products are phosphorescent and demonstrate appreciable quantum yield and emission in the green region of visible spectrum (at ca.…”