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

Anastasia I. Solomatina, Pavel S. Chelushkin, Tatiana O. Abakumova, Vladimir A. Zhemkov, Mee Whi Kim, Ilya Bezprozvanny, Vladislav V. Gurzhiy, Alexey S. Melnikov, Yuri A. Anufrikov, Igor O. Koshevoy, Shih Hao Su, Pi Tai Chou, Sergey P. Tunik

Research output: Contribution to journalArticle

Abstract

This work describes interaction of a family of [Pt(NC)(PR3)Cl] complexes with imidazole (Im), possible application of this chemistry for regioselective labeling of proteins through imidazole rings of histidine residues and employment of the resulting phosphorescent products in bioimaging. It was found that the complexes containing aliphatic phosphines display reversible substitution of chloride ligand for imidazole function that required considerable excess of imidazole to obtain full conversion into the substituted [Pt(ppy)(PR3)(Im)] product, whereas the substitution in the complexes with aromatic phosphines readily proceeds in 1:1.5 mixture of reagents. Rapid, selective, and quantitative coordination of imidazole to the platinum complexes enabled regioselective labeling of ubiquitin. X-ray protein crystallography of the {[Pt(ppy)(PPh3)]/ubiquitin} conjugate revealed direct bonding of the platinum center to unique histidine-68 residue through the nitrogen atom of imidazole function, the coordination being also supported by noncovalent interaction of the ligands with the protein secondary structure. The variations of the cyclometalating NC ligands gave a series of [Pt(NC)(PPh3)Cl] complexes (NC = 2-phenylpyridine, 2-(benzofuran-3-yl)pyridine, 2-(benzo[b]thiophen-3-yl)pyridine, methyl-2-phenylquinoline-4-carboxylate), which were used to investigate the impact of NC-ligand onto photophysical properties of the imidazole complexes and conjugates with human serum albumin (HSA). The chloride ligand substitution for imidazole and formation of the conjugates results in ignition of the platinum chromophore luminescence with substantially higher quantum yield in the latter case. Variation of the metalating NC-ligand made possible the shift of the emission to the red region of visible spectrum for both types of the products. Cell-viability tests revealed low cytotoxicity of all {[Pt(NC)(PPh3)Cl]/HSA} conjugates, while PLIM experiments demonstrated their high potential for oxygen sensing.

Original languageEnglish (US)
JournalInorganic Chemistry
DOIs
StateAccepted/In press - Jan 1 2018

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Biomolecules
Platinum
imidazoles
platinum
reactivity
Tuning
tuning
Ligands
ligands
Phosphines
Substitution reactions
histidine
substitutes
Ubiquitin
proteins
albumins
Histidine
phosphines
Serum Albumin
serums

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

Cite this

Reactions of Cyclometalated Platinum(II) [Pt(NC)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules : Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design. / Solomatina, Anastasia I.; Chelushkin, Pavel S.; Abakumova, Tatiana O.; Zhemkov, Vladimir A.; Kim, Mee Whi; Bezprozvanny, Ilya; Gurzhiy, Vladislav V.; Melnikov, Alexey S.; Anufrikov, Yuri A.; Koshevoy, Igor O.; Su, Shih Hao; Chou, Pi Tai; Tunik, Sergey P.

In: Inorganic Chemistry, 01.01.2018.

Research output: Contribution to journalArticle

Solomatina, Anastasia I. ; Chelushkin, Pavel S. ; Abakumova, Tatiana O. ; Zhemkov, Vladimir A. ; Kim, Mee Whi ; Bezprozvanny, Ilya ; Gurzhiy, Vladislav V. ; Melnikov, Alexey S. ; Anufrikov, Yuri A. ; Koshevoy, Igor O. ; Su, Shih Hao ; Chou, Pi Tai ; Tunik, Sergey P. / Reactions of Cyclometalated Platinum(II) [Pt(NC)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules : Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design. In: Inorganic Chemistry. 2018.
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abstract = "This work describes interaction of a family of [Pt(N∞C)(PR3)Cl] complexes with imidazole (Im), possible application of this chemistry for regioselective labeling of proteins through imidazole rings of histidine residues and employment of the resulting phosphorescent products in bioimaging. It was found that the complexes containing aliphatic phosphines display reversible substitution of chloride ligand for imidazole function that required considerable excess of imidazole to obtain full conversion into the substituted [Pt(ppy)(PR3)(Im)] product, whereas the substitution in the complexes with aromatic phosphines readily proceeds in 1:1.5 mixture of reagents. Rapid, selective, and quantitative coordination of imidazole to the platinum complexes enabled regioselective labeling of ubiquitin. X-ray protein crystallography of the {[Pt(ppy)(PPh3)]/ubiquitin} conjugate revealed direct bonding of the platinum center to unique histidine-68 residue through the nitrogen atom of imidazole function, the coordination being also supported by noncovalent interaction of the ligands with the protein secondary structure. The variations of the cyclometalating N∞C ligands gave a series of [Pt(N∞C)(PPh3)Cl] complexes (N∞C = 2-phenylpyridine, 2-(benzofuran-3-yl)pyridine, 2-(benzo[b]thiophen-3-yl)pyridine, methyl-2-phenylquinoline-4-carboxylate), which were used to investigate the impact of N∞C-ligand onto photophysical properties of the imidazole complexes and conjugates with human serum albumin (HSA). The chloride ligand substitution for imidazole and formation of the conjugates results in ignition of the platinum chromophore luminescence with substantially higher quantum yield in the latter case. Variation of the metalating N∞C-ligand made possible the shift of the emission to the red region of visible spectrum for both types of the products. Cell-viability tests revealed low cytotoxicity of all {[Pt(N∞C)(PPh3)Cl]/HSA} conjugates, while PLIM experiments demonstrated their high potential for oxygen sensing.",
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T2 - Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design

AU - Solomatina, Anastasia I.

AU - Chelushkin, Pavel S.

AU - Abakumova, Tatiana O.

AU - Zhemkov, Vladimir A.

AU - Kim, Mee Whi

AU - Bezprozvanny, Ilya

AU - Gurzhiy, Vladislav V.

AU - Melnikov, Alexey S.

AU - Anufrikov, Yuri A.

AU - Koshevoy, Igor O.

AU - Su, Shih Hao

AU - Chou, Pi Tai

AU - Tunik, Sergey P.

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N2 - This work describes interaction of a family of [Pt(N∞C)(PR3)Cl] complexes with imidazole (Im), possible application of this chemistry for regioselective labeling of proteins through imidazole rings of histidine residues and employment of the resulting phosphorescent products in bioimaging. It was found that the complexes containing aliphatic phosphines display reversible substitution of chloride ligand for imidazole function that required considerable excess of imidazole to obtain full conversion into the substituted [Pt(ppy)(PR3)(Im)] product, whereas the substitution in the complexes with aromatic phosphines readily proceeds in 1:1.5 mixture of reagents. Rapid, selective, and quantitative coordination of imidazole to the platinum complexes enabled regioselective labeling of ubiquitin. X-ray protein crystallography of the {[Pt(ppy)(PPh3)]/ubiquitin} conjugate revealed direct bonding of the platinum center to unique histidine-68 residue through the nitrogen atom of imidazole function, the coordination being also supported by noncovalent interaction of the ligands with the protein secondary structure. The variations of the cyclometalating N∞C ligands gave a series of [Pt(N∞C)(PPh3)Cl] complexes (N∞C = 2-phenylpyridine, 2-(benzofuran-3-yl)pyridine, 2-(benzo[b]thiophen-3-yl)pyridine, methyl-2-phenylquinoline-4-carboxylate), which were used to investigate the impact of N∞C-ligand onto photophysical properties of the imidazole complexes and conjugates with human serum albumin (HSA). The chloride ligand substitution for imidazole and formation of the conjugates results in ignition of the platinum chromophore luminescence with substantially higher quantum yield in the latter case. Variation of the metalating N∞C-ligand made possible the shift of the emission to the red region of visible spectrum for both types of the products. Cell-viability tests revealed low cytotoxicity of all {[Pt(N∞C)(PPh3)Cl]/HSA} conjugates, while PLIM experiments demonstrated their high potential for oxygen sensing.

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